Heat shock protein 27 regulates human prostate cancer cell motility and metastatic progression

PubMed Central

Voll, Eric A; Ogden, Irene M; Pavese, Janet M; Huang, XiaoKe; Xu, Li; Jovanovic, Borko D; Bergan, Raymond C

2014-01-01

Prostate cancer (PCa) is the most common form of cancer in American men. Mortality from PCa is caused by the movement of cancer cells from the primary organ to form metastatic tumors at distant sites. Heat shock protein 27 (HSP27) is known to increase human PCa cell invasion and its overexpression is associated with metastatic disease. The role of HSP27 in driving PCa cell movement from the prostate to distant metastatic sites is unknown. Increased HSP27 expression increased metastasis as well as primary tumor mass. In vitro studies further examined the mechanism of HSP27-induced metastatic behavior. HSP27 did not affect cell detachment, adhesion, or migration, but did increase cell invasion. Cell invasion was dependent upon matrix metalloproteinase 2 (MMP-2), whose expression was increased by HSP27. In vivo, HSP27 induced commensurate changes in MMP-2 expression in tumors. These findings demonstrate that HSP27 drives metastatic spread of cancer cells from the prostate to distant sites, does so across a continuum of expression levels, and identifies HSP27-driven increases in MMP-2 expression as functionally relevant. These findings add to prior studies demonstrating that HSP27 increases PCa cell motility, growth and survival. Together, they demonstrate that HSP27 plays an important role in PCa progression. PMID:24798191

Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement.

PubMed

Griffiths, R R; Chausmer, A L

2000-11-01

Caffeine is an excellent model compound for understanding drugs of abuse/dependence. The results of self-administration and choice studies in humans clearly demonstrate the reinforcing effects of low and moderate doses of caffeine. Caffeine reinforcement has been demonstrated in about 45% of normal subjects with histories of moderate and heavy caffeine use. Recent studies provide compelling evidence that caffeine physical dependence potentiates the reinforcing effects of caffeine through the mechanism of withdrawal symptom avoidance. Tolerance to the subjective and sleep-disrupting effects of caffeine in humans has been demonstrated. Physical dependence as reflected in a withdrawal syndrome in humans has been repeatedly demonstrated in adults and recently demonstrated in children. Withdrawal severity is an increasing function of caffeine maintenance dose, with withdrawal occurring at doses as low as 100 mg per day. Increased cerebral blood flow may be the physiological mechanism for caffeine withdrawal headache. Case studies in adults and adolescents clearly demonstrate that some individuals meet DSM-IV diagnostic criteria for a substance dependence syndrome on caffeine, including feeling compelled to continue caffeine use despite desires and recommendations to the contrary. Survey data suggest that 9% to 30% percent of caffeine consumers may be caffeine dependent according to DSM-IV criteria.

Gratitude and prosocial behavior: helping when it costs you.

PubMed

Bartlett, Monica Y; DeSteno, David

2006-04-01

The ability of the emotion gratitude to shape costly prosocial behavior was examined in three studies employing interpersonal emotion inductions and requests for assistance. Study 1 demonstrated that gratitude increases efforts to assist a benefactor even when such efforts are costly (i.e., hedonically negative), and that this increase differs from the effects of a general positive affective state. Additionally, mediational analyses revealed that gratitude, as opposed to simple awareness of reciprocity norms, drove helping behavior. Furthering the theory that gratitude mediates prosocial behavior, Study 2 replicated the findings of Study 1 and demonstrated gratitude's ability to function as an incidental emotion by showing it can increase assistance provided to strangers. Study 3 revealed that this incidental effect dissipates if one is made aware of the true cause of the emotional state. Implications of these findings for the role of gratitude in building relationships are discussed.

Hamstrings to quadriceps peak torque ratios diverge between sexes with increasing isokinetic angular velocity.

PubMed

Hewett, Timothy E; Myer, Gregory D; Zazulak, Bohdanna T

2008-09-01

Our purpose was to determine if females demonstrate decreased hamstrings to quadriceps peak torque (H/Q) ratios compared to males and if H/Q ratios increase with increased isokinetic velocity in both sexes. Maturation disproportionately increases hamstrings peak torque at high velocity in males, but not females. Therefore, we hypothesised that mature females would demonstrate decreased H/Q ratios compared to males and the difference in H/Q ratio between sexes would increase as isokinetic velocity increased. Studies that analysed the H/Q ratio with gravity corrected isokinetic strength testing reported between 1967 and 2004 were included in our review and analysis. Keywords were hamstrings/quadriceps, isokinetics, peak torque and gravity corrected. Medline and Smart databases were searched combined with cross-checked bibliographic reference lists of the publications to determine studies to be included. Twenty-two studies were included with a total of 1568 subjects (1145 male, 423 female). Males demonstrated a significant correlation between H/Q ratio and isokinetic velocity (R=0.634, p<0.0001), and a significant difference in the isokinetic H/Q ratio at the lowest angular velocity (47.8+/-2.2% at 30 degrees /s) compared to the highest velocity (81.4+/-1.1% at 360 degrees /s, p<0.001). In contrast, females did not demonstrate a significant relationship between H/Q ratio and isokinetic velocity (R=0.065, p=0.77) or a change in relative hamstrings strength as the speed increased (49.5+/-8.8% at 30 degrees /s; 51.0+/-5.7% at 360 degrees /s, p=0.84). Gender differences in isokinetic H/Q ratios were not observed at slower angular velocities. However, at high knee flexion/extension angular velocities, approaching those that occur during sports activities, significant gender differences were observed in the H/Q ratio. Females, unlike males, do not increase hamstrings to quadriceps torque ratios at velocities that approach those of functional activities.

Effect of 24 months of recombinant growth hormone on height and body proportions in SHOX haploinsufficiency.

PubMed

Munns, C F J; Berry, M; Vickers, D; Rappold, G A; Hyland, V J; Glass, I A; Batch, J A

2003-09-01

Leri-Weill syndrome (LWS) is a skeletal dysplasia with mesomelic short stature, bilateral Madelung deformity (BMD) and SHOX (short stature homeobox-containing gene) haploinsufficiency. The effect of 24 months of recombinant human growth hormone (rhGH) therapy on the stature and BMD of two females with SHOX haploinsufficiency (demonstrated by fluorescence in situ hybridisation) and LWS was evaluated. Both patients demonstrated an increase in height standard deviation score (SDS) and height velocity SDS over the 24 months of therapy. Patient 1 demonstrated a relative increase in arm-span and upper segment measurements with rhGH while patient 2 demonstrated a relative increase in lower limb length. There was appropriate advancement of bone age, no adverse events and no significant deterioration in BMD. In this study, 24 months of rhGH was a safe and effective therapy for the disproportionate short stature of SHOX haploinsufficiency, with no clinical deterioration of BMD.

A complex reaction time study (Sternberg) in space flight

NASA Technical Reports Server (NTRS)

Thornton, W.; Uri, John; Moore, Tom

1993-01-01

Simple and complex (Sternberg) reaction time studies were flown on three and seven day Shuttle flights in 1985. Three subjects did selftesting with an onboard handheld calculator without difficulty. There was little change in simple reaction time. One subject demonstrated a decrease in the processing rate during space motion sickness while a second exhibited an increase in complex reaction time without a change in processing rate during a period of high work load. The population was too small to demonstrate significant changes. This study demonstrates the ease and practicality of such measurements and indicates the potential value of such studies in space.

Temperature and Leaf Osmotic Potential as Factors in the Acclimation of Photosynthesis to High Temperature in Desert Plants 1

PubMed Central

Seemann, Jeffrey R.; Downton, W. John S.; Berry, Joseph A.

1986-01-01

Seasonal changes in the high temperature limit for photosynthesis of desert winter annuals growing under natural conditions in Death Valley, California were studied using an assay based upon chlorophyll fluorescence. All species of this group were 6 to 9°C more tolerant of high temperature at the end of the growing season (May) than at its beginning (February). Over this same time period, the mean daily maximum air temperatures increased by 12°C. Laboratory studies have demonstrated that increases in thermal tolerance could be induced by increasing growth temperature alone. For plants growing under field conditions there was also a good correlation between the thermal tolerance of leaves and the osmotic potential of leaf water, indicating that increases in the concentrations of some small molecules might also confer increased thermal tolerance. Isolated chloroplast thylakoids subjected to increasing concentrations of sorbitol could be demonstrated to have increased thermal tolerance. PMID:16664743

Structurally tailored graphene nanosheets as lithium ion battery anodes: an insight to yield exceptionally high lithium storage performance

NASA Astrophysics Data System (ADS)

Li, Xifei; Hu, Yuhai; Liu, Jian; Lushington, Andrew; Li, Ruying; Sun, Xueliang

2013-11-01

How to tune graphene nanosheets (GNSs) with various morphologies has been a significant challenge for lithium ion batteries (LIBs). In this study, three types of GNSs with varying size, edge sites, defects and layer numbers have been successfully achieved. It was demonstrated that controlling GNS morphology and microstructure has important effects on its cyclic performance and rate capability in LIBs. Diminished GNS layer number, decreased size, increased edge sites and increased defects in the GNS anode can be highly beneficial to lithium storage and result in increased electrochemical performance. Interestingly, GNSs treated with a hydrothermal approach delivered a high reversible discharge capacity of 1348 mA h g-1. This study demonstrates that the controlled design of high performance GNS anodes is an important concept in LIB applications.How to tune graphene nanosheets (GNSs) with various morphologies has been a significant challenge for lithium ion batteries (LIBs). In this study, three types of GNSs with varying size, edge sites, defects and layer numbers have been successfully achieved. It was demonstrated that controlling GNS morphology and microstructure has important effects on its cyclic performance and rate capability in LIBs. Diminished GNS layer number, decreased size, increased edge sites and increased defects in the GNS anode can be highly beneficial to lithium storage and result in increased electrochemical performance. Interestingly, GNSs treated with a hydrothermal approach delivered a high reversible discharge capacity of 1348 mA h g-1. This study demonstrates that the controlled design of high performance GNS anodes is an important concept in LIB applications. Electronic supplementary information (ESI) available: SEM morphologies of GNS-I-III at low magnification, the TEM image of GNSs hydrothermally treated with urea in a ratio of 1 : 0, XPS survey, and SEM morphology changes of the three GNS anodes at low magnification after 100 charge-discharge cycles. See DOI: 10.1039/c3nr04823c

Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding.

PubMed

Sharma, Jyoti; Rathnayaka, Nuvan; Green, Charles; Moeller, F Gerard; Schmitz, Joy M; Shoham, Daniel; Dougherty, Anne Hamilton

2016-01-01

Few studies have examined the effects of chronic cocaine use on the resting surface electrocardiogram (ECG) between exposures to cocaine. Researchers compared 12-lead ECGs from 97 treatment-seeking cocaine-dependent patients, with ECG parameters from 8,513 non-cocaine-using control patients from the Atherosclerosis Risk in Communities study. After matching and adjusting for relevant covariates, cocaine use demonstrated large and statistically reliable effects on early repolarization, bradycardia, severe bradycardia, and heart rate. Current cocaine dependence corresponds to an increased odds of demonstrating early repolarization by a factor of 4.92 and increased odds of bradycardia and severe bradycardia by factors 3.02 and 5.11, respectively. This study demonstrates the novel finding that long-lasting effects of cocaine use on both the cardiac conduction and the autonomic nervous system pose a risk of adverse cardiovascular events between episodes of cocaine use, and that bradycardia is a marker of chronic cocaine use.

Dropouts In Two-Year Colleges: Better Prediction With The Use Of Moderator Subgroups

ERIC Educational Resources Information Center

Capoor, Madan; Eagle, Norman

1977-01-01

This article demonstrates, through a case study, the use of pre-existing subgroups as moderator variables to increase the predictive effectiveness of educational research. Use of moderator variables in this study increased the amount of explained variance by 460 percent. (JDS)

Sex-related differences in sleep slow wave activity in major depressive disorder: a high-density EEG investigation.

PubMed

Plante, David T; Landsness, Eric C; Peterson, Michael J; Goldstein, Michael R; Riedner, Brady A; Wanger, Timothy; Guokas, Jeffrey J; Tononi, Giulio; Benca, Ruth M

2012-09-18

Sleep disturbance plays an important role in major depressive disorder (MDD). Prior investigations have demonstrated that slow wave activity (SWA) during sleep is altered in MDD; however, results have not been consistent across studies, which may be due in part to sex-related differences in SWA and/or limited spatial resolution of spectral analyses. This study sought to characterize SWA in MDD utilizing high-density electroencephalography (hdEEG) to examine the topography of SWA across the cortex in MDD, as well as sex-related variation in SWA topography in the disorder. All-night recordings with 256 channel hdEEG were collected in 30 unipolar MDD subjects (19 women) and 30 age and sex-matched control subjects. Spectral analyses of SWA were performed to determine group differences. SWA was compared between MDD and controls, including analyses stratified by sex, using statistical non-parametric mapping to correct for multiple comparisons of topographic data. As a group, MDD subjects demonstrated significant increases in all-night SWA primarily in bilateral prefrontal channels. When stratified by sex, MDD women demonstrated global increases in SWA relative to age-matched controls that were most consistent in bilateral prefrontal regions; however, MDD men showed no significant differences relative to age-matched controls. Further analyses demonstrated increased SWA in MDD women was most prominent in the first portion of the night. Women, but not men with MDD demonstrate significant increases in SWA in multiple cortical areas relative to control subjects. Further research is warranted to investigate the role of SWA in MDD, and to clarify how increased SWA in women with MDD is related to the pathophysiology of the disorder.

Association Between Serum 25-Hydroxy Vitamin D Levels and Blood Pressure Among Adolescents in Two Resource-Limited Settings in Peru

PubMed Central

Tomaino, Katherine; Romero, Karina M.; Robinson, Colin L.; Baumann, Lauren M.; Hansel, Nadia N.; Pollard, Suzanne L.; Gilman, Robert H.; Mougey, Edward; Lima, John J.

2015-01-01

INTRODUCTION Serum 25-hydroxyvitamin D (25OHD) deficiency (<50 nmol/l or 20ng/ml) has been associated with increased blood pressure (BP) in observational studies. A paucity of data on this relationship is available in Latin American or child populations. This study investigates the association between 25OHD levels and BP in adolescents at risk for vitamin D deficiency in 2 Peruvian settings. METHODS In a population-based study of 1,441 Peruvian adolescents aged 13–15 years, 1,074 (75%) provided a serum blood sample for 25OHD analysis and BP measurements. Relationships between 25OHD and BP metrics were assessed using multiple linear regressions, adjusted for anthropometrics and sociodemographic factors. RESULTS 25OHD deficiency was associated with an elevated diastolic BP (DBP) (1.09mm Hg increase, 95% confidence interval: 0.04 to 2.14; P = 0.04) compared to nondeficient adolescents. Systolic BP (SBP) trended to increase with vitamin D deficiency (1.30mm Hg increase, 95% confidence interval: −0.13 to 2.72; P = 0.08). Mean arterial pressure (MAP) was also greater in adolescents with 25OHD (1.16mm Hg increase, 95% confidence interval: 0.10 to 2.22; P = 0.03). SBP was found to demonstrate a U-shaped relationship with 25OHD, while DBP and MAP demonstrated inverse J-shaped relationships with serum 25OHD status. The association between 25OHD deficiency and BP was not different across study sites (all P ≥ 0.19). DISCUSSION Adolescents deficient in 25OHD demonstrated increased DBP and MAP and a trend toward increased SBP, when compared to nondeficient subjects. 25OHD deficiency early in life was associated with elevated BP metrics, which may predispose risk of hypertension later in adulthood. PMID:25600222

Gait modification strategies for altering medial knee joint load: a systematic review.

PubMed

Simic, Milena; Hinman, Rana S; Wrigley, Tim V; Bennell, Kim L; Hunt, Michael A

2011-03-01

To evaluate the effect of gait modification strategies on the external knee adduction moment (KAM), a marker of medial knee joint load; determine potentially adverse effects; assess the methodologic quality; and identify areas of future research. Five electronic databases were searched. Studies evaluating the effects of gait modifications on the KAM in either healthy individuals or those with knee osteoarthritis (OA) were included. Methodologic quality was evaluated by 2 reviewers using the Downs and Black checklist. Twenty-four studies met the inclusion criteria, exploring 14 different gait modifications of varying sample sizes, age groups, and OA classifications. Contralateral cane use, increased step width, medial knee thrust, increased hip internal rotation, weight transfer to the medial foot, and increased lateral trunk lean demonstrated KAM reductions. Tai Chi gait, ipsilateral cane use, Nordic walking poles, and increased knee flexion exhibited increases in the KAM, demonstrating a potential detriment to their use. The effects of reduced stride length, as well as increases and reductions in either toe-out or gait speed, were inconsistent across the studies and gait cycle. This review demonstrates that some gait modifications have the ability to alter knee load. Future research is required to determine the magnitude of modification required to maximize beneficial effects, the best method of training, long-term patient adherence, and if these biomechanical changes can translate into clinically relevant changes in symptoms or disease progression risk. Copyright © 2011 by the American College of Rheumatology.

Pharmacophysiology of atopic dermatitis.

PubMed

Hanifin, J M

1986-02-01

Atopic dermatitis is clearly characterized by altered cutaneous physiologic responses. There is a tendency to acral vasoconstriction. Rubbing causes skin pallor and white dermographism. Vascular instability is demonstrated by responses to cholinergic agents, histamine, and nicotinates. Psychophysiologic studies demonstrate exaggerated vasodilator responses to emotional stress with consequent pruritus and scratching. The itch threshold is low, duration is prolonged, and nighttime scratching movements may be frequent or almost continuous. Regardless of the inciting trigger factors, the scratching causes the damage and the severe dermatitis. Thermal as well as emotional stimuli to sweating cause severe itching in AD, yet the concept of a miliaria-type, poral occlusion mechanism remains unproven. Some studies suggest actually increased sweating along with erythema and pruritus during acute flares of AD. The concept of sweat-borne allergens causing skin reactions during sweating is interesting but has never been proven. Studies of sweat responses to pharmacologic agents have produced conflicting data, and attempts to link these responses to Szentivanyi's beta-adrenergic blockade theory are not convincing. The numerous variables of climate, season, sex, age, and habitus affect sweating greatly. Future studies must carefully control for each of these factors before pharmacologically induced sweat responses can be interpreted clearly. A number of lines of evidence suggest involvement of histamine and other mediators in the evolution of erythema, pruritus, and scratching in AD. Flares of the condition have been reproducibly evoked by only two incitants: experimental emotional stress interviews and specific food challenge in selected sensitive individuals. In the latter, increased plasma histamine has been demonstrated, presumably generated by antigen/IgE stimulated degranulation of mast cells in the gut and/or skin. The demonstrated increased histamine releasability of basophils from atopic individuals may be the result of defective cellular regulatory mechanisms. Recent studies have demonstrated increased cyclic AMP-phosphodiesterase activity in leukocytes from atopic individuals. The resultant decreased intracellular cyclic AMP removes an inhibitory factor, which in turn causes net cellular hyperresponsiveness. This effect has been shown to account, at least in part, for increased histamine release from leukocytes of patients with AD. These and other studies focused upon cell functional regulation are providing better understanding of basic biochemical abnormalities and may lead to improved diagnostic and therapeutic approaches in managing atopic disease.

Leiomyoma Cells in 3-Dimensional Cultures Demonstrate an Attenuated Response to Fasudil, a Rho-Kinase Inhibitor, When Compared to 2-Dimensional Cultures

PubMed Central

Malik, Minnie; Britten, Joy; Segars, James

2014-01-01

Uterine leiomyomata are common benign tumors in women of reproductive age and demonstrate an attenuated response to mechanical signaling that involves Rho and integrins. To further characterize the impairment in Rho signaling, we studied the effect of Rho-kinase inhibitor, fasudil, on extracellular matrix production, in 2-dimensional (2D) and 3-dimensional (3D) cultures of leiomyoma and myometrial cells. Leiomyoma 2D cultures demonstrated a rapid decrease in gene transcripts and protein for fibronectin, procollagen 1A, and versican. In 3D cultures, fibronectin and procollagen 1A proteins demonstrated increased levels at lower concentrations of fasudil, followed by a concentration-dependent decrease. Versican protein increased up to 3-fold, whereas fibromodulin demonstrated a significant decrease of 1.92-fold. Myometrial 2D or 3D cultures demonstrated a decrease in all proteins after 72 hours of treatment. The 3D leiomyoma cultures demonstrated a significant increase in active RhoA, followed by a concentration-dependent decrease at higher concentrations. A concentration-dependent increase in phospho-extracellular regulated signal kinase and proapoptotic protein Bax was observed in 3D leiomyoma cultures. Fasudil relaxed the contraction of the 3D collagen gels caused by myometrium and leiomyoma cell growth. These findings indicate that the altered state of Rho signaling in leiomyoma was more clearly observed in 3D cultures. The results also suggest that fasudil may have clinical applicability for treatment of uterine leiomyoma. PMID:25084783

Winning a competition predicts dishonest behavior

PubMed Central

Schurr, Amos; Ritov, Ilana

2016-01-01

Winning a competition engenders subsequent unrelated unethical behavior. Five studies reveal that after a competition has taken place winners behave more dishonestly than competition losers. Studies 1 and 2 demonstrate that winning a competition increases the likelihood of winners to steal money from their counterparts in a subsequent unrelated task. Studies 3a and 3b demonstrate that the effect holds only when winning means performing better than others (i.e., determined in reference to others) but not when success is determined by chance or in reference to a personal goal. Finally, study 4 demonstrates that a possible mechanism underlying the effect is an enhanced sense of entitlement among competition winners. PMID:26831083

Winning a competition predicts dishonest behavior.

PubMed

Schurr, Amos; Ritov, Ilana

2016-02-16

Winning a competition engenders subsequent unrelated unethical behavior. Five studies reveal that after a competition has taken place winners behave more dishonestly than competition losers. Studies 1 and 2 demonstrate that winning a competition increases the likelihood of winners to steal money from their counterparts in a subsequent unrelated task. Studies 3a and 3b demonstrate that the effect holds only when winning means performing better than others (i.e., determined in reference to others) but not when success is determined by chance or in reference to a personal goal. Finally, study 4 demonstrates that a possible mechanism underlying the effect is an enhanced sense of entitlement among competition winners.

N-acetylcysteine supplementation decreases osteoclast differentiation and increases bone mass in mice fed a high-fat diet

USDA-ARS?s Scientific Manuscript database

Studies have demonstrated that obesity induced by high-fat diets increases bone resorption, decreases trabecular bone mass, and reduces bone strength in various animal models. This study investigated whether N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, alters glutathione statu...

Soil erosion studies in buffelgrass pastures

Treesearch

Diego Valdez-Zamudio; D. Phillip Guertin

2000-01-01

The introduction of exotic grasses in native rangelands to increase the production of forage has been a good alternative for the cattle industry in North America. Different studies have demonstrated that buffelgrass (Cenchrus ciliaris L.), a plant introduced from Africa, increases the annual green forage production approximately three times in comparison to production...

A single exposure to particulate or gaseous air pollution increases the risk of aconitine-induced cardiac arrythmia in hypertensive rats

EPA Science Inventory

Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...

Aconitine Challenge Test Reveals a Single Exposure to Air Pollution Causes Increased Cardiac Arrhythmia Risk in Hypertensive Rats - Abstract

EPA Science Inventory

Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...

Organizational Effectiveness in Higher Education: Faculty Informal Structure as Social Capital

ERIC Educational Resources Information Center

Dose, Jennifer J.

2012-01-01

Higher education institutions encounter complex external environments, requiring increasing responsiveness and innovation. Research on social capital has demonstrated that highly connected employee relational networks are more creative, effective, and exhibit higher member satisfaction. The present study examines one college to demonstrate how…

Demonstrated high performance of gas-filled rugby-shaped hohlraums on Omega

NASA Astrophysics Data System (ADS)

Philippe, F.; Tassin, V.; Depierreux, S.; Gauthier, P.; Masson-Laborde, P. E.; Monteil, M. C.; Seytor, P.; Villette, B.; Lasinski, B.; Park, H. S.; Ross, J. S.; Amendt, P.; Döppner, T.; Hinkel, D. E.; Wallace, R.; Williams, E.; Michel, P.; Frenje, J.; Gatu-Johnson, M.; Li, C. K.; Petrasso, R.; Glebov, V.; Sorce, C.; Stoeckl, C.; Nikroo, A.; Giraldez, E.

2014-07-01

A direct experimental comparison of rugby-shaped and cylindrical shaped gas-filled hohlraums on the Omega laser facility demonstrates that higher coupling and minimal backscatter can be achieved in the rugby geometry, leading to significantly enhanced implosion performance. A nearly 50% increase of x-ray drive is associated with earlier bangtime and increase of neutron production. The observed drive enhancement from rugby geometry in this study is almost twice stronger than in previously published results.

Effect of gallium nitrate on the expression of osteoprotegerin and receptor activator of nuclear factor‑κB ligand in osteoblasts in vivo and in vitro.

PubMed

Li, Jingwu; Wang, Guang-Bin; Feng, Xue; Zhang, Jing; Fu, Qin

2016-01-01

Osteoporosis is characterized by the progressive loss of bone mass and the micro‑architectural deterioration of bone tissue, leading to bone fragility and an increased risk of fracture. Gallium has demonstrated efficacy in the treatment of several diverse disorders that are characterized by accelerated bone loss. Osteoblasts orchestrate bone degradation by expressing the receptor activator of NF‑κB ligand (RANKL), however they additionally protect the skeleton by secreting osteoprotegerin (OPG). Therefore, the relative concentration of RANKL and OPG in bone is a key determinant of bone mass and strength. The current study demonstrated that gallium nitrate (GaN) is able to counteract bone loss in an experimental model of established osteoporosis. Ovariectomized (OVX) rats exhibited significantly increased bone mineral density following GaN treatment for 4 and 8 weeks by 19.3 and 37.3%, respectively (P<0.05). The bone volume of the OVX + GaN group was increased by 40.9% (P<0.05) compared with the OVX group. In addition, the current study demonstrated that GaN stimulates the synthesis of OPG however has no effect on the expression of RANKL in osteoblasts, as demonstrated by RT‑qPCR, western blotting and ELISA, resulting in an increase in the OPG/RANKL ratio and a reduction in osteoclast differentiation in vivo and in vitro.

Effect of gallium nitrate on the expression of osteoprotegerin and receptor activator of nuclear factor-κB ligand in osteoblasts in vivo and in vitro

PubMed Central

LI, JINGWU; WANG, GUANG-BIN; FENG, XUE; ZHANG, JING; FU, QIN

2016-01-01

Osteoporosis is characterized by the progressive loss of bone mass and the micro-architectural deterioration of bone tissue, leading to bone fragility and an increased risk of fracture. Gallium has demonstrated efficacy in the treatment of several diverse disorders that are characterized by accelerated bone loss. Osteoblasts orchestrate bone degradation by expressing the receptor activator of NF-κB ligand (RANKL), however they additionally protect the skeleton by secreting osteoprotegerin (OPG). Therefore, the relative concentration of RANKL and OPG in bone is a key determinant of bone mass and strength. The current study demonstrated that gallium nitrate (GaN) is able to counteract bone loss in an experimental model of established osteoporosis. Ovariectomized (OVX) rats exhibited significantly increased bone mineral density following GaN treatment for 4 and 8 weeks by 19.3 and 37.3%, respectively (P<0.05). The bone volume of the OVX + GaN group was increased by 40.9% (P<0.05) compared with the OVX group. In addition, the current study demonstrated that GaN stimulates the synthesis of OPG however has no effect on the expression of RANKL in osteoblasts, as demonstrated by RT-qPCR, western blotting and ELISA, resulting in an increase in the OPG/RANKL ratio and a reduction in osteoclast differentiation in vivo and in vitro. PMID:26647856

34 CFR 377.1 - What is the Demonstration Projects to Increase Client Choice Program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false What is the Demonstration Projects to Increase Client... PROJECTS TO INCREASE CLIENT CHOICE PROGRAM General § 377.1 What is the Demonstration Projects to Increase Client Choice Program? The Demonstration Projects to Increase Client Choice Program is designed to...

Increasing donations to supermarket food-bank bins using proximal prompts.

PubMed

Farrimond, Samantha J; Leland, Louis S

2006-01-01

There has been little research into interventions to increase participation in donating items to food-bank bins. In New Zealand, there has been an increased demand from food banks (Stewart, 2002). This study demonstrated that point-of-sale prompts can be an effective method of increasing donations to a supermarket food-bank bin.

A Novel Role of Proline Oxidase in HIV-1 Envelope Glycoprotein-induced Neuronal Autophagy*

PubMed Central

Pandhare, Jui; Dash, Sabyasachi; Jones, Bobby; Villalta, Fernando; Dash, Chandravanu

2015-01-01

Proline oxidase (POX) catalytically converts proline to pyrroline-5-carboxylate. This catabolic conversion generates reactive oxygen species (ROS) that triggers cellular signaling cascades including autophagy and apoptosis. This study for the first time demonstrates a role of POX in HIV-1 envelope glycoprotein (gp120)-induced neuronal autophagy. HIV-1 gp120 is a neurotoxic factor and is involved in HIV-1-associated neurological disorders. However, the mechanism of gp120-mediated neurotoxicity remains unclear. Using SH-SY5Y neuroblastoma cells as a model, this study demonstrates that gp120 treatment induced POX expression and catalytic activity. Concurrently, gp120 also increased intracellular ROS levels. However, increased ROS had a minimal effect on neuronal apoptosis. Further investigation indicated that the immediate cellular response to increased ROS paralleled with induction of autophagy markers, beclin-1 and LC3-II. These data lead to the hypothesis that neuronal autophagy is activated as a cellular protective response to the toxic effects of gp120. A direct and functional role of POX in gp120-mediated neuronal autophagy was examined by inhibition and overexpression studies. Inhibition of POX activity by a competitive inhibitor “dehydroproline” decreased ROS levels concomitant with reduced neuronal autophagy. Conversely, overexpression of POX in neuronal cells increased ROS levels and activated ROS-dependent autophagy. Mechanistic studies suggest that gp120 induces POX by targeting p53. Luciferase reporter assays confirm that p53 drives POX transcription. Furthermore, data demonstrate that gp120 induces p53 via binding to the CXCR4 co-receptor. Collectively, these results demonstrate a novel role of POX as a stress response metabolic regulator in HIV-1 gp120-associated neuronal autophagy. PMID:26330555

Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats.

PubMed

Mattioli, Theresa-Alexandra M; Milne, Brian; Cahill, Catherine M

2010-04-16

The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone. This research provides further validation for using ultra-low dose opioid receptor antagonists in the treatment of various pain syndromes.

Female orgasm but not male ejaculation activates the pituitary. A PET-neuro-imaging study.

PubMed

Huynh, Hieu Kim; Willemsen, Antoon T M; Holstege, Gert

2013-08-01

The pituitary gland plays an important role in basic survival mechanisms by releasing fluctuating amounts of hormones into the bloodstream, depending on the circumstances the individual finds itself. However, despite these changes in pituitary hormonal production, neuroimaging studies have never been able to demonstrate changes in the activation level of the pituitary. The most apparent reason is the much higher blood flow rate in the pituitary than in the brain. However, the present PET-scanning study demonstrates for the first time that neuroimaging techniques can identify increased pituitary activity. In a study with 11 healthy women sexual orgasm compared to rest caused an increased blood supply to the pituitary. We assume that this increase signifies elevated pituitary activation in order to produce higher plasma concentrations of oxytocin and prolactin. These hormones induce vaginal and uterus movements, ovulation and enhancement of sperm and egg transport. No increased blood supply was observed comparing clitoral stimulation, orgasm attempt, and faked orgasm with rest. In a study with 11 healthy men comparing ejaculation with rest did not reveal increased pituitary activation, probably because ejaculation causes a much lower increase of oxytocin and prolactin plasma concentration than female orgasm. Copyright © 2013 Elsevier Inc. All rights reserved.

The Multi-Domain Fibroblast/Myocyte Coupling in the Cardiac Tissue: A Theoretical Study.

PubMed

Greisas, Ariel; Zlochiver, Sharon

2016-09-01

Cardiac fibroblast proliferation and concomitant collagenous matrix accumulation (fibrosis) develop during multiple cardiac pathologies. Recent studies have demonstrated direct electrical coupling between myocytes and fibroblasts in vitro, and assessed the electrophysiological implications of such coupling. However, in the living tissues, such coupling has not been demonstrated, and only indirect coupling via the extracellular space is likely to exist. In this study we employed a multi-domain model to assess the modulation of the cardiac electrophysiological properties by neighboring fibroblasts assuming only indirect coupling. Numerical simulations in 1D and 2D human atrial models showed that extracellular coupling sustains a significant impact on conduction velocity (CV) and a less significant effect on the action potential duration. Both CV and the slope of the CV restitution increased with increasing fibroblast density. This effect was more substantial for lower extracellular conductance. In 2D, spiral waves exhibited reduced frequency with increasing fibroblast density, and the propensity of wavebreaks and complex dynamics at high pacing rates significantly increased.

CANCER AND DEVELOPMENTAL EXPOSURE TO ENDOCRINE DISRUPTORS

EPA Science Inventory

ABSTRACT
Developing organisms have been shown to have increased susceptibility to cancer if exposed to environmental toxicants during rapid growth and differentiation. Human studies have demonstrated clear increases in cancer following prenatal exposure to ionizing radiatio...

Political polarization projection: social projection of partisan attitude extremity and attitudinal processes.

PubMed

Van Boven, Leaf; Judd, Charles M; Sherman, David K

2012-07-01

What influences perceptions of political polarization? The authors examine the polarization of people's own political attitudes as a source of perceived polarization: Individuals with more extreme partisan attitudes perceive greater polarization than individuals with less extreme partisan attitudes. This "polarization projection" was demonstrated in 3 studies in which people estimated the distribution of others' political attitudes: one study with a nationally representative sample concerning the 2008 presidential election, and 2 studies concerning university students evaluating a policy regarding scarce resource allocation. These studies demonstrate that polarization projection occurs simultaneously with and independently of simple projection, the tendency to assume that others share one's partisan political attitudes. Polarization projection may occur partly because people assume that others engage in similar attitudinal processes as the self, such as extensive thought and emotional arousal. The projection of various attitudinal processes was demonstrated in a study concerning health care reform policies. Further supporting this explanation, polarization projection increased when people introspected about their own attitudinal processes, which increased the accessibility of those processes. Implications for perceptions of partisanship, social judgment, and civic behavior are discussed.

Life-Span Exposure to Low Doses of Aspartame Beginning during Prenatal Life Increases Cancer Effects in Rats

PubMed Central

Soffritti, Morando; Belpoggi, Fiorella; Tibaldi, Eva; Esposti, Davide Degli; Lauriola, Michelina

2007-01-01

Background In a previous study conducted at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the first time that aspartame (APM) is a multipotent carcinogenic agent when various doses are administered with feed to Sprague-Dawley rats from 8 weeks of age throughout the life span. Objective The aim of this second study is to better quantify the carcinogenic risk of APM, beginning treatment during fetal life. Methods We studied groups of 70–95 male and female Sprague-Dawley rats administered APM (2,000, 400, or 0 ppm) with feed from the 12th day of fetal life until natural death. Results Our results show a) a significant dose-related increase of malignant tumor–bearing animals in males (p < 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a significant increase in incidence of lymphomas/leukemias in males treated with 2,000 ppm (p < 0.05) and a significant dose-related increase in incidence of lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p < 0.01); and c) a significant dose-related increase in incidence of mammary cancer in females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05). Conclusions The results of this carcinogenicity bioassay confirm and reinforce the first experimental demonstration of APM’s multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans. Furthermore, the study demonstrates that when life-span exposure to APM begins during fetal life, its carcinogenic effects are increased. PMID:17805418

Demecolcine-assisted enucleation for bovine cloning.

PubMed

Tani, Tetsuya; Shimada, Hiroaki; Kato, Yoko; Tsunoda, Yukio

2006-01-01

The present study demonstrated that demecolcine treatment for at least 30 min produces a membrane protrusion in metaphase II-stage bovine oocytes. The maternal chromosome mass is condensed within the protrusion, which makes it easy to remove the maternal chromosomes for nuclear transfer (NT). Maturation promoting factor activity, but not mitogen-activated protein kinase activity, increased up to 30% in oocytes during demecolcine treatment. One normal healthy calf was obtained after transfer of four NT blastocysts produced following demecolcine treatment. Demecolcine treatment did not increase the potential of NT oocytes to develop into blastocysts. The present study demonstrated that chemically-assisted removal of chromosomes is effective for bovine cloning.

Online Gambling Advertising Regulations in Spain. A Study on the Protection of Minors.

PubMed

Buil, Pilar; Solé Moratilla, Maria José; García Ruiz, Pablo

2015-09-15

This article examines the online gambling advertising regulations in Spain currently in effect to assess the actual protection of underage youth. In recent years, online gambling among youth has increased. Through advertising, online gambling companies incite and encourage an involvement that can be harmful for vulnerable audiences. Some studies have demonstrated that advertising influences youths' assessment of gambling by increasing its appeal. We demonstrate that the shortcomings of the legal framework in force results in effective vulnerability of minors. We claim that society should seek to implement a regulatory framework to protect children from the risk of developing an addiction.

Multishot Targeted PROPELLER Magnetic Resonance Imaging: Description of the Technique and Initial Applications

PubMed Central

Deng, Jie; Larson, Andrew C.

2010-01-01

Objectives To test the feasibility of combining inner-volume imaging (IVI) techniques with conventional multishot periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) techniques for targeted-PROPELLER magnetic resonance imaging. Materials and Methods Perpendicular section-selective gradients for spatially selective excitation and refocusing RF pulses were applied to limit the refocused field-of-view (FOV) along the phase-encoding direction for each rectangular blade image. We performed comparison studies in phantoms and normal volunteers by using targeted-PROPELLER methods for a wide range of imaging applications that commonly use turbo-spin-echo (TSE) approaches (brain, abdominal, vessel wall, cardiac). Results In these initial studies, we demonstrated the feasibility of using targeted-PROPELLER approaches to limit the imaging FOV thereby reducing the number of blades or permitting increased spatial resolution without commensurate increases in scan time. Both phantom and in vivo motion studies demonstrated the potential for more robust regional self-navigated motion correction compared with conventional full FOV PROPELLER methods. Conclusion We demonstrated that the reduced FOV targeted-PROPELLER technique offers the potential for reducing imaging time, increasing spatial resolution, and targeting specific areas for robust regional motion correction. PMID:19465860

Remote Sensing and Geographic Information Systems as Decision Support Tools for Malaria Control in the Republic of Korea

DTIC Science & Technology

2001-05-30

larviciding due to the larger number of at- risk personnel and the smaller size of the vector habitats. This study demonstrates the usefulness of remote sensing...climate and demonstrates both short and long incubation periods. Long incubation periods increase the risk of re-introducing malaria to the continental...United States, making malaria control in the ROK even more important (Walter Reed Army Institute of Research 1998). This increased risk is from U.S

Building a better mousetrap (exergame) to increase youth physical activity

USDA-ARS?s Scientific Manuscript database

While exergames have been demonstrated to induce moderate levels of physical activity (PA) if played as designed, there is conflicting evidence on use of exergaming leading to increased habitual PA. Exergames have increased PA in some home and school studies, but not others. Exergames have been us...

Using Shaping to Increase Foods Consumed by Children with Autism

ERIC Educational Resources Information Center

Hodges, Abby; Davis, Tonya; Crandall, Madison; Phipps, Laura; Weston, Regan

2017-01-01

The current study used differential reinforcement and shaping to increase the variety of foods accepted by children with autism who demonstrated significant feeding inflexibility. Participants were introduced to four new food items via a hierarchical exposure, which involved systematically increasing the desired response with the food item. Level…

Can Blogging Increase Extroverts' Satisfaction in the Classroom? Lessons from Multiple Case Studies

ERIC Educational Resources Information Center

Samuel-Azran, Tal; Ravid, Gilad

2016-01-01

In light of systematic evidence that extroverts are disadvantaged in the classroom, we examined whether an online environment assignment that builds on extroverts' character strengths can increase their overall course satisfaction. Based on previous studies demonstrating that extroverts are energized by feedback from outsiders, we asked 180…

Does Critical Mass Matter? Women's Political Representation and Child Health in Developing Countries

ERIC Educational Resources Information Center

Swiss, Liam; Fallon, Kathleen M.; Burgos, Giovani

2012-01-01

Studies on developed countries demonstrate that an increase in women legislators leads to a prioritization in health, an increase in social policy spending, and a decrease in poverty. Women representatives could therefore improve development trajectories in developing countries; yet, currently, no cross-national and longitudinal studies explore…

A Health Education Program for Parents and Children Who Exhibit High Risk Factors of Coronary Heart Disease.

ERIC Educational Resources Information Center

Hopp, Joyce W.; And Others

This study demonstrated the feasibility of joint parent-child education to change the behaviors known to be associated with increased risk of coronary heart disease. Earlier studies have shown that parents who are at increased risk of coronary heart disease can be identified by studying certain factors in the children. Utilizing a combined risk…

Development and demonstration of marketing techniques for establishment of ride-sharing corporations in New York State. Final report

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

Peters, E.W.

1987-10-01

Convincing commuters to join car or vanpools can be a challenging task. Through the Energy Authority project, two guides were produced to assist in establishing ride-sharing corporations and in marketing ride-sharing services in New York State. The first guide explains how to set up a ride-sharing corporation; the second guide, developed following the completion of a Commuter Behavior Study and a six-month demonstration, discusses marketing ride-share services. The Commuter Behavior Study centered on an 18-page questionnaire mailed to 6,000 households in Long Island and upstate New York. The study's findings were incorporated into a marketing plan followed by the contractor,more » Island Rides, a Long Island-based ridesharing corporation, during a six-month demonstration project. By using the promotional techniques identified in the study, Island Rides experienced a 68% increase in ride-sharing applications during this successful demonstration. The results of both the study and the demonstration are presented in the report.« less

Increasing Donations to Supermarket Food-Bank Bins Using Proximal Prompts

ERIC Educational Resources Information Center

Farrimond, Samantha J.; Leland, Louis S., Jr.

2006-01-01

There has been little research into interventions to increase participation in donating items to food-bank bins. In New Zealand, there has been an increased demand from food banks (Stewart, 2002). This study demonstrated that point-of-sale prompts can be an effective method of increasing donations to a supermarket food-bank bin. (Contains 1…

An analysis of heat effects in different subpopulations of Bangladesh

NASA Astrophysics Data System (ADS)

Burkart, Katrin; Breitner, Susanne; Schneider, Alexandra; Khan, Md. Mobarak Hossain; Krämer, Alexander; Endlicher, Wilfried

2014-03-01

A substantial number of epidemiological studies have demonstrated an association between atmospheric conditions and human all-cause as well as cause-specific mortality. However, most research has been performed in industrialised countries, whereas little is known about the atmosphere-mortality relationship in developing countries. Especially with regard to modifications from non-atmospheric conditions and intra-population differences, there is a substantial research deficit. Within the scope of this study, we aimed to investigate the effects of heat in a multi-stratified manner, distinguishing by the cause of death, age, gender, location and socio-economic status. We examined 22,840 death counts using semi-parametric Poisson regression models, adjusting for a multitude of potential confounders. Although Bangladesh is dominated by an increase of mortality with decreasing (equivalent) temperatures over a wide range of values, the findings demonstrated the existence of partly strong heat effects at the upper end of the temperature distribution. Moreover, the study demonstrated that the strength of these heat effects varied considerably over the investigated subgroups. The adverse effects of heat were particularly pronounced for males and the elderly above 65 years. Moreover, we found increased adverse effects of heat for urban areas and for areas with a high socio-economic status. The increase in, and acceleration of, urbanisation in Bangladesh, as well as the rapid aging of the population and the increase in non-communicable diseases, suggest that the relevance of heat-related mortality might increase further. Considering rising global temperatures, the adverse effects of heat might be further aggravated.

Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding

PubMed Central

Sharma, Jyoti; Rathnayaka, Nuvan; Green, Charles; Moeller, F. Gerard; Schmitz, Joy M.; Shoham, Daniel; Dougherty, Anne Hamilton

2014-01-01

Background Few studies have examined the effects of chronic cocaine use on the resting surface electrocardiogram (ECG) between exposures to cocaine. Methods 12-lead ECGs from 97 treatment-seeking cocaine-dependent subjects were compared to ECG parameters from 8513 non-cocaine-using control subjects from the Atherosclerosis Risk in Communities study. Results After matching and adjusting for relevant covariates, cocaine use demonstrated large and statistically reliable effects on early repolarization, bradycardia, severe bradycardia, and heart rate. Current cocaine dependence corresponds to an increased odds of demonstrating early repolarization by a factor of 4.92 and increased odds of bradycardia and severe bradycardia by factors 3.02 and 5.11, respectively. Conclusion This study demonstrates the novel finding that long-lasting effects of cocaine use on both the cardiac conduction and the autonomic nervous system pose a risk of adverse cardiovascular events between episodes of cocaine use, and that bradycardia is a marker of chronic cocaine use. PMID:24621090

Production of interleukin-10 by human bronchogenic carcinoma.

PubMed Central

Smith, D. R.; Kunkel, S. L.; Burdick, M. D.; Wilke, C. A.; Orringer, M. B.; Whyte, R. I.; Strieter, R. M.

1994-01-01

Interleukin-10 (IL-10) is a recently characterized cytokine with suppressive activity against various aspects of the cellular immune response. Our laboratory has previously demonstrated that another anti-inflammatory cytokine, IL-1 receptor antagonist (IRAP) is produced and secreted by human bronchogenic carcinomas. We speculated that tumor production of IRAP may mitigate host responses and confer increased tumor viability. In this study, we investigated the capacity of human bronchogenic tumors to produce IL-10 as another possible mechanism to attenuate host defenses. We found increased levels of antigenic IL-10 in tissue homogenates of human bronchogenic carcinomas compared with normal lung tissue (13.69 +/- 2.87 versus 5.84 +/- 0.84 ng/mg total protein). Immunohistochemical staining of tumors illustrate primary localization of antigenic IL-10 to individual tumor cells. Analysis of supernatants of several unstimulated human bronchogenic cell lines in vitro demonstrated the ability of tumor cells to constitutively produce IL-10. Functional studies of mononuclear cells, cultured in the presence of conditioned medium from a bronchogenic cell line, demonstrated their increased tumor necrosis factor and IL-6 production with the addition of neutralizing antibodies to IL-10. These findings demonstrate that human bronchogenic carcinomas elaborate functional IL-10, which may significantly impair immune effector cell function and enable the tumor to evade host defenses. Images Figure 1 Figure 2 PMID:8030748

Levothyroxine Dosing Following Bariatric Surgery.

PubMed

Gadiraju, Silpa; Lee, Clare J; Cooper, David S

2016-10-01

Based on the mechanisms of drug absorption, increased levothyroxine requirements are expected after bariatric surgery. However, there are conflicting data on this topic. This review evaluates the effects of bariatric surgery on levothyroxine dosing. Data were obtained from PubMed, Scopus, and review of published bibliographies. Six of 10 studies demonstrated decreased postoperative requirements. Most demonstrated correlations between weight loss and dose. Only 3 case reports and 1 case series demonstrated increased levothyroxine requirements, attributed to malabsorption. The loss of both fat and lean body mass may counteract malabsorptive effects from surgery, resulting in decreased postoperative levothyroxine requirements. In addition, the reversal of impaired levothyroxine pharmacokinetics and an altered set point of thyroid hormone homeostasis may also contribute to postoperative levothyroxine reductions.

Radiation Fibrosis of the Vocal Fold: From Man to Mouse

PubMed Central

Johns, Michael M.; Kolachala, Vasantha; Berg, Eric; Muller, Susan; Creighton, Frances X.; Branski, Ryan C.

2013-01-01

Objectives To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis to ultimately develop both treatment and prevention paradigms. Design Translational study using archived human and fresh murine irradiated vocal fold tissue. Methods 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis were identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray as well as real-time transcriptional analyses was performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. Results Human irradiated vocal folds demonstrated increased collagen transcription with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-β increased in the lamina propria. Conclusion Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability that occurs in patients following laryngeal irradiation. Irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis. PMID:23242839

Game-Based Augmented Visual Feedback for Enlarging Speech Movements in Parkinson's Disease.

PubMed

Yunusova, Yana; Kearney, Elaine; Kulkarni, Madhura; Haworth, Brandon; Baljko, Melanie; Faloutsos, Petros

2017-06-22

The purpose of this pilot study was to demonstrate the effect of augmented visual feedback on acquisition and short-term retention of a relatively simple instruction to increase movement amplitude during speaking tasks in patients with dysarthria due to Parkinson's disease (PD). Nine patients diagnosed with PD, hypokinetic dysarthria, and impaired speech intelligibility participated in a training program aimed at increasing the size of their articulatory (tongue) movements during sentences. Two sessions were conducted: a baseline and training session, followed by a retention session 48 hr later. At baseline, sentences were produced at normal, loud, and clear speaking conditions. Game-based visual feedback regarding the size of the articulatory working space (AWS) was presented during training. Eight of nine participants benefited from training, increasing their sentence AWS to a greater degree following feedback as compared with the baseline loud and clear conditions. The majority of participants were able to demonstrate the learned skill at the retention session. This study demonstrated the feasibility of augmented visual feedback via articulatory kinematics for training movement enlargement in patients with hypokinesia due to PD. https://doi.org/10.23641/asha.5116840.

Bisphenol A induces corticotropin-releasing hormone expression in the placental cells JEG-3.

PubMed

Huang, Hui; Tan, Wenjuan; Wang, C C; Leung, Lai K

2012-11-01

Bisphenol A is utilized to make polycarbonate plastics and is an environmental pollutant. Recent research has indicated that it is an endocrine disruptor and may interfere with reproduction. Placental corticotrophin-releasing hormone (CRH) is a peptide hormone which is involved in fetal development. Increased plasma CRH is associated with elevated risk of premature delivery. In the present study, we demonstrated that bisphenol A increased CRH mRNA expression in the placental JEG-3 cells at or above 25μM. Reporter gene assay also demonstrated that bisphenol A could induce CRH gene transactivity. Since cyclic AMP response element (CRE) is a major regulatory element located in CRH promoter, the sequence-specific binding activity was investigated by using electrophoretic mobility shift assay. Our data indicated that bisphenol A increased the CRE binding activity. Western analysis further illustrated that PKA could be the signal triggering the CRE binding and CRH gene transactivation. In summary, the present study demonstrated that bisphenol A could induce CRH expression in placental cells and the underlying signal transduction pathway was also described. Copyright © 2012 Elsevier Inc. All rights reserved.

Hepatoprotective effects of lycopene on liver enzymes involved in methionine and xenobiotic metabolism in hyperhomocysteinemic rats.

PubMed

Yefsah-Idres, Aicha; Benazzoug, Yasmina; Otman, Amel; Latour, Alizée; Middendorp, Sandrine; Janel, Nathalie

2016-06-15

Hyperhomocysteinemia, defined by an increased plasma homocysteine level, is commonly associated with chronic liver diseases. A link between the elevated homocysteine level and oxidative stress has been demonstrated. Indeed the pathogenesis of liver diseases in the case of hyperhomocysteinemia could be due to this production of oxidative stress. Many studies have demonstrated the antioxidative properties of lycopene, a carotenoid. Therefore, the present study was designed to induce hyperhomocysteinemia in male Wistar rats in order to analyze the effect of lycopene supplementation on homocysteine metabolism, on phase I and phase II xenobiotic-metabolizing enzyme activities, and on liver injury by histological examination and analysis of biochemical markers. We found that rats with a high methionine diet showed abnormal histological features, with an increase of serum homocysteine, alanine aminotransferase and aspartate aminotransferase levels, decreased hepatic cystathionine beta synthase and S-adenosyl-homocysteine hydrolase activities and an increased hepatic malondialdehyde level. We demonstrated the reversal effect of lycopene supplementation on hyperhomocysteinemia. Taken together, these findings provide additional clues on the hepatoprotective effects of lycopene.

Slug promoted vasculogenic mimicry in hepatocellular carcinoma

PubMed Central

Sun, Dan; Sun, Baocun; Liu, Tieju; Zhao, Xiulan; Che, Na; Gu, Qiang; Dong, Xueyi; Yao, Zhi; Li, Rui; Li, Jing; Chi, Jiadong; Sun, Ran

2013-01-01

Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumour cells to mimic the pattern of embryonic vasculogenic networks. Epithelial–mesenchymal transition (EMT) regulator slug have been implicated in the tumour invasion and metastasis of human hepatocellular carcinoma (HCC). However, the relationship between slug and VM formation is not clear. In the study, we demonstrated that slug expression was associated with EMT and cancer stem cell (CSCs) phenotype in HCC patients. Importantly, slug showed statistically correlation with VM formation. We consistently demonstrated that an overexpression of slug in HCC cells significantly increased CSCs subpopulation that was obvious by the increased clone forming efficiency in soft agar and by flowcytometry analysis. Meantime, the VM formation and VM mediator overexpression were also induced by slug induction. Finally, slug overexpression lead to the maintenance of CSCs phenotype and VM formation was demonstrated in vivo. Therefore, the results of this study indicate that slug induced the increase and maintenance of CSCs subpopulation and contributed to VM formation eventually. The related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis. PMID:23815612

Peroxisome proliferator-activated receptor gamma modulation and lipogenic response in adipocytes of small-for-gestational age offspring

PubMed Central

2012-01-01

Background Small-for-gestational age (SGA) at birth increases risk of development of adult obesity and insulin resistance. A model of SGA rat offspring has been shown to exhibit increased adipose tissue expression of a key adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), and increased fatty acid de novo synthesis during the nursing period, prior to onset of obesity. PPARγ agonists have been studied for potential use in the prevention of insulin resistance. Moreover, SGA adipocytes exhibit age-dependent differences in lipogenesis as mediated by PPARγ. The effects of PPARγ modulators on lipogenic gene expression and de novo lipogenesis on the age-dependent changes in SGA adipocytes are not known. The objectives of this study were: 1) to determine the adipogenic and lipogenic potential in SGA adipocytes at postnatal day 1 (p1) and day 21 (p21), 2) to determine how the PPARγ activator- and repressor-ligands affect the lipogenic potential, and 3) to determine the fatty acid metabolic response to PPARγ activator-ligand treatment. Methods Primary adipocyte cultures from p1 and p21 SGA and Control male offspring were established from a known maternal food-restriction model of SGA. Cell proliferation and Oil Red O (ORO) staining were quantified. Adipocytes were treated with increasing doses of rosiglitazone or bisphenol-A diglycidyl ether (BADGE). PPARγ and SREBP1 protein expression were determined. De novo lipogenesis with rosiglitazone treatment at p21 was studied using 50% U13C-glucose and gas chromatography/mass spectrometry. Results At p1 and p21, SGA demonstrated increased cell proliferation and increased ORO staining. At p21, SGA demonstrated increased lipogenic gene expression and increased glucose-mediated fatty acid de novo synthesis compared with Controls. In response to rosiglitazone, SGA adipocytes further increased glucose utilization for fatty acid synthesis. SGA lipogenic gene expression demonstrated resistance to BADGE treatment. Conclusions SGA adipocytes exhibit an enhanced adipogenic and lipogenic potential in early postnatal life. By p21, SGA demonstrated resistance to PPARγ repressor-ligand treatment, and selective response to high dose PPARγ activator-ligand treatment in adipogenic and lipogenic gene expression. p21 SGA adipocytes revealed increased fatty acid de novo synthesis through a complex relationship with glucose metabolism. PMID:22726273

Physical stress primes the immune response of Galleria mellonella larvae to infection by Candida albicans.

PubMed

Mowlds, Peter; Barron, Aoife; Kavanagh, Kevin

2008-05-01

Larvae of the greater wax moth (Galleria mellonella) that had been subjected to physical stress by shaking in cupped hands for 2 min showed reduced susceptibility to infection by Candida albicans when infected 24 h after the stress event. Physically stressed larvae demonstrated an increase in haemocyte density and elevated mRNA levels of galiomicin and an inducible metalloproteinase inhibitor (IMPI) but not transferrin or gallerimycin. In contrast, previous work has demonstrated that microbial priming of larvae resulted in the induction of all four genes. Examination of the expression of proteins in the insect haemolymph using 2D electrophoresis and MALDI TOF analysis revealed an increase in the intensity of a number of peptides showing some similarities with proteins associated with the insect immune response to infection. This study demonstrates that non-lethal physical stress primes the immune response of G. mellonella and this is mediated by elevated haemocyte numbers, increased mRNA levels of genes coding for two antimicrobial peptides and the appearance of novel peptides in the haemolymph. This work demonstrates that physical priming increases the insect immune response but the mechanism of this priming is different to that induced by low level exposure to microbial pathogens.

Biomolecule detection based on Si single-electron transistors for practical use

NASA Astrophysics Data System (ADS)

Nakajima, Anri; Kudo, Takashi; Furuse, Sadaharu

2013-07-01

Experimental and theoretical analyses demonstrated that ultra-sensitive biomolecule detection can be achieved using a Si single-electron transistor (SET). A multi-island channel structure was used to enable room-temperature operation. Coulomb oscillation increases transconductance without increasing channel width, which increases detection sensitivity to a charged target. A biotin-modified SET biosensor was used to detect streptavidin at a dilute concentration. In addition, an antibody-functionalized SET biosensor was used for immunodetection of prostate-specific antigen, demonstrating its suitability for practical use. The feasibility of ultra-sensitive detection of biomolecules for practical use by using a SET biosensor was clearly proven through this systematic study.

Self-Mobilization Using a Foam Roller Versus a Roller Massager: Which Is More Effective for Increasing Hamstrings Flexibility?

PubMed

DeBruyne, Danielle M; Dewhurst, Marina M; Fischer, Katelyn M; Wojtanowski, Michael S; Durall, Chris

2017-01-01

Clinical Scenario: Increasing the length of the muscle-tendon unit may prevent musculotendinous injury. Various methods have been proposed to increase muscle-tendon flexibility, including self-mobilization using foam rollers or roller massagers, although the effectiveness of these devices is uncertain. This review was conducted to determine if the use of foam rollers or roller massagers to improve hamstrings flexibility is supported by moderate- to high-quality evidence. Are foam rollers or roller massagers effective for increasing hamstrings flexibility in asymptomatic physically active adults? Summary of Key Findings: The literature was searched for studies on the effects of using foam rollers or roller massagers to increase hamstrings flexibility in asymptomatic physically active adults. Four randomized controlled trials were included; 2 studies provided level 2 or 3 evidence regarding foam rollers and 2 studies provided level 2 or 3 evidence regarding roller massagers. Both roller-massager studies reported increases in hamstrings flexibility after treatment. Data from the foam-roller studies did not demonstrate a statistically significant increase in hamstrings flexibility, but 1 study did demonstrate a strong effect size. Clinical Bottom Line: The reviewed moderate-quality studies support the use of roller massagers but provide limited evidence on the effectiveness of foam rolling to increase hamstrings flexibility in asymptomatic physically active adults. Flexibility gains may be improved by a longer duration of treatment and administration by a trained therapist. Gains appear to decline rapidly postrolling. Neither device has been shown to confer a therapeutic benefit superior to static stretching, and the effectiveness of these devices for preventing injury is unknown. Strength of Recommendation: Grade B evidence supports the use of roller massagers to increase hamstrings flexibility in asymptomatic physically active adults.

Power Doppler evaluation of joint effusions: investigation in a rabbit model.

PubMed

Strouse, P J; DiPietro, M A; Teo, E L; Doi, K; Chrisp, C E

1999-08-01

To study the power Doppler findings of septic arthritis and noninfectious synovitis in an animal model. The right knees of 10 rabbits were inoculated with an aqueous suspension of Staphylococcus aureus. The right knees of 5 rabbits were injected with talc suspension. The right knees of 5 rabbits were injected with saline. All 20 left knees were injected with saline. Serial power Doppler images were obtained using constant-imaging parameters. Images were reviewed by blinded observers who assessed for increased power Doppler signal. All 10 knees inoculated with S. aureus developed septic arthritis. Each infected rabbit knee demonstrated increased signal on power Doppler on at least one examination, ranging from 1-6 days after inoculation. Only 23 of 45 examinations of infected knees were unequivocally positive by power Doppler on examinations performed 1 to 6 days after inoculation. No knee with talc synovitis demonstrated increased power Doppler signal. No control knee demonstrated increased power Doppler signal. Increased power Doppler signal may be seen with septic arthritis; however, its intensity and timing may vary from subject to subject. A normal power Doppler examination does not exclude septic arthritis.

Beyond the Traditional Retention Data: A Qualitative Study of the Social Benefits of Living Learning Communities

ERIC Educational Resources Information Center

Arensdorf, Jill; Naylor-Tincknell, Janett

2016-01-01

Living Learning Communities (LLCs) have been shown to increase student retention rates and academic performance (Hotchkiss, Moore, & Pitts, 2006), as well as increase overall satisfaction with college (Baker & Pomerantz, 2000) and increase cognitive skills (Walker, 2003). These benefits have been demonstrated in a variety of institutions…

Historic and Ethnic Music Found to Increase Geographic Understanding: A Quasi-Experimental Study

ERIC Educational Resources Information Center

Richardson, Ronald; Brouillette, Liane

2013-01-01

This article summarizes a quasi-experimental study, which demonstrated that integration of historic and ethnic music into the American history curriculum may lead to increased knowledge of the cultural and physical geography of the United States as well as enhanced student engagement. An experiment (n = 215) conducted with eighth grade students…

STUDIES TO ADDRESS THE ASSOCIATION BETWEEN PARTICULATE MATTER (PM) EXPOSURE AND DEVELOPMENT/EXACERBATION OF LUNG INJURY, INFLAMMATION, AND INCREASED AIRWAY RESPONSIVENESS.

EPA Science Inventory

Asthma, an inflammatory airways disease, has become an urgent health problem affecting an estimated 17 million persons in the United States alone (CDC 1998 MMWR 47). Since 1979, the death rate from asthma has increased by almost 56%. Epidemiologic studies have demonstrated posit...

Fructose impairs glucose-induced hepatic triglyceride synthesis

PubMed Central

2011-01-01

Obesity, type 2 diabetes and hyperlipidemia frequently coexist and are associated with significantly increased morbidity and mortality. Consumption of refined carbohydrate and particularly fructose has increased significantly in recent years and has paralled the increased incidence of obesity and diabetes. Human and animal studies have demonstrated that high dietary fructose intake positively correlates with increased dyslipidemia, insulin resistance, and hypertension. Metabolism of fructose occurs primarily in the liver and high fructose flux leads to enhanced hepatic triglyceride accumulation (hepatic steatosis). This results in impaired glucose and lipid metabolism and increased proinflammatory cytokine expression. Here we demonstrate that fructose alters glucose-stimulated expression of activated acetyl CoA carboxylase (ACC), pSer hormone sensitive lipase (pSerHSL) and adipose triglyceride lipase (ATGL) in hepatic HepG2 or primary hepatic cell cultures in vitro. This was associated with increased de novo triglyceride synthesis in vitro and hepatic steatosis in vivo in fructose- versus glucose-fed and standard-diet fed mice. These studies provide novel insight into the mechanisms involved in fructose-mediated hepatic hypertriglyceridemia and identify fructose-uptake as a new potential therapeutic target for lipid-associated diseases. PMID:21261970

Unconscious Desire: The Affective and Motivational Aspects of Subliminal Sexual Priming.

PubMed

Gillath, Omri; Collins, Tara

2016-01-01

Sexual arousal is thought to be the result of the processing of sexual cues at two levels: conscious and unconscious. Whereas numerous studies have examined the affective and motivational responses to supraliminal (consciously processed) sexual cues, much less is known regarding the responses to subliminal (processed outside of one's awareness) sexual cues. Five studies examined responses to subliminal sexual cues. Studies 1–3 demonstrated increases in adults' positive affect following exposure to subliminal sexual cues compared to control cues. Study 4 demonstrated that the positive affect resulting from exposure to subliminal sexual cues increased motivation to further engage in a neutral task. Study 5 provided evidence suggesting that the affect and motivation found in Studies 1–4 were associated with motivation to engage in sex specifically, rather than a general approach motivation. The implications of these findings for the processing of subliminal sexual cues and for human sexuality are discussed.

Comparison of brain connectivity between Internet gambling disorder and Internet gaming disorder: A preliminary study.

PubMed

Bae, Sujin; Han, Doug Hyun; Jung, Jaebum; Nam, Ki Chun; Renshaw, Perry F

2017-12-01

Background and aims Given the similarities in clinical symptoms, Internet gaming disorder (IGD) is thought to be diagnostically similar to Internet-based gambling disorder (ibGD). However, cognitive enhancement and educational use of Internet gaming suggest that the two disorders derive from different neurobiological mechanisms. The goal of this study was to compare subjects with ibGD to those with IGD. Methods Fifteen patients with IGD, 14 patients with ibGD, and 15 healthy control subjects were included in this study. Resting-state functional magnetic resonance imaging data for all participants were acquired using a 3.0 Tesla MRI scanner (Philips, Eindhoven, The Netherlands). Seed-based analyses, the three brain networks of default mode, cognitive control, and reward circuitry, were performed. Results Both IGD and ibGD groups demonstrated decreased functional connectivity (FC) within the default-mode network (DMN) (family-wise error p < .001) compared with healthy control subjects. However, the IGD group demonstrated increased FC within the cognitive network compared with both the ibGD (p < .01) and healthy control groups (p < .01). In contrast, the ibGD group demonstrated increased FC within the reward circuitry compared with both IGD (p < .01) and healthy control subjects (p < .01). Discussion and conclusions The IGD and ibGD groups shared the characteristic of decreased FC in the DMN. However, the IGD group demonstrated increased FC within the cognitive network compared with both ibGD and healthy comparison groups.

Amygdala reactivity is inversely related to level of cannabis use in individuals with comorbid cannabis dependence and major depression.

PubMed

Cornelius, Jack R; Aizenstein, Howard J; Hariri, Ahmad R

2010-06-01

Phan et al. (2008) recently reported that an acute dose of oral THC is associated with a decrease in threat-related amygdala reactivity during a social threat stimulus task. However, to date, those findings have not been replicated, and have not been extended to clinical studies involving smoked rather than oral cannabis. In this study, we hypothesized that level of cannabis smoked by participants in our treatment study would be inversely related to the level of threat-related amygdala reactivity. Subjects were recruited from among participants in our double-blind, placebo-controlled trial of fluoxetine in comorbid youth with cannabis dependence/major depression. The threat-related amygdala reactivity task used by Hariri et al. (2009) was completed during BOLD fMRI scans at study baseline and then again 12 weeks later at the end of the trial. Data are available from six subjects with pre-and post-treatment fMRI data. During the course of the study, five of the six subjects demonstrated a decrease in their level of cannabis use, with a mean decrease of 64%, and those persons all demonstrated an increase in their level of amygdala reactivity. One subject demonstrated an increase in their level of cannabis use (a 79% increase) during the treatment trial, and that person demonstrated a decrease in their level of amygdala reactivity. Thus, a higher level of cannabis use was consistently associated with a lower level of amygdala reactivity across all subjects (matched pairs t = 2.70, df = 5, p < 0.05, two-tailed). These findings are consistent with the reports by Phan et al. (2008) and Hariri et al. (2009) suggesting that cannabinoids have an inhibitory effect on threat-related amygdala reactivity. Copyright 2010 Elsevier Ltd. All rights reserved.

A Study of Learning-Centered Leadership Skills of Principals in Career and Technical Education Schools

ERIC Educational Resources Information Center

Rodman, Mary E.

2012-01-01

Despite years of educational reform, secondary students have demonstrated only modest increases in achievement. Career and technical education students have not demonstrated the same level of performance as non-career and technical education students. Except for teachers, principals have the greatest influence over student achievement. What should…

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

Denholm, Paul

While it may seem obvious that wind and solar 'need' energy storage to be successfully integrated into the world's electricity grids, both detailed integration studies and real-world experience have shown that storage is only one of many options that could enable substantially increased growth of these renewable resources. This talk will discuss the potential role of energy storage in the integrating wind and solar, demonstrating that in the near term perhaps less exciting -- but often more cost-effective -- alternatives will likely provide much of the grid flexibility needed to add renewable resources. The talk will also demonstrate that themore » decreasing value of PV and wind and at increased penetration creates greater opportunities for storage. It also demonstrates the fact that 'the sun doesn't always shine and the wind always doesn't blow' is only one reason why energy storage may be an increasingly attractive solution to the challenges of operating the grid of the future.« less

Sympathetic vascular transduction is augmented in young normotensive blacks

NASA Technical Reports Server (NTRS)

Ray, Chester A.; Monahan, Kevin D.

2002-01-01

The purpose of the present study was to determine sympathetic vascular transduction in young normotensive black and white adults. We hypothesized that blacks would demonstrate augmented transduction of muscle sympathetic nerve activity (MSNA) into vascular resistance. To test this hypothesis, MSNA, forearm blood flow, heart rate, and arterial blood pressure were measured during lower body negative pressure (LBNP). At rest, no differences existed in arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance (FVR). Likewise, LBNP elicited comparable responses of these variables for blacks and whites. Baseline MSNA did not differ between blacks and whites, but whites demonstrated greater increases during LBNP (28 +/- 7 vs. 55 +/- 18%, 81 +/- 21 vs. 137 +/- 42%, 174 +/- 81 vs. 556 +/- 98% for -5, -15, and -40 mmHg LBNP, respectively; P < 0.001). Consistent with smaller increases in MSNA but similar FVR responses during LBNP, blacks demonstrated greater sympathetic vascular transduction (%FVR/%MSNA) than whites (0.95 +/- 0.07 vs. 0.82 +/- 0.07 U; 0.82 +/- 0.11 vs. 0.64 +/- 0.09 U; 0.95 +/- 0.37 vs. 0.35 +/- 0.09 U; P < 0.01). In summary, young whites demonstrate greater increases in MSNA during baroreceptor unloading than age-matched normotensive blacks. However, more importantly, for a given increase in MSNA, blacks demonstrate greater forearm vasoconstriction than whites. This finding may contribute to augmented blood pressure reactivity in blacks.

Increased Lung Cancer Mortality in Taconite Mining: The Potential for Disease from Elongate Mineral Particle Exposure.

PubMed

Mandel, Jeffrey H; Ramachandran, Gurumurthy; Alexander, Bruce H

2016-02-15

Taconite mining involves potential exposure to non-asbestiform amphibole mineral fiber. More recent studies have demonstrated increased mortality from respiratory cancers and heart disease among workers in the taconite industry. This finding is not consistent with recent exposure assessment findings, nor is the toxicology of this mineral suggestive of neoplastic disease. The understanding of respiratory disease in taconite mining is hampered by the lack of exposure data to asbestiform mineral fibers that occurred in the 1950s and 1960s. Other industries with similar mineral exposure have not demonstrated definitive associations with respiratory cancer, although non-malignant respiratory disease is a consistent finding in epidemiological studies.

Association Between Serum 25-Hydroxy Vitamin D Levels and Blood Pressure Among Adolescents in Two Resource-Limited Settings in Peru.

PubMed

Tomaino, Katherine; Romero, Karina M; Robinson, Colin L; Baumann, Lauren M; Hansel, Nadia N; Pollard, Suzanne L; Gilman, Robert H; Mougey, Edward; Lima, John J; Checkley, William

2015-08-01

Serum 25-hydroxyvitamin D (25OHD) deficiency (<50 nmol/l or 20 ng/ml) has been associated with increased blood pressure (BP) in observational studies. A paucity of data on this relationship is available in Latin American or child populations. This study investigates the association between 25OHD levels and BP in adolescents at risk for vitamin D deficiency in 2 Peruvian settings. In a population-based study of 1,441 Peruvian adolescents aged 13-15 years, 1,074 (75%) provided a serum blood sample for 25OHD analysis and BP measurements. Relationships between 25OHD and BP metrics were assessed using multiple linear regressions, adjusted for anthropometrics and sociodemographic factors. 25OHD deficiency was associated with an elevated diastolic BP (DBP) (1.09 mm Hg increase, 95% confidence interval: 0.04 to 2.14; P = 0.04) compared to nondeficient adolescents. Systolic BP (SBP) trended to increase with vitamin D deficiency (1.30 mm Hg increase, 95% confidence interval: -0.13 to 2.72; P = 0.08). Mean arterial pressure (MAP) was also greater in adolescents with 25OHD (1.16 mm Hg increase, 95% confidence interval: 0.10 to 2.22; P = 0.03). SBP was found to demonstrate a U-shaped relationship with 25OHD, while DBP and MAP demonstrated inverse J-shaped relationships with serum 25OHD status. The association between 25OHD deficiency and BP was not different across study sites (all P ≥ 0.19). Adolescents deficient in 25OHD demonstrated increased DBP and MAP and a trend toward increased SBP, when compared to nondeficient subjects. 25OHD deficiency early in life was associated with elevated BP metrics, which may predispose risk of hypertension later in adulthood. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Examining the impacts of increased corn production on groundwater quality using a coupled modeling system

EPA Science Inventory

This study demonstrates the value of a coupled chemical transport modeling system for investigating groundwater nitrate contamination responses associated with nitrogen (N) fertilizer application and increased corn production. The coupled Community Multiscale Air Quality Bidirect...

PROBABILISTIC RISK ASSESSMENT FOR THE EFFECTS OF SOLAR ULTRAVIOLET RADIATION ON AMPHIBIANS

EPA Science Inventory

Several studies have demonstrated that exposure to solar ultraviolet (UV) radiation can cause elevated mortality and an increased prevalence of eye and limb malformations in developing amphibian larvae. From these observations scientists have hypothesized that recent increases in...

Sodium citrate inhibits the proliferation of human gastric adenocarcinoma epithelia cells

PubMed Central

Xia, Yuan; Zhang, Xulong; Bo, Agula; Sun, Juan; Li, Minhui

2018-01-01

The objective of the present study was to investigate the cytotoxic effects of sodium citrate on human gastric adenocarcinoma epithelia AGS cells. Numerous cytotoxicity-associated sodium citrate-induced effects were assessed, including cell viability and proliferation, cytokine expression and caspase activity. In vitro studies demonstrated that incubation with sodium citrate (>3.125 mM) inhibited AGS cell viability and proliferation in a dose-dependent manner. Incubation with sodium citrate for 24 h revealed that the levels of interleukin-1β (IL-1β), IL-8 and tumor necrosis factor increased with an increasing of dose of sodium citrate, whereas the IL-6 levels exhibited only a slight alteration. In addition, increases in caspase-3 and −9 activities were associated with increased duration of treatment and dosage of sodium citrate. Collectively, the results of the present study demonstrated that treatment with sodium citrate at higher concentrations or for longer durations exerts a cytotoxic effect on AGS cells via the induction of the intrinsic apoptosis pathway and the alteration in the levels of certain cytokines. PMID:29616124

The most economical cadence increases with increasing workload.

PubMed

Foss, Øivind; Hallén, Jostein

2004-08-01

Several studies have suggested that the most economical cadence in cycling increases with increasing workload. However, none of these studies have been able to demonstrate this relationship with experimental data. The purpose of this study was to test the hypothesis that the most economical cadence in elite cyclists increases with increasing workload and to explore the effect of cadence on performance. Six elite road cyclists performed submaximal and maximal tests at four different cadences (60, 80, 100 and 120 rpm) on separate days. Respiratory data was measured at 0, 50, 125, 200, 275 and 350 W during the submaximal test and at the end of the maximal test. The maximal test was carried out as an incremental test, conducted to reveal differences in maximal oxygen uptake and time to exhaustion (short-term performance) between cadences. The results showed that the lowest oxygen uptake, i.e. the best work economy, shifted from 60 rpm at 0 W to 80 rpm at 350 W ( P<0.05). No difference was found in maximal oxygen uptake among cadences ( P>0.05), while the best performance was attained at the same cadence that elicited the best work economy (80 rpm) at 350 W ( P<0.05). This study demonstrated that the most economical cadence increases with increasing workload in elite cyclists. It was further shown that work economy and performance are related during short efforts (approximately 5 min) over a wide range of cadences.

Use of radiation protraction to escalate biologically effective dose to the treatment target

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

Kuperman, V. Y.; Spradlin, G. S.; Department of Mathematics, Embry-Riddle University, Daytona Beach, Florida 32114

2011-12-15

Purpose: The aim of this study is to evaluate how simultaneously increasing fraction time and dose per fraction affect biologically effective dose for the target (BED{sub tar}) while biologically effective dose for the normal tissue (BED{sub nt}) is fixed. Methods: In this investigation, BED{sub tar} and BED{sub nt} were studied by assuming mono-exponential repair of sublethal damage with tissue dependent repair half-time. Results: Our results demonstrate that under certain conditions simultaneously increasing fraction time and dose per fraction result in increased BED{sub tar} while BED{sub nt} is fixed. The dependence of biologically effective dose on fraction time is influenced bymore » the dose rate. In this investigation we analytically determined time-varying dose rate R-tilde which minimizes BED. Changes in BED with fraction time were compared for constant dose rate and for R-tilde. Conclusions: A number of recent experimental and theoretical studies have demonstrated that slow delivery of radiation (known as radiation protraction) leads to reduced therapeutic effect because of increased repair of sublethal damage. In contrast, our analysis shows that under certain conditions simultaneously increasing fraction time and dose per fraction are radiobiologically advantageous.« less

An analysis of heat effects in different subpopulations of Bangladesh.

PubMed

Burkart, Katrin; Breitner, Susanne; Schneider, Alexandra; Khan, Md Mobarak Hossain; Krämer, Alexander; Endlicher, Wilfried

2014-03-01

A substantial number of epidemiological studies have demonstrated an association between atmospheric conditions and human all-cause as well as cause-specific mortality. However, most research has been performed in industrialised countries, whereas little is known about the atmosphere-mortality relationship in developing countries. Especially with regard to modifications from non-atmospheric conditions and intra-population differences, there is a substantial research deficit. Within the scope of this study, we aimed to investigate the effects of heat in a multi-stratified manner, distinguishing by the cause of death, age, gender, location and socio-economic status. We examined 22,840 death counts using semi-parametric Poisson regression models, adjusting for a multitude of potential confounders. Although Bangladesh is dominated by an increase of mortality with decreasing (equivalent) temperatures over a wide range of values, the findings demonstrated the existence of partly strong heat effects at the upper end of the temperature distribution. Moreover, the study demonstrated that the strength of these heat effects varied considerably over the investigated subgroups. The adverse effects of heat were particularly pronounced for males and the elderly above 65 years. Moreover, we found increased adverse effects of heat for urban areas and for areas with a high socio-economic status. The increase in, and acceleration of, urbanisation in Bangladesh, as well as the rapid aging of the population and the increase in non-communicable diseases, suggest that the relevance of heat-related mortality might increase further. Considering rising global temperatures, the adverse effects of heat might be further aggravated.

Fibromyalgia survey criteria are associated with increased postoperative opioid consumption in women undergoing hysterectomy.

PubMed

Janda, Allison M; As-Sanie, Sawsan; Rajala, Baskar; Tsodikov, Alex; Moser, Stephanie E; Clauw, Daniel J; Brummett, Chad M

2015-05-01

The current study was designed to test the hypothesis that the fibromyalgia survey criteria would be directly associated with increased opioid consumption after hysterectomy even when accounting for other factors previously described as being predictive for acute postoperative pain. Two hundred eight adult patients undergoing hysterectomy between October 2011 and December 2013 were phenotyped preoperatively with the use of validated self-reported questionnaires including the 2011 fibromyalgia survey criteria, measures of pain severity and descriptors, psychological measures, preoperative opioid use, and health information. The primary outcome was the total postoperative opioid consumption converted to oral morphine equivalents. Higher fibromyalgia survey scores were significantly associated with worse preoperative pain characteristics, including higher pain severity, more neuropathic pain, greater psychological distress, and more preoperative opioid use. In a multivariate linear regression model, the fibromyalgia survey score was independently associated with increased postoperative opioid consumption, with an increase of 7-mg oral morphine equivalents for every 1-point increase on the 31-point measure (Estimate, 7.0; Standard Error, 1.7; P < 0.0001). In addition to the fibromyalgia survey score, multivariate analysis showed that more severe medical comorbidity, catastrophizing, laparotomy surgical approach, and preoperative opioid use were also predictive of increased postoperative opioid consumption. As was previously demonstrated in a total knee and hip arthroplasty cohort, this study demonstrated that increased fibromyalgia survey scores were predictive of postoperative opioid consumption in the posthysterectomy surgical population during their hospital stay. By demonstrating the generalizability in a second surgical cohort, these data suggest that patients with fibromyalgia-like characteristics may require a tailored perioperative analgesic regimen.

In vivo Host Environment Alters Pseudomonas aeruginosa Susceptibility to Aminoglycoside Antibiotics

PubMed Central

Pan, Xiaolei; Dong, Yuanyuan; Fan, Zheng; Liu, Chang; Xia, Bin; Shi, Jing; Bai, Fang; Jin, Yongxin; Cheng, Zhihui; Jin, Shouguang; Wu, Weihui

2017-01-01

During host infection, Pseudomonas aeruginosa coordinately regulates the expression of numerous genes to adapt to the host environment while counteracting host clearance mechanisms. As infected patients take antibiotics, the invading bacteria encounter antibiotics in the host milieu. P. aeruginosa is highly resistant to antibiotics due to multiple chromosomally encoded resistant determinants. And numerous in vitro studies have demonstrated the regulatory mechanisms of antibiotic resistance related genes in response to antibiotics. However, it is not well-known how host environment affects bacterial response to antibiotics. In this study, we found that P. aeruginosa cells directly isolated from mice lungs displayed higher susceptibility to tobramycin than in vitro cultured bacteria. In vitro experiments demonstrated that incubation with A549 and differentiated HL60 (dHL60) cells sensitized P. aeruginosa to tobramycin. Further studies revealed that reactive oxygen species produced by the host cells contributed to the increased bacterial susceptibility. At the same concentration of tobramycin, presence of A549 and dHL60 cells resulted in higher expression of heat shock proteins, which are known inducible by tobramycin. Further analyses revealed decreased membrane potential upon incubation with the host cells and modification of lipopolysaccharide, which contributed to the increased susceptibility to tobramycin. Therefore, our results demonstrate that contact with host cells increased bacterial susceptibility to tobramycin. PMID:28352614

Improving oral bioavailability of resveratrol by a UDP-glucuronosyltransferase inhibitory excipient-based self-microemulsion.

PubMed

Yang, Fei-Fei; Zhou, Jing; Hu, Xiao; Cong, Zhao-Qing; Liu, Chun-Yu; Pan, Rui-Le; Chang, Qi; Liu, Xin-Min; Liao, Yong-Hong

2018-03-01

Self-microemulsifying (SME) drug delivery system has been developed to increase oral bioavailabilities, and inhibitory excipients are capable of improving oral bioavailability by inhibiting enzyme mediated intestinal metabolism. However, the potential of enzyme inhibitory excipients containing SME in boosting resveratrol bioavailability remains largely uninvestigated. In this study, we set out to prepare SME-1 with UGT inhibitory excipients (excipients without inhibitory activities named SME-2 as control) to increase the bioavailability of RES by inhibiting intestinal metabolism. Results demonstrated that similar physicochemical properties such as size, polydistribution index and in vitro release, cellular uptake and permeability in Caco-2 cells as well as in vivo lymphatic distribution between inhibitory SME-1 and non-inhibitory SME-2 were observed. In vivo study demonstrated that the molar ratios of RES-G/RES were 7.25±0.48 and 5.06±2.42 for free drug and SME-2, respectively, and the molar ratio decreased to 0.36±0.10 in SME-1 group. Pharmacokinetic study confirmed that the inhibitory excipients containing SME demonstrated potential in increasing bioavailability of RES from 6.5% for the free RES and 12.9% for SME-2 to 76.1% in SME-1 through modulating the glucuronidation by UGT inhibitory excipients. Copyright © 2018 Elsevier B.V. All rights reserved.

Learning Increases the Survival of Newborn Neurons Provided that Learning Is Difficult to Achieve and Successful

ERIC Educational Resources Information Center

Curlik, Daniel M., II; Shors, Tracey J.

2011-01-01

Learning increases neurogenesis by increasing the survival of new cells generated in the adult hippocampal formation [Shors, T. J. Saving new brain cells. "Scientific American," 300, 46-52, 2009]. However, only some types of learning are effective. Recent studies demonstrate that animals that learn the conditioned response (CR) but require more…

Using goal setting and feedback to increase weekly running distance.

PubMed

Wack, Stephanie R; Crosland, Kimberly A; Miltenberger, Raymond G

2014-01-01

We evaluated goal setting with performance feedback to increase running distance among 5 healthy adults. Participants set a short-term goal each week and a long-term goal to achieve on completion of the study. Results demonstrated that goal setting and performance feedback increased running distance for all participants. © Society for the Experimental Analysis of Behavior.

Effectiveness of Foreign Humanitarian Assistance Operations

DTIC Science & Technology

2017-06-09

activities and money spent. This study investigates the lasting contribution to bilateral partnership from the conduct of U.S. military humanitarian...increasing scrutiny to demonstrate the effectiveness of activities and money spent. This study investigates the lasting contribution to bilateral...increased discussions concerning the money spent on U.S. overseas security commitments. Stemming from the Budget Control Act of 2011, which included

Graphene Nanoplatelet Reinforced Tantalum Carbide

DTIC Science & Technology

2015-08-27

testing showed an increase in thermal conductivity in GNP reinforced composites resulting in a reduction of peak sample surface temperature. This study...showed an increase in thermal conductivity in GNP reinforced composites resulting in a reduction of peak sample surface temperature. This study resulted...Wetting angle measurements are conducted to demonstrate the effectiveness of the PLC coating . Mechanical properties of the GrF-PLC hybrid are

Progression marker of Parkinson's disease: a 4-year multi-site imaging study.

PubMed

Burciu, Roxana G; Ofori, Edward; Archer, Derek B; Wu, Samuel S; Pasternak, Ofer; McFarland, Nikolaus R; Okun, Michael S; Vaillancourt, David E

2017-08-01

Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year decrease in striatal binding ratio in the putamen. Importantly, all longitudinal results were consistent across sites. In summary, this study demonstrates an increase over 1 year in free water in the posterior substantia nigra in a large cohort of de novo patients with Parkinson's disease from a multi-site cohort study and no change in healthy controls, and further demonstrates an increase of free water in Parkinson's disease over the course of 4 years. A key finding was that results are consistent across sites and the 1-year and 2-year increase in free water in the posterior substantia nigra predicts subsequent long-term progression on the Hoehn and Yahr staging system. Collectively, these findings demonstrate that free water in the posterior substantia nigra is a valid, progression imaging marker of Parkinson's disease, which may be used in clinical trials of disease-modifying therapies. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Efficacy of anti-osteoporotic medications in patients with type 1 and 2 diabetes mellitus: a systematic review.

PubMed

Anagnostis, Panagiotis; Paschou, Stavroula A; Gkekas, Nifon N; Artzouchaltzi, Aikaterini-Maria; Christou, Konstantinos; Stogiannou, Dimitrios; Vryonidou, Andromachi; Potoupnis, Michael; Goulis, Dimitrios G

2018-06-01

Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with bone fragility and increased fracture risk. However, little is known regarding the effect of anti-osteoporotic treatment on bone mineral density (BMD) and/or fracture risk in these patients. We aimed to systematically investigate the efficacy of anti-osteoporotic medications in patients with diabetes in comparison with non-diabetic subjects. MEDLINE and Scopus databases were searched (up to 31st October 2017). Nine studies fulfilled the pre-defined inclusion criteria [patients with T2DM (n = 8) or either T1DM or T2DM (n = 1)]. Regarding fracture risk, five studies were identified. Alendronate demonstrated comparable vertebral anti-fracture efficacy in patients with and without diabetes (n = 2), whereas non-vertebral fracture risk was either the same (n = 1) or higher in diabetic patients (n = 1). Raloxifene also demonstrated comparable vertebral anti-fracture efficacy in both groups (n = 2), without any effect on non-vertebral fractures in either group. In one study, diabetic patients exposed to raloxifene demonstrated the same vertebral and non-vertebral fracture risk with non-diabetic patients. Teriparatide (n = 1) demonstrated the same non-vertebral fracture rates in both patients with and without T2DM. Regarding BMD, equal increases in spine BMD were observed with alendronate (n = 4), risedronate (n = 1), and teriparatide (n = 1). With respect to hip BMD, similar increases were observed with teriparatide (n = 1), whereas data regarding alendronate were controversial (n = 3). No eligible study was found for zoledronic acid, ibandronate, strontium ranelate, denosumab, or bazedoxifene. The presence of diabetes does not alter anti-osteoporotic treatment response, regarding BMD increase and vertebral fracture risk reduction.

Polycyclic Aromatic Hydrocarbons (PAHs) Mediate Transcriptional Activation of the ATP Binding Cassette Transporter ABCB6 Gene via the Aryl Hydrocarbon Receptor (AhR)*

PubMed Central

Chavan, Hemantkumar; Krishnamurthy, Partha

2012-01-01

Liver is endowed with a mechanism to induce hepatic cytochromes P450 (CYP450s) in response to therapeutic drugs and environmental contaminants, leading to increased detoxification and elimination of the xenobiotics. Each CYP450 is composed of an apoprotein moiety and a heme prosthetic group, which is required for CYP450 activity. Thus, under conditions of CYP450 induction, there is a coordinate increase in heme biosynthesis to compensate for the increased expression of CYP450s. ABCB6, a mitochondrial ATP binding cassette transporter, which regulates coproporphyrinogen transport from the cytoplasm into the mitochondria to complete heme biosynthesis, represents a previously unrecognized rate-limiting step in heme biosynthesis. However, it is not known if exposure to drugs and environmental contaminants induces ABCB6 expression, to assure an adequate and apparently coordinated supply of heme for the generation of functional cytochrome holoprotein. In the present study, we demonstrate that polycyclic aromatic hydrocarbons (PAHs), the widely distributed environmental toxicants shown to induce porphyrin accumulation causing hepatic porphyria, up-regulate ABCB6 expression in both mice and humans. Using siRNA technology and Abcb6 knock-out mice, we demonstrate that PAH-mediated increase in hepatic porphyrins is compromised in the absence of ABCB6. Moreover, in vivo studies in aryl hydrocarbon receptor (AhR) knock-out mice demonstrate that PAH induction of ABCB6 is mediated by AhR. Promoter activation studies combined with electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrate direct interactions between the AhR binding sites in the ABCB6 promoter and the AhR receptor, implicating drug activation mechanisms for ABCB6 similar to those found in inducible cytochrome P450s. These studies are the first to describe direct transcriptional activation of both mouse and human ABCB6 by xenobiotics. PMID:22761424

The effects of mild and severe traumatic brain injury on speed of information processing as measured by the computerized tests of information processing (CTIP).

PubMed

Tombaugh, Tom N; Rees, Laura; Stormer, Peter; Harrison, Allyson G; Smith, Andra

2007-01-01

In spite of the fact that reaction time (RT) measures are sensitive to the effects of traumatic brain injury (TBI), few RT procedures have been developed for use in standard clinical evaluations. The computerized test of information processing (CTIP) [Tombaugh, T. N., & Rees, L. (2000). Manual for the computerized tests of information processing (CTIP). Ottawa, Ont.: Carleton University] was designed to measure the degree to which TBI decreases the speed at which information is processed. The CTIP consists of three computerized programs that progressively increase the amount of information that is processed. Results of the current study demonstrated that RT increased as the difficulty of the CTIP tests increased (known as the complexity effect), and as severity of injury increased (from mild to severe TBI). The current study also demonstrated the importance of selecting a non-biased measure of variability. Overall, findings suggest that the CTIP is an easy to administer and sensitive measure of information processing speed.

Interaction of Stress and Anxiogenic Drugs on Behaviors of Rats and Antagonism with Indomethacin

DTIC Science & Technology

2001-10-19

to result from a cascade of effects secondary to increased 5- HT . Stress increases prostaglandin levels in the plasma , which stimulate the...this effect is mediated via a stress-induced increase in plasma 5- HT levels. Data demonstrating that blocking serotonin Of effects secondary to...correlated with rises in plasma 5- HT . Another study using the same paradigm found essentially the same effect but, in th is study, adult rats were also

Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature.

PubMed

Maagaard, Marie; Heiberg, Johan

2016-09-01

Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3-168 patients, mean age-ranges of 5-33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22-34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O 2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac function should be integrated in the clinical assessment of patients with PE.

Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature

PubMed Central

Heiberg, Johan

2016-01-01

Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3–168 patients, mean age-ranges of 5–33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22–34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac function should be integrated in the clinical assessment of patients with PE. PMID:27747182

Use of cardiocerebral resuscitation or AHA/ERC 2005 Guidelines is associated with improved survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis.

PubMed

Salmen, Marcus; Ewy, Gordon A; Sasson, Comilla

2012-01-01

To determine whether the use of cardiocerebral resuscitation (CCR) or AHA/ERC 2005 Resuscitation Guidelines improved patient outcomes from out-of-hospital cardiac arrest (OHCA) compared to older guidelines. Systematic review and meta-analysis. MEDLINE, EMBASE, Web of Science and the Cochrane Library databases. We also hand-searched study references and consulted experts. Design: randomised controlled trials and observational studies. OHCA patients, age >17 years. 'Control' protocol versus 'Study' protocol. 'Control' protocol defined as AHA/ERC 2000 Guidelines for cardiopulmonary resuscitation (CPR). 'Study' protocol defined as AHA/ERC 2005 Guidelines for CPR, or a CCR protocol. Survival to hospital discharge. High-quality or medium-quality studies, as measured by the Newcastle Ottawa Scale using predefined categories. Twelve observational studies met inclusion criteria. All the three studies using CCR demonstrated significantly improved survival compared to use of AHA 2000 Guidelines, as did five of the nine studies using AHA/ERC 2005 Guidelines. Pooled data demonstrate that use of a CCR protocol has an unadjusted OR of 2.26 (95% CI 1.64 to 3.12) for survival to hospital discharge among all cardiac arrest patients. Among witnessed ventricular fibrillation/ventricular tachycardia (VF/VT) patients, CCR increased survival by an OR of 2.98 (95% CI 1.92 to 4.62). Studies using AHA/ERC 2005 Guidelines showed an overall trend towards increased survival, but significant heterogeneity existed among these studies. We demonstrate an association with improved survival from OHCA when CCR protocols or AHA/ERC 2005 Guidelines are compared to use of older guidelines. In the subgroup of patients with witnessed VF/VT, there was a threefold increase in OHCA survival when CCR was used. CCR appears to be a promising resuscitation protocol for Emergency Medical Services providers in increasing survival from OHCA. Future research will need to be conducted to directly compare AHA/ERC 2010 Guidelines with the CCR approach.

The more the merrier? Increasing group size may be detrimental to decision-making performance in nominal groups.

PubMed

Amir, Ofra; Amir, Dor; Shahar, Yuval; Hart, Yuval; Gal, Kobi

2018-01-01

Demonstrability-the extent to which group members can recognize a correct solution to a problem-has a significant effect on group performance. However, the interplay between group size, demonstrability and performance is not well understood. This paper addresses these gaps by studying the joint effect of two factors-the difficulty of solving a problem and the difficulty of verifying the correctness of a solution-on the ability of groups of varying sizes to converge to correct solutions. Our empirical investigations use problem instances from different computational complexity classes, NP-Complete (NPC) and PSPACE-complete (PSC), that exhibit similar solution difficulty but differ in verification difficulty. Our study focuses on nominal groups to isolate the effect of problem complexity on performance. We show that NPC problems have higher demonstrability than PSC problems: participants were significantly more likely to recognize correct and incorrect solutions for NPC problems than for PSC problems. We further show that increasing the group size can actually decrease group performance for some problems of low demonstrability. We analytically derive the boundary that distinguishes these problems from others for which group performance monotonically improves with group size. These findings increase our understanding of the mechanisms that underlie group problem-solving processes, and can inform the design of systems and processes that would better facilitate collective decision-making.

A pilot study investigating of the nature of point-of-sale alcohol promotions in bottle shops in a large Australian regional city.

PubMed

Jones, Sandra C; Lynch, Melissa

2007-08-01

The promotion of alcohol by retailers and media can contribute to a culture of excessive alcohol consumption, but the effect of non-advertising alcohol promotions has largely been neglected. This study sought to gather initial data on this important area. An observational study of alcohol point-of-sale promotions in the Wollongong CBD area, conducted in July-August 2005. We identified 17 different promotions in three categories: gift with purchase; competitions; and buy some, get some free. Given previous research demonstrating the relationship between increased alcohol consumption and both ownership of alcohol-related merchandise and reduced per unit price, it appears that point-of-sale promotions may have the potential to further increase alcohol consumption among young people. Only when the extent and impact of such promotions is demonstrated will we be in a position to effectively advocate for appropriate regulations to ensure young people are not exposed to marketing strategies that further increase their exposure to alcohol-related harms.

Effects of endocrine disrupting chemicals from leather industry effluents on male reproductive system.

PubMed

Kumar, Vikas; Majumdar, Chandrajeetbalo; Roy, Partha

2008-09-01

The leather tanning industry is characterized by the production of different kinds of effluents, generated in each step of leather processing. These effluents have various chemical compounds which may cause toxicity and endocrine disruption and are thus known as endocrine disrupting chemicals (EDC). This study was aimed to examine the androgenic potential of leather industry effluents collected from northern region of India. Hershberger assay data showed a significant increase (p<0.05) in the weight and structure of sex accessory tissues of castrated rats. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated a significant change (p<0.05) in the expression patterns of the major steroidogenic enzymes in adrenal and testes namely, cytochrome P450scc, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydorgenase in castrated and intact rats. This was further supported by increased enzymatic activities measured in vitro spectrophotometrically. Serum hormone profile demonstrated a dose dependent increase in testicular and adrenal testosterone productions in intact and castrated rats, respectively. This was further supported by decreased level of gonadotrophic hormones (LH and FSH) in treated groups of animals. Further, the effluent treatment resulted in the development of hyperplasia in seminiferous tubules of testes in treated rats as evident from histopathological studies and about two-fold increases in daily sperm production. On analysis of water samples using GC-MS, it was found to contain various aromatic compounds (nonylphenol, hexaclrobenzene and several azo dyes) some of which independently demonstrated similar effects as shown by water samples. Our data suggests that the effluents from leather industry have potential EDC demonstrating androgenic activities.

Primary Cilia Modulate IHH Signal Transduction in Response to Hydrostatic Loading of Growth Plate Chondrocytes

PubMed Central

Shao, Y, Yvonne Y.; Wang, Lai; Welter, J, Jean F.; Ballock, R. Tracy

2011-01-01

Indian Hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. PMID:21930256

The slippery slope: how small ethical transgressions pave the way for larger future transgressions.

PubMed

Welsh, David T; Ordóñez, Lisa D; Snyder, Deirdre G; Christian, Michael S

2015-01-01

Many recent corporate scandals have been described as resulting from a slippery slope in which a series of small infractions gradually increased over time (e.g., McLean & Elkind, 2003). However, behavioral ethics research has rarely considered how unethical behavior unfolds over time. In this study, we draw on theories of self-regulation to examine whether individuals engage in a slippery slope of increasingly unethical behavior. First, we extend Bandura's (1991, 1999) social-cognitive theory by demonstrating how the mechanism of moral disengagement can reduce ethicality over a series of gradually increasing indiscretions. Second, we draw from recent research connecting regulatory focus theory and behavioral ethics (Gino & Margolis, 2011) to demonstrate that inducing a prevention focus moderates this mediated relationship by reducing one's propensity to slide down the slippery slope. We find support for the developed model across 4 multiround studies. (c) 2015 APA, all rights reserved.

Artificial selection increased body weight but induced increase of runs of homozygosity in Hanwoo cattle

PubMed Central

Kim, Kwondo; Jung, Jaehoon; Caetano-Anollés, Kelsey; Sung, Samsun; Yoo, DongAhn; Choi, Bong-Hwan; Kim, Hyung-Chul; Jeong, Jin-Young; Cho, Yong-Min; Park, Eung-Woo; Choi, Tae-Jeong; Park, Byoungho; Lim, Dajeong

2018-01-01

Artificial selection has been demonstrated to have a rapid and significant effect on the phenotype and genome of an organism. However, most previous studies on artificial selection have focused solely on genomic sequences modified by artificial selection or genomic sequences associated with a specific trait. In this study, we generated whole genome sequencing data of 126 cattle under artificial selection, and 24,973,862 single nucleotide variants to investigate the relationship among artificial selection, genomic sequences and trait. Using runs of homozygosity detected by the variants, we showed increase of inbreeding for decades, and at the same time demonstrated a little influence of recent inbreeding on body weight. Also, we could identify ~0.2 Mb runs of homozygosity segment which may be created by recent artificial selection. This approach may aid in development of genetic markers directly influenced by artificial selection, and provide insight into the process of artificial selection. PMID:29561881

A Review on the Role of Inflammation in Attention-Deficit/Hyperactivity Disorder.

PubMed

Leffa, Douglas Teixeira; Torres, Iraci L S; Rohde, Luis Augusto

2018-06-06

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition that impairs quality of life in social, academic, and occupational contexts for both children and adults. Although a strong neurobiological basis has been demonstrated, the pathophysiology of ADHD is still poorly understood. Among the proposed mechanisms are glial activation, neuronal damage and degeneration, increased oxidative stress, reduced neurotrophic support, altered neurotransmitter metabolism, and blood-brain barrier disruption. In this way, a potential role of inflammation has been increasingly researched. However, evidence for the involvement of inflammation in ADHD is still scarce and comes mainly from (1) observational studies showing a strong comorbidity of ADHD with inflammatory and autoimmune disorders; (2) studies evaluating serum inflammatory markers; and (3) genetic studies. A co-occurrence of ADHD with inflammatory disorders has been demonstrated in a large number of subjects, suggesting a range of underlying mechanisms such as an altered immune response, common genetics, and environmental links. The evaluation of serum inflammatory markers has provided mixed results, likely due to the small sample sizes and high heterogeneity between biomarkers. However, there is evidence that increased inflammation during the early development may be a risk factor for ADHD symptoms. Although genetic studies have demonstrated a potential role for inflammation in this disorder, there is no clear evidence. To sum up, inflammation may be an important mechanism in ADHD pathophysiology, but more studies are still needed for a more precise conclusion. © 2018 S. Karger AG, Basel.

Effect of preventive dentistry training program for caregivers in community facilities on caregiver and client behavior and client oral hygiene.

PubMed

Glassman, Paul; Miller, Christine Ernst

2006-01-01

The influx of persons with developmental disabilities into community-based programs has required the development, expansion and improved integration of community-based services. The role of caregivers in these community settings has become pivotal. However, with regard to daily activities, oral hygiene is often a low priority. Few attempts have been made to study caregiver participation in oral disease prevention and practices. This study evaluated the effects of an indirect training program, where caregivers were trained but the ultimate effects were demonstrated in adult clients. In addition, these effects were demonstrated in community care settings. A multiple baseline design, across three group homes, included 11 adult clients with developmental disabilities. This study evaluated the effects of training, instruction to use training and coaching on the presence of caregivers during oral hygiene sessions, the duration of toothbrushing and plaque scores of the clients. The results of this investigation demonstrated that there was an increase in caregiver presence and duration of brushing with a concurrent decrease in plaque scores. Caregivers responding to social validation questionnaires believed that 8 out of 11 clients had increased skills. This study demonstrates that caregiver training, combined with specific instructions to use training information and coaching of caregivers, can have a positive impact on the oral health of individuals with developmental disabilities living in community settings.

[Glomerular filtration and renal volume in type II diabetes (non-insulin-dependent): study in normal and microalbuminuria patients].

PubMed

Signorini, A M; Tanganelli, I; Fondelli, C; Vattimo, A; Ferrari, F; Borgogni, P; Borgogni, L; Gragnoli, G

1991-08-01

In type 2 diabetes elevated glomerular filtration rate (GFR) and increased renal volume (RV), often accompanied to normo or microalbuminuria, were demonstrated. This condition is considered a pathogenetic factor for clinical nephropathy. As this topic is little studied in type 2 diabetes, we have investigated 73 type 2 diabetic patients (34 normo and 39 microalbuminuric), looking for a correlation between GFR, RV, hypertension, duration of diabetes and indexes of metabolic control. GFR was measured by a scintigraphy, after infusion of 99Tc-DTPA. Renal volume was determined by ultrasound scanning. Between the groups GFR and RV weren't different; elevated GFR was demonstrated in 3 patients; increased RV in 1 patient. In the hypertensive group GFR was lower than in normotensive group and in controls. Multivariate analysis in stepwise demonstrated that GFR presents a negative correlation to systolic blood pressure as in normo as in microalbuminuric patients. In the normotensive group GFR didn't correlate to the other variables. The present data suggest that in type 2 diabetes there is a little prevalence of glomerular hyperfiltration and increased renal volume and that hypertension plays a role on GFR of hypertensive diabetic patients.

Bilirubin and atherosclerotic diseases.

PubMed

Vítek, L

2017-04-05

Bilirubin is the final product of heme catabolism in the systemic circulation. For decades, increased serum/plasma bilirubin levels were considered an ominous sign of an underlying liver disease. However, data from recent years convincingly suggest that mildly elevated bilirubin concentrations are associated with protection against various oxidative stress-mediated diseases, atherosclerotic conditions being the most clinically relevant. Although scarce data on beneficial effects of bilirubin had been published also in the past, it took until 1994 when the first clinical study demonstrated an increased risk of coronary heart disease in subjects with low serum bilirubin levels, and bilirubin was found to be a risk factor for atherosclerotic diseases independent of standard risk factors. Consistent with these results, we proved in our own studies, that subjects with mild elevation of serum levels of unconjugated bilirubin (benign hyperbilirubinemia, Gilbert syndrome) have much lower prevalence/incidence of coronary heart as well as peripheral vascular disease. We have also demonstrated that this association is even more general, with serum bilirubin being a biomarker of numerous other diseases, often associated with increased risk of atherosclerosis. In addition, very recent data have demonstrated biological pathways modulated by bilirubin, which are responsible for observed strong clinical associations.

Leaky gut and mycotoxins: Aflatoxin B1 does not increase gut permeability in broiler chickens

USDA-ARS?s Scientific Manuscript database

Previous studies conducted in our laboratory have demonstrated that intestinal barrier function can be adversely affected by diet ingredients or feed restriction, resulting in increased intestinal inflammation-associated permeability. Two experiments were conducted in broilers to evaluate the effect...

INTERACTIONS OF SOLAR UV RADIATION AND DISSOLVED ORGANIC MATTER IN AQUATIC ENVIRONMENTS

EPA Science Inventory

Changes in the ozone layer over the past two decades have resulted in increases in solar ultraviolet (UV) radiation that reaches the surface of aquatic environments. Recent studies have demonstrated that these UV increases cause changes in photochemical reactions that affect the...

Early-Life Persistent Vitamin D Deficiency Alters Cardiopulmonary Responses to Particulate Matter-Enhanced Atmospheric Smog in Adult Mice

EPA Science Inventory

This study demonstrates that early-life persistent vitamin D deficiency alters the cardiopulmonary response to smog in mice and may increase risk of adverse effects. Early life nutritional deficiencies can lead to increased cardiovascular susceptibility to environme...

Aconitine "challenge" test reveals a single whole-body exposure to diesel exhaust increases cardiac arrhythmia risk in hypertensive rats

EPA Science Inventory

Epidemiological studies demonstrate a significant association between cardiac electrical dysfunction, arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electri...

High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization.

PubMed

Kastner, Elisabeth; Kaur, Randip; Lowry, Deborah; Moghaddam, Behfar; Wilkinson, Alexander; Perrie, Yvonne

2014-12-30

Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows for reproducible mixing in miliseconds on the nanoliter scale. Here we investigate microfluidics-based manufacturing of liposomes. The aim of these studies was to assess the parameters in a microfluidic process by varying the total flow rate (TFR) and the flow rate ratio (FRR) of the solvent and aqueous phases. Design of experiment and multivariate data analysis were used for increased process understanding and development of predictive and correlative models. High FRR lead to the bottom-up synthesis of liposomes, with a strong correlation with vesicle size, demonstrating the ability to in-process control liposomes size; the resulting liposome size correlated with the FRR in the microfluidics process, with liposomes of 50 nm being reproducibly manufactured. Furthermore, we demonstrate the potential of a high throughput manufacturing of liposomes using microfluidics with a four-fold increase in the volumetric flow rate, maintaining liposome characteristics. The efficacy of these liposomes was demonstrated in transfection studies and was modelled using predictive modeling. Mathematical modelling identified FRR as the key variable in the microfluidic process, with the highest impact on liposome size, polydispersity and transfection efficiency. This study demonstrates microfluidics as a robust and high-throughput method for the scalable and highly reproducible manufacture of size-controlled liposomes. Furthermore, the application of statistically based process control increases understanding and allows for the generation of a design-space for controlled particle characteristics. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Evaluation of respiratory parameters in rats and rabbits exposed to methyl iodide.

PubMed

DeLorme, Michael P; Himmelstein, Mathew W; Kemper, Raymond A; Kegelman, Thomas A; Gargas, Michael L; Kinzell, John H

2009-05-01

Laboratory animals exposed to methyl iodide (MeI) have previously demonstrated lesions of the olfactory epithelium that were associated with local metabolism in the nasal tissues. Interactions of MeI in the nasal passage may, therefore, alter systemic toxicokinetics. The current study used unrestrained plethysmographs to determine the MeI effect on the breathing frequency and minute volume (MV) in rats and rabbits. Groups of 4 rats each were exposed to 0, 25, or 100 ppm and groups of 4 rabbits each were exposed to 0 and 20 ppm MeI for 6 h. Breathing frequency and MV were measured and recorded during the exposure. Blood samples were collected for inorganic serum iodide and the globin adduct S-methylcysteine (SMC) as biomarkers of systemic kinetics immediately following exposure. No significant reductions in breathing frequency were observed for either rats or rabbits. Significant changes in minute volume were demonstrated by both rats and rabbits; however, the changes observed in rats were not concentration dependent. The MeI-induced changes in MV resulted in significant differences in the total volume of test substance atmosphere inhaled over the 6-h period. Rats demonstrated a concentration-dependent increase in both inorganic serum iodide and SMC. Rabbits exposed to 20 ppm MeI demonstrated a significant increase of inorganic serum iodide; SMC was also increased but was not statistically significant. The results of this study are consistent with previous kinetic studies with MeI, and the data presented here can be integrated into a computational fluid dynamics physiologically based pharmacokinetic model for both rats and rabbits.

A Pediatric Twin Study of Brain Morphometry

ERIC Educational Resources Information Center

Wallace, Gregory L.; Schmitt, J. Eric; Lenroot, Rhoshel; Viding, Essi; Ordaz, Sarah; Rosenthal, Michael A.; Molloy, Elizabeth A.; Clasen, Liv S.; Kendler, Kenneth S.; Neale, Michael C.; Giedd, Jay N.

2006-01-01

Background: Longitudinal pediatric neuroimaging studies have demonstrated increasing volumes of white matter and regionally-specific inverted U shaped developmental trajectories of gray matter volumes during childhood and adolescence. Studies of monozygotic and dyzygotic twins during this developmental period allow exploration of genetic and…

A systematic review of training programs for parents of children with autism spectrum disorders: single subject contributions.

PubMed

Patterson, Stephanie Y; Smith, Veronica; Mirenda, Pat

2012-09-01

The purpose of this systematic review was to examine research utilizing single subject research designs (SSRD) to explore the effectiveness of interventions designed to increase parents' ability to support communication and social development in children with autism spectrum disorders (ASDs). Included studies were systematically assessed for methodological quality (Logan et al., 2008; Smith et al., 2007) and intervention effects. Data examining participant characteristics, study methodology, outcomes, and analysis were systematically extracted. Eleven SSRD parent-training intervention studies examining 44 participants with ASD were included. Overall, the studies were of moderate quality and reported increases in parent skills and child language and communication outcomes. The results supported by improvement rate difference (IRD) analysis indicated several interventions demonstrated positive effects for both parent and child outcomes. However, limited generalization and follow-up data suggested only one intervention demonstrated parents' accurate and ongoing intervention implementation beyond training.

Effects of different mechanized soil fertilization methods on corn nutrient accumulation and yield

NASA Astrophysics Data System (ADS)

Shi, Qingwen; Bai, Chunming; Wang, Huixin; Wu, Di; Song, Qiaobo; Dong, Zengqi; Gao, Depeng; Dong, Qiping; Cheng, Xin; Zhang, Yahao; Mu, Jiahui; Chen, Qinghong; Liao, Wenqing; Qu, Tianru; Zhang, Chunling; Zhang, Xinyu; Liu, Yifei; Han, Xiaori

2017-05-01

Aim: Experiments for mechanized corn soil fertilization were conducted in Faku demonstration zone. On this basis, we studied effects on corn nutrient accumulation and yield traits at brown soil regions due to different mechanized soil fertilization measures. We also evaluated and optimized the regulation effects of mechanized soil fertilization for the purpose of crop yield increase and production efficiency improvement. Method: Based on the survey of soil background value in the demonstration zone, we collected plant samples during different corn growth periods to determine and make statistical analysis. Conclusions: Decomposed cow dung, when under mechanical broadcasting, was able to remarkably increase nitrogen and potassium accumulation content of corns at their ripe stage. Crushed stalk returning combined with deep tillage would remarkably increase phosphorus accumulation content of corn plants. When compared with top application, crushed stalk returning combined with deep tillage would remarkably increase corn thousand kernel weight (TKW). Mechanized broadcasting of granular organic fertilizer and crushed stalk returning combined with deep tillage, when compared with surface application, were able to boost corn yield in the in the demonstration zone.

Oxygenation, local muscle oxygen consumption and joint specific power in cycling: the effect of cadence at a constant external work rate.

PubMed

Skovereng, Knut; Ettema, Gertjan; van Beekvelt, Mireille C P

2016-06-01

The present study investigates the effect of cadence on joint specific power and oxygenation and local muscle oxygen consumption in the vastus lateralis and vastus medialis in addition to the relationship between joint specific power and local muscle oxygen consumption (mVO2). Seventeen recreationally active cyclists performed 6 stages of constant load cycling using cadences of 60, 70, 80, 90, 100 and 110 rpm. Joint specific power was calculated using inverse dynamics and mVO2 and oxygenation were measured using near-infrared spectroscopy. Increasing cadence led to increased knee joint power and decreased hip joint power while the ankle joint was unaffected. Increasing cadence also led to an increased deoxygenation in both the vastus lateralis and vastus medialis. Vastus lateralis mVO2 increased when cadence was increased. No effect of cadence was found for vastus medialis mVO2. This study demonstrates a different effect of cadence on the mVO2 of the vastus lateralis and vastus medialis. The combined mVO2 of the vastus lateralis and medialis showed a linear increase with increasing knee joint specific power, demonstrating that the muscles combined related to power generated over the joint.

Effect of Vicarious Fear Learning on Children’s Heart Rate Responses and Attentional Bias for Novel Animals

PubMed Central

2014-01-01

Research with children has shown that vicarious learning can result in changes to 2 of Lang’s (1968) 3 anxiety response systems: subjective report and behavioral avoidance. The current study extended this research by exploring the effect of vicarious learning on physiological responses (Lang’s final response system) and attentional bias. The study used Askew and Field’s (2007) vicarious learning procedure and demonstrated fear-related increases in children’s cognitive, behavioral, and physiological responses. Cognitive and behavioral changes were retested 1 week and 1 month later, and remained elevated. In addition, a visual search task demonstrated that fear-related vicarious learning creates an attentional bias for novel animals, which is moderated by increases in fear beliefs during learning. The findings demonstrate that vicarious learning leads to lasting changes in all 3 of Lang’s anxiety response systems and is sufficient to create attentional bias to threat in children. PMID:25151521

MRI change metrics of facioscapulohumeral muscular dystrophy: Stir and T1.

PubMed

Ferguson, Mark R; Poliachik, Sandra L; Budech, Christopher B; Gove, Nancy E; Carter, Gregory T; Wang, Leo H; Miller, Daniel G; Shaw, Dennis W W; Friedman, Seth D

2018-06-01

MRI evaluation in facioscapulohumeral muscular dystrophy (FSHD) demonstrates fatty replacement and inflammation/edema in muscle. Our previous work demonstrated short T1 inversion recovery (STIR)-hyperintense (STIR+) signal in muscle 2 years before fatty replacement. We evaluated leg muscle STIR changes and fatty replacement within 14 months. FSHD subjects received 2 MRI scans of thigh and calf over a 6.9- to 13.8-month interval. Quality of life measures were collected. One Radiologist rated muscle changes on a semi-quantitative scale. Fifteen subjects completed longitudinal imaging. Four STIR + muscles and 3 STIR-normal (STIR-) muscles were rated as progressing to fatty tissue over the study period. STIR + muscles with confluent regions of fat at baseline increased more in fat, while STIR- muscles had increases in septal-fat over the study period. These changes may reflect two phases of FSHD, demonstrating MRI sensitivity is weighted toward gross pathological phases of the disease. Muscle Nerve 57: 905-912, 2018. © 2017 Wiley Periodicals, Inc.

Optimization of Nanowire-Resistance Load Logic Inverter.

PubMed

Hashim, Yasir; Sidek, Othman

2015-09-01

This study is the first to demonstrate characteristics optimization of nanowire resistance load inverter. Noise margins and inflection voltage of transfer characteristics are used as limiting factors in this optimization. Results indicate that optimization depends on resistance value. Increasing of load resistor tends to increasing in noise margins until saturation point, increasing load resistor after this point will not improve noise margins significantly.

Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus.

PubMed

Bracey, James M; Kurz, Jonathan E; Low, Brian; Churn, Severn B

2009-08-04

Status epilepticus is a life-threatening form of seizure activity that represents a major medical emergency associated with significant morbidity and mortality. Protein Kinase A is an important regulator of synaptic strength that may play an important role in the development of status epilepticus-induced neuronal pathology. This study demonstrated an increase in PKA activity against exogenous and endogenous substrates during later stages of SE. As SE progressed, a significant increase in PKA-mediated phosphorylation of an exogenous peptide substrate was demonstrated in cortical structures. The increased activity was not due to altered expression of either regulatory or catalytic subunits of the enzyme. Through the use of phospho-specific antibodies, this study also investigated the effects of SE on the phosphorylation of the GluR1 subunit of the AMPA subtype of glutamate receptor. After the onset of continuous seizure activity, an increase in phosphorylation of the PKA site on the GluR1 subunit of the AMPA receptor was observed. These data suggest a potential mechanism by which SE may increase neuronal excitability in the cortex, potentially leading to maintenance of seizure activity or long-term neuronal pathology.

Social learning of an associative foraging task in zebrafish

NASA Astrophysics Data System (ADS)

Zala, Sarah M.; Määttänen, Ilmari

2013-05-01

The zebrafish ( Danio rerio) is increasingly becoming an important model species for studies on the genetic and neural mechanisms controlling behaviour and cognition. Here, we utilized a conditioned place preference (CPP) paradigm to study social learning in zebrafish. We tested whether social interactions with conditioned demonstrators enhance the ability of focal naïve individuals to learn an associative foraging task. We found that the presence of conditioned demonstrators improved focal fish foraging behaviour through the process of social transmission, whereas the presence of inexperienced demonstrators interfered with the learning of the control focal fish. Our results indicate that zebrafish use social learning for finding food and that this CPP paradigm is an efficient assay to study social learning and memory in zebrafish.

Functional Involvement of Carbonic Anhydrase in the Lysosomal Response to Cadmium Exposure in Mytilus galloprovincialis Digestive Gland

PubMed Central

Caricato, Roberto; Giordano, M. Elena; Schettino, Trifone; Lionetto, M. Giulia

2018-01-01

Carbonic anhydrase (CA) is a ubiquitous metalloenzyme, whose functions in animals span from respiration to pH homeostasis, electrolyte transport, calcification, and biosynthetic reactions. CA is sensitive to trace metals in a number of species. In mussels, a previous study demonstrated CA activity and protein expression to be enhanced in digestive gland by cadmium exposure. The aim of the present work was to investigate the functional meaning, if any, of this response. To this end the study addressed the possible involvement of CA in the lysosomal system response of digestive gland cells to metal exposure. The in vivo exposure to acetazolamide, specific CA inhibitor, significantly inhibited the acidification of the lysosomal compartment in the digestive gland cells charged with the acidotropic probe LysoSensor Green D-189, demonstrating in vivo the physiological contribution of CA to the acidification of the lysosomes. Under CdCl2 exposure, CA activity significantly increased in parallel to the increase of the fluorescence of LysoSensor Green charged cells, which is in turn indicative of proliferation and/or increase in size of lysosomes. Acetazolamide exposure was able to completely inhibit the cadmium induced Lysosensor fluorescence increase in digestive gland cells. In conclusion, our results demonstrated the functional role of CA in the lysosomal acidification of Mytilus galloprovincialis digestive gland and its involvement in the lysosomal activation following cadmium exposure. CA induction could physiologically respond to a prolonged increased requirement of H+ for supporting lysosomal acidification during lysosomal activation. PMID:29670538

A Cycle Ergometer Exercise Program Improves Exercise Capacity and Inspiratory Muscle Function in Hospitalized Patients Awaiting Heart Transplantation: a Pilot Study

PubMed Central

Forestieri, Patrícia; Guizilini, Solange; Peres, Monique; Bublitz, Caroline; Bolzan, Douglas W.; Rocco, Isadora S.; Santos, Vinícius B.; Moreira, Rita Simone L.; Breda, João R.; de Almeida, Dirceu R.; Carvalho, Antonio Carlos de C.; Arena, Ross; Gomes, Walter J.

2016-01-01

Objective The purpose of this study was to evaluate the effect of a cycle ergometer exercise program on exercise capacity and inspiratory muscle function in hospitalized patients with heart failure awaiting heart transplantation with intravenous inotropic support. Methods Patients awaiting heart transplantation were randomized and allocated prospectively into two groups: 1) Control Group (n=11) - conventional protocol; and 2) Intervention Group (n=7) - stationary cycle ergometer exercise training. Functional capacity was measured by the six-minute walk test and inspiratory muscle strength assessed by manovacuometry before and after the exercise protocols. Results Both groups demonstrated an increase in six-minute walk test distance after the experimental procedure compared to baseline; however, only the intervention group had a significant increase (P=0.08 and P=0.001 for the control and intervention groups, respectively). Intergroup comparison revealed a greater increase in the intervention group compared to the control (P<0.001). Regarding the inspiratory muscle strength evaluation, the intragroup analysis demonstrated increased strength after the protocols compared to baseline for both groups; statistical significance was only demonstrated for the intervention group, though (P=0.22 and P<0.01, respectively). Intergroup comparison showed a significant increase in the intervention group compared to the control (P<0.01). Conclusion Stationary cycle ergometer exercise training shows positive results on exercise capacity and inspiratory muscle strength in patients with heart failure awaiting cardiac transplantation while on intravenous inotropic support. PMID:27982348

Three-dimensional lumbar segment movement characteristics during paediatric cerebral palsy gait.

PubMed

Kiernan, D; Malone, A; O'Brien, T; Simms, C K

2017-03-01

Kinematic analysis of the trunk during cerebral palsy (CP) gait has been well described. In contrast, movement of the lumbar spine is generally ignored. This is most likely due to the complex nature of the spine. As an alternative to using complex sensor protocols, this study modelled the lumbar region as a single segment and investigated characteristic patterns of movement during CP gait. In addition, the impact of functional level of impairment and the relationship with lower lumbar spinal loading were examined. Fifty-two children with CP (26 GMFCS I and 26 GMFCS II) and 26 controls were recruited. A full barefoot 3-dimensional kinematic and kinetic analysis were conducted. Lumbar segment movement demonstrated increased forward flexion for CP children. This movement became more pronounced according to GMFCS level with GMFCS II children demonstrating increases of up to 8°. In addition, a moderate correlation was present between lumbar flexion/extension and L5/S1 sagittal moments (r=0.427 in the global frame and r=0.448 with respect to the pelvis, p<0.01). Children with CP demonstrated increased movement of the lumbar region compared to TD, with movement becoming more excessive as GMFCS level increased. Excessive forward flexion and loading at the lumbar spine were linked. However, the moderate correlation suggests other contributors to increased loading were present. In conclusion, this study is a first step at identifying how lumbar segment movement is altered during CP gait. Copyright © 2017 Elsevier B.V. All rights reserved.

Blinded with science: Trivial graphs and formulas increase ad persuasiveness and belief in product efficacy.

PubMed

Tal, Aner; Wansink, Brian

2016-01-01

The appearance of being scientific can increase persuasiveness. Even trivial cues can create such an appearance of a scientific basis. In our studies, including simple elements, such as graphs (Studies 1-2) or a chemical formula (Study 3), increased belief in a medication's efficacy. This appears to be due to the association of such elements with science, rather than increased comprehensibility, use of visuals, or recall. Belief in science moderates the persuasive effect of graphs, such that people who have a greater belief in science are more affected by the presence of graphs (Study 2). Overall, the studies contribute to past research by demonstrating that even trivial elements can increase public persuasion despite their not truly indicating scientific expertise or objective support. © The Author(s) 2014.

Regulation of fish growth hormone transcription.

PubMed

Farchi-Pisanty, O; Hackett, P B; Moav, B

1995-09-01

Regulation of endogenous fish growth hormone transcription was studied using carp pituitaries in vitro. It was demonstrated that thyroid hormone (T3) and 9-cis retinoic acid have increased the steady state levels of growth hormone messenger RNA in pituitary cells, as compared with beta-actin messenger RNA levels. In contrast, estrogen failed to increase growth hormone mRNA levels. The possible involvement of thyroid hormone receptor in pituitary gene expression was demonstrated by in situ localization of both growth hormone mRNA and thyroid hormone receptor mRNA in the pituitaries as early as 4 days after fertilization.

New Developments in Robotics and Single-site Gynecologic Surgery.

PubMed

Matthews, Catherine A

2017-06-01

Within the last 10 years there have been significant advances in minimal-access surgery. Although no emerging technology has demonstrated improved outcomes or fewer complications than standard laparoscopy, the introduction of the robotic surgical platform has significantly lowered abdominal hysterectomy rates. While operative time and cost were higher in robotic-assisted procedures when the technology was first introduced, newer studies demonstrate equivalent or improved robotic surgical efficiency with increased experience. Single-port hysterectomy has not improved postoperative pain or subjective cosmetic results. Emerging platforms with flexible, articulating instruments may increase the uptake of single-port procedures including natural orifice transluminal endoscopic cases.

Increasing Vocal Variability in Children with Autism Using a Lag Schedule of Reinforcement

ERIC Educational Resources Information Center

Esch, John W.; Esch, Barbara E.; Love, Jessa R.

2009-01-01

Variability has been demonstrated to be an operant dimension of behavior (Neuringer, 2002; Page & Neuringer, 1985). Recently, lag schedules have been used to demonstrate operant variability of verbal behavior in persons with a diagnosis of autism (e.g., Lee, McComas, & Jawor, 2002). The current study evaluated the effects of a Lag 1 schedule on…

Medicating Our Youth: Who Determines Rules of Evidence?

ERIC Educational Resources Information Center

Foltz, Robert

2010-01-01

There is increased use of medications with troubled youth and a corresponding increase in research about these drugs. However, even the most exhaustive efforts to demonstrate the effectiveness of medication strategies have resulted in less than robust outcomes. A critical review of the most prominent studies highlights this questionable trend in…

Math Interventions for Students with Autism Spectrum Disorder: A Best-Evidence Synthesis

ERIC Educational Resources Information Center

King, Seth A.; Lemons, Christopher J.; Davidson, Kimberly A.

2016-01-01

Educators need evidence-based practices to assist students with disabilities in meeting increasingly rigorous standards in mathematics. Students with autism spectrum disorder (ASD) are increasingly expected to demonstrate learning of basic and advanced mathematical concepts. This review identifies math intervention studies involving children and…

Salt-Induced Thirst Results in Increased Finickiness in Humans

ERIC Educational Resources Information Center

Stevenson, Richard J.; Case, Trevor I.; Oaten, Megan J.

2010-01-01

Common sense suggests that water-deprived or food-deprived organisms should be more willing to consume foods or fluids that would be deemed undesirable under lower states of deprivation. With food, evidence favoring this account has been observed; however other studies find that hungry participants demonstrate increased finickiness--avoiding less…

INTERACTIONS OF LIGHT AND CHEMICAL REACTIONS IN THE AQUATIC ENVIRONMENT: KINETIC AND MECHANISTIC ASPECTS

EPA Science Inventory

Changes in the ozone layer over the past two decades have resulted in increases in solar ultraviolet (UV) radiation that reaches the surface of aquatic environments. Recent studies have demonstrated that these UV increases cause changes in photochemical reactions that affect the...

Organizational Justice and Men's Likelihood to Sexually Harass: The Moderating Role of Sexism and Personality

ERIC Educational Resources Information Center

Krings, Franciska; Facchin, Stephanie

2009-01-01

This study demonstrated relations between men's perceptions of organizational justice and increased sexual harassment proclivities. Respondents reported higher likelihood to sexually harass under conditions of low interactional justice, suggesting that sexual harassment likelihood may increase as a response to perceived injustice. Moreover, the…

Sodium Lauryl Sulfate Stimulates the Generation of Reactive Oxygen Species through Interactions with Cell Membranes.

PubMed

Mizutani, Taeko; Mori, Ryota; Hirayama, Misaki; Sagawa, Yuki; Shimizu, Kenji; Okano, Yuri; Masaki, Hitoshi

2016-12-01

Sodium lauryl sulfate (SLS), a representative anionic surfactant, is well-known to induce rough skin following single or multiple topical applications. The mechanism by which SLS induces rough skin is thought to result from the disruption of skin moisture function consisting of NMF and epidermal lipids. However, a recent study demonstrated that topically applied SLS easily penetrates into the living cell layers of the epidermis, which suggests that physiological alterations of keratinocytes might cause the SLS-induced rough skin. This study was conducted to clarify the effects of SLS on keratinocytes to demonstrate the contribution of SLS to the induction of rough skin. In addition, the potentials of other widely used anionic surfactants to induce rough skin were evaluated. HaCaT keratinocytes treated with SLS had increased levels of intracellular ROS and IL-1α secretion. Application of SLS on the surface of a reconstructed epidermal equivalent also showed the increased generation of ROS. Further, SLS-treated cells showed an increase of intracellular calpain activity associated with the increase of intracellular Ca 2+ concentration. The increase of intracellular ROS was abolished by the addition of BAPTA-AM, a specific chelator of Ca 2+ . In addition, IL-1α also stimulated ROS generation by HaCaT keratinocytes. An ESR spin-labeling study demonstrated that SLS increased the fluidity of membranes of liposomes and cells. Together, those results indicate that SLS initially interacts with cell membranes, which results in the elevation of intracellular Ca 2+ influx. Ca 2+ stimulates the secretion of IL-1α due to the activation of calpain, and also increases ROS generation. IL-1α also stimulates ROS generation by HaCaT keratinocytes. We conclude from these results that the elevation of intracellular ROS levels is one of the causes of SLS-induced rough skin. Finally, among the other anionic surfactants tested, sodium lauryl phosphate has less potential to induce rough skin because of its lower generation of ROS.

Age-related sensitivity to endotoxin-induced liver inflammation: Implication of inflammasome/IL-1β for steatohepatitis

PubMed Central

Chung, Ki Wung; Lee, Eun Kyeong; Kim, Dae Hyun; An, Hye Jin; Kim, Nam Deuk; Im, Dong Soon; Lee, Jaewon; Yu, Byung Pal; Chung, Hae Young

2015-01-01

Aging is associated with increased vulnerability to inflammatory challenge. However, the effects of altered inflammatory response on the metabolic status of tissues or organs are not well documented. In this study, we present evidence demonstrating that lipopolysaccharide (LPS)-induced upregulation of the inflammasome/IL-1β pathway is accompanied with an increased inflammatory response and abnormal lipid accumulation in livers of aged rats. To monitor the effects of aging on LPS-induced inflammation, we administered LPS (2 mg kg−1) to young (6-month old) and aged (24-month old) rats and found abnormal lipid metabolism in only aged rats with increased lipid accumulation in the liver. This lipid accumulation in the liver was due to the dysregulation of PPARα and SREBP1c. We also observed severe liver inflammation in aged rats as indicated by increased ALT levels in serum and increased Kupffer cells in the liver. Importantly, among many inflammation-associated factors, the aged rat liver showed chronically increased IL-1β production. Increased levels of IL-1β were caused by the upregulation of caspase-1 activity and inflammasome activation. In vitro studies with HepG2 cells demonstrated that treatment with IL-1β significantly induced lipid accumulation in hepatocytes through the regulation of PPARα and SREBP1c. In summary, we demonstrated that LPS-induced liver inflammation and lipid accumulation were associated with a chronically overactive inflammasome/IL-1β pathway in aged rat livers. Based on the present findings, we propose a mechanism of aging-associated progression of steatohepatitis induced by endotoxin, delineating a pathogenic role of the inflammasome/IL-1β pathway involved in lipid accumulation in the liver. PMID:25847140

Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis

PubMed Central

2010-01-01

Background Previous observations demonstrate that Cftr-null cells and tissues exhibit alterations in cholesterol processing including perinuclear cholesterol accumulation, increased de novo synthesis, and an increase in plasma membrane cholesterol accessibility compared to wild type controls. The hypothesis of this study is that membrane cholesterol accessibility correlates with CFTR genotype and is in part influenced by de novo cholesterol synthesis. Methods Electrochemical detection of cholesterol at the plasma membrane is achieved with capillary microelectrodes with a modified platinum coil that accepts covalent attachment of cholesterol oxidase. Modified electrodes absent cholesterol oxidase serves as a baseline control. Cholesterol synthesis is determined by deuterium incorporation into lipids over time. Incorporation into cholesterol specifically is determined by mass spectrometry analysis. All mice used in the study are on a C57Bl/6 background and are between 6 and 8 weeks of age. Results Membrane cholesterol measurements are elevated in both R117H and ΔF508 mouse nasal epithelium compared to age-matched sibling wt controls demonstrating a genotype correlation to membrane cholesterol detection. Expression of wt CFTR in CF epithelial cells reverts membrane cholesterol to WT levels further demonstrating the impact of CFTR on these processes. In wt epithelial cell, the addition of the CFTR inhibitors, Gly H101 or CFTRinh-172, for 24 h surprisingly results in an initial drop in membrane cholesterol measurement followed by a rebound at 72 h suggesting a feedback mechanism may be driving the increase in membrane cholesterol. De novo cholesterol synthesis contributes to membrane cholesterol accessibility. Conclusions The data in this study suggest that CFTR influences cholesterol trafficking to the plasma membrane, which when depleted, leads to an increase in de novo cholesterol synthesis to restore membrane content. PMID:20487541

Head and Neck Ultrasound Education-A Multimodal Educational Approach in the Predoctoral Setting: A Pilot Study.

PubMed

Bernard, Stewart; Richardson, Clare; Hamann, Carsten R; Lee, Steve; Dinh, Vi Am

2015-08-01

With the increased implementation of ultrasound in medical education, it is important to continually improve instructional methods. In this study, we demonstrate that by augmenting the traditional methods of instructor demonstration and student practice on a healthy volunteer with additional modalities, such as didactic presentation, simulated pathologic cases, and simulated procedures, students gain a more comprehensive understanding of and confidence in ultrasound technique and pathology. A multimodal curriculum was developed and applied to head and neck ultrasound sessions of our institution's Ultrasound Symposium. Participants were asked to fill out surveys rating each instructional modality as well as preinstructional and postinstructional confidence. The survey results were divided into a group of first- and second-year medical students who had previous ultrasound training and a group of third- and fourth-year students who were ultrasound "naïve." The survey showed that the first- and second-year student group (n = 8) had an average preinstructional confidence of 4.14/10 compared to 1.44/10 in the third- and fourth-year student group (n = 9) (P = .003). Following the instructional sessions, the students' confidence increased respectively to 8.14/10 and 7.78/10 (P= .53), showing a 4.00 (96%) increase in the first- and second-year group and a 6.34 (440%) increase in the third- and fourth-year group. The combined results of all student teaching modality ratings showed that instructor demonstration was rated the highest (9.47) and computerized simulation lowest (8.25). Overall, our study shows that multimodal ultrasound instruction was beneficial in increasing both ultrasound-trained and ultrasound-naïve medical students' confidence in head and neck ultrasound. © 2015 by the American Institute of Ultrasound in Medicine.

Solid effervescent formulations as new approach for topical minoxidil delivery.

PubMed

Pereira, Maíra N; Schulte, Heidi L; Duarte, Natane; Lima, Eliana M; Sá-Barreto, Livia L; Gratieri, Tais; Gelfuso, Guilherme M; Cunha-Filho, Marcilio S S

2017-01-01

Currently marketed minoxidil formulations present inconveniences that range from a grease hard aspect they leave on the hair to more serious adverse reactions as scalp dryness and irritation. In this paper we propose a novel approach for minoxidil sulphate (MXS) delivery based on a solid effervescent formulation. The aim was to investigate whether the particle mechanical movement triggered by effervescence would lead to higher follicle accumulation. Preformulation studies using thermal, spectroscopic and morphological analysis demonstrated the compatibility between effervescent salts and the drug. The effervescent formulation demonstrated a 2.7-fold increase on MXS accumulation into hair follicles casts compared to the MXS solution (22.0±9.7μg/cm 2 versus 8.3±4.0μg/cm 2 ) and a significant drug increase (around 4-fold) in remaining skin (97.1±29.2μg/cm 2 ) compared to the drug solution (23.5±6.1μg/cm 2 ). The effervescent formulations demonstrated a prominent increase of drug permeation highly dependent on the effervescent mixture concentration in the formulation, confirming the hypothesis of effervescent reaction favoring drug penetration. Clinically, therapy effectiveness could be improved, increasing the administration interval, hence, patient compliance. More studies to investigate the follicular targeting potential and safety of new formulations are needed. Copyright © 2016 Elsevier B.V. All rights reserved.

Helping concerned family members of individuals with substance use and concurrent disorders: An evaluation of a family member-oriented treatment program.

PubMed

Denomme, William James; Benhanoh, Orry

2017-08-01

There is a growing body of research demonstrating that families of individuals with substance use and concurrent disorders (SUCD) experience a wide range of biopsychosocial problems that significantly impedes their quality of life and health. However, there has been a relative lack of treatment programs primarily focused on improving the well-being and quality of life of these family members. The current study assessed the efficacy of such a program at reducing stress, increasing perceived social support from family and friends, and increasing general, dyadic, and self-rated family functioning within these concerned family members. A sample of 125 family members of individuals with SUCDs was recruited, of which 97 participated in the treatment program and 28 were used as the comparison group. Results indicated that the treatment program significantly reduced stress, increased perceived social support from family and friends, and increased general, dyadic and self-rated family functioning. A perceived personal benefits questionnaire demonstrated that participants had a better understanding of SUCDs, better coping capabilities in regard to emotional difficulties, adopted stronger coping methods, participated in more leisure activities, and improved their relationship with the individual with a SUCD. The results of the current study further demonstrate the need to implement more of these family-member oriented psycho-educational treatment programs. Copyright © 2017 Elsevier Inc. All rights reserved.

First evidence for "The backup plan paradox".

PubMed

Napolitano, Christopher M; Freund, Alexandra M

2017-08-01

This research is a first test of the backup plan paradox. We hypothesized that investing in a backup plan may facilitate the conditions that it was developed to address: Plan A's insufficiency. Five studies provide initial, primarily correlative support for the undermining effect of investing in a backup plan. Study 1 (n= 160) demonstrated that the more participants perceived they had invested in developing a backup plan (preparing a "crib sheet"), the more likely they were to use it, although greater investments were unrelated to backup plan utility. Studies 2-4 used a simulated negotiation task. Study 2 (n = 247) demonstrated that when goal-relevant resources are limited, investing in developing backup plans and perceiving them as highly instrumental can decrease goal performance through the indirect effect of increased means replacing. Study 3 (n = 248) replicated this effect when goal-relevant resources were plentiful. Study 4 (n = 204) used an experimental variant of the simulated negotiation task and demonstrated that simply having a backup plan is not detrimental, but perceiving backup plans to be highly instrumental decreased goal performance, again through the indirect effect of increased means replacing. Study 5 (n = 160) replicated findings from Studies 1-4 using a lab-based motor task (throwing a ball). Together, these results provide first evidence that backup plans can introduce costs that may jeopardize goal performance. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

"Brief report: increase in production of spoken words in some children with autism after PECS teaching to Phase III".

PubMed

Carr, Deborah; Felce, Janet

2007-04-01

The context for this work was an evaluation study [Carr, D., & Felce, J. A. (in press)] of the early phases of the Picture Exchange Communication System (PECS) [Frost, L. A., & Bondy, A. S. (1994). The picture exchange communication system training manual. Cherry Hill, NJ: Pyramid Educational Consultants, Inc.; Frost, L. A., & Bondy, A. S. (2004). The picture exchange communication system training manual, 2nd edn. Newark, DE: Pyramid Educational Consultants, Inc.]. This paper reports that five of 24 children who received 15 h of PECS teaching towards Phase III over a period of 4-5 weeks, showed concomitant increases in speech production, either in initiating communication with staff or in responding, or both. No children in the PECS group demonstrated a decrease in spoken words after receiving PECS teaching. In the control group, only one of 17 children demonstrated a minimal increase and four of 17 children demonstrated a decrease in use of spoken words after a similar period without PECS teaching.

The Effects of Ultrasound on Biological Systems: Site

NASA Astrophysics Data System (ADS)

El-Karmi, Anan M.

Earlier studies (Dinno et al., Ultrasound Med. Biol. 15:461 -470; 1989) demonstrated that ultrasound at therapeutic intensities causes large increases in total conductance (G_{rm t}) of frog skin. These changes were attributed to non-thermal mechanisms, primarily, cavitation. In this study, the site(s) and mechanism(s) of action of ultrasound for the increase in G_{rm t} were examined. The reversible changes in G_{rm t } and sodium current were monitored in real time as a function of ultrasound exposure. Amiloride, a sodium channel blocker, was used to differentiate between cellular (G_{rm c}) and paracellular (G_{rm s}) pathways in the presence and absence of ultrasound. No significant changes were detected in G_ {rm c}. However, changes in G _{rm s} were significant. These results demonstrate that most of the increase in G _{rm t} due to ultrasound is taking place in the paracellular pathways. Sodium channels were not significantly affected by ultrasound. Thus, the changes in G_{rm c} are not specific. The effects of ultrasound were examined in the presence of radical scavengers and antioxidants. The increase in G_{rm t} due to ultrasound was significantly minimized in the presence of cystamine, cysteamine, and sodium ascorbate. This demonstrates that free radicals and other reactive species generated by cavitation are causing the increase in G_ {rm t}, possibly by acting from inside the cells. Radical scavengers and antioxidants are providing protection from oxidative damage but are not involved in the recovery of G_{ rm t} towards steady state values after sonication. The role of Ca^{2+} in the effects of ultrasound was examined since many of the cellular reactions involved in tissue recovery are dependent on the intracellular availability of free Ca^{2+}. The percentage increase in G_{rm t} in the presence of Ca^{2+} was larger than in its absence (140% vs. 27%). The time constant for G_{rm t} to return to steady state was longer in calcium-free solutions (122 vs. 18 minutes). This demonstrates that the biological effects of ultrasound are influenced by Ca^ {2+}. The larger increases in G _{rm t} and the time constants confirm other studies addressing the role of Ca ^{2+} in potentiating lipid peroxidation by free radicals, and the role of calcium ions in the formation of tight junctions.

Intraindividual variability in physical and emotional functioning: comparison of adults with traumatic brain injuries and healthy adults.

PubMed

Burton, Catherine L; Hultsch, David F; Strauss, Esther; Hunter, Michael A

2002-08-01

Recent research has shown that individuals with certain neurological conditions demonstrate greater intraindividual variability on cognitive tasks compared to healthy controls. The present study investigated intraindividual variability in the domains of physical functioning and affect/stress in three groups: adults with mild head injuries, adults with moderate/severe head injuries, and healthy adults. Participants were assessed on 10 occasions and results indicated that (a) individuals with head injuries demonstrated greater variability in dominant finger dexterity and right grip strength than the healthy controls; (b) increased variability tended to be associated with poorer performance/report both within and across tasks; and (c) increased variability on one task was associated with increased variability on other tasks. The findings suggest that increased variability in physical function, as well as cognitive function, represents an indicator of neurological compromise.

Quasi-experimental Study of Systematic Screening for Family Planning Services among Postpartum Women Attending Village Health and Nutrition Days in Jharkhand, India.

PubMed

Balasubramaniam, Sudharsanam; Kumar, Somesh; Sethi, Reena; Charurat, Elaine; Lalchandani, Kamlesh; Schuster, Anne; Sood, Bulbul

2018-01-25

Systematic screening helps increase family planning uptake through integration with other services, including immunization. Though successfully demonstrated at health facilities, this strategy has not been demonstrated in communities. This study assessed the effectiveness of systematic screening to increase postpartum family planning use during community health days in India without adversely affecting immunization services. The study was conducted during 180 individual Village Health and Nutrition Days in Jharkhand, India. All health workers were trained in postpartum family planning counseling. Intervention providers were also trained in systematic screening. 217 postpartum women aged 15-49 years participated in baseline and endline exit interviews and routine service statistics were analyzed from 2,485 facility visits at affiliated health centers. No difference in family planning service use was found in the intervention group, but significantly fewer interviewed women reported receiving family planning services at endline in the comparison group (p = 0.014). Family planning acceptance at affiliated health centers increased significantly in intervention areas (p < 0.001) but not in comparison areas, while immunization service use increased in both groups (p = 0.002 intervention, p < 0.001 comparison). The use of the postpartum systematic screening tool appears to increase acceptance of family planning services when integrated with community-based services in Jharkhand.

Increased Testosterone Decreases Medial Cortical Volume and Neurogenesis in Territorial Side-Blotched Lizards (Uta stansburiana)

PubMed Central

LaDage, Lara D.; Roth, Timothy C.; Downs, Cynthia J.; Sinervo, Barry; Pravosudov, Vladimir V.

2017-01-01

Variation in an animal's spatial environment can induce variation in the hippocampus, an area of the brain involved in spatial cognitive processing. Specifically, increased spatial area use is correlated with increased hippocampal attributes, such as volume and neurogenesis. In the side-blotched lizard (Uta stansburiana), males demonstrate alternative reproductive tactics and are either territorial—defending large, clearly defined spatial boundaries—or non-territorial—traversing home ranges that are smaller than the territorial males' territories. Our previous work demonstrated cortical volume (reptilian hippocampal homolog) correlates with these spatial niches. We found that territorial holders have larger medial cortices than non-territory holders, yet these differences in the neural architecture demonstrated some degree of plasticity as well. Although we have demonstrated a link among territoriality, spatial use, and brain plasticity, the mechanisms that underlie this relationship are unclear. Previous studies found that higher testosterone levels can induce increased use of the spatial area and can cause an upregulation in hippocampal attributes. Thus, testosterone may be the mechanistic link between spatial area use and the brain. What remains unclear, however, is if testosterone can affect the cortices independent of spatial experiences and whether testosterone differentially interacts with territorial status to produce the resultant cortical phenotype. In this study, we compared neurogenesis as measured by the total number of doublecortin-positive cells and cortical volume between territorial and non-territorial males supplemented with testosterone. We found no significant differences in the number of doublecortin-positive cells or cortical volume among control territorial, control non-territorial, and testosterone-supplemented non-territorial males, while testosterone-supplemented territorial males had smaller medial cortices containing fewer doublecortin-positive cells. These results demonstrate that testosterone can modulate medial cortical attributes outside of differential spatial processing experiences but that territorial males appear to be more sensitive to alterations in testosterone levels compared with non-territorial males. PMID:28298883

Formation and rupture of Ca(2+) induced pectin biopolymer gels.

PubMed

Basak, Rajib; Bandyopadhyay, Ranjini

2014-10-07

When calcium salts are added to an aqueous solution of polysaccharide pectin, ionic cross-links form between pectin chains, giving rise to a gel network in dilute solution. In this work, dynamic light scattering (DLS) is employed to study the microscopic dynamics of the fractal aggregates (flocs) that constitute the gels, while rheological measurements are carried out to study the process of gel rupture. As the calcium salt concentration is increased, DLS experiments reveal that the polydispersity of the flocs increase simultaneously with the characteristic relaxation times of the gel network. Above a critical salt concentration, the flocs become interlinked to form a reaction-limited fractal gel network. Rheological studies demonstrate that the limits of the linear rheological response and the critical stresses required to rupture these networks both decrease with the increase in salt concentration. These features indicate that the ion-mediated pectin gels studied here lie in a 'strong link' regime that is characterised by inter-floc links that are stronger than intra-floc links. A scaling analysis of the experimental data presented here demonstrates that the elasticities of the individual fractal flocs exhibit power-law dependences on the added salt concentration. We conclude that when both pectin and salt concentrations are increased, the number of fractal flocs of pectin increases simultaneously with the density of crosslinks, giving rise to very large values of the bulk elastic modulus.

Effect of descriptive information and experience on automation reliance.

PubMed

Yuviler-Gavish, Nirit; Gopher, Daniel

2011-06-01

The present research addresses the issue of reliance on decision support systems for the long-term (DSSLT), which help users develop decision-making strategies and long-term planning. It is argued that providing information about a system's future performance in an experiential manner, as compared with a descriptive manner, encourages users to increase their reliance level. Establishing appropriate reliance on DSSLT is contingent on the system developer's ability to provide users with information about the system's future performance. A sequence of three studies contrasts the effect on automation reliance of providing descriptive information versus experience for DSSLT with two different positive expected values of recommendations. Study I demonstrated that when automation reliance was determined solely on the basis of description, it was relatively low, but it increased significantly when a decision was made after experience with 50 training simulations. Participants were able to learn to increase their automation reliance levels when they encountered the same type of recommendation again. Study 2 showed that the absence of preliminary descriptive information did not affect the automation reliance levels obtained after experience. Study 3 demonstrated that participants were able to generalize their learning about increasing reliance levels to new recommendations. Using experience rather than description to give users information about future performance in DSSLT can help increase automation reliance levels. Implications for designing DSSLT and decision support systems in general are discussed.

Involvement of PUMA in pericyte migration induced by methamphetamine.

PubMed

Zhang, Yanhong; Zhang, Yuan; Bai, Ying; Chao, Jie; Hu, Gang; Chen, Xufeng; Yao, Honghong

2017-07-01

Mounting evidence indicates that methamphetamine causes blood-brain barrier damage, with emphasis on endothelial cells. The role of pericytes in methamphetamine-induced BBB damage remains unknown. Our study demonstrated that methamphetamine increased the migration of pericytes from the endothelial basement membrane. However, the detailed mechanisms underlying this process remain poorly understood. Thus, we examined the molecular mechanisms involved in methamphetamine-induced pericyte migration. The results showed that exposure of C3H/10T1/2 cells and HBVPs to methamphetamine increased PUMA expression via activation of the sigma-1 receptor, MAPK and Akt/PI3K pathways. Moreover, methamphetamine treatment resulted in the increased migration of C3H/10T1/2 cells and HBVPs. Knockdown of PUMA in pericytes transduced with PUMA siRNA attenuated the methamphetamine-induced increase in cell migration through attenuation of integrin and tyrosine kinase mechanisms, implicating a role of PUMA in the migration of C3H/10T1/2 cells and HBVPs. This study has demonstrated that methamphetamine-mediated pericytes migration involves PUMA up-regulation. Thus, targeted studies of PUMA could provide insights to facilitate the development of a potential therapeutic approach for alleviation of methamphetamine-induced pericyte migration. Copyright © 2017. Published by Elsevier Inc.

Relationships between changes in Sustained Fronto-Striatal Connectivity and Positive Affect with Antidepressant Treatment in Major Depression

PubMed Central

Heller, Aaron S.; Johnstone, Tom; Light, Sharee; Peterson, Michael J.; Kolden, Gregory G.; Kalin, Ned H.; Davidson, Richard J.

2012-01-01

Objective Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement over time of this network is unknown. Accordingly, we sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. Method Using fMRI, we assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients prior to, and after 2 months of antidepressant treatment. 14 healthy control subjects were scanned over the same interval. Results After 2 months of treatment, self-reported positive affect increased. Those patients demonstrating the largest increases in sustained nucleus accumbens activity over the 2 months were those demonstrating the largest increases in positive affect. In addition, those patients demonstrating the largest increases in sustained fronto-striatal connectivity were also those demonstrating the largest increases in positive affect when controlling for negative affect. Healthy controls showed none of these associations. Conclusions Treatment induced changes in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect. PMID:23223803

Smoking behaviors and attitudes during adolescence prospectively predict support for tobacco control policies in adulthood.

PubMed

Macy, Jonathan T; Chassin, Laurie; Presson, Clark C

2012-07-01

Several cross-sectional studies have examined factors associated with support for tobacco control policies. The current study utilized a longitudinal design to test smoking status and attitude toward smoking measured in adolescence as prospective predictors of support for tobacco control policies measured in adulthood. Participants (N = 4,834) were from a longitudinal study of a Midwestern community-based sample. Hierarchical multiple regression analyses tested adolescent smoking status and attitude toward smoking as prospective predictors (after controlling for sociodemographic factors, adult smoking status, and adult attitude toward smoking) of support for regulation of smoking in public places, discussion of the dangers of smoking in public schools, prohibiting smoking in bars, eliminating smoking on television and in movies, prohibiting smoking in restaurants, and increasing taxes on cigarettes. Participants who smoked during adolescence demonstrated more support for discussion of the dangers of smoking in public schools and less support for increasing taxes on cigarettes but only among those who smoked as adults. Those with more positive attitudes toward smoking during adolescence demonstrated less support as adults for prohibiting smoking in bars and eliminating smoking on television and in movies. Moreover, a significant interaction indicated that those with more positive attitudes toward smoking as adolescents demonstrated less support as adults for prohibiting smoking in restaurants, but only if they became parents as adults. This study's findings suggest that interventions designed to deter adolescent smoking may have future benefits in increasing support for tobacco control policies.

4β-Hydroxywithanolide E Modulates Alternative Splicing of Apoptotic Genes in Human Hepatocellular Carcinoma Huh-7 Cells.

PubMed

Lee, Chien-Chin; Chang, Wen-Hsin; Chang, Ya-Sian; Liu, Ting-Yuan; Chen, Yu-Chia; Wu, Yang-Chang; Chang, Jan-Gowth

2017-08-04

Alternative splicing is a mechanism for increasing protein diversity from a limited number of genes. Studies have demonstrated that aberrant regulation in the alternative splicing of apoptotic gene transcripts may contribute to the development of cancer. In this study, we isolated 4β-Hydroxywithanolide E (4bHWE) from the traditional herb Physalis peruviana and investigated its biological effect in cancer cells. The results demonstrated that 4bHWE modulates the alternative splicing of various apoptotic genes, including HIPK3, SMAC/DIABLO, and SURVIVIN. We also discovered that the levels of SRSF1 phospho-isoform were decreased and the levels of H3K36me3 were increased in 4bHWE treatment. Knockdown experiments revealed that the splicing site selection of SMAC/DIABLO could be mediated by changes in the level of H3K36me3 in 4bHWE-treated cells. Furthermore, we extended our study to apoptosis-associated molecules, and detected increased levels of poly ADP-ribose polymerase cleavage and the active form of CASPASE-3 in 4bHWE-induced apoptosis. In vivo experiments indicated that the treatment of tumor-bearing mice with 4bHWE resulted in a marked decrease in tumor size. This study is the first to demonstrate that 4bHWE affects alternative splicing by modulating splicing factors and histone modifications, and provides a novel view of the antitumor mechanism of 4bHWE.

Brain-controlled functional electrical stimulation therapy for gait rehabilitation after stroke: a safety study.

PubMed

McCrimmon, Colin M; King, Christine E; Wang, Po T; Cramer, Steven C; Nenadic, Zoran; Do, An H

2015-07-11

Many stroke survivors have significant long-term gait impairment, often involving foot drop. Current physiotherapies provide limited recovery. Orthoses substitute for ankle strength, but they provide no lasting therapeutic effect. Brain-computer interface (BCI)-controlled functional electrical stimulation (FES) is a novel rehabilitative approach that may generate permanent neurological improvements. This study explores the safety and feasibility of a foot-drop-targeted BCI-FES physiotherapy in chronic stroke survivors. Subjects (n = 9) operated an electroencephalogram-based BCI-FES system for foot dorsiflexion in 12 one-hour sessions over four weeks. Gait speed, dorsiflexion active range of motion (AROM), six-minute walk distance (6MWD), and Fugl-Meyer leg motor (FM-LM) scores were assessed before, during, and after therapy. The primary safety outcome measure was the proportion of subjects that deteriorated in gait speed by ≥0.16 m/s at one week or four weeks post-therapy. The secondary outcome measures were the proportion of subjects that experienced a clinically relevant decrease in dorsiflexion AROM (≥2.5°), 6MWD (≥20 %), and FM-LM score (≥10 %) at either post-therapy assessment. No subjects (0/9) experienced a clinically significant deterioration in gait speed, dorsiflexion AROM, 6MWT distance, or FM-LM score at either post-therapy assessment. Five subjects demonstrated a detectable increase (≥0.06 m/s) in gait speed, three subjects demonstrated a detectable increase (≥2.5°) in dorsiflexion AROM, five subjects demonstrated a detectable increase (≥10 %) in 6MWD, and three subjects demonstrated a detectable increase (≥10 %) in FM-LM. Five of the six subjects that exhibited a detectable increase in either post-therapy gait speed or 6MWD also exhibited significant (p < 0.01 using a Mann-Whitney U test) increases in electroencephalogram event-related synchronization/desynchronization. Additionally, two subjects experienced a clinically important increase (≥0.16 m/s) in gait speed, and four subjects experienced a clinically important increase (≥20 %) in 6MWD. Linear mixed models of gait speed, dorsiflexion AROM, 6MWD, and FM-LM scores suggest that BCI-FES therapy is associated with an increase in lower motor performance at a statistically, yet not clinically, significant level. BCI-FES therapy is safe. If it is shown to improve post-stroke gait function in future studies, it could provide a new gait rehabilitation option for severely impaired patients. Formal clinical trials are warranted.

Exercised-induced increase in lipid peroxidation parameters in amenorrheic female athletes.

PubMed

Ayres, S; Baer, J; Subbiah, M T

1998-01-01

To determine plasma lipid peroxidation parameters in eumenorrheic and amenorrheic athletes and to evaluate differences in their response to exercise-induced oxidative stress. In female athletes, intense physical exercise has been shown to be associated with an increased occurrence of menstrual dysfunction with lower levels of E2. Recently, a protective role has been demonstrated for estrogens as free radical scavengers. Comparison of eumenorrheic and amenorrheic athletes before and after an acute bout of exercise. Academic Research Environment. Seven eumenorrheic (normally menstruating) and seven amenorrheic (<3 menses/year) female athletes aged 18 to 35 years participating in regular training. Plasma and low-density lipoprotein oxidation parameters, plasma E2 and vitamin E levels, and creatine kinase activity. Both the amenorrheic and eumenorrheic athletes demonstrated a significant decrease in the lag time of conjugated diene formation after exercise (P < 0.01), with greater magnitude of change occurring in the amenorrheic athletes (P < 0.05). In addition, postexercise samples from amenorrheic (but not eumenorrhic) athletes showed a significant (P < 0.01) increase in oxysterol formation as compared to baseline values. Amenorrheic athletes also demonstrated a significantly higher baseline creatine kinase activity and a nonsignificant (P = 0.04) trend of an increase in creatine kinase activity after exercise. The results of this study shows that amenorrheic female athletes demonstrate an increased potential for lipid peroxidation after exercise. This could be related to lower plasma E2 levels in this group, considering the strong free radical scavenging ability of estrogens identified recently.

Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide

PubMed Central

Vandergriff, Adam; Huang, Ke; Shen, Deliang; Hu, Shiqi; Hensley, Michael Taylor; Caranasos, Thomas G.; Qian, Li; Cheng, Ke

2018-01-01

Rationale: Cardiac stem cell-derived exosomes have been demonstrated to promote cardiac regeneration following myocardial infarction in preclinical studies. Recent studies have used intramyocardial injection in order to concentrate exosomes in the infarct. Though effective in a research setting, this method is not clinically appealing due to its invasive nature. We propose the use of a targeting peptide, cardiac homing peptide (CHP), to target intravenously-infused exosomes to the infarcted heart. Methods: Exosomes were conjugated with CHP through a DOPE-NHS linker. Ex vivo targeting was analyzed by incubating organ sections with the CHP exosomes and analyzing with fluorescence microscopy. In vitro assays were performed on neonatal rat cardiomyocytes and H9C2 cells. For the animal study, we utilized an ischemia/reperfusion rat model. Animals were treated with either saline, scramble peptide exosomes, or CHP exosomes 24 h after surgery. Echocardiography was performed 4 h after surgery and 21 d after surgery. At 21 d, animals were sacrificed, and organs were collected for analysis. Results: By conjugating the exosomes with CHP, we demonstrate increased retention of the exosomes within heart sections ex vivo and in vitro with neonatal rat cardiomyocytes. In vitro studies showed improved viability, reduced apoptosis and increased exosome uptake when using CHP-XOs. Using an animal model of ischemia/reperfusion injury, we measured the heart function, infarct size, cellular proliferation, and angiogenesis, with improved outcomes with the CHP exosomes. Conclusions: Our results demonstrate a novel method for increasing delivery of for treatment of myocardial infarction. By targeting exosomes to the infarcted heart, there was a significant improvement in outcomes with reduced fibrosis and scar size, and increased cellular proliferation and angiogenesis. PMID:29556361

Glucocorticoid excess and the developmental origins of disease: two decades of testing the hypothesis--2012 Curt Richter Award Winner.

PubMed

Reynolds, Rebecca M

2013-01-01

Low birthweight, a marker of an adverse in utero environment, is associated with cardiometabolic disease and brain disorders in adulthood. The adaptive changes made by the fetus in response to the intra-uterine environment result in permanent changes in physiology, structure and metabolism, a phenomenon termed early life programming. One of the key hypotheses to explain programming, namely over exposure of the developing fetus to glucocorticoids, was proposed nearly two decades ago, following the observation that the fetus was protected from high glucocorticoid levels in the mother by the actions of the placental barrier enzyme, 11β-hydroxysteroid dehydrogenase, which converts active glucocorticoids into inactive products. Numerous mechanistic studies in animal models have been carried out to test this hypothesis using manipulations to increase maternal glucocorticoids. Overall, these have resulted in offspring of lower birthweight, with an activated hypothalamic-pituitary-adrenal (HPA) axis and an adverse metabolic profile and behavioural phenotype in adulthood. Altered glucocorticoid activity or action is a good candidate mechanism in humans to link low birthweight with cardiometabolic and brain disorders. We have carried out detailed studies in men and women showing that high levels of endogenous glucocorticoids, or treatment with exogenous glucocorticoids, is associated with an adverse metabolic profile, increased cardiovascular disease and altered mood and cognitive decline. Our laboratory carried out the first translational studies in humans to test the glucocorticoid hypothesis, firstly demonstrating in studies of adult men and women, that low birthweight was associated with high fasting cortisol levels. We went on to dissect the mechanisms underlying the high fasting cortisol, demonstrating activation of the HPA axis, with increased cortisol responses to stimulation with exogenous adrenocorticotrophin hormone, lack of habituation to the stress of venepuncture, and increased cortisol responses to psychosocial stress. We have developed new dynamic tests to dissect the mechanisms regulating HPA axis central negative feedback sensitivity in humans, and demonstrated that this may be altered in obesity, one component of the metabolic syndrome. There are now studies in humans demonstrating that high circulating levels of maternal cortisol during pregnancy correlate negatively with birthweight, suggesting that excess glucocorticoids can by-pass the placental barrier. Deficiencies in the barrier enzyme, potentially increasing fetal glucocorticoid exposure, can also arise in association with maternal stress, malnutrition and disease, and can be inhibited by consumption of liquorice, which contains glycyrrhizin, an HSD inhibitor. Importantly, studies in humans have now demonstrated that high maternal cortisol in pregnancy and/or inhibition of HSD2 are associated with programmed outcomes in childhood including higher blood pressure, behavioural disorders as well as altered brain structure. We are investigating this further, using novel magnetic resonance imaging techniques to study the developing fetal brain in utero. The translational studies in support of the glucocorticoid hypothesis, and demonstrating that glucocorticoids are both mediators and targets of programming, are exciting and raise the question of whether this information can be used to identify those individuals most at risk of later life disease. In a recent study we showed that alterations in DNA methylation at genes important in regulating cortisol levels, tissue glucocorticoid action, blood pressure and fetal growth, are present in adulthood in association with both early life parameters and cardiometabolic risk factors. These preliminary data add to the limited literature in humans indicating a persisting epigenetic link between early life events and subsequent disease risk. Such findings open novel avenues for further exploration of the contribution of glucocorticoids to later life disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

Conditional Sox9 ablation improves locomotor recovery after spinal cord injury by increasing reactive sprouting.

PubMed

McKillop, William M; York, Elisa M; Rubinger, Luc; Liu, Tony; Ossowski, Natalie M; Xu, Kathy; Hryciw, Todd; Brown, Arthur

2016-09-01

The absence of axonal regeneration after spinal cord injury (SCI) has been attributed to the up-regulation of axon-repelling molecules, such as chondroitin sulfate proteoglycans (CSPGs) present in the glial scar that forms post-SCI. We previously identified the transcription factor SOX9 as a key up-regulator of CSPG production and also demonstrated that conditional Sox9 ablation leads to decreased CSPG levels and improved recovery of hind limb function after SCI. We herein demonstrate increased neural input onto spinal neurons caudal to the lesion in spinal cord injured Sox9 conditional knock out mice as indicated by increased levels of the presynaptic markers synaptophysin and vesicular glutamate transporter 1 (VGLUT1) compared to controls. Axonal sparing, long-range axonal regeneration and reactive sprouting were investigated as possible explanations for the increase in neural inputs caudal to the lesion and for the improved locomotor outcomes in spinal cord-injured Sox9 conditional knock out mice. Whereas retrograde tract-tracing studies failed to reveal any evidence for increased axonal sparing or for long-range regeneration in the Sox9 conditional knock out mice, anterograde tract-tracing experiments demonstrated increased reactive sprouting caudal to the lesion after SCI. Finally we demonstrate that application of a broad spectrum MMP inhibitor to reduce CSPG degradation in Sox9 conditional knock out mice prevents the improvements in locomotor recovery observed in untreated Sox9 conditional knock out mice. These results suggest that improved recovery of locomotor function in Sox9 conditional knock out mice after SCI is due to increased reactive sprouting secondary to reduced CSPG levels distal to the lesion. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of PGE2 receptor EP4 in pathologic ocular angiogenesis.

PubMed

Yanni, Susan E; Barnett, Joshua M; Clark, Monika L; Penn, John S

2009-11-01

PGE(2) binds to PGE(2) receptors (EP(1-4)). The purpose of the present study was to investigate the role of the EP(4) receptor in angiogenic cell behaviors of retinal Müller cells and retinal microvascular endothelial cells (RMECs) and to assess the efficacy of an EP(4) antagonist in rat models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (LCNV). Müller cells derived from COX-2-null mice were treated with increasing concentrations of the EP(4) agonist PGE(1)-OH, and wild-type Müller cells were treated with increasing concentrations of the EP(4) antagonist L-161982; VEGF production was assessed. Human RMECs (HRMECs) were treated with increasing concentrations of L-161982, and cell proliferation and tube formation were assessed. Rats subjected to OIR or LCNV were administered L-161982, and the neovascular area was measured. COX-2-null mouse Müller cells treated with increasing concentrations of PGE(1)-OH demonstrated a significant increase in VEGF production (P < or = 0.0165). Wild-type mouse Müller cells treated with increasing concentrations of L-161982 demonstrated a significant decrease in VEGF production (P < or = 0.0291). HRMECs treated with increasing concentrations of L-161982 demonstrated a significant reduction in VEGF-induced cell proliferation (P < or = 0.0033) and tube formation (P < 0.0344). L-161982 treatment significantly reduced pathologic neovascularization in OIR (P < 0.0069) and LCNV (P < or = 0.0329). Preliminary investigation has demonstrated that EP(4) activation or inhibition influences the behaviors of two retinal cell types known to play roles in pathologic ocular angiogenesis. These findings suggest that the EP(4) receptor may be a valuable therapeutic target in neovascular eye disease.

Attention and Activity in the Young Child.

ERIC Educational Resources Information Center

Tyler, S.; And Others

1979-01-01

Study I examined activity spans in four types of preschool establishments. Overall span was greatest in the nursery school and lowest in the day nursery. Study II examined attention spans in a primary school. Both studies demonstrated the influence of adults in increasing children's attention. (Author/SJL)

Retinoic acid stimulates interstitial collagenase messenger ribonucleic acid in osteosarcoma cells

NASA Technical Reports Server (NTRS)

Connolly, T. J.; Clohisy, J. C.; Shilt, J. S.; Bergman, K. D.; Partridge, N. C.; Quinn, C. O.

1994-01-01

The rat osteoblastic osteosarcoma cell line UMR 106-01 secretes interstitial collagenase in response to retinoic acid (RA). The present study demonstrates by Northern blot analysis that RA causes an increase in collagenase messenger RNA (mRNA) at 6 h, which is maximal at 24 h (20.5 times basal) and declines toward basal level by 72 h. This stimulation is dose dependent, with a maximal response at 5 x 10(-7) M RA. Nuclear run-on assays show a greater than 20-fold increase in the rate of collagenase mRNA transcription between 12-24 h after RA treatment. Cycloheximide blocks RA stimulation of collagenase mRNA, demonstrating the need for de novo protein synthesis. RA not only causes an increase in collagenase secretion, but is known to decrease collagen synthesis in UMR 106-01 cells. In this study, the increase in collagenase mRNA is accompanied by a concomitant decrease in the level of alpha 1(I) procollagen mRNA, which is maximal at 24 h (70% decrease), with a return to near-control levels by 72 h. Nuclear run-on assays demonstrated that the decrease in alpha 1 (I) procollagen expression does not have a statistically significant transcriptional component. RA did not statistically decrease the stability of alpha 1 (I) procollagen mRNA (calculated t1/2 = 8.06 +/- 0.30 and 9.01 +/- 0.62 h in the presence and absence of RA, respectively). However, transcription and stability together probably contribute to the major decrease in stable alpha 1 (I) procollagen mRNA observed. Cycloheximide treatment inhibits basal level alpha 1 (I) procollagen mRNA accumulation, demonstrating the need for on-going protein synthesis to maintain basal expression of this gene.

Neuromuscular training improves performance and lower-extremity biomechanics in female athletes.

PubMed

Myer, Gregory D; Ford, Kevin R; Palumbo, Joseph P; Hewett, Timothy E

2005-02-01

The purpose of this study was to examine the effects of a comprehensive neuromuscular training program on measures of performance and lower-extremity movement biomechanics in female athletes. The hypothesis was that significant improvements in measures of performance would be demonstrated concomitant with improved biomechanical measures related to anterior cruciate ligament injury risk. Forty-one female basketball, soccer, and volleyball players (age, 15.3 +/- 0.9 years; weight, 64.8 +/- 9.96 kg; height, 171.2 +/- 7.21 cm) underwent 6 weeks of training that included 4 main components (plyometric and movement, core strengthening and balance, resistance training, and speed training). Twelve age-, height-, and weight-matched controls underwent the same testing protocol twice 6 weeks apart. Trained athletes demonstrated increased predicted 1 repetition maximum squat (92%) and bench press (20%). Right and left single-leg hop distance increased 10.39 cm and 8.53 cm, respectively, and vertical jump also increased from 39.9 +/- 0.9 cm to 43.2 +/- 1.1 cm with training. Speed in a 9.1-m sprint improved from 1.80 +/- 0.02 seconds to 1.73 +/- 0.01 seconds. Pre- and posttest 3-dimensional motion analysis demonstrated increased knee flexion-extension range of motion during the landing phase of a vertical jump (right, 71.9 +/- 1.4 degrees to 76.9 +/- 1.4 degrees ; left, 71.3 +/- 1.5 degrees to 77.3 +/- 1.4 degrees ). Training decreased knee valgus (28%) and varus (38%) torques. Control subjects did not demonstrate significant alterations during the 6-week interval. The results of this study support the hypothesis that the combination of multiple-injury prevention-training components into a comprehensive program improves measures of performance and movement biomechanics.

A stable pattern of EEG spectral coherence distinguishes children with autism from neuro-typical controls - a large case control study.

PubMed

Duffy, Frank H; Als, Heidelise

2012-06-26

The autism rate has recently increased to 1 in 100 children. Genetic studies demonstrate poorly understood complexity. Environmental factors apparently also play a role. Magnetic resonance imaging (MRI) studies demonstrate increased brain sizes and altered connectivity. Electroencephalogram (EEG) coherence studies confirm connectivity changes. However, genetic-, MRI- and/or EEG-based diagnostic tests are not yet available. The varied study results likely reflect methodological and population differences, small samples and, for EEG, lack of attention to group-specific artifact. Of the 1,304 subjects who participated in this study, with ages ranging from 1 to 18 years old and assessed with comparable EEG studies, 463 children were diagnosed with autism spectrum disorder (ASD); 571 children were neuro-typical controls (C). After artifact management, principal components analysis (PCA) identified EEG spectral coherence factors with corresponding loading patterns. The 2- to 12-year-old subsample consisted of 430 ASD- and 554 C-group subjects (n = 984). Discriminant function analysis (DFA) determined the spectral coherence factors' discrimination success for the two groups. Loading patterns on the DFA-selected coherence factors described ASD-specific coherence differences when compared to controls. Total sample PCA of coherence data identified 40 factors which explained 50.8% of the total population variance. For the 2- to 12-year-olds, the 40 factors showed highly significant group differences (P < 0.0001). Ten randomly generated split half replications demonstrated high-average classification success (C, 88.5%; ASD, 86.0%). Still higher success was obtained in the more restricted age sub-samples using the jackknifing technique: 2- to 4-year-olds (C, 90.6%; ASD, 98.1%); 4- to 6-year-olds (C, 90.9%; ASD 99.1%); and 6- to 12-year-olds (C, 98.7%; ASD, 93.9%). Coherence loadings demonstrated reduced short-distance and reduced, as well as increased, long-distance coherences for the ASD-groups, when compared to the controls. Average spectral loading per factor was wide (10.1 Hz). Classification success suggests a stable coherence loading pattern that differentiates ASD- from C-group subjects. This might constitute an EEG coherence-based phenotype of childhood autism. The predominantly reduced short-distance coherences may indicate poor local network function. The increased long-distance coherences may represent compensatory processes or reduced neural pruning. The wide average spectral range of factor loadings may suggest over-damped neural networks.

Effects of martial arts exercise on body composition, serum biomarkers and quality of life in overweight/obese premenopausal women: a pilot study

PubMed Central

Chyu, Ming-Chien; Zhang, Yan; Brismée, Jean-Michel; Dagda, Raul Y.; Chaung, Eugene; Von Bergen, Vera; Doctolero, Susan; Shen, Chwan-Li

2013-01-01

Various exercise interventions have been shown to benefit weight control and general health in different populations. However, very few studies have been conducted on martial arts exercise (MAE). The objective of this pilot study is to evaluate the efficacy of 12 weeks of MAE intervention on body composition, serum biomarkers and quality of life (QOL) in overweight/obese premenopausal women. We found that subjects in the MAE group did not lose body weight, while they significantly decreased fat-free mass and muscle mass as compared to those in the control group, who demonstrated an increase in these parameters. The MAE group demonstrated an increase in serum IGF-I concentration, but no change in others. MAE may be a feasible and effective approach to improve body composition and QOL in overweight/obese premenopausal women. Our study underscores the need for further studies using larger samples to establish possible benefits of MAE in various populations. PMID:24665215

Structural myocardial alterations in diabetes and hypertension: the role of galectin-3.

PubMed

Seferovic, Jelena P; Lalic, Nebojsa M; Floridi, Federico; Tesic, Milorad; Seferovic, Petar M; Giga, Vojislav; Lalic, Katarina; Jotic, Aleksandra; Jovicic, Snezana; Colak, Emina; Salerno, Gerardo; Cardelli, Patrizia; Di Somma, Salvatore

2014-10-01

Galectin-3 is a protein widely distributed in the heart, brain and blood vessels, and has a regulatory role in inflammation, immunology and cancer. Many studies demonstrated that the increased level of galectin-3 is associated with progressive fibrosis and stiffening of the myocardium. The aim of this study was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D) and/or arterial hypertension (HT). Study population included 189 patients, with no coronary artery disease, divided into three groups: group 1 (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine laboratory tests, as well as specific biomarkers assessment [galectin-3, glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide (NT-proBNP)]. Cardiological evaluation included physical examination, transthoracic tissue Doppler echocardiography and stress echocardiography. The results of this study demonstrated significantly increased levels of galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left ventricular (LV) diameters and IVS thickness were increased in this group of patients. Furthermore, in the same cohort a positive correlation between galectin-3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a negative correlation between galectin-3 and LV end-diastolic diameter was revealed. This study revealed that levels of galectin-3 were higher in patients with both T2D and HT, and correlated with LV mass, indicating the potential role of this biomarker for early detection of myocardial structural and functional alterations.

Children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood.

PubMed

Leppert, Katherine A; Kushner, Marissa; Smith, Victoria C; Lemay, Edward P; Dougherty, Lea R

2016-12-01

This study examined the stability of children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood. Ninety-six children (51 males) completed stress-inducing laboratory tasks and provided five salivary cortisol samples in early (W1) and middle (W2) childhood. Although W1 cortisol responses did not predict W2 cortisol responses, children's cortisol responses demonstrated change: compared to their W1 cortisol responses, children's W2 cortisol responses demonstrated an increased slope and more negative quadratic curvature. Furthermore, child psychiatric symptoms at W1 moderated the stability of children's cortisol responses. Children with fewer preschool psychiatric symptoms demonstrated greater inter-individual and intra-individual stability, whereas children with higher preschool psychiatric symptoms and comorbidity demonstrated systematic inter-individual and intra-individual instability in cortisol responses over time. Findings suggest a developmental shift toward increasing cortisol stress responses from early to middle childhood and highlight preschool psychopathology as a moderator of stability in children's cortisol responses over time. © 2016 Wiley Periodicals, Inc.

Alcohol and the risk of myocardial infarction.

PubMed

Flesch, M; Rosenkranz, S; Erdmann, E; Böhm, M

2001-04-01

Epidemiological studies have repeatedly demonstrated a beneficial effect of moderate alcohol consumption on the incidence of coronary heart disease, myocardial infarction and overall mortality. The latter increases with excessive alcohol consumption. Although most epidemiological studies demonstrate a beneficial effect of alcohol consumption independent from the specific kind of alcoholic beverage, there is increasing evidence that wine and in particular red wine might contain pharmacological substances, which prevent atherosclerosis and myocardial infarction independent from the wine ethanol. Pathophysiological mechanisms mediating these beneficial effects include effects of wine phenols and tannins on LDL-cholesterol oxidation status, thrombocyte aggregation, endothelial function and smooth muscle cell proliferation. Identification and characterization of the pharmacologically active substances might provide the stage for the development of new substances to be used in the prevention of coronary artery disease and myocardial infarction.

Effects of noise on vascular function, oxidative stress, and inflammation: mechanistic insight from studies in mice

PubMed Central

Münzel, Thomas; Daiber, Andreas; Steven, Sebastian; Tran, Lan P.; Ullmann, Elisabeth; Kossmann, Sabine; Schmidt, Frank P.; Oelze, Matthias; Xia, Ning; Li, Huige; Pinto, Antonio; Wild, Philipp; Pies, Kai; Schmidt, Erwin R.; Rapp, Steffen; Kröller-Schön, Swenja

2017-01-01

Abstract Aims Epidemiological studies indicate that traffic noise increases the incidence of coronary artery disease, hypertension and stroke. The underlying mechanisms remain largely unknown. Field studies with nighttime noise exposure demonstrate that aircraft noise leads to vascular dysfunction, which is markedly improved by vitamin C, suggesting a key role of oxidative stress in causing this phenomenon. Methods and results We developed a novel animal model to study the vascular consequences of aircraft noise exposure. Peak sound levels of 85 and mean sound level of 72 dBA applied by loudspeakers for 4 days caused an increase in systolic blood pressure, plasma noradrenaline and angiotensin II levels and induced endothelial dysfunction. Noise increased eNOS expression but reduced vascular NO levels because of eNOS uncoupling. Noise increased circulating levels of nitrotyrosine, interleukine-6 and vascular expression of the NADPH oxidase subunit Nox2, nitrotyrosine-positive proteins and of endothelin-1. FACS analysis demonstrated an increase in infiltrated natural killer-cells and neutrophils into the vasculature. Equal mean sound pressure levels of white noise for 4 days did not induce these changes. Comparative Illumina sequencing of transcriptomes of aortic tissues from aircraft noise-treated animals displayed significant changes of genes in part responsible for the regulation of vascular function, vascular remodelling, and cell death. Conclusion We established a novel and unique aircraft noise stress model with increased blood pressure and vascular dysfunction associated with oxidative stress. This animal model enables future studies of molecular mechanisms, mitigation strategies, and pharmacological interventions to protect from noise-induced vascular damage. PMID:28329261

Role of Resistant Starch in Improving Gut Health, Adiposity, and Insulin Resistance1234

PubMed Central

Keenan, Michael J; Zhou, June; Hegsted, Maren; Pelkman, Christine; Durham, Holiday A; Coulon, Diana B; Martin, Roy J

2015-01-01

The realization that low–glycemic index diets were formulated using resistant starch led to more than a decade of research on the health effects of resistant starch. Determination of the metabolizable energy of the resistant starch product allowed for the performance of isocaloric studies. Fermentation of resistant starch in rodent studies results in what appears to be a healthier gut, demonstrated by increased amounts of short-chain fatty acids, an apparent positive change in the microbiota, and increased gene expression for gene products involved in normal healthy proliferation and apoptosis of potential cancer cells. Additionally, consumption of resistant starch was associated with reduced abdominal fat and improved insulin sensitivity. Increased serum glucagon-like peptide 1 (GLP-1) likely plays a role in promoting these health benefits. One rodent study that did not use isocaloric diets demonstrated that the use of resistant starch at 8% of the weight of the diet reduced body fat. This appears to be approximately equivalent to the human fiber requirement. In human subjects, insulin sensitivity is increased with the feeding of resistant starch. However, only 1 of several studies reports an increase in serum GLP-1 associated with resistant starch added to the diet. This means that other mechanisms, such as increased intestinal gluconeogenesis or increased adiponectin, may be involved in the promotion of improved insulin sensitivity. Future research may confirm that there will be improved health if human individuals consume the requirement for dietary fiber and a large amount of the fiber is fermentable. PMID:25770258

Role of resistant starch in improving gut health, adiposity, and insulin resistance.

PubMed

Keenan, Michael J; Zhou, June; Hegsted, Maren; Pelkman, Christine; Durham, Holiday A; Coulon, Diana B; Martin, Roy J

2015-03-01

The realization that low-glycemic index diets were formulated using resistant starch led to more than a decade of research on the health effects of resistant starch. Determination of the metabolizable energy of the resistant starch product allowed for the performance of isocaloric studies. Fermentation of resistant starch in rodent studies results in what appears to be a healthier gut, demonstrated by increased amounts of short-chain fatty acids, an apparent positive change in the microbiota, and increased gene expression for gene products involved in normal healthy proliferation and apoptosis of potential cancer cells. Additionally, consumption of resistant starch was associated with reduced abdominal fat and improved insulin sensitivity. Increased serum glucagon-like peptide 1 (GLP-1) likely plays a role in promoting these health benefits. One rodent study that did not use isocaloric diets demonstrated that the use of resistant starch at 8% of the weight of the diet reduced body fat. This appears to be approximately equivalent to the human fiber requirement. In human subjects, insulin sensitivity is increased with the feeding of resistant starch. However, only 1 of several studies reports an increase in serum GLP-1 associated with resistant starch added to the diet. This means that other mechanisms, such as increased intestinal gluconeogenesis or increased adiponectin, may be involved in the promotion of improved insulin sensitivity. Future research may confirm that there will be improved health if human individuals consume the requirement for dietary fiber and a large amount of the fiber is fermentable. © 2015 American Society for Nutrition.

The effect of an online referral system on referrals to bariatric surgery.

PubMed

Doumouras, Aristithes G; Anvari, Sama; Breau, Ruth; Anvari, Mehran; Hong, Dennis; Gmora, Scott

2017-12-01

The Ontario Bariatric Network implemented an online referral system to completely replace a fax-based system in 2015. Strategies such as electronic information transfer have been suggested to improve the bariatric referral process but few studies exist demonstrating their efficacy. Therefore, the purpose of this study was to determine the impact on referral rates to bariatric surgery after converting to an online referral system from a fax-based system. All referrals from 2011 to 2015 were included in the study. The main outcomes included the total number of referrals and whether a practitioner increased referrals after the implementation of the online referral system. A hierarchical logistic regression model was used for the final analysis. Predictors of interest included physician and neighbourhood level factors RESULTS: Referrals more than doubled overall and increased significantly across all health regions. Compared to practitioners in their first five years, all other experience groups were approximately 50% less likely to increase referrals. Compared to those within 50 km of a bariatric facility, practitioners 50-99 km (OR 0.76 95% CI 0.58-0.98 p = 0.04) and 100-199 km (OR 0.73 95% CI 0.55-0.96 p = 0.03) away were both significantly less likely to increase referrals. This study found that referrals increased significantly after implementing an online referral system. Furthermore, physicians in their first five years of practice as well as those practicing closer to bariatric centers were more likely to increase referrals. Our findings demonstrate that an online referral system may aid in increasing referrals to bariatric surgery.

Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing autophagic flux disturbance and inhibiting apoptosis.

PubMed

Jeong, Ji Heun; Yu, Kwang Sik; Bak, Dong Ho; Lee, Je Hun; Lee, Nam Seob; Jeong, Young Gil; Kim, Dong Kwan; Kim, Jwa-Jin; Han, Seung-Yun

2016-11-01

Previous studies have demonstrated that autophagy induced by caloric restriction (CR) is neuroprotective against cerebral ischemia. However, it has not been determined whether intermittent fasting (IF), a variation of CR, can exert autophagy-related neuroprotection against cerebral ischemia. Therefore, the neuroprotective effect of IF was evaluated over the course of two weeks in a rat model of focal cerebral ischemia, which was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). Specifically, the role of autophagy modulation as a potential underlying mechanism for this phenomenon was investigated. It was demonstrated that IF reduced infarct volume and brain edema, improved neurobehavioral deficits, and rescued neuronal loss after MCAO/R. Furthermore, neuronal apoptosis was decreased by IF in the rat cortex. An increase in the number of autophagosomes (APs) was demonstrated in the cortices of IF-treated rats, using immunofluorescence staining and transmission electron microscopy. Using immunoblots, an IF-induced increase was detected in microtubule-associated protein 1 light chain 3 (LC3)-II, Rab7, and cathepsin D protein levels, which corroborated previous morphological studies. Notably, IF reduced the accumulation of APs and p62, demonstrating that IF attenuated the MCAO/R-induced disturbance of autophagic flux in neurons. The findings of the present study suggest that IF-induced neuroprotection in focal cerebral ischemia is due, at least in part, to the minimization of autophagic flux disturbance and inhibition of apoptosis.

Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

PubMed Central

Lee, Chun Geun; Herzog, Erica L.; Ahangari, Farida; Zhou, Yang; Gulati, Mridu; Lee, Chang-Min; Peng, Xueyan; Feghali-Bostwick, Carol; Jimenez, Sergio A.; Varga, John; Elias, Jack A.

2014-01-01

Interstitial lung disease (ILD) with pulmonary fibrosis is an important manifestation in systemic sclerosis (SSc, scleroderma) where it portends a poor prognosis. However, biomarkers that predict the development and or severity of SSc-ILD have not been validated, and the pathogenetic mechanisms that engender this pulmonary response are poorly understood. In this study, we demonstrate in two different patient cohorts that the levels of chitotriosidase (Chit1) bioactivity and protein are significantly increased in the circulation and lungs of SSc patients compared with demographically matched controls. We also demonstrate that, compared with patients without lung involvement, patients with ILD show high levels of circulating Chit1 activity that correlate with disease severity. Murine modeling shows that in comparison with wild-type mice, bleomycin-induced pulmonary fibrosis was significantly reduced in Chit1−/− mice and significantly enhanced in lungs from Chit1 overexpressing transgenic animals. In vitro studies also demonstrated that Chit1 interacts with TGF-β1 to augment fibroblast TGF-β receptors 1 and 2 expression and TGF-β–induced Smad and MAPK/ERK activation. These studies indicate that Chit1 is potential biomarker for ILD in SSc and a therapeutic target in SSc-associated lung fibrosis and demonstrate that Chit1 augments TGF-β1 effects by increasing receptor expression and canonical and noncanonical TGF-β1 signaling. PMID:22826322

Does sports participation (including level of performance and previous injury) increase risk of osteoarthritis? A systematic review and meta-analysis

PubMed Central

Tran, Gui; Smith, Toby O; Grice, Adam; Kingsbury, Sarah R; McCrory, Paul; Conaghan, Philip G

2016-01-01

Background To assess the relationship between sport and osteoarthritis (OA), and specifically to determine whether previous participation, in terms of level (elite or non-elite), type of sport, intensity or previous injury, was associated with OA. Methods This systematic review was developed using PRISMA guidelines. Databases were searched (to May 2016). Narrative review and meta-analysis (with risk ratio (RR) and 95% CIs) approaches were undertaken where appropriate. Study quality was assessed using GRADE. Results 46 studies were included. Narratively, 31 studies reported an increased risk of OA, with 19 demonstrating an increased risk in elite athletes. There was an increased risk after sports exposure (irrespective of type; RR 1.37; 95% CI 1.14 to 1.64; 21 studies). It remained uncertain whether there was a difference in risk of OA between elite and non-elite athletes (RR 1.37; 95% CI 0.84 to 2.22; 17 studies). The risk was higher in soccer (RR 1.42; 95% CI 1.14 to 1.77; 15 studies) but lower in runners (RR 0.86; 95% CI 0.53 to 1.41; 12 studies). 9 studies showed an association with the intensity of sport undertaken and OA. 5 studies demonstrated a higher prevalence of OA following meniscectomies and anterior cruciate ligament tears. Overall, the evidence was of GRADE ‘very low’ quality. Conclusions There was very low-quality evidence to support an increased relationship between sports participation and OA in elite participants. It is unclear whether there is a difference in risk between elite and non-elite participants with further prospective studies needed to evaluate this. Pooled findings suggested that significant injuries were associated with OA in soccer players. PMID:27683348

Topographic and sex-related differences in sleep spindles in major depressive disorder: a high-density EEG investigation.

PubMed

Plante, D T; Goldstein, M R; Landsness, E C; Peterson, M J; Riedner, B A; Ferrarelli, F; Wanger, T; Guokas, J J; Tononi, G; Benca, R M

2013-03-20

Sleep spindles are believed to mediate several sleep-related functions including maintaining disconnection from the external environment during sleep, cortical development, and sleep-dependent memory consolidation. Prior studies that have examined sleep spindles in major depressive disorder (MDD) have not demonstrated consistent differences relative to control subjects, which may be due to sex-related variation and limited spatial resolution of spindle detection. Thus, this study sought to characterize sleep spindles in MDD using high-density electroencephalography (hdEEG) to examine the topography of sleep spindles across the cortex in MDD, as well as sex-related variation in spindle topography in the disorder. All-night hdEEG recordings were collected in 30 unipolar MDD participants (19 women) and 30 age and sex-matched controls. Topography of sleep spindle density, amplitude, duration, and integrated spindle activity (ISA) were assessed to determine group differences. Spindle parameters were compared between MDD and controls, including analysis stratified by sex. As a group, MDD subjects demonstrated significant increases in frontal and parietal spindle density and ISA compared to controls. When stratified by sex, MDD women demonstrated increases in frontal and parietal spindle density, amplitude, duration, and ISA; whereas MDD men demonstrated either no differences or decreases in spindle parameters. Given the number of male subjects, this study may be underpowered to detect differences in spindle parameters in male MDD participants. This study demonstrates topographic and sex-related differences in sleep spindles in MDD. Further research is warranted to investigate the role of sleep spindles and sex in the pathophysiology of MDD. Copyright © 2012 Elsevier B.V. All rights reserved.

Increasing Parent Engagement in Student Learning Using an Intelligent Tutoring System

ERIC Educational Resources Information Center

Broderick, Zachary; O'Connor, Christine; Mulcahy, Courtney; Heffernan, Neil; Heffernan, Christina

2011-01-01

This study demonstrates the ability of an Intelligent Tutoring System (ITS) to increase parental engagement in student learning. A parent notification feature was developed for the web-based ASSISTment ITS that allows parents to log into their own accounts and access detailed data about their students' performance. Parents from a local middle…

The Development of Gamified Learning Activities to Increase Student Engagement in Learning

ERIC Educational Resources Information Center

Poondej, Chanut; Lerdpornkulrat, Thanita

2016-01-01

In the literature, the potential efficacy of the gamification of education has been demonstrated. The aim of this study was to explore the influence of applying gamification techniques to increase student engagement in learning. The quasi-experimental nonequivalent-control group design was used with 577 undergraduate students from six classes. The…

Writers Develop Skills through Collaboration: An Action Research Approach

ERIC Educational Resources Information Center

Ferguson-Patrick, Kate

2007-01-01

Collaborative approaches designed to increase writing productivity (amount written) as well as writing quality were implemented over a period of six months with a small group of 12 six-year-olds in a Primary School in Newcastle, NSW, Australia. The study demonstrated the positive nature of peer interactions with an increase in quality and…

Reaction rates of oxygen with hemoglobin measured by non-equilibrium facilitated oxygen diffusion through hemoglobin solutions.

PubMed

Bouwer, S T; Hoofd, L; Kreuzer, F

2001-02-16

The purpose of this study was to verify the concept of non-equilibrium facilitated oxygen diffusion. This work succeeds our previous study, where facilitated oxygen diffusion by hemoglobin was measured at conditions of chemical equilibrium, and which yielded diffusion coefficients of hemoglobin and of oxygen. In the present work chemical non-equilibrium was induced using very thin diffusion layers. As a result, facilitation was decreased as predicted by theory. Thus, this work presents the first experimental demonstration of non-equilibrium facilitated oxygen diffusion. In addition, association and dissociation rate parameters of the reaction between oxygen and bovine and human hemoglobin were calculated and the effect of the homotropic and heterotropic interactions on each rate parameter was demonstrated. The results indicate that the homotropic interaction--which leads to increasing oxygen affinity with increasing oxygenation--is predominantly due to an increase in the association rate. The heterotropic interaction--which leads to decreasing oxygen affinity by anionic ligands--appears to be effected in two ways. Cl- increases the dissociation rate. In contrast, 2,3-diphosphoglycerate decreases the association rate.

Carbohydrate and exercise performance: the role of multiple transportable carbohydrates.

PubMed

Jeukendrup, Asker E

2010-07-01

Carbohydrate feeding has been shown to be ergogenic, but recently substantial advances have been made in optimizing the guidelines for carbohydrate intake during prolonged exercise. It was found that limitations to carbohydrate oxidation were in the absorptive process most likely because of a saturation of carbohydrate transporters. By using a combination of carbohydrates that use different intestinal transporters for absorption it was shown that carbohydrate delivery and oxidation could be increased. Studies demonstrated increases in exogenous carbohydrate oxidation rates of up to 65% of glucose: fructose compared with glucose only. Exogenous carbohydrate oxidation rates reach values of 1.75 g/min whereas previously it was thought that 1 g/min was the absolute maximum. The increased carbohydrate oxidation with multiple transportable carbohydrates was accompanied by increased fluid delivery and improved oxidation efficiency, and thus the likelihood of gastrointestinal distress may be diminished. Studies also demonstrated reduced fatigue and improved exercise performance with multiple transportable carbohydrates compared with a single carbohydrate. Multiple transportable carbohydrates, ingested at high rates, can be beneficial during endurance sports in which the duration of exercise is 3 h or more.

Camera system resolution and its influence on digital image correlation

DOE PAGES

Reu, Phillip L.; Sweatt, William; Miller, Timothy; ...

2014-09-21

Digital image correlation (DIC) uses images from a camera and lens system to make quantitative measurements of the shape, displacement, and strain of test objects. This increasingly popular method has had little research on the influence of the imaging system resolution on the DIC results. This paper investigates the entire imaging system and studies how both the camera and lens resolution influence the DIC results as a function of the system Modulation Transfer Function (MTF). It will show that when making spatial resolution decisions (including speckle size) the resolution limiting component should be considered. A consequence of the loss ofmore » spatial resolution is that the DIC uncertainties will be increased. This is demonstrated using both synthetic and experimental images with varying resolution. The loss of image resolution and DIC accuracy can be compensated for by increasing the subset size, or better, by increasing the speckle size. The speckle-size and spatial resolution are now a function of the lens resolution rather than the more typical assumption of the pixel size. The study will demonstrate the tradeoffs associated with limited lens resolution.« less

Effects of poly(lactic-co-glycolic acid) on preparation and characteristics of plasmid DNA-loaded solid lipid nanoparticles.

PubMed

Zhu, L; Xie, S; Dong, Z; Wang, X; Wang, Y; Zhou, W

2011-09-01

Poly(lactic-co-glycolic acid) (PLGA) was used as a polymeric emulsifier to encapsulate plasmid DNA into hydrogenated castor oil (HCO)-solid lipid nanoparticles (SLN) by w/o/w double emulsion and solvent evaporation techniques. The effects of PLGA on the preparation, characteristics and transfection efficiency of DNA-loaded SLN were studied. The results showed that PLGA was essential to form the primary w/o emulsion and the stability of the emulsion was enhanced with the increase of PLGA content. DNA-loaded SLN were spherical with smooth surfaces. The SLN had a negative charge in weak acid and alkaline environment but acquired a positive charge in acidic pH and the cationisation capacity of the SLN increased with the increase of PLGA/HCO ratio. Agarose gel electrophoresis demonstrated that the majority of the DNA maintained its structural integrity after preparation and being extracted or released from DNA-loaded SLN. When PLGA/HCO ratio increased from 5 to 15%, the encapsulation efficiency, loading capacity and transfection efficiency of the nanoparticles increased significantly, whereas the changes of particle size and polydispersity index were insignificant. Cytotoxicity study in cell culture demonstrated that the SLN was not toxic.

Bridging the Performance Gap with Ergonomics: A Case Study

ERIC Educational Resources Information Center

Rethaber, James D.

2011-01-01

Faced with increased incidences of work-related strain and sprain injuries and OSHA-recordable injuries, the organization in this case study details how it resolved these performance-related issues. This case study also demonstrates the effectiveness of Thomas Gilbert's (1978) Behavior Engineering Model as a tool for analyzing, defining, and…

Restricted emigration, system inescapability, and defense of the status quo: system-justifying consequences of restricted exit opportunities.

PubMed

Laurin, Kristin; Shepherd, Steven; Kay, Aaron C

2010-08-01

The freedom to emigrate at will from a geographic location is an internationally recognized human right. However, this right is systematically violated by restrictive migration policies. In three experiments, we explored the psychological consequences of violating the right to mobility. Our results suggest that, ironically, restricted freedom of movement can lead to increased system justification (i.e., increased support of the status quo). In Study 1, we found that participants who read that their country was difficult to leave became stronger defenders of their system's legitimacy than before, even in domains unrelated to emigration policy (e.g., gender relations). In Study 2, we demonstrated that this increased system defense was the result of a motivated process. In Study 3, we broadened the scope of this psychological phenomenon by conceptually replicating it using a different system (participants' university) and measure of system defense. The importance of these two findings-the first experimental demonstration of the psychological consequences of restrictive emigration policies and the introduction of a novel psychological phenomenon-is discussed.

Evaluation of the challenges faced in increasing contraceptive access within a community college population.

PubMed

Lamme, Jacqueline; Edelman, Alison; Padua, Emily; Jensen, Jeffrey T

2017-01-01

Research demonstrates removing barriers to access, decreasing costs and offering same-day placement of long-acting reversible contraception (LARC) increases contraceptive uptake in young women. For those in community college (CC), LARC utilization might reduce the risk of dropout and improve degree completion. We identified a local school who had documented an unmet need for on-campus services through a recent student assessment. We then established an on-campus, same day contraceptive clinic at the CC as part of a clinical trial. We found that students did not use the service even after multiple attempts to increase awareness and we ended the study. Here, we report lessons learned from attempting research in this environment in addition to results from a follow-up survey to determine why students did not access the clinical resource. Students reported that they already had good access to contraception and preferred to get their healthcare off-campus. This study demonstrates the complexities of studying highly focused interventions to influence access to care in the current health care environment with ever changing regulations. NCT02735551 . Registered April 6, 2016.

Usefulness of two clinical chorioamnionitis definitions in predicting neonatal infectious outcomes: a systematic review.

PubMed

Avila, Cecilia; Willins, Jennifer L; Jackson, Matthew; Mathai, Jacob; Jabsky, Marina; Kong, Alex; Callaghan, Fiona; Ishkin, Selda; Shroyer, A Laurie W

2015-09-01

To assess the usefulness of two definitions of acute clinical chorioamnionitis (ACCA) in predicting risk of neonatal infectious outcomes (NIO) and mortality, the first definition requiring maternal fever alone (Fever), and the second requiring ≥ 1 Gibbs criterion besides fever (Fever + 1). PubMed, Web of Science, and the Cochrane Database of Systematic Reviews were searched from January 1, 1979 to April 9, 2013. Twelve studies were reviewed (of 316 articles identified): three studies with term patients, four with preterm premature rupture of membranes (PPROM) patients, and five mixed studies with mixed gestational ages and/or membrane status (intact and/or ruptured). Both definitions demonstrated an increased NIO risk for ACCA versus non-ACCA patients, with an odds ratio increase for the Fever + 1 definition that was about twofold larger than the Fever definition. As the Fever definition demonstrated increased NIO risk for ACCA versus non-ACCA patients, the Fever alone ACCA definition should be used to trigger future clinical treatment in many clinical situations. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Targeting, Segmenting and Positioning the Market for College Students to Increase Customer Satisfaction and Overall Performance

ERIC Educational Resources Information Center

Wright, Robert E.

2008-01-01

Numerous studies have explored the relationship between marketing efforts and firm financial performance. Studies have looked at potential lifetime value of customers, to demonstrate the value of keeping customers. Various other studies have looked at the relationship between customer satisfaction and firm performance. However, few studies have…

Using Dynamic Walking Models to Identify Factors that Contribute to Increased Risk of Falling in Older Adults

PubMed Central

Roos, Paulien E.; Dingwell, Jonathan B.

2013-01-01

Falls are common in older adults. The most common cause of falls is tripping while walking. Simulation studies demonstrated that older adults may be restricted by lower limb strength and movement speed to regain balance after a trip. This review examines how modeling approaches can be used to determine how different measures predict actual fall risk and what some of the causal mechanisms of fall risk are. Although increased gait variability predicts increased fall risk experimentally, it is not clear which variability measures could best be used, or what magnitude of change corresponded with increased fall risk. With a simulation study we showed that the increase in fall risk with a certain increase in gait variability was greatly influenced by the initial level of variability. Gait variability can therefore not easily be used to predict fall risk. We therefore explored other measures that may be related to fall risk and investigated the relationship between stability measures such as Floquet multipliers and local divergence exponents and actual fall risk in a dynamic walking model. We demonstrated that short-term local divergence exponents were a good early predictor for fall risk. Neuronal noise increases with age. It has however not been fully understood if increased neuronal noise would cause an increased fall risk. With our dynamic walking model we showed that increased neuronal noise caused increased fall risk. Although people who are at increased risk of falling reduce their walking speed it had been questioned whether this slower speed would actually cause a reduced fall risk. With our model we demonstrated that a reduced walking speed caused a reduction in fall risk. This may be due to the decreased kinematic variability as a result of the reduced signal-dependent noise of the smaller muscle forces that are required for slower. These insights may be used in the development of fall prevention programs in order to better identify those at increased risk of falling and to target those factors that influence fall risk most. PMID:24120280

Using dynamic walking models to identify factors that contribute to increased risk of falling in older adults.

PubMed

Roos, Paulien E; Dingwell, Jonathan B

2013-10-01

Falls are common in older adults. The most common cause of falls is tripping while walking. Simulation studies demonstrated that older adults may be restricted by lower limb strength and movement speed to regain balance after a trip. This review examines how modeling approaches can be used to determine how different measures predict actual fall risk and what some of the causal mechanisms of fall risk are. Although increased gait variability predicts increased fall risk experimentally, it is not clear which variability measures could best be used, or what magnitude of change corresponded with increased fall risk. With a simulation study we showed that the increase in fall risk with a certain increase in gait variability was greatly influenced by the initial level of variability. Gait variability can therefore not easily be used to predict fall risk. We therefore explored other measures that may be related to fall risk and investigated the relationship between stability measures such as Floquet multipliers and local divergence exponents and actual fall risk in a dynamic walking model. We demonstrated that short-term local divergence exponents were a good early predictor for fall risk. Neuronal noise increases with age. It has however not been fully understood if increased neuronal noise would cause an increased fall risk. With our dynamic walking model we showed that increased neuronal noise caused increased fall risk. Although people who are at increased risk of falling reduce their walking speed it had been questioned whether this slower speed would actually cause a reduced fall risk. With our model we demonstrated that a reduced walking speed caused a reduction in fall risk. This may be due to the decreased kinematic variability as a result of the reduced signal-dependent noise of the smaller muscle forces that are required for slower. These insights may be used in the development of fall prevention programs in order to better identify those at increased risk of falling and to target those factors that influence fall risk most. Copyright © 2013 Elsevier B.V. All rights reserved.

Biomimetic nanoparticles with enhanced affinity towards activated endothelium as versatile tools for theranostic drug delivery

PubMed Central

Martinez, Jonathan O.; Molinaro, Roberto; Hartman, Kelly A.; Boada, Christian; Sukhovershin, Roman; De Rosa, Enrica; Kirui, Dickson; Zhang, Shanrong; Evangelopoulos, Michael; Carter, Angela M.; Bibb, James A.; Cooke, John P.; Tasciotti, Ennio

2018-01-01

Activation of the vascular endothelium is characterized by increased expression of vascular adhesion molecules and chemokines. This activation occurs early in the progression of several diseases and triggers the recruitment of leukocytes. Inspired by the tropism of leukocytes, we investigated leukocyte-based biomimetic nanoparticles (i.e., leukosomes) as a novel theranostic platform for inflammatory diseases. Methods: Leukosomes were assembled by combining phospholipids and membrane proteins from leukocytes. For imaging applications, phospholipids modified with rhodamine and gadolinium were used. Leukosomes incubated with antibodies blocking lymphocyte function-associated antigen 1 (LFA-1) and CD45 were administered to explore their roles in targeting inflammation. In addition, relaxometric assessment of NPs was evaluated. Results: Liposomes and leukosomes were both spherical in shape with sizes ranging from 140-170 nm. Both NPs successfully integrated 8 and 13 µg of rhodamine and gadolinium, respectively, and demonstrated less than 4% variation in physicochemical features. Leukosomes demonstrated a 16-fold increase in breast tumor accumulation relative to liposomes. Furthermore, quantification of leukosomes in tumor vessels demonstrated a 4.5-fold increase in vessel lumens and a 14-fold increase in vessel walls. Investigating the targeting mechanism of action revealed that blockage of LFA-1 on leukosomes resulted in a 95% decrease in tumor accumulation. Whereas blockage of CD45 yielded a 60% decrease in targeting and significant increases in liver and spleen accumulation. In addition, when administered in mice with atherosclerotic plaques, leukosomes exhibited a 4-fold increase in the targeting of inflammatory vascular lesions. Lastly, relaxometric assessment of NPs demonstrated that the incorporation of membrane proteins into leukosomes did not impact the r1 and r2 relaxivities of the NPs, demonstrating 6 and 30 mM-1s-1, respectively. Conclusion: Our study demonstrates the ability of leukosomes to target activated vasculature and exhibit superior accumulation in tumors and vascular lesions. The versatility of the phospholipid backbone within leukosomes permits the incorporation of various contrast agents. Furthermore, leukosomes can potentially be loaded with therapeutics possessing diverse physical properties and thus warrant further investigation toward the development of powerful theranostic agents. PMID:29464004

Experimental and DFT Studies of the Electron-Withdrawing Ability of Perfluoroalkyl (R F) Groups: Electron Affinities of PAH(R F) n Increase Significantly with Increasing R F Chain Length

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

San, Long K.; Spisak, Sarah N.; Dubceac, Cristina

Two series of aromatic compounds with perfluoroalkyl (RF) groups of increasing length, 1,3,5,7-naphthalene(RF)4 and 1,3,5,7,9-corannulene(RF)5, have been prepared and their electronic properties studied by low-temperature PES (i.e., gas-phase electron affinity (EA) measurements). These and many related compounds were also studied by DFT calculations. The data demonstrate unambiguously that the electron-withdrawing ability of RF substituents increases significantly and uniformly from CF3 to C2F5 to n-C3F7 to n-C4F9.

Experimental and DFT Studies of the Electron-Withdrawing Ability of Perfluoroalkyl (R-F) Groups: Electron Affinities of PAH(R-F)(n) Increase Significantly with Increasing R-F Chain Length

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

San, Long K.; Spisak, Sarah N.; Dubceac, Cristina

2018-01-26

Two series of aromatic compounds with perfluoroalkyl (RF) groups of increasing length, 1,3,5,7-naphthalene(RF)4 and 1,3,5,7,9-corannulene(RF)5, have been prepared and their electronic properties studied by low-temperature PES (i.e., gas-phase electron affinity (EA) measurements). These and many related compounds were also studied by DFT calculations. The data demonstrate unambiguously that the electron-withdrawing ability of RF substituents increases significantly and uniformly from CF3 to C2F5 to n-C3F7 to n-C4F9.

Affordable Development and Demonstration of a Small NTR engine and Stage: A Preliminary NASA, DOE, and Industry Assessment

NASA Technical Reports Server (NTRS)

Borowski, S. K.; Sefcik, R. J.; Fittje, J. E.; McCurdy, D. R.; Qualls, A. L.; Schnitzler, B. G; Werner, J.; Weitzberg, A.; Joyner, C. R.

2015-01-01

In FY'11, Nuclear Thermal Propulsion (NTP) was identified as a key propulsion option under the Advanced In-Space Propulsion (AISP) component of NASA's Exploration Technology Development and Demonstration (ETDD) program A strategy was outlined by GRC and NASA HQ that included 2 key elements -"Foundational Technology Development" followed by specific "Technology Demonstration" projects. The "Technology Demonstration "element proposed ground technology demonstration (GTD) testing in the early 2020's, followed by a flight technology demonstration (FTD) mission by approx. 2025. In order to reduce development costs, the demonstration projects would focus on developing a small, low thrust (approx. 7.5 -16.5 klb(f)) engine that utilizes a "common" fuel element design scalable to the higher thrust (approx. 25 klb(f)) engines used in NASA's Mars DRA 5.0 study(NASA-SP-2009-566). Besides reducing development costs and allowing utilization of existing, flight proven engine hard-ware (e.g., hydrogen pumps and nozzles), small, lower thrust ground and flight demonstration engines can validate the technology and offer improved capability -increased payloads and decreased transit times -valued for robotic science missions identified in NASA's Decadal Study.

Sex differences and structural brain maturation from childhood to early adulthood.

PubMed

Koolschijn, P Cédric M P; Crone, Eveline A

2013-07-01

Recent advances in structural brain imaging have demonstrated that brain development continues through childhood and adolescence. In the present cross-sectional study, structural MRI data from 442 typically developing individuals (range 8-30) were analyzed to examine and replicate the relationship between age, sex, brain volumes, cortical thickness and surface area. Our findings show differential patterns for subcortical and cortical areas. Analysis of subcortical volumes showed that putamen volume decreased with age and thalamus volume increased with age. Independent of age, males demonstrated larger amygdala and thalamus volumes compared to females. Cerebral white matter increased linearly with age, at a faster pace for females than males. Gray matter showed nonlinear decreases with age. Sex-by-age interactions were primarily found in lobar surface area measurements, with males demonstrating a larger cortical surface up to age 15, while cortical surface in females remained relatively stable with increasing age. The current findings replicate some, but not all prior reports on structural brain development, which calls for more studies with large samples, replications, and specific tests for brain structural changes. In addition, the results point toward an important role for sex differences in brain development, specifically during the heterogeneous developmental phase of puberty. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microbial community analysis of an Alabama coastal salt marsh impacted by the Deepwater Horizon Oil Spill

NASA Astrophysics Data System (ADS)

Beazley, M. J.; Martinez, R.; Rajan, S.; Powell, J.; Piceno, Y.; Tom, L.; Andersen, G. L.; Hazen, T. C.; Van Nostrand, J. D.; Zhou, J.; Mortazavi, B.; Sobecky, P. A.

2011-12-01

Microbial community responses of an Alabama coastal salt marsh environment to the Deepwater Horizon oil spill were studied by 16S rRNA (PhyloChip) and functional gene (GeoChip) microarray-based analysis. Oil and tar balls associated with the oil spill arrived along the Alabama coast in June 2010. Marsh and inlet sediment samples collected in June, July, and September 2010 from a salt marsh ecosystem at Point Aux Pines Alabama were analyzed to determine if bacterial community structure changed as a result of oil perturbation. Sediment total petroleum hydrocarbon (TPH) concentrations ranged from below detection to 189 mg kg-1 and were randomly dispersed throughout the salt marsh sediments. Total DNA extracted from sediment and particulates were used for PhyloChip and GeoChip hybridization. A total of 4000 to 8000 operational taxonomic units (OTUs) were detected in marsh and inlet samples. Distinctive changes in the number of detectable OTUs were observed between June, July, and September 2010. Surficial inlet sediments demonstrated a significant increase in the total number of OTUs between June and September that correlated with TPH concentrations. The most significant increases in bacterial abundance were observed in the phyla Actinobacteria, Firmicutes, Gemmatimonadetes, Proteobacteria, and Verrucomicrobia. Bacterial richness in marsh sediments also correlated with TPH concentrations with significant changes primarily in Acidobacteria, Actinobacteria, Firmicutes, Fusobacteria, Nitrospirae, and Proteobacteria. GeoChip microarray analysis detected 5000 to 8300 functional genes in marsh and inlet samples. Surficial inlet sediments demonstrated distinctive increases in the number of detectable genes and gene signal intensities in July samples compared to June. Signal intensities increased (> 1.5-fold) in genes associated with petroleum degradation. Genes related to metal resistance, stress, and carbon cycling also demonstrated increases in oiled sediments. This study demonstrates the value of applying phylogenetic and functional gene microarray technology to characterize the extensive microbial diversity of marsh environments. Moreover, this technology provides significant insight into bacterial community responses to anthropogenic oil events.

The effects of laughter on post-prandial glucose levels and gene expression in type 2 diabetic patients.

PubMed

Hayashi, Takashi; Murakami, Kazuo

2009-07-31

This report mainly summarizes the results of our study in which the physiological effects of laughter--as a positive emotional expression--were analyzed with respect to gene expression changes to demonstrate the hypothesis that the mind and genes mutually influence each other. We observed that laughter suppressed 2-h postprandial blood glucose level increase in patients with type 2 diabetes and analyzed gene expression changes. Some genes showed specific changes in their expression. In addition, we revealed that laughter decreased the levels of prorenin in blood; prorenin is involved in the onset of diabetic complications. Further, laughter normalized the expression of the prorenin receptor gene on peripheral blood leukocytes, which had been reduced in diabetic patients; this demonstrated that the inhibitory effects of laughter on the onset/deterioration of diabetic complications at the gene-expression level. In a subsequent study, we demonstrated the effects of laughter by discriminating 14 genes, related to natural killer (NK) cell activity, to exhibit continuous increases in expression as a result of laughter. Our results supported NK cell-mediated improvement in glucose tolerance at the gene-expression level. In this report, we also review other previous studies on laughter.

Testimony psychotherapy in Bosnian refugees: a pilot study.

PubMed

Weine, S M; Kulenovic, A D; Pavkovic, I; Gibbons, R

1998-12-01

The authors sought to describe the use of the testimony method of psychotherapy in a group of traumatized adult refugees from genocide in Bosnia-Herzegovina. The subjects were 20 Bosnian refugees in Chicago who gave written informed consent to participate in a case series study of testimony psychotherapy. All subjects received testimony psychotherapy, averaging six sessions, approximately 90 minutes, weekly or biweekly. Subjects received standardized instruments for posttraumatic stress disorder (PTSD), depression, traumatic events, global functioning, and prior psychiatric history. The instruments were administered before treatment, at the conclusion of the treatment, and at the 2- and 6-month follow-ups. The posttreatment assessments demonstrated significant decreases in the rate of PTSD diagnosis, PTSD symptom severity, and the severity of reexperiencing, avoidance, and hyperarousal symptom clusters. Depressive symptoms demonstrated a significant decrease, and there was a significant increase in scores on the Global Assessment of Functioning Scale. Two-month and 6-month follow-up assessments demonstrated further significant decreases in all symptoms and an increase in scores on the Global Assessment of Functioning Scale. This pilot study provides preliminary evidence that testimony psychotherapy may lead to improvements in PTSD and depressive symptoms, as well as to improvement of functioning, in survivors of state-sponsored violence.

Changes in materials properties explain the effects of humidity on gecko adhesion.

PubMed

Puthoff, Jonathan B; Prowse, Michael S; Wilkinson, Matt; Autumn, Kellar

2010-11-01

Geckos owe their remarkable stickiness to millions of dry setae on their toes, and the mechanism of adhesion in gecko setae has been the topic of scientific scrutiny for over two centuries. Previously, we demonstrated that van der Waals forces are sufficient for strong adhesion and friction in gecko setae, and that water-based capillary adhesion is not required. However, recent studies demonstrated that adhesion increases with relative humidity (RH) and proposed that surface hydration and capillary water bridge formation is important or even necessary. In this study, we confirmed a significant effect of RH on gecko adhesion, but rejected the capillary adhesion hypothesis. While contact forces of isolated tokay gecko setal arrays increased with humidity, the increase was similar on hydrophobic and hydrophilic surfaces, inconsistent with a capillary mechanism. Contact forces increased with RH even at high shear rates, where capillary bridge formation is too slow to affect adhesion. How then can a humidity-related increase in adhesion and friction be explained? The effect of RH on the mechanical properties of setal β-keratin has escaped consideration until now. We discovered that an increase in RH softens setae and increases viscoelastic damping, which increases adhesion. Changes in setal materials properties, not capillary forces, fully explain humidity-enhanced adhesion, and van der Waals forces remain the only empirically supported mechanism of adhesion in geckos.

The NIOSH CROPS Demonstration Project: A Study in New York and Virginia with an Emphasis on Youth

PubMed Central

Hard, David L.; McKenzie, Eugene A.; Cantis, Douglas; May, John; Sorensen, Julie; Bayes, Barbara; Madden, Erin; Stone, Bruce; Maass, Jimmy

2016-01-01

The agriculture, forestry, and fishing (AgFF) industry sector has had the highest rate of work-related deaths over the past several years. Tractors are the single largest source of occupational fatalities in this industry sector, and tractor rollovers are the largest category of tractor fatalities. The risk of death due to tractor rollovers has been found to be reduced considerably when rollover protective structures (ROPS) are used in conjunction with seatbelts. Increasing the number of tractors with ROPS and seatbelts is one way in which tractor rollover fatalities can be mitigated. The NIOSH cost-effective rollover protective structure (CROPS) project was designed as a demonstration project to determine if CROPS, a type of ROPS, could be retrofitted in the field and were acceptable to farmers. To this end, the CROPS project was successful, with 50 tractors being retrofitted with CROPS in the field. All study participants were asked to complete a pretest, test, and posttest regarding the CROPS retrofit demonstration and their knowledge and attitudes toward ROPS. CROPS demonstrators were the participants who retrofitted their tractors with CROPS. Demonstrators were asked to recruit three to five other participants, known as observers, to watch the demonstration. The rationale was to generate interest in ROPS/CROPS among other farmers and community leaders. Overall, 16% of the participants had youth operating tractors on their farms. Participants reported that 44 youth operated tractors on their farms, more than 25% of these young tractor operators were 4 to 10 years old, and half of the youth operating tractors on participant farms were 13 years old or younger. Only one participant group (demonstrators) included individuals who had all of their tractors protected with ROPS/CROPS for young tractor operators (28%), but they accounted for only one farm each among the New York and Virginia demonstrators. The survey question on ROPS importance did not show an overall increase after respondents participated in the CROPS demonstration project. However, one Virginia observer asked to become a Virginia demonstrator and installed a CROPS on his tractor. Additionally, the questions on attitude toward ROPS showed a general increase in mean scores, with the some of the lowest response categories on the follow-up survey not being selected by respondents, indicating a potentially positive impact on participants' safety attitudes toward ROPS. For the safety attitude questions, the majority remained the same. This study indicates there is still much work to be done to reduce the number of deaths in production agriculture due to tractor rollovers. CROPS could be a valuable addition to the efforts of retrofitting ROPS on tractors in order to reduce the number of deaths due to tractor rollovers. PMID:27857511

The NIOSH CROPS Demonstration Project: A Study in New York and Virginia with an Emphasis on Youth.

PubMed

Hard, David L; McKenzie, Eugene A; Cantis, Douglas; May, John; Sorensen, Julie; Bayes, Barbara; Madden, Erin; Stone, Bruce; Maass, Jimmy

2016-01-01

The agriculture, forestry, and fishing (AgFF) industry sector has had the highest rate of work-related deaths over the past several years. Tractors are the single largest source of occupational fatalities in this industry sector, and tractor rollovers are the largest category of tractor fatalities. The risk of death due to tractor rollovers has been found to be reduced considerably when rollover protective structures (ROPS) are used in conjunction with seatbelts. Increasing the number of tractors with ROPS and seatbelts is one way in which tractor rollover fatalities can be mitigated. The NIOSH cost-effective rollover protective structure (CROPS) project was designed as a demonstration project to determine if CROPS, a type of ROPS, could be retrofitted in the field and were acceptable to farmers. To this end, the CROPS project was successful, with 50 tractors being retrofitted with CROPS in the field. All study participants were asked to complete a pretest, test, and posttest regarding the CROPS retrofit demonstration and their knowledge and attitudes toward ROPS. CROPS demonstrators were the participants who retrofitted their tractors with CROPS. Demonstrators were asked to recruit three to five other participants, known as observers, to watch the demonstration. The rationale was to generate interest in ROPS/CROPS among other farmers and community leaders. Overall, 16% of the participants had youth operating tractors on their farms. Participants reported that 44 youth operated tractors on their farms, more than 25% of these young tractor operators were 4 to 10 years old, and half of the youth operating tractors on participant farms were 13 years old or younger. Only one participant group (demonstrators) included individuals who had all of their tractors protected with ROPS/CROPS for young tractor operators (28%), but they accounted for only one farm each among the New York and Virginia demonstrators. The survey question on ROPS importance did not show an overall increase after respondents participated in the CROPS demonstration project. However, one Virginia observer asked to become a Virginia demonstrator and installed a CROPS on his tractor. Additionally, the questions on attitude toward ROPS showed a general increase in mean scores, with the some of the lowest response categories on the follow-up survey not being selected by respondents, indicating a potentially positive impact on participants' safety attitudes toward ROPS. For the safety attitude questions, the majority remained the same. This study indicates there is still much work to be done to reduce the number of deaths in production agriculture due to tractor rollovers. CROPS could be a valuable addition to the efforts of retrofitting ROPS on tractors in order to reduce the number of deaths due to tractor rollovers.

Alcohols enhance the rate of acetic acid diffusion in S. cerevisiae: biophysical mechanisms and implications for acetic acid tolerance.

PubMed

Lindahl, Lina; Genheden, Samuel; Faria-Oliveira, Fábio; Allard, Stefan; Eriksson, Leif A; Olsson, Lisbeth; Bettiga, Maurizio

2017-12-01

Microbial cell factories with the ability to maintain high productivity in the presence of weak organic acids, such as acetic acid, are required in many industrial processes. For example, fermentation media derived from lignocellulosic biomass are rich in acetic acid and other weak acids. The rate of diffusional entry of acetic acid is one parameter determining the ability of microorganisms to tolerance the acid. The present study demonstrates that the rate of acetic acid diffusion in S. cerevisiae is strongly affected by the alcohols ethanol and n-butanol. Ethanol of 40 g/L and n-butanol of 8 g/L both caused a 65% increase in the rate of acetic acid diffusion, and higher alcohol concentrations caused even greater increases. Molecular dynamics simulations of membrane dynamics in the presence of alcohols demonstrated that the partitioning of alcohols to the head group region of the lipid bilayer causes a considerable increase in the membrane area, together with reduced membrane thickness and lipid order. These changes in physiochemical membrane properties lead to an increased number of water molecules in the membrane interior, providing biophysical mechanisms for the alcohol-induced increase in acetic acid diffusion rate. n-butanol affected S. cerevisiae and the cell membrane properties at lower concentrations than ethanol, due to greater and deeper partitioning in the membrane. This study demonstrates that the rate of acetic acid diffusion can be strongly affected by compounds that partition into the cell membrane, and highlights the need for considering interaction effects between compounds in the design of microbial processes.

Alcohols enhance the rate of acetic acid diffusion in S. cerevisiae: biophysical mechanisms and implications for acetic acid tolerance

PubMed Central

Lindahl, Lina; Genheden, Samuel; Faria-Oliveira, Fábio; Allard, Stefan; Eriksson, Leif A.; Olsson, Lisbeth; Bettiga, Maurizio

2017-01-01

Microbial cell factories with the ability to maintain high productivity in the presence of weak organic acids, such as acetic acid, are required in many industrial processes. For example, fermentation media derived from lignocellulosic biomass are rich in acetic acid and other weak acids. The rate of diffusional entry of acetic acid is one parameter determining the ability of microorganisms to tolerance the acid. The present study demonstrates that the rate of acetic acid diffusion in S. cerevisiae is strongly affected by the alcohols ethanol and n-butanol. Ethanol of 40 g/L and n-butanol of 8 g/L both caused a 65% increase in the rate of acetic acid diffusion, and higher alcohol concentrations caused even greater increases. Molecular dynamics simulations of membrane dynamics in the presence of alcohols demonstrated that the partitioning of alcohols to the head group region of the lipid bilayer causes a considerable increase in the membrane area, together with reduced membrane thickness and lipid order. These changes in physiochemical membrane properties lead to an increased number of water molecules in the membrane interior, providing biophysical mechanisms for the alcohol-induced increase in acetic acid diffusion rate. n-butanol affected S. cerevisiae and the cell membrane properties at lower concentrations than ethanol, due to greater and deeper partitioning in the membrane. This study demonstrates that the rate of acetic acid diffusion can be strongly affected by compounds that partition into the cell membrane, and highlights the need for considering interaction effects between compounds in the design of microbial processes. PMID:29354649

Micromanaging alloimmunity.

PubMed

Ford, Mandy L

2016-07-01

Increasing evidence indicates that microbes have a large influence on immune function. Previous studies have linked pathogenic microorganisms with decreased allograft tolerance and subsequent rejection. In this issue of the JCI, Lei and colleagues demonstrate that commensal organisms also influence the host response to allograft transplantation. Using murine skin and cardiac transplant models, the authors demonstrate that allograft rejection is accelerated in mice with a normal microbiome compared with germ-free animals and antibiotic-treated mice. The increased graft rejection observed in conventional animals was due to enhanced T cell priming and was mediated through type I IFN. Together, these results suggest that altering a patient's microbial community prior to transplant could improve allograft acceptance.

An Internet intervention as adjunctive therapy for pediatric encopresis.

PubMed

Ritterband, Lee M; Cox, Daniel J; Walker, Lynn S; Kovatchev, Boris; McKnight, Lela; Patel, Kushal; Borowitz, Stephen; Sutphen, James

2003-10-01

This study evaluated the benefits of enhanced toilet training delivered through the Internet for children with encopresis. Twenty-four children with encopresis were randomly assigned to the Internet intervention group (Web) or no Internet intervention group (No-Web). All participants continued to receive routine care from their primary care physician. The Web participants demonstrated greater improvements in terms of reduced fecal soiling, increased defecation in the toilet, and increased unprompted trips to the toilet (ps<.02). Both groups demonstrated similar improvements in knowledge and toileting behaviors. Internet interventions may be an effective way of delivering sophisticated behavioral interventions to a large and dispersed population in a convenient format.

The current status of ethnobiological research in Latin America: gaps and perspectives.

PubMed

Albuquerque, Ulysses Paulino; Silva, Josivan Soares; Campos, Juliana Loureiro Almeida; Sousa, Rosemary Silva; Silva, Taline Cristina; Alves, Rômulo Romeu Nóbrega

2013-10-16

Recent reviews have demonstrated an increase in the number of papers on ethnobiology in Latin America. Among factors that have influenced this increase are the biological and cultural diversity of these countries and the general scientific situation in some countries. This study aims to assess the panorama of ethnobiological research in Latin America by analyzing its evolution, trends, and future prospects. To conduct this study, we searched for papers in the Scopus (http://www.scopus.com) and Web of Science (http://www.isiknowledge.com) databases. The search was performed using combinations of keywords and the name of each Latin American country. The following countries were included in this study: Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador, Guatemala, Haiti, Honduras, Mexico, Panama, Paraguay, Peru, Venezuela, and Uruguay. According to our inclusion criteria, 679 ethnobiological studies conducted in Latin America were found for the period between 1963 and 2012. Of these studies, 289 (41%) were conducted in Brazil, 153 in Mexico (22%), 61 in Peru (9%), 58 in Argentina (8%), 45 in Bolivia (6%), and 97 (14%) in other Latin American countries. The increased number of publications related to this area of knowledge in recent years demonstrates the remarkable growth of ethnobiology as a science. Ethnobiological research may be stimulated by an increase in the number of scientific events and journals for study dissemination and by the creation of undergraduate courses and graduate programs to train ethnoscientists who will produce high-quality studies, especially in certain countries.

Increased plantar force and impulse in American football players with high arch compared to normal arch

PubMed Central

Carson, Daniel W.; Myer, Gregory D.; Hewett, Timothy E.; Heidt, Robert S.; Ford, Kevin R.

2014-01-01

Background Risk of overuse injury among athletes is high due in part to repeated loading of the lower extremities. Compared to individuals with normal arch (NA) structure, those with high (HA) or low arch (LA) may be at increased risk of specific overuse injuries, including stress fractures. A high medial longitudinal arch may result in decreased shock absorbing properties due to increased rigidity in foot mechanics. While the effect of arch structure on dynamic function has been examined in straight line walking and running, the relationship between the two during multi-directional movements remains unstudied. Objective The purpose of this study was to determine if differences in plantar loading in football players occur during both walking and pivoting movements. Method Plantar loading was examined in 9 regions of the foot for 26 participants (16 NA, 10 HA). Results High arch athletes demonstrated increased maximum force in the lateral rear foot and medial forefoot, and force time integral in the medial forefoot while walking. HA athletes also demonstrated increased maximum force in the medial rear foot and medial and central forefoot during rapid pivoting. Conclusions The current findings demonstrate that loading patterns differ between football players with high and normal arch structure, which could possibly influence injury risk in this population. PMID:23141809

Thermal Assisted In Vivo Gene Electrotransfer

PubMed Central

Donate, Amy; Bulysheva, Anna; Edelblute, Chelsea; Jung, Derrick; Malik, Mohammad A.; Guo, Siqi; Burcus, Niculina; Schoenbach, Karl; Heller, Richard

2016-01-01

Gene electrotransfer is an effective approach for delivering plasmid DNA to a variety of tissues. Delivery of molecules with electric pulses requires control of the electrical parameters to achieve effective delivery. Since discomfort or tissue damage may occur with high applied voltage, the reduction of the applied voltage while achieving the desired expression may be an important improvement. One possible approach is to combine electrotransfer with exogenously applied heat. Previous work performed in vitro demonstrated that increasing temperature before pulsing can enhance gene expres sion and made it possible to reduce electric fields while maintaining expression levels. In the study reported here, this combination was evaluated in vivo using a novel electrode device designed with an inserted laser for application of heat. The results obtained in this study demonstrated that increased temperature during electrotransfer increased expression or maintained expression with a reduction in applied voltage. With further optimization this approach may provide the basis for both a novel method and a novel instrument that may greatly enhance translation of gene electrotransfer. PMID:27029944

Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes.

PubMed

Shao, Yvonne Y; Wang, Lai; Welter, Jean F; Ballock, R Tracy

2012-01-01

Indian hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. Copyright © 2011 Elsevier Inc. All rights reserved.

Advanced Demonstration and Test Reactor Options Study

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

Petti, David Andrew; Hill, R.; Gehin, J.

Global efforts to address climate change will require large-scale decarbonization of energy production in the United States and elsewhere. Nuclear power already provides 20% of electricity production in the United States (U.S.) and is increasing in countries undergoing rapid growth around the world. Because reliable, grid-stabilizing, low emission electricity generation, energy security, and energy resource diversity will be increasingly valued, nuclear power’s share of electricity production has a potential to grow. In addition, there are non electricity applications (e.g., process heat, desalination, hydrogen production) that could be better served by advanced nuclear systems. Thus, the timely development, demonstration, and commercializationmore » of advanced nuclear reactors could diversify the nuclear technologies available and offer attractive technology options to expand the impact of nuclear energy for electricity generation and non-electricity missions. The purpose of this planning study is to provide transparent and defensible technology options for a test and/or demonstration reactor(s) to be built to support public policy, innovation and long term commercialization within the context of the Department of Energy’s (DOE’s) broader commitment to pursuing an “all of the above” clean energy strategy and associated time lines. This planning study includes identification of the key features and timing needed for advanced test or demonstration reactors to support research, development, and technology demonstration leading to the commercialization of power plants built upon these advanced reactor platforms. This planning study is consistent with the Congressional language contained within the fiscal year 2015 appropriation that directed the DOE to conduct a planning study to evaluate “advanced reactor technology options, capabilities, and requirements within the context of national needs and public policy to support innovation in nuclear energy”. Advanced reactors are defined in this study as reactors that use coolants other than water. Advanced reactor technologies have the potential to expand the energy applications, enhance the competitiveness, and improve the sustainability of nuclear energy.« less

The effectiveness of humane teaching methods in veterinary education.

PubMed

Knight, Andrew

2007-01-01

Animal use resulting in harm or death has historically played an integral role in veterinary education, in disciplines such as surgery, physiology, biochemistry, anatomy, pharmacology, and parasitology. However, many non-harmful alternatives now exist, including computer simulations, high quality videos, ''ethically-sourced cadavers'' such as from animals euthanased for medical reasons, preserved specimens, models and surgical simulators, non-invasive self-experimentation, and supervised clinical experiences. Veterinary students seeking to use such methods often face strong opposition from faculty members, who usually cite concerns about their teaching efficacy. Consequently, studies of veterinary students were reviewed comparing learning outcomes generated by non-harmful teaching methods with those achieved by harmful animal use. Of eleven published from 1989 to 2006, nine assessed surgical training--historically the discipline involving greatest harmful animal use. 45.5% (5/11) demonstrated superior learning outcomes using more humane alternatives. Another 45.5% (5/11) demonstrated equivalent learning outcomes, and 9.1% (1/11) demonstrated inferior learning outcomes. Twenty one studies of non-veterinary students in related academic disciplines were also published from 1968 to 2004. 38.1% (8/21) demonstrated superior, 52.4% (11/21) demonstrated equivalent, and 9.5% (2/21) demonstrated inferior learning outcomes using humane alternatives. Twenty nine papers in which comparison with harmful animal use did not occur illustrated additional benefits of humane teaching methods in veterinary education, including: time and cost savings, enhanced potential for customisation and repeatability of the learning exercise, increased student confidence and satisfaction, increased compliance with animal use legislation, elimination of objections to the use of purpose-killed animals, and integration of clinical perspectives and ethics early in the curriculum. The evidence demonstrates that veterinary educators can best serve their students and animals, while minimising financial and time burdens, by introducing well-designed teaching methods not reliant on harmful animal use.

Elevated concentrations of nonesterified fatty acids increase monocyte expression of CD11b and adhesion to endothelial cells.

PubMed

Zhang, Wei-Yang; Schwartz, Eric; Wang, Yingjie; Attrep, Jeanne; Li, Zhi; Reaven, Peter

2006-03-01

Monocyte proinflammatory activity has been demonstrated in obesity, insulin resistance, and type 2 diabetes, metabolic conditions that are frequently associated with elevated levels of nonesterified fatty acids (NEFA). We therefore tested the hypothesis that NEFA may induce monocyte inflammation. Monocytes exposed to NEFA for 2 days demonstrated a dose-related increase in intracellular reactive oxygen species (ROS) formation and adhesion to endothelial cells. All of these effects were inhibited by the coaddition of antioxidants such as glutathione or butylated hydroxytoluene, by inhibition of ROS generation by NADPH oxidase inhibitors, and by inhibition of protein kinase C, a recognized stimulator of NAPDH oxidase. Monocytes exposed to NEFA also demonstrated a significant increase in CD11b message expression. Stimulation of monocyte adhesion to endothelial cells by NEFA was inhibited by addition of neutralizing antibodies to either CD11b or CD18. Finally, surface expression of CD11b increased significantly on monocytes as measured by flow cytometry, after their incubation with NEFA. These studies indicate that elevated concentrations of NEFA may enhance integrin facilitated monocyte adhesion to endothelial cells and these effects appear mediated, in part, through activation of NADPH oxidase and oxidative stress.

Cognitive load during route selection increases reliance on spatial heuristics.

PubMed

Brunyé, Tad T; Martis, Shaina B; Taylor, Holly A

2018-05-01

Planning routes from maps involves perceiving the symbolic environment, identifying alternate routes and applying explicit strategies and implicit heuristics to select an option. Two implicit heuristics have received considerable attention, the southern route preference and initial segment strategy. This study tested a prediction from decision-making theory that increasing cognitive load during route planning will increase reliance on these heuristics. In two experiments, participants planned routes while under conditions of minimal (0-back) or high (2-back) working memory load. In Experiment 1, we examined how memory load impacts the southern route heuristic. In Experiment 2, we examined how memory load impacts the initial segment heuristic. Results replicated earlier results demonstrating a southern route preference (Experiment 1) and initial segment strategy (Experiment 2) and further demonstrated that evidence for heuristic reliance is more likely under conditions of concurrent working memory load. Furthermore, the extent to which participants maintained efficient route selection latencies in the 2-back condition predicted the magnitude of this effect. Together, results demonstrate that working memory load increases the application of heuristics during spatial decision making, particularly when participants attempt to maintain quick decisions while managing concurrent task demands.

Improving the Isotretinoin Photostability by Incorporating in Microemulsion Matrix

PubMed Central

Patel, Mrunali R.; Patel, Rashmin B.; Parikh, Jolly R.; Patel, Bharat G.

2011-01-01

The present paper demonstrates the increased photostability of isotretinoin when loaded in microemulsion. The photodegradation of isotretinoin, in methanol and microemulsion formulation was studied under direct sun light. The photodegradation process was monitored by UV spectrophotometry. In methanol solution, isotretinoin undergoes complete photodegradation just within a few minutes of light exposure. Isotretinoin incorporated in microemulsion formulation showed an increased stability in comparison to the methanol solutions. In particular for isotretinoin, a residual concentration of 75% was still present after a light irradiance versus a residual value of just 16% measured at the same time in methanol solution. Further, degradation kinetic parameters of isotretinoin-loaded microemulsion formulation were demonstrated increase isotretinoin half-life about five-times in comparison with a methanol solution under a direct sun light. PMID:22389863

Limb Correction of Individual Infrared Channels Used in RGB Composite Products

NASA Technical Reports Server (NTRS)

Elmer, Nicholas J.; Berndt, Emily; Jedlovec, Gary J.; Lafontaine, Frank J.

2015-01-01

This study demonstrates that limb-cooling can be removed from infrared imagery using latitudinally and seasonally dependent limb correction coefficients, which account for an increasing optical path length as scan angle increases. Furthermore, limb-corrected RGB composites provide multiple advantages over uncorrected RGB composites, including increased confidence in the interpretation of RGB features, improved situation awareness for operational forecasters, seamless transition between overlaid RGB composites, easy comparison of RGB products from different sensors, and the availability of high quality proxy products for the GOES-R era, as demonstrated by the case examples presented in Section 3. This limb correction methodology can also be applied to additional infrared channels used to create other RGB products, including those created from other satellite sensors, such as Suomi NPP Visible Infrared Imaging Radiometer Suite (VIIRS).

Multi-walled carbon nanotubes increase anxiety levels in rats and reduce exploratory activity in the open field test.

PubMed

Sayapina, N V; Batalova, T A; Chaika, V V; Kuznetsov, V L; Sergievich, A A; Kolosov, V P; Perel'man, Yu M; Golokhvast, K S

2015-01-01

The results of the first study on the effects of multi-walled carbon nanotubes (MWNTs) on the exploratory activity and the emotional state in laboratory rats assessed by the open field test are reported. During three or ten days, rats received 8-10 nm MWNTs added to their food at a dose of 500 mg/kg. It was demonstrated that, in the group of rats which were fed with MWNTs, the integrated anxiety level index began to increase as early as the third day of the experiment; on the tenth day, it appeared to be twice increased. It was also demonstrated that MWNTs decreased the integrated exploratory activity index nearly twofold on the third day and nearly fourfold on the tenth day.

Topical nitroglycerin: a potential treatment for impotence.

PubMed

Owen, J A; Saunders, F; Harris, C; Fenemore, J; Reid, K; Surridge, D; Condra, M; Morales, A

1989-03-01

The effect of 2 per cent nitroglycerin paste applied to the penile shaft of impotent subjects was evaluated in a placebo controlled double-blind study under laboratory conditions. After application of nitroglycerin paste or a placebo ointment base, penile tumescence was recorded through a strain gauge transducer while subjects viewed an erotic video presentation. Relative to the placebo paste the number of subjects demonstrating an increase in penile circumference after nitroglycerin (18 of 26) was significantly different than all other outcome possibilities (p less than 0.05). Noninvasive vascular assessment by ultrasonography demonstrated an increase in diameter and blood flow in the cavernous arteries after application of nitroglycerin paste. Nitroglycerin paste increases blood flow in the cavernous arteries and improves tumescence after erotic stimulation. This agent may represent a new therapy for impotence.

How thermal energy storage enhances the economic viability of concentrating solar power

DOE PAGES

Madaeni, Seyed Hossein; Sioshansi, Ramteen; Denholm, Paul

2011-06-20

This study examines the economic performance and rationale of concentrating solar power (CSP) with and without thermal energy storage (TES). We demonstrate that TES can increase the energy and capacity value of CSP and also show that adding TES to a CSP plant can increase its economic viability by increasing its operating revenues to the point that the capital cost of CSP can be justified.

Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation

PubMed Central

Cheng, Chih-Chung; Yang, Ya Lan; Liao, Kate Hsiurong; Lai, Ted Weita

2016-01-01

Conventional methods for therapeutic blood-brain barrier (BBB) disruption facilitate drug delivery but are cumbersome to perform. A previous study demonstrated that adenosine receptor (AR) stimulation by 5′-N-ethylcarboxamide adenosine (NECA) increased the extravasation of intravascular tracers into the brain and proposed that AR agonism may be an effective method for therapeutic BBB disruption. We attempted to confirm the extravasation of tracers into the brain and also investigated tracer extravasation into peripheral organs and tracer retention in the blood. We found that NECA not only increased the extravasation of intravascular fluorescein and low molecular weight dextran into the brain of mice but also increased the concentrations of these tracers in the blood. In fact, the brain:blood ratio-normalized BBB permeability for either tracer is actually decreased by NECA administration. Elevated blood urea nitrogen levels in mice following NECA treatment suggested that renal function impairment was a probable cause of tracer retention. Therefore, NECA has almost no effect on the extravasation of intravascular Evans blue dye (EBD), an albumin-binding tracer with little renal clearance. Rather than inducing BBB disruption, our study demonstrated that NECA increased tracer extravasation into the brain by increasing the concentration gradient of the tracer across the BBB. PMID:27025761

Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation.

PubMed

Cheng, Chih-Chung; Yang, Ya Lan; Liao, Kate Hsiurong; Lai, Ted Weita

2016-03-30

Conventional methods for therapeutic blood-brain barrier (BBB) disruption facilitate drug delivery but are cumbersome to perform. A previous study demonstrated that adenosine receptor (AR) stimulation by 5'-N-ethylcarboxamide adenosine (NECA) increased the extravasation of intravascular tracers into the brain and proposed that AR agonism may be an effective method for therapeutic BBB disruption. We attempted to confirm the extravasation of tracers into the brain and also investigated tracer extravasation into peripheral organs and tracer retention in the blood. We found that NECA not only increased the extravasation of intravascular fluorescein and low molecular weight dextran into the brain of mice but also increased the concentrations of these tracers in the blood. In fact, the brain:blood ratio-normalized BBB permeability for either tracer is actually decreased by NECA administration. Elevated blood urea nitrogen levels in mice following NECA treatment suggested that renal function impairment was a probable cause of tracer retention. Therefore, NECA has almost no effect on the extravasation of intravascular Evans blue dye (EBD), an albumin-binding tracer with little renal clearance. Rather than inducing BBB disruption, our study demonstrated that NECA increased tracer extravasation into the brain by increasing the concentration gradient of the tracer across the BBB.

When Science Replaces Religion: Science as a Secular Authority Bolsters Moral Sensitivity

PubMed Central

2015-01-01

Scientific and religious thinking compete with each other on several levels. For example, activating one generally weakens the other. Since priming religion is known to increase moral behaviour and moral sensitivity, priming science might be expected to have the opposite effect. However, it was recently demonstrated that, on the contrary, science priming increases moral sensitivity as well. The present set of studies sought to replicate this effect and test two explanations for it. Study 1 used a sentence unscrambling task for implicitly priming the concept of science but failed to replicate its effect on moral sensitivity, presumably due to a ceiling effect. Study 2 replicated the effect with a new measure of moral sensitivity. Study 3 tested whether science-related words create this effect by activating the idea of secular authority or by activating analytic thinking. It was demonstrated that words related to secular authority, but not words related to analytic thinking, produced a similar increase in moral sensitivity. Religiosity level of the participants did not influence this basic finding. The results are consistent with the hypothesis that science as a secular institution has overtaken some of the functions of religion in modern societies. PMID:26360826

When Science Replaces Religion: Science as a Secular Authority Bolsters Moral Sensitivity.

PubMed

Yilmaz, Onurcan; Bahçekapili, Hasan G

2015-01-01

Scientific and religious thinking compete with each other on several levels. For example, activating one generally weakens the other. Since priming religion is known to increase moral behaviour and moral sensitivity, priming science might be expected to have the opposite effect. However, it was recently demonstrated that, on the contrary, science priming increases moral sensitivity as well. The present set of studies sought to replicate this effect and test two explanations for it. Study 1 used a sentence unscrambling task for implicitly priming the concept of science but failed to replicate its effect on moral sensitivity, presumably due to a ceiling effect. Study 2 replicated the effect with a new measure of moral sensitivity. Study 3 tested whether science-related words create this effect by activating the idea of secular authority or by activating analytic thinking. It was demonstrated that words related to secular authority, but not words related to analytic thinking, produced a similar increase in moral sensitivity. Religiosity level of the participants did not influence this basic finding. The results are consistent with the hypothesis that science as a secular institution has overtaken some of the functions of religion in modern societies.

Rapid Increase in Scrub Typhus Incidence in Mainland China, 2006-2014.

PubMed

Wu, Yi-Cheng; Qian, Quan; Magalhaes, Ricardo J Soares; Han, Zhi-Hai; Haque, Ubydul; Weppelmann, Thomas A; Hu, Wen-Biao; Liu, Yun-Xi; Sun, Yan-Song; Zhang, Wen-Yi; Li, Shen-Long

2016-03-01

Scrub typhus is a vector-borne disease, which has recently reemerged in China. In this study, we describe the distribution and incidence of scrub typhus cases in China from 2006 to 2014 and quantify differences in scrub typhus cases with respect to sex, age, and occupation. The results of our study indicate that the annual incidence of scrub typhus has increased during the study period. The number of cases peaked in 2014, which was 12.8 times greater than the number of cases reported in 2006. Most (77.97%) of the cases were reported in five provinces (Guangdong, Yunnan, Anhui, Fujian, and Shandong). Our study also demonstrates that the incidence rate of scrub typhus was significantly higher in females compared to males (P < 0.001) and was highest in the 60-69 year age group, and that farmers had a higher incidence rate than nonfarmers (P < 0.001). Different seasonal trends were identified in the number of reported cases between the northern and southern provinces of China. These findings not only demonstrate that China has experienced a large increase in scrub typhus incidence, but also document an expansion in the geographic distribution throughout the country. © The American Society of Tropical Medicine and Hygiene.

Passengers' perception of the safety demonstration on board an aircraft

NASA Astrophysics Data System (ADS)

Ruenruoy, Ratchada

The cabin safety demonstration on board an aircraft is one of the methods to provide safety information for passengers before aircraft takeoff. However, passengers' enthusiasm toward safety demonstrations is normally low. Therefore, the study of passengers' perception toward safety briefings on board an aircraft is important in increasing the safety awareness for the travelling public on commercial aircraft. A survey was distributed to measure the perceptions of Middle Tennessee State University (MTSU) faculty and staff, Aerospace students, and international students who have traveled in the last year. It was generally found that watching the cabin safety demonstration before aircraft takeoff was believed to be important for passengers. However, the attention to the safety demonstration remained low because the safety briefings were not good enough in terms of clear communication, particularly in the recorded audio demonstration and the live safety demonstration methods of briefing.

Manipulation method for the treatment of ankle equinus.

PubMed

Dananberg, H J; Shearstone, J; Guillano, M

2000-09-01

Ankle equinus is a well-known clinical entity that has previously been shown to compound a variety of foot and ankle conditions. Treatments for this disorder have included surgery to lengthen the Achilles tendon and daily stretching. This article describes a method of manual manipulation that can immediately and substantially increase ankle joint dorsiflexion. Patients treated with manipulation in the current study demonstrated nearly twice as much dorsiflexion motion as that demonstrated by patients in a prior study who were treated with a 5-minute daily stretching program for 6 months.

Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

PubMed

Ferreira, Gabriela Kozuchovski; Cardoso, Eria; Vuolo, Francieli Silva; Michels, Monique; Zanoni, Elton Torres; Carvalho-Silva, Milena; Gomes, Lara Mezari; Dal-Pizzol, Felipe; Rezin, Gislaine Tezza; Streck, Emilio L; Paula, Marcos Marques da Silva

2015-12-01

This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

Lessons from SMD experience with approaches to the evaluation of fare changes

DOT National Transportation Integrated Search

1980-01-01

Over the past several years UMTA's Service and Methods Demonstration Program (SMD) has undertaken a large number of studies of the effects of fare changes, both increases and decreases. Some of these studies have been large scale efforts directed at ...

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells.

PubMed

Al-Qatati, Abeer; Aliwaini, Saeb

2017-12-01

Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anti-cancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death. Cell cycle analyses further revealed that this combined treatment resulted in a G1 cell cycle arrest, as well as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and an increase in the levels of active caspase 3 and cleaved poly (ADP-ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs through the intrinsic pathway, evident from the release of cytochrome c. Finally, combined DTIC and pitavastatin treatment was demonstrated to also activate autophagy as part of a cell death mechanism. The present study provides novel evidence to suggest that the combined treatment of DTIC and pitavastatin may be effective in the treatment of melanoma.

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells

PubMed Central

Al-Qatati, Abeer; Aliwaini, Saeb

2017-01-01

Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anti-cancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death. Cell cycle analyses further revealed that this combined treatment resulted in a G1 cell cycle arrest, as well as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and an increase in the levels of active caspase 3 and cleaved poly (ADP-ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs through the intrinsic pathway, evident from the release of cytochrome c. Finally, combined DTIC and pitavastatin treatment was demonstrated to also activate autophagy as part of a cell death mechanism. The present study provides novel evidence to suggest that the combined treatment of DTIC and pitavastatin may be effective in the treatment of melanoma. PMID:29344241

Physician and Staff Acceptance of Care Managers in Primary Care Offices.

PubMed

Malouin, Jean M; Malouin, Rebecca A; Sarinopoulos, Issidoros; Beisel, Marie; Bechel-Marriot, Diane; First, Amanda; Gamble, Ginger M; Tanner, Clare

2017-01-01

Embedded care managers are increasingly implemented as part of the care team within primary care practices, yet previous studies have indicated variability in acceptance by physicians and staff. This study assesses the acceptability of care managers among staff and physicians within the Michigan Primary Care Transformation (MiPCT) demonstration. Care manager acceptance was measured using a web-based survey distributed to practices participating in the MiPCT demonstration. Both physicians and staff reported high levels of care manager acceptance. Longer length of care manager employment at the practice, higher care manager FTE dedicated to care management, and care manager employed by practice were all significantly associated with care manager acceptance. The MiPCT demonstration found high care manager acceptance across all care team members. The high level of acceptance may be due to the structures and processes developed by MiPCT to support implementation of care managers and the length of the intervention period. The MiPCT demonstration confirms that following three years of implementation, embedded care managers are acceptable to both physicians and staff within primary care practices. Importantly, embeddedness, or the amount of time care managers are located within practices, is associated with increased acceptance. © Copyright 2017 by the American Board of Family Medicine.

Incorporating Platelet-Rich Plasma into Electrospun Scaffolds for Tissue Engineering Applications

PubMed Central

Wolfe, Patricia S.; Ericksen, Jeffery J.; Simpson, David G.; Bowlin, Gary L.

2011-01-01

Platelet-rich plasma (PRP) therapy has seen a recent spike in clinical interest due to the potential that the highly concentrated platelet solutions hold for stimulating tissue repair and regeneration. The aim of this study was to incorporate PRP into a number of electrospun materials to determine how growth factors are eluted from the structures, and what effect the presence of these factors has on enhancing electrospun scaffold bioactivity. PRP underwent a freeze-thaw-freeze process to lyse platelets, followed by lyophilization to create a powdered preparation rich in growth factors (PRGF), which was subsequently added to the electrospinning process. Release of protein from scaffolds over time was quantified, along with the quantification of human macrophage and adipose-derived stem cell (ADSC) chemotaxis and proliferation. Protein assays demonstrated a sustained release of protein from PRGF-containing scaffolds at up to 35 days in culture. Scaffold bioactivity was enhanced as ADSCs demonstrated increased proliferation in the presence of PRGF, whereas macrophages demonstrated increased chemotaxis to PRGF. In conclusion, the work performed in this study demonstrated that the incorporation of PRGF into electrospun structures has a significant positive influence on the bioactivity of the scaffolds, and may prove beneficial in a number of tissue engineering applications. PMID:21679135

The effect of a backrest and seatpan inclination on sitting discomfort and trunk muscle activation in subjects with extension-related low back pain.

PubMed

Curran, Máire; Dankaerts, Wim; O'Sullivan, Peter; O'Sullivan, Leonard; O'Sullivan, Kieran

2014-01-01

Few studies have demonstrated that seating modifications reduce low back pain (LBP). One recent study found that a forward-inclined seatpan reduced low back discomfort (LBD), however this was only examined in people with flexion-related LBP. No study has yet investigated its effectiveness among people with extension-related LBP. This crossover study examined 12 subjects with extension-related LBP. Sitting discomfort and surface electromyography of three trunk muscles were recorded during a 10-minute typing task while sitting with two different seatpan inclinations, both with and without a backrest. LBD (p < 0.001) and overall body discomfort (OBD) (p = 0.016) were significantly greater on the forward-inclined seatpan. The backrest did not alter trunk muscle activation or sitting discomfort. The results demonstrate that in a specific subgroup of people with extension-related LBP, increasing forward seatpan inclination significantly increased LBD and OBD. Future research should consider matching ergonomics prescriptions according to the individual presentation of people with LBP.

Arginase 2 deletion leads to enhanced M1 macrophage activation and upregulated polyamine metabolism in response to Helicobacter pylori infection

PubMed Central

Hardbower, Dana M.; Asim, Mohammad; Murray-Stewart, Tracy; Casero, Robert A.; Verriere, Thomas; Lewis, Nuruddeen D.; Chaturvedi, Rupesh; Piazuelo, M. Blanca; Wilson, Keith T.

2016-01-01

We reported that arginase 2 (ARG2) deletion results in increased gastritis and decreased bacterial burden during Helicobacter pylori infection in mice. Our studies implicated a potential role for inducible nitric oxide (NO) synthase (NOS2), as Arg2−/− mice exhibited increased NOS2 levels in gastric macrophages, and NO can kill H. pylori. We now bred Arg2−/− to Nos2−/− mice, and infected them with H. pylori. Compared to wild-type mice, both Arg2−/− and Arg2−/−;Nos2−/− mice exhibited increased gastritis and decreased colonization, the latter indicating that the effect of ARG2 deletion on bacterial burden was not mediated by NO. While Arg2−/− mice demonstrated enhanced M1 macrophage activation, Nos2−/− and Arg2−/−;Nos2−/− mice did not demonstrate these changes, but exhibited increased CXCL1 and CXCL2 responses. There was an increased expression of the Th1/ Th17 cytokines, interferon gamma and interleukin 17, in gastric tissues and splenic T-cells from Arg2−/−, but not Nos2−/− or Arg2−/−;Nos2−/− mice. Gastric tissues from infected Arg2−/− mice demonstrated increased expression of arginase 1, ornithine decarboxylase, adenosylmethionine decarboxylase 1, spermidine/spermine N1-acetyltransferase 1, and spermine oxidase, along with increased spermine levels. These data indicate that ARG2 deletion results in compensatory upregulation of gastric polyamine synthesis and catabolism during H. pylori infection, which may contribute to increased gastric inflammation and associated decreased bacterial load. Overall, the finding of this study is that ARG2 contributes to the immune evasion of H. pylori by restricting M1 macrophage activation and polyamine metabolism. PMID:27074721

In vitro investigation of antifungal activity of allicin alone and in combination with azoles against Candida species.

PubMed

Khodavandi, Alireza; Alizadeh, Fahimeh; Aala, Farzad; Sekawi, Zamberi; Chong, Pei Pei

2010-04-01

Candidiasis is a term describing infections by yeasts from the genus Candida, and the type of infection encompassed by candidiasis ranges from superficial to systemic. Treatment of such infections often requires antifungals such as the azoles, but increased use of these drugs has led to selection of yeasts with increased resistance to these drugs. In this study, we used allicin, an allyl sulfur derivative of garlic, to demonstrate both its intrinsic antifungal activity and its synergy with the azoles, in the treatment of these yeasts in vitro. In this study, the MIC(50) and MIC(90) of allicin alone against six Candida spp. ranged from 0.05 to 25 microg/ml. However, when allicin was used in combination with fluconazole or ketoconazole, the MICs were decreased in some isolates. Our results demonstrated the existing synergistic effect between allicin and azoles in some of the Candida spp. such as C. albicans, C. glabrata and C. tropicalis, but synergy was not demonstrated in the majority of Candida spp. tested. Nonetheless, In vivo testing needs to be performed to support these findings.

Nitinol-based Nanotubular and Nanowell Coatings for the Modulation of Human Vascular Cell Functions

NASA Astrophysics Data System (ADS)

Lee, Phin Peng

Current approaches to reducing restenosis do not balance the reduction of vascular smooth muscle cell proliferation with the increase in the healing of the endothelium. Here, I present my study on the synthesis and characterization of a nanotubular coating on Nitinol substrates. I found that the coating demonstrated 'pro-healing' properties by increasing primary human aortic endothelial cell spreading, migration and collagen and elastin production. Certain cellular functions such as collagen and elastin production were also found to be affected by changes in nanotube diameter. The coating also reduced the proliferation and mRNA expression of collagen I and MMP2 for primary human aortic smooth muscle cells. I will also demonstrate the synthesis of a nanowell coating on Nitinol stents as well as an additional poly(lactic-co-glycolic acid) coating on top of the nanowells that has the potential for controlling drug release. These findings demonstrate the potential for the coatings to aid in the prevention of restenosis and sets up future explorations of ex vivo and in vivo studies.

Visual acuity in young elite motorsport athletes: a preliminary report.

PubMed

Schneiders, Anthony G; Sullivan, S John; Rathbone, Emma J; Louise Thayer, A; Wallis, Laura M; Wilson, Alexandra E

2010-05-01

To determine whether elite motorsport athletes demonstrate superior levels of Visual Acuity than age and sex-matched controls. A cross-sectional observational study. A University vision and balance laboratory. Young male motorsport athletes from the New Zealand Elite Motorsport Academy and healthy age and sex-matched controls. Vision performance tests comprising; Static Visual Acuity (SVA), Dynamic Visual Acuity (DVA), Gaze Stabilization Test (GST), and the Perception Time Test (PTT). Motorsport athletes demonstrated superior visual acuity compared to age and sex-matched controls for all measures, and while this was not statistically significant for SVA, GST and DVA, it reached statistical significance for the PTT (p

Hemodialysis Catheter Heat Transfer for Biofilm Prevention and Treatment.

PubMed

Richardson, Ian P; Sturtevant, Rachael; Heung, Michael; Solomon, Michael J; Younger, John G; VanEpps, J Scott

2016-01-01

Central line-associated bloodstream infections (CLABSIs) are not easily treated, and many catheters (e.g., hemodialysis catheters) are not easily replaced. Biofilms (the source of infection) on catheter surfaces are notoriously difficult to eradicate. We have recently demonstrated that modest elevations of temperature lead to increased staphylococcal susceptibility to vancomycin and significantly soften the biofilm matrix. In this study, using a combination of microbiological, computational, and experimental studies, we demonstrate the efficacy, feasibility, and safety of using heat as an adjuvant treatment for infected hemodialysis catheters. Specifically, we show that treating with heat in the presence of antibiotics led to additive killing of Staphylococcus epidermidis with similar trends seen for Staphylococcus aureus and Klebsiella pneumoniae. The magnitude of temperature elevation required is relatively modest (45-50°C) and similar to that used as an adjuvant to traditional cancer therapy. Using a custom-designed benchtop model of a hemodialysis catheter, positioned with tip in the human vena cava as well as computational fluid dynamic simulations, we demonstrate that these temperature elevations are likely achievable in situ with minimal increased in overall blood temperature.

Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation

PubMed Central

Takahashi, Kazue; Chang, Wei-Chuan; Takahashi, Minoru; Pavlov, Vasile; Ishida, Yumi; La Bonte, Laura; Shi, Lei; Fujita, Teizo; Stahl, Gregory L.; Van Cott, Elizabeth M.

2010-01-01

The first line of host defense is the innate immune system that includes coagulation factors and pattern recognition molecules, one of which is mannose-binding lectin (MBL). Previous studies have demonstrated that MBL deficiency increases susceptibility to infection. Several mechanisms are associated with increased susceptibility to infection, including reduced opsonophagocytic killing and reduced lectin complement pathway activation. In this study, we demonstrate that MBL and MBL-associated serine protease (MASP)-1/3 together mediate coagulation factor-like activities, including thrombin-like activity. MBL and/or MASP-1/3 deficient hosts demonstrate in vivo evidence that MBL and MASP-1/3 are involved with hemostasis following injury. Staphylococcus aureus infected MBL null mice developed disseminated intravascular coagulation (DIC), which was associated with elevated blood IL-6 levels (but not TNF-α and multi-organ inflammatory responses). Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases. PMID:20399528

Elevated streamflows increase dam passage by juvenile coho salmon during winter: Implications of climate change in the Pacific Northwest

USGS Publications Warehouse

Kock, Tobias J.; Liedtke, Theresa L.; Rondorf, Dennis W.; Serl, John D.; Kohn, Mike; Bumbaco, Karin A.

2012-01-01

A 4-year evaluation was conducted to determine the proportion of juvenile coho salmon Oncorhynchus kisutch passing Cowlitz Falls Dam, on the Cowlitz River, Washington, during winter. River and reservoir populations of coho salmon parr were monitored using radiotelemetry to determine if streamflow increases resulted in increased downstream movement and dam passage. This was of interest because fish that pass downstream of Cowlitz Falls Dam become landlocked in Riffe Lake and are lost to the anadromous population. Higher proportions of reservoir-released fish (0.391-0.480) passed Cowlitz Falls Dam than did river-released fish (0.037-0.119). Event-time analyses demonstrated that streamflow increases were important predictors of dam passage rates during the study. The estimated effect of increasing streamflows on the risk of dam passage varied annually and ranged from 9% to 75% for every 28.3 m3/s increase in streamflow. These results have current management implications because they demonstrate the significance of dam passage by juvenile coho salmon during winter months when juvenile fish collection facilities are typically not operating. The results also have future management implications because climate change predictions suggest that peak streamflow timing for many watersheds in the Pacific Northwest will shift from late spring and early summer to winter. Increased occurrence of intense winter flood events is also expected. Our results demonstrate that juvenile coho salmon respond readily to streamflow increases and initiate downstream movements during winter months, which could result in increased passage at dams during these periods if climate change predictions are realized in the coming decades.

Online pre-race education improves test scores for volunteers at a marathon.

PubMed

Maxwell, Shane; Renier, Colleen; Sikka, Robby; Widstrom, Luke; Paulson, William; Christensen, Trent; Olson, David; Nelson, Benjamin

2017-09-01

This study examined whether an online course would lead to increased knowledge about the medical issues volunteers encounter during a marathon. Health care professionals who volunteered to provide medical coverage for an annual marathon were eligible for the study. Demographic information about medical volunteers including profession, specialty, education level and number of marathons they had volunteered for was collected. A 15-question test about the most commonly encountered medical issues was created by the authors and administered before and after the volunteers took the online educational course and compared to a pilot study the previous year. Seventy-four subjects completed the pre-test. Those who participated in the pilot study last year (N = 15) had pre-test scores that were an average of 2.4 points higher than those who did not (mean ranks: pilot study = 51.6 vs. non-pilot = 33.9, p = 0.004). Of the 74 subjects who completed the pre-test, 54 also completed the post-test. The overall post-pre mean score difference was 3.8 ± 2.7 (t = 10.5 df = 53 p < 0.001). While subjects with all levels of volunteer experience demonstrated improvement, only change among first time marathon volunteers was significantly different from the others. Subjects reporting all degree/certification levels demonstrated improvement, but no difference in improvement was found between degree/certification levels. In this follow-up to the previous year's pilot study, online education demonstrated a long-term (one-year) increase in test scores. Testing also continued to show short-term improvement in post-course test scores, compared to pre-course test scores. In general, marathon medical volunteers who had no volunteer experience demonstrated greater improvement than those who had prior volunteer experience.

Factors associated with falls in older patients with diffuse polyneuropathy.

PubMed

Richardson, James K

2002-11-01

To identify clinical factors associated with falls by older persons with polyneuropathy (PN). A cross-sectional study of 82 subjects aged 50 to 85 with clinical and electrodiagnostic evidence of PN. Electrodiagnostic and biomechanical research laboratories. Patients referred to the electrodiagnostic laboratory. History and physical examination, including semiquantitative methods of peripheral nerve function, and clinical balance testing. Falls were defined by retrospective self-report over a 2-year period. Forty (48.8%), 28 (34.1%), and 18 (22.0%) subjects reported a history of at least one fall, multiple falls, and injurious falls, respectively. Factors associated with single and multiple falls were similar, so only results for multiple and injurious falls are reported. Bivariate analysis showed that an increased body mass index (BMI) and more severe PN (as determined by the Michigan Diabetes Neuropathy Score) were associated with both fall categories. Men reporting falls also demonstrated a decreased unipedal stance time. Age, sex, nerve conduction study parameters, Romberg testing, medications, and comorbidities were not consistently associated with either fall category. Logistic regression demonstrated that multiple and injurious falls were associated with an increased BMI and more severe PN, controlling for age, sex, medications, and comorbidities (pseudo R2 = 0.458 and 0.484, respectively). Although previous work has demonstrated that all older persons with PN are at increased risk for falls, patients with increased BMI and more severe PN are at particularly high risk and should be targeted for intervention.

AMPKα2 Suppresses Murine Embryonic Fibroblast Transformation and Tumorigenesis

PubMed Central

Phoenix, Kathryn N.; Devarakonda, Charan V.; Fox, Melissa M.; Stevens, Laura E.

2012-01-01

AMP-activated kinase (AMPK) is a key metabolic sensor and stress signaling kinase. AMPK activity is known to suppress anabolic processes such as protein and lipid biosynthesis and promote energy-producing pathways including fatty acid oxidation, resulting in increased cellular energy. In addition, AMPK localizes to centrosomes during cell division, plays a role in cellular polarization, and directly targets p53, affecting apoptosis. Two distinct catalytic AMPKα isoforms exist: α1 and α2. Multiple reports indicate that both common and distinct functions exist for each of the 2 α isoforms. AMPK activation has been shown to repress tumor growth, and it has been suggested that AMPK may function as a metabolic tumor suppressor. To evaluate the potential role of each of the AMPKα isoforms in modulating cellular transformation, susceptibility to Ras-induced transformation was evaluated in normal murine embryonic fibroblasts (MEFs) obtained from genetically deleted AMPKα1- or AMPKα2-null mice. This study demonstrated that while AMPKα1 is the dominant AMPK isoform expressed in MEFs, only the AMPKα2-null MEFs displayed increased susceptibility to H-RasV12 transformation in vitro and tumorigenesis in vivo. Conversely, AMPKα1-null MEFs, which demonstrated compensation with increased expression of AMPKα2, displayed minimal transformation susceptibility, decreased cell survival, decreased cell proliferation, and increased apoptosis. Finally, this study demonstrates that AMPKα2 was selectively responsible for targeting p53, thus contributing to the suppression of transformation and tumorigenic mechanisms. PMID:22893790

Use of cardiocerebral resuscitation or AHA/ERC 2005 Guidelines is associated with improved survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis

PubMed Central

Salmen, Marcus; Ewy, Gordon A; Sasson, Comilla

2012-01-01

Objective To determine whether the use of cardiocerebral resuscitation (CCR) or AHA/ERC 2005 Resuscitation Guidelines improved patient outcomes from out-of-hospital cardiac arrest (OHCA) compared to older guidelines. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE, Web of Science and the Cochrane Library databases. We also hand-searched study references and consulted experts. Study selection Design: randomised controlled trials and observational studies. Population OHCA patients, age >17 years. Comparators ‘Control’ protocol versus ‘Study’ protocol. ‘Control’ protocol defined as AHA/ERC 2000 Guidelines for cardiopulmonary resuscitation (CPR). ‘Study’ protocol defined as AHA/ERC 2005 Guidelines for CPR, or a CCR protocol. Outcome Survival to hospital discharge. Quality High-quality or medium-quality studies, as measured by the Newcastle Ottawa Scale using predefined categories. Results Twelve observational studies met inclusion criteria. All the three studies using CCR demonstrated significantly improved survival compared to use of AHA 2000 Guidelines, as did five of the nine studies using AHA/ERC 2005 Guidelines. Pooled data demonstrate that use of a CCR protocol has an unadjusted OR of 2.26 (95% CI 1.64 to 3.12) for survival to hospital discharge among all cardiac arrest patients. Among witnessed ventricular fibrillation/ventricular tachycardia (VF/VT) patients, CCR increased survival by an OR of 2.98 (95% CI 1.92 to 4.62). Studies using AHA/ERC 2005 Guidelines showed an overall trend towards increased survival, but significant heterogeneity existed among these studies. Conclusions We demonstrate an association with improved survival from OHCA when CCR protocols or AHA/ERC 2005 Guidelines are compared to use of older guidelines. In the subgroup of patients with witnessed VF/VT, there was a threefold increase in OHCA survival when CCR was used. CCR appears to be a promising resuscitation protocol for Emergency Medical Services providers in increasing survival from OHCA. Future research will need to be conducted to directly compare AHA/ERC 2010 Guidelines with the CCR approach. PMID:23036985

Bioresorbable nanofiber-based systems for wound healing and drug delivery: optimization of fabrication parameters.

PubMed

Katti, Dhirendra S; Robinson, Kyle W; Ko, Frank K; Laurencin, Cato T

2004-08-15

Wound healing is a complex process that often requires treatment with antibiotics. This article reports the initial development of a biodegradable polymeric nanofiber-based antibiotic delivery system. The functions of such a system would be (a) to serve as a biodegradable gauze, and (b) to serve as an antibiotic delivery system. The polymer used in this study was poly(lactide-co-glycolide) (PLAGA), and nanofibers of PLAGA were fabricated with the use of the electrospinning process. The objective of this study was to determine the effect of fabrication parameters: orifice diameter (needle gauge), polymer solution concentration, and voltage per unit length, on the morphology and diameter of electrospun nanofibers. The needle gauges studied were 16 (1.19 mm), 18 (0.84 mm), and 20 (0.58 mm), and the range of polymer solution concentration studied was from 0.10 g/mL to 0.30 g/mL. The effect of voltage was determined by varying the voltage per unit electrospinning distance, and the range studied was from 0.375 kV/cm to 1.5 kV/cm. In addition, the mass per unit area of the electrospun nanofibers as a function of time was determined and the feasibility of antibiotic (cefazolin) loading into the nanofibers was also studied. The results indicate that the diameter of nanofibers decreased with an increase in needle gauge (decrease in orifice diameter), and increased with an increase in the concentration of the polymer solution. The voltage study demonstrated that the average diameter of the nanofibers decreased with an increase in voltage. However, the effect of voltage on fiber diameter was less pronounced as compared to polymer solution concentration. The results of the areal density study indicated that the mass per unit area of the electrospun nanofibers increased linearly with time. Feasibility of drug incorporation into the nanofibers was demonstrated with the use of cefazolin, a broad-spectrum antibiotic. Overall, these studies demonstrated that PLAGA nanofibers can be tailored to desired diameters through modifications in processing parameters, and that antibiotics such as cefazolin can be incorporated into these nanofibers. Therefore, PLAGA nanofibers show potential as antibiotic delivery systems for the treatment of wounds. Copyright 2004 Wiley Periodicals, Inc.

The Effect of Visual Perceptual Load on Auditory Awareness in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Tillmann, Julian; Olguin, Andrea; Tuomainen, Jyrki; Swettenham, John

2015-01-01

Recent work on visual selective attention has shown that individuals with Autism Spectrum Disorder (ASD) demonstrate an increased perceptual capacity. The current study examined whether increasing visual perceptual load also has less of an effect on auditory awareness in children with ASD. Participants performed either a high- or low load version…

Increasing Social Engagement in Young Children with Autism Spectrum Disorders Using Video Self-Modeling

ERIC Educational Resources Information Center

Bellini, Scott; Akullian, Jennifer; Hopf, Andrea

2007-01-01

An emerging body of research demonstrates the effectiveness of video self-modeling (VSM) in addressing social, communication, and behavioral functioning of children with autism spectrum disorders. The primary purpose of this study was to examine the benefits of a VSM intervention in increasing the social engagement of young children with autism…

Sulfate Addition Increases Methylmercury Production in an Experimental Wetland

Treesearch

Jeff D. Jeremiason; Daniel R. Engstrom; Edward B. Swain; Edward A. Nater; Brian M. Johnson; James E. Almendinger; Bruce A. Monson; Randy K. Kolka

2006-01-01

Atmospheric mercury is the dominant Hg source to fish in northern Minnesota and elsewhere. However, atmospherically derived Hg must be methylated prior to accumulating in fish. Sulfate-reducing bacteria are thought to be the primary methylators of Hg in the environment. Previous laboratory and field mesocosm studies have demonstrated an increase in methylmercury (MeHg...

Increases in Parent Attendance to Behavioral Parent Training Due to Concurrent Child Treatment Groups

ERIC Educational Resources Information Center

Jensen, Scott A.; Grimes, Lisa K.

2010-01-01

Though behavioral parent training has been demonstrated to be an effective intervention for child behavior problems, it continues to suffer from high attrition rates. Few variables have been found to predict or decrease high attrition rates from parent training classes. The present study found 43-52% increases in attendance rates for parents whose…

Electron paramagnetic resonance investigation on modulatory effect of benidipine on membrane fluidity of erythrocytes in essential hypertension.

PubMed

Tsuda, Kazushi

2008-03-01

It has been shown that benidipine, a long-lasting calcium (Ca) channel blocker, may exert its protective effect against vascular disorders by increasing nitric oxide (NO) production. The purpose of the present study was to investigate whether orally administered benidipine might influence the membrane function in patients with essential hypertension. We measured the membrane fluidity of erythrocytes by using an electron paramagnetic resonance (EPR) and spin-labeling method. In the preliminary study using erythrocytes obtained from healthy volunteers, benidipine decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS in the EPR spectra in vitro. The finding indicated that benidipine increased the membrane fluidity and improved the microviscosity of erythrocytes. In addition, it was demonstrated that the effect of benidipine on membrane fluidity of erythrocytes was significantly potentiated by the NO-substrate, L-arginine. In the separate series of the study, we observed that orally administered benidipine for 4 weeks significantly increased the membrane fluidity of erythrocytes with a concomitant increase in plasma NO metabolite levels in hypertensive subjects. The results of the present study demonstrated that benidipine might increase the membrane fluidity and improve the microviscosity of erythrocytes both in vitro and in vivo, to some extent, by the NO-dependent mechanism. Furthermore, it is strongly suggested that orally administered benidipine might have a beneficial effect on the rheologic behavior of erythrocytes and the improvement of the microcirculation in hypertensive subjects.

Developmental Reorganization of the Core and Extended Face Networks Revealed by Global Functional Connectivity.

PubMed

Wang, Xu; Zhu, Qi; Song, Yiying; Liu, Jia

2017-08-28

Prior studies on development of functional specialization in human brain mainly focus on age-related increases in regional activation and connectivity among regions. However, a few recent studies on the face network demonstrate age-related decrease in face-specialized activation in the extended face network (EFN), in addition to increase in activation in the core face network (CFN). Here we used a voxel-based global brain connectivity approach to investigate whether development of the face network exhibited both increase and decrease in network connectivity. We found the voxel-wise resting-state functional connectivity (FC) within the CFN increased with age in bilateral posterior superior temporal sulcus, suggesting the integration of the CFN during development. Interestingly, the FC of the voxels in the EFN to the right fusiform face area and occipital face area decreased with age, suggesting that the CFN segregated from the EFN during development. Moreover, the age-related connectivity in the CFN was related to behavioral performance in face processing. Overall, our study demonstrated developmental reorganization of the face network achieved by both integration within the CFN and segregation of the CFN from the EFN, which may account for the simultaneous increases and decreases in neural activation during the development of the face network. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Trans-synaptic (GABA-dopamine) modulation of cocaine induced dopamine release: A potential therapeutic strategy for cocaine abuse

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

Dewey, S.L.; Straughter-Moore, R.; Chen, R.

We recently developed a new experimental strategy for measuring interactions between functionally-linked neurotransmitter systems in the primate and human brain with PET. As part of this research, we demonstrated that increases in endogenous GABA concentrations significantly reduced striatal dopamine concentrations in the primate brain. We report here the application of the neurotransmitter interaction paradigm with PET and with microdialysis to the investigation of a novel therapeutic strategy for treating cocaine abuse based on the ability of GABA to inhibit cocaine induced increases in striatal dopamine. Using gamma-vinyl GABA (GVG, a suicide inhibitor of GABA transaminase), we performed a series ofmore » PET studies where animals received a baseline PET scan with labeled raclopride injection, animals received cocaine (2.0 mg/kg). Normally, a cocaine challenge significantly reduces the striatal binding of {sup 11}C-raclopride. However, in animals pretreated with GVG, {sup 11}C-raclopride binding was less affected by a cocaine challenge compared to control studies. Furthermore, microdialysis studies in freely moving rats demonstrate that GVG (300 mg/kg) significantly inhibited cocaine-induced increases in extracellular dopamine release. GVG also attenuated cocaine-induced increases in locomotor activity. However, at a dose of 100 mg/kg, GVG had no effect. Similar findings were obtained with alcohol. Alcohol pretreatment dose dependantly (1-4 g/kg) inhibited cocaine-induced increases in extracellular dopamine concentrations in freely moving rats. Taken together, these studies suggest that therapeutic strategies targeted at increasing central GABA concentrations may be beneficial for the treatment of cocaine abuse.« less

School Integrated Pest Management (IPM) Grants

EPA Pesticide Factsheets

EPA's IPM in schools grant program supports projects that include research, development, monitoring, public education, training, demonstrations, or studies to support recipients’ efforts to increase IPM adoption by public and tribal schools (K-12).

Smoking Behaviors and Attitudes During Adolescence Prospectively Predict Support for Tobacco Control Policies in Adulthood

PubMed Central

Chassin, Laurie; Presson, Clark C.

2012-01-01

Introduction: Several cross-sectional studies have examined factors associated with support for tobacco control policies. The current study utilized a longitudinal design to test smoking status and attitude toward smoking measured in adolescence as prospective predictors of support for tobacco control policies measured in adulthood. Methods: Participants (N = 4,834) were from a longitudinal study of a Midwestern community-based sample. Hierarchical multiple regression analyses tested adolescent smoking status and attitude toward smoking as prospective predictors (after controlling for sociodemographic factors, adult smoking status, and adult attitude toward smoking) of support for regulation of smoking in public places, discussion of the dangers of smoking in public schools, prohibiting smoking in bars, eliminating smoking on television and in movies, prohibiting smoking in restaurants, and increasing taxes on cigarettes. Results: Participants who smoked during adolescence demonstrated more support for discussion of the dangers of smoking in public schools and less support for increasing taxes on cigarettes but only among those who smoked as adults. Those with more positive attitudes toward smoking during adolescence demonstrated less support as adults for prohibiting smoking in bars and eliminating smoking on television and in movies. Moreover, a significant interaction indicated that those with more positive attitudes toward smoking as adolescents demonstrated less support as adults for prohibiting smoking in restaurants, but only if they became parents as adults. Conclusions: This study’s findings suggest that interventions designed to deter adolescent smoking may have future benefits in increasing support for tobacco control policies. PMID:22193576

Tumorigenic Potential of Extracellular Matrix Metalloproteinase Inducer

PubMed Central

Zucker, Stanley; Hymowitz, Michelle; Rollo, Ellen E.; Mann, Richard; Conner, Cathleen E.; Cao, Jian; Foda, Hussein D.; Tompkins, David C.; Toole, Bryan P.

2001-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs. PMID:11395366

Inclusion, Exclusion and the Queering of Spaces in Two Icelandic Upper Secondary Schools

ERIC Educational Resources Information Center

Kjaran, Jón Ingvar; Jóhannesson, Ingólfur Ásgeir

2015-01-01

The concept of space is gaining increased attention in studies of sexuality and gender, not least those focusing on heterosexism and heteronormativity. Such studies have demonstrated that space is sexualised, gendered and actively produced. In this article, we present the findings from an ethnographic study of two Icelandic upper secondary…

24-Hydroxylase: potential key regulator in hypervitaminosis D3 in growing dogs.

PubMed

Tryfonidou, M A; Oosterlaken-Dijksterhuis, M A; Mol, J A; van den Ingh, T S G A M; van den Brom, W E; Hazewinkel, H A W

2003-03-01

A group of growing dogs supplemented with cholecalciferol (vitamin D(3); HVitD) was studied vs. a control group (CVitD; 54,000 vs. 470 IU vitamin D(3)/kg diet, respectively) from 3 to 21 wk of age. There were no differences in plasma levels of P(i) and growth-regulating hormones between groups and no signs of vitamin D(3) intoxication in HVitD. For the duration of the study in HVitD vs. CVitD, plasma 25-hydroxycholecalciferol levels increased 30- to 75-fold; plasma 24,25-dihydroxycholecalciferol levels increased 12- to 16-fold and were accompanied by increased renal 24-hydroxylase gene expression, indicating increased renal 24-hydroxylase activity. Although the synthesis of 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)] was increased in HVitD vs. CVitD (demonstrated by [(3)H]1,25(OH)(2)D(3) and increased renal 1alpha-hydroxylase gene expression), plasma 1,25(OH)(2)D(3) levels decreased by 40% as a result of the even more increased metabolic clearance of 1,25(OH)(2)D(3) (demonstrated by [(3)H]1,25(OH)(2)D(3) and increased gene expression of intestinal and renal 24-hydroxylase). A shift of the Ca set point for parathyroid hormone to the left indicated increased sensitivity of the chief cells. Effective counterbalance was provided by hypoparathyroidism, hypercalcitoninism, and the key regulator 24-hydroxylase, preventing the development of vitamin D(3) toxicosis.

Redistribution of pulmonary blood flow impacts thermodilution-based extravascular lung water measurements in a model of acute lung injury

PubMed Central

Easley, R. Blaine; Mulreany, Daniel G.; Lancaster, Christopher T.; Custer, Jason W.; Fernandez-Bustamante, Ana; Colantuoni, Elizabeth; Simon, Brett A.

2009-01-01

Background Studies using transthoracic thermodilution have demonstrated increased extravascular lung water (EVLW) measurements attributed to progression of edema and flooding during sepsis and acute lung injury. We hypothesize that redistribution of pulmonary blood flow can cause increased apparent EVLW secondary to increased perfusion of thermally silent tissue, not increased lung edema. Methods Anesthetized, mechanically ventilated canines were instrumented with PiCCO® (Pulsion Medical, Munich, Germany) catheters and underwent lung injury by repetitive saline lavage. Hemodynamic and respiratory physiologic data were recorded. After stabilized lung injury, endotoxin was administered to inactivate hypoxic pulmonary vasoconstriction. Computerized tomographic imaging was performed to quantify in vivo lung volume, total tissue (fluid) and air content, and regional distribution of blood flow. Results Lavage injury caused an increase in airway pressures and decreased arterial oxygen content with minimal hemodynamic effects. EVLW and shunt fraction increased after injury and then markedly following endotoxin administration. Computerized tomographic measurements quantified an endotoxin-induced increase in pulmonary blood flow to poorly aerated regions with no change in total lung tissue volume. Conclusions The abrupt increase in EVLW and shunt fraction after endotoxin administration is consistent with inactivation of hypoxic pulmonary vasoconstriction and increased perfusion to already flooded lung regions that were previously thermally silent. Computerized tomographic studies further demonstrate in vivo alterations in regional blood flow (but not lung water) and account for these alterations in shunt fraction and EVLW. PMID:19809280

Market diffusion and the effect of demonstrations: A study of Denver metro passive solar home program

NASA Astrophysics Data System (ADS)

Lilien, G. L.

1981-10-01

The reactions to and effects of the Denver metro passive solar home demonstration program, conducted in the spring of 1981 are reported. The program provides impetus to builders for incorporating passive solar designs in spec built homes and demonstrates those designs to prospective buyers to increase buyer receptivity. A pre-post exposure analysis of the effect of the program is reported and four separate groups of prospective new home buyers are studied. The first group heard publicity about and voluntarily visited a demonstration home. The second group saw the home, but was recruited to come to the side. The third group, also in Denver, did not see the site, but answered the same set of questions after receiving a description of and pictures of passive solar homes. The fourth group was a control group, similar to the third, but located in Kansas City.

External Validity of the New York University Caregiver Intervention: Key Caregiver Outcomes Across Multiple Demonstration Projects.

PubMed

Fauth, Elizabeth B; Jackson, Mark A; Walberg, Donna K; Lee, Nancy E; Easom, Leisa R; Alston, Gayle; Ramos, Angel; Felten, Kristen; LaRue, Asenath; Mittelman, Mary

2017-06-01

The Administration on Aging funded six New York University Caregiver Intervention (NYUCI) demonstration projects, a counseling/support intervention targeting dementia caregivers and families. Three sites (Georgia, Utah, Wisconsin) pooled data to inform external validity in nonresearch settings. This study (a) assesses collective changes over time, and (b) compares outcomes across sites on caregiver burden, depressive symptoms, satisfaction with social support, family conflict, and quality of life. Data included baseline/preintervention ( N = 294) and follow-up visits (approximately 4, 8, 12 months). Linear mixed models showed that social support satisfaction increased ( p < .05) and family conflict decreased ( p < .05; Cohen's d = 0.49 and 0.35, respectively). Marginally significant findings emerged for quality of life increases ( p = .05) and burden decreases ( p < .10). Depressive symptoms remained stable. Slopes did not differ much by site. NYUCI demonstrated external validity in nonresearch settings across diverse caregiver samples.

Masking Period Patterns and Forward Masking for Speech-Shaped Noise: Age-Related Effects.

PubMed

Grose, John H; Menezes, Denise C; Porter, Heather L; Griz, Silvana

2016-01-01

The purpose of this study was to assess age-related changes in temporal resolution in listeners with relatively normal audiograms. The hypothesis was that increased susceptibility to nonsimultaneous masking contributes to the hearing difficulties experienced by older listeners in complex fluctuating backgrounds. Participants included younger (n = 11), middle-age (n = 12), and older (n = 11) listeners with relatively normal audiograms. The first phase of the study measured masking period patterns for speech-shaped noise maskers and signals. From these data, temporal window shapes were derived. The second phase measured forward-masking functions and assessed how well the temporal window fits accounted for these data. The masking period patterns demonstrated increased susceptibility to backward masking in the older listeners, compatible with a more symmetric temporal window in this group. The forward-masking functions exhibited an age-related decline in recovery to baseline thresholds, and there was also an increase in the variability of the temporal window fits to these data. This study demonstrated an age-related increase in susceptibility to nonsimultaneous masking, supporting the hypothesis that exacerbated nonsimultaneous masking contributes to age-related difficulties understanding speech in fluctuating noise. Further support for this hypothesis comes from limited speech-in-noise data, suggesting an association between susceptibility to forward masking and speech understanding in modulated noise.

Inhibition of SIRT1 by a small molecule induces apoptosis in breast cancer cells.

PubMed

Kalle, Arunasree M; Mallika, A; Badiger, Jayasree; Alinakhi; Talukdar, Pinaki; Sachchidanand

2010-10-08

Overexpression of SIRT1, a NAD+-dependent class III histone deacetylases (HDACs), is implicated in many cancers and therefore could become a promising antitumor target. Here we demonstrate a small molecule SIRT1 inhibitor, ILS-JGB-1741(JGB1741) with potent inhibitory effects on the proliferation of human metastatic breast cancer cells, MDA-MB 231. The molecule has been designed using medicinal chemistry approach based on known SIRT1 inhibitor, sirtinol. The molecule showed a significant inhibition of SIRT1 activity compared to sirtinol. Studies on the antitumor effects of JGB on three different cancer cell lines, K562, HepG2 and MDA-MB 231 showed an IC₅₀ of 1, 10 and 0.5 μM, respectively. Further studies on MDA-MB 231 cells showed a dose-dependent increase in K9 and K382 acetylation of H3 and p53, respectively. Results also demonstrated that JGB1741-induced apoptosis is associated with increase in cytochrome c release, modulation in Bax/Bcl2 ratio and cleavage of PARP. Flowcytometric analysis showed increased percentage of apoptotic cells, decrease in mitochondrial membrane potential and increase in multicaspase activation. In conclusion, the present study indicates the potent apoptotic effects of JGB1741 in MDA-MB 231 cells. Copyright © 2010 Elsevier Inc. All rights reserved.

Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.

PubMed

Vazana, Udi; Veksler, Ronel; Pell, Gaby S; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio; Friedman, Alon

2016-07-20

The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. Copyright © 2016 the authors 0270-6474/16/367727-13$15.00/0.

Stressful life experiences, alcohol consumption, and alcohol use disorders: the epidemiologic evidence for four main types of stressors

PubMed Central

Keyes, Katherine M.; Hatzenbuehler, Mark L.; Hasin, Deborah S.

2013-01-01

Background Exposure to stress is potentially important in the pathway to alcohol use and alcohol use disorders. Stressors occur at multiple time points across the life course, with varying degrees of chronicity and severity. Method We review evidence from epidemiologic studies on the relationship between four different stressors (fateful/catastrophic events, child maltreatment, common adult stressful life events in interpersonal, occupational, financial, and legal domains, and minority stress) and alcohol consumption and alcohol use disorders. Results Studies generally demonstrate an increase in alcohol consumption in response to exposure to terrorism or other disasters. Research has demonstrated little increase in incident alcohol use disorders, but individuals with a history of alcohol use disorders are more likely to report drinking to cope with the traumatic event. Childhood maltreatment is a consistent risk factor for early onset of drinking in adolescence and adult alcohol use disorders, and accumulating evidence suggests that specific polymorphisms may interact with child maltreatment to increase risk for alcohol consumption and disorder. Stressful life events such as divorce and job loss increase the risk of alcohol disorders, but epidemiologic consensus on the specificity of these associations across gender has not been reached. Finally, both perceptions of discrimination and objective indicators of discrimination are associated with alcohol use and alcohol use disorders among racial/ethnic and sexual minorities. Conclusion Taken together, these literatures demonstrate that exposure to stress is an important component in individual differences in risk for alcohol consumption and alcohol use disorders. However, many areas of this research remain to be studied, including greater attention to the role of various stressors in the course of alcohol use disorders and potential risk moderators when individuals are exposed to stressors. PMID:21373787

Glutamate-Mediated Blood–Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery

PubMed Central

Vazana, Udi; Veksler, Ronel; Pell, Gaby S.; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio

2016-01-01

The blood–brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood–brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood–brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo. Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood–brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood–brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT In this study, we reveal a new mechanism that governs blood–brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. PMID:27445149

Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.

PubMed

Sinder, B P; White, L E; Salemi, J D; Ominsky, M S; Caird, M S; Marini, J C; Kozloff, K M

2014-08-01

Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect. Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1. Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

Adolescents with Major Depression Demonstrate Increased Amygdala Activation

ERIC Educational Resources Information Center

Yang, Tony T.; Simmons, Alan N.; Matthews, Scott C.; Tapert, Susan F.; Frank, Guido K.; Max, Jeffrey E.; Bischoff-Grethe, Amanda; Lansing, Amy E.; Brown, Gregory; Strigo, Irina A.; Wu, Jing; Paulus, Martin P.

2010-01-01

Objective: Functional neuroimaging studies have led to a significantly deeper understanding of the underlying neural correlates and the development of several mature models of depression in adults. In contrast, our current understanding of the underlying neural substrates of adolescent depression is very limited. Although numerous studies have…

Readers Theatre plus Comprehension and Word Study

ERIC Educational Resources Information Center

Young, Chase; Stokes, Faida; Rasinski, Timothy

2017-01-01

Readers Theatre has been used to introduce critical issues, promote fluency among English learners and non-English learners, teach vocabulary, and integrate content in the classroom. Previous studies of Readers Theatre application have demonstrated an increase in student reading fluency, motivation, and confidence. The focus of this systemic…

Enhancing Employee Skills.

ERIC Educational Resources Information Center

1999

This document contains four symposium papers on enhancing employee skills. "The Effect of Study Skills Training Intervention on United States Air Force Aeromedical Apprentices" (John C. Griffith) demonstrates how study skills intervention resulted in a significant increase in the end-of-course scores of a sample of 90 randomly selected Air Force…

Scaling-up Fermentation of Pichia pastoris to demonstration-scale using new methanol-feeding strategy and increased air pressure instead of pure oxygen supplement

PubMed Central

Liu, Wan-Cang; Gong, Ting; Wang, Qing-Hua; Liang, Xiao; Chen, Jing-Jing; Zhu, Ping

2016-01-01

Scaling-up of high-cell-density fermentation (HCDF) of Pichia pastoris from the lab or pilot scale to the demonstration scale possesses great significance because the latter is the final technological hurdle in the decision to go commercial. However, related investigations have rarely been reported. In this paper, we study the scaling-up processes of a recombinant P. pastoris from the pilot (10 to 100-L) to the demonstration (1,000-L) scales, which can be used to convert 7-β-xylosyl-10-deacetyltaxol into 10-deacetyltaxol by the β-xylosidase for semi-synthesis of Taxol. We demonstrated that a pure oxygen supplement can be omitted from the HCDF if the super atmospheric pressure was increased from 0.05 to 0.10 ± 0.05 MPa, and we developed a new methanol feeding biomass-stat strategy (0.035 mL/g/h) with 1% dissolved oxygen and 100 g/L initial induction biomass (dry cell weight). The scaling-up was reproducible, and the best results were obtained from the 1,000-L scale, featuring a shorter induction time and the highest enzyme activities and productions, respectively. The specific growth and specific production rates were also determined. This study lays a solid foundation for the commercial preparation of 10-deacetyltaxol through the recombinant yeast. It also provides a successful paradigm for scaling-up HCDF of P. pastoris to the demonstration scale. PMID:26790977

Relationship between occupational exposure to lead and local arterial stiffness and left ventricular diastolic function in individuals with arterial hypertension

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

Poreba, Rafal, E-mail: sogood@poczta.onet.pl; Gac, Pawel; Poreba, Malgorzata

Relationship between occupational exposure to lead and frequency of complications in persons with arterial hypertension has been poorly investigated. This study aimed at evaluation of the relationship between occupational exposure to lead and manifestation of an increased local arterial stiffness and left ventricular diastolic dysfunction. The studies included 105 men (mean age: 44.47 {+-} 9.12 years) with arterial hypertension, treated with hypotensive drugs: group I - men occupationally exposed to lead (n = 53), and group II - men not exposed to lead (n = 52). In echocardiographic examination, the left ventricular diastolic dysfunction was diagnosed significantly more frequently inmore » group I than in group II. In eTracking examination mean values of stiffness parameter ({beta}), augmentation index (AI) and one-point pulse wave velocity (PWV-{beta}) were significantly higher and mean values of arterial compliance (AC) were significantly lower in group I than in group II. The logistic regression showed that in the group of persons with arterial hypertension occupationally exposed to lead a more advanced age, higher blood lead concentration and higher mean values of augmentation index represent independent risk factors of left ventricular diastolic dysfunction. The multifactorial regression showed that amongst persons with arterial hypertension occupationally exposed to lead higher blood zinc protoporphyrin concentration, a more advanced age and higher value of body mass index (BMI) represent independent risk factors of an increased local arterial stiffness. In summary, we should note that in the group of persons with arterial hypertension occupationally exposed to lead the study has demonstrated a significantly more frequent manifestation of left ventricular diastolic dysfunction and an increase in local arterial stiffness. - Highlights: > Amongst persons with AH exposed to Pb higher ZnPP represent independent risk factor of increased local arterial stiffness. > Higher Pb-B represent independent risk factor of left ventricular diastolic dysfunction. > The study has demonstrated a more frequent manifestation of left ventricular diastolic dysfunction in group exposed to Pb. > Also, in this group the study has demonstrated a more frequent manifestation of increase in local arterial stiffness.« less

Health impact of external funding for HIV, tuberculosis and malaria: systematic review

PubMed Central

de Jongh, Thyra E; Harnmeijer, Joanne H; Atun, Rifat; Korenromp, Eline L; Zhao, Jinkou; Puvimanasinghe, John; Baltussen, Rob

2014-01-01

Background Since 2002, development assistance for health has substantially increased, especially investments for HIV, tuberculosis (TB) and malaria control. We undertook a systematic review to assess and synthesize the existing evidence in the scientific literature on the health impacts of these investments. Methods and findings We systematically searched databases for peer-reviewed and grey literature, using tailored search strategies. We screened studies for study design and relevance, using predefined inclusion criteria, and selected those that enabled us to link health outcomes or impact to increased external funding. For all included studies, we recorded dataset and study characteristics, health outcomes and impacts. We analysed the data using a causal-chain framework to develop a narrative summary of the published evidence. Thirteen articles, representing 11 individual studies set in Africa and Asia reporting impacts on HIV, tuberculosis and malaria, met the inclusion criteria. Only two of these studies documented the entire causal-chain spanning from funding to programme scale-up, to outputs, outcomes and impacts. Nonetheless, overall we find a positive correlation between consecutive steps in the causal chain, suggesting that external funds for HIV, tuberculosis and malaria programmes contributed to improved health outcomes and impact. Conclusions Despite the large number of supported programmes worldwide and despite an abundance of published studies on HIV, TB and malaria control, we identified very few eligible studies that adequately demonstrated the full process by which external funding has been translated to health impact. Most of these studies did not move beyond demonstrating statistical association, as opposed to contribution or causation. We thus recommend that funding organizations and researchers increase the emphasis on ensuring data capture along the causal pathway to demonstrate effect and contribution of external financing. The findings of these comprehensive and rigorously conducted impact evaluations should also be made publicly accessible. PMID:23921987

Health impact of external funding for HIV, tuberculosis and malaria: systematic review.

PubMed

de Jongh, Thyra E; Harnmeijer, Joanne H; Atun, Rifat; Korenromp, Eline L; Zhao, Jinkou; Puvimanasinghe, John; Baltussen, Rob

2014-08-01

Since 2002, development assistance for health has substantially increased, especially investments for HIV, tuberculosis (TB) and malaria control. We undertook a systematic review to assess and synthesize the existing evidence in the scientific literature on the health impacts of these investments. We systematically searched databases for peer-reviewed and grey literature, using tailored search strategies. We screened studies for study design and relevance, using predefined inclusion criteria, and selected those that enabled us to link health outcomes or impact to increased external funding. For all included studies, we recorded dataset and study characteristics, health outcomes and impacts. We analysed the data using a causal-chain framework to develop a narrative summary of the published evidence. Thirteen articles, representing 11 individual studies set in Africa and Asia reporting impacts on HIV, tuberculosis and malaria, met the inclusion criteria. Only two of these studies documented the entire causal-chain spanning from funding to programme scale-up, to outputs, outcomes and impacts. Nonetheless, overall we find a positive correlation between consecutive steps in the causal chain, suggesting that external funds for HIV, tuberculosis and malaria programmes contributed to improved health outcomes and impact. Despite the large number of supported programmes worldwide and despite an abundance of published studies on HIV, TB and malaria control, we identified very few eligible studies that adequately demonstrated the full process by which external funding has been translated to health impact. Most of these studies did not move beyond demonstrating statistical association, as opposed to contribution or causation. We thus recommend that funding organizations and researchers increase the emphasis on ensuring data capture along the causal pathway to demonstrate effect and contribution of external financing. The findings of these comprehensive and rigorously conducted impact evaluations should also be made publicly accessible. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2013; all rights reserved.

Short and long term modulation of tissue minerals concentrations following oral administration of black cumin (Nigella sativa L.) seed oil to laboratory rats.

PubMed

Basheer, Irum; Qureshi, Irfan Zia

2018-01-15

Nigella sativa, or commonly called black cumin is a small herb of family Ranunculaceae is a well-known medicinal plant but its effects on tissue mineral concentrations of animal bodies is unknown. To study the effect of oral administration of fixed oil of black cumin seeds on tissues mineral content using laboratory rats as experimental model. Experimental animals were exposed to two oral doses of seed oil (60 and 120 ml kg -1 body weight). Short- and long term experiments lasted 24 h and 60 days respectively, with three replicates each. Oil extracted from black cumin seeds was subjected to GC-MS to identify chemical components. Following the wet digestion in nitric acid, samples of whole blood and organs of rats were subjected to atomic absorption spectrophotometry for determination of elements concentrations. Data were compared statistically at p < .05. Compared to control, Cr, Mn, Ni, Cu, Zn showed decrease, whereas Co, Na, Mg and K demonstrated increase, but Ca showed both increase and decrease in most of the tissues upon short term exposure to low and high doses of black cumin oil. During long term exposure, Cr, Fe, Mn, Cu exhibited decrease; Co, Na, Mg and Ca concentrations demonstrated an upregulation, whereas Ni and Zn showed increase and decrease in most of the tissues. Comparison of short term with long term experiments at low dose revealed increases in Fe, Zn, Cu, Mg, K and Ca, a decrease in Cr, Mn, Ni and Cu in most tissues, but both increase and decrease in Na. At high dose, an increase occurred in Fe, Ni, Zn, K, Ca, Mg, a decrease in Cr, while both increase and decrease in Cu, Co and Na concentrations. Our study demonstrates that oral administration of black cumin seeds oil to laboratory rats significantly alters tissue trace elements and electrolytes concentrations. The study appears beneficial but indicates modulatory role of black cumin oil as regards mineral metabolism with far reaching implications in health and disease. Copyright © 2017. Published by Elsevier GmbH.

Body mass index and gastroesophageal reflux disease: a systematic review and meta-analysis.

PubMed

Corley, Douglas A; Kubo, Ai

2006-11-01

Gastroesophageal reflux disease (GERD) is a common cause of morbidity and health-care utilization in many countries. Obesity is a potentially modifiable risk factor, but existing studies have conflicting results, possibly due to differences in study design, definitions, or populations. We performed a systematic review and meta-analysis of studies identified using MEDLINE, the Web of Science electronic database, manual literature review, and a review of expert bibliographies. Studies were included if they: (1) evaluated obesity, body mass index (BMI), or another measure of body size; (2) included data on reflux symptoms, esophagitis, or a GERD-related hospitalization; and (3) reported a relative risk or odds ratio (OR) with confidence intervals or provided sufficient data to permit their calculation. We identified 20 studies that included 18,346 patients with GERD. Studies from the United States demonstrated an association between increasing BMI and the presence of GERD (95% confidence interval [CI]= 1.36-1.80, overweight, OR = 1.57, P value homogeneity = 0.51, 95% CI = 1.89-2.45, obese, OR = 2.15, P= 0.10). Studies from Europe provided heterogeneous results despite stratification for several factors; individual studies demonstrated both positive associations and no association. This analysis demonstrates a positive association between increasing BMI and the presence of GERD within the United States; this relationship became apparent only after stratification by country and level of BMI. These results support the evaluation of weight reduction as a potential therapy for GERD. Further studies are needed to evaluate potential mechanisms and any differences in this relationship among different study populations.

Solid polymer electrolyte (SPE) fuel cell technology program, phase 1/1A. [design and fabrication

NASA Technical Reports Server (NTRS)

1975-01-01

A solid polymer electrolyte fuel cell was studied for the purpose of improving the characteristics of the technology. Several facets were evaluated, namely: (1) reduced fuel cell costs; (2) reduced fuel cell weight; (3) improved fuel cell efficiency; and (4) increased systems compatibility. Demonstrated advances were incorporated into a full scale hardware design. A single cell unit was fabricated. A substantial degree of success was demonstrated.

Brain-computer interface for alertness estimation and improving

NASA Astrophysics Data System (ADS)

Hramov, Alexander; Maksimenko, Vladimir; Hramova, Marina

2018-02-01

Using wavelet analysis of the signals of electrical brain activity (EEG), we study the processes of neural activity, associated with perception of visual stimuli. We demonstrate that the brain can process visual stimuli in two scenarios: (i) perception is characterized by destruction of the alpha-waves and increase in the high-frequency (beta) activity, (ii) the beta-rhythm is not well pronounced, while the alpha-wave energy remains unchanged. The special experiments show that the motivation factor initiates the first scenario, explained by the increasing alertness. Based on the obtained results we build the brain-computer interface and demonstrate how the degree of the alertness can be estimated and controlled in real experiment.

An expectancy-value theory approach to the long-term modification of smoking behavior.

PubMed

Rogers, R W; Deckner, C W; Mewborn, C R

1978-04-01

Despite the research interest in modifying smoking behavior, therapeutic treatments that can produce long-term cessation have not been demonstrated rigorously. A follow-up study of two attitude change experiments (N = 173) examined the effects of a fear appeal, that is, increasing smokers' awareness and appreciation of the highly noxious consequences of smoking. Although this familiar type of information may be an integral component of many smoking treatment programs, its long-term suppressive effect has not been demonstrated in well-controlled experiments. The results disclosed that 3 months and also 1 year after treatment, a high-fear manipulation had increased significantly the percentage of smokers who were able to stop smoking completely.

Pulsed-dosing with oral sodium phenylbutyrate increases hemoglobin F in a patient with sickle cell anemia.

PubMed

Hines, Patrick; Dover, George J; Resar, Linda M S

2008-02-01

Increasing hemoglobin F (HbF) appears to be beneficial for patients with sickle cell anemia. We previously demonstrated that daily, oral sodium phenylbutyrate (OSPB) induces HbF synthesis in pediatric and adult patients with hemoglobin SS (HbSS). The high doses and need for daily therapy, however, have limited its use. Here, we report a patient treated with pulsed-dosing of OSPB for over 3 years. This patient developed a modest, but sustained elevation in HbF over the course of therapy without side effects. Although larger studies are needed, this case demonstrates that pulsed-dosing with OSPB enhances HbF synthesis. (c) 2007 Wiley-Liss, Inc.

Adding Fuel to the Fire: The Impacts of Non-Native Grass Invasion on Fire Management at a Regional Scale

PubMed Central

Setterfield, Samantha A.; Rossiter-Rachor, Natalie A.; Douglas, Michael M.; Wainger, Lisa; Petty, Aaron M.; Barrow, Piers; Shepherd, Ian J.; Ferdinands, Keith B.

2013-01-01

Background Widespread invasion by non-native plants has resulted in substantial change in fire-fuel characteristics and fire-behaviour in many of the world's ecosystems, with a subsequent increase in the risk of fire damage to human life, property and the environment. Models used by fire management agencies to assess fire risk are dependent on accurate assessments of fuel characteristics but there is little evidence that they have been modified to reflect landscape-scale invasions. There is also a paucity of information documenting other changes in fire management activities that have occurred to mitigate changed fire regimes. This represents an important limitation in information for both fire and weed risk management. Methodology/Principal Findings We undertook an aerial survey to estimate changes to landscape fuel loads in northern Australia resulting from invasion by Andropogon gayanus (gamba grass). Fuel load within the most densely invaded area had increased from 6 to 10 t ha−1 in the past two decades. Assessment of the effect of calculating the Grassland Fire Danger Index (GFDI) for the 2008 and 2009 fire seasons demonstrated that an increase from 6 to 10 t ha−1 resulted in an increase from five to 38 days with fire risk in the ‘severe’ category in 2008 and from 11 to 67 days in 2009. The season of severe fire weather increased by six weeks. Our assessment of the effect of increased fuel load on fire management practices showed that fire management costs in the region have increased markedly (∼9 times) in the past decade due primarily to A. gayanus invasion. Conclusions/Significance This study demonstrated the high economic cost of mitigating fire impacts of an invasive grass. This study demonstrates the need to quantify direct and indirect invasion costs to assess the risk of further invasion and to appropriately fund fire and weed management strategies. PMID:23690917

Adding fuel to the fire: the impacts of non-native grass invasion on fire management at a regional scale.

PubMed

Setterfield, Samantha A; Rossiter-Rachor, Natalie A; Douglas, Michael M; Wainger, Lisa; Petty, Aaron M; Barrow, Piers; Shepherd, Ian J; Ferdinands, Keith B

2013-01-01

Widespread invasion by non-native plants has resulted in substantial change in fire-fuel characteristics and fire-behaviour in many of the world's ecosystems, with a subsequent increase in the risk of fire damage to human life, property and the environment. Models used by fire management agencies to assess fire risk are dependent on accurate assessments of fuel characteristics but there is little evidence that they have been modified to reflect landscape-scale invasions. There is also a paucity of information documenting other changes in fire management activities that have occurred to mitigate changed fire regimes. This represents an important limitation in information for both fire and weed risk management. We undertook an aerial survey to estimate changes to landscape fuel loads in northern Australia resulting from invasion by Andropogon gayanus (gamba grass). Fuel load within the most densely invaded area had increased from 6 to 10 t ha(-1) in the past two decades. Assessment of the effect of calculating the Grassland Fire Danger Index (GFDI) for the 2008 and 2009 fire seasons demonstrated that an increase from 6 to 10 t ha(-1) resulted in an increase from five to 38 days with fire risk in the 'severe' category in 2008 and from 11 to 67 days in 2009. The season of severe fire weather increased by six weeks. Our assessment of the effect of increased fuel load on fire management practices showed that fire management costs in the region have increased markedly (∼9 times) in the past decade due primarily to A. gayanus invasion. This study demonstrated the high economic cost of mitigating fire impacts of an invasive grass. This study demonstrates the need to quantify direct and indirect invasion costs to assess the risk of further invasion and to appropriately fund fire and weed management strategies.

Social goals, social behavior, and social status in middle childhood.

PubMed

Rodkin, Philip C; Ryan, Allison M; Jamison, Rhonda; Wilson, Travis

2013-06-01

This study examines motivational precursors of social status and the applicability of a dual-component model of social competence to middle childhood. Concurrent and longitudinal relationships between self-reported social goals (social development, demonstration-approach, demonstration-avoid goal orientations), teacher-rated prosocial and aggressive behavior, and peer nominations of social status (preference, popularity) were examined over the course of an academic year among 980 3rd- to 5th-grade children. Findings support dual-component expectations. Confirmatory factor analyses verified the expected 3-factor structure of social goals and 2-factor structure of social status. Structural equation modeling (SEM) found that (a) social development goals were associated with prosocial behavior and increased preference, and (b) demonstration-approach goals were associated with aggressive behavior and increased popularity. Demonstration-avoid goals were associated with a popularity decrease. SEMs were invariant across grade, gender, and ethnicity. Discussion concerns the potential risks of high social status, extensions to the dual-component model, and the generality of an achievement goal approach to child social development. PsycINFO Database Record (c) 2013 APA, all rights reserved

Teaching About South Korea.

ERIC Educational Resources Information Center

Schisgall, Jane

1983-01-01

Identifies reasons why social studies educators should improve their teaching about South Korea. Included in the list is the increasing numbers of Koreans being educated in the United States, the summer Olympics in 1988, and the use of Korean culture as a case study demonstrating the effects of cultural transmission and society in transition. (JDH)

Current Trends in Social Dialectology.

ERIC Educational Resources Information Center

Shuy, Roger W.

The formal study of social dialects has received increasing attention since about the middle of the sixties. In linguistics, the study of social dialectology has resulted in the clear demonstration of the importance of sociolinguistic variation in linguistic theory in contrast to the former preoccupation with linguistic universals. In education,…

Case Study Method in Business Education in the USA

ERIC Educational Resources Information Center

Velushchak, Maryna

2014-01-01

Business Education is dynamic in nature and needs diverse information to deal with different business problems. To understand the peculiar situations and to manage them effectively, case studies are widely used. Researchers in education have already demonstrated that students' active participation in the educational process increases their…

Emotional Intelligence and Academic Achievement in 11th Grade At-Risk Students

ERIC Educational Resources Information Center

Nelson, Patricia Diane

2009-01-01

As the emphasis on measures of student academic achievement increases, educational researchers and practitioners are interested in identifying factors that demonstrate effectiveness in supporting student achievement. This quantitative, correlational study explored the influence of emotional intelligence on closing the achievement gap. A study of…

Testing Promotes Eyewitness Accuracy with a Warning: Implications for Retrieval Enhanced Suggestibility

ERIC Educational Resources Information Center

Thomas, Ayanna K.; Bulevich, John B.; Chan, Jason C. K.

2010-01-01

Numerous studies have demonstrated that repeated retrieval boosts later retention. However, recent research has shown that testing can increase eyewitness susceptibility to misleading post-event information (e.g., Chan, Thomas, & Bulevich, 2009). The present study examines the effects of warning on this counterintuitive finding. In two…

A Delphi Study on Collaborative Learning in Distance Education: The Faculty Perspective

ERIC Educational Resources Information Center

O'Neill, Susan; Scott, Murray; Conboy, Kieran

2011-01-01

This paper focuses on the factors that influence collaborative learning in distance education. Distance education has been around for many years and the use of collaborative learning techniques in distance education is becoming increasingly popular. Several studies have demonstrated the superiority of collaborative learning over traditional modes…

Association of Autism Spectrum Disorders and Inflammatory Bowel Disease

ERIC Educational Resources Information Center

Lee, Maunoo; Krishnamurthy, Jayasree; Susi, Apryl; Sullivan, Carolyn; Gorman, Gregory H.; Hisle-Gorman, Elizabeth; Erdie-Lalena, Christine R.; Nylund, Cade M.

2018-01-01

Autism spectrum disorders (ASD) and inflammatory bowel disease (IBD) both have multifactorial pathogenesis with an increasing number of studies demonstrating gut-brain associations. We aim to examine the association between ASD and IBD using strict classification criteria for IBD. We conducted a retrospective case-cohort study using records from…

Acute and delayed effects of intermittant ozone on cardiovascular and thermoregulatory responses of young and aged rats

EPA Science Inventory

Ozone (03) is associated with cardiovascular and respiratory diseases. The aged population is considered to be more sensitive to air pollutants but relatively few studies have demonstrated increased susceptibility in animal models of aging. To study the acute and delayed physiolo...

Video Games as Moral Educators?

ERIC Educational Resources Information Center

Khoo, Angeline

2012-01-01

The growing interest in video gaming is matched by a corresponding increase in concerns about the harmful effects on children and adolescents. There are numerous studies on aggression and addiction which spark debates on the negative effects of video gaming. At the same time, there are also studies demonstrating prosocial effects. This paper…

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

Ritter, Boyd

Insensitive high explosives (IHEs) based on 1,3,5-triamino 2,4,6-trinitro-benzene (TATB) are the IHEs of choice for use in nuclear warheads over conventional high explosives when safety is the only consideration, because they are very insensitive to thermal or mechanical initiation stimuli. It is this inherent insensitivity to high temperatures, shock, and impact, which provides detonation design challenges when designing TATB explosive systems while at the same time providing a significant level of protection against accidental initiation. Although classified as IHE, over the past few years the focus on explosive safety has demonstrated that the shock sensitivity of TATB is influenced withmore » respect to temperature. A number of studies have been performed on TATB and TATB formulations, plastic bonded explosives (PBX) 9502, and LX-17-01 (LX-17), which demonstrates the increase in shock sensitivity of the explosive after it has been preheated or thermally cycled over various temperature ranges. Many studies suggest the change in sensitivity is partly due to the decomposition rates of the temperature elevated TATB. Others point to the coefficient of thermal expansion, the crystalline structures of TATB and/or the combination of all factors, which create voids which can become active hot spots. During thermal cycling, TATB is known to undergo an irreversible increase in specific volume called ratchet growth. This increase in specific volume correlates to a decrease in density. This decrease in density and increase in volume, demonstrate the creations of additional void spaces which could serve as potential new initiation hot spots thus, increasing the overall sensitivity of the HE. This literature review evaluates the published works to understand why the shock sensitivity of TATB-based plastic bonded explosives (PBXs) changes with temperature.« less

Pathophysiological levels of soluble P-selectin mediate adhesion of leukocytes to the endothelium through Mac-1 activation.

PubMed

Woollard, Kevin J; Suhartoyo, Andreas; Harris, Emma E; Eisenhardt, Steffen U; Jackson, Shaun P; Peter, Karlheinz; Dart, Anthony M; Hickey, Michael J; Chin-Dusting, Jaye P F

2008-11-07

Plasma soluble P-selectin (sP-selectin) levels are increased in pathologies associated with atherosclerosis, including peripheral arterial occlusive disease (PAOD). However, the role of sP-selectin in regulating leukocyte-endothelial adhesion is unclear. The aim of this study was to assess the ability of exogenous and endogenous sP-selectin to induce leukocyte responses that promote their adhesion to various forms of endothelium. In flow chamber assays, sP-selectin dose-dependently increased neutrophil adhesion to resting human iliac artery endothelial cells. Similarly, sP-selectin induced neutrophil adhesion to the endothelial surface of murine aortae and human radial venous segments in ex vivo flow chamber experiments. Using intravital microscopy to examine postcapillary venules in the mouse cremaster muscle, in vivo administration of sP-selectin was also found to significantly increase leukocyte rolling and adhesion in unstimulated postcapillary venules. Using a Mac-1-specific antibody and P-selectin knockout mouse, it was demonstrated that this finding was dependent on a contribution of Mac-1 to leukocyte rolling and endothelial P-selectin expression. This was confirmed in an ex vivo perfusion model using viable mouse aorta and human radial vessels. In contrast, with tumor necrosis factor-alpha-activated endothelial cells and intact endothelium, where neutrophil adhesion was already elevated, sP-selectin failed to further increase adhesion. Plasma samples from PAOD patients containing pathologically elevated concentrations of sP-selectin also increased neutrophil adhesion to the endothelium in a sP-selectin-dependent manner, as demonstrated by immunodepletion of sP-selectin. These studies demonstrate that raised plasma sP-selectin may influence the early progression of vascular disease by promoting leukocyte adhesion to the endothelium in PAOD, through Mac-1-mediated rolling and dependent on endothelial P-selectin expression.

The current status of ethnobiological research in Latin America: gaps and perspectives

PubMed Central

2013-01-01

Background Recent reviews have demonstrated an increase in the number of papers on ethnobiology in Latin America. Among factors that have influenced this increase are the biological and cultural diversity of these countries and the general scientific situation in some countries. This study aims to assess the panorama of ethnobiological research in Latin America by analyzing its evolution, trends, and future prospects. Methods To conduct this study, we searched for papers in the Scopus (http://www.scopus.com) and Web of Science (http://www.isiknowledge.com) databases. The search was performed using combinations of keywords and the name of each Latin American country. The following countries were included in this study: Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador, Guatemala, Haiti, Honduras, Mexico, Panama, Paraguay, Peru, Venezuela, and Uruguay. Results and conclusions According to our inclusion criteria, 679 ethnobiological studies conducted in Latin America were found for the period between 1963 and 2012. Of these studies, 289 (41%) were conducted in Brazil, 153 in Mexico (22%), 61 in Peru (9%), 58 in Argentina (8%), 45 in Bolivia (6%), and 97 (14%) in other Latin American countries. The increased number of publications related to this area of knowledge in recent years demonstrates the remarkable growth of ethnobiology as a science. Ethnobiological research may be stimulated by an increase in the number of scientific events and journals for study dissemination and by the creation of undergraduate courses and graduate programs to train ethnoscientists who will produce high-quality studies, especially in certain countries. PMID:24131758

Transcription factor CREB is involved in CaSR-mediated cytoskeleton gene expression.

PubMed

Huang, Shuaishuai; Ren, Yu; Wang, Ping; Li, Yanyuan; Wang, Xue; Zhuang, Haihui; Fang, Rong; Wang, Yuduo; Liu, Ningsheng; Hehir, Michael; Zhou, Jeff X

2015-03-01

Our previous studies illustrated that a steady increase of intracellular calcium concentration ([Ca2+]i) was important for maintaining microtubules (MTs) rearrangement in apoptotic cells. However, little is known about the effect of calcium sensing receptor (CaSR)-mediated increase in [Ca2+]i on cytoskeleton gene expression. We examined the impact of taxol or CaSR agonist/antagonist on the regulation of [Ca2+]i concentration, cytoskeleton arrangement, phosphorylated CREB and cytoskeleton gene expressions in HeLa cells with dominant negative plasmid of CREB (PM). This study demonstrated that Gdcl3 (a specific CaSR agonist) evoked a rapid increase of [Ca2+]i, formed a rigid bundle of MTs which surrounded the nucleus and decreased the cytoskeleton gene expressions in HeLa cells. These effects were rescued by addition of NPS2390 (a specific CaSR antagonist). Moreover, CaSR activity affected cytoskeleton gene expression through transcription factor CREB. Histoscores of pCREB immunoreactivity in tissues of cervical adenocarcinoma, renal clear cell carcinoma, and diffuse large B-cell lymphoma were markedly increased compared with non malignant tissue. These data demonstrate, for the first time, that CaSR-mediated increase in [Ca2+]i probably modulate cytoskeleton organization and gene expression via transcription factor. © 2014 Wiley Periodicals, Inc.

Use of the Exponential and Exponentiated Demand Equations to Assess the Behavioral Economics of Negative Reinforcement

PubMed Central

Fragale, Jennifer E. C.; Beck, Kevin D.; Pang, Kevin C. H.

2017-01-01

Abnormal motivation and hedonic assessment of aversive stimuli are symptoms of anxiety and depression. Symptoms influenced by motivation and anhedonia predict treatment success or resistance. Therefore, a translational approach to the study of negatively motivated behaviors is needed. We describe a novel use of behavioral economics demand curve analysis to investigate negative reinforcement in animals that separates hedonic assessment of footshock termination (i.e., relief) from motivation to escape footshock. In outbred Sprague Dawley (SD) rats, relief increased as shock intensity increased. Likewise, motivation to escape footshock increased as shock intensity increased. To demonstrate the applicability to anxiety disorders, hedonic and motivational components of negative reinforcement were investigated in anxiety vulnerable Wistar Kyoto (WKY) rats. WKY rats demonstrated increased motivation for shock cessation with no difference in relief as compared to control SD rats, consistent with a negative bias for motivation in anxiety vulnerability. Moreover, motivation was positively correlated with relief in SD, but not in WKY. This study is the first to assess the hedonic and motivational components of negative reinforcement using behavioral economic analysis. This procedure can be used to investigate positive and negative reinforcement in humans and animals to gain a better understanding of the importance of motivated behavior in stress-related disorders. PMID:28270744

Study of wettability and cell viability of H implanted stainless steel

NASA Astrophysics Data System (ADS)

Shafique, Muhammad Ahsan; Ahmad, Riaz; Rehman, Ihtesham Ur

2018-03-01

In the present work, the effect of hydrogen ion implantation on surface wettability and biocompatibility of stainless steel is investigated. Hydrogen ions are implanted in the near-surface of stainless steel to facilitate hydrogen bonding at different doses with constant energy of 500 KeV, which consequently improve the surface wettability. Treated and untreated sample are characterized for surface wettability, incubation of hydroxyapatite and cell viability. Contact angle (CA) study reveals that surface wettability increases with increasing H-ion dose. Raman spectroscopy shows that precipitation of hydroxyapatite over the surface increase with increasing dose of H-ions. Cell viability study using MTT assay describes improved cell viability in treated samples as compared to the untreated sample. It is found that low dose of H-ions is more effective for cell proliferation and the cell count decreases with increasing ion dose. Our study demonstrates that H ion implantation improves the surface wettability and biocompatibility of stainless steel.

Preparing Pupils to Cooperate during Cooperative Controversy in Grade 6: A Way to Increase Positive Interactions and Learning?

ERIC Educational Resources Information Center

Golub, Mijal; Buchs, Céline

2014-01-01

Research has underlined the necessity to prepare pupils to cooperate in order to boost cooperative learning benefits. However, this kind of training may appear very demanding. The present study aims to demonstrate that a short preparation related to social support and targeted cooperative rules relevant for the task increases constructive…

Alcohol Intoxication Impact on Outcome from Traumatic Injury

DTIC Science & Technology

2008-05-01

emergency department. Previously we have demonstrated that ICV choline increased basal MABP (+17%) and produced a similar increase in basal MABP in...alcohol intoxicated. However, ICV choline did not alter the initial % decrease in blood pressure nor did it improve MABP throughout hemorrhagic...shock or fluid resuscitation in alcohol-treated animals. These studies showed that intracerebroventricular (ICV) choline (acetylcholine precursor

Novel daidzein analogs enhance osteogenic activity of bone marrow-derived mesenchymal stem cells and adipose-derived stromal/stem cells through estrogen receptor dependent and independent mechanisms

USDA-ARS?s Scientific Manuscript database

Osteoporosis is a disease characterized by low bone mineral density (BMD) and increased risk of fractures. Studies have demonstrated the use of phytoestrogens, or plant-derived estrogens, such as genistein anddaidzein, to effectively increase osteogenic activity of bone marrow-derived mesenchymal s...

Engaging Actively with Issues in the Responsible Conduct of Science: Lessons from International Efforts Are Relevant for Undergraduate Education in the United States

ERIC Educational Resources Information Center

Clements, John D.; Connell, Nancy D.; Dirks, Clarissa; El-Faham, Mohamed; Hay, Alastair; Heitman, Elizabeth; Stith, James H.; Bond, Enriqueta C.; Colwell, Rita R.; Anestidou, Lida; Husbands, Jo L.; Labov, Jay B.

2013-01-01

Numerous studies are demonstrating that engaging undergraduate students in original research can improve their achievement in the science, technology, engineering, and mathematics (STEM) fields and increase the likelihood that some of them will decide to pursue careers in these disciplines. Associated with this increased prominence of research in…

"Now It Is about Me Having to Learn Something …." Partners' Experiences with a Dutch Conversation Partner Training Programme (PACT)

ERIC Educational Resources Information Center

Wielaert, Sandra M.; Berns, Philine; van de Sandt-Koenderman, Mieke W. M. E.; Dammers, Nina; Sage, Karen

2017-01-01

Background: The increase in the number of reported conversation partner programmes for conversation partners of people with aphasia demonstrates increased awareness of partner needs and the positive effect of trained partners on the communicative abilities of the person with aphasia. Predominantly small-scale studies describe the effectiveness of…

Regional patterns in foliar 15N across a gradient of nitrogen deposition in the northeastern US

Treesearch

Linda H. Pardo; Steven G. McNulty; Johnny L. Boggs; Sara Duke

2007-01-01

Recent studies have demonstrated that natural abundance 15N can be a useful tool for assessing nitrogen saturation, because as nitrification and nitrate loss increase, d15N of foliage and soil also increases. We measured foliar d15N at 11 high-elevation spruce-fir stands along an N deposition gradient...

Regional patterns in foliar 15N across a gradient of nitrogen deposition in the northeastern US

Treesearch

Linda H. Pardo; Steven G. McNulty; Johnny L. Boggs; Sara Duke

2007-01-01

Recent studies have demonstrated that natural abundance 15N can be a useful tool for assessing nitrogen saturation, because as nitrification and nitrate loss increase, a15N of foliage and soil also increases. We measured foliar a15N at 11 high-elevation spruce-fir stands along an N deposition gradient...

Interleukin 6 trigged ataxia-telangiectasia mutated activation facilitates lung cancer metastasis via MMP-3/MMP-13 up-regulation.

PubMed

Jiang, Yi Na; Yan, Hong Qiong; Huang, Xiao Bo; Wang, Yi Nan; Li, Qing; Gao, Feng Guang

2015-12-01

Our previous studies show that the phosphorylation of ataxia-telangiectasia mutated (ATM) induced by interleukin 6 (IL-6) treatment contributes to multidrug resistance formation in lung cancer cells, but the exact role of ATM activation in IL-6 increased metastasis is still elusive. In the present study, matrix metalloproteinase-3 (MMP-3) and MMP-13 were firstly demonstrated to be involved in IL-6 correlated cell migration. Secondly, IL-6 treatment not only increased MMP-3/MMP-13 expression but also augmented its activities. Thirdly, the inhibition of ATM phosphorylation efficiently abolished IL-6 up-regulating MMP-3/MMP-13 expression and increasing abilities of cell migration. Most importantly, the in vivo test showed that the inhibition of ATM abrogate the effect of IL-6 on lung cancer metastasis via MMP-3/MMP-13 down-regulation. Taken together, these findings demonstrate that IL-6 inducing ATM phosphorylation increases the expression of MMP-3/MMP-13, augments the abilities of cell migration, and promotes lung cancer metastasis, indicating that ATM is a potential target molecule to overcome IL-6 correlated lung cancer metastasis.

Bilirubin Binding to PPARα Inhibits Lipid Accumulation

PubMed Central

Stec, David E.; John, Kezia; Trabbic, Christopher J.; Luniwal, Amarjit; Hankins, Michael W.; Baum, Justin

2016-01-01

Numerous clinical and population studies have demonstrated that increased serum bilirubin levels protect against cardiovascular and metabolic diseases such as obesity and diabetes. Bilirubin is a potent antioxidant, and the beneficial actions of moderate increases in plasma bilirubin have been thought to be due to the antioxidant effects of this bile pigment. In the present study, we found that bilirubin has a new function as a ligand for PPARα. We show that bilirubin can bind directly to PPARα and increase transcriptional activity. When we compared biliverdin, the precursor to bilirubin, on PPARα transcriptional activation to known PPARα ligands, WY 14,643 and fenofibrate, it showed that fenofibrate and biliverdin have similar activation properties. Treatment of 3T3-L1 adipocytes with biliverdin suppressed lipid accumulation and upregulated PPARα target genes. We treated wild-type and PPARα KO mice on a high fat diet with fenofibrate or bilirubin for seven days and found that both signal through PPARα dependent mechanisms. Furthermore, the effect of bilirubin on lowering glucose and reducing body fat percentage was blunted in PPARα KO mice. These data demonstrate a new function for bilirubin as an agonist of PPARα, which mediates the protection from adiposity afforded by moderate increases in bilirubin. PMID:27071062

A stable pattern of EEG spectral coherence distinguishes children with autism from neuro-typical controls - a large case control study

PubMed Central

2012-01-01

Background The autism rate has recently increased to 1 in 100 children. Genetic studies demonstrate poorly understood complexity. Environmental factors apparently also play a role. Magnetic resonance imaging (MRI) studies demonstrate increased brain sizes and altered connectivity. Electroencephalogram (EEG) coherence studies confirm connectivity changes. However, genetic-, MRI- and/or EEG-based diagnostic tests are not yet available. The varied study results likely reflect methodological and population differences, small samples and, for EEG, lack of attention to group-specific artifact. Methods Of the 1,304 subjects who participated in this study, with ages ranging from 1 to 18 years old and assessed with comparable EEG studies, 463 children were diagnosed with autism spectrum disorder (ASD); 571 children were neuro-typical controls (C). After artifact management, principal components analysis (PCA) identified EEG spectral coherence factors with corresponding loading patterns. The 2- to 12-year-old subsample consisted of 430 ASD- and 554 C-group subjects (n = 984). Discriminant function analysis (DFA) determined the spectral coherence factors' discrimination success for the two groups. Loading patterns on the DFA-selected coherence factors described ASD-specific coherence differences when compared to controls. Results Total sample PCA of coherence data identified 40 factors which explained 50.8% of the total population variance. For the 2- to 12-year-olds, the 40 factors showed highly significant group differences (P < 0.0001). Ten randomly generated split half replications demonstrated high-average classification success (C, 88.5%; ASD, 86.0%). Still higher success was obtained in the more restricted age sub-samples using the jackknifing technique: 2- to 4-year-olds (C, 90.6%; ASD, 98.1%); 4- to 6-year-olds (C, 90.9%; ASD 99.1%); and 6- to 12-year-olds (C, 98.7%; ASD, 93.9%). Coherence loadings demonstrated reduced short-distance and reduced, as well as increased, long-distance coherences for the ASD-groups, when compared to the controls. Average spectral loading per factor was wide (10.1 Hz). Conclusions Classification success suggests a stable coherence loading pattern that differentiates ASD- from C-group subjects. This might constitute an EEG coherence-based phenotype of childhood autism. The predominantly reduced short-distance coherences may indicate poor local network function. The increased long-distance coherences may represent compensatory processes or reduced neural pruning. The wide average spectral range of factor loadings may suggest over-damped neural networks. PMID:22730909

Impact of acoustic airflow on intrasinus drug deposition: New insights into the vibrating mode and the optimal acoustic frequency to enhance the delivery of nebulized antibiotic.

PubMed

Leclerc, Lara; Merhie, Amira El; Navarro, Laurent; Prévôt, Nathalie; Durand, Marc; Pourchez, Jérémie

2015-10-15

We investigated the impact of vibrating acoustic airflow, the high frequency (f≥100 Hz) and the low frequency (f≤45 Hz) sound waves, on the enhancement of intrasinus drug deposition. (81m)Kr-gas ventilation study was performed in a plastinated human cast with and without the addition of vibrating acoustic airflow. Similarly, intrasinus drug deposition in a nasal replica using gentamicin as a marker was studied with and without the superposition of different modes of acoustic airflow. Ventilation experiments demonstrate that no sinus ventilation was observed without acoustic airflow although sinus ventilation occurred whatever the modes of acoustic airflow applied. Intrasinus drug deposition experiments showed that the high frequency acoustic airflow led to 4-fold increase in gentamicin deposition into the left maxillary sinus and to 2-fold deposition increase into the right maxillary sinus. Besides, the low frequency acoustic airflow demonstrated a significant increase of 4-fold and 2-fold in the right and left maxillary sinuses, respectively. We demonstrated the benefit of different modes of vibrating acoustic airflow for maxillary sinus ventilation and intrasinus drug deposition. The degree of gentamicin deposition varies as a function of frequency of the vibrating acoustic airflow and the geometry of the ostia. Copyright © 2015 Elsevier B.V. All rights reserved.

Cooled Ceramic Matrix Composite Propulsion Structures Demonstrated

NASA Technical Reports Server (NTRS)

Jaskowiak, Martha H.; Dickens, Kevin W.

2005-01-01

NASA's Next Generation Launch Technology (NGLT) Program has successfully demonstrated cooled ceramic matrix composite (CMC) technology in a scramjet engine test. This demonstration represented the world s largest cooled nonmetallic matrix composite panel fabricated for a scramjet engine and the first cooled nonmetallic composite to be tested in a scramjet facility. Lightweight, high-temperature, actively cooled structures have been identified as a key technology for enabling reliable and low-cost space access. Tradeoff studies have shown this to be the case for a variety of launch platforms, including rockets and hypersonic cruise vehicles. Actively cooled carbon and CMC structures may meet high-performance goals at significantly lower weight, while improving safety by operating with a higher margin between the design temperature and material upper-use temperature. Studies have shown that using actively cooled CMCs can reduce the weight of the cooled flow-path component from 4.5 to 1.6 lb/sq ft and the weight of the propulsion system s cooled surface area by more than 50 percent. This weight savings enables advanced concepts, increased payload, and increased range. The ability of the cooled CMC flow-path components to operate over 1000 F hotter than the state-of-the-art metallic concept adds system design flexibility to space-access vehicle concepts. Other potential system-level benefits include smaller fuel pumps, lower part count, lower cost, and increased operating margin.

The biological assessment of flora and fauna as standards for changes in the near-shore ocean environment: a study of Barbers Point Harbor.

PubMed

Hokama, Y; Wachi, K M; Shiraki, A; Goo, C; Ebesu, J S

2001-02-01

The biological assessments of the flora and fauna in the near-shore ocean environment, specifically Barbers Point Harbor (BPH), demonstrate the usefulness of these biological analyses for evaluation of the changes occurring following man-made excavation for expansion of the harbor. The study included identification and enumeration of macroalgae and dinoflagellates and analyses of herbivores and carnivores in four areas within the perimeter of the harbor and the north and south entrances into the harbor. Numbers of macroalgae varied between 1994 and 1999 surveys, with significant decrease in numbers in stations C, D and E. Stations A and B were similar between 1994 and 1999 with a slight increase in 1999. The significant differences were shown with the appearance of Gambierdiscus toxicus (G toxicus) in 1999 among the algae in stations A and B. Assessment of herbivores and carnivores with the immunological membrane immunobead assay using monoclonal antibody to ciguatoxin and related polyethers demonstrated an increase in fish toxicity among the herbivore from 1994-1999 (22% increase) with a decrease (22%) in non-toxic fish. This was also demonstrated in the carnivores, but to a lesser degree. It is suggested that the biological analyses of the flora and the fauna of the near-shore ocean environment are appropriate to assess the changes that occur from natural and man-made alterations.

Adipose‑derived stem cells and hyaluronic acid based gel compatibility, studied in vitro.

PubMed

Guo, Jiayan; Guo, Shu; Wang, Yuxin; Yu, Yanqiu

2017-10-01

Minimally invasive aesthetic and cosmetic procedures have increased in popularity. Injectable dermal fillers provide soft tissue augmentation, improve facial rejuvenation and wrinkles, and correct tissue defects. To investigate the use of adipose‑derived stem cells integrated with a hyaluronic acid based gel as a dermal filler, the present study used cytotoxicity studies, proliferation studies, adipogenic and osteogenic differentiation, apoptosis assays and scanning electron microscopy. Although hyaluronic acid induced low levels of apoptosis in adipose‑derived stem cells, its significantly promoted proliferation of adipose‑derived stem cells. Hyaluronic acid demonstrates little toxicity against adipose‑derived stem cells. Adipose‑derived stem cells were able to differentiate into adipocytes and osteoblasts. Furthermore, scanning electron microscopy revealed that adipose‑derived stem cells maintained intact structures on the surface of hyaluronic acid as well as in it, and demonstrated abundant cell attachments. The present study demonstrated the compatibility of adipose‑derived stem cells and hyaluronic acid based gels in vitro.

Trust, trolleys and social dilemmas: A replication study.

PubMed

Bostyn, Dries H; Roets, Arne

2017-05-01

The present manuscript addresses how perceived trustworthiness of cooperative partners in a social dilemma context is influenced by the moral judgments those partners make on Trolley-type moral dilemmas; an issue recently investigated by Everett, Pizarro, and Crockett (2016). The present research comprises 2 studies that were conducted independently, simultaneously with, and incognizant of the Everett studies. Whereas the present studies aimed at investigating the same research hypothesis, a different and more elaborate methodology was used, as such providing a conceptual replication opportunity and extension to the Everett et al. Overall, the present studies clearly confirmed the main finding of Everett et al., that deontologists are more trusted than consequentialists in social dilemma games. Study 1 replicates Everett et al.'s effect in the context of trust games. Study 2 generalizes the effect to public goods games, thus demonstrating that it is not specific to the type of social dilemma game used in Everett et al. Finally, both studies build on these results by demonstrating that the increased trust in deontologists may sometimes, but not always, be warranted: deontologists displayed increased cooperation rates but only in the public goods game and not in trust games. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Inhibition of 5-LOX, COX-1, and COX-2 increases tendon healing and reduces muscle fibrosis and lipid accumulation after rotator cuff repair.

PubMed

Oak, Nikhil R; Gumucio, Jonathan P; Flood, Michael D; Saripalli, Anjali L; Davis, Max E; Harning, Julie A; Lynch, Evan B; Roche, Stuart M; Bedi, Asheesh; Mendias, Christopher L

2014-12-01

The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries. While previous studies have demonstrated that nonsteroidal anti-inflammatory drugs and selective inhibitors of COX-2 (coxibs) may prevent the proper healing of muscles and tendons, studies about bone and cartilage have demonstrated that drugs that inhibit 5-LOX concurrently with COX-1 and COX-2 may enhance tissue regeneration. After the repair of a chronic rotator cuff tear in rats, licofelone would increase the load to failure of repaired tendons and increase the force production of muscle fibers. Controlled laboratory study. Rats underwent supraspinatus release followed by repair 28 days later. After repair, rats began a treatment regimen of either licofelone or a vehicle for 14 days, at which time animals were euthanized. Supraspinatus muscles and tendons were then subjected to contractile, mechanical, histological, and biochemical analyses. Compared with controls, licofelone-treated rats had a grossly apparent decrease in inflammation and increased fibrocartilage formation at the enthesis, along with a 62% increase in the maximum load to failure and a 51% increase in peak stress to failure. Licofelone resulted in a marked reduction in fibrosis and lipid content in supraspinatus muscles as well as reduced expression of several genes involved in fatty infiltration. Despite the decline in fibrosis and fat accumulation, muscle fiber specific force production was reduced by 23%. The postoperative treatment of cuff repair with licofelone may reduce fatty degeneration and enhance the development of a stable bone-tendon interface, although decreases in muscle fiber specific force production were observed, and force production in fact declined. This study demonstrates that the inhibition of 5-LOX, COX-1, and COX-2 modulates the healing process of repaired rotator cuff tendons. Although further studies are necessary, the treatment of patients with licofelone after cuff repair may improve the development of a stable enthesis and enhance postoperative outcomes. © 2014 The Author(s).

Mechanisms of axonal dysfunction in diabetic and uraemic neuropathies.

PubMed

Arnold, Ria; Kwai, Natalie C G; Krishnan, Arun V

2013-11-01

The global burden imposed by metabolic diseases and associated complications continue to escalate. Neurological complications, most commonly peripheral neuropathy, represent a significant cause of morbidity and disability in patients with diabetes and chronic kidney disease. Furthermore, health care costs are substantially increased by the presence of complications making investigation into treatment a matter of high priority. Over the last decade nerve excitability techniques have entered the clinical realm and enabled in vivo assessment of biophysical properties and function of peripheral nerves in health and disease. Studies of excitability in diabetic neuropathy have demonstrated alteration in biophysical properties, including changes in Na(+) conductances and Na(+)/K(+) pump function, which may contribute to the development of neuropathic symptoms. Interventional studies have demonstrated that these changes are responsive to pharmacological agents. Excitability studies in patients with chronic kidney disease have demonstrated prominent changes that may contribute to the development of uraemic neuropathy. In particular, these studies have demonstrated strong correlation between hyperkalaemia and the development of nerve dysfunction. These studies have provided a basis for future work assessing the benefits of potassium restriction as a therapeutic strategy in this condition. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Effects of amorphous calcium phosphate stabilized by casein phosphopeptides on enamel de- and remineralization in primary teeth: an in vitro study.

PubMed

Bar-Hillel, Rita; Feuerstein, Osnat; Tickotsky, Nili; Shapira, Joseph; Moskovitz, Moti

2012-01-01

Amorphous calcium phosphate, stabilized by casein phosphopeptides, has been found to enhance remineralization of subsurface lesions in permanent teeth. The purpose of the present in vitro study was to evaluate the potential of GC Tooth Mousse to enhance remineralization of initial demineralized enamel sites in primary teeth. Forty-four demineralization sites were created in 22 extracted primary teeth. Samples were randomly assigned to 6 treatment groups (GC Tooth Mousse covering, GC Tooth Mousse covering and demineralization, and control groups). The mineral content of each sample was evaluated using energy dispersive X-ray analysis, performed from the enamel surface of each lesion inwards. The results were analyzed using analysis of variance, with a significance level P<.05. Samples treated with GC Tooth Mousse demonstrated an increase in the calcium-phosphate ratio by approximately 2% near the surface, a minimal increase of 1% at a depth over 60 μm, and no change at a depth from 40 to 60 μm, with no statistically significant differences (P>.05). This study demonstrates a minimal increase in the subsurface calcium-phosphate ratio following GC Tooth Mousse treatment, especially in demineralized enamel tissue.

Modulation of induced gamma band activity in the human EEG by attention and visual information processing.

PubMed

Müller, M M; Gruber, T; Keil, A

2000-12-01

Here we present a series of four studies aimed to investigate the link between induced gamma band activity in the human EEG and visual information processing. We demonstrated and validated the modulation of spectral gamma band power by spatial selective visual attention. When subjects attended to a certain stimulus, spectral power was increased as compared to when the same stimulus was ignored. In addition, we showed a shift in spectral gamma band power increase to the contralateral hemisphere when subjects shifted their attention to one visual hemifield. The following study investigated induced gamma band activity and the perception of a Gestalt. Ambiguous rotating figures were used to operationalize the law of good figure (gute Gestalt). We found increased gamma band power at posterior electrode sites when subjects perceived an object. In the last experiment we demonstrated a differential hemispheric gamma band activation when subjects were confronted with emotional pictures. Results of the present experiments in combination with other studies presented in this volume are supportive for the notion that induced gamma band activity in the human EEG is closely related to visual information processing and attentional perceptual mechanisms.

Modeling changes in rill erodibility and critical shear stress on native surface roads

Treesearch

Randy B. Foltz; Hakjun Rhee; William J. Elliot

2008-01-01

This study investigated the effect of cumulative overland flow on rill erodibility and critical shear stress on native surface roads in central Idaho. Rill erodibility decreased exponentially with increasing cumulative overland flow depth; however, critical shear stress did not change. The study demonstrated that road erodibility on the studied road changes over the...

Do Prior Studies Matter?: Predicting Proficiencies Required to Excel Academically in Law School at Makerere University, Uganda

ERIC Educational Resources Information Center

Nalukenge, Betty; Wamala, Robert; Ocaya, Bruno

2016-01-01

Purpose: Introduction of law school admission examinations has increased the debate regarding the relevance of prior studies for the enrollees in the program. The key issues of contention are whether prior studies reliably predict academic achievement of enrollees, and demonstrate proficiencies required for admission in the program. The purpose of…

National Studies Find TRIO Programs Effective at Increasing College Enrollment and Graduation

ERIC Educational Resources Information Center

Pell Institute for the Study of Opportunity in Higher Education, 2009

2009-01-01

Since 1997, four national studies conducted by the U.S. Department of Education have been completed on the Federal TRIO programs. Data from these studies demonstrate that participation in a TRIO program has a significant impact on the educational outcomes of low-income, first-generation students and students with disabilities. This paper provides…

The Cumulative Burden Borne by Offspring Whose Mothers Were Sexually Abused as Children: Descriptive Results from a Multigenerational Study

ERIC Educational Resources Information Center

Noll, Jennie G.; Trickett, Penelope K.; Harris, William W.; Putnam, Frank W.

2009-01-01

This multigenerational study empirically demonstrates the extent to which offspring whose parents experienced childhood abuse are at increased risk of being abused or neglected. Females with substantiated childhood sexual abuse and nonabused comparison females were assessed at six points spanning 18 years in a prospective, longitudinal study.…

A Case-Based Approach Increases Student Learning Outcomes and Comprehension of Cellular Respiration Concepts

ERIC Educational Resources Information Center

Rybarczyk, Brian J.; Baines, Antonio T.; McVey, Mitch; Thompson, Joseph T.; Wilkins, Heather

2007-01-01

This study investigated student learning outcomes using a case-based approach focused on cellular respiration. Students who used the case study, relative to students who did not use the case study, exhibited a significantly greater learning gain, and demonstrated use of higher-order thinking skills. Preliminary data indicate that after engaging…

High inorganic phosphate causes DNMT1 phosphorylation and subsequent fibrotic fibroblast activation

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

Tan, Xiaoying; Department of Cardiology and Pneumology, Göttingen University Medical Center, Georg August University, Göttingen; Xu, Xingbo

Phosphate is an essential constituent of critical cellular functions including energy metabolism, nucleic acid synthesis and phosphorylation-dependent cell signaling. Increased plasma phosphate levels are an independent risk factor for lowered life-expectancy as well as for heart and kidney failure. Nevertheless, direct cellular effects of elevated phosphate concentrations within the microenvironment are poorly understood and have been largely neglected in favor of phosphor-regulatory hormones. Because interstitial fibrosis is the common determinant of chronic progressive kidney disease, and because fibroblasts are major mediators of fibrogenesis, we here explored the effect of high extracellular phosphate levels on renal fibroblasts. We demonstrate that highmore » inorganic phosphate directly induces fibrotic fibroblast activation associated with increased proliferative activity, increased expression of α-smooth muscle actin and increased synthesis of type I collagen. We further demonstrate that such fibroblast activation is dependent on phosphate influx, aberrant phosphorylation of DNA methyltransferase DNMT1 and aberrant CpG island promoter methylation. In summary, our studies demonstrate that elevated phosphate concentrations induce pro-fibrotic fibroblast activation independent of phospho-regulatory hormones. - Highlights: • We exposed human kidney fibroblasts to media containing 1 mM or 3 mM phosphate. • Increased phosphate influx causes phosphorylation of DNA methyltransferase Dnmt1. • Phosphorylated Dnmt1 causes promoter methylation and transcriptional silencing of RASAL1. • Depletion of RASAL1 causes increased intrinsic Ras-GTP activity and fibroblast activation. • Inorganic phosphate causes fibroblast activation independent of phospho-regulatory hormones.« less

Adrenal hormones mediate melatonin-induced increases in aggression in male Siberian hamsters (Phodopus sungorus).

PubMed

Demas, Gregory E; Polacek, Kelly M; Durazzo, Alfredo; Jasnow, Aaron M

2004-12-01

Among the suite of seasonal adaptations displayed by nontropical rodents, some species demonstrate increased territorial aggression in short compared with long day lengths despite basal levels of testosterone. The precise physiological mechanisms mediating seasonal changes in aggression, however, remain largely unknown. The goal of the present study was to examine the role of melatonin, as well as adrenal hormones, in the regulation of seasonal aggression in male Siberian hamsters (Phodopus sungorus). In Experiment 1, male Siberian hamsters received either daily (s.c.) injections of melatonin (15 microg/day) or saline 2 h before lights out for 10 consecutive days. In Experiment 2, hamsters received adrenal demedullations (ADMEDx), whereas in Experiment 3 animals received adrenalectomies (ADx); control animals in both experiments received sham surgeries. Animals in both experiments subsequently received daily injections of melatonin or vehicle as in Experiment 1. Animals in all experiments were tested using a resident-intruder model of aggression. In Experiment 1, exogenous melatonin treatment increased aggression compared with control hamsters. In Experiment 2, ADMEDx had no effect on melatonin-induced aggression. In Experiment 3, the melatonin-induced increase in aggression was significantly attenuated by ADx. Collectively, the results of the present study demonstrate that short day-like patterns of melatonin increase aggression in male Siberian hamsters and suggest that increased aggression is due, in part, to changes in adrenocortical steroids.

Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States

PubMed Central

2017-01-01

During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes. PMID:28317001

Extracellular Alkalinization as a Defense Response in Potato Cells.

PubMed

Moroz, Natalia; Fritch, Karen R; Marcec, Matthew J; Tripathi, Diwaker; Smertenko, Andrei; Tanaka, Kiwamu

2017-01-01

A quantitative and robust bioassay to assess plant defense response is important for studies of disease resistance and also for the early identification of disease during pre- or non-symptomatic phases. An increase in extracellular pH is known to be an early defense response in plants. In this study, we demonstrate extracellular alkalinization as a defense response in potatoes. Using potato suspension cell cultures, we observed an alkalinization response against various pathogen- and plant-derived elicitors in a dose- and time-dependent manner. We also assessed the defense response against a variety of potato pathogens, such as protists ( Phytophthora infestans and Spongospora subterranea ) and fungi ( Verticillium dahliae and Colletotrichum coccodes ). Our results show that extracellular pH increases within 30 min in proportion to the number of pathogen spores added. Consistently with the alkalinization effect, the higher transcription level of several defense-related genes and production of reactive oxygen species was observed. Our results demonstrate that the alkalinization response is an effective marker to study early stages of defense response in potatoes.

Effects of the synthetic corticosteroid dexamethasone on bovine herpesvirus 1 productive infection.

PubMed

Zhu, Liqian; Thompson, Jesse; Ma, Fangrui; Eudy, James; Jones, Clinton

2017-05-01

Sensory neurons are a primary site for life-long latency of bovine herpesvirus 1 (BoHV-1). The synthetic corticosteroid dexamethasone induces reactivation from latency and productive infection, in part because the BoHV-1 genome contains more than 100 glucocorticoid receptor (GR) responsive elements (GREs). Two GREs in the immediate early transcription unit 1 promoter are required for dexamethasone induction. Recent studies also demonstrated that the serum and glucocorticoid receptor protein kinase (SGK) family stimulated BoHV-1 replication. Consequently, we hypothesized that dexamethasone influences several aspects of productive infection. In this study, we demonstrated that dexamethasone increased expression of the immediate early protein bICP4, certain late transcripts, and UL23 (thymidine kinase) by four hours after infection. SGK1 expression and Akt phosphorylation were also stimulated during early stages of infection and dexamethasone treatment further increased this effect. These studies suggest that stress, as mimicked by dexamethasone treatment, has the potential to stimulate productive infection by multiple pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Behavioral State Modulates the Activity of Brainstem Sensorimotor Neurons

PubMed Central

McArthur, Kimberly L.

2011-01-01

Sensorimotor processing must be modulated according to the animal's behavioral state. A previous study demonstrated that motion responses were strongly state dependent in birds. Vestibular eye and head responses were significantly larger and more compensatory during simulated flight, and a flight-specific vestibular tail response was also characterized. In the current study, we investigated the neural substrates for these state-dependent vestibular behaviors by recording extracellularly from neurons in the vestibular nuclear complex and comparing their spontaneous activity and sensory responses during default and simulated flight states. We show that motion-sensitive neurons in the lateral vestibular nucleus are state dependent. Some neurons increased their spontaneous firing rates during flight, though their increased excitability was not reflected in higher sensory gains. However, other neurons exhibited state-dependent gating of sensory inputs, responding to rotational stimuli only during flight. These results demonstrate that vestibular processing in the brainstem is state dependent and lay the foundation for future studies to investigate the synaptic mechanisms responsible for these modifications. PMID:22090497

Non-Invasive Radiofrequency Field Treatment of 4T1 Breast Tumors Induces T-cell Dependent Inflammatory Response.

PubMed

Newton, Jared M; Flores-Arredondo, Jose H; Suki, Sarah; Ware, Matthew J; Krzykawska-Serda, Martyna; Agha, Mahdi; Law, Justin J; Sikora, Andrew G; Curley, Steven A; Corr, Stuart J

2018-02-22

Previous work using non-invasive radiofrequency field treatment (RFT) in cancer has demonstrated its therapeutic potential as it can increase intratumoral blood perfusion, localization of intravenously delivered drugs, and promote a hyperthermic intratumoral state. Despite the well-known immunologic benefits that febrile hyperthermia can induce, an investigation of how RFT could modulate the intra-tumoral immune microenvironment had not been studied. Thus, using an established 4T1 breast cancer model in immune competent mice, we demonstrate that RFT induces a transient, localized, and T-cell dependent intratumoral inflammatory response. More specifically we show that multi- and singlet-dose RFT promote an increase in tumor volume in immune competent Balb/c mice, which does not occur in athymic nude models. Further leukocyte subset analysis at 24, 48, and 120 hours after a single RFT show a rapid increase in tumoral trafficking of CD4+ and CD8+ T-cells 24 hours post-treatment. Additional serum cytokine analysis reveals an increase in numerous pro-inflammatory cytokines and chemokines associated with enhanced T-cell trafficking. Overall, these data demonstrate that non-invasive RFT could be an effective immunomodulatory strategy in solid tumors, especially for enhancing the tumoral trafficking of lymphocytes, which is currently a major hindrance of numerous cancer immunotherapeutic strategies.

Solanine induced apoptosis and increased chemosensitivity to Adriamycin in T-cell acute lymphoblastic leukemia cells.

PubMed

Yi, Ying-Jie; Jia, Xiu-Hong; Wang, Jian-Yong; Chen, Jie-Ru; Wang, Hong; Li, You-Jie

2018-05-01

Solanine is an alkaloid and is the main extract of the traditional Chinese herb, Solanum nigrum Linn . It has been reported that Solanine has anti-inflammatory and antitumor properties. The present study aimed to investigate the antitumor effect of Solanine in Jurkat cells and demonstrate the molecular mechanism of antitumor activity of Solanine. A Cell Counting Kit-8 assay demonstrated that Solanine inhibited the proliferation of Jurkat cells in a dose-and time-dependent manner. Cell apoptosis was measured by flow cytometry. Flow cytometry revealed that Solanine induced apoptosis in a dose-dependent manner in Jurkat cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that Solanine modulated the mRNA levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Additionally, Bcl-2 and Bax expression was measured using western blot analysis. Western blot analysis revealed a significant increase in the expression of Bax and decrease in the expression of Bcl-2. Solanine increased the chemosensitivity of Jurkat cells to Adriamycin. In summary, the present results indicated that the antitumor activity of Solanine was associated with inhibition of cell proliferation, induction of apoptosis and increasing cytotoxicity of Adriamycin. Therefore, Solanine may have potential as a novel agent for the treatment of acute lymphocytic leukemia.

A parasitic selfish gene that affects host promiscuity.

PubMed

Giraldo-Perez, Paulina; Goddard, Matthew R

2013-11-07

Selfish genes demonstrate transmission bias and invade sexual populations despite conferring no benefit to their hosts. While the molecular genetics and evolutionary dynamics of selfish genes are reasonably well characterized, their effects on hosts are not. Homing endonuclease genes (HEGs) are one well-studied family of selfish genes that are assumed to be benign. However, we show that carrying HEGs is costly for Saccharomyces cerevisiae, demonstrating that these genetic elements are not necessarily benign but maybe parasitic. We estimate a selective load of approximately 1-2% in 'natural' niches. The second aspect we examine is the ability of HEGs to affect hosts' sexual behaviour. As all selfish genes critically rely on sex for spread, then any selfish gene correlated with increased host sexuality will enjoy a transmission advantage. While classic parasites are known to manipulate host behaviour, we are not aware of any evidence showing a selfish gene is capable of affecting host promiscuity. The data presented here show a selfish element may increase the propensity of its eukaryote host to undergo sex and along with increased rates of non-Mendelian inheritance, this may counterbalance mitotic selective load and promote spread. Demonstration that selfish genes are correlated with increased promiscuity in eukaryotes connects with ideas suggesting that selfish genes promoted the evolution of sex initially.

A parasitic selfish gene that affects host promiscuity

PubMed Central

Giraldo-Perez, Paulina; Goddard, Matthew R.

2013-01-01

Selfish genes demonstrate transmission bias and invade sexual populations despite conferring no benefit to their hosts. While the molecular genetics and evolutionary dynamics of selfish genes are reasonably well characterized, their effects on hosts are not. Homing endonuclease genes (HEGs) are one well-studied family of selfish genes that are assumed to be benign. However, we show that carrying HEGs is costly for Saccharomyces cerevisiae, demonstrating that these genetic elements are not necessarily benign but maybe parasitic. We estimate a selective load of approximately 1–2% in ‘natural’ niches. The second aspect we examine is the ability of HEGs to affect hosts' sexual behaviour. As all selfish genes critically rely on sex for spread, then any selfish gene correlated with increased host sexuality will enjoy a transmission advantage. While classic parasites are known to manipulate host behaviour, we are not aware of any evidence showing a selfish gene is capable of affecting host promiscuity. The data presented here show a selfish element may increase the propensity of its eukaryote host to undergo sex and along with increased rates of non-Mendelian inheritance, this may counterbalance mitotic selective load and promote spread. Demonstration that selfish genes are correlated with increased promiscuity in eukaryotes connects with ideas suggesting that selfish genes promoted the evolution of sex initially. PMID:24048156

OXIDATIVE DNA DAMAGE IN DIESEL BUS MECHANICS

EPA Science Inventory

Rationale:

Diesel exposure has been associated with adverse health effects, including susceptibility to asthma, allergy and cancer. Previous epidemiological studies demonstrated increased cancer incidence among workers exposed to diesel. This is likely due to oxid...

Seasonal patterns of gastrointestinal illness and streamflow along the Ohio River

EPA Science Inventory

Waterborne gastrointestinal (GI) illnesses demonstrate seasonal increases associated with water quality and meteorological characteristics. However, few studies have been conducted on the association of hydrological parameters, such as streamflow, and seasonality of GI illnesses....

Serving first in isolation increases vegetable intake among elementary schoolchildren.

PubMed

Redden, Joseph P; Mann, Traci; Vickers, Zata; Mykerezi, Elton; Reicks, Marla; Elsbernd, Stephanie

2015-01-01

Many people want to eat healthier, but they often fail in these attempts. We report two field studies in an elementary school cafeteria that each demonstrate children eat more of a vegetable (carrots, broccoli) when we provide it first in isolation versus alongside other more preferred foods. We propose this healthy first approach succeeds by triggering one's inherent motivation to eat a single food placed in front of them, and works even though they have prior knowledge of the full menu available and no real time constraints. Consistent with this theory, and counter to simple contrast effects, an additional lab study found that presenting a food first in isolation had the unique ability to increase intake whether the food was healthy (carrots) or less healthy (M&M's). Our findings demonstrate the effectiveness of this simple intervention in promoting healthier eating, which should interest consumers, food marketers, health professionals, and policy makers.

Morning reduction of photosynthetic capacity before midday depression.

PubMed

Koyama, Kohei; Takemoto, Shuhei

2014-03-17

Midday depression of photosynthesis has important consequences for ecosystem carbon exchange. Recent studies of forest trees have demonstrated that latent reduction of photosynthetic capacity can begin in the early morning, preceding the midday depression. We investigated whether such early morning reduction also occurs in an herbaceous species, Oenothera biennis. Diurnal changes of the photosynthetic light response curve (measured using a light-emitting diode) and incident sunlight intensity were measured under field conditions. The following results were obtained: (1) the light-saturated photosynthetic rate decreased beginning at sunrise; (2) the incident sunlight intensity on the leaves increased from sunrise; and (3) combining (1) and (2), the net photosynthetic rate under natural sunlight intensity increased from sunrise, reached a maximum at mid-morning, and then showed midday depression. Our results demonstrate that the latent morning reduction of photosynthetic capacity begins at sunrise, preceding the apparent midday depression, in agreement with previous studies of forest trees.

Neuroendocrine mediators up-regulate alpha1b- and alpha1d-adrenergic receptor subtypes in human monocytes.

PubMed

Rouppe van der Voort, C; Kavelaars, A; van de Pol, M; Heijnen, C J

1999-03-01

Beta2- and alpha2-adrenergic receptors (AR) are thought to be the main AR subtypes to exert the effects of catecholamines on the immune system. However, in the present study, we demonstrate that another subtype of AR can be induced in human monocytes. Expression of alpha1b- and alpha1d-AR mRNA can be obtained by culturing freshly isolated human peripheral blood monocytes with the neuroendocrine mediators dexamethasone or the beta2-AR agonist terbutaline. Using the human monocytic cell line THP-1, we demonstrate that increased levels of alpha1b- and alpha1d-mRNA are accompanied by increased levels of receptor protein as determined by Western blot analysis and radioligand binding assays. This study describes for the first time regulated expression of alpha1-AR subtypes in human monocytes.

Real-time divergent evolution in plants driven by pollinators

PubMed Central

Gervasi, Daniel D. L.; Schiestl, Florian P

2017-01-01

Pollinator-driven diversification is thought to be a major source of floral variation in plants. Our knowledge of this process is, however, limited to indirect assessments of evolutionary changes. Here, we employ experimental evolution with fast cycling Brassica rapa plants to demonstrate adaptive evolution driven by different pollinators. Our study shows pollinator-driven divergent selection as well as divergent evolution in plant traits. Plants pollinated by bumblebees evolved taller size and more fragrant flowers with increased ultraviolet reflection. Bumblebees preferred bumblebee-pollinated plants over hoverfly-pollinated plants at the end of the experiment, showing that plants had adapted to the bumblebees' preferences. Plants with hoverfly pollination became shorter, had reduced emission of some floral volatiles, but increased fitness through augmented autonomous self-pollination. Our study demonstrates that changes in pollinator communities can have rapid consequences on the evolution of plant traits and mating system. PMID:28291771

Emissions impacts of wind and energy storage in a market environment.

PubMed

Sioshansi, Ramteen

2011-12-15

This study examines the emissions impacts of adding wind and energy storage to a market-based electric power system. Using Texas as a case study, we demonstrate that market power can greatly effect the emissions benefits of wind, due to most of the coal-fired generation being owned by the two dominant firms. Wind tends to have less emissions benefits when generators exercise market power, since coal-fired generation is withheld from the market and wind displaces natural gas-fired generators. We also show that storage can have greater negative emissions impacts in the presence of wind than if only storage is added to the system. This is due to wind increasing on- and off-peak electricity price differences, which increases the amount that storage and coal-fired generation are used. We demonstrate that this effect is exacerbated by market power.

Serving First in Isolation Increases Vegetable Intake among Elementary Schoolchildren

PubMed Central

Redden, Joseph P.; Mann, Traci; Vickers, Zata; Mykerezi, Elton; Reicks, Marla; Elsbernd, Stephanie

2015-01-01

Many people want to eat healthier, but they often fail in these attempts. We report two field studies in an elementary school cafeteria that each demonstrate children eat more of a vegetable (carrots, broccoli) when we provide it first in isolation versus alongside other more preferred foods. We propose this healthy first approach succeeds by triggering one’s inherent motivation to eat a single food placed in front of them, and works even though they have prior knowledge of the full menu available and no real time constraints. Consistent with this theory, and counter to simple contrast effects, an additional lab study found that presenting a food first in isolation had the unique ability to increase intake whether the food was healthy (carrots) or less healthy (M&M’s). Our findings demonstrate the effectiveness of this simple intervention in promoting healthier eating, which should interest consumers, food marketers, health professionals, and policy makers. PMID:25830337

An Evaluation of a Social Skills Intervention for Adults with Autism Spectrum Disorder and Intellectual Disabilities preparing for Employment in Ireland: A Pilot Study.

PubMed

Walsh, Edith; Holloway, Jennifer; Lydon, Helena

2018-05-01

Individuals with autism spectrum disorder (ASD) are faced with significant barriers relating to employment opportunities and workplace participation. This study evaluated the effectiveness of the Walker social skills curriculum: the ACCESS program and video modeling to increase social communication skills necessary for workplace inclusion. Participants attended two sessions (i.e., 3 h) per week across a period of 20 weeks. A multiple-probe design was used to demonstrate social skills outcomes across three broad curricular areas (i.e., peer-related, adult-related, and self-related social skills). Pre-and post-intervention standardized assessments were also taken. Results showed significant increases in target social skills and a significant decrease in problem behaviors following intervention. Evidence of maintenance and generalization were also demonstrated. Implications for practice and research are discussed.

Resveratrol Reactivates Latent HIV through Increasing Histone Acetylation and Activating Heat Shock Factor 1.

PubMed

Zeng, Xiaoyun; Pan, Xiaoyan; Xu, Xinfeng; Lin, Jian; Que, Fuchang; Tian, Yuanxin; Li, Lin; Liu, Shuwen

2017-06-07

The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under cotreatment with resveratrol and conventional LRAs. Collectively, this research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.

Ma Huang Tang ameliorates asthma though modulation of Th1/Th2 cytokines and inhibition of Th17 cells in ovalbumin-sensitized mice.

PubMed

Ma, Chun-Hua; Ma, Zhan-Qiang; Fu, Qiang; Ma, Shi-Ping

2014-05-01

Ma Huang Tang (Ephedra decoction, MHT) is a famous classical formula from Shang Han Lun by Zhang Zhongjing in the Han Dynasty. The anti-asthmatic effects of MHT and the possible mechanisms were tested. An asthma model was established by ovalbumin (OVA)-induction in mice. A total of forty-eight mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg·kg(-1)) and MHT (5, 10, and 20 mg·kg(-1)). Airway resistance (Raw) was measured by the forced oscillation technique, histological studies were evaluated by hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and Th17 cells were evaluated by flow cytometry (FCM). This study demonstrated that MHT inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4 and IL-17 levels were recovered in bronchoalveolar lavage fluid, increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that MHT substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that MHT substantially inhibited Th17 cells. These findings suggest that MHT may effectively ameliorate the progression of asthma, and could be further investigated for potential use as a therapy for patients with allergic asthma. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

A study on the use of Gumbel approximation with the Bernoulli spatial scan statistic.

PubMed

Read, S; Bath, P A; Willett, P; Maheswaran, R

2013-08-30

The Bernoulli version of the spatial scan statistic is a well established method of detecting localised spatial clusters in binary labelled point data, a typical application being the epidemiological case-control study. A recent study suggests the inferential accuracy of several versions of the spatial scan statistic (principally the Poisson version) can be improved, at little computational cost, by using the Gumbel distribution, a method now available in SaTScan(TM) (www.satscan.org). We study in detail the effect of this technique when applied to the Bernoulli version and demonstrate that it is highly effective, albeit with some increase in false alarm rates at certain significance thresholds. We explain how this increase is due to the discrete nature of the Bernoulli spatial scan statistic and demonstrate that it can affect even small p-values. Despite this, we argue that the Gumbel method is actually preferable for very small p-values. Furthermore, we extend previous research by running benchmark trials on 12 000 synthetic datasets, thus demonstrating that the overall detection capability of the Bernoulli version (i.e. ratio of power to false alarm rate) is not noticeably affected by the use of the Gumbel method. We also provide an example application of the Gumbel method using data on hospital admissions for chronic obstructive pulmonary disease. Copyright © 2013 John Wiley & Sons, Ltd.

Analgesic use in pregnancy and male reproductive development

PubMed Central

Hurtado-Gonzalez, Pablo; Mitchell, Rod T.

2017-01-01

Purpose of review Male reproductive disorders are common and increasing in incidence in many countries. Environmental factors (including pharmaceuticals) have been implicated in the development of these disorders. This review aims to summarise the emerging epidemiological and experimental evidence for a potential role of in-utero exposure to analgesics in the development of male reproductive disorders. Recent findings A number of epidemiological studies have demonstrated an association between in-utero exposure to analgesics and the development of cryptorchidism, although these findings are not consistent across all studies. Where present, these associations primarily relate to exposure during the second trimester of pregnancy. In-vivo and in-vitro experimental studies have demonstrated variable effects of exposure to analgesics on Leydig cell function in the fetal testis of rodents, particularly in terms of testosterone production. These effects frequently involve exposures that are in excess of those to which humans are exposed. Investigation of the effects of analgesics on human fetal testis have also demonstrated effects on Leydig cell function. Variation in species, model system, dosage and timing of exposure is likely to contribute to differences in the findings between studies. Summary There is increasing evidence for analgesic effects on the developing testis that have the potential to impair reproductive function. However, the importance of these findings in relation to human-relevant exposures and the risk of male reproductive disorders remains unclear. PMID:28277341

Myeloid cells are capable of synthesizing aldosterone to exacerbate damage in muscular dystrophy.

PubMed

Chadwick, Jessica A; Swager, Sarah A; Lowe, Jeovanna; Welc, Steven S; Tidball, James G; Gomez-Sanchez, Celso E; Gomez-Sanchez, Elise P; Rafael-Fortney, Jill A

2016-12-01

FDA-approved mineralocorticoid receptor (MR) antagonists are used to treat heart failure. We have recently demonstrated efficacy of MR antagonists for skeletal muscles in addition to heart in Duchenne muscular dystrophy mouse models and that mineralocorticoid receptors are present and functional in skeletal muscles. The goal of this study was to elucidate the underlying mechanisms of MR antagonist efficacy on dystrophic skeletal muscles. We demonstrate for the first time that infiltrating myeloid cells clustered in damaged areas of dystrophic skeletal muscles have the capacity to produce the natural ligand of MR, aldosterone, which in excess is known to exacerbate tissue damage. Aldosterone synthase protein levels are increased in leukocytes isolated from dystrophic muscles compared with controls and local aldosterone levels in dystrophic skeletal muscles are increased, despite normal circulating levels. All genes encoding enzymes in the pathway for aldosterone synthesis are expressed in muscle-derived leukocytes. 11β-HSD2, the enzyme that inactivates glucocorticoids to increase MR selectivity for aldosterone, is also increased in dystrophic muscle tissues. These results, together with the demonstrated preclinical efficacy of antagonists, suggest MR activation is in excess of physiological need and likely contributes to the pathology of muscular dystrophy. This study provides new mechanistic insight into the known contribution of myeloid cells to muscular dystrophy pathology. This first report of myeloid cells having the capacity to produce aldosterone may have implications for a wide variety of acute injuries and chronic diseases with inflammation where MR antagonists may be therapeutic. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effects of trait self-esteem and death cognitions on worldview defense and search for meaning.

PubMed

Juhl, Jacob; Routledge, Clay

2014-01-01

Terror management theory asserts that attaining self-esteem by adhering to the standards of meaning-providing worldviews helps manage death concerns. Research has shown that mortality salience (MS) increases worldview defense, however, there are conflicting results concerning how trait self-esteem moderates this effect. Studies 1 and 2 demonstrated that MS increases worldview defense for high, but not low, trait self-esteem individuals. These studies raised the question as to whether those with low trait self-esteem engage in efforts to find meaning in response to MS. Study 3 showed that MS increased the search for meaning for low, but not high, trait self-esteem individuals.

Cellular and Animal Studies: Insights into Pathophysiology and Therapy of PCOS.

PubMed

Indran, Inthrani Raja; Lee, Bao Hui; Yong, Eu-Leong

2016-11-01

Basic science studies have advanced our understanding of the role of key enzymes in the steroidogenesis pathway and those that affect the pathophysiology of PCOS. Studies with ovarian theca cells taken from women with PCOS have demonstrated increased androgen production due to increased CYP17A1 and HSD3B2 enzyme activities. Furthermore, overexpression of DENND1A variant 2 in normal theca cells resulted in a PCOS phenotype with increased androgen production. Notably, cellular steroidogenesis models have facilitated the understanding of the mechanistic effects of pharmacotherapies, including insulin sensitizers (e.g., pioglitazone and metformin) used for the treatment of insulin resistance in PCOS, on androgen production. In addition, animal models of PCOS have provided a critical platform to study the effects of therapeutic agents in a manner closer to the physiological state. Indeed, recent breakthroughs have demonstrated that natural derivatives such as the dietary medium-chain fatty acid decanoic acid (DA) can restore estrous cyclicity and lower androgen levels in an animal model of PCOS, thus laying the platform for novel therapeutic developments in PCOS. This chapter reviews the current understanding on the pathways modulating androgen biosynthesis, and the cellular and animal models that form the basis for preclinical research in PCOS, and sets the stage for clinical research. Copyright © 2016. Published by Elsevier Ltd.

A randomized controlled trial of the effectiveness of a pre-recruitment primer letter to increase participation in a study of colorectal screening and surveillance.

PubMed

Paul, Christine; Courtney, Ryan; Sanson-Fisher, Rob; Carey, Mariko; Hill, David; Simmons, Jody; Rose, Shiho

2014-04-01

Recruiting cancer patients is a barrier often encountered in research trials. However, very few randomized trials explore strategies to improve participation rates. The purpose of this study was to evaluate the effectiveness of a pre-recruitment primer letter to recruit persons diagnosed with colorectal cancer for a research trial. Potentially eligible participants were identified by the Victorian Cancer Registry. A total of 1,062 participants were randomized to receive either a mailed explanatory primer letter designed to encourage research participation, or no primer letter. Two weeks after the intervention, the Victorian Cancer Registry sought permission from patients to release their contact details to researchers. Those who agreed were contacted and invited to the study. Pre-recruitment encouragement was not effective at increasing recruitment, with no significant differences demonstrated between experimental groups. Overall, 40% (n = 425) consented to participate, 25% (n = 243) refused and 35% (n = 394) did not respond. While this study demonstrated disappointing outcomes, pre-recruitment letters should not be ruled out as an approach altogether. Rather, future research should explore whether other factors to increase motivation, such as intensity and timing, are feasible and acceptable for contacting cancer patients. Australian and New Zealand Clinical Trials Registry, ACTRN12609000628246.

Increased Water Storage in the Qaidam Basin, the North Tibet Plateau from GRACE Gravity Data

PubMed Central

Jiao, Jiu Jimmy; Zhang, Xiaotao; Liu, Yi; Kuang, Xingxing

2015-01-01

Groundwater plays a key role in maintaining the ecology and environment in the hyperarid Qaidam Basin (QB). Indirect evidence and data from sparse observation wells suggest that groundwater in the QB is increasing but there has been no regional assessment of the groundwater conditions in the entire basin because of its remoteness and the severity of the arid environment. Here we report changes in the spatial and temporal distribution of terrestrial water storage (TWS) in the northern Tibetan Plateau (NTP) using Gravity Recovery and Climate Experiment (GRACE) data. Our study confirms long-term (2003–2012) TWS increases in the NTP. Between 2003 and 2012 the TWS increased by 88.4 and 20.6 km3 in the NTP and the QB, respectively, which is 225% and 52% of the capacity of the Three Gorges Reservoir, respectively. Soil and water changes from the Global Land Data Assimilation System (GLDAS) were also used to identify groundwater storage in the TWS and to demonstrate a long-term increase in groundwater storage in the QB. We demonstrate that increases in groundwater, not lake water, are dominant in the QB, as observed by groundwater levels. Our study suggests that the TWS increase was likely caused by a regional increase in precipitation and a decrease in evaporation. Degradation of the permafrost increases the thickness of the active layers providing increased storage for infiltrated precipitation and snow and ice melt water, which may also contribute to the increased TWS. The huge increase of water storage in the NTP will have profound effects, not only on local ecology and environment, but also on global water storage and sea level changes. PMID:26506230

Increased Water Storage in the Qaidam Basin, the North Tibet Plateau from GRACE Gravity Data.

PubMed

Jiao, Jiu Jimmy; Zhang, Xiaotao; Liu, Yi; Kuang, Xingxing

2015-01-01

Groundwater plays a key role in maintaining the ecology and environment in the hyperarid Qaidam Basin (QB). Indirect evidence and data from sparse observation wells suggest that groundwater in the QB is increasing but there has been no regional assessment of the groundwater conditions in the entire basin because of its remoteness and the severity of the arid environment. Here we report changes in the spatial and temporal distribution of terrestrial water storage (TWS) in the northern Tibetan Plateau (NTP) using Gravity Recovery and Climate Experiment (GRACE) data. Our study confirms long-term (2003-2012) TWS increases in the NTP. Between 2003 and 2012 the TWS increased by 88.4 and 20.6 km3 in the NTP and the QB, respectively, which is 225% and 52% of the capacity of the Three Gorges Reservoir, respectively. Soil and water changes from the Global Land Data Assimilation System (GLDAS) were also used to identify groundwater storage in the TWS and to demonstrate a long-term increase in groundwater storage in the QB. We demonstrate that increases in groundwater, not lake water, are dominant in the QB, as observed by groundwater levels. Our study suggests that the TWS increase was likely caused by a regional increase in precipitation and a decrease in evaporation. Degradation of the permafrost increases the thickness of the active layers providing increased storage for infiltrated precipitation and snow and ice melt water, which may also contribute to the increased TWS. The huge increase of water storage in the NTP will have profound effects, not only on local ecology and environment, but also on global water storage and sea level changes.

Perspective-taking increases willingness to engage in intergroup contact.

PubMed

Wang, Cynthia S; Kenneth, Tai; Ku, Gillian; Galinsky, Adam D

2014-01-01

The current research explored whether perspective-taking increases willingness to engage in contact with stereotyped outgroup members. Across three studies, we find that perspective-taking increases willingness to engage in contact with negatively-stereotyped targets. In Study 1, perspective-takers sat closer to, whereas stereotype suppressors sat further from, a hooligan compared to control participants. In Study 2, individual differences in perspective-taking tendencies predicted individuals' willingness to engage in contact with a hooligan, having effects above and beyond those of empathic concern. Finally, Study 3 demonstrated that perspective-taking's effects on intergroup contact extend to the target's group (i.e., another homeless man), but not to other outgroups (i.e., a man of African descent). Consistent with other perspective-taking research, our findings show that perspective-taking facilitates the creation of social bonds by increasing contact with stereotyped outgroup members.

Demonstration of Resolving Urban Problems by Applying Smart Technology.

NASA Astrophysics Data System (ADS)

Kim, Y.

2016-12-01

Recently, movements to seek various alternatives are becoming more active around the world to resolve urban problems related to energy, water, a greenhouse gas, and disaster by utilizing smart technology system. The purpose of this study is to evaluate service verification aimed at demonstration region applied with actual smart technology in order to raise the efficiency of the service and explore solutions for urban problems. This process must be required for resolving urban problems in the future and establishing `integration platform' for sustainable development. The demonstration region selected in this study to evaluate service verification is `Busan' in Korea. Busan adopted 16 services in 4 sections last year and begun demonstration to improve quality of life and resolve urban environment problems. In addition, Busan participated officially in `Global City Teams Challenge (GCTC)' held by National Institute of Standards and Technology (NIST) in USA last year and can be regarded as representative demonstration region in Korea. The result of survey showed that there were practical difficulties as explained below in the demonstration for resolving urban problems by applying smart technology. First, the participation for demonstration was low because citizens were either not aware or did not realize the demonstration. Second, after demonstrating various services at low cost, it resulted in less effect of service demonstration. Third, as functions get fused, it was found that management department, application criteria of technology and its process were ambiguous. In order to increase the efficiency of the demonstration for the rest of period through the result of this study, it is required to draw demand that citizens requires in order to raise public participation. In addition, it needs to focus more on services which are wanted to demonstrate rather than various service demonstrations. Lastly, it is necessary to build integration platform through cooperation between departments and branches. The data collected from various source while conducting service demonstration will provide meaningful suggestion in order to explore solution for resolving urban problems by applying smart technology in the future.

Constitutive activation of CaMKKα signaling is sufficient but not necessary for mTORC1 activation and growth in mouse skeletal muscle.

PubMed

Ferey, Jeremie L A; Brault, Jeffrey J; Smith, Cheryl A S; Witczak, Carol A

2014-10-15

Skeletal muscle loading/overload stimulates the Ca²⁺-activated, serine/threonine kinase Ca²⁺/calmodulin-dependent protein kinase kinase-α (CaMKKα); yet to date, no studies have examined whether CaMKKα regulates muscle growth. The purpose of this study was to determine if constitutive activation of CaMKKα signaling could stimulate muscle growth and if so whether CaMKKα is essential for this process. CaMKKα signaling was selectively activated in mouse muscle via expression of a constitutively active form of CaMKKα using in vivo electroporation. After 2 wk, constitutively active CaMKKα expression increased muscle weight (~10%) and protein content (~10%), demonstrating that activation of CaMKKα signaling can stimulate muscle growth. To determine if active CaMKKα expression stimulated muscle growth via increased mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis, [³H]phenylalanine incorporation into proteins was assessed with or without the mTORC1 inhibitor rapamycin. Constitutively active CaMKKα increased protein synthesis ~60%, and this increase was prevented by rapamycin, demonstrating a critical role for mTORC1 in this process. To determine if CaMKKα is essential for growth, muscles from CaMKKα knockout mice were stimulated to hypertrophy via unilateral ablation of synergist muscles (overload). Surprisingly, compared with wild-type mice, muscles from CaMKKα knockout mice exhibited greater growth (~15%) and phosphorylation of the mTORC1 substrate 70-kDa ribosomal protein S6 kinase (Thr³⁸⁹; ~50%), demonstrating that CaMKKα is not essential for overload-induced mTORC1 activation or muscle growth. Collectively, these results demonstrate that activation of CaMKKα signaling is sufficient but not necessary for activation of mTORC1 signaling and growth in mouse skeletal muscle. Copyright © 2014 the American Physiological Society.

Constitutive activation of CaMKKα signaling is sufficient but not necessary for mTORC1 activation and growth in mouse skeletal muscle

PubMed Central

Ferey, Jeremie L. A.; Brault, Jeffrey J.; Smith, Cheryl A. S.

2014-01-01

Skeletal muscle loading/overload stimulates the Ca2+-activated, serine/threonine kinase Ca2+/calmodulin-dependent protein kinase kinase-α (CaMKKα); yet to date, no studies have examined whether CaMKKα regulates muscle growth. The purpose of this study was to determine if constitutive activation of CaMKKα signaling could stimulate muscle growth and if so whether CaMKKα is essential for this process. CaMKKα signaling was selectively activated in mouse muscle via expression of a constitutively active form of CaMKKα using in vivo electroporation. After 2 wk, constitutively active CaMKKα expression increased muscle weight (∼10%) and protein content (∼10%), demonstrating that activation of CaMKKα signaling can stimulate muscle growth. To determine if active CaMKKα expression stimulated muscle growth via increased mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis, [3H]phenylalanine incorporation into proteins was assessed with or without the mTORC1 inhibitor rapamycin. Constitutively active CaMKKα increased protein synthesis ∼60%, and this increase was prevented by rapamycin, demonstrating a critical role for mTORC1 in this process. To determine if CaMKKα is essential for growth, muscles from CaMKKα knockout mice were stimulated to hypertrophy via unilateral ablation of synergist muscles (overload). Surprisingly, compared with wild-type mice, muscles from CaMKKα knockout mice exhibited greater growth (∼15%) and phosphorylation of the mTORC1 substrate 70-kDa ribosomal protein S6 kinase (Thr389; ∼50%), demonstrating that CaMKKα is not essential for overload-induced mTORC1 activation or muscle growth. Collectively, these results demonstrate that activation of CaMKKα signaling is sufficient but not necessary for activation of mTORC1 signaling and growth in mouse skeletal muscle. PMID:25159322

From the Cover: Fenretinide, Troglitazone, and Elmiron Add to Weight of Evidence Support for Hemangiosarcoma Mode-of-Action From Studies in Mice.

PubMed

Cook, Jon C; Obert, Leslie A; Koza-Taylor, Petra; Coskran, Timothy M; Opsahl, Alan C; Ziemek, Daniel; Roy, Marc; Qian, Jessie; Lawton, Michael P; Criswell, Kay A

2018-01-01

Pharmaceuticals and chemicals produce hemangiosarcomas (HS) in mice, often by nongenotoxic, proliferative mechanisms. A mode-of-action (MOA) for hemangiosarcoma was proposed based on information presented at an international workshop (Cohen et al., Hemangiosarcoma in rodents: Mode-of-action evaluation and human relevance. Toxicol. Sci. 111, 4-18.). Five key elements of the MOA were articulated and included hypoxia, macrophage activation, increased angiogenic growth factors, dysregulated angiogenesis/erythropoiesis, and endothial cell proliferation. The goal of the current study was to add to the weight-of-evidence for the proposed MOA by assessing these key elements with 3 different compounds of varying potency for HS induction: fenretinide (high), troglitazone (intermediate), and elmiron (low). Multiple endpoints, including hypoxia (hyproxyprobe, transcriptomics), endothelial cell (EC) proliferation, and clinical and anatomic pathology, were assessed after 2, 4, and 13-weeks of treatment in B6C3F1 mice. All 3 compounds demonstrated strong evidence for dysregulated erythropoiesis (decrease in RBC and a failure to increase reticulocytes) and macrophage activation (4- to 11-fold increases); this pattern of hematological changes in mice might serve as an early biomarker to evaluate EC proliferation in suspected target organs for potential HS formation. Fenretinide demonstrated all 5 key elements, while troglitazone demonstrated 4 and elmiron demonstrated 3. Transcriptomics provided support for the 5 elements of the MOA, but was not any more sensitive than hypoxyprobe immunohistochemistry for detecting hypoxia. The overall transcriptional evidence for the key elements of the proposed MOA was also consistent with the potency of HS induction. These data, coupled with the previous work with 2-butoxyethanol and pregablin, increase the weight-of-evidence for the proposed MOA for HS formation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

PubMed Central

Christensen, Jeppe Romme; Börnsen, Lars; Ratzer, Rikke; Piehl, Fredrik; Khademi, Mohsen; Olsson, Tomas; Sørensen, Per Soelberg; Sellebjerg, Finn

2013-01-01

Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH) cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship with disease progression, using flow cytometry and gene expression analysis of CD4+ and CD8+T-cells, B-cells, monocytes and dendritic cells. Furthermore, gene expression of cerebrospinal fluid cells was studied. Flow cytometry studies revealed increased frequencies of ICOS+TFH-cells in peripheral blood from relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients. All MS subtypes had decreased frequencies of Th1 TFH-cells, while primary progressive (PPMS) MS patients had increased frequency of Th17 TFH-cells. The Th17-subset, interleukin-23-receptor+CD4+T-cells, was significantly increased in PPMS and SPMS. In the analysis of B-cells, we found a significant increase of plasmablasts and DC-SIGN+ and CD83+B-cells in SPMS. ICOS+TFH-cells and DC-SIGN+B-cells correlated with disease progression in SPMS patients. Gene expression analysis of peripheral blood cell subsets substantiated the flow cytometry findings by demonstrating increased expression of IL21, IL21R and ICOS in CD4+T-cells in progressive MS. Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and PPMS patients) had increased expression of TFH-cell and plasmablast markers. In conclusion, this study is the first to demonstrate the potential involvement of activated TFH-cells in MS. The increased frequencies of Th17-cells, activated TFH- and B-cells parallel findings from pathology studies which, along with the correlation between activated TFH- and B-cells and disease progression, suggest a pathogenic role of systemic inflammation in progressive MS. These observations may have implications for the treatment of progressive MS. PMID:23469245

Impaired gut contractility following hemorrhagic shock is accompaied by IL-6 and G-CSF production and neutrophil infiltration.

PubMed

Hierholzer, C; Kalff, J C; Chakraborty, A; Watkins, S C; Billiar, T R; Bauer, A J; Tweardy, D J

2001-02-01

Recovery from hemorrhagic shock (HS) is frequently accompanied by bowel stasis. The aim of this study was to examine whether or not HS initiates an inflammatory response that includes production of cytokines, specifically G-CSF and interleukin-6 (IL-6), and recruitment of leukocytes within the intestinal muscularis which contribute to impaired muscle contractility. Sprague-Dawley rats were subjected to HS (MAP 40 mm Hg for 156 min) followed by resuscitation, and then they were killed at 4 hr. Shock animals demonstrated accumulation of PMNs in the jejunal muscularis and decreased spontaneous and bethanechol-stimulated muscle contractility. Semiquantitative RT-PCR demonstrated elevated levels of IL-6 and G-CSF mRNA in shock animals in full-thickness jejunum and in mucosa and muscularis layers compared to sham controls. Immunostaining demonstrated increased IL-6 protein production within the muscularis externa and submucosa. In situ hybridization studies localized G-CSF mRNA production to the submucosa. Gel shift assays revealed increased NF-kappaB and Stat3 activity in full-thickness jejunum and jejunal layers of shock animals. Activation of Stat3 also was demonstrated in normal muscularis tissue exposed to IL-6 and G-CSF in vitro. IL-6 and G-CSF are produced in the muscularis and mucosa layers of the gut in HS where they may contribute to PMN recruitment and smooth muscle dysfunction.

Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

PubMed

He, Zhi; Hu, Min; Zha, Yun-hong; Li, Zi-cheng; Zhao, Bo; Yu, Ling-ling; Yu, Min; Qian, Ying

2014-05-01

Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.

Exercise attenuates neuropathology and has greater benefit on cognitive than motor deficits in the R6/1 Huntington's disease mouse model.

PubMed

Harrison, David J; Busse, Monica; Openshaw, Rebecca; Rosser, Anne E; Dunnett, Stephen B; Brooks, Simon P

2013-10-01

Huntington's disease (HD) is a neurodegenerative disease caused by a mutation within the huntingtin gene that induces degeneration within the striatal nuclei, progressing to widespread brain atrophy and death. The neurodegeneration produces symptoms that reflect a corticostriatal disconnection syndrome involving motor, cognitive and psychiatric disturbance. Environmental enrichment has been demonstrated to be beneficial to patients with neurological disorders, with exercise being central to this effect. Rodent studies have confirmed exercise-induced neurogenesis and increased growth factor levels in the brain and improved behavioural function. The present study sought to determine whether an extended regime of exercise could retard disease progression in the R6/1 mouse model of HD. The study was designed specifically with a translational focus, selecting behavioural assessments with high clinical predictive validity. We found that exercise improved gait function in both control and HD mice and selectively improved performance in the R6/1 mice on a motor coordination aspect of the balance beam task. Exercise also retarded the progression of cognitive dysfunction on water T-maze procedural and reversal learning probes presented serially to probe cognitive flexibility. In addition, exercise reduced striatal neuron loss in the R6/1 mice but increased striatal neuronal intra-nuclear inclusion size and number relative to non-exercised R6/1 mice which demonstrated increased numbers of extra-neuronal inclusions, suggesting that the functional effects were striatally mediated. These results confirm and extend those from previous studies that demonstrate that HD may be amenable to exercise-mediated therapeutics, but suggest that the impact of such interventions may be primarily cognitive. © 2013.

The impact of detergents on the tissue decellularization process: A ToF-SIMS study.

PubMed

White, Lisa J; Taylor, Adam J; Faulk, Denver M; Keane, Timothy J; Saldin, Lindsey T; Reing, Janet E; Swinehart, Ilea T; Turner, Neill J; Ratner, Buddy D; Badylak, Stephen F

2017-03-01

Biologic scaffolds are derived from mammalian tissues, which must be decellularized to remove cellular antigens that would otherwise incite an adverse immune response. Although widely used clinically, the optimum balance between cell removal and the disruption of matrix architecture and surface ligand landscape remains a considerable challenge. Here we describe the use of time of flight secondary ion mass spectroscopy (ToF-SIMS) to provide sensitive, molecular specific, localized analysis of detergent decellularized biologic scaffolds. We detected residual detergent fragments, specifically from Triton X-100, sodium deoxycholate and sodium dodecyl sulphate (SDS) in decellularized scaffolds; increased SDS concentrations from 0.1% to 1.0% increased both the intensity of SDS fragments and adverse cell outcomes. We also identified cellular remnants, by detecting phosphate and phosphocholine ions in PAA and CHAPS decellularized scaffolds. The present study demonstrates ToF-SIMS is not only a powerful tool for characterization of biologic scaffold surface molecular functionality, but also enables sensitive assessment of decellularization efficacy. We report here on the use of a highly sensitive analytical technique, time of flight secondary ion mass spectroscopy (ToF-SIMS) to characterize detergent decellularized scaffolds. ToF-SIMS detected cellular remnants and residual detergent fragments; increased intensity of the detergent fragments correlated with adverse cell matrix interactions. This study demonstrates the importance of maintaining a balance between cell removal and detergent disruption of matrix architecture and matrix surface ligand landscape. This study also demonstrates the power of ToF-SIMS for the characterization of decellularized scaffolds and capability for assessment of decellularization efficacy. Future use of biologic scaffolds in clinical tissue reconstruction will benefit from the fundamental results described in this work. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Designing Intervention Studies: Selected Populations, Range Restrictions, and Statistical Power

PubMed Central

Miciak, Jeremy; Taylor, W. Pat; Stuebing, Karla K.; Fletcher, Jack M.; Vaughn, Sharon

2016-01-01

An appropriate estimate of statistical power is critical for the design of intervention studies. Although the inclusion of a pretest covariate in the test of the primary outcome can increase statistical power, samples selected on the basis of pretest performance may demonstrate range restriction on the selection measure and other correlated measures. This can result in attenuated pretest-posttest correlations, reducing the variance explained by the pretest covariate. We investigated the implications of two potential range restriction scenarios: direct truncation on a selection measure and indirect range restriction on correlated measures. Empirical and simulated data indicated direct range restriction on the pretest covariate greatly reduced statistical power and necessitated sample size increases of 82%–155% (dependent on selection criteria) to achieve equivalent statistical power to parameters with unrestricted samples. However, measures demonstrating indirect range restriction required much smaller sample size increases (32%–71%) under equivalent scenarios. Additional analyses manipulated the correlations between measures and pretest-posttest correlations to guide planning experiments. Results highlight the need to differentiate between selection measures and potential covariates and to investigate range restriction as a factor impacting statistical power. PMID:28479943

Designing Intervention Studies: Selected Populations, Range Restrictions, and Statistical Power.

PubMed

Miciak, Jeremy; Taylor, W Pat; Stuebing, Karla K; Fletcher, Jack M; Vaughn, Sharon

2016-01-01

An appropriate estimate of statistical power is critical for the design of intervention studies. Although the inclusion of a pretest covariate in the test of the primary outcome can increase statistical power, samples selected on the basis of pretest performance may demonstrate range restriction on the selection measure and other correlated measures. This can result in attenuated pretest-posttest correlations, reducing the variance explained by the pretest covariate. We investigated the implications of two potential range restriction scenarios: direct truncation on a selection measure and indirect range restriction on correlated measures. Empirical and simulated data indicated direct range restriction on the pretest covariate greatly reduced statistical power and necessitated sample size increases of 82%-155% (dependent on selection criteria) to achieve equivalent statistical power to parameters with unrestricted samples. However, measures demonstrating indirect range restriction required much smaller sample size increases (32%-71%) under equivalent scenarios. Additional analyses manipulated the correlations between measures and pretest-posttest correlations to guide planning experiments. Results highlight the need to differentiate between selection measures and potential covariates and to investigate range restriction as a factor impacting statistical power.

Effect of light on the production of bioelectricity and added-value microalgae biomass in a Photosynthetic Alga Microbial Fuel Cell.

PubMed

Gouveia, Luísa; Neves, Carole; Sebastião, Diogo; Nobre, Beatriz P; Matos, Cristina T

2014-02-01

This study demonstrates the simultaneous production of bioelectricity and added-value pigments in a Photosynthetic Alga Microbial Fuel Cell (PAMFC). A PAMFC was operated using Chlorella vulgaris in the cathode compartment and a bacterial consortium in the anode. The system was studied at two different light intensities and the maximum power produced was 62.7 mW/m(2) with a light intensity of 96 μE/(m(2)s). The results showed that increasing light intensity from 26 to 96 μE/(m(2)s) leads to an increase of about 6-folds in the power produced. Additionally, the pigments produced by the microalga were analysed and the results showed that the light intensity and PAMFC operation potentiated the carotenogenesis in the cathode compartment. The demonstrated possibility of producing added-value microalgae biomass in microbial fuel cell cathodes will increase the economic feasibility of these bioelectrochemical systems, allowing the development of energy efficient systems for wastewater treatment and carbon fixation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

PubMed Central

Moszczynska, Anna; Flack, Amanda; Qiu, Ping; Muotri, Alysson R.; Killinger, Bryan A.

2015-01-01

Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum. PMID:26463126

Melioidosis in Mexico, Central America, and the Caribbean

PubMed Central

Sanchez-Villamil, Javier I.; Torres, Alfredo G.

2018-01-01

Burkholderia pseudomallei is the causative agent of melioidosis, an endemic disease in tropical areas around the world. Cumulative human cases have demonstrated that melioidosis is prevalent and increasingly recognized in the American continent. Even though the first reports of melioidosis in Mexico, Central America, and the Caribbean Islands date back to the late 1940s, the potential of the disease as a public health concern in the region has not been fully appreciated. Unfortunately, recent studies predicting the global distribution of the disease and the demonstration of melioidosis endemicity in Puerto Rico have not increased recognition of the disease by health professionals in this region. Furthermore, a lack of both diagnostic capacity and awareness of the disease has resulted in a limited number of studies that have attempted to accurately determine its prevalence and geographical distribution. In this review, a summary of reported cases in the countries of this region are presented, as well as recommendations to increase the diagnosis and awareness of the disease as an important public health problem in Mexico, Central America, and the Caribbean islands. PMID:29780897

Summary of studies on the blue-green autofluorescence and light transmission of the ocular lens

NASA Astrophysics Data System (ADS)

Van Best, Jaap A.; Kuppens, Esmeralda V.

1996-07-01

This paper reviews previous work done to demonstrate the clinical relevance of the measurement of blue-green autofluorescence and light transmission of the ocular lens. These can be determined quantitatively with fluorophotometry in a few seconds. Autofluorescence and transmission values are determined in healthy volunteers, in patients with insulin-dependent diabetes mellitus, and in patients with untreated glaucoma or untreated ocular hypertension. The lens autofluorescence of healthy volunteers increased linearly and transmission decreased exponentially with age. Each year of diabetes induced an increase of autofluorescence equal to one extra year of age. Untreated glaucoma or ocular hypertension had no significant effect on lens autofluorescence and transmission. Increased autofluorescence and decreased transmission values in comparison with values of a healthy population are proved to be indicative for an increased risk of developing cataract and the clinical usefulness of these measures is demonstrated. Diabetes is a risk factor for developing cataracts while untreated glaucoma or ocular hypertension is not.

Higher social class predicts increased unethical behavior.

PubMed

Piff, Paul K; Stancato, Daniel M; Côté, Stéphane; Mendoza-Denton, Rodolfo; Keltner, Dacher

2012-03-13

Seven studies using experimental and naturalistic methods reveal that upper-class individuals behave more unethically than lower-class individuals. In studies 1 and 2, upper-class individuals were more likely to break the law while driving, relative to lower-class individuals. In follow-up laboratory studies, upper-class individuals were more likely to exhibit unethical decision-making tendencies (study 3), take valued goods from others (study 4), lie in a negotiation (study 5), cheat to increase their chances of winning a prize (study 6), and endorse unethical behavior at work (study 7) than were lower-class individuals. Mediator and moderator data demonstrated that upper-class individuals' unethical tendencies are accounted for, in part, by their more favorable attitudes toward greed.

Technetium-99m galactosyl-neoglycoalbumin (Tc-NGA) liver imaging: Application in liver transplantation

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

Woodle, E.S.; Ward, R.E.; Vera, D.R.

1985-05-01

Tc-NGA is a new liver imaging agent which binds to hepatic binding protein (HBP), a hepatocyte-specific membrane receptor. The purpose of the present study was to evaluate the potential role of Tc-NGA imaging in liver transplantation. The molar Tc-NGA dose was standardized according to patient weight (0.7 nmole/kg). After a 30 minute dynamic imaging study (5 mCi, IV), kinetic analysis of time activity data (heart, liver), provided values for receptor concentration, (HBP), and hepatic blood flow, Q. Eleven Tc-NGA imaging studies were performed in transplant candidates and 22 studies were performed in seven transplant recipients. Preservation damage was manifested bymore » diffuse patchiness in tracer distribution which resolved during the following two weeks. Histologically proven, localized hepatic infarcts were demonstrated in three recipients. Lobar infarction was demonstrated in one recipient. Hepatic regeneration was later demonstrated in this patient after hepatic lobectomy. Hepatic blood flow was markedly decreased in the early postoperative period, but improved with time. Increased (HBP) was demonstrated with regeneration. Markedly decreased (HBP) and Q were obtained in several candidates who died awaiting transplantation. These studies indicate that TC-NGA liver imaging provides a valuable new means for: (1) evaluation of preservation damage, (2) early demonstration of hepatic infarction, (3) evaluation of hepatic rejection, and (4) selection of patients for hepatic transplantation.« less

Interrelationship of salinity shift with oxidative stress and lipid metabolism in the monogonont rotifer Brachionus koreanus.

PubMed

Lee, Min-Chul; Park, Jun Chul; Kim, Duck-Hyun; Kang, Sujin; Shin, Kyung-Hoon; Park, Heum Gi; Han, Jeonghoon; Lee, Jae-Seong

2017-12-01

Salinity is a critical key abiotic factor affecting biological processes such as lipid metabolism, yet the relationship between salinity and lipid metabolism has not been studied in the rotifer. To understand the effects of salinity on the monogonont rotifer B. koreanus, we examined high saline (25 and 35psu) conditions compared to the control (15psu). In vivo life cycle parameters (e.g. cumulative offspring and life span) were observed in response to 25 and 35psu compared to 15psu. In addition, to investigate whether high salinity induces oxidative stress, the level of reactive oxygen species (ROS) and glutathione S-transferase activity (GST) were measured in a salinity- (15, 25, and 35psu; 24h) and time-dependent manner (3, 6, 12, 24h; 35psu). Furthermore composition of fatty acid (FA) and lipid metabolism-related genes (e.g. elongases and desaturases) were examined in response to different salinity conditions. As a result, retardation in cumulative offspring and significant increase in life span were demonstrated in the 35psu treatment group compared to the control (15psu). Furthermore, ROS level and GST activity have both demonstrated a significant increase (P<0.05) in the 35psu treatment. In general, the quantity of FA and mRNA expression of the lipid metabolism-related genes was significantly decreased (P<0.05) in response to high saline condition with exceptions for both GST-S4 and S5 demonstrated a significant increase in their mRNA expression. This study demonstrates that high salinity induces oxidative stress, leading to a negative impact on lipid metabolism in the monogonont rotifer, B. koreanus. Copyright © 2017 Elsevier Inc. All rights reserved.

A numerical study of fundamental shock noise mechanisms. Ph.D. Thesis - Cornell Univ.

NASA Technical Reports Server (NTRS)

Meadows, Kristine R.

1995-01-01

The results of this thesis demonstrate that direct numerical simulation can predict sound generation in unsteady aerodynamic flows containing shock waves. Shock waves can be significant sources of sound in high speed jet flows, on helicopter blades, and in supersonic combustion inlets. Direct computation of sound permits the prediction of noise levels in the preliminary design stage and can be used as a tool to focus experimental studies, thereby reducing cost and increasing the probability of a successfully quiet product in less time. This thesis reveals and investigates two mechanisms fundamental to sound generation by shocked flows: shock motion and shock deformation. Shock motion is modeled by the interaction of a sound wave with a shock. During the interaction, the shock wave begins to move and the sound pressure is amplified as the wave passes through the shock. The numerical approach presented in this thesis is validated by the comparison of results obtained in a quasi-one dimensional simulation with linear theory. Analysis of the perturbation energy demonstrated for the first time that acoustic energy is generated by the interaction. Shock deformation is investigated by the numerical simulation of a ring vortex interacting with a shock. This interaction models the passage of turbulent structures through the shock wave. The simulation demonstrates that both acoustic waves and contact surfaces are generated downstream during the interaction. Analysis demonstrates that the acoustic wave spreads cylindrically, that the sound intensity is highly directional, and that the sound pressure level increases significantly with increasing shock strength. The effect of shock strength on sound pressure level is consistent with experimental observations of shock noise, indicating that the interaction of a ring vortex with a shock wave correctly models a dominant mechanism of shock noise generation.

Schistosomal-derived lysophosphatidylcholine triggers M2 polarization of macrophages through PPARγ dependent mechanisms.

PubMed

Assunção, Leonardo Santos; Magalhães, Kelly G; Carneiro, Alan Brito; Molinaro, Raphael; Almeida, Patrícia E; Atella, Georgia C; Castro-Faria-Neto, Hugo C; Bozza, Patrícia T

2017-02-01

Mansonic schistosomiasis is a disease caused by the trematode Schistosoma mansoni, endemic to tropical countries. S. mansoni infection induces the formation of granulomas and potent polarization of Th2-type immune response. There is great interest in understanding the mechanisms used by this parasite that causes a modulation of the immune system. Recent studies from our group demonstrated that lipids of S. mansoni, including lysophosphatidylcholine (LPC) have immunomodulatory activity. In the present study, our aim was to investigate the role of lipids derived from S. mansoni in the activation and polarization of macrophages and to characterize the mechanisms involved in this process. Peritoneal macrophages obtained from wild type C57BL/6mice or bone marrow derived macrophages were stimulated in vitro with lipids extracted from adult worms of S. mansoni. We demonstrated that total schistosomal-derived lipids as well as purified LPC induced alternatively activated macrophages/M2 profile observed by increased expression of arginase-1, mannose receptor, Chi3l3, TGFβ and production of IL-10 and PGE 2 24h after stimulation. The involvement of the nuclear receptor PPARγ in macrophage response against LPC was investigated. Through Western blot and immunofluorescence confocal microscopy we demonstrated that schistosomal-derived LPC induces increased expression of PPARγ in macrophages. The LPC-induced increased expression of arginase-1 were significantly inhibited by the PPAR-γ antagonist GW9662. Together, these results demonstrate an immunomodulatory role of schistosomal-derived LPC in activating macrophages to a profile of the type M2 through PPARγ-dependent mechanisms, indicating a novel pathway for macrophage polarization triggered by parasite-derived LPC with potential implications to disease pathogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Potassium Inhibits Dietary Salt-Induced Transforming Growth Factor-β Production

PubMed Central

Ying, Wei-Zhong; Aaron, Kristal; Wang, Pei-Xuan; Sanders, Paul W.

2009-01-01

Human and animal studies demonstrate an untoward effect of excess dietary NaCl (salt) intake on cardiovascular function and life span. The endothelium in particular augments the production of transforming growth factor (TGF)-β, a fibrogenic growth factor, in response to excess dietary salt intake. This study explored the initiating mechanism that regulates salt-induced endothelial cell production of TGF-β. Male Sprague-Dawley rats were given diets containing different amounts of NaCl and potassium for 4 days. A bioassay for TGF-β demonstrated increased (35.2%) amounts of active TGF-β in the medium of aortic ring segments from rats on the high-salt diet compared with rats maintained on a 0.3% NaCl diet. Inhibition of the large-conductance, calcium-activated potassium channel inhibited dietary salt-induced vascular production of TGF-β but did not affect production of TGF-β by ring segments from rats on the low-salt diet. Immunohistochemical and Western analyses demonstrated the α subunit of the calcium-activated potassium channel in endothelial cells. Increasing medium [K+] inhibited production of dietary salt-induced vascular production levels of total and active TGF-β but did not alter TGF-β production by aortic rings from rats on the 0.3% NaCl diet. Increasing dietary potassium content decreased urinary active TGF-β in animals receiving the high-salt diet but did not change urinary active TGF-β in animals receiving the low-salt diet. The findings demonstrated an interesting interaction between the dietary intake of potassium and excess NaCl and further showed the fundamental role of the endothelial calcium-activated potassium channel in the vascular response to excess salt intake. PMID:19738156

Increased Small-World Network Topology Following Deployment-Acquired Traumatic Brain Injury Associated with the Development of Post-Traumatic Stress Disorder.

PubMed

Rowland, Jared A; Stapleton-Kotloski, Jennifer R; Dobbins, Dorothy L; Rogers, Emily; Godwin, Dwayne W; Taber, Katherine H

2018-05-01

Cross-sectional and longitudinal studies in active duty and veteran cohorts have both demonstrated that deployment-acquired traumatic brain injury (TBI) is an independent risk factor for developing post-traumatic stress disorder (PTSD), beyond confounds such as combat exposure, physical injury, predeployment TBI, and pre-deployment psychiatric symptoms. This study investigated how resting-state brain networks differ between individuals who developed PTSD and those who did not following deployment-acquired TBI. Participants included postdeployment veterans with deployment-acquired TBI history both with and without current PTSD diagnosis. Graph metrics, including small-worldness, clustering coefficient, and modularity, were calculated from individually constructed whole-brain networks based on 5-min eyes-open resting-state magnetoencephalography (MEG) recordings. Analyses were adjusted for age and premorbid IQ. Results demonstrated that participants with current PTSD displayed higher levels of small-worldness, F(1,12) = 5.364, p < 0.039, partial eta squared = 0.309, and Cohen's d = 0.972, and clustering coefficient, F(1, 12) = 12.204, p < 0.004, partial eta squared = 0.504, and Cohen's d = 0.905, than participants without current PTSD. There were no between-group differences in modularity or the number of modules present. These findings are consistent with a hyperconnectivity hypothesis of the effect of TBI history on functional networks rather than a disconnection hypothesis, demonstrating increased levels of clustering coefficient rather than a decrease as might be expected; however, these results do not account for potential changes in brain structure. These results demonstrate the potential pathological sequelae of changes in functional brain networks following deployment-acquired TBI and represent potential neurobiological changes associated with deployment-acquired TBI that may increase the risk of subsequently developing PTSD.

Chronic administration of branched-chain amino acids impairs spatial memory and increases brain-derived neurotrophic factor in a rat model.

PubMed

Scaini, Giselli; Comim, Clarissa M; Oliveira, Giovanna M T; Pasquali, Matheus A B; Quevedo, João; Gelain, Daniel P; Moreira, José Cláudio F; Schuck, Patrícia F; Ferreira, Gustavo C; Bogo, Maurício R; Streck, Emilio L

2013-09-01

Maple syrup urine disease (MSUD) is a neurometabolic disorder that leads to the accumulation of branched-chain amino acids (BCAAs) and their α-keto branched-chain by-products. Because the neurotoxic mechanisms of MSUD are poorly understood, this study aimed to evaluate the effects of chronic administration of a BCAA pool (leucine, isoleucine and valine). This study examined the effects of BCAA administration on spatial memory and the levels of brain-derived neurotrophic factor (BNDF). We examined both pro-BDNF and bdnf mRNA expression levels after administration of BCAAs. Furthermore, this study examined whether antioxidant treatment prevented the alterations induced by BCAA administration. Our results demonstrated an increase in BDNF in the hippocampus and cerebral cortex, accompanied by memory impairment in spatial memory tasks. Additionally, chronic administration of BCAAs did not induce a detectable change in pro-BDNF levels. Treatment with N-acetylcysteine and deferoxamine prevented both the memory deficit and the increase in the BDNF levels induced by BCAA administration. In conclusion, these results suggest that when the brain is chronically exposed to high concentrations of BCAA (at millimolar concentrations) an increase in BDNF levels occurs. This increase in BDNF may be related to the impairment of spatial memory. In addition, we demonstrated that antioxidant treatment prevented the negative consequences related to BCAA administration, suggesting that oxidative stress might be involved in the pathophysiological mechanism(s) underlying the brain damage observed in MSUD.

Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

PubMed Central

Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

2013-01-01

Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

Suprathreshold contrast summation over area using drifting gratings.

PubMed

McDougall, Thomas J; Dickinson, J Edwin; Badcock, David R

2018-04-01

This study investigated contrast summation over area for moving targets applied to a fixed-size contrast pedestal-a technique originally developed by Meese and Summers (2007) to demonstrate strong spatial summation of contrast for static patterns at suprathreshold contrast levels. Target contrast increments (drifting gratings) were applied to either the entire 20% contrast pedestal (a full fixed-size drifting grating), or in the configuration of a checkerboard pattern in which the target increment was applied to every alternate check region. These checked stimuli are known as "Battenberg patterns" and the sizes of the checks were varied (within a fixed overall area), across conditions, to measure summation behavior. Results showed that sensitivity to an increment covering the full pedestal was significantly higher than that for the Battenberg patterns (areal summation). Two observers showed strong summation across all check sizes (0.71°-3.33°), and for two other observers the summation ratio dropped to levels consistent with probability summation once check size reached 2.00°. Therefore, areal summation with moving targets does operate at high contrast, and is subserved by relatively large receptive fields covering a square area extending up to at least 3.33° × 3.33° for some observers. Previous studies in which the spatial structure of the pedestal and target covaried were unable to demonstrate spatial summation, potentially due to increasing amounts of suppression from gain-control mechanisms which increases as pedestal size increases. This study shows that when this is controlled, by keeping the pedestal the same across all conditions, extensive summation can be demonstrated.

Hepatic drug clearance following traumatic injury.

PubMed

Slaughter, R L; Hassett, J M

1985-11-01

Trauma is a complex disease state associated with physiologic changes that have the potential to alter hepatic drug clearance mechanisms. These responses include alterations in hepatic blood flow, reduction in hepatic microsomal activity, reduction in hepatic excretion processes, and changes in protein binding. Hepatic blood flow is influenced by sympathomimetic activity. Both animal and human studies demonstrate an initial reduction and subsequent increase in hepatic blood flow, which coincides with an observed increase and subsequent return to normal in serum catecholamine concentrations. Unfortunately, there are no human studies that address the importance these findings may have to the clearance processes of high intrinsic clearance compounds. Animal studies of trauma indicate that hepatic microsomal activity is depressed during the post-traumatic period. Reduction in the hepatic clearance of antipyrine, a model low intrinsic compound, has also been demonstrated in animal models of trauma. In addition to these effects, hepatic excretion of substances such as indocyanine green and bilirubin have been demonstrated to be impaired in both traumatized animals and humans. Finally, substantial increases in the serum concentration of the binding protein alpha 1-acid glycoprotein occur in trauma patients. This has been reported to be associated with subsequent decreases in the free fraction of lidocaine and quinidine. In addition to changing serum drug concentration/response relationships, the pharmacokinetic behavior of drugs bound to alpha 1-acid glycoprotein should also change. Preliminary observations in our laboratory in a dog model of surgically-induced trauma have shown a reduction in the total clearance of lidocaine and reduction in free lidocaine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone marrow lesions in hip osteoarthritis are characterized by increased bone turnover and enhanced angiogenesis.

PubMed

Shabestari, M; Vik, J; Reseland, J E; Eriksen, E F

2016-10-01

Bone marrow lesions (BML), previously denoted bone marrow edema, are detected as water signals by magnetic resonance imaging (MRI). Previous histologic studies were unable to demonstrate any edematous changes at the tissue level. Therefore, our aim was to investigate the underlying biological mechanisms of the water signal in MRI scans of bone affected by BML. Tetracycline labeling in addition to water sensitive MRI scans of 30 patients planned for total hip replacement surgery was undertaken. Twenty-one femoral heads revealed BML on MRI, while nine were negative and used as controls (CON). Guided by the MRI images cylindrical biopsies were extracted from areas with BML in the femoral heads. Tissue sections from the biopsies were subjected to histomorphometric image analyses of the cancellous bone envelope. Patients with BML exhibited an average 40- and 18-fold increase of bone formation rate and mineralizing surface, respectively. Additionally, samples with BML demonstrated 2-fold reduction of marrow fat and 28-fold increase of woven bone. Immunohistochemical analysis showed a 4-fold increase of angiogenesis markers CD31 and von Willebrand Factor (vWF) in the BML-group compared to CON. This study indicates that BML are characterized by increased bone turnover, vascularity and angiogenesis in keeping with it being a reparatory process. Thus, the water signal, which is the hallmark of BML on MRI, is most probably reflecting increased tissue vascularity accompanying increased remodeling activity. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Are the frail destined to fail? Frailty index as predictor of surgical morbidity and mortality in the elderly.

PubMed

Farhat, Joseph S; Velanovich, Vic; Falvo, Anthony J; Horst, H Mathilda; Swartz, Andrew; Patton, Joe H; Rubinfeld, Ilan S

2012-06-01

America's aging population has led to an increase in the number of elderly patients necessitating emergency general surgery. Previous studies have demonstrated that increased frailty is a predictor of outcomes in medicine and surgical patients. We hypothesized that use of a modification of the Canadian Study of Health and Aging Frailty Index would be a predictor of morbidity and mortality in patients older than 60 years undergoing emergency general surgery. Data were obtained from the National Surgical Quality Improvement Program Participant Use Files database in compliance with the National Surgical Quality Improvement Program Data Use Agreement. We selected all emergency cases in patients older than 60 years performed by general surgeons from 2005 to 2009. The effect of increasing frailty on multiple outcomes including wound infection, wound occurrence, any infection, any occurrence, and mortality was then evaluated. Total sample size was 35,334 patients. As the modified frailty index increased, associated increases occurred in wound infection, wound occurrence, any infection, any occurrence, and mortality. Logistic regression of multiple variables demonstrated that the frailty index was associated with increased mortality with an odds ratio of 11.70 (p < 0.001). Frailty index is an important predictive variable in emergency general surgery patients older than 60 years. The modified frailty index can be used to evaluate risk of both morbidity and mortality in these patients. Frailty index will be a valuable preoperative risk assessment tool for the acute care surgeon. Prognostic study, level II. Copyright © 2012 by Lippincott Williams & Wilkins

Yohimbine Increases Opioid-Seeking Behavior in Heroin-Dependent, Buprenorphine-Maintained Individuals

PubMed Central

Greenwald, Mark K.; Lundahl, Leslie H.; Steinmiller, Caren L.

2012-01-01

Rationale In laboratory animals, the biological stressor yohimbine (α2-noradrenergic autoreceptor antagonist) promotes drug seeking. Human laboratory studies have demonstrated that psychological stressors can increase drug craving but not that stressors alter drug seeking. Objectives This clinical study tested whether yohimbine increases opioid seeking behavior. Methods Ten heroin-dependent, buprenorphine (8-mg/day) stabilized volunteers, sampled two doses of hydromorphone (12 and 24 mg IM in counterbalanced order, labeled Drug A [session 1] and Drug B [session 2]). During each of six later sessions (within-subject, double blind, randomized crossover design), volunteers could respond on a 12-trial choice progressive ratio task to earn units (1 or 2 mg) of the sampled hydromorphone dose (Drug A or B) vs. money ($2) following different oral yohimbine pretreatment doses (0, 16.2 and 32.4 mg). Results Behavioral economic demand intensity and peak responding (Omax) were significantly higher for hydromorphone 2-mg than 1-mg. Relative to placebo, yohimbine significantly increased hydromorphone demand inelasticity, more so for hydromorphone 1-mg units (Pmax = 909, 3647 and 3225 for placebo, 16.2 and 32.4 mg yohimbine doses, respectively) than hydromorphone 2-mg units (Pmax = 2656, 3193 and 3615, respectively). Yohimbine produced significant but clinically modest dose-dependent increases in blood pressure (systolic ≈15 and diastolic ≈10 mmHg) and opioid withdrawal symptoms, and decreased opioid agonist symptoms and elated mood. Conclusions These findings concur with preclinical data by demonstrating that yohimbine increases drug seeking; in this study, these effects occurred without clinically significant subjective distress or elevated craving, and partly depended on opioid unit dose. PMID:23161001

Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage.

PubMed

Barker, Catherine R; McNamara, Anne V; Rackstraw, Stephen A; Nelson, David E; White, Mike R; Watson, Alastair J M; Jenkins, John R

2006-01-01

Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the increase in topoisomerase II mediated DNA damage. Importantly we demonstrate that Hsp90 inhibition results in an increased topoiosmerase II activity but not degradation of topoisomerase II and it is this, in the presence of a topoisomerase II poison that causes the increase in cell death. Our results suggest a novel mechanism of action where the inhibition of Hsp90 disrupts the Hsp90-topoisomerase II interaction leading to an increase in and activation of unbound topoisomerase II, which, in the presence of a topoisomerase II poison leads to the formation of an increased number of cleavable complexes ultimately resulting in rise in DNA damage and a subsequent increase cell death.

Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage

PubMed Central

Barker, Catherine R.; McNamara, Anne V.; Rackstraw, Stephen A.; Nelson, David E.; White, Mike R.; Watson, Alastair J. M.; Jenkins, John R.

2006-01-01

Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the increase in topoisomerase II mediated DNA damage. Importantly we demonstrate that Hsp90 inhibition results in an increased topoiosmerase II activity but not degradation of topoisomerase II and it is this, in the presence of a topoisomerase II poison that causes the increase in cell death. Our results suggest a novel mechanism of action where the inhibition of Hsp90 disrupts the Hsp90–topoisomerase II interaction leading to an increase in and activation of unbound topoisomerase II, which, in the presence of a topoisomerase II poison leads to the formation of an increased number of cleavable complexes ultimately resulting in rise in DNA damage and a subsequent increase cell death. PMID:16504968

Characterization of LDPC-coded orbital angular momentum modes transmission and multiplexing over a 50-km fiber.

PubMed

Wang, Andong; Zhu, Long; Chen, Shi; Du, Cheng; Mo, Qi; Wang, Jian

2016-05-30

Mode-division multiplexing over fibers has attracted increasing attention over the last few years as a potential solution to further increase fiber transmission capacity. In this paper, we demonstrate the viability of orbital angular momentum (OAM) modes transmission over a 50-km few-mode fiber (FMF). By analyzing mode properties of eigen modes in an FMF, we study the inner mode group differential modal delay (DMD) in FMF, which may influence the transmission capacity in long-distance OAM modes transmission and multiplexing. To mitigate the impact of large inner mode group DMD in long-distance fiber-based OAM modes transmission, we use low-density parity-check (LDPC) codes to increase the system reliability. By evaluating the performance of LDPC-coded single OAM mode transmission over 50-km fiber, significant coding gains of >4 dB, 8 dB and 14 dB are demonstrated for 1-Gbaud, 2-Gbaud and 5-Gbaud quadrature phase-shift keying (QPSK) signals, respectively. Furthermore, in order to verify and compare the influence of DMD in long-distance fiber transmission, single OAM mode transmission over 10-km FMF is also demonstrated in the experiment. Finally, we experimentally demonstrate OAM multiplexing and transmission over a 50-km FMF using LDPC-coded 1-Gbaud QPSK signals to compensate the influence of mode crosstalk and DMD in the 50 km FMF.

The Social Modulation of Imitation Fidelity in School-Age Children

PubMed Central

Marsh, Lauren E.; Ropar, Danielle; Hamilton, Antonia F. de C.

2014-01-01

Children copy the actions of others with high fidelity, even when they are not causally relevant. This copying of visibly unnecessary actions is termed overimitation. Many competing theories propose mechanisms for overimitation behaviour. The present study examines these theories by studying the social factors that lead children to overimitate actions. Ninety-four children aged 5- to 8-years each completed five trials of an overimitation task. Each trial provided the opportunity to overimitate an action on familiar objects with minimal causal reasoning demands. Social cues (live or video demonstration) and eye contact from the demonstrator were manipulated. After the imitation, children's ratings of action rationality were collected. Substantial overimitation was seen which increased with age. In older children, overimitation was higher when watching a live demonstrator and when eye contact was absent. Actions rated as irrational were more likely to be imitated than those rated as rational. Children overimitated actions on familiar objects even when they rated those actions as irrational, suggesting that failure of causal reasoning cannot be driving overimitation. Our data support social explanations of overimitation and show that the influence of social factors increases with age over the 5- to 8-year-old age range. PMID:24465913

TMPRSS4 induces cancer cell invasion through pro-uPA processing.

PubMed

Min, Hye-Jin; Lee, Myung Kyu; Lee, Jung Weon; Kim, Semi

2014-03-28

TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed on the cell surface in pancreatic, thyroid, colon, and other cancer tissues. Previously, we demonstrated that TMPRSS4 mediates cancer cell invasion, epithelial-mesenchymal transition, and metastasis and that increased TMPRSS4 expression correlates with colorectal cancer progression. We also demonstrated that TMPRSS4 upregulates urokinase-type plasminogen activator (uPA) gene expression to induce cancer cell invasion. However, it remains unknown how proteolytic activity of TMPRSS4 contributes to invasion. In this study, we report that TMPRSS4 directly converted inactive pro-uPA into the active form through its proteolytic activity. Analysis of conditioned medium from cells overexpressing TMPRSS4 demonstrated that the active TMPRSS4 protease domain is released from the cells and is associated with the plasma membrane. Furthermore, TMPRSS4 could increase pro-uPA-mediated invasion in a serine proteolytic activity-dependent manner. These observations suggest that TMPRSS4 is an upstream regulator of pro-uPA activation. This study provides valuable insights into the proteolytic function of TMPRSS4 as well as mechanisms for the control of invasion. Copyright © 2014 Elsevier Inc. All rights reserved.

Nanophase hydroxyapatite coatings for dental and orthopedic applications

NASA Astrophysics Data System (ADS)

Sato, Michiko

In order to improve dental and orthopedic implant performance, the objective of this study was to synthesize nanocrystalline hydroxyapatite (HA) powders to coat metals (specifically, titanium and tantalum). Precipitated HA powders were either sintered in order to produce UltraCaP HA (or microcrystalline size HA) or were treated hydrothermally to produce nanocrystalline HA. Some of the UltraCaP and nanocrystalline HA powders were doped with yttrium (Y) since previous in vitro studies demonstrated that Y-doped HA in bulk improved osteoblast (or bone-forming cell) function over undoped HA. The nanocrystalline HA powders were also mixed with nanophase titania powders because previous studies demonstrated that titania/HA composite coatings increased coating adhesive strength and HA nucleation. These powders were then deposited onto titanium by a novel room-temperature process, called IonTiteT(TM). The results demonstrated that the chemical properties and crystallite size of the original HA powders were maintained in the coatings. More importantly, in vitro studies showed increased osteoblast (bone-forming cell) adhesion on the single phase nanocrystalline HA and nano-titania/HA coatings compared to traditionally used plasma-sprayed HA coatings and uncoated metals. Results further demonstrated greater amounts of calcium deposition by osteoblasts cultured on nanocrystalline HA coatings compared to UltraCaP coatings and conventionally used plasma-sprayed HA coatings. To elucidate mechanisms that influenced osteoblast functions on the HA coatings, the amount of proteins (fibronectin and vitronectin) onto the HA powders and the adsorbed fibronectin conformation were investigated. Exposure of cell integrin binding domains (in fibronectin III10 segments) was greater in fibronectin adsorbed onto 1.2 mole% Y-doped UltraCaP HA coatings compared to nanocrystalline HA coatings tested. However, 1.2 mole% Y-doped UltraCaP HA coatings did not increase mineralization by osteoblasts compared to the nanocrystalline HA coatings. These results suggested that the availability of integrin binding domains in fibronectin did not correlate to enhanced mineralization by osteoblasts on nanocrystalline HA coatings. Lastly, undoped nanocrystalline HA coatings were studied using a well-established rat calvaria in vivo. Histological analysis showed that nanocrystalline HA coated on tantalum scaffolds increased bone and fibrous tissue infiltration into the scaffolds while uncoated and UltraCaP HA coated scaffolds did not after as early as 6 weeks. In summary, these results encourage further studies on nanocrystalline IonTiteTM HA coatings on various metals for orthopedic and dental applications.

Multi-walled carbon nanotubes increase antibody-producing B cells in mice immunized with a tetravalent vaccine candidate for dengue virus.

PubMed

Calegari, Luan P; Dias, Roberto S; de Oliveira, Michelle D; Pessoa, Carine Ribeiro; de Oliveira, André S; Oliveira, Ana F C S; da Silva, Cynthia C; Fonseca, Flavio G; Versiani, Alice F; De Paula, Sérgio O

2016-07-27

In recent times, studies have demonstrated that carbon nanotubes are good candidates for use as vehicles for transfection of exogenous material into the cells. However, there are few studies evaluating the behavior of carbon nanotubes as DNA vectors and few of these studies have used multi-walled carbon nanotubes (MWCNTs) or carboxylated MWCNTs. Thus, this study aims to assess the MWCNTs' (carboxylated or not) efficiency in the increase in expression of the tetravalent vaccine candidate (TVC) plasmid vector for dengue virus in vitro using Vero cells, and in vivo, through the intramuscular route, to evaluate the immunological response profile. Multi-walled carbon nanotubes internalized by Vero cells, have been found in the cytoplasm and nucleus associated with the plasmid. However, it was not efficient to increase the messenger ribonucleic acid (mRNA) compared to the pure vaccine candidate associated with Lipofectamine(®) 2000. The in vivo experiments showed that the use of intramuscular injection of the TVC in combination with MWCNTs reduced the immune response compared to pure TVC, in a general way, although an increase was observed in the population of the antibody-producing B cells, as compared to pure TVC. The results confirm the data found by other authors, which demonstrate the ability of nanotubes to penetrate target cells and reach both the cytoplasm and the cell nucleus. The cytotoxicity values are also in accordance with the literature, which range from 5 to 20 µg/mL. This has been found to be 10 µg/mL in this study. Although the expression levels are higher in cells that receive the pure TVC transfected using Lipofectamine(®) 2000, the nanotubes show an increase in B-cells producing antibodies.

Parallelization of a hydrological model using the message passing interface

USGS Publications Warehouse

Wu, Yiping; Li, Tiejian; Sun, Liqun; Chen, Ji

2013-01-01

With the increasing knowledge about the natural processes, hydrological models such as the Soil and Water Assessment Tool (SWAT) are becoming larger and more complex with increasing computation time. Additionally, other procedures such as model calibration, which may require thousands of model iterations, can increase running time and thus further reduce rapid modeling and analysis. Using the widely-applied SWAT as an example, this study demonstrates how to parallelize a serial hydrological model in a Windows® environment using a parallel programing technology—Message Passing Interface (MPI). With a case study, we derived the optimal values for the two parameters (the number of processes and the corresponding percentage of work to be distributed to the master process) of the parallel SWAT (P-SWAT) on an ordinary personal computer and a work station. Our study indicates that model execution time can be reduced by 42%–70% (or a speedup of 1.74–3.36) using multiple processes (two to five) with a proper task-distribution scheme (between the master and slave processes). Although the computation time cost becomes lower with an increasing number of processes (from two to five), this enhancement becomes less due to the accompanied increase in demand for message passing procedures between the master and all slave processes. Our case study demonstrates that the P-SWAT with a five-process run may reach the maximum speedup, and the performance can be quite stable (fairly independent of a project size). Overall, the P-SWAT can help reduce the computation time substantially for an individual model run, manual and automatic calibration procedures, and optimization of best management practices. In particular, the parallelization method we used and the scheme for deriving the optimal parameters in this study can be valuable and easily applied to other hydrological or environmental models.

Naringin Protects Ovalbumin-Induced Airway Inflammation in a Mouse Model of Asthma.

PubMed

Guihua, Xiong; Shuyin, Liu; Jinliang, Gao; Wang, Shumin

2016-04-01

Many plant species containing flavonoids have been widely used in traditional Chinese medicine. Naringin, a well-known flavanone glycoside of citrus fruits, possesses antioxidant, anti-inflammatory, anti-apoptotic, anti-ulcer, anti-osteoporosis, and anti-carcinogenic properties. The aim of the study was to investigate the anti-asthmatic effects of naringin and the possible mechanisms. Asthma model was established by ovalbumin. A total of 50 mice were randomly assigned to five experimental groups: control, model, and dexamethasone (2 mg/kg, orally) and naringin (5 mg/kg, 10 mg/kg, orally). Airway resistance (Raw) were measured, histological studies were evaluated by the hematoxylin and eosin (HE) staining, OVA-specific serum and BALF IgE levels and Th1/Th2 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and Th1/Th2 cells was evaluated by flow cytometry (FCM). T-bet and GABA3 in the lung were evaluated by Western blot. Our study demonstrated that naringin inhibited OVA-induced increases in Raw and eosinophil count; OVA-induced effects on interleukin (IL)-4 and INF-gamma levels were blunted with naringin administration. Histological studies demonstrated that naringin substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue. Flow cytometry studies demonstrated that naringin substantially inhibited Th2 cells and enhanced Th1 cells. Naringin substantially inhibited GABA3 and increased T-bet. These findings suggest that naringin may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

Integrated modeling of water supply and demand under management options and climate change scenarios in Chifeng City, China

Treesearch

Lu Hao; Ge Sun; Yongqiang Liu; Hong Qian

2015-01-01

Water resource management is becoming increasingly challenging in northern China because of the rapid increase in water demand and decline in water supply due to climate change. We provide a case study demonstrating the importance of integrated watershed management in sustaining water resources in Chifeng City, northern China. We examine the consequences of various...

The Urban Stream Food Web: Synthesis of Recent Investigations and a Look Ahead

EPA Science Inventory

Research has repeatedly demonstrated declines in assemblage richness, diversity, and biotic integrity with increasing urbanization. Benthic macroinvertebrates are among the most widely studied organisms and have exhibited consistent responses to urbanization. Some recent macroinv...

The response to unfolded protein is involved in osmotolerance of Pichia pastoris

PubMed Central

2010-01-01

Background The effect of osmolarity on cellular physiology has been subject of investigation in many different species. High osmolarity is of importance for biotechnological production processes, where high cell densities and product titers are aspired. Several studies indicated that increased osmolarity of the growth medium can have a beneficial effect on recombinant protein production in different host organisms. Thus, the effect of osmolarity on the cellular physiology of Pichia pastoris, a prominent host for recombinant protein production, was studied in carbon limited chemostat cultures at different osmolarities. Transcriptome and proteome analyses were applied to assess differences upon growth at different osmolarities in both, a wild type strain and an antibody fragment expressing strain. While our main intention was to analyze the effect of different osmolarities on P. pastoris in general, this was complemented by studying it in context with recombinant protein production. Results In contrast to the model yeast Saccharomyces cerevisiae, the main osmolyte in P. pastoris was arabitol rather than glycerol, demonstrating differences in osmotic stress response as well as energy metabolism. 2D Fluorescence Difference Gel electrophoresis and microarray analysis were applied and demonstrated that processes such as protein folding, ribosome biogenesis and cell wall organization were affected by increased osmolarity. These data indicated that upon increased osmolarity less adaptations on both the transcript and protein level occurred in a P. pastoris strain, secreting the Fab fragment, compared with the wild type strain. No transcriptional activation of the high osmolarity glycerol (HOG) pathway was observed at steady state conditions. Furthermore, no change of the specific productivity of recombinant Fab was observed at increased osmolarity. Conclusion These data point out that the physiological response to increased osmolarity is different to S. cerevisiae. Increased osmolarity resulted in an unfolded protein response (UPR) like response in P. pastoris and lead to pre-conditioning of the recombinant Fab producing strain of P. pastoris to growth at high osmolarity. The current data demonstrate a strong similarity of environmental stress response mechanisms and recombinant protein related stresses. Therefore, these results might be used in future strain and bioprocess engineering of this biotechnologically relevant yeast. PMID:20346137

Designing Intervention Studies: Selected Populations, Range Restrictions, and Statistical Power

ERIC Educational Resources Information Center

Miciak, Jeremy; Taylor, W. Pat; Stuebing, Karla K.; Fletcher, Jack M.; Vaughn, Sharon

2016-01-01

An appropriate estimate of statistical power is critical for the design of intervention studies. Although the inclusion of a pretest covariate in the test of the primary outcome can increase statistical power, samples selected on the basis of pretest performance may demonstrate range restriction on the selection measure and other correlated…

Stories in Conversations and Presentations--A Comparative Study

ERIC Educational Resources Information Center

Brophy, Barry; Guerin, Suzanne

2018-01-01

Students receive little guidance on how to give the oral presentations that increasingly feature in third level modules. It has been observed that several communication tools employed effectively in conversation--in particular stories--are not used in presentations. The aim of this study was to demonstrate this effect and explore possible reasons…

Klebsiella pneumoniae Antimicrobial Drug Resistance, United States, 1998–2010

PubMed Central

Sanchez, Guillermo V.; Master, Ronald N.; Clark, Richard B.; Fyyaz, Madiha; Duvvuri, Padmaraj; Ekta, Gupta

2013-01-01

We studied antimicrobial-resistant Klebsiella pneumoniae for 1998–2010 by using data from The Surveillance Network. Susceptibility results (n = 3,132,354) demonstrated significant increases in resistance to all antimicrobial drugs studied, except tetracycline. Cross-resistance among carbapenem-resistant K. pneumoniae was lower for tetracycline and amikacin. PMID:23260464

Impact of lifestage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice.

EPA Science Inventory

Epidemiological studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Previous experimental studies have demonstrated increased incidence of liver, lung, ovary, and uterine tumo...

Anxiety Sensitivity and Panic Attacks: A 1-Year Longitudinal Study

ERIC Educational Resources Information Center

Li, Wen; Zinbarg, Richard E.

2007-01-01

The hypothesis that anxiety sensitivity (AS) is a risk factor for panic genesis has obtained compelling support, but the clinical/practical importance of AS in panic genesis has been questioned. In addition, the association between panic experience and AS increase has not been clearly demonstrated. Through this 1-year longitudinal study among…

Developing a heme iron database for meats according to meat type, cooking method and doneness level

USDA-ARS?s Scientific Manuscript database

Background: Animal studies have demonstrated that iron may be related to carcinogenesis, and human studies found that heme iron can increase the formation of N-nitroso compounds, which are known carcinogens. Objectives: One of the postulated mechanisms linking red meat intake to cancer risk involves...

The Metropolitan Studies Institute at USC Upstate: Translational Research that Drives Community Decision-Making

ERIC Educational Resources Information Center

Brady, Kathleen

2012-01-01

The Metropolitan Studies Institute (MSI) at the University of South Carolina Upstate (USC Upstate) demonstrates a robust and unique record of community impact through community indicators research and other translational research. The MSI's work drives programmatic priorities and funding decisions, generates revenue, and increases the community's…

Electronic versus Traditional Print Textbooks: A Comparison Study on the Influence of University Students' Learning

ERIC Educational Resources Information Center

Rockinson- Szapkiw, Amanda J.; Courduff, Jennifer; Carter, Kimberly; Bennett, David

2013-01-01

University students are increasingly choosing to purchase e-textbooks for their mobile devices as an alternative to traditional textbooks. This study examines the relationship between textbook format and 538 university students' grades and perceived learning scores. Results demonstrate that there was no difference in cognitive learning and grades…

THE URINARY BLADDER EXHIBITS A U-SHAPED GENOMIC DOSE-RESPONSE FOLLOWING SHORT- AND LONG-TERM EXPOSURE OF MICE TO ARSENATE IN DRINKING WATER

EPA Science Inventory

A number of studies have demonstrated increased urinary bladder tumor incidence in populations exposed to inorganic arsenic in drinking water at concentrations on the order of several hundred micrograms per liter, but experimental animal studies at much higher concentrations have...

Selective Learning and Teaching among Japanese and German Children

ERIC Educational Resources Information Center

Kim, Sunae; Paulus, Markus; Sodian, Beate; Itakura, Shoji; Ueno, Mika; Senju, Atsushi; Proust, Joëlle

2018-01-01

Despite an increasing number of studies demonstrating that young children selectively learn from others, and a few studies of children's selective teaching, the evidence almost exclusively comes from Western cultures, and cross-cultural comparison in this line of work is very rare. In the present research, we investigated Japanese and German…

Early Numeracy Intervention: Does Quantity Discrimination Really Work?

ERIC Educational Resources Information Center

Hansmann, Paul

2013-01-01

Scope and Method of Study: The current study demonstrates that a taped problem intervention is an effective tool for increasing the early numeracy skill of QD. A taped problems intervention was used with two variations of the quantity discrimination measure (triangle and traditional). A 3x2 doubly multivariate multivariate analysis of variance was…

Teaching of the International Component in the Introductory Marketing Course: A Replication Study

ERIC Educational Resources Information Center

Zimmer, Robert; Koernig, Stephen K.; Greene, Scott

2004-01-01

For almost three decades, the AACSB and business leaders have sought increased emphasis on internationalizing students' perspectives. Recent studies demonstrate mixed results in the extent to which business schools have globalized their curricula. With decreasing student interest in the marketing major, Introductory Marketing emerges as a critical…

Complexity in Student Writing: The Relationship between the Task and Vocabulary Uptake

ERIC Educational Resources Information Center

Wolsey, Thomas D.

2010-01-01

Cognitive flexibility theory posits that some tasks or cognitive activities resist oversimplification, a lens through which the present study is cast. High school writing tasks that promote complex thinking may also promote increased uptake of academic vocabulary. The study described in this article demonstrates how essential questions and other…

Left-handedness and language lateralization in children.

PubMed

Szaflarski, Jerzy P; Rajagopal, Akila; Altaye, Mekibib; Byars, Anna W; Jacola, Lisa; Schmithorst, Vincent J; Schapiro, Mark B; Plante, Elena; Holland, Scott K

2012-01-18

This fMRI study investigated the development of language lateralization in left- and righthanded children between 5 and 18 years of age. Twenty-seven left-handed children (17 boys, 10 girls) and 54 age- and gender-matched right-handed children were included. We used functional MRI at 3T and a verb generation task to measure hemispheric language dominance based on either frontal or temporo-parietal regions of interest (ROIs) defined for the entire group and applied on an individual basis. Based on the frontal ROI, in the left-handed group, 23 participants (85%) demonstrated left-hemispheric language lateralization, 3 (11%) demonstrated symmetric activation, and 1 (4%) demonstrated right-hemispheric lateralization. In contrast, 50 (93%) of the right-handed children showed left-hemispheric lateralization and 3 (6%) demonstrated a symmetric activation pattern, while one (2%) demonstrated a right-hemispheric lateralization. The corresponding values for the temporo-parietal ROI for the left-handed children were 18 (67%) left-dominant, 6 (22%) symmetric, 3 (11%) right-dominant and for the right-handed children 49 (91%), 4 (7%), 1 (2%), respectively. Left-hemispheric language lateralization increased with age in both groups but somewhat different lateralization trajectories were observed in girls when compared to boys. The incidence of atypical language lateralization in left-handed children in this study was similar to that reported in adults. We also found similar rates of increase in left-hemispheric language lateralization with age between groups (i.e., independent of handedness) indicating the presence of similar mechanisms for language lateralization in left- and right-handed children. Copyright © 2011 Elsevier B.V. All rights reserved.

Behavioral Recommendations in Health Research News as Cues to Action: Self-Relevancy and Self-Efficacy Processes.

PubMed

Chang, Chingching

2016-08-01

This study argues that behavioral recommendations in health news function as cues to action. A proposed self-oriented model seeks to explore the impacts of behavioral recommendations in health research news as cues to action through their influences on self-relevancy and self-efficacy. A content analysis (Study 1) first establishes that health research news commonly features behavioral recommendations. A message experiment (Study 2) then explores the utility of behavioral recommendations as cues to action by demonstrating a self-relevancy effect: Health research news with, as opposed to without, behavioral recommendations increases the self-relevancy of advocated health behaviors, which then improve people's attitudes toward and intentions to adopt those behaviors. A second message experiment (Study 3) tests whether varying presentations of behavioral recommendations alter their effectiveness as cues to action and thus people's behavioral intentions through a dual effect process. In addition to the previously demonstrated self-relevancy effect, this experiment shows that concrete, as opposed to abstract, behavioral recommendations trigger a self-efficacy effect, increasing perceived self-efficacy and further improving behavioral intentions.

Exercise therapy in polycystic ovary syndrome.

PubMed

Hoeger, Kathleen M

2008-01-01

Women with polycystic ovary syndrome (PCOS) demonstrate a high prevalence of obesity across all populations studied. The role of decreased energy expenditure through reduced physical activity in contributing to obesity in PCOS is not well studied. The independent benefits of exercise in improving metabolic disease, cardiovascular health, and diabetes have been shown in the general population. Moderate activity incorporated into daily activities appears to be as effective in the reduction in diabetes risk and cardiovascular disease as that achieved with vigorous activity and may be more sustainable over the long-term. The role of physical activity in the management of the reproductive dysfunction of PCOS is less established, although lifestyle change incorporating increased physical activity with reduced caloric intake has shown benefit in small published trials. Studies of weight loss demonstrate an essential role for increased physical activity in maintenance of weight loss over the long-term although minimal effect in the achievement of weight loss with exercise alone. Further studies of the role for exercise in the management of reproductive dysfunction in PCOS as well as clarification of the type, frequency, and duration of exercise to achieve the best outcomes are needed.

Cysteine Cathepsins in Human Carious Dentin

PubMed Central

Nascimento, F.D.; Minciotti, C.L.; Geraldeli, S.; Carrilho, M.R.; Pashley, D.H.; Tay, F.R.; Nader, H.B.; Salo, T.; Tjäderhane, L.; Tersariol, I.L.S.

2011-01-01

Matrix metalloproteinases (MMPs) are important in dentinal caries, and analysis of recent data demonstrates the presence of other collagen-degrading enzymes, cysteine cathepsins, in human dentin. This study aimed to examine the presence, source, and activity of cysteine cathepsins in human caries. Cathepsin B was detected with immunostaining. Saliva and dentin cysteine cathepsin and MMP activities on caries lesions were analyzed spectrofluorometrically. Immunostaining demonstrated stronger cathepsins B in carious than in healthy dentin. In carious dentin, cysteine cathepsin activity increased with increasing depth and age in chronic lesions, but decreased with age in active lesions. MMP activity decreased with age in both active and chronic lesions. Salivary MMP activities were higher in patients with active than chronic lesions and with increasing lesion depth, while cysteine cathepsin activities showed no differences. The results indicate that, along with MMPs, cysteine cathepsins are important, especially in active and deep caries. PMID:21248362

Chefs move to schools. A pilot examination of how chef-created dishes can increase school lunch participation and fruit and vegetable intake.

PubMed

Just, David R; Wansink, Brian; Hanks, Andrew S

2014-12-01

To demonstrate the feasibility of introducing a main dish designed by a professional chef in the National School Lunch Program and to document the impact on child participation, a chef was recruited to design pizza to be served in an upstate New York school district. The pizza was designed to meet both the cost and ingredient requirements of the NSLP. High school students were significantly more likely to select the pizza prepared by the chef. While the chef had no significant impact on main dish consumption given selection, more students took a vegetable and vegetable consumption increased by 16.5%. This pilot study demonstrates the plausibility of using chefs to boost participation in the school lunch program, and potentially increase nutrition through side selection, among high school students. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sex differences in attention to disgust facial expressions.

PubMed

Kraines, Morganne A; Kelberer, Lucas J A; Wells, Tony T

2017-12-01

Research demonstrates that women experience disgust more readily and with more intensity than men. The experience of disgust is associated with increased attention to disgust-related stimuli, but no prior study has examined sex differences in attention to disgust facial expressions. We hypothesised that women, compared to men, would demonstrate increased attention to disgust facial expressions. Participants (n = 172) completed an eye tracking task to measure visual attention to emotional facial expressions. Results indicated that women spent more time attending to disgust facial expressions compared to men. Unexpectedly, we found that men spent significantly more time attending to neutral faces compared to women. The findings indicate that women's increased experience of emotional disgust also extends to attention to disgust facial stimuli. These findings may help to explain sex differences in the experience of disgust and in diagnoses of anxiety disorders in which disgust plays an important role.

Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B. mallei–like Variation in the bimA Motility Gene, Australia

PubMed Central

Fane, Anne; Sarovich, Derek S.; Price, Erin P.; Rush, Catherine M.; Govan, Brenda L.; Parker, Elizabeth; Mayo, Mark; Currie, Bart J.; Ketheesan, Natkunam

2017-01-01

Neurologic melioidosis is a serious, potentially fatal form of Burkholderia pseudomallei infection. Recently, we reported that a subset of clinical isolates of B. pseudomallei from Australia have heightened virulence and potential for dissemination to the central nervous system. In this study, we demonstrate that this subset has a B. mallei–like sequence variation of the actin-based motility gene, bimA. Compared with B. pseudomallei isolates having typical bimA alleles, isolates that contain the B. mallei–like variation demonstrate increased persistence in phagocytic cells and increased virulence with rapid systemic dissemination and replication within multiple tissues, including the brain and spinal cord, in an experimental model. These findings highlight the implications of bimA variation on disease progression of B. pseudomallei infection and have considerable clinical and public health implications with respect to the degree of neurotropic threat posed to human health. PMID:28418830

Brain cholinesterase activity of nestling great egrets, snowy egrets, and black-crowned night-herons

USGS Publications Warehouse

Custer, T.W.; Ohlendorf, H.M.

1989-01-01

Inhibition of brain cholinesterase (ChE) activity in birds is often used to diagnose exposure or death from organophosphorus or carbmate pesticides. Brain ChE activity in the young of altricial species increase with age; however, this relationship has only been demonstrated in the European starling (Sturnus vulgaris). Brain ChE activity of nestling great egrets (Casmerodius albus) collected from a colony in Texas increased significantly with age and did not differ among individuals from different nests. Brain ChE activity of nestling snowy egrets (Egretta thula) and black-crowned night -herons (Nycticorax nycticorax) collected in one colony each from Rhode Island, Texas, and California also increased significantly with age and did not differ among individuals from different nests or colonies. This study further demonstrates that age must be considered when evaluating exposure of nestling altricial birds to ChE inhibitors.

Brain cholinesterase activity of nestling great egrets snowy egrets and black-crowned night-herons

USGS Publications Warehouse

Custer, T.W.; Ohlendorf, H.M.

1989-01-01

Inhibition of brain cholinesterase (ChE) activity in birds is often used to diagnose exposure or death from organophosphorus or carbamate pesticides. Brain ChE activity in the young of altricial species increases with age; however, this relationship has only been demonstrated in the European starling (Sturnus vulgaris). Brain ChE activity of nestling great egrets (Casmerodius albus) collected from a colony in Texas (USA) increased significantly with age and did not differ among individuals from different nests. Brain ChE activity of nestling snowy egrets (Egretta thula) and black-crowned night-herons (Nycticorax nycticorax) collected in one colony each from Rhode Island, Texas and California (USA) also increased significantly with age and did not differ among individuals from different nests or colonies. This study further demonstrates that age must be considered when evaluating exposure of nestling altricial birds to ChE inhibitors.

Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B. mallei-like Variation in the bimA Motility Gene, Australia.

PubMed

Morris, Jodie L; Fane, Anne; Sarovich, Derek S; Price, Erin P; Rush, Catherine M; Govan, Brenda L; Parker, Elizabeth; Mayo, Mark; Currie, Bart J; Ketheesan, Natkunam

2017-05-01

Neurologic melioidosis is a serious, potentially fatal form of Burkholderia pseudomallei infection. Recently, we reported that a subset of clinical isolates of B. pseudomallei from Australia have heightened virulence and potential for dissemination to the central nervous system. In this study, we demonstrate that this subset has a B. mallei-like sequence variation of the actin-based motility gene, bimA. Compared with B. pseudomallei isolates having typical bimA alleles, isolates that contain the B. mallei-like variation demonstrate increased persistence in phagocytic cells and increased virulence with rapid systemic dissemination and replication within multiple tissues, including the brain and spinal cord, in an experimental model. These findings highlight the implications of bimA variation on disease progression of B. pseudomallei infection and have considerable clinical and public health implications with respect to the degree of neurotropic threat posed to human health.

The effect of increased consumer demand on fees for aesthetic surgery: an economic analysis.

PubMed

Krieger, L M; Shaw, W W

1999-12-01

Economic theory dictates that changes in consumer demand have predictable effects on prices. Demographics represents an important component of demand for aesthetic surgery. Between the years of 1997 and 2010, the U.S. population is projected to increase by 12 percent. The population increase will be skewed such that those groups undergoing the most aesthetic surgery will see the largest increase. Accounting for the age-specific frequencies of aesthetic surgery and the population increase yields an estimate that the overall market for aesthetic surgery will increase by 19 percent. Barring unforeseen changes in general economic conditions or consumer tastes, demand should increase by an analogous amount. An economic demonstration shows the effects of increasing demand for aesthetic surgery on its fees. Between the years of 1992 and 1997, there was an increase in demand for breast augmentation as fears of associated autoimmune disorders subsided. Similarly, there was increased male acceptance of aesthetic surgery. The number of breast augmentations and procedures to treat male pattern baldness, plastic surgeons, and fees for the procedures were tracked. During the study period, the supply of surgeons and consumer demand increased for both of these procedures. Volume of breast augmentation increased by 275 percent, whereas real fees remained stable. Volume of treatment for male pattern baldness increased by 107 percent, and the fees increased by 29 percent. Ordinarily, an increase in supply leads to a decrease in prices. This did not occur during the study period. Economic analysis demonstrates that the increased supply of surgeons performing breast augmentation was offset by increased consumer demand for the procedure. For this reason, fees were not lowered. Similarly, increased demand for treatment of male pattern baldness more than offset the increased supply of surgeons performing it. The result was higher fees. Emphasis should be placed on using these economic relationships to expand the demand for aesthetic surgery.

Ignoring correlation in uncertainty and sensitivity analysis in life cycle assessment: what is the risk?

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

Groen, E.A., E-mail: Evelyne.Groen@gmail.com; Heijungs, R.; Leiden University, Einsteinweg 2, Leiden 2333 CC

Life cycle assessment (LCA) is an established tool to quantify the environmental impact of a product. A good assessment of uncertainty is important for making well-informed decisions in comparative LCA, as well as for correctly prioritising data collection efforts. Under- or overestimation of output uncertainty (e.g. output variance) will lead to incorrect decisions in such matters. The presence of correlations between input parameters during uncertainty propagation, can increase or decrease the the output variance. However, most LCA studies that include uncertainty analysis, ignore correlations between input parameters during uncertainty propagation, which may lead to incorrect conclusions. Two approaches to include correlationsmore » between input parameters during uncertainty propagation and global sensitivity analysis were studied: an analytical approach and a sampling approach. The use of both approaches is illustrated for an artificial case study of electricity production. Results demonstrate that both approaches yield approximately the same output variance and sensitivity indices for this specific case study. Furthermore, we demonstrate that the analytical approach can be used to quantify the risk of ignoring correlations between input parameters during uncertainty propagation in LCA. We demonstrate that: (1) we can predict if including correlations among input parameters in uncertainty propagation will increase or decrease output variance; (2) we can quantify the risk of ignoring correlations on the output variance and the global sensitivity indices. Moreover, this procedure requires only little data. - Highlights: • Ignoring correlation leads to under- or overestimation of the output variance. • We demonstrated that the risk of ignoring correlation can be quantified. • The procedure proposed is generally applicable in life cycle assessment. • In some cases, ignoring correlation has a minimal effect on decision-making tools.« less

Liraglutide attenuates the osteoblastic differentiation of MC3T3-E1 cells by modulating AMPK/mTOR signaling

PubMed Central

Hu, Xiong-Ke; Yin, Xin-Hua; Zhang, Hong-Qi; Guo, Chao-Feng; Tang, Ming-Xing

2016-01-01

Liraglutide, a synthetic analogue of glucagon-like peptide-1, is utilized in the treatment of type 2 diabetes and obesity. Liraglutide has been previously demonstrated to prevent osteoblastic differentiation of human vascular smooth muscle cells, resulting in the slowing of arterial calcification, however, its effect on bone formation remains unclear. The present study investigated the effect of liraglutide on osteoblastic differentiation using Alizarin Red S staining, and examined the molecular mechanisms underlying the regulatory effect by western blot analysis. The present study demonstrated that protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were downregulated in MC3T3-E1 cells during osteoblastic differentiation in commercial osteogenic differentiation medium, whereas protein expression levels of transforming growth factor-β (TGF-β) and phosphorylated mammalian target of rapamycin (p-mTOR) increased. Liraglutide was subsequently demonstrated to dose-dependently attenuate the osteoblastic differentiation of MC3T3-E1 cells, to upregulate p-AMPK, and downregulate p-mTOR and TGF-β protein expression levels. Treatment with an AMPK-specific inhibitor, Compound C, eradicated the effect of liraglutide on osteoblastic differentiation, and p-mTOR and TGF-β downregulation. An mTOR activator, MHY1485, also abolished the inhibitory effect of liraglutide on osteoblastic differentiation, and resulted in p-mTOR and TGF-β downregulation, but did not attenuate the liraglutide-induced increase in p-AMPK protein expression levels. The results of the present study demonstrate that liraglutide attenuates osteoblastic differentiation of MC3T3-E1 cells via modulation of AMPK/mTOR signaling. The present study revealed a novel function of liraglutide, which contributes to the understanding of its pharmacological and physiological effects in clinical settings. PMID:27600753

Picosecond Pulse Recirculation for High Average Brightness Thomson Scattering-based Gamma-ray Sources

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

Semenov, V. A.

2009-06-12

Pulse recirculation has been successfully demonstrated with the interaction laser system of LLNL's Thomson-Radiated Extreme X-ray (T-REX) source. The recirculation increased twenty-eight times the intensity of the light coming out of the laser system, demonstrating the capability of increasing the gamma-ray flux emitted by T-REX. The technical approach demonstrated could conceivably increase the average gamma-ray flux output by up to a hundred times.

Masking Period Patterns & Forward Masking for Speech-Shaped Noise: Age-related effects

PubMed Central

Grose, John H.; Menezes, Denise C.; Porter, Heather L.; Griz, Silvana

2015-01-01

Objective The purpose of this study was to assess age-related changes in temporal resolution in listeners with relatively normal audiograms. The hypothesis was that increased susceptibility to non-simultaneous masking contributes to the hearing difficulties experienced by older listeners in complex fluctuating backgrounds. Design Participants included younger (n = 11), middle-aged (n = 12), and older (n = 11) listeners with relatively normal audiograms. The first phase of the study measured masking period patterns for speech-shaped noise maskers and signals. From these data, temporal window shapes were derived. The second phase measured forward-masking functions, and assessed how well the temporal window fits accounted for these data. Results The masking period patterns demonstrated increased susceptibility to backward masking in the older listeners, compatible with a more symmetric temporal window in this group. The forward-masking functions exhibited an age-related decline in recovery to baseline thresholds, and there was also an increase in the variability of the temporal window fits to these data. Conclusions This study demonstrated an age-related increase in susceptibility to non-simultaneous masking, supporting the hypothesis that exacerbated non-simultaneous masking contributes to age-related difficulties understanding speech in fluctuating noise. Further support for this hypothesis comes from limited speech-in-noise data suggesting an association between susceptibility to forward masking and speech understanding in modulated noise. PMID:26230495

C57BL/6 Substrains Exhibit Different Responses to Acute Carbon Tetrachloride Exposure: Implications for Work Involving Transgenic Mice

PubMed Central

McCracken, Jennifer M.; Chalise, Prabhakar; Briley, Shawn M.; Dennis, Katie L.; Jiang, Lu; Duncan, Francesca E.; Pritchard, Michele T.

2017-01-01

Biological differences exist between strains of laboratory mice, and it is becoming increasingly evident that there are differences between substrains. In the C57BL/6 mouse, the primary substrains are called 6J and 6N. Previous studies have demonstrated that 6J and 6N mice differ in response to many experimental models of human disease. The aim of our study was to determine if differences exist between 6J and 6N mice in terms of their response to acute carbon tetrachloride (CCl4) exposure. Mice were given CCl4 once and were euthanized 12 to 96 h later. Relative to 6J mice, we found that 6N mice had increased liver injury but more rapid repair. This was because of the increased speed with which necrotic hepatocytes were removed in 6N mice and was directly related to increased recruitment of macrophages to the liver. In parallel, enhanced liver regeneration was observed in 6N relative to 6J mice. Hepatic stellate cell activation occurred earlier in 6N mice, but there was no difference in matrix metabolism between substrains. Taken together, these data demonstrate specific and significant differences in how the C57BL/6 substrains respond to acute CCl4, which has important implications for all mouse studies utilizing this model. PMID:28234577

Relatively fast! Efficiency advantages of comparative thinking.

PubMed

Mussweiler, Thomas; Epstude, Kai

2009-02-01

Comparisons are a ubiquitous process in information processing. Seven studies examine whether, how, and when comparative thinking increases the efficiency of judgment and choice. Studies 1-4 demonstrate that procedurally priming participants to engage in more vs. less comparison influences how they process information about a target. Specifically, they retrieve less information about the target (Studies 1A, 1B), think more about an information-rich standard (Study 2) about which they activate judgment-relevant information (Study 3), and use this information to compensate for missing target information (Study 4). Studies 2-5 demonstrate the ensuing efficiency advantages. Participants who are primed on comparative thinking are faster in making a target judgment (Studies 2A, 2B, 4, 5) and have more residual processing capacities for a secondary task (Study 5). Studies 6 and 7 establish two boundary conditions by demonstrating that comparative thinking holds efficiency advantages only if target and standard are partly characterized by alignable features (Study 6) that are difficult to evaluate in isolation (Study 7). These findings indicate that comparative thinking may often constitute a useful mechanism to simplify information processing. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

The Effects of Silicone Hydrogel Lens Wear on the Corneal Epithelium and Risk for Microbial Keratitis

PubMed Central

Robertson, Danielle M.

2012-01-01

Previous studies using animal models and human clinical trials have demonstrated that the use of low oxygen transmissible contact lens materials produce corneal epithelial surface damage resulting in increased Pseudomonas aeruginosa (PA) adhesion and raft-mediated internalization into surface corneal epithelial cells. These findings led to the testable clinical predictions that: (1) microbial keratitis (MK) risk is expected to be greatest during the first 6 months of wear; (2) there is no difference between 6 and 30 night extended wear; and (3) that wear of hyper-oxygen transmissible lenses would reduce the reported incidence of infection. Subsequent epidemiological studies have confirmed the first two predictions; however, increased oxygen transmissibility with silicone hydrogel (SiHy) lens wear has not altered the overall incidence of MK. In this review, more recent clinical and basic studies that investigate epithelial alterations and bacterial adhesion to corneal epithelial cells following wear of SiHy lenses with and without concomitant exposure to chemically preserved multipurpose solutions (MPS) will be examined. The collective results of these studies demonstrate that even in the absence of lens-related hypoxia, MPS induce ocular surface changes during SiHy lens wear which are associated with a pathophysiological increase in PA adherence and internalization in the corneal epithelium, and therefore, predict an increased risk for PA-MK. In addition, new data supporting an interactive role for inflammation in facilitating PA adherence and internalization in the corneal epithelium will also be discussed. PMID:23266590

The mnemonic mover: nostalgia regulates avoidance and approach motivation.

PubMed

Stephan, Elena; Wildschut, Tim; Sedikides, Constantine; Zhou, Xinyue; He, Wuming; Routledge, Clay; Cheung, Wing-Yee; Vingerhoets, Ad J J M

2014-06-01

In light of its role in maintaining psychological equanimity, we proposed that nostalgia--a self-relevant, social, and predominantly positive emotion--regulates avoidance and approach motivation. We advanced a model in which (a) avoidance motivation triggers nostalgia and (b) nostalgia, in turn, increases approach motivation. As a result, nostalgia counteracts the negative impact of avoidance motivation on approach motivation. Five methodologically diverse studies supported this regulatory model. Study 1 used a cross-sectional design and showed that avoidance motivation was positively associated with nostalgia. Nostalgia, in turn, was positively associated with approach motivation. In Study 2, an experimental induction of avoidance motivation increased nostalgia. Nostalgia then predicted increased approach motivation. Studies 3-5 tested the causal effect of nostalgia on approach motivation and behavior. These studies demonstrated that experimental nostalgia inductions strengthened approach motivation (Study 3) and approach behavior as manifested in reduced seating distance (Study 4) and increased helping (Study 5). The findings shed light on nostalgia's role in regulating the human motivation system.

Oxidative Stress Induces Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines in a Well-Matched Case Control Cohort

PubMed Central

Rose, Shannon; Frye, Richard E.; Slattery, John; Wynne, Rebecca; Tippett, Marie; Pavliv, Oleksandra; Melnyk, Stepan; James, S. Jill

2014-01-01

There is increasing recognition that mitochondrial dysfunction is associated with the autism spectrum disorders. However, little attention has been given to the etiology of mitochondrial dysfunction or how mitochondrial abnormalities might interact with other physiological disturbances associated with autism, such as oxidative stress. In the current study we used respirometry to examine reserve capacity, a measure of the mitochondrial ability to respond to physiological stress, in lymphoblastoid cell lines (LCLs) derived from children with autistic disorder (AD) as well as age and gender-matched control LCLs. We demonstrate, for the first time, that LCLs derived from children with AD have an abnormal mitochondrial reserve capacity before and after exposure to increasingly higher concentrations of 2,3-dimethoxy-1,4-napthoquinone (DMNQ), an agent that increases intracellular reactive oxygen species (ROS). Specifically, the AD LCLs exhibit a higher reserve capacity at baseline and a sharper depletion of reserve capacity when ROS exposure is increased, as compared to control LCLs. Detailed investigation indicated that reserve capacity abnormalities seen in AD LCLs were the result of higher ATP-linked respiration and maximal respiratory capacity at baseline combined with a marked increase in proton leak respiration as ROS was increased. We further demonstrate that these reserve capacity abnormalities are driven by a subgroup of eight (32%) of 25 AD LCLs. Additional investigation of this subgroup of AD LCLs with reserve capacity abnormalities revealed that it demonstrated a greater reliance on glycolysis and on uncoupling protein 2 to regulate oxidative stress at the inner mitochondria membrane. This study suggests that a significant subgroup of AD children may have alterations in mitochondrial function which could render them more vulnerable to a pro-oxidant microenvironment derived from intrinsic and extrinsic sources of ROS such as immune activation and pro-oxidant environmental toxicants. These findings are consistent with the notion that AD is caused by a combination of genetic and environmental factors. PMID:24416410

Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells

NASA Technical Reports Server (NTRS)

Hughes-Fulford, M.; Chen, Y.; Tjandrawinata, R. R.

2001-01-01

It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells.

PubMed

Hughes-Fulford, M; Chen, Y; Tjandrawinata, R R

2001-05-01

It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

Increased prevalence of low back pain among physiotherapy students compared to medical students.

PubMed

Falavigna, Asdrubal; Teles, Alisson Roberto; Mazzocchin, Thaís; de Braga, Gustavo Lisbôa; Kleber, Fabrício Diniz; Barreto, Felipe; Santin, Juliana Tosetto; Barazzetti, Daniel; Lazzaretti, Lucas; Steiner, Bruna; Beckenkamp, Natália Laste

2011-03-01

Some studies have demonstrated that physiotherapists have a high prevalence of low back pain (LBP). The association between physiotherapy students, who are potentially exposed to the same LBP occupational risks as graduates, and LBP has never been demonstrated. The objective of the study is to evaluate the association between undergraduate physiotherapy study and LBP. The study design includes a cross-sectional study. A questionnaire-based study was carried out with physiotherapy and medical students. LBP was measured as lifetime, 1-year and point prevalence. Bivariate and multivariate analyses were performed to find the factors associated with LBP. Bivariate analyses were also performed to assess differences between LBP characteristics in the two courses. 77.9% of the students had LBP at some point in their lives, 66.8% in the last year and 14.4% of them reported they were suffering from LBP at the moment of answering the questionnaire. Physiotherapy students reported a higher prevalence of LBP when compared with the medical students in all measures. In the logistic regression model, physiotherapy students (A-OR 2.51; 95% CI 1.35-4.67; p = 0.003), and being exposed to the undergraduate study for more than four semesters (A-OR 2.55; 95% CI 1.43-4.55; p = 0.001) were independently associated with LBP. There were no differences between the courses concerning pain intensity and disability. As it was a cross-sectional study, we were not able to observe accurately if there is an increasing incidence of LBP during the course. Also, we did not intend to identify which activities in the course were associated with the development of LBP. This study clearly demonstrated an association between undergraduate physiotherapy study and LBP. The length of course exposure is also associated with LBP.

From Research to Practice: The Effect of Multi-Component Vocabulary Instruction on Increasing Vocabulary and Comprehension Performance in Social Studies

ERIC Educational Resources Information Center

Graham, Lori; Graham, Anna; West, Courtney

2015-01-01

This study was designed to demonstrate the effect of implementing multi-component vocabulary strategy instruction in fourth grade social studies. Curriculum was designed for a six-week period and was intended to actively engage students and reinforce retention of word meanings in isolation and in context. Teachers were randomly chosen for…

Enjoying food without caloric cost: The impact of brief mindfulness on laboratory eating outcomes.

PubMed

Arch, Joanna J; Brown, Kirk Warren; Goodman, Robert J; Della Porta, Matthew D; Kiken, Laura G; Tillman, Shanna

2016-04-01

Mindfulness-based interventions have been increasingly applied to treat eating-related problems ranging from obesity to eating disorders. Yet few studies have empirically examined the mechanisms of a mindful approach to eating. The current studies examine the potential of brief mindfulness instructions to enhance the psychological and behavioral dimensions of eating. In three experiments (total N = 319 undergraduates), we examined whether brief mindfulness instructions would enhance the positive sensory experience involved in tasting food as well as healthy eating behaviors. Relative to distraction control instructions, the first two studies demonstrated that brief mindfulness instructions increased the enjoyment of a commonly pleasurable food (chocolate; Study 1), and a food with generally more mixed associations (raisins; Study 2). The third study replicated and extended these findings to show that brief mindfulness instructions also led to lower calorie consumption of unhealthy food relative to distracted or no-instruction control conditions, an effect mediated by greater eating enjoyment. Findings demonstrated the power of brief mindfulness instructions to positively impact both health-relevant behavior and sensory experience associated with eating food. Implications for both theory and clinical applications of mindfulness are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Proteome Analyses of Staphylococcus aureus Biofilm at Elevated Levels of NaCl

PubMed Central

Islam, Nazrul; Ross, Julia M; Marten, Mark R

2016-01-01

Our studies demonstrate that sodium chloride (NaCl) induces changes in biofilm, mediated by increased production of polysaccharides intercellular adhesion (PIA). We identified 12 proteins that showed higher abundance in increased level of NaCl. This includes one important protein (IsaA) known to be associated with biofilm stability. In addition, we also found higher abundance of a cold shock protein, CspA, at higher NaCl. We have also identified several other proteins that are differentially expressed to the elevated levels of NaCl and mapped them in the regulatory pathways of PIA. The majority of proteins are involved with various aspects bacterial metabolic function. Our results demonstrated that NaCl influences gene regulatory networks controlling exopolysaccharide expression. PMID:26973848

Animal-Assisted Intervention and Dementia: A Systematic Review.

PubMed

Yakimicki, Michelle L; Edwards, Nancy E; Richards, Elizabeth; Beck, Alan M

2018-02-01

This review discusses the relationship between animal-assisted interventions (AAI) and behavioral and psychological symptoms of dementia (BPSD). A systematic search was conducted within CINAHL, Web of Science CAB Abstracts, PubMed, Abstracts in Social Gerontology, Google Scholar, and PsycINFO for primary research articles. A total of 32 studies were included in the final review. Variation was noted in study designs and in study setting. Twenty-seven of 32 studies used dogs as the intervention. Agitation/aggression showed a significant decrease in nine of 15 studies. Eleven of 12 studies demonstrated increased social interaction with AAI. Mood had mixed results in nine studies. Quality of life was increased in three of four studies. Resident activity and nutritional intake were each increased in two studies. Animal assisted activities/interventions showed a strong positive effect on social behaviors, physical activity, and dietary intake in dementia patients and a positive effect on agitation/aggression and quality of life.

Increase of infiltrating monocytes in the livers of patients with chronic liver diseases.

PubMed

Huang, Rui; Wu, Hongyan; Liu, Yong; Yang, Chenchen; Pan, Zhiyun; Xia, Juan; Xiong, Yali; Wang, Guiyang; Sun, Zhenhua; Chen, Jun; Yan, Xiaomin; Zhang, Zhaoping; Wu, Chao

2016-01-01

Infiltrating monocytes have been demonstrated to contribute to tissue damage in experimental models of liver injury and fibrosis. However, less is known about monocyte infiltration in the livers of patients with chronic liver diseases (CLD). In the present study, we demonstrated that CD68+ hepatic macrophages and MAC387+ infiltrating monocytes were significantly increased in the livers of CLD patients with different etiologies as compared with normal liver tissue. In addition, CLD patients with higher inflammatory grading scores had more CD68+ macrophages and MAC387+ monocytes infiltration in their livers compared to those with lower scores. Significantly more MAC387+ infiltrating monocytes were found in the liver tissue of CLD patients with higher fibrotic staging scores compared to those with lower scores. Monocyte chemoattractant protein-1 (MCP-1) expression was significantly increased in the livers of CLD patients with different etiologies. MCP-1 staining scores were significantly positively associated with the numbers of MAC387+ infiltrating monocytes in CLD patients. Taken together, our results demonstrate that infiltrating monocytes may play a pathological role in exacerbating chronic liver inflammation and fibrosis in CLD. MCP-1 may be involved in the monocyte infiltration and progression of liver inflammation and fibrosis in CLD.

EGFR blockade enriches for lung cancer stem-like cells through Notch3-dependent signaling

PubMed Central

Arasada, Rajeswara Rao; Amann, Joseph M.; Rahman, Mohammad A; Huppert, Stacey S.; Carbone, David P.

2014-01-01

Mutations in the epidermal growth factor receptor (EGFR) are the most common actionable genetic abnormalities yet discovered in lung cancer. However, targeting these mutations with kinase inhibitors is not curative in advanced disease and has yet to demonstrate an impact on potentially curable, early-stage disease, with some data suggesting adverse outcomes. Here, we report that treatment of EGFR-mutated lung cancer cell lines with erlotinib, while showing robust cell death, enriches the ALDH+ stem-like cells through EGFR-dependent activation of Notch3. Additionally, we demonstrate that erlotinib treatment increases the clonogenicity of lung cancer cells in a sphere-forming assay, suggesting increased stem-like cell potential. We demonstrate that inhibition of EGFR kinase activity leads to activation of Notch transcriptional targets in a gamma secretase inhibitor sensitive manner and causes Notch activation. leading to an increase in ALDH high+ cells. We also find a kinase-dependent physical association between the Notch3 and EGFR receptors and tyrosine phosphorylation of Notch3. This could explain the worsened survival observed in some studies of erlotinib treatment at early-stage disease, and suggests that specific dual targeting might overcome this adverse effect. PMID:25125655

Patterns of human local cerebral glucose metabolism during epileptic seizures

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

Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.

1982-10-01

Ictal patterns of local cerebral metabolic rate have been studied in epileptic patients by positron computed tomography with /sup 18/F-labeled 2-fluoro-2-deoxy-D-glucose. Partial seizures were associated with activation of anatomic structures unique to each patient studied. Ictal increases and decreases in local cerebral metabolism were observed. Scans performed during generalized convulsions induced by electroshock demonstrated a diffuse ictal increase and postictal decrease in cerebral metabolism. Petit mal absences were associated with a diffuse increase in cerebral metabolic rate. The ictal fluorodeoxyglucose patterns obtained from patients do not resemble autoradiographic patterns obtained from common experimental animal models of epilepsy.

Using 3D computer simulations to enhance ophthalmic training.

PubMed

Glittenberg, C; Binder, S

2006-01-01

To develop more effective methods of demonstrating and teaching complex topics in ophthalmology with the use of computer aided three-dimensional (3D) animation and interactive multimedia technologies. We created 3D animations and interactive computer programmes demonstrating the neuroophthalmological nature of the oculomotor system, including the anatomy, physiology and pathophysiology of the extra-ocular eye muscles and the oculomotor cranial nerves, as well as pupillary symptoms of neurological diseases. At the University of Vienna we compared their teaching effectiveness to conventional teaching methods in a comparative study involving 100 medical students, a multiple choice exam and a survey. The comparative study showed that our students achieved significantly better test results (80%) than the control group (63%) (diff. = 17 +/- 5%, p = 0.004). The survey showed a positive reaction to the software and a strong preference to have more subjects and techniques demonstrated in this fashion. Three-dimensional computer animation technology can significantly increase the quality and efficiency of the education and demonstration of complex topics in ophthalmology.

Current Options for the Treatment of Food Allergy

PubMed Central

Lanser, Bruce J.; Wright, Benjamin L.; Orgel, Kelly A.; Vickery, Brian P.; Fleischer, David M.

2016-01-01

Food allergy is increasing in prevalence; as a result, there is intense focus on developing safe and effective therapies. Current methods of specific immunotherapy include oral, sublingual, and epicutaneous, while nonspecific methods that have been investigated include: Chinese herbal medicine, probiotics, and anti-IgE antibodies. Although some studies have demonstrated efficacy in inducing desensitization, questions regarding safety and the potential for achieving immune tolerance remain. Although some of these therapies demonstrate promise, further investigation is required before their incorporation into routine clinical practice. PMID:26456449

[Evaluating work intensity in major and auxiliary occupations of by-product coke industry].

PubMed

Smagulov, N K; Alpysbayeva, Zh T

2015-01-01

The article covers evaluation of work strain in major and auxiliary occupations of by-product coke industry. The study results conclude that occupational activity of by-product coke industry workers, under exposure to occupational hazards, affects the workers' performance. Major occupations workers demonstrate higher level of functional strain of CNS, poor concentration of attention and lower ability to switch over, decreased general performance, vs. the auxiliary occupations workers who demonstrated increased cardiovascular and neuro-muscular strain due to occupational activity.

Low-Level Light Therapy Potentiates NPe6-mediated Photodynamic Therapy in a Human Osteosarcoma Cell Line via Increased ATP

PubMed Central

Tsai, Shang-Ru; Yin, Rui; Huang, Ying-Ying; Sheu, Bor-Ching; Lee, Si-Chen; Hamblin, Michael R.

2015-01-01

Background Low-Level Light Therapy (LLLT) is used to stimulate healing, reduce pain and inflammation, and preserve tissue from dying. LLLT has been shown to protect cells in culture from dying after various cytotoxic insults, and LLLT is known to increase the cellular ATP content. Previous studies have demonstrated that maintaining a sufficiently high ATP level is necessary for the efficient induction and execution of apoptosis steps after photodynamic therapy (PDT). Methods We asked whether LLLT would protect cells from cytotoxicity due to PDT, or conversely whether LLLT would enhance the efficacy of PDT mediated by mono-L-aspartyl chlorin(e6) (NPe6). Increased ATP could lead to enhanced cell uptake of NPe6 by the energy dependent process of endocytosis, and also to more efficient apoptosis. In this study, human osteosarcoma cell line MG-63 was subjected to 1.5 J/cm2 of 810 nm near infrared radiation (NIR) followed by addition of 10 μM NPe6 and after 2 h incubation by 1.5 J/cm2 of 652 nm red light for PDT. Results PDT combined with LLLT led to higher cell death and increased intracellular reactive oxygen species compared to PDT alone. The uptake of NPe6 was moderately increased by LLLT, and cellular ATP was increased. The mitochondrial respiratory chain inhibitor antimycin A abrogated the LLLT-induced increase in cytotoxicity. Conclusions Taken together, these results demonstrate that LLLT potentiates NPe6-mediated PDT via increased ATP synthesis and is a potentially promising strategy that could be applied in clinical PDT. PMID:25462575

Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster longevity.

PubMed

Danilov, Anton; Shaposhnikov, Mikhail; Shevchenko, Oksana; Zemskaya, Nadezhda; Zhavoronkov, Alex; Moskalev, Alexey

2015-08-14

Most age-related diseases and aging itself are associated with chronic inflammation. Thus pharmacological inhibition of inflammatory processes may be effective antiaging strategy. In this study we demonstrated that treatment of Drosophila melanogaster with 10 non-steroidal anti-inflammatory drugs (NSAIDs: CAY10404, aspirin, APHS, SC-560, NS-398, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, licofelone) leads to extension of lifespan, delays age-dependent decline of locomotor activity and increases stress resistance. The effect of the lifespan increase was associated with decrease of fecundity. Depending on the concentration, NSAIDs demonstrated both anti- and pro-oxidant properties in Drosophila tissues. However, we failed to identify clear correlation between antioxidant properties of NSAIDs and their pro-longevity effects. The lifespan extending effects of APHS, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, and licofelone were more pronounced in males, valdecoxib and aspirin - in females. We demonstrated that lifespan extension effect of NSAIDs was abolished in flies with defective genes involved in Pkh2-ypk1-lem3-tat2 pathway.

Surfactant protein-A nanobody-conjugated liposomes loaded with methylprednisolone increase lung-targeting specificity and therapeutic effect for acute lung injury.

PubMed

Li, Nan; Weng, Dong; Wang, Shan-Mei; Zhang, Yuan; Chen, Shan-Shan; Yin, Zhao-Fang; Zhai, Jiali; Scoble, Judy; Williams, Charlotte C; Chen, Tao; Qiu, Hui; Wu, Qin; Zhao, Meng-Meng; Lu, Li-Qin; Mulet, Xavier; Li, Hui-Ping

2017-11-01

The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb. MPS-NSSLs-SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS-NSSLs-SPANb to the lung. Treatment with MPS-NSSLs-SPANb reduced the levels of TNF-α, IL-8, and TGF-β1 in rat bronchoalveolar lavage fluid and the expression of NK-κB in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.

VGLUT2-dependent sensory neurons in the TRPV1 population regulate pain and itch.

PubMed

Lagerström, Malin C; Rogoz, Katarzyna; Abrahamsen, Bjarke; Persson, Emma; Reinius, Björn; Nordenankar, Karin; Olund, Caroline; Smith, Casey; Mendez, José Alfredo; Chen, Zhou-Feng; Wood, John N; Wallén-Mackenzie, Asa; Kullander, Klas

2010-11-04

The natural response to itch sensation is to scratch, which relieves the itch through an unknown mechanism. Interaction between pain and itch has been frequently demonstrated, and the selectivity hypothesis of itch, based on data from electrophysiological and behavioral experiments, postulates the existence of primary pain afferents capable of repressing itch. Here, we demonstrate that deletion of vesicular glutamate transporter (VGLUT) 2 in a subpopulation of neurons partly overlapping with the vanilloid receptor (TRPV1) primary afferents resulted in a dramatic increase in itch behavior accompanied by a reduced responsiveness to thermal pain. The increased itch behavior was reduced by administration of antihistaminergic drugs and by genetic deletion of the gastrin-releasing peptide receptor, demonstrating a dependence on VGLUT2 to maintain normal levels of both histaminergic and nonhistaminergic itch. This study establishes that VGLUT2 is a major player in TRPV1 thermal nociception and also serves to regulate a normal itch response. Copyright © 2010 Elsevier Inc. All rights reserved.

Uteroplacental insufficiency temporally exacerbates salt-induced hypertension associated with a reduced natriuretic response in male rat offspring.

PubMed

Gallo, Linda A; Walton, Sarah L; Mazzuca, Marc Q; Tare, Marianne; Parkington, Helena C; Wlodek, Mary E; Moritz, Karen M

2018-03-31

Low weight at birth increases the risk of developing chronic diseases in adulthood A diet that is high in salt is known to elevate blood pressure, which is a major risk factor for cardiovascular and kidney diseases The present study demonstrates that growth restricted male rats have a heightened sensitivity to high dietary salt, in the context of raised systolic blood pressure, reduced urinary sodium excretion and stiffer mesenteric resistance vessels Other salt-induced effects, such as kidney hyperfiltration, albuminuria and glomerular damage, were not exacerbated by being born small The present study demonstrates that male offspring born small have an increased cardiovascular susceptibility to high dietary salt, such that that minimizing salt intake is probably of particular benefit to this at-risk population ABSTRACT: Intrauterine growth restriction increases the risk of developing chronic diseases in adulthood. Lifestyle factors, such as poor dietary choices, may elevate this risk. We determined whether being born small increases the sensitivity to a dietary salt challenge, in the context of hypertension, kidney disease and arterial stiffness. Bilateral uterine vessel ligation or sham surgery (offspring termed Restricted and Control, respectively) was performed on 18-day pregnant Wistar Kyoto rats. Male offspring were allocated to receive a diet high in salt (8% sodium chloride) or remain on standard rat chow (0.52% sodium chloride) from 20 to 26 weeks of age for 6 weeks. Systolic blood pressure (tail-cuff), renal function (24 h urine excretions) and vascular stiffness (pressure myography) were assessed. Restricted males were born 15% lighter than Controls and remained smaller throughout the study. Salt-induced hypertension was exacerbated in Restricted offspring, reaching a peak systolic pressure of ∼175 mmHg earlier than normal weight counterparts. The natriuretic response to high dietary salt in Restricted animals was less than in Controls and may explain the early rise in arterial pressure. Growth restricted males allocated to a high salt diet also had increased passive arterial stiffness of mesenteric resistance arteries. Other aspects of renal function, including salt-induced hyperfiltration, albuminuria and glomerular damage, were not exacerbated by uteroplacental insufficiency. The present study demonstrates that male offspring exposed to uteroplacental insufficiency and born small have an increased sensitivity to salt-induced hypertension and arterial remodelling. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Increasing frequency of low summer precipitation synchronizes dynamics and compromises metapopulation stability in the Glanville fritillary butterfly

PubMed Central

Tack, Ayco J. M.; Mononen, Tommi; Hanski, Ilkka

2015-01-01

Climate change is known to shift species' geographical ranges, phenologies and abundances, but less is known about other population dynamic consequences. Here, we analyse spatio-temporal dynamics of the Glanville fritillary butterfly (Melitaea cinxia) in a network of 4000 dry meadows during 21 years. The results demonstrate two strong, related patterns: the amplitude of year-to-year fluctuations in the size of the metapopulation as a whole has increased, though there is no long-term trend in average abundance; and there is a highly significant increase in the level of spatial synchrony in population dynamics. The increased synchrony cannot be explained by increasing within-year spatial correlation in precipitation, the key environmental driver of population change, or in per capita growth rate. On the other hand, the frequency of drought during a critical life-history stage (early larval instars) has increased over the years, which is sufficient to explain the increasing amplitude and the expanding spatial synchrony in metapopulation dynamics. Increased spatial synchrony has the general effect of reducing long-term metapopulation viability even if there is no change in average metapopulation size. This study demonstrates how temporal changes in weather conditions can lead to striking changes in spatio-temporal population dynamics. PMID:25854888

Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

PubMed Central

Fernandez-Twinn, Denise S.; Chen, Jian Hua; Hargreaves, Iain P.; Neergheen, Viruna; Aiken, Catherine E.; Ozanne, Susan E.

2016-01-01

ABSTRACT ‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’) in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb) and an increased frequency of short telomeres (4.2-1.3 kb) in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), and increased xanthine oxidase (XO), p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by increased tumor necrosis factor-α (TNFα) and interleukin-1β (IL1β) protein levels. Taken together, we demonstrate, for the first time to our knowledge, an accelerated aging phenotype in skeletal muscle in the context of developmental programming. These findings may pave the way for suitable interventions in at-risk populations. PMID:27585884

Sex-Based Differences in Knee Kinetics With Anterior Cruciate Ligament Strain on Cadaveric Impact Simulations

PubMed Central

Schilaty, Nathan D.; Bates, Nathaniel A.; Nagelli, Christopher; Krych, Aaron J.; Hewett, Timothy E.

2018-01-01

Background: Females are at an increased risk of sustaining noncontact knee ligament injuries as compared with their male counterparts. The kinetics that load the anterior cruciate ligament (ACL) are still under dispute in the literature. Purpose/Hypothesis: The purpose of this study was to determine whether there are differences in knee kinetics between the sexes that lead to greater ACL strain in females when similar external loads are applied during a simulated drop vertical jump landing task. It was hypothesized that female limbs would demonstrate significant differences in knee abduction moment that predispose females to ACL injury when compared with males. Study Design: Controlled laboratory study. Methods: Motion analysis data of 67 athletes who performed a drop vertical jump were collected. The kinematic and kinetic data were used to categorize tertiles of relative risk, and these values were input into a cadaveric impact simulator to assess ligamentous loads during the simulated landing task. Uni- and multiaxial load cells and differential variable reluctance transducer strain sensors were utilized to collect kinetic data and maximum ACL strain for analysis. Conditions of external loads applied to the cadaveric limbs were systematically varied and randomized. Data were analyzed with 2-way repeated-measures analysis of variance and the Fisher exact test. Results: Five kinetic parameters were evaluated. Of the 5 kinetic variables, only knee abduction moment (KAM) demonstrated significant differences in females as compared with males (F 1,136 = 4.398, P = .038). When normalized to height and weight, this difference between males and females increased in significance (F 1,136 = 7.155, P = .008). Compared with males, females exhibited a 10.3-N·m increased knee abduction torque at 66 milliseconds postimpact and a 22.3-N·m increased abduction torque at 100 milliseconds postimpact. For loading condition, the condition of “maximum ACL strain” demonstrated a maximum difference of 54.3-N·m increased abduction torque and 74.5-N·m increased abduction torque at 66 milliseconds postimpact. Conclusion: Under the tested conditions, increased external loads led to increased medial knee translation force, knee abduction moment, and external knee moment. Females exhibited greater forces and moments at the knee, especially at KAM, when loaded in similar conditions. As these KAM loads are associated with increased load and strain on the ACL, the sex-based differences observed in the present study may account for a portion of the underlying mechanics that predispose females to ACL injury as compared with males in a controlled simulated athletic task. Clinical Relevance: KAM increases strain to the ACL under clinically representative loading. Additionally, this work establishes the biomechanical characteristics of knee loading between sexes. PMID:29568787

Is death really the worm at the core? Converging evidence that worldview threat increases death-thought accessibility.

PubMed

Schimel, Jeff; Hayes, Joseph; Williams, Todd; Jahrig, Jesse

2007-05-01

According to terror management theory, if the cultural worldview protects people from thoughts about death, then weakening this structure should increase death-thought accessibility (DTA). Five studies tested this DTA hypothesis. Study 1 showed that threatening Canadian participants' cultural values (vs. those of another culture) increased DTA on a word-fragment completion task. Study 2 showed that when participants could dismiss the threat, DTA remained low. Study 3 replicated the results of Study 1, but DTA was measured using a lexical decision task. Response latencies to death, negative, and neutral content were measured. Worldview threat increased DTA relative to accessibility for negative and neutral content. Study 4 showed that the DTA effect emerged independently of the arousal of anger or anxiety. Finally, Study 5 demonstrated that participants with a pro-creation (vs. pro-evolution) worldview had higher DTA after reading an anti-creation article. Discussion focused on theoretical implications and directions for further research. ((c) 2007 APA, all rights reserved).

PARTICULATE MATTER (PM) AND HOSPITAL ADMISSIONS AMONG U.S. VETERANS

EPA Science Inventory

Epidemiological studies have consistently demonstrated that exposure to particulate matter (PM) can result in increased mortality and morbidity. The susceptible population, the nature of morbidity and cause of death, however, have not been clearly identified. To accomplish these ...

Curcumin uptake enhancement using low dose light illumination during incubation in Candida albicans

NASA Astrophysics Data System (ADS)

Romano, Renan A.; Pratavieira, Sebastião.; da Silva, Ana P.; Kurachi, Cristina; Bagnato, Vanderlei S.; Guimarães, Francisco E. G.

2017-07-01

A new PDI protocol is presented in this study. C. albicans cells pre-illuminated with a low dose light demonstrated an increase of curcumin uptake when compared to dark incubation, leading to a higher PDI efficacy.

Classroom Use of Martial Arts Exhibitions

NASA Astrophysics Data System (ADS)

Landry, Shane Garrett; Denn, Grant R.

2006-10-01

Martial arts are becoming increasingly popular, and many of the techniques used by martial artists can provide effective demonstrations to showcase basic physics concepts. Many students have martial arts experience by the time they reach the senior level of high school or college. In one conceptual physics course, seven students out of 40 had studied some form of martial arts. Teachers can use experienced students as a resource and exploit the popularity of martial arts to demonstrate some basic points in Newtonian mechanics via martial arts demonstrations. This interactive mode of learning, we have found, is very popular and highly motivational for the students. In this paper we provide some of the possible examples of effective classroom demonstrations; there are many additional examples that your students may want to introduce.

Effects of nutrient loading on the carbon balance of coastal wetland sediments

USGS Publications Warehouse

Morris, J.T.; Bradley, P.M.

1999-01-01

Results of a 12-yr study in an oligotrophic South Carolina salt marsh demonstrate that soil respiration increased by 795 g C m-2 yr-1 and that carbon inventories decreased in sediments fertilized with nitrogen and phosphorus. Fertilized plots became net sources of carbon to the atmosphere, and sediment respiration continues in these plots at an accelerated pace. After 12 yr of treatment, soil macroorganic matter in the top 5 cm of sediment was 475 g C m-2 lower in fertilized plots than in controls, which is equivalent to a constant loss rate of 40 g C m-2 yr-1. It is not known whether soil carbon in fertilized plots has reached a new equilibrium or continues to decline. The increase in soil respiration in the fertilized plots was far greater than the loss of sediment organic matter, which indicates that the increase in soil respiration was largely due to an increase in primary production. Sediment respiration in laboratory incubations also demonstrated positive effects of nutrients. Thus, the results indicate that increased nutrient loading of oligotrophic wetlands can lead to an increased rate of sediment carbon turnover and a net loss of carbon from sediments.

Why do shape aftereffects increase with eccentricity?

PubMed

Gheorghiu, Elena; Kingdom, Frederick A A; Bell, Jason; Gurnsey, Rick

2011-12-20

Studies have shown that spatial aftereffects increase with eccentricity. Here, we demonstrate that the shape-frequency and shape-amplitude aftereffects, which describe the perceived shifts in the shape of a sinusoidal-shaped contour following adaptation to a slightly different sinusoidal-shaped contour, also increase with eccentricity. Why does this happen? We first demonstrate that the perceptual shift increases with eccentricity for stimuli of fixed sizes. These shifts are not attenuated by variations in stimulus size; in fact, at each eccentricity the degree of perceptual shift is scale-independent. This scale independence is specific to the aftereffect because basic discrimination thresholds (in the absence of adaptation) decrease as size increases. Structural aspects of the displays were found to have a modest effect on the degree of perceptual shift; the degree of adaptation depends modestly on distance between stimuli during adaptation and post-adaptation testing. There were similar temporal rates of decline of adaptation across the visual field and higher post-adaptation discrimination thresholds in the periphery than in the center. The observed results are consistent with greater sensitivity reduction in adapted mechanisms following adaptation in the periphery or an eccentricity-dependent increase in the bandwidth of the shape-frequency- and shape-amplitude-selective mechanisms.

School burnout: increased sympathetic vasomotor tone and attenuated ambulatory diurnal blood pressure variability in young adult women.

PubMed

May, Ross W; Sanchez-Gonzalez, Marcos A; Fincham, Frank D

2015-01-01

Two studies examined autonomic and cardiovascular functioning that may link school burnout to cardiovascular risk factors in young healthy adult females. Study 1 (N = 136) investigated whether school burnout was related to resting values of blood pressure (BP) and blood pressure variability (BPV) through laboratory beat-to-beat BP assessment. Study 2 (N = 94) examined the link between school burnout and diurnal BPV through ambulatory BP monitoring. Controlling for anxiety and depressive symptomatology, school burnout demonstrated strong positive relationships with indices of cardiac sympathovagal tone, sympathetic vasomotor tone, inefficient myocardial oxygen consumption, increased 24-h ambulatory heart rate and BP, blunted BP diurnal variability, and increased arterial stiffness. These studies establish cardiovascular biomarkers of school burnout and suggest that even in a seemingly healthy sample school burnout may predispose females to increased cardiovascular risk. Several future lines of research are outlined.

Perspective-Taking Increases Willingness to Engage in Intergroup Contact

PubMed Central

Wang, Cynthia S.; Kenneth, Tai; Ku, Gillian; Galinsky, Adam D.

2014-01-01

The current research explored whether perspective-taking increases willingness to engage in contact with stereotyped outgroup members. Across three studies, we find that perspective-taking increases willingness to engage in contact with negatively-stereotyped targets. In Study 1, perspective-takers sat closer to, whereas stereotype suppressors sat further from, a hooligan compared to control participants. In Study 2, individual differences in perspective-taking tendencies predicted individuals' willingness to engage in contact with a hooligan, having effects above and beyond those of empathic concern. Finally, Study 3 demonstrated that perspective-taking's effects on intergroup contact extend to the target's group (i.e., another homeless man), but not to other outgroups (i.e., a man of African descent). Consistent with other perspective-taking research, our findings show that perspective-taking facilitates the creation of social bonds by increasing contact with stereotyped outgroup members. PMID:24465648

Correlation of Urine Biomarkers: Microalbuminuria and Spot Urine Protein among Diabetic Patients. Application of Spot Urine Protein in Diabetic Kidney Disease, Nephropathy, Proteinuria Estimation, Diagnosing and Monitoring.

PubMed

Aziz, Kamran M A

2015-01-01

Current study has invented a new method for utilizing spot urine protein among diabetic patients. There have been various efforts and strategies in research internationally to detect, diagnose and monitor nephropathy/DKD. Although 24-hour urine studies are gold standard, however, there exist some controversies about microalbuminuria and spot urine protein. The current study was designed to utilize spot urine protein among diabetic patients and to find its association with routine dipstick urine test for albumin, and microalbuminuria. The study demonstrated significant association of spot urine protein with urine dipstick albumin, and has demonstrated increasing spot urine protein with increasing albumin in urine (p-value < 0.0001). This study also demonstrated significantly higher levels of spot urine protein between the groups with nephropathy/DKD as compared to those without nephropathy/DKD (p-value < 0.0001). Similarly, spot urine protein and spot urine protein/creatinine were also significantly associated with microalbumin and microalbumin/creatinine in urine. Significant regression models for spot urine protein and microalbuminuria were also developed and proposed to detect and estimate microalbumin in urine while utilizing spot urine protein (< 0.0001). Synthesized regression equations and models can be used confidently to detect, rule out and monitor proteinuria and DKD. ROC curves were utilized to detect spot urine protein cutoff points for nephropathy and DKD with high specificity and sensitivity. Some important patents were also discussed in the paper regarding albuminuria/proteinuria detection and management. Current study has demonstrated and concluded, for the first time, that there exists a significant association of spot urine protein with routine dipstick albumin in urine and microalbuminuria. It is also essential to detect early, monitor and manage proteinuria, hypertension and dyslipidemia with good glycemic control to prevent diabetes complications.

Breakthrough Capability for the NASA Astrophysics Explorer Program: Reaching the Darkest Sky

NASA Technical Reports Server (NTRS)

Greenhouse, Matthew A.; Benson, Scott W.; Falck, Robert D.; Fixsen, Dale J.; Gardner, Joseph P.; Garvin, James B.; Kruk, Jeffrey W.; Oleson, Stephen R.; Thronson, Harley A.

2012-01-01

We describe a mission architecture designed to substantially increase the science capability of the NASA Science Mission Directorate (SMD) Astrophysics Explorer Program for all AO proposers working within the near-UV to far-infrared spectrum. We have demonstrated that augmentation of Falcon 9 Explorer launch services with a 13 kW Solar Electric Propulsion (SEP) stage can deliver a 700 kg science observatory payload to extra-Zodiacal orbit. This new capability enables up to 13X increased photometric sensitivity and 160X increased observing speed relative to a Sun- Earth L2, Earth-trailing, or Earth orbit with no increase in telescope aperture. All enabling SEP stage technologies for this launch service augmentation have reached sufficient readiness (TRL-6) for Explorer Program application in conjunction with the Falcon 9. We demonstrate that enabling Astrophysics Explorers to reach extra-zodiacal orbit will allow this small payload program to rival the science performance of much larger long development time systems; thus, providing a means to realize major science objectives while increasing the SMD Astrophysics portfolio diversity and resiliency to external budget pressure. The SEP technology employed in this study has strong applicability to SMD Planetary Science community-proposed missions. SEP is a stated flight demonstration priority for NASA's Office of the Chief Technologist (OCT). This new mission architecture for astrophysics Explorers enables an attractive realization of joint goals for OCT and SMD with wide applicability across SMD science disciplines.

A cost/benefit analysis of commercial fusion-fission hybrid reactor development

NASA Astrophysics Data System (ADS)

Kostoff, Ronald N.

1983-04-01

A simple algorithm was developed that allows rapid computation of the ratio, R, of present worth of benefits to present worth of hybrid R&D program costs as a function of potential hybrid unit electricity cost savings, discount rate, electricity demand growth rate, total hybrid R&D program cost, and time to complete a demonstration reactor. In the sensitivity study, these variables were assigned nominal values (unit electricity cost savings of 4 mills/kW-hr, discount rate of 4%/year, growth rate of 2.25%/year, total R&D program cost of 20 billion, and time to complete a demonstration reactor of 30 years), and the variable of interest was varied about its nominal value. Results show that R increases with decreasing discount rate and increasing unit electricity savings and ranges from 4 to 94 as discount rate ranges from 5 to 3%/year and unit electricity savings range from 2 to 6 mills/kW-hr. R increases with increasing growth rate and ranges from 3 to 187 as growth rate ranges from 1 to 3.5%/year and unit electricity cost savings range from 2 to 6 mills/kW-hr. R attains a maximum value when plotted against time to complete a demonstration reactor. The location of this maximum value occurs at shorter completion times as discount rate increases, and this optimal completion time ranges from 20 years for a discount rate of 4%/year to 45 years for a discount rate of 3%/year.

Evolution of match performance parameters for various playing positions in the English Premier League.

PubMed

Bush, Michael; Barnes, Chris; Archer, David T; Hogg, Bob; Bradley, Paul S

2015-02-01

This study aimed to investigate position-specific evolution of physical and technical performance parameters in the English Premier League (EPL). Match performance observations (n=14700) were collected using a multiple-camera computerized tracking system across seven seasons (2006-07 to 2012-13). Data were analyzed relative to five playing positions: central defenders (n=3792), full backs (n=3420), central midfielders (n=3200), wide midfielders (n=2136) and attackers (n=2152). High-intensity running distance increased in the final season versus the first season in all playing positions (p<.05, ES: 0.9-1.3) with full backs displaying the greatest increase (∼36% higher in 2012-13). Similar trends were observed for sprint distance with full backs demonstrating the most pronounced increase across the seven seasons (36-63%, p<.001, ES: 0.8-1.3). Central players (central defenders and midfielders) illustrated the most pronounced increases in total passes and pass success rate (p<.05, ES: 0.7-0.9) whilst wide players (full backs and wide midfielders) demonstrated only small-moderate increases in total passes and pass success rate (p<.05, ES: 0.6-0.8). The data demonstrates that evolving tactics in the EPL have impacted on the physical demands of wide players and the technical requirements of central players. These findings could be used for talent identification or position-specific physical and technical training. Copyright © 2014 Elsevier B.V. All rights reserved.

Polytrauma Increases Susceptibility to Pseudomonas Pneumonia in Mature Mice.

PubMed

Turnbull, Isaiah R; Ghosh, Sarbani; Fuchs, Anja; Hilliard, Julia; Davis, Christopher G; Bochicchio, Grant V; Southard, Robert E

2016-05-01

Pneumonia is the most common complication observed in patients with severe injuries. Although the average age of injured patients is 47 years, existing studies of the effect of injury on the susceptibility to infectious complications have focused on young animals, equivalent to a late adolescent human. We hypothesized that mature adult animals are more susceptible to infection after injury than younger counterparts. To test this hypothesis, we challenged 6 to 8-month-old mature mice to a polytrauma injury followed by Pseudomonas aeruginosa pneumonia and compared them to young (8-10-week-old) animals. We demonstrate that polytrauma injury increases mortality from pneumonia in mature animals (sham-pneumonia 21% vs. polytrauma-pneumonia 62%) but not younger counterparts. After polytrauma, pneumonia in mature mice is associated with higher bacterial burden in lung, increased incidence of bacteremia, and elevated levels of bacteria in the blood, demonstrating that injury decreases the ability to control the infectious challenge. We further find that polytrauma did not induce elevations in circulating cytokine levels (TNF-alpha, IL-6, KC, and IL-10) 24  h after injury. However, mature mice subjected to polytrauma demonstrated an exaggerated circulating inflammatory cytokine response to subsequent Pseudomonas pneumonia. Additionally, whereas prior injury increases LPS-stimulated IL-6 production by peripheral blood leukocytes from young (8-10-week-old) mice, injury does not prime IL-6 production by cell from mature adult mice. We conclude that in mature mice polytrauma results in increased susceptibility to Pseudomonas pneumonia while priming an exaggerated but ineffective inflammatory response.

Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells

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

Ryu, Gyeong Ryul; Lee, Esder; Chun, Hyun-Ji

Highlights: •High glucose increased production of reactive oxygen species in cultured pancreatic stellate cells. •High glucose facilitated the activation of these cells. •Antioxidant treatment attenuated high glucose-induced activation of these cells. -- Abstract: The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive β-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated andmore » cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2–5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-β and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation.« less

Incidence of tonsillar cancer in northern Sweden: Impact of human papilloma virus.

PubMed

Loizou, Christos; Laurell, Göran; Lindquist, David; Öfverman, Charlotte; Stefansson, Kristina; Nylander, Karin; Olofsson, Katarina

2015-12-01

The incidence rate of tonsillar cancer is increasing worldwide. The current study identifies a parallel increase in the incidence of tonsillar cancer, human papilloma virus (HPV) and p16 expression among a population from northern Sweden, a sparsely populated area, confirming the strong association between p16 and HPV infection in tonsillar tissue. Data from the Swedish Cancer Registry was assessed to identify cases of tonsillar cancer in the northern territorial area of Sweden. HPV DNA was extracted from paraffin embedded diagnostic biopsies and detected by polymerase chain reaction using general primers Gp5+/6+ and CpI/IIG. Expression of p16 was identified by immunochemistry. Patients were grouped into urban or rural residence categories. A total of 214 cases were identified, comprising 155 (72.4%) men and 59 (27.6%) women, and 65 of these patients, who presented between 2000 and 2012, were analyzed. The overall median age for the analyzed patients was 58 years; 48 (74%) were males (median age, 57.5 years) and 17 (26%) were females (median age, 65 years). Of the 65 specimens, 59 (91%) were positive for HPV, and 62 (95%) expressed p16. The incidence of tonsillar cancer in the cohort demonstrated a 2-fold increase between 1990 and 2013; specifically, a 2.7-fold increase was observed in men whilst the female group exhibited only a small increase. These findings demonstrate a strong association between p16 expression and HPV infection in tonsillar malignancies. The incidence of HPV-positive tonsillar cancer has increased in recent years, even in sparsely populated regions, as demonstrated in northern Sweden.

Evaluation of a faculty development program aimed at increasing residents' active learning in lectures.

PubMed

Desselle, Bonnie C; English, Robin; Hescock, George; Hauser, Andrea; Roy, Melissa; Yang, Tong; Chauvin, Sheila W

2012-12-01

Active engagement in the learning process is important to enhance learners' knowledge acquisition and retention and the development of their thinking skills. This study evaluated whether a 1-hour faculty development workshop increased the use of active teaching strategies and enhanced residents' active learning and thinking. Faculty teaching in a pediatrics residency participated in a 1-hour workshop (intervention) approximately 1 month before a scheduled lecture. Participants' responses to a preworkshop/postworkshop questionnaire targeted self-efficacy (confidence) for facilitating active learning and thinking and providing feedback about workshop quality. Trained observers assessed each lecture (3-month baseline phase and 3-month intervention phase) using an 8-item scale for use of active learning strategies and a 7-item scale for residents' engagement in active learning. Observers also assessed lecturer-resident interactions and the extent to which residents were asked to justify their answers. Responses to the workshop questionnaire (n  =  32/34; 94%) demonstrated effectiveness and increased confidence. Faculty in the intervention phase demonstrated increased use of interactive teaching strategies for 6 items, with 5 reaching statistical significance (P ≤ .01). Residents' active learning behaviors in lectures were higher in the intervention arm for all 7 items, with 5 reaching statistical significance. Faculty in the intervention group demonstrated increased use of higher-order questioning (P  =  .02) and solicited justifications for answers (P  =  .01). A 1-hour faculty development program increased faculty use of active learning strategies and residents' engagement in active learning during resident core curriculum lectures.

Analysis of a large dataset of mycorrhiza inoculation field trials on potato shows highly significant increases in yield.

PubMed

Hijri, Mohamed

2016-04-01

An increasing human population requires more food production in nutrient-efficient systems in order to simultaneously meet global food needs while reducing the environmental footprint of agriculture. Arbuscular mycorrhizal fungi (AMF) have the potential to enhance crop yield, but their efficiency has yet to be demonstrated in large-scale crop production systems. This study reports an analysis of a dataset consisting of 231 field trials in which the same AMF inoculant (Rhizophagus irregularis DAOM 197198) was applied to potato over a 4-year period in North America and Europe under authentic field conditions. The inoculation was performed using a liquid suspension of AMF spores that was sprayed onto potato seed pieces, yielding a calculated 71 spores per seed piece. Statistical analysis showed a highly significant increase in marketable potato yield (ANOVA, P < 0.0001) for inoculated fields (42.2 tons/ha) compared with non-inoculated controls (38.3 tons/ha), irrespective of trial year. The average yield increase was 3.9 tons/ha, representing 9.5 % of total crop yield. Inoculation was profitable with a 0.67-tons/ha increase in yield, a threshold reached in almost 79 % of all trials. This finding clearly demonstrates the benefits of mycorrhizal-based inoculation on crop yield, using potato as a case study. Further improvements of these beneficial inoculants will help compensate for crop production deficits, both now and in the future.

Doppler ultrasound of the central retinal artery in microgravity.

PubMed

Sirek, Adam S; Garcia, Kathleen; Foy, Millennia; Ebert, Doug; Sargsyan, Ashot; Wu, Jimmy H; Dulchavsky, Scott A

2014-01-01

Ocular changes have been noted during long-duration spaceflight; we studied central retinal artery (CRA) blood flow using Doppler before, during, and after long-term microgravity exposure in astronauts compared with data from a control group of nonastronauts subjected to head-down tilt (HDT). Available Doppler spectra of International Space Station (ISS) crewmembers were obtained from the NASA Lifetime Surveillance of Astronaut Health database, along with 2D ultrasound-derived measurements of the optic nerve sheath diameter (ONSD). CRA Doppler spectra and optic nerve sheath images were also obtained from healthy test subjects in an acute HDT experiment at 20 min of exposure (the ground-based analogue). HDT CRA peak systolic velocity in the ground-based analogue group increased by an average of 3 cm -s(-1) (33%) relative to seated values. ONSD at 300 of HDT increased by 0.5 mm relative to supine values. CRA Doppler spectra obtained on orbit were of excellent quality and demonstrated in-flight changes of +5 cm x s(-1) (50%) compared to preflight. ONSD increased in ISS crewmembers during flight relative to before flight, with some reversal postflight. A significant ONSD response to acute postural change and to spaceflight was demonstrated in this preliminary study. Increases in Doppler peak flow velocities correlated with increases in ONSD. Further investigations are warranted to corroborate the relationship between ONSD, intracranial pressure, and central retinal blood flow for occupational surveillance and research purposes.

A longitudinal study of serum ferritin in 319 adolescent Danish boys and girls examined in 1986 and 1992.

PubMed

Milman, N; Byg, K E; Backer, V; Ulrik, C; Graudal, N

1999-10-01

This study examined trends in iron status in adolescents. Serum ferritin was measured in 1986 and 1992 in 319 Danes (161 males) stratified into 5 groups: I. median age 9 yr in 1986 vs. 15 yr in 1992; II. 11 vs. 17 yr; III. 13 vs. 19 yr; IV. 15 vs. 21 yr; V. 17 vs. 23 yr. Males in group I demonstrated no change in ferritin or estimated iron stores in mg/kg; groups II-V displayed an increase in iron status parameters. All groups showed an increase in estimated total iron stores. Changes in iron status parameters were inversely correlated with height velocity in group III, and positively correlated with height velocity in group V. Females in age groups I and II demonstrated a fall in ferritin and estimated iron stores in mg/kg in association with menarche; values were unchanged in groups III and IV, and increased in group V. All groups showed an increase in estimated total iron stores. Changes in iron status parameters were inversely correlated with height velocity in groups I and II. In conclusion, ferritin levels in adolescents display great variation during growth spurt and at menarche. Changes in ferritin showed no consistent association with growth velocity. In both genders, estimated total iron stores increased with age.

Icaritin opposes the development of social aversion after defeat stress via increases of GR mRNA and BDNF mRNA in mice.

PubMed

Wu, Xiao; Wu, Jinfeng; Xia, Shijin; Li, Bei; Dong, Jingcheng

2013-11-01

Icariin is a major constituent of flavonoids isolated from Herba Epimedii. Several previous studies have demonstrated the antidepressant-like effects of icariin. After oral administration of icariin, 19 metabolites of icariin were detected in rat plasma. Icaritin is one such of metabolite of icariin. In this study, a chronic social defeat protocol is used as a mouse model for depression, and the effects of icaritin administration on social avoidance are investigated. The data indicates that icaritin (5mg/kg and 10mg/kg) oral administration opposes the development of social aversion after defeat stress. In vitro corticosterone sensitivity assay demonstrated that icaritin partially restored social defeat-induced impairment of glucocorticoid sensitivity. The expressions of GR mRNA and BDNFmRNA in the hippocampus were increased after icaritin treatment. Meanwhile, the social defeat-induced increases in CRH mRNA in hypothalamus were restored by icaritin administration. Our data also suggests that icaritin administration remarkably attenuated the increases in serum IL-6 and TNF-α level that occur following exposure to social defeat. In conclusion, icaritin is a novel antidepressant. It partially restored social defeat-induced impairment of glucocorticoid sensitivity, HPA axis hyperactivity. These effects are at least partially attributed to normalization of the GR function and increases in BDNF expression. Copyright © 2013 Elsevier B.V. All rights reserved.

Cavitation for improved sludge conversion into biogas

NASA Astrophysics Data System (ADS)

Stoop, A. H.; Bakker, T. W.; Kramer, H. J. M.

2015-12-01

In several studies the beneficial influence of pre-treatment of waste activated sludge with cavitation on the biogas production was demonstrated. It is however, still not fully certain whether this effect should be mainly contributed to an increase in conversion rate of organics into biogas by anaerobic bacteria, and how much cavitation increases the total biogas yield. An increase in yield is only the case if cavitation can further disrupt otherwise inaccessible cell membrane structures and long chain organic molecules. In this study the influence of hydrodynamic cavitation on sludge that was already digested for 30 days was investigated. The total biogas yield could indeed be increased. The effect of the backpressure behind the venturi tube on the yield could not yet be established.

On the vibrational characteristics of single- and double-walled carbon nanotubes containing ice nanotube in aqueous environment

NASA Astrophysics Data System (ADS)

Ansari, R.; Ajori, S.; Ameri, A.

2015-10-01

The properties and behavior of carbon nanotubes (CNTs) in aqueous environment due to their considerable potential applications in nanobiotechnology and designing nanobiosensors have attracted the attention of researchers. In this study, molecular dynamics simulations are carried out to investigate the vibrational characteristics of single- and double-walled CNTs containing ice nanotubes (a new phase of ice) in vacuum and aqueous environments. The results demonstrate that formation of ice nanotubes inside the CNTs reduces the natural frequency of pure CNTs. Moreover, it is demonstrated that increasing the number of walls considerably reduces the sensitivity of frequency to the presence of ice nanotube inside CNT. Additionally, it is shown that increasing the length decreases the effect of ice nanotube on reducing the frequency. The calculation of natural frequency of CNTs in aqueous media demonstrates that the interaction of CNTs with water molecules considerably reduces the natural frequency up to 50 %. Finally, it is demonstrated that in the case of CNTs with one free end in aqueous environment, the CNT does not vibrate in its first mode, and its frequency is between the frequencies of first and second modes of vibration.

The Epidemiology and Demographics of Hip Dysplasia

PubMed Central

Loder, Randall T.; Skopelja, Elaine N.

2011-01-01

The etiology of developmental dysplasia of the hip (DDH) is unknown. There are many insights, however, from epidemiologic/demographic information. A systematic medical literature review regarding DDH was performed. There is a predominance of left-sided (64.0%) and unilateral disease (63.4%). The incidence per 1000 live births ranges from 0.06 in Africans in Africa to 76.1 in Native Americans. There is significant variability in incidence within each racial group by geographic location. The incidence of clinical neonatal hip instability at birth ranges from 0.4 in Africans to 61.7 in Polish Caucasians. Predictors of DDH are breech presentation, positive family history, and gender (female). Children born premature, with low birth weights, or to multifetal pregnancies are somewhat protected from DDH. Certain HLA A, B, and D types demonstrate an increase in DDH. Chromosome 17q21 is strongly associated with DDH. Ligamentous laxity and abnormalities in collagen metabolism, estrogen metabolism, and pregnancy-associated pelvic instability are well-described associations with DDH. Many studies demonstrate an increase of DDH in the winter, both in the northern and southern hemispheres. Swaddling is strongly associated with DDH. Amniocentesis, premature labor, and massive radiation exposure may increase the risk of DDH. Associated conditions are congenital muscular torticollis and congenital foot deformities. The opposite hip is frequently abnormal when using rigorous radiographic assessments. The role of acetabular dysplasia and adult hip osteoarthritis is complex. Archeological studies demonstrate that the epidemiology of DDH may be changing. PMID:24977057

Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism.

PubMed

Martínez-Vega, Raquel; Garrido, Francisco; Partearroyo, Teresa; Cediel, Rafael; Zeisel, Steven H; Martínez-Álvarez, Concepción; Varela-Moreiras, Gregorio; Varela-Nieto, Isabel; Pajares, María A

2015-02-01

Nutritional imbalance is emerging as a causative factor of hearing loss. Epidemiologic studies have linked hearing loss to elevated plasma total homocysteine (tHcy) and folate deficiency, and have shown that folate supplementation lowers tHcy levels potentially ameliorating age-related hearing loss. The purpose of this study was to address the impact of folate deficiency on hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2 groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8 wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold increase in tHcy levels. FD mice exhibited severe hearing loss measured by auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT-quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing homocysteine (Hcy) production and recycling, together with a 30% increase in protein homocysteinylation. Redox stress was demonstrated by decreased expression of catalase, glutathione peroxidase 4, and glutathione synthetase genes, increased levels of manganese superoxide dismutase, and NADPH oxidase-complex adaptor cytochrome b-245, α-polypeptide (p22phox) proteins, and elevated concentrations of glutathione species. Altogether, our findings demonstrate, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear Hcy metabolism and associated oxidative stress. © FASEB.

Pre-existing Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced BRONJ Lesions in Mice

PubMed Central

Song, Minju; Alshaikh, Abdullah; Kim, Terresa; Kim, Sol; Dang, Michelle; Mehrazarin, Shebli; Shin, Ki-Hyuk; Kang, Mo; Park, No-Hee; Kim, Reuben H.

2016-01-01

Introduction Surgical interventions such as tooth extraction increase a chance of developing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for treatment of bone-related diseases. Tooth extraction is often performed to eliminate pre-existing pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related ONJ (BRONJ) development following tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction-induced BRONJ development in mice. Methods Periapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BP. The same tooth was extracted, and after 3 additional weeks, the mice were harvested for histological, histomorphometric, and histochemical staining analyses. Results Pulp exposure induced periapical radiolucency as demonstrated by increased inflammatory cells, TRAP+ osteoclasts, and bone resorption. When BP was administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and TRAP+ osteoclasts. While tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as demonstrated by the presence of more bone necrosis. Conclusion Our study demonstrates that pre-existing pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development following tooth extraction. Our study further provides a clinical implication whereby periapical periodontitis should be controlled before performing tooth extraction in BP-users in order to reduce the risk of developing BRONJ. PMID:27637460

A forced titration study of the antioxidant and immunomodulatory effects of Ambrotose AO supplement

PubMed Central

2010-01-01

Background Oxidative stress plays a role in acute and chronic inflammatory disease and antioxidant supplementation has demonstrated beneficial effects in the treatment of these conditions. This study was designed to determine the optimal dose of an antioxidant supplement in healthy volunteers to inform a Phase 3 clinical trial. Methods The study was designed as a combined Phase 1 and 2 open label, forced titration dose response study in healthy volunteers (n = 21) to determine both acute safety and efficacy. Participants received a dietary supplement in a forced titration over five weeks commencing with a no treatment baseline through 1, 2, 4 and 8 capsules. The primary outcome measurement was ex vivo changes in serum oxygen radical absorbance capacity (ORAC). The secondary outcome measures were undertaken as an exploratory investigation of immune function. Results A significant increase in antioxidant activity (serum ORAC) was observed between baseline (no capsules) and the highest dose of 8 capsules per day (p = 0.040) representing a change of 36.6%. A quadratic function for dose levels was fitted in order to estimate a dose response curve for estimating the optimal dose. The quadratic component of the curve was significant (p = 0.047), with predicted serum ORAC scores increasing from the zero dose to a maximum at a predicted dose of 4.7 capsules per day and decreasing for higher doses. Among the secondary outcome measures, a significant dose effect was observed on phagocytosis of granulocytes, and a significant increase was also observed on Cox 2 expression. Conclusion This study suggests that Ambrotose AO® capsules appear to be safe and most effective at a dosage of 4 capsules/day. It is important that this study is not over interpreted; it aimed to find an optimal dose to assess the dietary supplement using a more rigorous clinical trial design. The study achieved this aim and demonstrated that the dietary supplement has the potential to increase antioxidant activity. The most significant limitation of this study was that it was open label Phase 1/Phase 2 trial and is subject to potential bias that is reduced with the use of randomization and blinding. To confirm the benefits of this dietary supplement these effects now need to be demonstrated in a Phase 3 randomised controlled trial (RCT). Trial Registration Australian and New Zealand Clinical Trials Register: ACTRN12605000258651 PMID:20433711

Teaching High School Chemistry in the Context of Pharmacology Helps Both Teachers and Students Learn

PubMed Central

Schwartz-Bloom, Rochelle D.; Halpin, Myra J.; Reiter, Jerome P.

2014-01-01

Few studies demonstrate the impact of teaching chemistry embedded in a context that has relevance to high school students. We build upon our prior work showing that pharmacology topics (i.e., drugs), which are inherently interesting to high school students, provide a useful context for teaching chemistry and biology. In those studies, teachers were provided professional development for the Pharmacology Education Partnership (PEP) in an onsite venue (either five-day or one-day workshop). Given financial difficulties to travel, teachers have asked for alternatives for professional development. Thus, we developed the same PEP training workshop using a distance learning (DL) (two-way live video) approach. In this way, 121 chemistry and biology teachers participated in the DL workshops to learn how to incorporate the PEP modules into their teaching. They field-tested the modules over the year in high school chemistry and biology classes. Teacher knowledge of chemistry and biology increased significantly after the workshop and was maintained for at least a year. Their students (N = 2309) demonstrated a significant increase in knowledge of chemistry and biology concepts, with higher scores as the number of modules used increased. The increase in both teacher and student knowledge in these subjects was similar to that found previously when teachers were provided with onsite professional development. PMID:24882881

Enteric bacterial proteases in inflammatory bowel disease- pathophysiology and clinical implications

PubMed Central

Carroll, Ian M; Maharshak, Nitsan

2013-01-01

Numerous reports have identified a dysbiosis in the intestinal microbiota in patients suffering from inflammatory bowel diseases (IBD), yet the mechanism(s) in which this complex microbial community initiates or perpetuates inflammation remains unclear. The purpose of this review is to present evidence for one such mechanism that implicates enteric microbial derived proteases in the pathogenesis of IBD. We highlight and discuss studies demonstrating that proteases and protease receptors are abundant in the digestive system. Additionally, we investigate studies demonstrating an association between increased luminal protease activity and activation of protease receptors, ultimately resulting in increased intestinal permeability and exacerbation of colitis in animal models as well as in human IBD. Proteases are essential for the normal functioning of bacteria and in some cases can serve as virulence factors for pathogenic bacteria. Although not classified as traditional virulence factors, proteases originating from commensal enteric bacteria also have a potential association with intestinal inflammation via increased enteric permeability. Reports of increased protease activity in stools from IBD patients support a possible mechanism for a dysbiotic enteric microbiota in IBD. A better understanding of these pathways and characterization of the enteric bacteria involved, their proteases, and protease receptors may pave the way for new therapeutic approaches for these diseases. PMID:24431894

Platelet-activating factor receptor agonists mediate xeroderma pigmentosum A photosensitivity.

PubMed

Yao, Yongxue; Harrison, Kathleen A; Al-Hassani, Mohammed; Murphy, Robert C; Rezania, Samin; Konger, Raymond L; Travers, Jeffrey B

2012-03-16

To date, oxidized glycerophosphocholines (Ox-GPCs) with platelet-activating factor (PAF) activity produced non-enzymatically have not been definitively demonstrated to mediate any known disease processes. Here we provide evidence that these Ox-GPCs play a pivotal role in the photosensitivity associated with the deficiency of the DNA repair protein xeroderma pigmentosum type A (XPA). It should be noted that XPA-deficient cells are known to have decreased antioxidant defenses. These studies demonstrate that treatment of human XPA-deficient fibroblasts with the pro-oxidative stressor ultraviolet B (UVB) radiation resulted in increased reactive oxygen species and PAF receptor (PAF-R) agonistic activity in comparison with gene-corrected cells. The UVB irradiation-generated PAF-R agonists were inhibited by antioxidants. UVB irradiation of XPA-deficient (Xpa-/-) mice also resulted in increased PAF-R agonistic activity and skin inflammation in comparison with control mice. The increased UVB irradiation-mediated skin inflammation and TNF-α production in Xpa-/- mice were blocked by systemic antioxidants and by PAF-R antagonists. Structural characterization of PAF-R-stimulating activity in UVB-irradiated XPA-deficient fibroblasts using mass spectrometry revealed increased levels of sn-2 short-chain Ox-GPCs along with native PAF. These studies support a critical role for PAF-R agonistic Ox-GPCs in the pathophysiology of XPA photosensitivity.

Reduction of protection from laser eyewear with ultrashort exposure

NASA Astrophysics Data System (ADS)

Stolarski, David J.; Stolarski, Jacob; Noojin, Gary D.; Rockwell, Benjamin A.; Thomas, Robert J.

2001-07-01

We have measured the optical density of various laser eye protection samples as a function of increasing irradiance. We show that the protective quality of some eyewear degrades as irradiance increases. In previous studies this problem has been demonstrated in samples irradiated by nanosecond pulses, but the current study shows that the modern laser eye protection seems to be robust except for the irradiance possible with ultrashort laser pulse exposure. We discuss the most likely saturation mechanisms in this pulse duration regime and discuss relevance to laser safety.

Oral health promotion: the economic benefits to the NHS of increased use of sugarfree gum in the UK.

PubMed

Claxton, L; Taylor, M; Kay, E

2016-02-12

The effect of sugarfree gum (SFG) on the prevention of dental caries has been established for some time. With increased constraints placed on healthcare budgets, the importance of economic considerations in decision-making about oral health interventions has increased. The aim of this study was to demonstrate the potential cost savings in dental care associated with increased levels of SFG usage. The analysis examined the amount of money which would hypothetically be saved if the UK 12-year-old population chewed more SFG. The number of sticks chewed per year and the caries risk reduction were modelled to create a dose response curve. The costs of tooth restoration, tooth extraction in primary care settings and under general anaesthetic were considered, and the effects of caries reduction on these costs calculated. If all members of the UK 12-year-old population chewed SFG frequently (twice a day), the potential cost savings for the cohort over the course of one year were estimated to range from £1.2 to £3.3 million and if they chewed three times a day, £8.2 million could be saved each year. Sensitivity analyses of the key parameters demonstrated that cost savings would still be likely to be observed even in scenarios with less significant increases in SFG use. This study shows that if levels of SFG usage in the teenage population in the UK could be increased, substantial cost savings might be achieved.

Cyclic Adenosine Monophosphate Regulation of Ion Transport in Porcine Vocal Fold Mucosae

PubMed Central

Sivasankar, Mahalakshmi; Nofziger, Charity; Blazer-Yost, Bonnie

2012-01-01

Objectives/Hypothesis Cyclic adenosine monophosphate (cAMP) is an important biological molecule that regulates ion transport and inflammatory responses in epithelial tissue. The present study examined whether the adenylyl cyclase activator, forskolin, would increase cAMP concentration in porcine vocal fold mucosa and whether the effects of increased cAMP would be manifested as a functional increase in transepithelial ion transport. Additionally, changes in cAMP concentrations following exposure to an inflammatory mediator, tumor necrosis factor-α (TNFα) were investigated. Study Design In vitro experimental design with matched treatment and control groups. Methods Porcine vocal fold mucosae (N = 30) and tracheal mucosae (N = 20) were exposed to forskolin, TNFα, or vehicle (dimethyl sulfoxide) treatment. cAMP concentrations were determined with enzyme-linked immunosorbent assay. Ion transport was measured using electrophysiological techniques. Results Thirty minute exposure to forskolin significantly increased cAMP concentration and ion transport in porcine vocal fold and tracheal mucosae. However, 30-minute and 2-hour exposure to TNFα did not significantly alter cAMP concentration. Conclusions We demonstrate that forskolin-sensitive adenylyl cyclase is present in vocal fold mucosa, and further, that the product, cAMP increases vocal fold ion transport. The results presented here contribute to our understanding of the intracellular mechanisms underlying vocal fold ion transport. As ion transport is important for maintaining superficial vocal fold hydration, data demonstrating forskolin-stimulated ion transport in vocal fold mucosa suggest opportunities for developing pharmacological treatments that increase surface hydration. PMID:18596479

DLX3 regulates bone mass by targeting genes supporting osteoblast differentiation and mineral homeostasis in vivo

PubMed Central

Isaac, J; Erthal, J; Gordon, J; Duverger, O; Sun, H-W; Lichtler, A C; Stein, G S; Lian, J B; Morasso, M I

2014-01-01

Human mutations and in vitro studies indicate that DLX3 has a crucial function in bone development, however, the in vivo role of DLX3 in endochondral ossification has not been established. Here, we identify DLX3 as a central attenuator of adult bone mass in the appendicular skeleton. Dynamic bone formation, histologic and micro-computed tomography analyses demonstrate that in vivo DLX3 conditional loss of function in mesenchymal cells (Prx1-Cre) and osteoblasts (OCN-Cre) results in increased bone mass accrual observed as early as 2 weeks that remains elevated throughout the lifespan owing to increased osteoblast activity and increased expression of bone matrix genes. Dlx3OCN-conditional knockout mice have more trabeculae that extend deeper in the medullary cavity and thicker cortical bone with an increased mineral apposition rate, decreased bone mineral density and increased cortical porosity. Trabecular TRAP staining and site-specific Q-PCR demonstrated that osteoclastic resorption remained normal on trabecular bone, whereas cortical bone exhibited altered osteoclast patterning on the periosteal surface associated with high Opg/Rankl ratios. Using RNA sequencing and chromatin immunoprecipitation-Seq analyses, we demonstrate that DLX3 regulates transcription factors crucial for bone formation such as Dlx5, Dlx6, Runx2 and Sp7 as well as genes important to mineral deposition (Ibsp, Enpp1, Mepe) and bone turnover (Opg). Furthermore, with the removal of DLX3, we observe increased occupancy of DLX5, as well as increased and earlier occupancy of RUNX2 on the bone-specific osteocalcin promoter. Together, these findings provide novel insight into mechanisms by which DLX3 attenuates bone mass accrual to support bone homeostasis by osteogenic gene pathway regulation. PMID:24948010

The Use of Interrupted Case Studies to Enhance Critical Thinking Skills in Biology

PubMed Central

White, Tracy K.; Whitaker, Paul; Gonya, Terri; Hein, Richard; Kroening, Dubear; Lee, Kevin; Lee, Laura; Lukowiak, Andrea; Hayes, Elizabeth

2009-01-01

There has been a dramatic increase in the availability of case studies for use in the biology classroom, and perceptions of the effectiveness of case-study-based learning are overwhelmingly positive. Here we report the results of a study in which we evaluated the ability of interrupted case studies to improve critical thinking in the context of experimental design and the conventions of data interpretation. Students were assessed using further case studies designed to evaluate their ability to recognize and articulate problematic approaches to these elements of experimentation. Our work reveals that case studies have broad utility in the classroom. In addition to demonstrating a small but statistically significant increase in the number of students capable of critically evaluating selected aspects of experimental design, we also observed increased student engagement and documented widespread misconceptions regarding the conventions of data acquisition and analysis. PMID:23653687

Neural and Behavioral Evidence for the Role of Mental Simulation in Meaning in Life

PubMed Central

Waytz, Adam; Hershfield, Hal E; Tamir, Diana I

2014-01-01

Mental simulation, the process of self-projection into alternate temporal, spatial, social, or hypothetical realities is a distinctively human capacity. Numerous lines of research also suggest that the tendency for mental simulation is associated with enhanced meaning. The present research tests this association specifically examining the relationship between two forms of simulation (temporal and spatial) and meaning in life. Study 1 uses neuroimaging to demonstrate that enhanced connectivity in the medial temporal lobe network, a subnetwork of the brain’s default network implicated in prospection and retrospection, correlates with self-reported meaning in life. Study 2 demonstrates that experimentally inducing people to think about the past or future versus the present enhances self-reported meaning in life, through the generation of more meaningful events. Study 3 demonstrates that experimentally inducing people to think specifically versus generally about the past or future enhances self-reported meaning in life. Study 4 turns to spatial simulation to demonstrate that experimentally inducing people to think specifically about an alternate spatial location (from the present) increases meaning derived from this simulation compared to thinking generally about another location or specifically about one’s present location. Study 5 demonstrates that experimentally inducing people to think about an alternate spatial location versus one’s present location enhances meaning in life, through meaning derived from this simulation. Study 6 demonstrates that simply asking people to imagine completing a measure of meaning in life in an alternate location compared to asking them to do so in their present location enhances reports of meaning. This research sheds light on an important determinant of meaning in life and suggests that undirected mental simulation benefits psychological well-being. PMID:25603379

Electrolytic Lesions of the Medial Prefrontal Cortex Do Not Interfere with Long-Term Memory of Extinction of Conditioned Fear

ERIC Educational Resources Information Center

Garcia, Rene; Chang, Chun-hui; Maren, Stephen

2006-01-01

Lesion studies indicate that rats without the medial prefrontal cortex (mPFC) have difficulty recalling fear extinction acquired the previous day. Several electrophysiological studies have also supported this observation by demonstrating that extinction-related increases in neuronal activity in the mPFC participate in expression of fear…

An "egr-1" ("zif268") Antisense Oligodeoxynucleotide Infused into the Amygdala Disrupts Fear Conditioning

ERIC Educational Resources Information Center

Donley, Melanie P.; Rosen, Jeffrey B.; Malkani, Seema; Wallace, Karin J.

2004-01-01

Studies of gene expression following fear conditioning have demonstrated that the inducible transcription factor, "egr-1," is increased in the lateral nucleus of the amygdala shortly following fear conditioning. These studies suggest that "egr-1" and its protein product Egr-1 in the amygdala are important for learning and memory of fear. To…

Functional Developmental Similarities and Differences in the Neural Correlates of Verbal and Nonverbal Working Memory Tasks

ERIC Educational Resources Information Center

Brahmbhatt, Shefali B.; McAuley, Tara; Barch, Deanna M.

2008-01-01

Relatively little is known about the functional development of verbal and nonverbal working memory during adolescence. Behavioral studies have demonstrated that WM capacity increases with age, yet relatively few studies have assessed the relationship between brain-activity and age-related changes in WM capacity, especially as it differs across…

High or Low Target Prevalence Increases the Dual-Target Cost in Visual Search

ERIC Educational Resources Information Center

Menneer, Tamaryn; Donnelly, Nick; Godwin, Hayward J.; Cave, Kyle R.

2010-01-01

Previous studies have demonstrated a dual-target cost in visual search. In the current study, the relationship between search for one and search for two targets was investigated to examine the effects of target prevalence and practice. Color-shape conjunction stimuli were used with response time, accuracy and signal detection measures. Performance…

Study and program plan for improved heavy duty gas turbine engine ceramic component development

NASA Technical Reports Server (NTRS)

Helms, H. E.

1977-01-01

Fuel economy in a commercially viable gas turbine engine was demonstrated through use of ceramic materials. Study results show that increased turbine inlet and generator inlet temperatures, through the use of ceramic materials, contribute the greatest amount to achieving fuel economy goals. Improved component efficiencies show significant additional gains in fuel economy.

An Explanation of the Effectiveness of Written Corrective Feedback in Second-Language Acquisition

ERIC Educational Resources Information Center

Wagner, Jason

2016-01-01

The purpose of this study is to provide a theoretical explanation for the effectiveness of Written Corrective Feedback (WCF) in increasing second-language (L2) students' grammatical accuracy. WCF is examined via Skill Acquisition Theory (SAT) in order to account for uneven patterns of its effectiveness. As the study demonstrates, WCF is effective…

Model Dropout Prevention Program at Reidsville Middle School: A Case Study Evaluation.

ERIC Educational Resources Information Center

O'Sullivan, Rita G.

This case study describes a 2-year (1988-90) demonstration dropout prevention program, a collaboration between a rural school and a university. The dropout prevention program attempts to identify effective teaching strategies that will increase the academic successes of at-risk sixth-grade students and expand the use of those strategies among the…