High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients

Directory of Open Access Journals (Sweden)

Kanda Eiichiro

2013-01-01

Full Text Available Abstract Background Metabolic acidosis leads to chronic kidney disease (CKD progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression. Methods One hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR or starting dialysis. We used Cox proportional hazard models adjusted for patients’ characteristics to examine the association between serum bicarbonate level and the outcome. Results Female patients were 36.3%: average age (SD, 70.4 (6.6 years; eGFR, 25.7 (13.6 ml/min/1.73 m2; serum bicarbonate level, 27.4 (3.2 mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8 mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3 mEq/l]: adjusted hazard ratio (HR, 3.511 (95% CI, 1.342-9.186. A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI, 0.684-0.914]. Conclusions In elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression.

CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis

DEFF Research Database (Denmark)

Romme Christensen, Jeppe; Börnsen, Lars; Khademi, Mohsen

2013-01-01

BACKGROUND: The mechanism underlying disease progression in progressive multiple sclerosis (MS) is uncertain. Pathological studies found widespread inflammation in progressive MS brains correlating with disease progression and axonal damage. OBJECTIVES: To study cerebrospinal fluid (CSF) biomarkers...... and clarify whether inflammation and axonal damage are associated in progressive MS. METHODS: Using enzyme-linked immunosorbent assay (ELISA), we analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing-remitting (RRMS) and 20 non-inflammatory neurological disease...... (NIND) patients. Twenty-two of the SPMS patients participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year. RESULTS: Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MS patients while CXCL13...

Does global progress on sanitation really lag behind water? An analysis of global progress on community- and household-level access to safe water and sanitation.

Science.gov (United States)

Cumming, Oliver; Elliott, Mark; Overbo, Alycia; Bartram, Jamie

2014-01-01

Safe drinking water and sanitation are important determinants of human health and wellbeing and have recently been declared human rights by the international community. Increased access to both were included in the Millennium Development Goals under a single dedicated target for 2015. This target was reached in 2010 for water but sanitation will fall short; however, there is an important difference in the benchmarks used for assessing global access. For drinking water the benchmark is community-level access whilst for sanitation it is household-level access, so a pit latrine shared between households does not count toward the Millennium Development Goal (MDG) target. We estimated global progress for water and sanitation under two scenarios: with equivalent household- and community-level benchmarks. Our results demonstrate that the "sanitation deficit" is apparent only when household-level sanitation access is contrasted with community-level water access. When equivalent benchmarks are used for water and sanitation, the global deficit is as great for water as it is for sanitation, and sanitation progress in the MDG-period (1990-2015) outstrips that in water. As both drinking water and sanitation access yield greater benefits at the household-level than at the community-level, we conclude that any post-2015 goals should consider a household-level benchmark for both.

Increased plasma levels of soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1) in women by moderate exercise and increased plasma levels of VEGF in overweight/obese women

Science.gov (United States)

Makey, Kristina L.; Patterson, Sharla G.; Robinson, James; Loftin, Mark; Waddell, Dwight E.; Miele, Lucio; Chinchar, Edmund; Huang, Min; Smith, Andrew D.; Weber, Mark; Gu, Jian-Wei

2012-01-01

The incidence of breast cancer is increasing worldwide, and this seems to be related to an increase in lifestyle risk factors, including physical inactivity, and overweight/obesity. We previously reported that exercise induced a circulating angiostatic phenotype characterized by increased sFlt-1 and endostatin and decreased unbound-VEGF in men. However, there is no data on women. The present study determines the following: 1) whether moderate exercise increased sFlt-1 and endostatin and decreased unbound-VEGF in the circulation of adult female volunteers; 2) whether overweight/obese women have a higher plasma level of unbound-VEGF than lean women. 72 African American and Caucasian adult women volunteers aged from 18–44 were enrolled into the exercise study. All the participants walked on a treadmill for 30 minutes at a moderate intensity (55–59% heart rate reserve), and oxygen consumption (VO2) was quantified by utilizing a metabolic cart. We had the blood samples before and immediately after exercise from 63 participants. ELISA assays (R&D Systems) showed that plasma levels of sFlt-1 were 67.8±3.7 pg/ml immediately after exercise (30 minutes), significantly higher than basal levels, 54.5±3.3 pg/ml, before exercise (P < 0.01; n=63). There was no significant difference in the % increase of sFlt-1 levels after exercise between African American and Caucasian (P=0.533) or between lean and overweight/obese women (P=0.892). There was no significant difference in plasma levels of unbound VEGF (35.28±5.47 vs. 35.23±4.96 pg/ml; P=0.99) or endostatin (111.12±5.48 vs. 115.45±7.15 ng/ml; P=0.63) before and after exercise. Basal plasma levels of unbound-VEGF in overweight/obese women were 52.26±9.6 pg/ml, significantly higher than basal levels of unbound-VEGF in lean women, 27.34±4.99 pg/ml (P < 0.05). The results support our hypothesis that exercise-induced plasma levels of sFlt-1 could be an important clinical biomarker to explore the mechanisms of exercise

1989 Annual report on low-level radioactive waste management progress

International Nuclear Information System (INIS)

1990-10-01

This report summarizes the progress during 1989 of states and compacts in establishing new low-level radioactive waste disposal facilities. It also provides summary information on the volume of low-level waste received for disposal in 1989 by commercially operated low-level waste disposal facilities. This report is in response to Section 7(b) of Title I of Public Law 99--240, the Low-Level Radioactive Waste Policy Amendments Act of 1985. 2 figs., 5 tabs

Report to Congress: 1995 Annual report on low-level radioactive waste management progress

International Nuclear Information System (INIS)

1996-06-01

This report is prepared in response to the Low-Level Radioactive Waste Policy Act, Public Law 96-573, 1980, as amended by the Low-Level Radioactive Waste Policy Amendments Act of 1985, Public Law 99-240. The report summarizes the progress of states and compact regions during calendar year 1995 in establishing new disposal facilities for commercially-generated low-level radioactive waste. The report emphasizes significant issues and events that have affected progress, and also includes an introduction that provides background information and perspective on United States policy for low-level radioactive waste disposal

Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation

Science.gov (United States)

Butcher, Joshua T.; Frisbee, Stephanie J.; Olfert, I. Mark; Chantler, Paul D.; Tabone, Lawrence E.; d'Audiffret, Alexandre C.; Shrader, Carl D.; Goodwill, Adam G.; Stapleton, Phoebe A.; Brooks, Steven D.; Brock, Robert W.; Lombard, Julian H.

2015-01-01

To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning “healthy” to “high PVD risk” and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2 levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk. PMID:26702145

A process for developing and revising a learning progression on sea level rise using learners' explanations

Science.gov (United States)

McDonald, Robert Christopher

The purpose of this study was to explore the process of developing a learning progression (LP) on constructing explanations about sea level rise. I used a learning progressions theoretical framework informed by the situated cognition learning theory. During this exploration, I explicitly described my decision-making process as I developed and revised a hypothetical learning progression. Correspondingly, my research question was: What is a process by which a hypothetical learning progression on sea level rise is developed into an empirical learning progression using learners' explanations? To answer this question, I used a qualitative descriptive single case study with multiple embedded cases (Yin, 2014) that employed analytic induction (Denzin, 1970) to analyze data collected on middle school learners (grades 6-8). Data sources included written artifacts, classroom observations, and semi-structured interviews. Additionally, I kept a researcher journal to track my thinking about the learning progression throughout the research study. Using analytic induction to analyze collected data, I developed eight analytic concepts: participant explanation structures varied widely, global warming and ice melt cause sea level rise, participants held alternative conceptions about sea level rise, participants learned about thermal expansion as a fundamental aspect of sea level rise, participants learned to incorporate authentic scientific data, participants' mental models of the ocean varied widely, sea ice melt contributes to sea level rise, and participants held vague and alternative conceptions about how pollution impacts the ocean. I started with a hypothetical learning progression, gathered empirical data via various sources (especially semi-structured interviews), revised the hypothetical learning progression in response to those data, and ended with an empirical learning progression comprising six levels of learner thinking. As a result of developing an empirically based LP

Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

Science.gov (United States)

Laddha, Naresh C.; Dwivedi, Mitesh; Begum, Rasheedunnisa

2012-01-01

Abstract Tumor Necrosis Factor (TNF)-α, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-α. Genetic polymorphisms in the promoter region of TNF-α are involved in the regulation of its expression. The present study explores TNF-α promoter polymorphisms and correlates them with TNF-α transcript and protein levels in vitiligo patients and controls of Gujarat along with its effect on disease onset and progression. PCR-RFLP technique was used for genotyping of these polymorphisms in 977 vitiligo patients and 990 controls. TNF-α transcript and protein levels were measured by Real time PCR and ELISA respectively. The genotype and allele frequencies for the investigated polymorphisms were significantly associated with vitiligo patients. The study revealed significant increase in TNF-α transcript and protein levels in vitiligo patients compared to controls. In particular, haplotypes: AATCC, AACCT, AGTCT, GATCT, GATCC and AGCCT were found to increase the TNF-α levels in vitiligo patients. Analysis of TNF-α levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-α. Also, the TNF-α levels were high in patients with generalized vitiligo as compared to localized vitiligo. Age of onset analysis of the disease suggests that the haplotypes: AACAT, AACCT, AATCC and AATCT had a profound effect in the early onset of the disease. Moreover, the analysis suggests that female patients had an early onset of vitiligo. Overall, our results suggest that TNF-α promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-α transcript and protein levels in individuals with susceptible haplotypes advocates

Worsening Cognitive Impairment and Neurodegenerative Pathology Progressively Increase Risk for Delirium

Science.gov (United States)

Davis, Daniel H.J.; Skelly, Donal T.; Murray, Carol; Hennessy, Edel; Bowen, Jordan; Norton, Samuel; Brayne, Carol; Rahkonen, Terhi; Sulkava, Raimo; Sanderson, David J.; Rawlins, J. Nicholas; Bannerman, David M.; MacLullich, Alasdair M.J.; Cunningham, Colm

2015-01-01

Background Delirium is a profound neuropsychiatric disturbance precipitated by acute illness. Although dementia is the major risk factor this has typically been considered a binary quantity (i.e., cognitively impaired versus cognitively normal) with respect to delirium risk. We used humans and mice to address the hypothesis that the severity of underlying neurodegenerative changes and/or cognitive impairment progressively alters delirium risk. Methods Humans in a population-based longitudinal study, Vantaa 85+, were followed for incident delirium. Odds for reporting delirium at follow-up (outcome) were modeled using random-effects logistic regression, where prior cognitive impairment measured by Mini-Mental State Exam (MMSE) (exposure) was considered. To address whether underlying neurodegenerative pathology increased susceptibility to acute cognitive change, mice at three stages of neurodegenerative disease progression (ME7 model of neurodegeneration: controls, 12 weeks, and 16 weeks) were assessed for acute cognitive dysfunction upon systemic inflammation induced by bacterial lipopolysaccharide (LPS; 100 μg/kg). Synaptic and axonal correlates of susceptibility to acute dysfunction were assessed using immunohistochemistry. Results In the Vantaa cohort, 465 persons (88.4 ± 2.8 years) completed MMSE at baseline. For every MMSE point lost, risk of incident delirium increased by 5% (p = 0.02). LPS precipitated severe and fluctuating cognitive deficits in 16-week ME7 mice but lower incidence or no deficits in 12-week ME7 and controls, respectively. This was associated with progressive thalamic synaptic loss and axonal pathology. Conclusion A human population-based cohort with graded severity of existing cognitive impairment and a mouse model with progressing neurodegeneration both indicate that the risk of delirium increases with greater severity of pre-existing cognitive impairment and neuropathology. PMID:25239680

Personalized Age Progression with Bi-Level Aging Dictionary Learning.

Science.gov (United States)

Shu, Xiangbo; Tang, Jinhui; Li, Zechao; Lai, Hanjiang; Zhang, Liyan; Yan, Shuicheng

2018-04-01

Age progression is defined as aesthetically re-rendering the aging face at any future age for an individual face. In this work, we aim to automatically render aging faces in a personalized way. Basically, for each age group, we learn an aging dictionary to reveal its aging characteristics (e.g., wrinkles), where the dictionary bases corresponding to the same index yet from two neighboring aging dictionaries form a particular aging pattern cross these two age groups, and a linear combination of all these patterns expresses a particular personalized aging process. Moreover, two factors are taken into consideration in the dictionary learning process. First, beyond the aging dictionaries, each person may have extra personalized facial characteristics, e.g., mole, which are invariant in the aging process. Second, it is challenging or even impossible to collect faces of all age groups for a particular person, yet much easier and more practical to get face pairs from neighboring age groups. To this end, we propose a novel Bi-level Dictionary Learning based Personalized Age Progression (BDL-PAP) method. Here, bi-level dictionary learning is formulated to learn the aging dictionaries based on face pairs from neighboring age groups. Extensive experiments well demonstrate the advantages of the proposed BDL-PAP over other state-of-the-arts in term of personalized age progression, as well as the performance gain for cross-age face verification by synthesizing aging faces.

Increased plasma levels of soluble vascular endothelial growth factor receptor 1 (sFlt-1) in women by moderate exercise and increased plasma levels of vascular endothelial growth factor in overweight/obese women.

Science.gov (United States)

Makey, Kristina L; Patterson, Sharla G; Robinson, James; Loftin, Mark; Waddell, Dwight E; Miele, Lucio; Chinchar, Edmund; Huang, Min; Smith, Andrew D; Weber, Mark; Gu, Jian-Wei

2013-01-01

The incidence of breast cancer is increasing worldwide, and this seems to be related to an increase in lifestyle risk factors, including physical inactivity and overweight/obesity. We have reported previously that exercise induced a circulating angiostatic phenotype characterized by increased soluble fms-like tyrosine kinase-1 (sFlt-1) and endostatin and decreased unbound vascular endothelial growth factor (VEGF) in men. However, there are no data on women. The present study determines the following: (a) whether moderate exercise increased sFlt-1 and endostatin and decreased unbound VEGF in the circulation of adult female volunteers and (b) whether overweight/obese women have a higher plasma level of unbound VEGF than lean women. A total of 72 African American and White adult women volunteers ranging in age from 18 to 44 years were enrolled in the exercise study. All the participants walked on a treadmill for 30 min at a moderate intensity (55-59% heart rate reserve), and oxygen consumption (VO(2)) was quantified utilizing a metabolic cart. We obtained blood samples before and immediately after exercise from 63 participants. ELISA assays showed that the plasma levels of sFlt-1 were 67.8±3.7 pg/ml immediately after exercise (30 min), significantly higher than the basal levels, 54.5±3.3 pg/ml, before exercise (P<0.01; n=63). There was no significant difference in the % increase in the sFlt-1 levels after exercise between African American and White (P=0.533) women or between lean and overweight/obese women (P=0.892). There was no significant difference in the plasma levels of unbound VEGF (35.28±5.47 vs. 35.23±4.96 pg/ml; P=0.99) or endostatin (111.12±5.48 vs. 115.45±7.15 ng/ml; P=0.63) before and after exercise. The basal plasma levels of unbound VEGF in overweight/obese women were 52.26±9.6 pg/ml, significantly higher than the basal levels of unbound VEGF in lean women, 27.34±4.99 pg/ml (P<0.05). The results support our hypothesis that exercise

Androgen receptor levels during progression of prostate cancer in the transgenic adenocarcinoma of mouse prostate model

Directory of Open Access Journals (Sweden)

Krisna Murti

2010-02-01

Full Text Available Aim To construct tissue microarrays (TMAs that consisted of prostate tumours from the transgenic adenocarcinoma of mouse prostate (TRAMP mice and non-transgenic murine prostates and to assess androgen receptor (AR levels during progression of prostate cancer in TRAMP mice by immunohistochemistry.Methods Haematoxylin and eosin (H&E sections from the ventral and dorso-lateral prostate lobes of non-transgenic, intact TRAMP and castrated TRAMP were used to demarcate regions of interest for TMAs construction. The samples on TMAs were used to evaluate AR expression using video image analysis (VIA.Results AR was expressed during cancer progression, but AR levels were reduced or absent in late stage disease. Furthermore, when AR levels were compared in tumours from intact and castrate animals, a significant increase in AR levels was observed following androgen ablation.Conclusion Similar to clinical prostate cancer, in the TRAMP model, prostate tumours evolve mechanisms to maintain AR expression and AR responsive gene pathways following castration to facilitate continued tumour growth. (Med J Indones 2010; 19:5-13Keywords : androgen ablation therapy, tissue microarrays, haematoxylin and eosin, video image analysis

The grey areas in soil pollution risk mapping : The distinction between cases of soil pollution and increased background levels

NARCIS (Netherlands)

Gaast, N. van der; Leenaers, H.; Zegwaard, J.

1998-01-01

The progress of soil clean up in the Netherlands is severely hindered by the lack of common agreement on how to describe the grey areas of increased background levels of pollutants. In this study practical methods are proposed in which background levels are described as distribution functions within

Progressive senile scoliosis: Seven cases of increasing spinal curves in elderly patients

Energy Technology Data Exchange (ETDEWEB)

Gillespy, T. III; Gillespy, T. Jr.; Revak, C.S.

1985-04-01

An increasing scoliosis was documented in seven elderly women. The average curve at the most recent examination was 43/sup 0/ (range 26/sup 0/-78/sup 0/). Previous films, from 5 to 26 years before, demonstrated an average increase of 2.3/sup 0//year (range 1/sup 0/-4.8/sup 0//year). There were three lumbar and four thoracolumbar curves. Three curves were to the right and four were to the left. Only one patient had osteoporotic vertebral body crush fractures. The common underlying mechanism in the progression of senile scoliosis appears to be asymmetric loading of the spine which can be caused by a previously established scoliosis, spondylolysis/spondylolisthesis, lumbosacral anomalies, or leg length discrepancy. Subsequently, factors that can cause a curve to increase include degenerative disc disease with lateral disc space narrowing, soft tissue failure, and osteoporosis. Since even minor scoliosis can potentially progress in the older adult, increased monitoring of scoliosis in patients over age 50 years may be warranted.

Progressive senile scoliosis: Seven cases of increasing spinal curves in elderly patients

International Nuclear Information System (INIS)

Gillespy, T. III; Revak, C.S.

1985-01-01

An increasing scoliosis was documented in seven elderly women. The average curve at the most recent examination was 43 0 (range 26 0 -78 0 ). Previous films, from 5 to 26 years before, demonstrated an average increase of 2.3 0 /year (range 1 0 -4.8 0 /year). There were three lumbar and four thoracolumbar curves. Three curves were to the right and four were to the left. Only one patient had osteoporotic vertebral body crush fractures. The common underlying mechanism in the progression of senile scoliosis appears to be asymmetric loading of the spine which can be caused by a previously established scoliosis, spondylolysis/spondylolisthesis, lumbosacral anomalies, or leg length discrepancy. Subsequently, factors that can cause a curve to increase include degenerative disc disease with lateral disc space narrowing, soft tissue failure, and osteoporosis. Since even minor scoliosis can potentially progress in the older adult, increased monitoring of scoliosis in patients over age 50 years may be warranted. (orig.)

Impact of the Level of State Tax Code Progressivity on Children's Health Outcomes

Science.gov (United States)

Granruth, Laura Brierton; Shields, Joseph J.

2011-01-01

This research study examines the impact of the level of state tax code progressivity on selected children's health outcomes. Specifically, it examines the degree to which a state's tax code ranking along the progressive-regressive continuum relates to percentage of low birthweight babies, infant and child mortality rates, and percentage of…

Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage

Directory of Open Access Journals (Sweden)

Agnieszka Morel

2015-01-01

Full Text Available Multiple sclerosis (MS is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases were examined to evaluate the biological activity of blood platelets (adhesion, aggregation, especially their response to the most important physiological agonists (thrombin, ADP, and collagen and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2-∙ in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets.

Ovine progressive pneumonia provirus levels are unaffected by the prion 171R allele in an Idaho sheep flock.

Science.gov (United States)

Harrington, Robert D; Herrmann-Hoesing, Lynn M; White, Stephen N; O'Rourke, Katherine I; Knowles, Donald P

2009-01-22

Selective breeding of sheep for arginine (R) at prion gene (PRNP) codon 171 confers resistance to classical scrapie. However, other effects of 171R selection are uncertain. Ovine progressive pneumonia/Maedi-Visna virus (OPPV) may infect up to 66% of a flock thus any affect of 171R selection on OPPV susceptibility or disease progression could have major impact on the sheep industry. Hypotheses that the PRNP 171R allele is 1) associated with the presence of OPPV provirus and 2) associated with higher provirus levels were tested in an Idaho ewe flock. OPPV provirus was found in 226 of 358 ewes by quantitative PCR. The frequency of ewes with detectable provirus did not differ significantly among the 171QQ, 171QR, and 171RR genotypes (p > 0.05). Also, OPPV provirus levels in infected ewes were not significantly different among codon 171 genotypes (p > 0.05). These results show that, in the flock examined, the presence of OPPV provirus and provirus levels are not related to the PRNP 171R allele. Therefore, a genetic approach to scrapie control is not expected to increase or decrease the number of OPPV infected sheep or the progression of disease. This study provides further support to the adoption of PRNP 171R selection as a scrapie control measure.

Assessment of a progressive electricity tax

International Nuclear Information System (INIS)

2000-01-01

Progressive electricity tax implies that the tax rate increases with consumption so that the tax paid per kWh consumed increases when the consumption increases beyond a certain level. This elucidation discusses principal and practical aspects of such a tax. It is advised against the establishment of a progressive electricity tax. The objections are of principal, economical and administrative character

Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model.

Science.gov (United States)

Gorden, D Lee; Ivanova, Pavlina T; Myers, David S; McIntyre, J Oliver; VanSaun, Michael N; Wright, J Kelly; Matrisian, Lynn M; Brown, H Alex

2011-01-01

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to cirrhosis. While differences in liver lipids between disease states have been reported, precise composition of phospholipids and diacylglycerols (DAG) at a lipid species level has not been previously described. The goal of this study was to characterize changes in lipid species through progression of human NAFLD using advanced lipidomic technology and compare this with a murine model of early and advanced NAFLD. Utilizing mass spectrometry lipidomics, over 250 phospholipid and diacylglycerol species (DAGs) were identified in normal and diseased human and murine liver extracts. Significant differences between phospholipid composition of normal and diseased livers were demonstrated, notably among DAG species, consistent with previous reports that DAG transferases are involved in the progression of NAFLD and liver fibrosis. In addition, a novel phospholipid species (ether linked phosphatidylinositol) was identified in human cirrhotic liver extracts. Using parallel lipidomics analysis of murine and human liver tissues it was determined that mice maintained on a high-fat diet provide a reproducible model of NAFLD in regards to specificity of lipid species in the liver. These studies demonstrated that novel lipid species may serve as markers of advanced liver disease and importantly, marked increases in DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels characteristic of the disease and specific DAG species might be important lipid signaling molecules in the progression of NAFLD.

Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

KAUST Repository

Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W.; Riebesell, Ulf; Gao, Kunshan

2015-01-01

Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130–160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28–48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

KAUST Repository

Jin, Peng

2015-10-27

Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130–160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28–48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

Measuring progress of the global sea level observing system

Science.gov (United States)

Woodworth, Philip L.; Aarup, Thorkild; Merrifield, Mark; Mitchum, Gary T.; Le Provost, Christian

Sea level is such a fundamental parameter in the sciences of oceanography geophysics, and climate change, that in the mid-1980s, the Intergovernmental Oceanographic Commission (IOC) established the Global Sea Level Observing System (GLOSS). GLOSS was to improve the quantity and quality of data provided to the Permanent Service for Mean Sea Level (PSMSL), and thereby, data for input to studies of long-term sea level change by the Intergovernmental Panel on Climate Change (IPCC). It would also provide the key data needed for international programs, such as the World Ocean Circulation Experiment (WOCE) and later, the Climate Variability and Predictability Programme (CLIVAR).GLOSS is now one of the main observation components of the Joint Technical Commission for Oceanography and Marine Meteorology (JCOMM) of IOC and the World Meteorological Organization (WMO). Progress and deficiencies in GLOSS were presented in July to the 22nd IOC Assembly at UNESCO in Paris and are contained in the GLOSS Assessment Report (GAR) [IOC, 2003a].

Does nerve-sparing radical prostatectomy increase the risk of positive surgical margins and biochemical progression?

Directory of Open Access Journals (Sweden)

Alkhateeb Sultan

2010-01-01

Full Text Available Background: Since the introduction of nerve-sparing radical prostatectomy (NSRP, there have been concerns about the increased risks of positive surgical margins (PSM and biochemical progression (BP. We examined the relationship of NSRP with PSM and BP using a large, mature dataset. Materials and Methods: Patients who underwent RP for clinically localized prostate cancer at our center between 1997 and 2008 were identified. Patients who received neoadjuvant therapy were excluded. We examined the relation of NSRP to the rate of PSM and BP in univariate and multivariate analyses adjusting for clinical and pathological variables including age, pretreatment prostate-specific antigen (PSA levels and doubling time, and pathological stage and grade. Results: In total, 856 patients were included, 70.9% underwent NSRP and 29.1% had non-NSRP. PSM rates were 13.5% in the NSRP group compared to 17.7% in non-NSRP (P=0.11. In a multivariate analysis, non-NSRP was preformed in patients with a higher pathological stage (HR 1.95, 95% CI 1.25-3.04, P=0.003 and a higher baseline PSA level (HR 1.04, 95% CI 1.01-1.08, P=0.005. With a median follow-up of 41 months, BP-free survival was 88% for non-NSRP compared to 92% for the NSRP group (log rank P=0.018; this difference was not significant in a multivariate Cox regression analysis (HR 0.54, 95% CI 0.28-1.06, P=0.09. Conclusion: When used in properly selected patients, NSRP does not seem to increase the risk of PSM and disease progression. The most effective way of resolving this issue is through a randomized clinical trial; however, such a trial is not feasible.

Ovine progressive pneumonia provirus levels are unaffected by the prion 171R allele in an Idaho sheep flock

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Herrmann-Hoesing Lynn M

2009-01-01

Full Text Available Abstract Selective breeding of sheep for arginine (R at prion gene (PRNP codon 171 confers resistance to classical scrapie. However, other effects of 171R selection are uncertain. Ovine progressive pneumonia/Maedi-Visna virus (OPPV may infect up to 66% of a flock thus any affect of 171R selection on OPPV susceptibility or disease progression could have major impact on the sheep industry. Hypotheses that the PRNP 171R allele is 1 associated with the presence of OPPV provirus and 2 associated with higher provirus levels were tested in an Idaho ewe flock. OPPV provirus was found in 226 of 358 ewes by quantitative PCR. The frequency of ewes with detectable provirus did not differ significantly among the 171QQ, 171QR, and 171RR genotypes (p > 0.05. Also, OPPV provirus levels in infected ewes were not significantly different among codon 171 genotypes (p > 0.05. These results show that, in the flock examined, the presence of OPPV provirus and provirus levels are not related to the PRNP 171R allele. Therefore, a genetic approach to scrapie control is not expected to increase or decrease the number of OPPV infected sheep or the progression of disease. This study provides further support to the adoption of PRNP 171R selection as a scrapie control measure.

Significant progress towards development of the low-level radioactive waste disposal facility in Illinois

International Nuclear Information System (INIS)

Klebe, M.; Henry, T.L.; Corpstein, P.

1996-01-01

Development of disposal sites for low-level radioactive waste is a complicated legal, regulatory and public sector process. Development of the low-level radioactive waste disposal facility to support generators in Illinois and Kentucky is well under way. Significant progress has been made to re-engineer the siting development process capitalizing on prior lessons learned and a recommitment from Illinois state leadership assuring the future success of the program. Comparisons of why this new process will succeed are the major focus of this paper. Specific changes in approach from the previous process including changes in the Illinois Management Act (Management Act), creation of the Illinois Low-Level Radioactive Waste Siting Task Group (Task Group), new roles for the Illinois State Geologic Survey and Illinois State Water Survey (Scientific Surveys) and the Illinois Department of Nuclear Safety (IDNS), a new contractor reliance approach and increased confidence on the open-quote science close-quote are the major contrasts between the previous process and the new process currently underway

Is TB Testing Associated With Increased Blood Interferon-Gamma Levels?

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Aideen E. Kennedy

2017-10-01

Full Text Available The Republic of Ireland reports a relatively low prevalence of Johne’s disease (JD compared to international counterparts. Postulated reasons for this include a lower average herd size and a grass-based production system. Ireland also engages in high levels of bovine tuberculosis (bTB testing. As interferon-gamma (IFN-γ is believed to play a key role in protecting against JD, it is our hypothesis that administration of purified protein derivative (PPD, as part of the bTB test, is associated with a systemic increase in IFN-γ production, which may potentially limit clinical progression of the disease. We studied 265 cows (202 Friesian and 63 “Non-Friesian,” e.g., JerseyX, Norwegian Red to assess IFN-γ levels and Mycobacterium avium subspecies paratuberculosis (MAP antibody response before and after the bTB test. As part of the compulsory annual bTB test, avian and bovine PPD were administered at two separate cervical sites. To assess IFN-γ production, blood samples were taken before and 72 h after PPD administration. MAP antibody response was assessed before and 10 days post-PPD administration. A significant increase in MAP antibody response was identified post-bTB compared to pre-bTB response (p < 0.001. Additionally, IFN-γ production significantly increased at the post-bTB time point (p < 0.001 compared to the pre-bTB test readings. This may indicate a beneficial effect of bTB testing in controlling JD.

Homelessness Outcome Reporting Normative Framework: Systems-Level Evaluation of Progress in Ending Homelessness

Science.gov (United States)

Austen, Tyrone; Pauly, Bernie

2012-01-01

Homelessness is a serious and growing issue. Evaluations of systemic-level changes are needed to determine progress in reducing or ending homelessness. The report card methodology is one means of systems-level assessment. Rather than solely establishing an enumeration, homelessness report cards can capture pertinent information about structural…

INCREASED FAT INTAKE MAY STABILIZED CKD PROGRESSION IN LOW-FAT INTAKE PATIENTS

Directory of Open Access Journals (Sweden)

Min-Yu Chang

2012-06-01

Inadequate calories intake will induce excessive protein catabolism, which can cause accumulation of uremic toxins and acceleration of renal failure. Increasing fats intake is an easy way to achieve adequate calories acquirement and may stabilize the progression of CKD especially in low-fat intake patients.

Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection.

Science.gov (United States)

Suh, Joome; Sinclair, Elizabeth; Peterson, Julia; Lee, Evelyn; Kyriakides, Tassos C; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Price, Richard W; Gisslen, Magnus; Spudich, Serena

2014-12-03

Central nervous system (CNS) inflammation is a mediator of brain injury in HIV infection. To study the natural course of CNS inflammation in the early phase of infection, we analyzed longitudinal levels of soluble and cellular markers of inflammation in cerebrospinal fluid (CSF) and blood, beginning with primary HIV-1 infection (PHI). Antiretroviral-naïve subjects identified as having PHI (less than one year since HIV transmission) participated in phlebotomy and lumbar puncture at baseline and at variable intervals thereafter. Mixed-effects models were used to analyze longitudinal levels of CSF neopterin and percentages of activated cluster of differentiation (CD)4+ and CD8+ T-cells (co-expressing CD38 and human leukocyte antigen-D-related (HLA-DR)) in blood and CSF. A total of 81 subjects were enrolled at an average of 100 days after HIV transmission and had an average follow-up period of 321 days, with the number of visits ranging from one to 13. At baseline, the majority of subjects had CSF neopterin concentrations above the upper limit of normal. The baseline concentration was associated with the longitudinal trajectory of CSF neopterin. In subjects with baseline levels of less than 21 nmol/L, a cutoff value obtained from a mixed-effects model, CSF neopterin increased by 2.9% per 10 weeks (n = 33; P <0.001), whereas it decreased by 6.7% in subjects with baseline levels of more than 21 nmol/L (n = 11; P = 0.001). In a subset with available flow cytometry data (n = 42), the percentages of activated CD4+ and CD8+ T-cells in CSF increased by 0.8 (P <0.001) and 0.73 (P = 0.02) per 10 weeks, respectively. Neopterin levels and the percentages of activated CD4+ and CD8+ T-cells in CSF progressively increase in most subjects without treatment during early HIV-1 infection, suggesting an accrual of intrathecal inflammation, a major contributor to neuropathology in HIV infection.

1994 annual report on low-level radioactive waste management progress

International Nuclear Information System (INIS)

1995-04-01

This report for calendar year 1994 summarizes the progress that states and compact regions made during the year in establishing new low-level radioactive waste disposal facilities. Although events that have occurred in 1995 greatly alter the perspective in terms of storage versus disposal, the purpose of this report is to convey the concerns as evidenced during calendar year 1994. Significant developments occurring in 1995 are briefly outlined in the transmittal letter and will be detailed in the report for calendar year 1995. The report also provides summary information on the volume of low-level radioactive waste received for disposal in 1994 by commercially operated low-level radioactive waste disposal facilities, and is prepared is in response to Section 7(b) of Title I of Public Law 99-240, the Low-Level Radioactive Waste Policy Amendments Act of 1985

D-dimer levels and stroke progression in patients with acute ischemic stroke and atrial fibrillation

DEFF Research Database (Denmark)

Krarup, L-H; Sandset, E C; Sandset, P M

2011-01-01

Krarup L-H, Sandset EC, Sandset PM, Berge E. D-dimer levels and stroke progression in patients with acute ischemic stroke and atrial fibrillation. Acta Neurol Scand: 2011: 124: 40-44. © 2010 John Wiley & Sons A/S. Background -  Patients with acute ischemic stroke and atrial fibrillation are at in......Krarup L-H, Sandset EC, Sandset PM, Berge E. D-dimer levels and stroke progression in patients with acute ischemic stroke and atrial fibrillation. Acta Neurol Scand: 2011: 124: 40-44. © 2010 John Wiley & Sons A/S. Background -  Patients with acute ischemic stroke and atrial fibrillation.......96), and the combined endpoint of stroke progression, recurrent stroke, and death (D-dimer: 991 ng/ml vs 970 ng/ml, P = 0.91). Multivariable analyses did not alter the results. Conclusion -  D-dimer and other markers of hemostatic activation were not associated with stroke progression, recurrent stroke, or death...

Increase in serum albumin concentration is associated with prediabetes development and progression to overt diabetes independently of metabolic syndrome.

Science.gov (United States)

Jun, Ji Eun; Lee, Seung-Eun; Lee, You-Bin; Jee, Jae Hwan; Bae, Ji Cheol; Jin, Sang-Man; Hur, Kyu Yeon; Lee, Moon-Kyu; Kim, Jae Hyeon

2017-01-01

Serum albumin concentration is associated with both type 2 diabetes and metabolic syndrome (MetS). We sought to investigate whether baseline serum albumin and change in serum albumin could be independent risk factors for prediabetes in subjects without MetS. We further examined the effect of serum albumin on progression to overt diabetes in subjects who developed prediabetes. Among 10,792 participants without diabetes and MetS who consecutively underwent yearly health check-ups over six years, 9,807 subjects without incident MetS were enrolled in this longitudinal retrospective study. The risk of developing prediabetes (impared fasting glucose or hemoglobin A1c) was analyzed according to baseline and percent change in serum albumin concentration using Cox regression analysis. Serial changes in serum albumin concentration were measured from baseline to one year before prediabetes diagnosis, and then from the time of prediabetes diagnosis to progression to overt diabetes or final follow-up. A total of 4,398 incident cases of prediabetes developed during 35,807 person-years (median 3.8 years). The hazard ratio for incident prediabetes decreased as percent change in serum albumin concentration (quartiles and per 1%) increased in a crude and fully adjusted model. However, baseline serum albumin concentration itself was not associated with prediabetic risk. Serum albumin levels kept increasing until the end of follow-up in prediabetic subjects who returned to normal glycemic status, whereas these measures did not change in prediabetic subjects who developed type 2 diabetes. Serum albumin concentration measured at the end of follow-up was the highest in the regression group, compared to the stationary (p = 0.014) or progression groups (p = 0.009). Increase in serum albumin concentration might protect against early glycemic deterioration and progression to type 2 diabetes even in subjects without MetS.

Crossfit training changes brain-derived neurotrophic factor and irisin levels at rest, after wingate and progressive tests, and improves aerobic capacity and body composition of young physically active men and women.

Science.gov (United States)

Murawska-Cialowicz, E; Wojna, J; Zuwala-Jagiello, J

2015-12-01

Brain-derived neurotrophic factor (BDNF) is a protein that stimulates processes of neurogenesis, the survival of neurons and microglia, stimulates neuroplasticity, and takes part in the differentiation of cells developed in the hippocampus. BDNF is also released from skeletal muscles during exercise and can facilitate cross-talk between the nervous and muscular system. Irisin, the exercise hormone, is also released from skeletal muscles and is involved in oxidation processes in the organism. It is a vital issue from the point of view of prophylaxis and treatment through exercise of age-related diseases (e.g. senile dementia), obesity, type-2 diabetes. The aim of the study was to assess the changes in BDNF and irisin levels in young people after a 3-month CrossFit training program. At baseline and after the training, levels of BDNF and irisin were assayed before and after Wingate and progressive tests. Physical performance, body mass and composition, and muscle circumferences were also measured. There were noted: an improvement in aerobic capacity, an increase in VO2max, a reduction in adipose tissue percentage in women and an increase in LBM in all subjects. After CrossFit training the resting BDNF level increased significantly in all subjects while the resting level of irisin decreased in women, without changes in men. The resting level of BDNF at baseline was higher in men than in women. At baseline we observed an increased level of BDNF in women after Wingate and progressive tests, but in men only after the progressive test. After 3 months of CrossFit training the level of BDNF increased in all subjects, and also was higher in men than in women. In women we did not observe significant differences after both tests in comparison to rest. After the training BDNF was lower in men after Wingate and progressive tests than at rest. At baseline irisin level decreased in women after the Wingate and progressive tests. Changes in men were not observed after both tests

Progress on the national low level radioactive waste repository and national intermediate level waste store

International Nuclear Information System (INIS)

Perkins, C.

2001-01-01

Over the last few years, significant progress has been made towards siting national, purpose-built facilities for Australian radioactive waste. In 2001, after an eight year search, a preferred site and two alternatives were identified in central-north South Australia for a near-surface repository for Australian low level (low level and short-lived intermediate level) radioactive waste. Site 52a at Everts Field West on the Woomera Prohibited Area was selected as the preferred site as it performs best against the selection criteria, particularly with respect to geology, ground water, transport and security. Two alternative sites, Site 45a and Site 40a, east of the Woomera-Roxby Downs Road, were also found to be highly suitable for the siting of the national repository. A project has commenced to site a national store for intermediate (long-lived intermediate level) radioactive waste on Commonwealth land for waste produced by Commonwealth agencies. Public input has been sought on relevant selection criteria

Development of new low level radioactive waste disposal sites: A progress report

International Nuclear Information System (INIS)

Anderson, Robert T.; Antonucci, George J.; Ryan, Michael T.

1992-01-01

The status of the development of three new low level radioactive waste disposal facilities for the Central Midwest (Illinois), Southeastern (North Carolina) and Appalachian (Pennsylvania) compacts is presented. These three sites will dispose of about 50-65 percent of the commercial low-level waste (LLW) generated in the U.S. annually. Chem-Nuclear, as developer and proposed operator of all three sites has used a common approach to site development. This approach has been based on their twenty-plus years of operating experience and a standard technical approach. The technology employed is an above-grade, multiple engineered barrier design. The paper also contrasts actual progress at each site with a generalized project schedule. Areas of schedule delays are noted along with the steps being taken to accelerate schedule. Finally, we note that continued progress and timely start-up of operations of these new sites is critical on a national basis. This is due to the possibility of near-term closure of the existing LLW disposal sites. (author)

High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma.

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Firdaus S Dhabhar

Full Text Available In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2-3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED, 3 times/week, 10-weeks. The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome, and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th, cytolytic (CTL, and regulatory (Treg T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden, increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression, lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity, and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis. These results suggest that the deleterious effects of high trait anxiety

Association of low baseline free thyroxin levels with progression of coronary artery calcification over 4 years in euthyroid subjects: the Kangbuk Samsung Health Study.

Science.gov (United States)

Park, Hye-Jeong; Kim, Jihyun; Han, Eun Jin; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

2016-06-01

Overt and subclinical hypothyroidism are risk factors for atherosclerosis and cardiovascular diseases. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). This study aimed to examine the relationship between normal variations in thyroid function and changes in CAC. We conducted a 4-year retrospective study of 2173 apparently healthy men and women with normal thyroid hormone levels. Their free thyroxin (FT4), free triiodothyronin (FT3) and thyroid-stimulating hormone (TSH) levels were measured by electrochemiluminescent immunoassay. The CAC score (CACS) of each subject was measured by multidetector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years > 0. The mean CACS changes over 4 years by quartiles of baseline FT4 level (lowest to highest) were 12·9, 8·43, 7·82 and 7·81 (P = 0·028). CAC progression was not significantly associated with either the baseline FT3 or TSH levels. The odds ratios (OR) for CAC progression over 4 years (highest vs lowest quartile for baseline FT4) were 0·647 (95% confidence interval (CI) 0·472-0·886) after adjustment for confounding factor, which were attenuated with further adjustment for lipid profiles, homoeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein and hypertension [0·747 (95% CI 0·537-1·038)]. Quartiles of baseline FT3 or TSH level did not show any increased OR for CAC progression after adjustment for confounding factors. In this cohort of euthyroid men and women, a low baseline FT4 level was associated with a high risk of CACS progression over 4 years. © 2015 John Wiley & Sons Ltd.

Electrophysiological response of chicken's jejunal epithelium to increasing levels of T-2 toxin.

Science.gov (United States)

Yunus, Agha Waqar; Kröger, Susan; Tichy, Alexander; Zentek, Jürgen; Böhm, Josef

2013-02-01

The present investigations were conducted to test the effects of T-2 toxin on electrophysiological variables of jejunal epithelium of chicken. Jejunal segments of broilers were monitored in Ussing chambers in the presence of T-2 toxin at the levels of 0 (negative control), 0 (methanol/vehicle control), 0.1, 1, 5, and 10 μg/ml of buffer. T-2 toxin did not affect basal values of short circuit current (I(sc)), transmural potential difference, or tissue conductivity in the jejunal epithelium. T-2 toxin also did not statistically affect glucose-induced electrophysiological variables during the first 3 min of glucose induction. Compared to the vehicle control, the ouabain-sensitive I(sc) was negatively affected (P = 0.008) only under 5 μg of T-2 toxin/ml. Increasing levels of T-2 toxin negatively affected the ouabain-sensitive I(sc) in a cubic (P = 0.007) fashion. These data indicate that acute exposure to moderate levels of T-2 toxin may progressively impair the cation gradient across the jejunal epithelium.

Progressive Tinnitus Management Level 3 Skills Education: A 5-Year Clinical Retrospective.

Science.gov (United States)

Edmonds, Catherine M; Ribbe, Cheri; Thielman, Emily J; Henry, James A

2017-09-18

The primary purpose of this study was to determine whether progressive tinnitus management Level 3 skills education workshops conducted at the Bay Pines and Boston Veterans Affairs hospitals result in consistent use of the presented tinnitus management strategies by patients 1-5 years after completing the workshops. In fiscal year (FY) 2015, the tinnitus workshop follow-up form was mailed to all veterans who completed the Level 3 workshops between FY 2010 and FY 2014. Data were compiled to determine which, if any, of the skills taught in the workshops were being used 1-5 years after completion of the workshops and the impact on quality-of-life indicators. All self-management skills were being utilized up to 5 years postcompletion; therapeutic sound was utilized the most. The majority of patients reported an improved ability to manage reactions to tinnitus and improved quality-of-life indicators. Over 90% of patients from both sites recommended the program to others with tinnitus. The self-management skills taught in the progressive tinnitus management Level 3 workshops are sustained over time even when limited resources prevent the full complement of workshops or the involvement of mental health services. The workshops can also be successfully implemented through remote delivery via videoconferencing (telehealth). https://doi.org/10.23641/asha.5370883.

Progressive periodontal disease has a simultaneous incremental elevation of gingival crevicular fluid and serum CRP levels.

Science.gov (United States)

Pradeep, A R; Manjunath, R G Shiva; Kathariya, Rahul

2010-11-01

Increased C-reactive protein levels have been found in all active inflammations, including periodontitis. This study aims to assess the C-reactive protein levels in periodontal disease progression. Forty-five patients were divided into the following three groups (n=15) based on gingival index, probing pocket depth, and clinical attachment level: healthy (group I), gingivitis (group II), and chronic periodontitis (group III). Gingival crevicular fluid and serum samples were quantified for C-reactive protein using enzyme-linked immunosorbent assay. The mean C-reactive protein concentration in gingival crevicular fluid and serum was found to be highest in group III (1233.33ng/mL for gingival crevicular fluid, 5483.33ng/mL for serum), and least in group I (60 ng/mL and 413 ng/mL for gingival crevicular fluid and serum, respectively) The mean C-reactive protein concentration in group II (453.33ng/mL for gingival crevicular fluid and 3565.33 ng/mL for serum) was found to be intermediate. C-reactive protein levels in gingival crevicular fluid and serum increased proportionately with the severity of periodontal disease. They correlated positively with clinical parameters, including gingival index, probing pocket depth, and clinical attachment level. Thus, it can be considered as a periodontal inflammatory biomarker and deserves further consideration. © 2010 Blackwell Publishing Asia Pty Ltd.

1996 annual report on low-level radioactive waste management progress. Report to Congress

International Nuclear Information System (INIS)

1997-11-01

This report is prepared in response to the Low-Level Radioactive Waste Policy Act (the Act), Public Law 96-573, 1980, as amended by the Low-Level Radioactive Waste Policy Amendments Act of 1985, Public Law 99-240. The report summarizes the activities during calendar year 1996 related to the establishment of new disposal facilities for commercially-generated low-level radioactive waste. The report emphasizes significant issues and events that have affected progress in developing new disposal facilities, and also includes an introduction that provides background information and perspective on US policy for low-level radioactive waste disposal

Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decrease elastase-induced AAA development

DEFF Research Database (Denmark)

Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel

2017-01-01

Abdominal aortic aneurysm (AAA) evolution is unpredictable. Moreover, no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA have not been addressed. Galectin-3 levels were increased in plasma...... of AAA patients (n=225) compared to controls (n=100). Moreover, galectin-3 concentrations were associated with need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared to healthy aortas. Experimental AAA...... in mice was induced by aortic elastase perfusion. Mice were treated i.v. with the galectin-3 inhibitor modified citrus pectin (MCP, 10mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared to control mice...

Progressive resistance training increases strength after stroke but this may not carry over to activity: a systematic review.

Science.gov (United States)

Dorsch, Simone; Ada, Louise; Alloggia, Daniella

2018-04-01

Does progressive resistance training improve strength and activity after stroke? Does any increase in strength carry over to activity? Systematic review of randomised trials with meta-analysis. Adults who have had a stroke. Progressive resistance training compared with no intervention or placebo. The primary outcome was change in strength. This measurement had to be of maximum voluntary force production and performed in muscles congruent with the muscles trained in the intervention. The secondary outcome was change in activity. This measurement had to be a direct measure of performance that produced continuous or ordinal data, or with scales that produced ordinal data. Eleven studies involving 370 participants were included in this systematic review. The overall effect of progressive resistance training on strength was examined by pooling change scores from six studies with a mean PEDro score of 5.8, representing medium quality. The effect size of progressive resistance training on strength was 0.98 (95% CI 0.67 to 1.29, I 2 =0%). The overall effect of progressive resistance training on activity was examined by pooling change scores from the same six studies. The effect size of progressive resistance training on activity was 0.42 (95% CI -0.08 to 0.91, I 2 =54%). After stroke, progressive resistance training has a large effect on strength compared with no intervention or placebo. There is uncertainty about whether these large increases in strength carry over to improvements in activity. PROSPERO CRD42015025401. [Dorsch S, Ada L, Alloggia D (2018) Progressive resistance training increases strength after stroke but this may not carry over to activity: a systematic review. Journal of Physiotherapy 64: 84-90]. Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Progress and challenges in the development and qualification of multi-level multi-physics coupled methodologies for reactor analysis

International Nuclear Information System (INIS)

Ivanov, K.; Avramova, M.

2007-01-01

Current trends in nuclear power generation and regulation as well as the design of next generation reactor concepts along with the continuing computer technology progress stimulate the development, qualification and application of multi-physics multi-scale coupled code systems. The efforts have been focused on extending the analysis capabilities by coupling models, which simulate different phenomena or system components, as well as on refining the scale and level of detail of the coupling. This paper reviews the progress made in this area and outlines the remaining challenges. The discussion is illustrated with examples based on neutronics/thermohydraulics coupling in the reactor core modeling. In both fields recent advances and developments are towards more physics-based high-fidelity simulations, which require implementation of improved and flexible coupling methodologies. First, the progresses in coupling of different physics codes along with the advances in multi-level techniques for coupled code simulations are discussed. Second, the issues related to the consistent qualification of coupled multi-physics and multi-scale code systems for design and safety evaluation are presented. The increased importance of uncertainty and sensitivity analysis are discussed along with approaches to propagate the uncertainty quantification between the codes. The incoming OECD LWR Uncertainty Analysis in Modeling (UAM) benchmark is the first international activity to address this issue and it is described in the paper. Finally, the remaining challenges with multi-physics coupling are outlined. (authors)

Progress and challenges in the development and qualification of multi-level multi-physics coupled methodologies for reactor analysis

Energy Technology Data Exchange (ETDEWEB)

Ivanov, K.; Avramova, M. [Pennsylvania State Univ., University Park, PA (United States)

2007-07-01

Current trends in nuclear power generation and regulation as well as the design of next generation reactor concepts along with the continuing computer technology progress stimulate the development, qualification and application of multi-physics multi-scale coupled code systems. The efforts have been focused on extending the analysis capabilities by coupling models, which simulate different phenomena or system components, as well as on refining the scale and level of detail of the coupling. This paper reviews the progress made in this area and outlines the remaining challenges. The discussion is illustrated with examples based on neutronics/thermohydraulics coupling in the reactor core modeling. In both fields recent advances and developments are towards more physics-based high-fidelity simulations, which require implementation of improved and flexible coupling methodologies. First, the progresses in coupling of different physics codes along with the advances in multi-level techniques for coupled code simulations are discussed. Second, the issues related to the consistent qualification of coupled multi-physics and multi-scale code systems for design and safety evaluation are presented. The increased importance of uncertainty and sensitivity analysis are discussed along with approaches to propagate the uncertainty quantification between the codes. The incoming OECD LWR Uncertainty Analysis in Modeling (UAM) benchmark is the first international activity to address this issue and it is described in the paper. Finally, the remaining challenges with multi-physics coupling are outlined. (authors)

Role of bronchodilation and pattern of breathing in increasing tidal expiratory flow with progressive induced hypercapnia in chronic obstructive pulmonary disease.

Science.gov (United States)

Finucane, Kevin E; Singh, Bhajan

2018-01-01

Hypercapnia (HC) in vitro relaxes airway smooth muscle; in vivo, it increases respiratory effort, tidal expiratory flows (V̇ exp ), and, by decreasing inspiratory duration (Ti), increases elastic recoil pressure (Pel) via lung viscoelasticity; however, its effect on airway resistance is uncertain. We examined the contributions of bronchodilation, Ti, and expiratory effort to increasing V̇ exp with progressive HC in 10 subjects with chronic obstructive pulmonary disease (COPD): mean forced expiratory volume in 1 s (FEV 1 ) 53% predicted. Lung volumes (Vl), V̇ exp , esophageal pressure (Pes), Ti, and end-tidal Pco 2 ([Formula: see text]) were measured during six tidal breaths followed by an inspiratory capacity (IC), breathing air, and at three levels of HC. V̇ exp and V̇ with submaximal forced vital capacities breathing air (V̇ sFVC ) were compared. Pulmonary resistance ( Rl) was measured from the Pes-V̇ relationship. V̇ exp and Pes at end-expiratory lung volume (EELV) + 0.3 tidal volume [V̇ (0.3Vt) and Pes (0.3Vt) , respectively], Ti, and Rl correlated with [Formula: see text] ( P pulmonary disease (COPD), progressive HC increases tidal expiratory flows by inducing bronchodilation and via an increased rate of inspiration and lung viscoelasticity, a probable increase in lung elastic recoil pressure, both changes increasing expiratory flows, promoting lung emptying and a stable end-expiratory volume. Bronchodilation with HC occurred despite optimal standard bronchodilator therapy, suggesting that in COPD further bronchodilation is possible.

Gender differences in the progression of target organ damage in patients with increased insulin resistance: the LOD-DIABETES study.

Science.gov (United States)

Gómez-Marcos, Manuel Ángel; Recio-Rodríguez, José Ignacio; Gómez-Sánchez, Leticia; Agudo-Conde, Cristina; Rodríguez-Sanchez, Emiliano; Maderuelo-Fernandez, JoseAngel; Gomez-Sanchez, Marta; García-Ortiz, Luís

2015-10-01

The purpose of this study was to analyze the evolution of vascular, cardiac and renal target organ damage (TOD) in patients with increased insulin resistance over a 3.5 year follow-up and to investigate gender difference and factors that influence its progression. We performed a prospective observational study involving 112 patients (71 men, 41 women) who were followed for 3.5 years. Measurements included blood pressure, blood glucose, lipids, smoking, body mass index (BMI) and HOMA-Ir Vascular TOD included carotid intima-media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index (ABI). Cardiac TOD included Cornell voltage-duration product and Sokolow. Renal TOD included creatinine, glomerular filtration and albumin/creatinine ratio. The IMT increased in both genders. Each year, the IMT increased 0.005 mm in men and 0.011 in women and the PWV 0.024 and 0.020 m/sec, respectively. The highest increase was in women with type 2 diabetes mellitus, who had an increase in TOD carotid (40%), PWV (24%) and renal TOD (20 %). Multiple regression analysis, after adjusting for age and gender, showed a negative association between duration since diabetes diagnosis and ABI (β = -0.006; p = 0.017) and between BMI and glomerular filtration (β = -0.813; p = 0.014). HbA1c was positively associated with PWV (β = 0.501; p = 0.014). This study showed that the progression of vascular and renal TOD differs by gender. The increase in vascular and renal TOD was higher in women, especially in diabetic women. The PWV increase showed a positive association with mean HbA1c levels during the follow-up. Glomerular filtration was associated with BMI and the ABI was associated with duration since type 2 diabetes mellitus diagnosis. Clinical Trials.gov Identifier NCT01065155.

State-Level Point-of-Sale Tobacco News Coverage and Policy Progression Over a 2-Year Period.

Science.gov (United States)

Myers, Allison E; Southwell, Brian G; Ribisl, Kurt M; Moreland-Russell, Sarah; Bowling, J Michael; Lytle, Leslie A

2018-01-01

Mass media content may play an important role in policy change. However, the empirical relationship between media advocacy efforts and tobacco control policy success has rarely been studied. We examined the extent to which newspaper content characteristics (volume, slant, frame, source, use of evidence, and degree of localization) that have been identified as important in past descriptive studies were associated with policy progression over a 2-year period in the context of point-of-sale (POS) tobacco control. We used regression analyses to test the relationships between newspaper content and policy progression from 2012 to 2014. The dependent variable was the level of implementation of state-level POS tobacco control policies at Time 2. Independent variables were newspaper article characteristics (volume, slant, frame, source, use of evidence, and degree of localization) and were collected via content analysis of the articles. State-level policy environment contextual variables were examined as confounders. Positive, significant bivariate relationships exist between characteristics of news content (e.g., high overall volume, public health source present, local quote and local angle present, and pro-tobacco control slant present) and Time 2 POS score. However, in a multivariate model controlling for other factors, significant relationships did not hold. Newspaper coverage can be a marker of POS policy progression. Whether media can influence policy implementation remains an important question. Future work should continue to tease out and confirm the unique characteristics of media content that are most associated with subsequent policy progression, in order to inform media advocacy efforts.

Increased Nucleosomes and Neutrophil Activation Link to Disease Progression in Patients with Scrub Typhus but Not Murine Typhus in Laos.

Science.gov (United States)

Paris, Daniel H; Stephan, Femke; Bulder, Ingrid; Wouters, Diana; van der Poll, Tom; Newton, Paul N; Day, Nicholas P J; Zeerleder, Sacha

2015-01-01

Cell-mediated immunity is essential in protection against rickettsial illnesses, but the role of neutrophils in these intracellular vasculotropic infections remains unclear. This study analyzed the plasma levels of nucleosomes, FSAP-activation (nucleosome-releasing factor), and neutrophil activation, as evidenced by neutrophil-elastase (ELA) complexes, in sympatric Lao patients with scrub typhus and murine typhus. In acute scrub typhus elevated nucleosome levels correlated with lower GCS scores, raised respiratory rate, jaundice and impaired liver function, whereas neutrophil activation correlated with fibrinolysis and high IL-8 plasma levels, a recently identified predictor of severe disease and mortality. Nucleosome and ELA complex levels were associated with a 4.8-fold and 4-fold increased risk of developing severe scrub typhus, beyond cut off values of 1,040 U/ml for nucleosomes and 275 U/ml for ELA complexes respectively. In murine typhus, nucleosome levels associated with pro-inflammatory cytokines and the duration of illness, while ELA complexes correlated strongly with inflammation markers, jaundice and increased respiratory rates. This study found strong correlations between circulating nucleosomes and neutrophil activation in patients with scrub typhus, but not murine typhus, providing indirect evidence that nucleosomes could originate from neutrophil extracellular trap (NET) degradation. High circulating plasma nucleosomes and ELA complexes represent independent risk factors for developing severe complications in scrub typhus. As nucleosomes and histones exposed on NETs are highly cytotoxic to endothelial cells and are strongly pro-coagulant, neutrophil-derived nucleosomes could contribute to vascular damage, the pro-coagulant state and exacerbation of disease in scrub typhus, thus indicating a detrimental role of neutrophil activation. The data suggest that increased neutrophil activation relates to disease progression and severe complications, and

Undergraduate Use of Library Databases Decreases as Level of Study Progresses

Directory of Open Access Journals (Sweden)

Kimberly Miller

2014-09-01

had the lowest percentage of use, with 38% of enrolled students at each level accessing the library’s databases. The study also found that November was the peak of database search activity, accounting for 37% of database searches for the Fall 2009 semester. Database use varied by the schools or colleges in which students were enrolled, with the School of Nursing having the highest percentage of enrolled undergraduates using library databases (54%. The authors also report that the College of Literature, Science, and the Arts had the fourth highest proportion of users at 46%, representing 7,523 unique students, more than double the combined number of undergraduate users from all other programs. Since the College of Literature, Science, and the Arts accounts for more than 60% of the total undergraduate enrollment, the authors suggest that information literacy instruction targeted to these programs would have the greatest campus-wide impact. Conclusion – Although the library conducts a number of library instruction sessions with freshman students each Fall semester, the authors conclude that database use patterns suggest that the proportion of students who continue to use library databases decreases as level of study progresses. This finding does not support the study’s hypothesis that database use increases as students advance through their undergraduate studies.

A survey on the progress with implementation of the radiography profession's career progression framework in UK radiotherapy centres

International Nuclear Information System (INIS)

James, Sarah; Beardmore, Charlotte; Dumbleton, Claire

2012-01-01

Aim: The purpose of the survey was to benchmark the progress with implementing the radiography profession's career progression framework within radiotherapy centres across the United Kingdom (UK). Methods: A survey questionnaire was constructed using the Survey Monkey™ tool to assess implementation of the career progression framework of the Society and College of Radiographers. Once constructed, an on line link to the survey questionnaire was emailed to all radiotherapy centre managers in the UK (N = 67) who were invited to provide one response per centre. The survey comprised twenty nine questions which were grouped into nine sections. Key results: The workforce profile indicates that increases in assistant, advanced and consultant level practitioners are required to meet National Radiotherapy Advisory Group recommendations with only a small number of centres having fully implemented the career progression framework. The overall vacancy level across the therapeutic radiography workforce was 4.6% at the time of the survey. Conclusions: and Recommendations: The survey has highlighted some progress with implementation of the career progression framework across the UK since its launch in 2000. However the current level of implementation demonstrated is disappointing considering it is a key recommendation within the NRAG Report 2007 with respect to England. It is recommended that all centres undertake a multi-professional workforce review to embed the career progression framework within their service in order to meet the workforce challenge associated with the required anticipated large growth in radiotherapy capacity.

Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus.

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Carmela Giordano

Full Text Available Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs.

A High-Fat, High-Fructose Diet Induces Antioxidant Imbalance and Increases the Risk and Progression of Nonalcoholic Fatty Liver Disease in Mice

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Kanokwan Jarukamjorn

2016-01-01

Full Text Available Excessive fat liver is an important manifestation of nonalcoholic fatty liver disease (NAFLD, associated with obesity, insulin resistance, and oxidative stress. In the present study, the effects of a high-fat, high-fructose diet (HFFD on mRNA levels and activities of the antioxidant enzymes, including superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx, were determined in mouse livers and brains. The histomorphology of the livers was examined and the state of nonenzymatic reducing system was evaluated by measuring the glutathione system and the lipid peroxidation. Histopathology of the liver showed that fat accumulation and inflammation depended on the period of the HFFD-consumption. The levels of mRNA and enzymatic activities of SOD, CAT, and GPx were raised, followed by the increases in malondialdehyde levels in livers and brains of the HFFD mice. The oxidized GSSG content was increased while the total GSH and the reduced GSH were decreased, resulting in the increase in the GSH/GSSG ratio in both livers and brains of the HFFD mice. These observations suggested that liver damage and oxidative stress in the significant organs were generated by continuous HFFD-consumption. Imbalance of antioxidant condition induced by long-term HFFD-consumption might increase the risk and progression of NAFLD.

Niacin treatment increases plasma homocyst(e)ine levels.

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Garg, R; Malinow, M; Pettinger, M; Upson, B; Hunninghake, D

1999-12-01

Studies have reported high levels of plasma homocyst(e)ine as an independent risk factor for arterial occlusive disease. The Cholesterol Lowering Atherosclerosis Study reported an increase in plasma homocyst(e)ine levels in patients receiving both colestipol and niacin compared with placebo. Thus the objective of this study was to examine the effect of niacin treatment on plasma homocyst(e)ine levels. The Arterial Disease Multiple Intervention Trial, a multicenter randomized, placebo-controlled trial, examined the effect of niacin compared with placebo on homocyst(e)ine in a subset of 52 participants with peripheral arterial disease. During the screening phase, titration of niacin dose from 100 mg to 1000 mg daily resulted in a 17% increase in mean plasma homocyst(e)ine level from 13.1 +/- 4.4 micromol/L to 15.3 +/- 5.6 micromol/L (P ine levels in the niacin group and a 7% decrease in the placebo group (P =.0001). This difference remained statistically significant at the end of follow-up at 48 weeks. Niacin substantially increased plasma homocyst(e)ine levels, which could potentially reduce the expected benefits of niacin associated with lipoprotein modification. However, plasma homocyst(e)ine levels can be decreased by folic acid supplementation. Thus further studies are needed to determine whether B vitamin supplementation to patients undergoing long-term niacin treatment would be beneficial.

Increased common carotid artery wall thickness is associated with rapid progression of asymptomatic carotid stenosis.

Science.gov (United States)

Diomedi, Marina; Scacciatelli, Daria; Misaggi, Giulia; Balestrini, Simona; Balucani, Clotilde; Sallustio, Fabrizio; Di Legge, Silvia; Stanzione, Paolo; Silvestrini, Mauro

2014-01-01

This study aimed to identify clinical and ultrasound imaging predictors of progression of carotid luminal narrowing in subjects with asymptomatic moderate internal carotid artery (ICA) stenosis. A total of 571 subjects with asymptomatic moderate (50-69%) ICA stenoses were enrolled. They underwent ultrasound examination at baseline and after 12 months. Demographics, vascular risk factors, medications, plaque characteristics (surface and echogenicity) and common carotid intima-media thickness (IMT) were collected. At the follow-up examination, any change of ICA stenosis was graded in three categories (i) ≥70% to near occlusion, (ii) near occlusion, and (iii) occlusion. Progression of stenosis was defined as an increase in the stenosis degree by at least one category from baseline to follow-up. At 12 months, progression occurred in 142 subjects (prevalence rate 25%). At the multivariable logistic model, pathological IMT values (considered as binary variable: normal: ≤1 mm vs. pathologic: >1 mm) significantly predicted the risk for plaque progression after adjusting the model for possible confounders (OR 2.28, 95% CI 1.18-4.43, P = .014, multivariable logistic model). Our results confirm the role of carotid wall thickening as a marker of atherosclerosis. Carotid IMT measurement should be considered to implement risk stratification in patients with asymptomatic carotid disease.

ERG Protein Expression in Diagnostic Specimens Is Associated with Increased Risk of Progression During Active Surveillance for Prostate Cancer

DEFF Research Database (Denmark)

Berg, Kasper Drimer; Vainer, Ben; Thomsen, Frederik Birkebæk

2014-01-01

with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal...

Circulating Oxidized Low-Density Lipoprotein Levels Independently Predict 10-Year Progression of Subclinical Carotid Atherosclerosis: A Community-Based Cohort Study.

Science.gov (United States)

Gao, Shen; Zhao, Dong; Qi, Yue; Wang, Wei; Wang, Miao; Sun, Jiayi; Liu, Jun; Li, Yan; Liu, Jing

2018-03-07

To investigate the association between circulating oxidized low-density lipoprotein (ox-LDL) levels and progression of subclinical atherosclerosis and to examine whether this link is independent of other low-density lipoprotein (LDL)-related parameters. Totally, 804 subjects who were free of cardiovascular disease at baseline completed risk factor surveys and carotid ultrasound measurements in 2002 and 2012. Modified Poisson regression was performed to examine the association between baseline serum ox-LDL levels and the 10-year risk of progression of carotid atherosclerosis which was defined as the development of at least one new plaque in a previously plaque-free carotid segment at re-examination. The mean age of the subjects was 58.6±7.7 years at baseline and 43.3% were men. A total of 504 (62.7%) subjects had carotid plaque progression at re-examination. Subjects in the intermediate and highest tertiles of ox-LDL had a significantly higher adjusted risk of atherosclerosis progression than those in the lowest tertile [relative risk (95% confidence interval) 1.17 (1.01-1.34) for the intermediate tertile and 1.23 (1.07-1.42) for the highest tertile]. This association was independent of baseline levels of LDL-C, total LDL particle number, and small LDL particle number. This study demonstrates that serum ox-LDL levels predict 10-year progression of subclinical atherosclerosis. Moreover, this effect is independent of the cholesterol content, the number, and the size of LDL particles.

1991 annual report on low-level radioactive waste management progress

International Nuclear Information System (INIS)

1992-11-01

This report summarizes the progress during 1991 of States and compact regions in establishing new low-level radioactive waste disposal capacity. It has been prepared in response to requirements in Section 7 (b) of Title I of Public Law 99-240, the Low-Level Radioactive Waste Policy Amendments Act of 1985 (the Act). By the end of 1991, 9 compact regions (totaling 42 States) were functioning with plans to establish low-level radioactive waste disposal facilities: Appalachian, Central, Central Midwest, Midwest, Northeast, Northwest, Rocky Mountain, Southeast, and Southwestern. Also planning to construct disposal facilities, but unaffiliated with a compact region, are Maine, Massachusetts, New York, Texas, and Vermont. The District of Columbia, New Hampshire, Puerto Rico, Rhode Island and Michigan are unaffiliated with a compact region and do not plan to construct a disposal facility. Michigan was the host State for the Midwest compact region until July 1991 when the Midwest Interstate Compact Commission revoked Michigan's membership. Only the Central, Central Midwest, and Southwestern compact regions met the January 1, 1992, milestone in the Act to submit a complete disposal license application. None of the States or compact regions project meeting the January 1, 1993, milestone to have an operational low-level radioactive waste disposal facility. Also summarized are significant events that occurred in low-level radioactive waste management in 1991 and early 1992, including the 1992 United States Supreme Court decision in New York v. United States in which New York challenged the constitutionality of the Act, particularly the ''take-title'' provision. Summary information is also provided on the volume of low-level radioactive waste received for disposal in 1991 by commercially operated low-level radioactive waste disposal facilities

Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy.

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Song, Guohong; Wang, Xiaoli; Jia, Jun; Yuan, Yanhua; Wan, Fengling; Zhou, Xinna; Yang, Huabing; Ren, Jun; Gu, Jiezhun; Lyerly, Herbert Kim

2013-06-01

Suppression of cellular immunity resulting from tumorigenesis and/or therapy might promote cancer cells' growth, progression and invasion. Here, we explored whether T lymphocyte subtypes from peripheral blood of metastatic breast cancer (MBC) female patients could be used as alternative surrogate markers for cancer progress. Additionally, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and transforming growth factor-β1 were quantitated from MBC and healthy volunteers. This study included 89 female MBC patients during the post-salvage chemotherapy follow-up and 50 age- and sex-matched healthy volunteers as control. The percentages of T lymphocyte subpopulations from peripheral blood and plasma levels of cytokines were measured. Both CD8(+)CD28(-) and CD4(+)CD25(+) were elevated in MBC patients compared to the control cohort (P < 0.05). In contrast, CD3(+) and CD8(+)CD28(+)cells were significantly lower in MBC patients (P < 0.0001, P = 0.045, respectively). MBC patients had elevated levels of immunosuppressive cytokines IL-6 and IL-10. Patients with elevated CD8(+)CD28(-) and CD4(+)CD25(+) cells showed increased levels of IL-6, and only patients with elevated CD8(+)CD28(-) had decreased interferon-γ. Univariate analysis indicated increased CD3(+)CD4(+) or CD8(+)CD28(+)correlated with prolonged progression-free survival (PFS), while elevated CD8(+)CD28(-)associated with shorten PFS. The percent of CD8(+)CD28(-) T lymphocytes is an independent predictor for PFS through multivariate analysis. This study suggests that progressive elevated levels of CD8(+)CD28(-) suppressor T lymphocytes represent a novel independent predictor of PFS during post-chemotherapy follow-up.

Allopurinol Against Progression of Chronic Kidney Disease.

Science.gov (United States)

Golmohammadi, Sima; Almasi, Afshin; Manouchehri, M; Omrani, Hamid Reza; Zandkarimi, Mohammad Reza

2017-07-01

Hyperuricemia is common in approximately 50% of patients with kidney failure due to decreased uric acid excretion, and it has been recently known as an independent factor in the progression of renal insufficiency. Allopurinol inhibits the production of uric acid. The aim of this study was to evaluate the effect of allopurinol on chronic kidney disease progression. In a clinical trial, patients with stages 3 and 4 of chronic kidney disease were divided into two groups to receive allopurinol, 100 mg, daily and placebo for 12 months. Patients' kidney function and serum uric acid levels were assessed at baseline and 3, 6, and 12 months after initial administration. Subgroups of patients with severe and mild glomerular filtration rate (GFR) impairment (GFR, 15 mL/min/1.73 m2 to 30 mL/min/1.73 m2 and 30 mL/min/1.73 m2 to 60 mL/min/1.73 m2, respectively), were compared between the groups. Serum uric acid levels decreased significantly during after 12 months of allopurinol administration (P = .004). In patients with severe GFR impairment, serum creatinine levels did not decrease significantly and there was no significant increase in GFR, but in those with mild GFR impairment, serum creatinine levels decreased and GFR increase significantly (P kidney disease progression and could be administered with other effective medications for controlling the kidney disease.

Increased fear of progression in cancer patients with recurrence.

Science.gov (United States)

Shim, Eun-Jung; Shin, Yong-Wook; Oh, Do-Youn; Hahm, Bong-Jin

2010-01-01

This study investigated the fear of progression (FoP) in cancer patients and the discriminant ability of the Fear of Progression Questionnaire (FoP-Q) against the Hospital Anxiety and Depression Scale (HADS), while also examining relationships between FoP, satisfaction outcomes and supportive needs. The FoP-Q and HADS were administered to 112 cancer patients in Korea during June and July 2006. The FoP-Q totals and subscales, and the HADS scores were compared across three groups (patients with recurrence, patients with metastases and controls experiencing neither). Comparison of the FoP-Q total score to HADS anxiety (HADS-A) and depression (HADS-D) scores showed higher FoP in the recurrence group compared to the control group (P=.009). Subscale score comparisons revealed a heightened "affective reaction" (P=.003) to cancer progression and fear of "loss of autonomy" (P=.011) in recurrence patients. FoP-Q score showed a moderate association with HADS-A (r=.54, P=.000) and a significant association with treatment satisfaction (r=-.26, P=.007), medical staff and communication (r=-.31, P=.001), and supportive needs (r=.41, P=.000). The importance of providing supportive interventions tailored to the specific emotional concerns of cancer patients, assessed via appropriate, disease-specific instruments, and the need to pay special attention to the concerns of recurrence patients are suggested. Copyright 2010 Elsevier Inc. All rights reserved.

Progression of structural damage is not related to rituximab serum levels in rheumatoid arthritis patients

NARCIS (Netherlands)

Boumans, Maria; Teng, Onno; Thurlings, Rogier; Bijlsma, Johannes; Gerlag, Danielle; Huizinga, Tom; Vos, Koen; Stapel, Steven; Wolbink, Gertjan; Tekstra, Janneke; van Laar, Jaap; Tak, Paul P.

2013-01-01

The most cost-effective dosing regimen for rituximab treatment in RA is currently unknown. The objective of this study is to determine whether low rituximab serum levels are associated with progression of structural damage in RA patients. Sixty-two RA patients were treated with rituximab in three

Progressive taxation and the subjective well-being of nations.

Science.gov (United States)

Oishi, Shigehiro; Schimmack, Ulrich; Diener, Ed

2012-01-01

Using data from the Gallup World Poll, we examined whether progressive taxation is associated with increased levels of subjective well-being. Consistent with Rawls's theory of justice, our results showed that progressive taxation was positively associated with the subjective well-being of nations. However, the overall tax rate and government spending were not associated with the subjective well-being of nations. Furthermore, controlling for the wealth of nations and income inequality, we found that respondents living in a nation with more-progressive taxation evaluated their lives as closer to the best possible life and reported having more positive and less negative daily experiences than did respondents living in a nation with less-progressive taxation. Finally, we found that the association between more-progressive taxation and higher levels of subjective well-being was mediated by citizens' satisfaction with public goods, such as education and public transportation.

Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression.

Science.gov (United States)

Steinacker, Petra; Verde, Federico; Fang, Lubin; Feneberg, Emily; Oeckl, Patrick; Roeber, Sigrun; Anderl-Straub, Sarah; Danek, Adrian; Diehl-Schmid, Janine; Fassbender, Klaus; Fliessbach, Klaus; Foerstl, Hans; Giese, Armin; Jahn, Holger; Kassubek, Jan; Kornhuber, Johannes; Landwehrmeyer, G Bernhard; Lauer, Martin; Pinkhardt, Elmar Hans; Prudlo, Johannes; Rosenbohm, Angela; Schneider, Anja; Schroeter, Matthias L; Tumani, Hayrettin; von Arnim, Christine A F; Weishaupt, Jochen; Weydt, Patrick; Ludolph, Albert C; Yilmazer Hanke, Deniz; Otto, Markus

2018-03-01

Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1). Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con). CHIT1 and neurofilament levels were determined in cerebrospinal fluid (CSF) and blood and analysed with regard to diagnostic sensitivity and specificity and prognostic performance. Additionally, postmortem tissue was analysed for CHIT1 expression. In ALS, CHIT1 CSF levels were higher compared with Con (pdifferential diagnosis and prediction of disease progression in ALS and, therefore, seems suitable as a supplemental marker for patient stratification in therapeutic trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Increased serum procalcitonin levels in pregnant patients with asymptomatic bacteriuria.

Science.gov (United States)

Bilir, Filiz; Akdemir, Nermin; Ozden, Selcuk; Cevrioglu, A Serhan; Bilir, Cemil

2013-09-05

Among the pregnancy urinary tract infections, asymptomatic bacteriuria (ASB) is the most common one. Untreated ASB can progress to pyelonephritis in 30-50% of the patients and can also result in prematurity in 27% of the pregnancy so it needs immediate diagnosis and treatment. In this study, we wanted to evaluate procalcitonin levels, compared to other inflammatory in pregnant women with ASB. The study was designed between the period of January 2012 and February 2013 at Sakarya University School of Medicine, Department of Gynecology and Obstetrics. The study population included 30 pregnant patients with asymptomatic bacteriuria and 39 healthy pregnant controls. Mean age was 28 (SD, 5.5) of the study population; mean maternal weight was 70 (SD, 8) kilogram. There were no statically significant differences between the groups according to the routine biochemical parameters, but gestational age was significantly lower in the ASB group compared to the controls (20.4 vs 28.6, respectively; p 0.05 ng/ml and 21(70%) patients had negative procalcitonin levels (Chi-squrae, p treatment of the first ASB diagnosis. Procalcitonin levels were significantly higher in ASB group than the control group and serum procalcitonin levels were higher in pregnant women with recurrent ASB. This finding is an important result revealed that high procalcitonin level can predict the further urinary tract infection risk. Finally, serum procalcitonin levels were normal in healthy pregnant women while other inflammatory markers such as WBC, ESR and CRP levels were higher.

Periodontitis increases rheumatic factor serum levels and citrullinated proteins in gingival tissues and alter cytokine balance in arthritic rats.

Directory of Open Access Journals (Sweden)

Mônica G Corrêa

Full Text Available This study investigated some immunological features by experimental periodontitis (EP and rheumatoid arthritis (RA disease interact in destructive processes in arthritic rats. Rats were assigned to the following groups: EP +RA; RA; EP; and Negative Control. RA was induced by immunizations with type-II collagen and a local immunization with Complete Freund's adjuvant in the paw. Periodontitis was induced by ligating the right first molars. The serum level of rheumatoid factor (RF and anti-citrullinated protein antibody (ACCPA were measured before the induction of EP (T1 and at 28 days after (T2 by ELISA assay. ACCPA levels were also measured in the gingival tissue at T2. The specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for the quantification of interleukin IL-1β, IL-4, IL-6, IL-17 and TNF-α using a Luminex/MAGpix assay. Paw edema was analyzed using a plethysmometer. Periodontitis increased the RF and ACCPA levels in the serum and in the gingival tissue, respectively. Besides, the level of paw swelling was increased by EP and remained in progress until the end of the experiment, when EP was associated with RA. Greater values of IL-17 were observed only when RA was present, in spite of PE. It can be concluded that periodontitis increases rheumatic factor serum levels and citrullinated proteins level in gingival tissues and alter cytokine balance in arthritic rats; at the same time, arthritis increases periodontal destruction, confirming the bidirectional interaction between diseases.

Increased RhoA prenylation in the loechrig (loe mutant leads to progressive neurodegeneration.

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Mandy Cook

Full Text Available The Drosophila mutant loechrig (loe shows age-dependent degeneration of the nervous system and is caused by the loss of a neuronal isoform of the AMP-activated protein kinase (AMPK γ-subunit (also known as SNF4Aγ. The trimeric AMPK complex is activated by low energy levels and metabolic insults and regulates multiple important signal pathways that control cell metabolism. A well-known downstream target of AMPK is hydroxyl-methylglutaryl-CoA reductase (HMGR, a key enzyme in isoprenoid synthesis, and we have previously shown that HMGR genetically interacts with loe and affects the severity of the degenerative phenotype. Prenylation of proteins like small G-proteins is an important posttranslational modification providing lipid moieties that allow the association of these proteins with membranes, thereby facilitating their subsequent activation. Rho proteins have been extensively studied in neuronal outgrowth, however, much less is known about their function in neuronal maintenance. Here we show that the loe mutation interferes with isoprenoid synthesis, leading to increased prenylation of the small GTPase Rho1, the fly orthologue of vertebrate RhoA. We also demonstrate that increased prenylation and Rho1 activity causes neurodegeneration and aggravates the behavioral and degenerative phenotypes of loe. Because we cannot detect defects in the development of the central nervous system in loe, this suggests that loe only interferes with the function of the RhoA pathway in maintaining neuronal integrity during adulthood. In addition, our results show that alterations in isoprenoids can result in progressive neurodegeneration, supporting findings in vertebrates that prenylation may play a role in neurodegenerative diseases like Alzheimer's Disease.

Increased carboxyhemoglobin level during liver resection with inflow occlusion.

Science.gov (United States)

Godai, Kohei; Hasegawa-Moriyama, Maiko; Kuniyoshi, Tamotsu; Matsunaga, Akira; Kanmura, Yuichi

2013-04-01

Controlling stress responses associated with ischemic changes due to bleeding and ischemia/reperfusion injury is essential for anesthetic management. Endogenous carboxyhemoglobin (COHb) is produced in the oxidative degradation of heme proteins by the stress-response enzyme heme oxygenase. Although the COHb level is elevated in critically ill patients, changes in endogenous COHb during anesthesia have not been well investigated. Therefore, we evaluated changes in endogenous COHb levels in patients undergoing liver resections with inflow occlusion. Levels of COHb were significantly increased after the Pringle maneuver. The inflow occlusion time in patients with increased COHb after the Pringle maneuver (∆COHb > 0.3 %) was significantly longer than in patients without increased COHb (∆COHb < 0.3 %) (P = 0.01). In addition, COHb changes were correlated with inflow occlusion time (P = 0.005, R(2) = 0.21). Neither total blood loss, transfusion volume of packed red blood cells, operation time, nor anesthetic time differed between patients with and without increased COHb. The results indicated that endogenous COHb levels were increased by inflow occlusion in patients undergoing liver resections, which suggests that changes in COHb may correlate with hepatic ischemia/reperfusion injury induced by inflow occlusion.

Serum klotho protein levels and their correlations with the progression of type 2 diabetes mellitus.

Science.gov (United States)

Nie, Fang; Wu, Dongming; Du, Hongfei; Yang, Xianggui; Yang, Min; Pang, Xueli; Xu, Ying

2017-03-01

To investigate the associations of serum α-Klotho and β-Klotho levels with type 2 diabetes mellitus (T2DM) progression. We evaluated 106 healthy controls and 261 cases of T2DM with or without diabetic complications (range: 45-84years). Serum α-Klotho and β-Klotho levels were analyzed using enzyme-linked immunosorbent assays. Compared to the healthy controls, α-Klotho and β-Klotho levels were significantly lower among patients with T2DM and with or without diabetic complications (Pdiabetes, and the positive correlation of α-Klotho and β-Klotho levels indicates that they might have similar mechanisms in T2DM. Copyright © 2016 Elsevier Inc. All rights reserved.

Decreased synovial fluid ghrelin levels are linked with disease severity in primary knee osteoarthritis patients and are increased following laser therapy.

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Zou, Yu-Cong; Deng, Hong-Yu; Mao, Zheng; Zhao, Chang; Huang, Ju; Liu, Gang

2017-07-01

Ghrelin has been proved to inhibit inflammation and promote cartilage growth. So far, its role in patients with primary knee osteoarthritis has not been investigated. The current study was performed to explore the serum and synovial ghrelin levels as well as the relationship between ghrelin levels and disease severity in primary knee OA patients. 52 primary knee OA patients were recruited in the study. 52 sex and age-matched patients visiting our hospital for regular body check were selected as controls. The serum and synovial fluid ghrelin levels were examined by enzyme linked immunosorbent assay (ELISA) before treatment, one week and four weeks after laser therapy, respectively. The inflammation markers IL-6 and TNF-α were also investigated. The radiographic progression was assessed by Kellgren-Lawrence (K-L) grade scale and the symptomatic severity was evaluated by visual analog scale (VAS), Lequesne index and Lysholm scores. The Receiver Operating Characteristic (ROC) analysis curve was conducted to test the diagnostic value of ghrelin, IL-6 and TNF-α for radiographic progression. No significant difference of serum ghrelin levels was found between knee OA patients and healthy controls. Synovial fluid ghrelin concentrations were significantly negatively correlated with K-L grading (r=-0.591, Pghrelin levels were also related to clinical severity determined by Lequesne index (r=-0.308, P=0.025),VAS scores (r=-0.591, Pghrelin levels were also negatively associated with TNF-α (r=-0.424, P=0.002) and IL-6 concentrations (r=-0.428, P=0.002). ROC curve analysis demonstrated that ghrelin exhibited more diagnostic value than IL-6 and TNF-α for assessing radiographic progression in medium-late stage. Decreased synovial fluid ghrelin levels are related to disease severity in patients with primary osteoarthritis and are increased following laser therapy. Local application of ghrelin may serve as an adjunctive therapy for knee OA. Copyright © 2017. Published by

PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease.

Science.gov (United States)

Toapanta Gaibor, Néstor Gabriel; Nava Pérez, Nathasha Carolina; Martínez Echevers, Yeleine; Montes Delgado, Rafael; Guerrero Riscos, María Ángeles

At present, there is a high incidence of elderly patients with advanced chronic kidney disease (CKD) and it is important to know the long term progression and the factors that influence it. To analyse the progression of advanced CKD in elderly patients and the influence of bone-mineral metabolism. Retrospective study of 125 patients ≥70years of age with CKD stages 4-5 who started follow-up from January 1, 2007 to December 31, 2008, showing the progression of CKD (measured by the slope of the regression line of the estimated glomerular filtration rate [eGFR] by MDRD-4) over 5years. Progression in the entire group (median and 25th and 75th percentiles): -1.15 (-2.8/0.17) ml/min/1.73m 2 /year, CKD-4: -1.3 (-2.8/0.03) ml/min/1.73m 2 /year, CKD-5: -1.03 (-3.0/0.8) ml/min/1.73m 2 /year; the slope of the regression line was positive in 35 patients (28%: CKD does not progress) and negative in 90 patients (72%: CKD progresses). Negative correlation (Spearman) (slower progression): PTH, albumin/Cr ratio and daily Na excretion (all baseline measurements). No correlation with eGFR, serum P, urinary P excretion, protein intake and intake of P (all baseline measurements). In the linear regression analysis (dependent variable: slope of progression): albuminuria and PTH (both at baseline measurements) influenced this variable independently. Logistic regression (progresses vs. does not progress): PTH, albuminuria and eGFR (all at baseline measurements) influenced significantly. In our group of elderly patients, impairment of renal function is slow, particularly in CKD-5 patients. Albuminuria and PTH at baseline levels are prognostic factors in the evolution of renal function. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Plasma adiponectin levels correlate positively with an increasing number of components of frailty in male elders.

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Jaw-Shiun Tsai

Full Text Available OBJECTIVE: Frailty is an important geriatric syndrome. Adiponectin is an important adipokine that regulates energy homeostasis. The aim of this study is to investigate the relationship between plasma adiponectin levels and frailty in elders. METHODS: The demographic data, body weight, metabolic and inflammatory parameters, including plasma glucose, total cholesterol, triglyceride, tumor necrosis factor alpha (TNF-α, c-reactive protein (CRP and adiponectin levels, were assessed. The frailty score was assessed using the Fried Frailty Index (FFI. RESULTS: The mean (SD age of the 168 participants [83 (49.4% men and 85 (50.6% women] was 76.86 (6.10 years. Judged by the FFI score, 42 (25% elders were robust, 92 (54.7% were pre-frail, and 34 (20.3% were frail. The mean body mass index was 25.19 (3.42 kg/m(2. The log-transformed mean (SD plasma adiponectin (µg/mL level was 1.00 (0.26. The log-transformed mean plasma adiponectin (µg/mL levels were 0.93 (0.23 in the robust elders, 1.00 (0.27 in the pre-frail elders, and 1.10 (0.22 in the frail elders, and the differences between these values were statistically significant (p  = 0.012. Further analysis showed that plasma adiponectin levels rose progressively with an increasing number of components of frailty in all participants as a whole (p for trend  = 0.024 and males (p for trend  = 0.037, but not in females (p for trend  = 0.223. CONCLUSION: Plasma adiponectin levels correlate positively with an increasing number of components of frailty in male elders. The difference between the sexes suggests that certain sex-specific mechanisms may exist to affect the association between adiponectin levels and frailty.

Glycine facilitates gamma-glutamylcysteinylethyl ester-mediated increase in liver glutathione level.

Science.gov (United States)

Nishida, K; Ohta, Y; Ishiguro, I

1997-08-27

gamma-Glutamylcysteinylethyl ester (gamma-GCE) increases reduced glutathione (GSH) levels in GSH-depleted rat hepatocytes. Because glycine, a constituent of GSH, exists at 0.3 to 0.4 mM in rat plasma, we examined the influence of glycine added to the medium on the action of gamma-GCE to increase GSH levels in the rat hepatocytes. Glycine (0.2-0.8 mM) dose-dependently enhanced gamma-GCE-mediated increase in intracellular GSH levels with an increase in intracellular gamma-GCE levels. These results indicate that exogenous glycine facilitates gamma-GCE-mediated increase in intracellular GSH levels in rat hepatocytes possibly by enhancing the uptake of gamma-GCE into the cells.

Serum Levels of Toxic AGEs (TAGE May Be a Promising Novel Biomarker for the Onset/Progression of Lifestyle-Related Diseases

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Masayoshi Takeuchi

2016-06-01

Full Text Available Advanced glycation end-products (AGEs generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose/fructose metabolism intermediate glyceraldehyde (Glycer-AGEs; termed toxic AGEs (TAGE, were recently shown to be closely involved in the onset/progression of diabetic vascular complications via the receptor for AGEs (RAGE. TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer’s disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset/progression of lifestyle-related diseases (LSRD and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or Nε-(carboxymethyllysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE/sugar intake restrictions reduce the generation/accumulation of TAGE, thereby preventing the onset/progression of LSRD.

Increased Risk of Progression of Coronary Artery Calcification in Male Subjects with High Baseline Waist-to-Height Ratio: The Kangbuk Samsung Health Study.

Science.gov (United States)

Oh, Hyung Geun; Nallamshetty, Shriram; Rhee, Eun Jung

2016-02-01

The waist-to-height ratio (WHtR) is an easy and inexpensive adiposity index that reflects central obesity. In this study, we examined the association of baseline WHtR and progression of coronary artery calcification (CAC) over 4 years of follow-up in apparently healthy Korean men. A total of 1,048 male participants (mean age, 40.9 years) in a health-screening program in Kangbuk Samsung Hospital, Seoul, Korea who repeated a medical check-up in 2010 and 2014 were recruited. Baseline WHtR was calculated using the value for the waist in 2010 divided by the value for height in 2010. The CAC score (CACS) of each subject was measured by multi-detector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years greater than 0. During the follow-up period, progression of CAC occurred in 278 subjects (26.5%). The subjects with CAC progression had slightly higher but significant baseline WHtR compared to those who did not show CAC progression (0.51±0.04 vs. 0.50±0.04, P<0.01). The proportion of subjects with CAC progression significantly increased as the baseline WHtR increased from the 1st quartile to 4th quartile groups (18.3%, 18.7%, 28.8%, and 34.2%; P<0.01). The risk for CAC progression was elevated with an odds ratio of 1.602 in the 4th quartile group of baseline WHtR even after adjustment for confounding variables (95% confidence interval, 1.040 to 2.466). Increased baseline WHtR was associated with increased risk for CAC progression. WHtR might be a useful screening tool to identify individuals at high risk for subclinical atherosclerosis.

Keratoconus Progression Induced by In Vitro Fertilization Treatment.

Science.gov (United States)

Yuksel, Erdem; Yalinbas, Duygu; Aydin, Bahri; Bilgihan, Kamil

2016-01-01

To evaluate patients with keratoconus who manifested progression after in vitro fertilization (IVF) treatment. Patients with keratoconus who received IVF treatment were included in this study. None of the patients became pregnant as a result of the IVF treatment. Progression of keratoconus was determined by changes in corrected distance visual acuity and/or topographic changes and subjective assessments. Three patients with keratoconus received IVF treatment and keratoconus progression was detected in all 6 eyes of the patients. The mean age of the patients was 32.3 ± 3.6 years (range: 28 to 36 years) and the mean follow-up duration was 15.6 ± 3.2 months (range: 12 to 18 months). The mean and the maximum keratometry values increased and corrected distance visual acuity decreased after 2.3 IVF treatments. Drugs used in IVF treatment increase estrogen levels, which may affect corneal biomechanics and induce progression of keratoconus. Corneal cross-linking treatment could be offered to minimize the risk of keratoconus progression before IVF treatment. Copyright 2016, SLACK Incorporated.

Infiltrating T Cells Promote Bladder Cancer Progression via Increasing IL1→Androgen Receptor→HIF1α→VEGFa Signals.

Science.gov (United States)

Tao, Le; Qiu, Jianxin; Jiang, Ming; Song, Wenbin; Yeh, Shuyuan; Yu, Hong; Zang, Lijuan; Xia, Shujie; Chang, Chawnshang

2016-08-01

The tumor microenvironment impacts tumor progression and individual cells, including CD4(+) T cells, which have been detected in bladder cancer tissues. The detailed mechanism of how these T cells were recruited to the bladder cancer tumor and their impact on bladder cancer progression, however, remains unclear. Using a human clinical bladder cancer sample survey and in vitro coculture system, we found that bladder cancer has a greater capacity to recruit T cells than surrounding normal bladder tissues. The consequences of higher levels of recruited T cells in bladder cancer included increased bladder cancer metastasis. Mechanism dissection revealed that infiltrating T cells might function through secreting the cytokine IL1, which increases the recruitment of T cells to bladder cancer and enhances the bladder cancer androgen receptor (AR) signaling that results in increased bladder cancer cell invasion via upregulation of hypoxia-inducible factor-1α (HIF1α)/VEGFa expression. Interruption of the IL1→AR→HIF1α→VEGFa signals with inhibitors of HIF1α or VEGFa partially reversed the enhanced bladder cancer cell invasion. Finally, in vivo mouse models of xenografted bladder cancer T24 cells with CD4(+) T cells confirmed in vitro coculture studies and concluded that infiltrating CD4(+) T cells can promote bladder cancer metastasis via modulation of the IL1→AR→HIF1α→VEGFa signaling. Future clinical trials using small molecules to target this newly identified signaling pathway may facilitate the development of new therapeutic approaches to better suppress bladder cancer metastasis. Mol Cancer Ther; 15(8); 1943-51. ©2016 AACR. ©2016 American Association for Cancer Research.

Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

Science.gov (United States)

Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

2014-01-01

Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

Exogenous t-PA administration increases hippocampal mature BDNF levels. plasmin- or NMDA-dependent mechanism?

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Marion Rodier

Full Text Available Brain-derived neurotrophic factor (BDNF through TrkB activation is central for brain functioning. Since the demonstration that plasmin is able to process pro-BDNF to mature BDNF and that these two forms have opposite effects on neuronal survival and plasticity, a particular attention has been paid to the link between tissue plasminogen activator (tPA/plasmin system and BDNF metabolism. However, t-PA via its action on different N-methyl-D-aspartate (NMDA receptor subunits is also considered as a neuromodulator of glutamatergic transmission. In this context, the aim of our study was to investigate the effect of recombinant (rt-PA administration on brain BDNF metabolism in rats. In the hippocampus, we found that rt-PA (10 mg/kg administration induced a progressive increase in mature BDNF levels associated with TrkB activation. In order to delineate the mechanistic involved, plasmin activity was assessed and its inhibition was attempted using tranexamic acid (30 or 300 mg/kg, i.v. while NMDA receptors were antagonized with MK801 (0.3 or 3 mg/kg, i.p. in combination with rt-PA treatment. Our results showed that despite a rise in rt-PA activity, rt-PA administration failed to increase hippocampal plasmin activity suggesting that the plasminogen/plasmin system is not involved whereas MK801 abrogated the augmentation in mature BDNF levels observed after rt-PA administration. All together, our results show that rt-PA administration induces increase in hippocampal mature BDNF expression and suggests that rt-PA contributes to the control of brain BDNF synthesis through a plasmin-independent potentiation of NMDA receptors signaling.

Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells.

Science.gov (United States)

Banerjee, Aditi; Banerjee, Vivekjyoti; Czinn, Steven; Blanchard, Thomas

2017-04-18

Chemotherapy continues to play an essential role in the management of many cancers including colon cancer, the third leading cause of death due to cancer in the United States. Many naturally occurring plant compounds have been demonstrated to possess anti-cancer cell activity and have the potential to supplement existing chemotherapy strategies. The plant metabolite andrographolide induces cell death in cancer cells and apoptosis is dependent upon the induction of endoplasmic reticulum stress (ER stress) leading to the unfolded protein response (UPR). The goal of the present study was to determine the mechanism by which andrographolide induces ER stress and to further evaluate its role in promoting cell death pathways. The T84 and COLO 205 cancer cell lines were used to demonstrate that andrographolide induces increased ROS levels, corresponding anti-oxidant response molecules, and reduced mitochondrial membrane potential. No increases in ROS levels were detected in control colon fibroblast cells. Andrographolide-induced cell death, UPR signaling, and CHOP, Bax, and caspase 3 apoptosis elements were all inhibited in the presence of the ROS scavenger NAC. Additionally, andrographolide-induced suppression of cyclins B1 and D1 were also reversed in the presence of NAC. Finally, Akt phosphorylation and phospho-mTOR levels that are normally suppressed by andrographolide were also expressed at normal levels in the absence of ROS. These data demonstrate that andrographolide induces ER stress leading to apoptosis through the induction of ROS and that elevated ROS also play an important role in down-regulating cell cycle progression and cell survival pathways as well.

Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington's disease.

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Anna Bobrowska

Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder for which there is no effective disease modifying treatment. Following-on from studies in HD animal models, histone deacetylase (HDAC inhibition has emerged as an attractive therapeutic option. In parallel, several reports have demonstrated a role for histone deacetylase 6 (HDAC6 in the modulation of the toxicity caused by the accumulation of misfolded proteins, including that of expanded polyglutamine in an N-terminal huntingtin fragment. An important role for HDAC6 in kinesin-1 dependent transport of brain-derived neurotrophic factor (BDNF from the cortex to the striatum has also been demonstrated. To elucidate the role that HDAC6 plays in HD progression, we evaluated the effects of the genetic depletion of HDAC6 in the R6/2 mouse model of HD. Loss of HDAC6 resulted in a marked increase in tubulin acetylation throughout the brain. Despite this, there was no effect on the onset and progression of a wide range of behavioural, physiological, molecular and pathological HD-related phenotypes. We observed no change in the aggregate load or in the levels of soluble mutant exon 1 transprotein. HDAC6 genetic depletion did not affect the efficiency of BDNF transport from the cortex to the striatum. Therefore, we conclude that HDAC6 inhibition does not modify disease progression in R6/2 mice and HDAC6 should not be prioritized as a therapeutic target for HD.

Dietary guanidinoacetic acid increases brain creatine levels in healthy men

DEFF Research Database (Denmark)

Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik

2017-01-01

OBJECTIVE: Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA......, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. RESULTS: Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation......, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8...

The spectrum of progressive derecho formation environments

Science.gov (United States)

Guastini, Corey T.

Progressive derechos are severe mesoscale convective systems that often form east of the Rocky Mountains during the warm season (May--August) and cause, by definition, straight-line wind damage along paths upwards of 400 km long. This study develops a subjective, seven-category classification scheme that spans the spectrum of progressive derecho formation environments from those dominated by robust upper-level ridges to those characterized by vigorous upper-level troughs. A climatology of 256 progressive derecho events is created for 1996--2013 and is categorized according to the developed classification scheme. Derecho initiation-relative composites are constructed for each of the seven groups using 0.5° Climate Forecast System Reanalysis data to document the environmental characteristics unique to each group as well as those shared among them. Finally, two in-depth case studies and five cursory case studies provide examples of the seven categories and reveal important nuances in mesoscale dynamic and thermodynamic structure inherent to all derecho cases. Results of the climatology show progressive derecho activity increases from 1 May through 1 July before decreasing again through the end of August and follows a northward trend in latitude from 1 May through 1 August before shifting slightly southward through the end of the warm season. Upslope flow in the vicinity of the Rocky Mountains initiates 28 percent of progressive derechos, upper-level troughs initiate 20 percent, 47 percent form in benign synoptic environments, and 5 percent are unclassifiable. Composite results show all progressive derecho initiation environments are marked by a long axis of instability caused by the overlap of high atmospheric moisture content and steep midlevel lapse rates, but the relative positions and strengths of upper-level troughs and ridges are crucial in determining how the instability axis develops and what its orientation in space will be. Case studies reveal instability

Investigation of Increased Mercury Levels in the Fisheries of Lower East Fork Poplar Creek (LEFPC), Oak Ridge Reservation, Tennessee

International Nuclear Information System (INIS)

Byrne-Kelly, D.; Cornish, J.; Hart, A.; Southworth, G.; Simms, L.

2006-01-01

The DOE Western Environmental Technology Office (WETO) is supporting Oak Ridge's remediation efforts by performing this study. MSE Technology Applications, Inc. (MSE) has performed a series of literature reviews and bench-scale testing to further evaluate the mercury problem in the Lower East Fork Poplar Creek (LEFPC) at Oak Ridge. The primary problem is that total mercury (HgT) levels in LEFPC water decrease, while HgT levels in sunfish muscle tissue increase, with distance away from the National Security Complex (NSC), despite extensive source control efforts at the facility. Furthermore, dissolved methylmercury (d-MeHg) levels increase downstream from the NSC, especially during warm weather and/or high flow events. MSE performed four test series that focused on conversion of dissolved and colloidal forms of elemental mercury (Hg deg.A) to methyl mercury (MeHg) by algal-bacterial bio-films (periphyton) present in the stream-bed of LEFPC; MeHg production by these bio-films under anoxic versus oxic conditions was the critical measurement taken. The bench-scale testing for Phase I was completed November 2005. The final reporting and the planning for Phase II testing are in progress. (authors)

Recent progress in low-level gamma imaging

International Nuclear Information System (INIS)

Mahe, C.; Girones, Ph.; Lamadie, F.; Le Goaller, C.

2007-01-01

The CEA's Aladin gamma imaging system has been operated successfully for several years in nuclear plants and during decommissioning projects with additional tools such as gamma spectrometry detectors and dose rate probes. The radiological information supplied by these devices is becoming increasingly useful for establishing robust and optimized decommissioning scenarios. Recent technical improvements allow this gamma imaging system to be operated in low-level applications and with shorter acquisition times suitable for decommissioning projects. The compact portable system can be used in places inaccessible to operators. It is quick and easy to implement, notably for onsite component characterization. Feasibility trials and in situ measurements were recently carried out under low-level conditions, mainly on waste packages and glove boxes for decommissioning projects. This paper describes recent low-level in situ applications. These characterization campaigns mainly concerned gamma emitters with γ energy < 700 keV. In many cases, the localization of hot spots by gamma camera was confirmed by additional measurements such as dose rate mapping and gamma spectrometry measurements. These complementary techniques associated with advanced calculation codes (MCNP, Mercure 6.2, Visiplan and Siren) offer a mobile and compact tool for specific assessment of waste packages and glove boxes. (authors)

Northern European trees show a progressively diminishing response to increasing atmospheric carbon dioxide concentrations

CSIR Research Space (South Africa)

Waterhouse, JS

2004-04-01

Full Text Available Reviews 23 (2004) 803?810 Northern European trees show a progressively diminishing response to increasing atmospheric carbon dioxide concentrations J.S. Waterhousea,*, V.R. Switsura,b, A.C. Barkera, A.H.C. Cartera,b,{, D.L. Hemmingc, N.J. Loaderd, I..., V.R., Waterhouse, J.S., Heaton, T.H.E., Carter, A.H.C., 1998. Climatic variation andthe stable carbon isotope composition of tree ring cellulose: an intercomparison of Quercus robur, Fagus sylvatica and Pinus silvestris. Tellus 50B, 25?33. J.ggi, M...

MIF functional polymorphisms (-794 CATT5-8 and -173 G>C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population.

Science.gov (United States)

Castañeda-Moreno, V A; De la Cruz-Mosso, U; Torres-Carrillo, N; Macías-Islas, M A; Padilla-De la Torre, O; Mireles-Ramírez, M A; González-Pérez, O; Ruiz-Sandoval, J L; Huerta, M; Trujillo, X; Ortuño-Sahagún, D; Jf, Muñoz-Valle

2018-07-15

Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT 5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT 5-8 MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population. Copyright © 2018 Elsevier B.V. All rights reserved.

1987 annual report on low-level radioactive waste management progress: Report to Congress in response to Public Law 99-240

International Nuclear Information System (INIS)

1988-08-01

In response to Section 7(b) of the Low-Level Radioactive Waste Policy Amendments Act of 1985 (Public Law 99-240), this report summarizes the progress of states and low-level radioactive waste compacts in 1987 in establishing new low-level waste disposal facilities. It also reports the volume of low-level waste received for disposal in 1987 by commercially operated low-level waste disposal facilities

Restoration of microRNA‑218 increases cellular chemosensitivity to cervical cancer by inhibiting cell‑cycle progression.

Science.gov (United States)

Dong, Ruofan; Qiu, Haifeng; Du, Guiqiang; Wang, Yuan; Yu, Jinjin; Mao, Caiping

2014-12-01

We previously reported frequent loss of microRNA‑218 (miR‑218) in human cervical cancer, which was associated with tumor progression and poor prognosis. In this study, we investigated whether restoration of the miR‑218 level is a valid strategy for the treatment of cervical cancer. The expression of miR‑218 in cervical cancer samples and cell lines was quantified by reverse transcription TaqMan quantitative (RT‑q)PCR. Overexpression of miR‑218 was achieved by both transient and stable transfection, using a miR‑218 mimic and a miR‑218‑expressing plasmid, respectively. Alterations in cellular proliferation and cell‑cycle progression were measured by the MTT assay and flow cytometry analysis. Nude mice bearing SiHa xenografts were used to investigate the functions of miR‑218 and carboplatin on tumor growth and weight. The expression of cycle‑related proteins was detected by western blotting and immunohistochemical staining. In vitro, miR‑218 significantly inhibited cellular growth in all four cell lines tested (P=0.021 for CaSki, P=0.009 for HeLa, P=0.016 for SiHa, and P=0.029 for C33A). Overexpression of miR‑218 induced G1 phase arrest and reduced expression of cyclin D1 and CDK4. In vivo, restoration of miR‑218 notably inhibited tumor growth and decreased tumor weight. In primary cultured samples, tumors with high levels of miR‑218 were more sensitive to carboplatin (R2=0.3319, P=0.0026); consistently, miR‑218 overexpression suppressed tumor growth, induced cell‑cycle arrest, and reduced the cyclin D1 level. Based on these and previous results, we conclude that restoration of the miR‑218 level inhibits the growth of cervical cancer cells both in vitro and in vivo; furthermore, overexpression of miR‑218 sensitizes cervical cancer cells to carboplatin. Our findings suggest a novel therapy for cervical cancer based on miR‑218, especially in patients with reduced levels of miR‑218.

Influence of fatigue time and level on increases in postural sway.

Science.gov (United States)

Pline, Kevin M; Madigan, Michael L; Nussbaum, Maury A

2006-12-15

The purpose of this study was to investigate the influence of fatigue time and fatigue level on the increases in postural sway during quiet standing. Centre of pressure-based measures of postural sway were collected both before and after fatiguing participants using three different fatigue levels and two different fatigue times. Results showed increasing fatigue time increased sway velocity and sway area, and increasing fatigue level increased sway velocity. Fatigue time effects are important to consider when applying laboratory-based findings to the field given that the fatigue time can differ substantially between the two. Fatigue level effects imply a dose - response relationship between localized muscle fatigue and risk of falling that can have important implications in work/rest cycle scheduling for occupations at risk of injurious falls.

Benchmarking Successional Progress in a Quantitative Food Web

Science.gov (United States)

Boit, Alice; Gaedke, Ursula

2014-01-01

Central to ecology and ecosystem management, succession theory aims to mechanistically explain and predict the assembly and development of ecological communities. Yet processes at lower hierarchical levels, e.g. at the species and functional group level, are rarely mechanistically linked to the under-investigated system-level processes which drive changes in ecosystem properties and functioning and are comparable across ecosystems. As a model system for secondary succession, seasonal plankton succession during the growing season is readily observable and largely driven autogenically. We used a long-term dataset from large, deep Lake Constance comprising biomasses, auto- and heterotrophic production, food quality, functional diversity, and mass-balanced food webs of the energy and nutrient flows between functional guilds of plankton and partly fish. Extracting population- and system-level indices from this dataset, we tested current hypotheses about the directionality of successional progress which are rooted in ecosystem theory, the metabolic theory of ecology, quantitative food web theory, thermodynamics, and information theory. Our results indicate that successional progress in Lake Constance is quantifiable, passing through predictable stages. Mean body mass, functional diversity, predator-prey weight ratios, trophic positions, system residence times of carbon and nutrients, and the complexity of the energy flow patterns increased during succession. In contrast, both the mass-specific metabolic activity and the system export decreased, while the succession rate exhibited a bimodal pattern. The weighted connectance introduced here represents a suitable index for assessing the evenness and interconnectedness of energy flows during succession. Diverging from earlier predictions, ascendency and eco-exergy did not increase during succession. Linking aspects of functional diversity to metabolic theory and food web complexity, we reconcile previously disjoint bodies of

Benchmarking successional progress in a quantitative food web.

Directory of Open Access Journals (Sweden)

Alice Boit

Full Text Available Central to ecology and ecosystem management, succession theory aims to mechanistically explain and predict the assembly and development of ecological communities. Yet processes at lower hierarchical levels, e.g. at the species and functional group level, are rarely mechanistically linked to the under-investigated system-level processes which drive changes in ecosystem properties and functioning and are comparable across ecosystems. As a model system for secondary succession, seasonal plankton succession during the growing season is readily observable and largely driven autogenically. We used a long-term dataset from large, deep Lake Constance comprising biomasses, auto- and heterotrophic production, food quality, functional diversity, and mass-balanced food webs of the energy and nutrient flows between functional guilds of plankton and partly fish. Extracting population- and system-level indices from this dataset, we tested current hypotheses about the directionality of successional progress which are rooted in ecosystem theory, the metabolic theory of ecology, quantitative food web theory, thermodynamics, and information theory. Our results indicate that successional progress in Lake Constance is quantifiable, passing through predictable stages. Mean body mass, functional diversity, predator-prey weight ratios, trophic positions, system residence times of carbon and nutrients, and the complexity of the energy flow patterns increased during succession. In contrast, both the mass-specific metabolic activity and the system export decreased, while the succession rate exhibited a bimodal pattern. The weighted connectance introduced here represents a suitable index for assessing the evenness and interconnectedness of energy flows during succession. Diverging from earlier predictions, ascendency and eco-exergy did not increase during succession. Linking aspects of functional diversity to metabolic theory and food web complexity, we reconcile

Benchmarking successional progress in a quantitative food web.

Science.gov (United States)

Boit, Alice; Gaedke, Ursula

2014-01-01

Central to ecology and ecosystem management, succession theory aims to mechanistically explain and predict the assembly and development of ecological communities. Yet processes at lower hierarchical levels, e.g. at the species and functional group level, are rarely mechanistically linked to the under-investigated system-level processes which drive changes in ecosystem properties and functioning and are comparable across ecosystems. As a model system for secondary succession, seasonal plankton succession during the growing season is readily observable and largely driven autogenically. We used a long-term dataset from large, deep Lake Constance comprising biomasses, auto- and heterotrophic production, food quality, functional diversity, and mass-balanced food webs of the energy and nutrient flows between functional guilds of plankton and partly fish. Extracting population- and system-level indices from this dataset, we tested current hypotheses about the directionality of successional progress which are rooted in ecosystem theory, the metabolic theory of ecology, quantitative food web theory, thermodynamics, and information theory. Our results indicate that successional progress in Lake Constance is quantifiable, passing through predictable stages. Mean body mass, functional diversity, predator-prey weight ratios, trophic positions, system residence times of carbon and nutrients, and the complexity of the energy flow patterns increased during succession. In contrast, both the mass-specific metabolic activity and the system export decreased, while the succession rate exhibited a bimodal pattern. The weighted connectance introduced here represents a suitable index for assessing the evenness and interconnectedness of energy flows during succession. Diverging from earlier predictions, ascendency and eco-exergy did not increase during succession. Linking aspects of functional diversity to metabolic theory and food web complexity, we reconcile previously disjoint bodies of

e-Learning for expanding distance education in tertiary level in Bangladesh: Problems and progress

Directory of Open Access Journals (Sweden)

Md. Abdullah Al-Masum

2013-11-01

Full Text Available E-learning has broadly become an important enabler to promote distance education (DE and lifelong learning in most of the developed countries, but in Bangladesh it is still a new successful progressive system for the learning communities. Distance education is thought to be introduced as an effective way of educating people of all sections in Bangladesh. Bangladesh Open University (BOU, the only distance education provider in Bangladesh, has been trying to adopt the use of various e-learning materials for its distance delivery. This paper has tried to describe the current progress of quality e-learning for expanding distance education, identifying the major problems of e-learning in distance education at tertiary level in Bangladesh, with special reference to BOU, and finally to put forward some valuable recommendations for solving the problems. The study is based on both primary and secondary sources. It is observed from the research that e-learning is going to ensure its bright prospect as an alternative mode of education at the tertiary level in Bangladesh. There are several problems that are identified and can be mitigated and solved through Information and Communication Technology (ICT development, greater acceptance by learners, and much research in this sector in Bangladesh to face globalization.   DOI: 10.18870/hlrc.v3i4.171

Diffuse radiation increases global ecosystem-level water-use efficiency

Science.gov (United States)

Moffat, A. M.; Reichstein, M.; Cescatti, A.; Knohl, A.; Zaehle, S.

2012-12-01

Current environmental changes lead not only to rising atmospheric CO2 levels and air temperature but also to changes in air pollution and thus the light quality of the solar radiation reaching the land-surface. While rising CO2 levels are thought to enhance photosynthesis and closure of stomata, thus leading to relative water savings, the effect of diffuse radiation on transpiration by plants is less clear. It has been speculated that the stimulation of photosynthesis by increased levels of diffuse light may be counteracted by higher transpiration and consequently water depletion and drought stress. Ultimately, in water co-limited systems, the overall effect of diffuse radiation will depend on the sensitivity of canopy transpiration versus photosynthesis to diffuse light, i.e. whether water-use efficiency changes with relative levels of diffuse light. Our study shows that water-use efficiency increases significantly with higher fractions of diffuse light. It uses the ecosystem-atmosphere gas-exchange observations obtained with the eddy covariance method at 29 flux tower sites. In contrast to previous global studies, the analysis is based directly on measurements of diffuse radiation. Its effect on water-use efficiency was derived by analyzing the multivariate response of carbon and water fluxes to radiation and air humidity using a purely empirical approach based on artificial neural networks. We infer that per unit change of diffuse fraction the water-use efficiency increases up to 40% depending on diffuse fraction levels and ecosystem type. Hence, in regions with increasing diffuse radiation positive effects on primary production are expected even under conditions where water is co-limiting productivity.

Value of HBsAg level in dynamic monitoring of disease progression in patients with chronic HBV infection

Directory of Open Access Journals (Sweden)

BAO Teng

2017-08-01

Full Text Available ObjectiveTo investigate the clinical value of HBsAg level in dynamic monitoring of disease progression in patients with chronic HBV infection. MethodsA retrospective analysis was performed for the clinical data of 1107 patients with different clinical stages of chronic HBV infection who had not received antiviral therapy at the time of hospitalization in The Second Affiliated Hospital of Anhui Medical University from May 2011 to December 2015, and according to the disease status, they were divided into HBeAg-positive chronic hepatitis B (CHB group, HBeAg-negative CHB group, compensated liver cirrhosis group (LC-C group, decompensated liver cirrhosis group (LC-D group, and primary liver cancer (PLC group. These groups were compared in terms of HBsAg expression and the association between HBsAg and clinical features. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between any two groups; the t-test was used for comparison of continuous data between two groups. The chi-square test was used for comparison of categorical data between these groups. Pearson correlation analysis was also performed. ResultsThere was a significant difference in serum HBsAg level between the HBeAg-positive CHB group, HBeAg-negative CHB group, LC-C group, LC-D group, and PLC group (F=100.45, P＜0.001. The HBeAg-positive CHB group had significantly higher levels of HBsAg and HBV DNA than the HBeAg-negative CHB group (t= 16.67 an 16.22, both P＜0.001. There were significant differences in HBsAg and HBV DNA levels between the HBeAg-positive CHB group, LC-C group, LC-D group, and PLC group (F= 42.92 and 27.38, both P＜0.001, as well as between the HBeAg-negative CHB group, LC-C group, LC-D group, and PLC group (F=6.04 and 4.10, both P＜0.05. HBV DNA level was significantly different across patients with different HBsAg levels (＜1000 IU/ml, 1000-20 000 IU

Self-reported levels of education and disability progression in multiple sclerosis

NARCIS (Netherlands)

D'hooghe, M. B.; Haentjens, P.; Van Remoortel, A.; De Keyser, J.; Nagels, G.

2016-01-01

ObjectivesThe purpose of our study is to investigate whether socioeconomic indicators such as education, financial concerns, employment, and living status are associated with disease progression in relapsing-onset and progressive-onset Multiple Sclerosis (MS). Materials and methodsWe performed a

1992 annual report on low-level radioactive waste management progress; Report to Congress in response to Public Law 99-240

Energy Technology Data Exchange (ETDEWEB)

NONE

1993-11-01

This report summarizes the progress States and compact regions made during 1992 in establishing new low-level radioactive waste disposal facilities. It also provides summary information on the volume of low-level radioactive waste received for disposal in 1992 by commercially operated low-level radioactive waste disposal facilities. This report is in response to section 7 (b) of the Low-Level Radioactive Waste Policy Act.

When Progressive Disease Does Not Mean Treatment Failure: Reconsidering the Criteria for Progression

Science.gov (United States)

2012-01-01

Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of “objective progression” is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology. PMID:22927506

Determination of lactic acid level in systemic liquids in children with progressive encephalopathies.

Science.gov (United States)

Marszał, Elzbieta; Wojaczyńska-Stanek, Katarzyna; Pietruszewski, Jerzy; Emich-Widera, Ewa; Bielińska-Bujniewicz, Eugenia

2002-03-01

This article reports the results of research into the activities of lactic acid concentrations in the body fluids of children with progressive encephalopathies (PE) in comparison to patients with non-progressive encephalopathies (NPE) and those with non-progressive encephalopathies with concomitant epilepsy (NPEE). The study was designed to determine whether there is difference between the serum and CSF lactic acid concentrations in children with progressive encephalopathies (PE), static (non-progressive) encephalopathies (NPE) and non progressive encephalopathies with concomitant epilepsy (NPEE), and whether the clinical status correlates with the concentration of these biochemical markers in children with PE. The assessment involved 138 children of both sexes, whose age ranged between 8 months and 15 years, diagnosed and treated in the Neurology Department at the Pediatric Clinic of the Silesian Medical Academy in Katowice between 1995 and 1997. Lactate concentrations were determined in serum and cerebro-spinal fluid and analyzed statistically. The findings showed higher serum and CSF concentrations in children with PE than in patients who manifested non-progressive forms of encephalopathy. The degree of clinical symptom aggravation in PE children was likewise analyzed and compared to the values of lactate concentrations in body fluids; however, no correlation was found between these parameters. Children with progressive encephalopathies present higher lactate concentrations in serum and cerebrospinal fluid than patients with static (non-progressive) encephalopathy.

Endozepine-4 levels are increased in hepatic coma.

Science.gov (United States)

Malaguarnera, Giulia; Vacante, Marco; Drago, Filippo; Bertino, Gaetano; Motta, Massimo; Giordano, Maria; Malaguarnera, Michele

2015-08-14

To evaluate the serum levels of endozepine-4, their relation with ammonia serum levels, the grading of coma and the severity of cirrhosis, in patients with hepatic coma. In this study we included 20 subjects with Hepatic coma, 20 subjects with minimal hepatic encephalopathy (MHE) and 20 subjects control. All subjects underwent blood analysis, Child Pugh and Model for End - stage liver disease (MELD) assessment, endozepine-4 analysis. Subjects with hepatic coma showed significant difference in endozepine-4 (P blood ammonia concentration was noted to be raised in patients with hepatic coma, with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia (P < 0.001). In patients with grade IV hepatic coma, endozepine levels were significantly higher compared to other groups. This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion, data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.

[The effect of EMG level by EMG biofeedback with progressive muscle relaxation training on tension headache].

Science.gov (United States)

Ro, U J; Kim, N C; Kim, H S

1990-08-01

The purpose of this study is to assess if EMG biofeedback training with progressive muscle relaxation training is effective in reducing the EMG level in patients with tension headaches. This study which lasted from 23 October to 30 December 1989, was conducted on 10 females who were diagnosed as patients with tension headaches and selected from among volunteers at C. University in Seoul. The process of the study was as follows: First, before the treatment, the baseline was measured for two weeks and the level of EMG was measured five times in five minutes. And then EMG biofeedback training was used for six weeks, 12 sessions in all, and progressive muscle relaxation was done at home by audio tape over eight weeks. Each session was composed of a 5-minute baseline, two 5-minute EMG biofeedback training periods and a 5-minute self-control stage. Each stage was followed by a five minute rest period. So each session took a total of 40 minutes. The EMG level was measured by EMG biofeedback (Autogenic-Cyborg: M 130 EMG module). The results were as follows: 1. The average age of the subjects was 44.1 years and the average history of headache was 10.6 years (range: 6 months-20 years). 2. The level of EMG was lowest between the third and the fourth week of the training except in Cases I and IV. 3. The patients began to show a nonconciliatory attitude at the first session of the fifth week of the training.

Increased expression of OX40 is associated with progressive disease in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.

Science.gov (United States)

Saito, Mineki; Tanaka, Reiko; Arishima, Shiho; Matsuzaki, Toshio; Ishihara, Satoshi; Tokashiki, Takashi; Ohya, Yusuke; Takashima, Hiroshi; Umehara, Fujio; Izumo, Shuji; Tanaka, Yuetsu

2013-05-07

OX40 is a member of the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells and promotes the development of effector and memory T cells. Although OX40 has been reported to be a target gene of human T-cell leukemia virus type-1 (HTLV-1) viral transactivator Tax and is overexpressed in vivo in adult T-cell leukemia (ATL) cells, an association between OX40 and HTLV-1-associated inflammatory disorders, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), has not yet been established. Moreover, because abrogation of OX40 signals ameliorates chronic inflammation in animal models of autoimmune disease, novel monoclonal antibodies against OX40 may offer a potential treatment for HTLV-1-associated diseases such as ATL and HAM/TSP. In this study, we showed that OX40 was specifically expressed in CD4+ T cells naturally infected with HTLV-1 that have the potential to produce pro-inflammatory cytokines along with Tax expression. We also showed that OX40 was overexpressed in spinal cord infiltrating mononuclear cells in a clinically progressive HAM/TSP patient with a short duration of illness. The levels of the soluble form of OX40 (sOX40) in the cerebrospinal fluid (CSF) from chronic progressive HAM/TSP patients or from patients with other inflammatory neurological diseases (OINDs) were not different. In contrast, sOX40 levels in the CSF of rapidly progressing HAM/TSP patients were higher than those in the CSF from patients with OINDs, and these patients showed higher sOX40 levels in the CSF than in the plasma. When our newly produced monoclonal antibody against OX40 was added to peripheral blood mononuclear cells in culture, HTLV-1-infected T cells were specifically removed by a mechanism that depends on antibody-dependent cellular cytotoxicity. Our study identified OX40 as a key molecule and biomarker for rapid progression of HAM/TSP. Furthermore, blocking OX40 may have potential in therapeutic intervention for

Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease.

Science.gov (United States)

Ramachandran, Surya; Venugopal, Anila; Kutty, V Raman; A, Vinitha; G, Divya; Chitrasree, V; Mullassari, Ajit; Pratapchandran, N S; Santosh, K R; Pillai, M Radhakrishna; Kartha, C C

2014-02-07

Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD). Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored. Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease. Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular disease in type 2 diabetes. Considering the evidence that

What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 micromol/L.

Science.gov (United States)

Hackam, D G; Peterson, J C; Spence, J D

2000-01-01

High levels of plasma homocyst(e)ine (H[e]) are associated with increased vascular risk. Treatment is being contemplated, but the level at which patients should be treated is not known. We compared the response of carotid plaque to vitamin therapy in patients with H(e) above and below 14 micromol/L, a level commonly regarded as high enough to warrant treatment. Two-dimensional B-mode ultrasound measurement of carotid plaque was used to assess the response to vitamin therapy with folic acid 2.5 mg, pyridoxine 25 mg, and cyanocobalamin 250 microg daily, in 101 patients with vascular disease (51 with initial plasma levels above, and 50 below 14 micromol/L). Among patients with plasma H(e) >14 micromol/L, the rate of progression of plaque area was 0.21 +/- 0.41 cm2/year before vitamin therapy, and -0.049 +/- 0.24 cm2/year after vitamin therapy (P2 = .0001; paired t test). Among patients with levels ine and atherosclerosis and, taken with epidemiologic evidence, suggest that in patients with vascular disease, the level to treat may be <9 micromol/L.

Assessing the sensitivity of human skin hyperspectral responses to increasing anemia severity levels

Science.gov (United States)

Baranoski, Gladimir V. G.; Dey, Ankita; Chen, Tenn F.

2015-09-01

Anemia is a prevalent medical condition that seriously affects millions of people all over the world. In many regions, not only its initial detection but also its monitoring are hindered by limited access to laboratory facilities. This situation has motivated the development of a wide range of optical devices and procedures to assist physicians in these tasks. Although noticeable progress has been achieved in this area, the search for reliable, low-cost, and risk-free solutions still continues, and the strengthening of the knowledge base about this disorder and its effects is essential for the success of these initiatives. We contribute to these efforts by closely examining the sensitivity of human skin hyperspectral responses (within and outside the visible region of the light spectrum) to reduced hemoglobin concentrations associated with increasing anemia severity levels. This investigation, which involves skin specimens with distinct biophysical and morphological characteristics, is supported by controlled in silico experiments performed using a predictive light transport model and measured data reported in the biomedical literature. We also propose a noninvasive procedure to be employed in the monitoring of this condition at the point-of-care.

Capital Income Taxation and Progressivity in a Global Economy

OpenAIRE

Rosanne Altshuler; Benjamin Harris; Eric Toder

2011-01-01

The increase in international capital mobility over the past two decades has put pressure on the tax treatment of corporate equity income. Corporate-level taxes distort investment flows across locations and create opportunities for tax avoidance by shifting income across jurisdictions. Outward flows of capital shift part of the burden of the corporate-level tax on equity income from capital to labor, thereby making its incidence less progressive. Individual-level taxes on corporate equity inc...

Level 1 - level 2 interface

International Nuclear Information System (INIS)

Boneham, P.

2003-01-01

The Plant Damage States (PDS) are the starting point for the level 2 analysis. A PDS is group of core damage sequences that are expected to have similar severe accident progressions. In this paper an overview of Level 1/Level 2 interface, example PDS parameters, example PDS definitions using codes and example Bridge Tree are presented. PDS frequency calculation (identification of sequences for each PDS in level 1,split some CD sequences which have different level 2 progressions), code calculations providing support for grouping decisions and timings as well as PDS frequencies and definitions input to level 2 are also discussed

Report to Congress in response to Public Law 99-240: 1990 Annual report on low-level radioactive waste management progress

International Nuclear Information System (INIS)

1991-09-01

This report summarizes the progress during 1990 of states and compact regions in establishing new low-level radioactive waste disposal facilities. It also provides summary information on the volume of low-level radioactive waste received for disposal in 1990 by commercially operated low-level radioactive waste disposal facilities. This report is in response to section 7 (b) of the Low-Level Radioactive Waste Policy Act, as amended by Public Law 99-240

INCREASING SAVING BEHAVIOR THROUGH AGE-PROGRESSED RENDERINGS OF THE FUTURE SELF

Science.gov (United States)

HERSHFIELD, HAL E.; GOLDSTEIN, DANIEL G.; SHARPE, WILLIAM F.; FOX, JESSE; YEYKELIS, LEO; CARSTENSEN, LAURA L.; BAILENSON, JEREMY N.

2014-01-01

Many people fail to save what they need to for retirement (Munnell, Webb, and Golub-Sass 2009). Research on excessive discounting of the future suggests that removing the lure of immediate rewards by pre-committing to decisions, or elaborating the value of future rewards can both make decisions more future-oriented. In this article, we explore a third and complementary route, one that deals not with present and future rewards, but with present and future selves. In line with thinkers who have suggested that people may fail, through a lack of belief or imagination, to identify with their future selves (Parfit 1971; Schelling 1984), we propose that allowing people to interact with age-progressed renderings of themselves will cause them to allocate more resources toward the future. In four studies, participants interacted with realistic computer renderings of their future selves using immersive virtual reality hardware and interactive decision aids. In all cases, those who interacted with virtual future selves exhibited an increased tendency to accept later monetary rewards over immediate ones. PMID:24634544

INCREASING SAVING BEHAVIOR THROUGH AGE-PROGRESSED RENDERINGS OF THE FUTURE SELF.

Science.gov (United States)

Hershfield, Hal E; Goldstein, Daniel G; Sharpe, William F; Fox, Jesse; Yeykelis, Leo; Carstensen, Laura L; Bailenson, Jeremy N

2011-11-01

Many people fail to save what they need to for retirement (Munnell, Webb, and Golub-Sass 2009). Research on excessive discounting of the future suggests that removing the lure of immediate rewards by pre-committing to decisions, or elaborating the value of future rewards can both make decisions more future-oriented. In this article, we explore a third and complementary route, one that deals not with present and future rewards, but with present and future selves. In line with thinkers who have suggested that people may fail, through a lack of belief or imagination, to identify with their future selves (Parfit 1971; Schelling 1984), we propose that allowing people to interact with age-progressed renderings of themselves will cause them to allocate more resources toward the future. In four studies, participants interacted with realistic computer renderings of their future selves using immersive virtual reality hardware and interactive decision aids. In all cases, those who interacted with virtual future selves exhibited an increased tendency to accept later monetary rewards over immediate ones.

Both experimental hypothyroidism and hyperthyroidism increase cardiac irisin levels in rats.

Science.gov (United States)

Atici, E; Menevse, E; Baltaci, A K; Mogulkoc, R

2018-01-01

Irisin is a newly discovered myokine and adipokine that increases total body energy expenditure. The aim of this study was to determine the effect of experimental hypothyroidism and hyperthyroidism on the levels of irisin in heart tissue in rats. The study was performed on the 40 male Sprague-Dawley rats. Experimental groups were designed as; Control, Hypothyroidism, Hypothyroidism+L-Thyroxine, Hyperthyroidism and Hyperthyroidism + PTU. Following 3 weeks experimental period, irisin levels were determined in heart tissues. Hypothyroidism group values of irisin were higher than in the control group, but lower than in the hyperthyroidism group. The hyperthyroidism group had the highest levels of cardiac irisin. The results of the study showed that the experimental hypothyroidism and hyperthyroidism increased the heart irisin levels, but the increase in the hyperthyroidism group was much higher than in the hypothyroidism group. However, treatment of hypothyroidism and hyperthyroidism corrected cardiac irisin levels (Fig. 1, Ref. 28).

Effects of Water Level Increase on Phytoplankton Assemblages in a Drinking Water Reservoir

Directory of Open Access Journals (Sweden)

Yangdong Pan

2018-03-01

Full Text Available Excessive water level fluctuation may affect physico-chemical characteristics, and consequently ecosystem function, in lakes and reservoirs. In this study, we assessed the changes of phytoplankton assemblages in response to water level increase in Danjiangkou Reservoir, one of the largest drinking water reservoirs in Asia. The water level increased from a low of 137 m to 161 m in 2014 as a part of the South–North Water Diversion Project. Phytoplankton assemblages were sampled four times per year before, during and after the water level increase, at 10 sites. Environmental variables such as total nitrogen as well as phytoplankton biomass decreased after the water level increase. Non-metric multi-dimensional scaling analysis indicated that before the water level increase, phytoplankton assemblages showed distinct seasonal variation with diatom dominance in both early and late seasons while such seasonal variation was much less evident after the water level increase. Month and year (before and after explained 13% and 6% of variance in phytoplankton assemblages (PERMANOVA, p < 0.001 respectively, and phytoplankton assemblages were significantly different before and after the water level increase. Both chlorophytes and cyanobacteria became more abundant in 2015. Phytoplankton compositional change may largely reflect the environmental changes, such as hydrodynamics mediated by the water level increase.

Do levels of perceived stress increase with increasing age after age 65? A population-based study.

Science.gov (United States)

Osmanovic-Thunström, Almira; Mossello, Enrico; Åkerstedt, Torbjörn; Fratiglioni, Laura; Wang, Hui-Xin

2015-09-01

psychological and health-related stressors often occur in advanced ages, but little is known about perceived stress in adults aged 65 and over. This study aimed to test the hypothesis that levels of perceived stress increase with increasing age and to detect factors that may account for the association. a dementia-free cohort of 1,656 adults aged 66-97 years living at home or in institutions, participating in the Swedish National Aging and Care study, Kungsholmen (SNAC-K) was assessed for levels of perceived stress using the 10-item perceived stress scale (PSS). prevalence of high stress according to the top tertile of the population (PSS score 20+) was 7.8% in adults aged 81+ years, 7.5% in adults aged 72-78 and 6.2% in adults aged 66 years (P = 0.020). More women than men reported high stress, 8.3 versus 5.4% (P = 0.001). Levels of stress increased with increasing age (P = 0.001) in the linear regression model. This association remained after adjustment for demographic and psychosocial factors, but no longer was present after adjusting for health-related factors. health-related stress is highly prevalent in older adults and seems to play an important role in the association between levels of perceived stress and age in older adults. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Serum Uric Acid and Progression of Kidney Disease: A Longitudinal Analysis and Mini-Review.

Directory of Open Access Journals (Sweden)

Ching-Wei Tsai

Full Text Available Increasing evidence supports the association between hyperuricemia and incident chronic kidney disease (CKD; however, there are conflicting data regarding the role of hyperuricemia in the progression of CKD. This study retrospectively assessed the longitudinal association between uric acid (UA level and CKD progression in a Chinese population lived in Taiwan.Patients with physician diagnosis of hyperuricemia or receiving urate-lowering therapy between 2003 and 2005 were identified in the electronic medical records (EMR of a tertiary medical center and were followed up until December 31, 2011. Patients were divided into four UA categories at the cut-off 6, 8, and 10 mg/dL. CKD progression was estimated by the change of estimated glomerular filtration rate (eGFR in the linear mixed models. Kidney failure was defined as an eGFR less than 15 mL/min/1.73 m2 or requiring renal replacement therapy.A total of 739 patients were analyzed. In the full-adjusted model, patients with a baseline UA level ≥6 mg/dL had greater decline in eGFR ((β = -9.6, 95% CI -16.1, -3.1, comparing to those with a UA level less than 6 mg/dL. When stratifying patients into four UA categories, all three hyperuricemia categories (UA6-8, 8-10, ≥10 mg/dL associated with a greater decline in eGFR over the follow-up period with an increasing dose-response, comparing to the lowest UA category. The risk of progression to renal failure increased 7% (hazard ratio 1.07, 95% CI 1.00, 1.14 for each 1mg/dL increase in baseline UA level. The influences of hyperuricemia on eGFR decline and the risk of kidney failure were more prominent in patients without proteinuria than those with proteinuria.Our study showed a higher uric acid level is associated with a significant rapid decline in eGFR and a higher risk of kidney failure, particularly in patients without proteinuria. Our findings suggest hyperuricemia is a potential modifiable factor of CKD progression.

"A case report of Pott’s disease with unusual involvement of two separate levels of spine and delayed progressive Kyphosis "

Directory of Open Access Journals (Sweden)

Rahimi Movaghar V

2001-05-01

Full Text Available In Pott’s disease (tuberculous spondylitis, involvement of two separate levels of spine is rare. Attention to stability of spine prevents delayed progressive kyphosis. A 12-year-old girl presented with neck pain, tenderness and swelling Imaging showed Cl—C2 and T9-T10 and destruction. Mild spastic paraparesis was noticed. Preoperative diagnosis was metastasis. T9, T10 and T11 laminectomy and cervical operations were done in 2 sessions. Both pathologic examinations confirmed tuberculosis. Although antituberculous medications and casting were performed, kyhosis progressed and neurologic deficit restrated. Reportation was done for spinal cord decompression and stabilzation. Tuberculosis could involve multiple spinal levels. Laminectomy is not suggested in children. Bone fusion and serial observations are important.

Emotionally arousing pictures increase blood glucose levels and enhance recall.

Science.gov (United States)

Blake, T M; Varnhagen, C K; Parent, M B

2001-05-01

Arousal enhances memory in human participants and this enhancing effect is likely due to the release of peripheral epinephrine. As epinephrine does not readily enter the brain, one way that peripheral epinephrine may enhance memory is by increasing circulating blood glucose levels. The present study investigated the possibility that emotionally arousing color pictures would improve memory and elevate blood glucose levels in human participants. Blood glucose levels were measured before, 15 min, and 30 min after male university students viewed 60 emotionally arousing or relatively neutral pictures. Participants viewed each picture for 6 s and then had 10 s to rate the arousal (emotional intensity) and valence (pleasantness) of each picture. A free-recall memory test was given 30 min after the last picture was viewed. Although the emotionally arousing and neutral picture sets were given comparable valence ratings, participants who viewed the emotionally arousing pictures rated the pictures as being more arousing, recalled more pictures, and had higher blood glucose levels after viewing the pictures than did participants who viewed the neutral pictures. These findings indicate that emotionally arousing pictures increase blood glucose levels and enhance memory, and that this effect is not due to differences in the degree of pleasantness of the stimuli. These findings support the possibility that increases in circulating blood glucose levels in response to emotional arousal may be part of the biological mechanism that allows emotional arousal to enhance memory. Copyright 2001 Academic Press.

Increased levels of circulating platelet-derived microparticles are associated with metastatic cutaneous melanoma.

Science.gov (United States)

Moreau, Joséphine; Pelletier, Fabien; Biichle, Sabeha; Mourey, Guillaume; Puyraveau, Marc; Badet, Nicolas; Caubet, Matthieu; Laresche, Claire; Garnache-Ottou, Francine; Saas, Philippe; Seilles, Estelle; Aubin, François

2017-10-01

We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 μL -1 ) than in patients with stage III (2041 μL -1 ) melanoma (P=.0001). We calculated a highly specific (93.3%) and predictive (91.7%) cut-off value (5311 μL -1 ) allowing the distinction between high-risk stage III and metastatic stage IV melanoma. The thrombogenic activity of PMPs was significantly higher in patients with stage IV melanoma (clotting time: 40.7 second vs 65 second, P=.0001). There was no significant association between the radiological tumoral syndrome and the plasma level of PMPs. Our data suggest the role of PMPs in metastatic progression of melanoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia

Science.gov (United States)

Cao, Chuanhai; Loewenstein, David A.; Lin, Xiaoyang; Zhang, Chi; Wang, Li; Duara, Ranjan; Wu, Yougui; Giannini, Alessandra; Bai, Ge; Cai, Jianfeng; Greig, Maria; Schofield, Elizabeth; Ashok, Raj; Small, Brent; Potter, Huntington; Arendash, Gary W.

2017-01-01

Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer’s disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65–88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2–4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (−51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 µM) in MCI subjects were associated with no conversion to dementia during the ensuing 2–4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI. PMID:22430531

Progressive activation of paratrigeminal nucleus during entrance to hibernation

International Nuclear Information System (INIS)

Kilduff, T.S.; Sharp, F.R.; Heller, H.C.

1988-01-01

The paratrigeminal nucleus (Pa5) undergoes a progressive increase in its uptake of 2-[ 14 C]deoxyglucose (2DG) relative to other brain structures during entrance to hibernation in the ground squirrel. This highly significant increase results in the Pa5 becoming the most highly labeled brain region during hibernation, even though it exhibits one of the lowest levels of 2DG uptake in the brain during the nonhibernating state. The progressive activation of the Pa5 observed during entrance is reversed during arousal from hibernation. These observations and the neuroanatomical projections of the Pa5 implicate this nucleus as playing a role in the entrance and maintenance of the hibernating state

Progressive practice promotes motor learning and repeated transient increases in corticospinal excitability across multiple days

DEFF Research Database (Denmark)

Christiansen, Lasse; Madsen, Mads Alexander Just; Bojsen-Møller, Emil

2018-01-01

Background: A session of motor skill learning is accompanied by transient increases in corticospinal excitability (CSE), which are thought to reflect acute changes in neuronal connectivity associated with improvements in sensorimotor performance. Factors influencing changes in excitability...... and motor skill with continued practice remain however to be elucidated. Objective/Hypothesis: Here we investigate the hypothesis that progressive motor practice during consecutive days can induce repeated transient increases in corticospinal excitability and promote motor skill learning. Methods: Changes...... in motor performance and CSE were assessed during 4 consecutive days of skill learning and 8 days after the last practice session. CSE was assessed as area under recruitment curves (RC) using transcranial magnetic stimulation (TMS). Two groups of participants (n = 12) practiced a visuomotor tracking...

Increased plasma agmatine levels in patients with schizophrenia.

Science.gov (United States)

Uzbay, Tayfun; Goktalay, Gokhan; Kayir, Hakan; Eker, Salih S; Sarandol, Asli; Oral, Sema; Buyukuysal, Levent; Ulusoy, Gokhan; Kirli, Selcuk

2013-08-01

Agmatine is an endogenous substance, synthesized from l-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p  0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Trophic assimilation efficiency markedly increases at higher trophic levels in four-level host-parasitoid food chain.

Science.gov (United States)

Sanders, Dirk; Moser, Andrea; Newton, Jason; van Veen, F J Frank

2016-03-16

Trophic assimilation efficiency (conversion of resource biomass into consumer biomass) is thought to be a limiting factor for food chain length in natural communities. In host-parasitoid systems, which account for the majority of terrestrial consumer interactions, a high trophic assimilation efficiency may be expected at higher trophic levels because of the close match of resource composition of host tissue and the consumer's resource requirements, which would allow for longer food chains. We measured efficiency of biomass transfer along an aphid-primary-secondary-tertiary parasitoid food chain and used stable isotope analysis to confirm trophic levels. We show high efficiency in biomass transfer along the food chain. From the third to the fourth trophic level, the proportion of host biomass transferred was 45%, 65% and 73%, respectively, for three secondary parasitoid species. For two parasitoid species that can act at the fourth and fifth trophic levels, we show markedly increased trophic assimilation efficiencies at the higher trophic level, which increased from 45 to 63% and 73 to 93%, respectively. In common with other food chains, δ(15)N increased with trophic level, with trophic discrimination factors (Δ(15)N) 1.34 and 1.49‰ from primary parasitoids to endoparasitic and ectoparasitic secondary parasitoids, respectively, and 0.78‰ from secondary to tertiary parasitoids. Owing to the extraordinarily high efficiency of hyperparasitoids, cryptic higher trophic levels may exist in host-parasitoid communities, which could alter our understanding of the dynamics and drivers of community structure of these important systems. © 2016 The Authors.

Progressive geometric algorithms

NARCIS (Netherlands)

Alewijnse, S.P.A.; Bagautdinov, T.M.; de Berg, M.T.; Bouts, Q.W.; ten Brink, Alex P.; Buchin, K.A.; Westenberg, M.A.

2015-01-01

Progressive algorithms are algorithms that, on the way to computing a complete solution to the problem at hand, output intermediate solutions that approximate the complete solution increasingly well. We present a framework for analyzing such algorithms, and develop efficient progressive algorithms

Progressive geometric algorithms

NARCIS (Netherlands)

Alewijnse, S.P.A.; Bagautdinov, T.M.; Berg, de M.T.; Bouts, Q.W.; Brink, ten A.P.; Buchin, K.; Westenberg, M.A.

2014-01-01

Progressive algorithms are algorithms that, on the way to computing a complete solution to the problem at hand, output intermediate solutions that approximate the complete solution increasingly well. We present a framework for analyzing such algorithms, and develop efficient progressive algorithms

Technical reliability of geological disposal for high-level radioactive wastes in Japan. The second progress report. Part 1. Geological environment of Japan

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-11-01

Based on the Advisory Committee Report on Nuclear Fuel Cycle Backend Policy submitted to the Japanese Government in 1997, JNC documents the progress of research and development program in the form of the second progress report (the first one published in 1992). It summarizes an evaluation of the technical reliability and safety of the geological disposal concept for high-level radioactive wastes (HLW) in Japan. The present document, the part 1 of the progress report, describes first in detail the role of geological environment in high-level radioactive wastes disposal, the features of Japanese geological environment, and programs to proceed the investigation in geological environment. The following chapter summarizes scientific basis for possible existence of stable geological environment, stable for a long period needed for the HLW disposal in Japan including such natural phenomena as volcano and faults. The results of the investigation of the characteristics of bed-rocks and groundwater are presented. These are important for multiple barrier system construction of deep geological disposal. The report furthermore describes the present status of technical and methodological progress in investigating geological environment and finally on the results of natural analog study in Tono uranium deposits area. (Ohno, S.)

Increased cellular levels of spermidine or spermine are required for optimal DNA synthesis in lymphocytes activated by concanavalin A.

Science.gov (United States)

Fillingame, R H; Jorstad, C M; Morris, D R

1975-01-01

There are large increases in cellular levels of the polyamines spermidine and spermine in lymphocytes induced to transform by concanavalin A. The anti-leukemic agent methylglyoxal bis(guanylhydrazone) (MGBG) blocks synthesis of these polyamines by inhibiting S-adenosylmethionine decarboxylase. Previous results showed that when cells are activated in the presence of MGBG the synthesis and processing of RNA, as well as protein synthesis, proceed as in the absence of the drug. In contrast, the incorporation of [methyl-3H]thymidine into DNA and the rate of entry of the cells into mitosis are inhibited by 60% in the presence of MGBG. Several experiments suggest that MGBG inhibits cell proliferation by directly blocking polyamine synthesis and not by an unrelated pharmacological effect: (1) the inhibitory action of MGBG is reversed by exogenously added spermidine or spermine; (2) inhibition of DNA synthesis by MGBG shows the same dose-response curve as does inhibition of spermidine and spermine synthesis; and (3) if MGBG is added to cells which have been allowed to accumulate their maximum complement of polyamines, there is no inhibition of thymidine incorporation. MGBG-treated and control cultures initiate DNA synthesis at the same time and show the same percentage of labeled cells by autoradiography. Therefore, it appears that in the absence of increased cellular levels of polyamines, lymphocytes progress normally from G0 through G1 and into S-phase. Furthermore, these experiments suggest that the increased levels of spermidine and spermine generally seen in rapidly proliferating eukaryotic systems are necessary for enhanced rates of DNA replication. PMID:1060087

Increased levels of metallothionein in placenta of smokers

International Nuclear Information System (INIS)

Ronco, Ana Maria; Arguello, Graciela; Suazo, Myriam; Llanos, Miguel N.

2005-01-01

Experiments were designed to evaluate and compare metallothionein (MT), zinc and cadmium levels in human placentas of smoking and non-smoking women. Smoking was assessed by self-reported cigarette consumption and urine cotinine levels before delivery. Smoking pregnant women with urine cotinine levels higher than 130 ng/ml were included in the smoking group. Determination of placental MT was performed by western blot analysis after tissue homogenization and saturation with cadmium chloride (1000 ppm). Metallothionein was analyzed with a monoclonal antibody raised against MT-1 and MT-2 and with a second anti mouse antibody conjugated to alkaline phosphatase. Zinc and cadmium were determined by neutron activation analysis and atomic absorption spectrometry respectively. Smokers showed higher placental MT and cadmium levels, together with decreased newborn birth weights, as compared to non-smokers. The semi-quantitative analysis of western blots by band densitometry indicated that darker bands corresponded to MT present in smokers' samples. This study confirms that cigarette smoking increases cadmium accumulation in placental tissue and suggests that this element has a stimulatory effect on placental MT production

Evasion of Cell Senescence Leads to Medulloblastoma Progression

Directory of Open Access Journals (Sweden)

Lukas Tamayo-Orrego

2016-03-01

Full Text Available How brain tumors progress from precancerous lesions to advanced cancers is not well understood. Using Ptch1+/− mice to study medulloblastoma progression, we found that Ptch1 loss of heterozygosity (LOH is an early event that is associated with high levels of cell senescence in preneoplasia. In contrast, advanced tumors have evaded senescence. Remarkably, we discovered that the majority of advanced medulloblastomas display either spontaneous, somatic p53 mutations or Cdkn2a locus inactivation. Consistent with senescence evasion, these p53 mutations are always subsequent to Ptch1 LOH. Introduction of a p53 mutation prevents senescence, accelerates tumor formation, and increases medulloblastoma incidence. Altogether, our results show that evasion of senescence associated with Ptch1 LOH allows progression to advanced tumors.

Progress and future direction for the interim safe storage and disposal of Hanford high level waste (HLW)

International Nuclear Information System (INIS)

Wodrich, D.D.

1996-01-01

This paper describes the progress made at the largest environmental cleanup program in the United States. Substantial advances in methods to start interim safe storage of Hanford Site high-level wastes, waste characterization to support both safety- and disposal-related information needs, and proceeding with cost-effective disposal by the US DOE and its Hanford Site contractors, have been realized. Challenges facing the Tank Waste Remediation System Program, which is charged with the dual and parallel missions of interim safe storage and disposal of the high-level tank waste stored at the Hanford Site, are described

Arginase-1 expressing microglia in close proximity to motor neurons were increased early in disease progression in canine degenerative myelopathy, a model of amyotrophic lateral sclerosis.

Science.gov (United States)

Toedebusch, Christine M; Snyder, John C; Jones, Maria R; Garcia, Virginia B; Johnson, Gayle C; Villalón, Eric L; Coates, Joan R; Garcia, Michael L

2018-04-01

Toxicity within superoxide dismutase-1 (SOD1)-associated familial amyotrophic lateral sclerosis (ALS) is non-cell autonomous with direct contribution from microglia. Microglia exhibit variable expression of neuroprotective and neurotoxic molecules throughout disease progression. The mechanisms regulating microglial phenotype within ALS are not well understood. This work presents a first study to examine the specific microglial phenotypic response in close association to motor neurons in a naturally occurring disease model of ALS, canine degenerative myelopathy (DM). Microglia closely associated with motor neurons were increased in all stages of DM progression, although only DM Late reached statistical significance. Furthermore, the number of arginase-1 expressing microglia per motor neuron were significantly increased in early stages of DM, whereas the number of inducible nitric oxide synthase (iNOS)-expressing microglia per motor neuron was indistinguishable from aged controls at all stages of disease. Fractalkine, a chemotactic molecule for microglia, was expressed in motor neurons, and the fractalkine receptor was specifically localized to microglia. However, we found no correlation between microglial response and lumbar spinal cord fractalkine levels. Taken together, these data suggest that arginase-1-expressing microglia are recruited to the motor neuron early in DM disease through a fractalkine-independent mechanism. Copyright © 2018 Elsevier Inc. All rights reserved.

Cervical Lordosis Actually Increases With Aging and Progressive Degeneration in Spinal Deformity Patients.

Science.gov (United States)

Kim, Han Jo; Lenke, Lawrence G; Oshima, Yasushi; Chuntarapas, Tapanut; Mesfin, Addisu; Hershman, Stuart; Fogelson, Jeremy L; Riew, K Daniel

2014-09-01

Retrospective. The authors hypothesized that cervical lordosis (CL) would decrease with aging and increasing degeneration. It is theorized that with age and degeneration, the cervical spine loses lordosis and becomes progressively more kyphotic; however, no studies support these conclusions in patients with various spinal deformities. The authors performed a radiographic analysis of asymptomatic adults (referring to their cervical spine) of varying ages, with differing forms of spinal deformity to the thoracic/lumbar spine to see how cervical lordosis changes with increasing age. A total of 104 total spine EOS X-rays of adult (aged >18 years) spinal deformity patients without documented neck pain, prior neck surgery, or cervical deformity were reviewed. The researchers only reviewed EOS X-rays because they allow complete visualization from occiput to feet. Cervical lordosis, standard Cobb measurements, sagittal balance parameters, and cervical degeneration were quantified radiographically by the method previously described by Gore et al. Statistical analysis was performed with 1-way analysis of variance to compare significant differences between groups aged 60 years as well as changes in sagittal balance. A p-value 60 years, respectively; p 60 years, respectively; p < .01), with the highest degeneration at the C5-6 and C6-7 disc spaces (3.7 ± 3.3 and 3.2 ± 2.9, respectively; p < .01). This increase did not correlate with the increase in CL seen with aging (r = 0.02; p = .84). Cervical lordosis increased with aging in adult spinal deformity patients. There was no relationship between cervical degeneration and lordosis despite the strong relationship seen between increasing CL in older age groups. Copyright © 2014 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Decreased total antioxidant levels and increased oxidative stress in ...

African Journals Online (AJOL)

21–25 ... Decreased total antioxidant levels and increased oxidative stress in South ... antioxidant-rich diet and lifestyle changes in T2DM patients would help to avert the .... glycation of proteins and the formation of advanced glycosylation.

Serum levels of polyamine synthesis enzymes increase in diabetic patients with breast cancer

Directory of Open Access Journals (Sweden)

V Kenan Çelik

2017-09-01

Full Text Available In this study, it was aimed to investigate the relationship between diabetes and breast cancer and the detection of enzymes and ornithine levels in polyamine synthesis pathway in diabetes, breast cancer and diabetic breast cancer patients. Methods: Ornithine, arginine decarboxylase, ornithine decarboxylase and agmatinase levels have been measured in serum of all groups. Ornithine levels were measured spectrophotometrically. Arginine decarboxylase, ornithine decarboxylase and agmatinase levels were determined by ELISA kits. Results: Except for the diabetic group, the levels of enzymes in the polyamine synthesis pathway were increased in all and statistically significant (P < 0.05. The increase in the levels of agmatinase was very important among the enzymes (P < 0.001. Conclusions: Decreased levels of polyamine synthase enzymes in diabetes mellitus were found to be increased patients with breast cancer. Whether and how diabetes-based breast cancer development relates to increase activity of enzymes responsible for polyamine synthesis requires further mechanistic and prospective monitoring studies in larger patient cohorts.

Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals.

Directory of Open Access Journals (Sweden)

Shashi Bala

Full Text Available Binge drinking, the most common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its biological consequences are poorly defined. Previous studies demonstrated that chronic alcohol use results in increased gut permeability and increased serum endotoxin levels that contribute to many of the biological effects of chronic alcohol, including alcoholic liver disease. In this study, we evaluated the effects of acute binge drinking in healthy adults on serum endotoxin levels. We found that acute alcohol binge resulted in a rapid increase in serum endotoxin and 16S rDNA, a marker of bacterial translocation from the gut. Compared to men, women had higher blood alcohol and circulating endotoxin levels. In addition, alcohol binge caused a prolonged increase in acute phase protein levels in the systemic circulation. The biological significance of the in vivo endotoxin elevation was underscored by increased levels of inflammatory cytokines, TNFα and IL-6, and chemokine, MCP-1, measured in total blood after in vitro lipopolysaccharide stimulation. Our findings indicate that even a single alcohol binge results in increased serum endotoxin levels likely due to translocation of gut bacterial products and disturbs innate immune responses that can contribute to the deleterious effects of binge drinking.

Increased DNA damage in progression of COPD: a response by poly(ADP-ribose polymerase-1.

Directory of Open Access Journals (Sweden)

Ingrid Oit-Wiscombe

Full Text Available Chronic oxidative stress (OS, a major mechanism of chronic obstructive pulmonary disease (COPD, may cause significant damage to DNA. Poly(ADP-ribose polymerase (PARP-1 is rapidly activated by OS-induced DNA lesions. However, the degree of DNA damage along with the evolution of COPD is unclear. In peripheral blood mononuclear cells of non-smoking individuals, non-obstructive smokers, patients with COPD of all stages and those with COPD exacerbation, we evaluated DNA damage, PARP activity and PARP-1 mRNA expression using Comet Assay IV, biotinylated-NAD incorporation assay and qRT-PCR, respectively and subjected results to ordinal logistic regression modelling. Adjusted for demographics, smoking-related parameters and lung function, novel comet parameters, tail length/cell length ratio and tail migration/cell length ratio, showed the greatest increase along the study groups corresponding to the evolution of COPD [odds ratio (OR 7.88, 95% CI 4.26-14.57; p<0.001 and OR 3.91, 95% CI 2.69-5.66; p<0.001, respectively]. Analogously, PARP activity increased significantly over the groups (OR = 1.01; 95%; p<0.001. An antioxidant tetrapeptide UPF17 significantly reduced the PARP-1 mRNA expression in COPD, compared to that in non-obstructive individuals (p = 0.040. Tail length/cell length and tail migration/cell length ratios provide novel progression-sensitive tools for assessment of DNA damage. However, it remains to be elucidated whether inhibition of an elevated PARP-1 activity has a safe enough potential to break the vicious cycle of the development and progression of COPD.

Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels, supplement to: Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W; Riebesell, Ulf; Gao, Kunshan (2015): Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels. Nature Communications, 6, 8714

KAUST Repository

Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W; Riebesell, Ulf; Gao, Kunshan

2016-01-01

Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46-212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130-160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28-48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury.

Science.gov (United States)

Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

2015-07-31

Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the

Peripheral ovine progressive pneumonia provirus levels correlate with and predict histological tissue lesion severity in naturally infected sheep.

Science.gov (United States)

Herrmann-Hoesing, Lynn M; Noh, Susan M; White, Stephen N; Snekvik, Kevin R; Truscott, Thomas; Knowles, Donald P

2009-04-01

Studies were undertaken to determine whether anti-ovine progressive pneumonia virus (OPPV) antibody responses in serum or OPP provirus levels in peripheral blood associate with the degree of histologically measured tissue lesions in naturally OPPV-infected sheep. Sections of formalin-fixed, paraffin-embedded, and hematoxylin- and eosin-stained lung, mammary gland, carpal synovial membrane, and brain tissues from 11 OPPV-infected ewes (mean age of 8.6 years) and 5 OPPV-uninfected ewes (mean age of 6 years) were evaluated for lesion severity. Ovine progressive pneumonia (OPP) provirus levels and anti-OPPV antibody titers in peripheral blood and serum samples, respectively, were measured upon euthanasia and 3 years prior to euthanasia. Both mean peripheral OPP provirus levels and mean serum anti-surface envelope glycoprotein (anti-SU) antibody titers at the time of euthanasia were significantly higher in ewes with moderate to severe histological lesions than in ewes with no to mild histological lesions. However, although mean peripheral blood OPP provirus levels at euthanasia and 3 years prior to euthanasia significantly correlated with the highest histological lesion score for any affected tissue (two-tailed P values, 0.03 and 0.02), mean serum anti-SU antibody titers, anti-capsid antibody titers, and anti-transmembrane 90 antibody titers at euthanasia did not show a significant correlation with the highest histological lesion score for any tissue (two-tailed P values, 0.32, 0.97, and 0.18, respectively). These data are the first to show that OPP provirus levels predict and correlate with the extent of OPPV-related histological lesions in various OPPV-affected tissues. These findings suggest that peripheral OPP provirus levels quantitatively contribute more to the development of histological lesions than the systemic anti-SU antibody host immune response.

Impaired left ventricular systolic function and increased brachial-ankle pulse-wave velocity are independently associated with rapid renal function progression.

Science.gov (United States)

Chen, Szu-Chia; Lin, Tsung-Hsien; Hsu, Po-Chao; Chang, Jer-Ming; Lee, Chee-Siong; Tsai, Wei-Chung; Su, Ho-Ming; Voon, Wen-Chol; Chen, Hung-Chun

2011-09-01

Heart failure and increased arterial stiffness are associated with declining renal function. Few studies have evaluated the association between left ventricular ejection fraction (LVEF) and brachial-ankle pulse-wave velocity (baPWV) and renal function progression. The aim of this study was to assess whether LVEFfunction was estimated by eGFR slope. The renal end point was defined as ≥25% decline in eGFR. Clinical and echocardiographic parameters were compared and analyzed. After a multivariate analysis, serum hematocrit was positively associated with eGFR slope, and diabetes mellitus, baPWV (P=0.031) and LVEFfunction decline and progression to the renal end point.

Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model.

Science.gov (United States)

Iijima, H; Ito, A; Nagai, M; Tajino, J; Yamaguchi, S; Kiyan, W; Nakahata, A; Zhang, J; Wang, T; Aoyama, T; Nishitani, K; Kuroki, H

2017-06-01

To evaluate the dose-response relationship of exercise loading in the cartilage-subchondral bone (SB) unit in surgically-induced post-traumatic osteoarthritis (PTOA) of the knee. Destabilized medial meniscus (DMM) surgery was performed on the right knee of 12-week-old male Wistar rats, and sham surgery was performed on the contralateral knee. Four weeks after the surgery, the animals were subjected to moderate (12 m/min) or intense (21 m/min) treadmill exercises for 30 min/day, 5 days/week for 4 weeks. PTOA development in articular cartilage and SB was examined using histological and immunohistochemical analyses, micro-computed tomography (micro-CT) analysis, and biomechanical testing at 8 weeks after surgery. Gremlin-1 was injected to determine the role of bone morphogenetic protein (BMP) signaling on PTOA development following moderate exercise. Moderate exercise increased BMP-2, BMP-4, BMP-6, BMP receptor 2, pSmad-5, and inhibitor of DNA binding protein-1 expression in the superficial zone chondrocytes and suppressed cartilage degeneration, osteophyte growth, SB damage, and osteoclast-mediated SB resorption. However, intense exercise had little effect on BMP expression and even caused progression of these osteoarthritis (OA) changes. Gremlin-1 injection following moderate exercise caused progression of the PTOA development down to the level of the non-exercise DMM-operated knee. Exercise regulated cartilage-SB PTOA development in DMM-operated knees in a dose-dependent manner. Our findings shed light on the important role of BMP expression in superficial zone chondrocytes in attenuation of PTOA development following physiological exercise loading. Further studies to support a mechanism by which BMPs would be beneficial in preventing PTOA progression are warranted. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

International Nuclear Information System (INIS)

Straub, Adam C.; Stolz, Donna B.; Vin, Harina; Ross, Mark A.; Soucy, Nicole V.; Klei, Linda R.; Barchowsky, Aaron

2007-01-01

The vascular effects of arsenic in drinking water are global health concerns contributing to human disease worldwide. Arsenic targets the endothelial cells lining blood vessels, and endothelial cell activation or dysfunction may underlie the pathogenesis of both arsenic-induced vascular diseases and arsenic-enhanced tumorigenesis. The purpose of the current studies was to demonstrate that exposing mice to drinking water containing environmentally relevant levels of arsenic promoted endothelial cell dysfunction and pathologic vascular remodeling. Increased angiogenesis, neovascularization, and inflammatory cell infiltration were observed in Matrigel plugs implanted in C57BL/6 mice following 5-week exposures to 5-500 ppb arsenic [Soucy, N.V., Mayka, D., Klei, L.R., Nemec, A.A., Bauer, J.A., Barchowsky, A., 2005. Neovascularization and angiogenic gene expression following chronic arsenic exposure in mice. Cardiovasc.Toxicol 5, 29-42]. Therefore, functional in vivo effects of arsenic on endothelial cell function and vessel remodeling in an endogenous vascular bed were investigated in the liver. Liver sinusoidal endothelial cells (LSEC) became progressively defenestrated and underwent capillarization to decrease vessel porosity following exposure to 250 ppb arsenic for 2 weeks. Sinusoidal expression of PECAM-1 and laminin-1 proteins, a hallmark of capillarization, was also increased by 2 weeks of exposure. LSEC caveolin-1 protein and caveolae expression were induced after 2 weeks of exposure indicating a compensatory change. Likewise, CD45/CD68-positive inflammatory cells did not accumulate in the livers until after LSEC porosity was decreased, indicating that inflammation is a consequence and not a cause of the arsenic-induced LSEC phenotype. The data demonstrate that the liver vasculature is an early target of pathogenic arsenic effects and that the mouse liver vasculature is a sensitive model for investigating vascular health effects of arsenic

Lipoprotein Lipase and PPAR Alpha Gene Polymorphisms, Increased Very-Low-Density Lipoprotein Levels, and Decreased High-Density Lipoprotein Levels as Risk Markers for the Development of Visceral Leishmaniasis by Leishmania infantum

Directory of Open Access Journals (Sweden)

Márcia Dias Teixeira Carvalho

2014-01-01

Full Text Available In visceral leishmaniasis (VL endemic areas, a minority of infected individuals progress to disease since most of them develop protective immunity. Therefore, we investigated the risk markers of VL within nonimmune sector. Analyzing infected symptomatic and, asymptomatic, and noninfected individuals, VL patients presented with reduced high-density lipoprotein cholesterol (HDL-C, elevated triacylglycerol (TAG, and elevated very-low-density lipoprotein cholesterol (VLDL-C levels. A polymorphism analysis of the lipoprotein lipase (LPL gene using HindIII restriction digestion (N = 156 samples (H+ = the presence and H− = the absence of mutation revealed an increased adjusted odds ratio (OR of VL versus noninfected individuals when the H+/H+ was compared with the H−/H− genotype (OR = 21.3; 95% CI = 2.32–3335.3; P = 0.003. The H+/H+ genotype and the H+ allele were associated with elevated VLDL-C and TAG levels (P < 0.05 and reduced HDL-C levels (P < 0.05. An analysis of the L162V polymorphism in the peroxisome proliferator-activated receptor alpha (PPARα gene (n = 248 revealed an increased adjusted OR when the Leu/Val was compared with the Leu/Leu genotype (OR = 8.77; 95% CI = 1.41–78.70; P = 0.014. High TAG (P = 0.021 and VLDL-C (P = 0.023 levels were associated with susceptibility to VL, whereas low HDL (P = 0.006 levels with resistance to infection. The mutated LPL and the PPARα Leu/Val genotypes may be considered risk markers for the development of VL.

Exercise increases endostatin in circulation of healthy volunteers

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Makey Ian

2004-01-01

Full Text Available Abstract Background Physical inactivity increases the risk of atherosclerosis. However, the molecular mechanisms of this relation are poorly understood. A recent report indicates that endostatin, an endogenous angiostatic factor, inhibits the progression of atherosclerosis, and suggests that reducing intimal and atherosclerotic plaque tissue neovascularization can inhibit the progression atherosclerosis in animal models. We hypothesize that exercise can elevate the circulatory endostatin level. Hence, exercise can protect against one of the mechanisms of atherosclerosis. Results We examined treadmill exercise tests in healthy volunteers to determine the effect of exercise on plasma levels of endostatin and other angiogenic regulators. Oxygen consumption (VO2 was calculated. Plasma levels of endostatin, vascular endothelial growth factor (VEGF, and basic fibroblast growth factor (bFGF were determined using ELISA. The total peak VO2 (L in 7 male subjects was 29.5 ± 17.8 over a 4–10 minute interval of exercise. Basal plasma levels of endostatin (immediately before exercise were 20.3 ± 3.2 pg/ml, the plasma levels increased to 29.3 ± 4.2, 35.2 ± 1.8, and 27.1 ± 2.2 ng/ml, at 0.5, 2, and 6 h, respectively, after exercise. There was a strong linear correlation between increased plasma levels of endostatin (% and the total peak VO2 (L related to exercise (R2 = 0.9388; P Conclusions The results suggest that circulating endostatin can be significantly increased by exercise in proportion to the peak oxygen consumption under physiological conditions in healthy volunteers. These findings may provide new insights into the molecular links between physical inactivity and the risk of angiogenesis dependent diseases such as atherosclerosis.

An Increase in Religiousness/Spirituality Occurs After HIV Diagnosis and Predicts Slower Disease Progression over 4 Years in People with HIV

Science.gov (United States)

Ironson, Gail; Stuetzle, Rick; Fletcher, Mary Ann

2006-01-01

BACKGROUND Most studies on religion/spirituality predicting health outcomes have been limited to church attendance as a predictor and have focused on healthy people. However, confronting a major medical crisis may be a time when people turn to the sacred. OBJECTIVE The purpose of this study was to determine the extent to which changes in spirituality/religiousness occur after HIV diagnosis and whether changes predict disease progression. DESIGN/PARTICIPANTS This longitudinal study examined the relationship between changes in spirituality/religiousness from before with after the diagnosis of HIV, and disease progression (CD4 and viral load [VL] every 6 months) over 4 years in 100 people with HIV. Measures included change in religiousness/spirituality after diagnosis of HIV, religiousness/spirituality at various times in one’s life, church attendance, depression, hopelessness, optimism, coping (avoidant, proactive), social support, CD4/VL, and health behaviors. RESULTS Forty-five percent of the sample showed an increase in religiousness/spirituality after the diagnosis of HIV, 42% remained the same, and 13% decreased. People reporting an increase in spirituality/religiousness after the diagnosis had significantly greater preservation of CD4 cells over the 4-year period, as well as significantly better control of VL. Results were independent of (i.e., held even after controlling for) church attendance and initial disease status (CD4/VL), medication at every time point, age, gender, race, education, health behaviors (adherence, risky sex, alcohol, cocaine), depression, hopelessness, optimism, coping (avoidant, proactive), and social support. CONCLUSIONS There is an increase in spirituality/religiousness after HIV diagnosis, and this increase predicts slower disease progression; medical personnel should be aware of its potential importance. PMID:17083503

Home Environmental Factors Influencing Performance and Progress ...

African Journals Online (AJOL)

Our findings support other studies which found that parents' educational level and income level have a bearing on school progress and performance. Contrary to most research findings mother tongue instruction did not eme1rge as an important explanatory factor on school progress and performance, however; home ...

Efficiency of fisheries is increasing at the ecosystem level

DEFF Research Database (Denmark)

Jacobsen, Nis Sand; Burgess, Matthew G; Andersen, Ken Haste

2017-01-01

examine the efficiency of North Sea and Baltic Sea fisheries with respect to economic rent and ecosystem impact, finding both to be inefficient but steadily improving. Our results suggest the following: (i) a broad and encouraging trend towards ecosystem-level efficiency of fisheries; (ii) that ecosystem......Managing fisheries presents trade-offs between objectives, for example yields, profits, minimizing ecosystem impact, that have to be weighed against one another. These trade-offs are compounded by interacting species and fisheries at the ecosystem level. Weighing objectives becomes increasingly...... regressing at least one other. We investigate the ecosystem-level efficiency of fisheries in five large marine ecosystems (LMEs) with respect to yield and an aggregate measure of ecosystem impact using a novel calibration of size-based ecosystem models. We estimate that fishing patterns in three LMEs (North...

[Influence of elevated homocystein level and selected lipid parameters in kidney transplant patients on the progression of atherosclerotic changes assessed by intima-media thickness index (CCA-IMT)].

Science.gov (United States)

Janda, Katarzyna; Aksamit, Dariusz; Drozdz, Maciej; Krzanowski, Marcin; Ignacak, Ewa; Kowalczyk-Michałek, Martyna; Tabor-Ciepiela, Barbara; Sułowicz, Władysław

2012-01-01

The aim of the study was to evaluate the influence of elevated homocystein (Hcy) level and selected lipid parameters on the progression of atherosclerotic changes in patients after kidney transplantation (KTx). The study included 51 pts (17 F, 34 M) aged 15-62 years (median 38.1) after cadaver KTx. The mean observation period equaled 21.2 months (6-24 months); while total observation period was 90 patients/ years. Hcy levels was measured using HPLC, Lp(a) and Apo-B levels using the nephelometric method and total cholesterol with its' HDL and LDL fractions, triglycerides and creatinine based on the Hitachi 917 analyzer. Patients' blood was drawn before renal transplantation and 3, 6, 9, 12, 15, 18, 21 and 24 months after KTx. Common carotid artery intima media thickness (CCA-IMT) was evaluated by ultrasound on 14 days, 12 and 24 months after KTx. CCA-IMT correlated significantly with Hcy levels after 12 months (R=0.53; p=0.0009) and 24 months (R=0.38; p=0.0356) after KTx. Significant differences were found 12 and 24 months after KTx in CCA-IMT between patients with normal (15 micromol/ l) mean Hcy concentrations: p=0.0035 and p= 0.015, respectively. Analyzing changes in CCA-IMT, significant differences were noted when comparing the CCA-IMT increment after 12 and 24 months post KTx in patients with normal (15 micromol/l) homocystein concentrations: p=0.049 and p=0.0039, respectively. Increment of CCA-IMT 12 months after KTx, significantly correlated with mean total cholesterol level (R=0.35; p=0.0333), whereas 24 months after procedure correlated significantly with 0.0315). Hcy level is an independent risk factor for atherosclerosis development in patients after KTx. Elevated Hcy level as well as increased cholesterol and Lp(a) levels enhance the progression of atherosclerotic changes evaluated by CCA-IMT in KTx patients.

Decreased total antioxidant levels and increased oxidative stress in ...

African Journals Online (AJOL)

Background: Chronic hyperglycaemia in diabetes mellitus leads to increased lipid peroxidation in the body, followed by the development of chronic complications due to oxidative stress. Objective: The aim of this study was to compare total antioxidant (TAO) levels and oxidative stress in type 2 diabetes mellitus (T2DM) ...

Increased cytosine DNA-methyltransferase activity in A/J mouse lung cells following carcinogen exposure and during tumor progression

International Nuclear Information System (INIS)

Belinsky, S.A.; Issa, J.-P.J.; Baylin, S.B.

1994-01-01

Considerable evidence has accumulated that 5-methylcytosine modification of mammalian DNA, both in exons and CpG rich islands located in promoter regions, is important in gene regulation. For example, a decrease of 5-methylcytosine in 5' flanking regions or exons of genes has been associated with increased gene transcription. In addition, hypermethylation at specific regions of chromosomes 17p and 3p have also been observed in lung and colon cancer. During colon cancer development, these hypermethylation changes precede allelic loss. In addition, the activity of the enzyme which maintains the methylation status at CpG dinucleotides, DNA methyltransferase (MT), has been shown to increase during colon cancer progression. These observations suggest changes in methylation patterns within specific genes could result in either inappropriate gene expression or gene deletion, both of which would contribute to the establishment of the malignant phenotype. The purpose of this investigation was to determine if DNA MT activity is elevated in target (alveolar type II), but not in nontarget (Clara, endothelial, macrophage) lung cells isolated from the A/J mouse following exposure to nitrosamine 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK). In addition, the activity of this enzyme during tumor progression was examined

Elevated levels of ferritin in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.

Science.gov (United States)

Zheng, Y; Gao, L; Wang, D; Zang, D

2017-08-01

The aim of the study was to detect changes in the levels of ferritin heavy chain (FHC), ferritin light chain (FLC), and transferrin in the cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients and to analyze the correlations between the levels of these proteins and various clinical parameters. Cerebrospinal fluid and serum samples were obtained from 54 ALS patients and 46 non-inflammatory neurological disease control (non-INDC) patients. CSF and serum FHC, FLC, and transferring levels were measured via the enzyme-linked immunosorbent method using a commercial ELISA kit, and the times from onset (durations), ALS functional rating scale-revised (ALSFRS-r) scores, and disease progression rates (DPRs) were analyzed by registered neurologists. Statistical analysis was performed via Prism software. Compared with controls, ALS patients exhibited significantly increased FHC and FLC levels in CSF, which were positively correlated with DPR and negatively correlated with duration. Serum transferrin levels were significantly increased in ALS patients but were not correlated with disease progression. FHC and FLC in CSF rapidly increased as the disease worsened. This study demonstrated that the clinical measurement of FHC and FLC in CSF may be beneficial for disease differentiation and evaluating progression in patients with ALS. Compared with levels in serum, the levels of FHC and FLC in CSF might be more reliable for diagnosing and assessing the progression of ALS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

Science.gov (United States)

Akirov, Amit; Greenman, Yona; Glaser, Benjamin; S'chigol, Irena; Mansiterski, Yossi; Eizenberg, Yoav; Shraga-Slutzky, Ilana; Shimon, Ilan

2018-05-04

Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

Methodological developments in US state-level Genuine Progress Indicators: toward GPI 2.0

Science.gov (United States)

Bagstad, Kenneth J.; Berik, Günseli; Gaddis, Erica J. Brown

2014-01-01

The Genuine Progress Indicator (GPI) has emerged as an important monetary measure of economic well-being. Unlike mainstream economic indicators, primarily Gross Domestic Product (GDP), the GPI accounts for both the benefits and costs of economic production across diverse economic, social, and environmental domains in a more comprehensive manner. Recently, the GPI has gained traction in subnational policy in the United States, with GPI studies being conducted in a number of states and with their formal adoption by several state governments. As the GPI is applied in different locations, new methods are developed, different data sources are available, and new issues of policy relevance are addressed using its component indicators. This has led to a divergence in methods, reducing comparability between studies and yielding results that are of varying methodological sophistication. In this study, we review the “state of the art” in recent US state-level GPI studies, focusing on those from Hawaii, Maryland, Ohio, Utah, and Vermont. Through adoption of a consistent approach, these and future GPI studies could utilize a framework that supports more uniform, comparable, and accurate measurements of progress. We also identify longer-term issues, particularly related to treatment of nonrenewable resource depletion, government spending, income inequality, and ecosystem services. As these issues are successfully addressed and disseminated, a “GPI 2.0” will emerge that better measures economic well-being and has greater accuracy and policy relevance than past GPI measurements. As the GPI expands further into mainstream policy analysis, a more formal process by which methods could be updated, standardized, and applied is needed.

Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease.

Science.gov (United States)

Liu, Bin; Li, Chenghai; Liu, Zijuan; Dai, Zonghan; Tao, Yunxia

2012-09-11

Polycystic Kidney Disease (PKD) kidneys exhibit increased extracellular matrix (ECM) collagen expression and metalloproteinases (MMPs) activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. We examined the role of type I collagen (collagen I) and membrane bound type 1 MMP (MT1-MMP) on cyst development using both in vitro 3 dimensional (3D) collagen gel culture and in vivo PCK rat model of PKD. We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease

Directory of Open Access Journals (Sweden)

Liu Bin

2012-09-01

Full Text Available Abstract Background Polycystic Kidney Disease (PKD kidneys exhibit increased extracellular matrix (ECM collagen expression and metalloproteinases (MMPs activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. Methods We examined the role of type I collagen (collagen I and membrane bound type 1 MMP (MT1-MMP on cyst development using both in vitro 3 dimensional (3D collagen gel culture and in vivo PCK rat model of PKD. Results We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Conclusions Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

Plasma viscosity increase with progression of peripheral arterial atherosclerotic disease.

Science.gov (United States)

Poredos, P; Zizek, B

1996-03-01

-macroglobulin (r=0.78, P < 0.01). These results indicate that in patients with peripheral arterial disease plasma viscosity increases with the progression of the atherosclerotic process and is correlated with the clinical stages of the disease.

Increasing occurrence of multiple sclerosis in women correlates to hygiene level

Directory of Open Access Journals (Sweden)

Wojciech Cendrowski

2014-12-01

Full Text Available Introduction: The increasing incidence of multiple sclerosis, particularly among women in Europe and North America, has a multifactorial aetiology. Method: The aim of the current study was to ascertain the relation between the hygiene level and occurrence of multiple sclerosis in women in Poland. The study was based on a large cohort of 14,200 multiple sclerosis individuals (male – 6,106, female – 8,094 who died in the years 1981–2010 in Poland. The female to male ratio (the F:M ratio in the multiple sclerosis group was calculated using the number of deaths per year. The rate of late mortality in infants (LMI per 1,000 live births yearly was used as a marker of the hygiene level. A correlation analysis was carried out between the rate of LMI and the F:M ratio in the multiple sclerosis cohort in the years 1981–2010. Demographic data were obtained from the Central Statistical Office in Warsaw. Results: The F:M ratio in the multiple sclerosis group evidently increased (range 1.08–1.79 in the years 1981–2010, showing increasing occurrence of multiple sclerosis in women (p < 0.0001. A significant, strong and inverse correlation was found between the marker of the hygiene level (LMI rate and the F:M ratio in the multiple sclerosis group over three decades: linear correlation coefficient by Pearson: r = –0.693, p < 0.0001. By contrast with this result, no correlation was established between the hygiene level marker and proportion of women to men in the general population on account of extremely low variance of the F:M ratio (0.000025. Conclusion: The improvement of the hygiene level showed association with the increasing occurrence of multiple sclerosis in women in the years 1981–2010. The higher the hygiene level was, the greater the occurrence of female multiple sclerosis in Poland.

Progress and trends in patients' mindset on dental implants. I: level of information, sources of information and need for patient information.

Science.gov (United States)

Pommer, Bernhard; Zechner, Werner; Watzak, Georg; Ulm, Christian; Watzek, Georg; Tepper, Gabor

2011-02-01

Little is known about the level of information on implant dentistry in the public. A representative opinion poll on dental implants in the Austrian population was published in 2003 (Clinical Oral Implants Research 14:621-642). Seven years later, the poll was rerun to assess the up-to-date information level and evaluate recent progress and trends in patients' mindset on dental implants. One thousand adults--representative for the Austrian population--were presented with a total of 19 questionnaire items regarding the level and the sources of information about dental implants as well as the subjective and objective need for patient information. Compared with the survey of 2003, the subjective level of patient information about implant dentistry has significantly increased in the Austrian population. The patients' implant awareness rate was 79%. The objective level of general knowledge about dental implants was still all but satisfactory revealing unrealistic patient expectations. Three-quarters trusted their dentists for information about dental implants, while one-quarter turned to the media. The patients' wish for high-quality implant restorations was significantly higher than in 2003, yet the majority felt that only specialists should perform implant dentistry. This representative survey reveals that dentists are still the main source of patient information, but throws doubt on the quality of their public relations work. Dentists must improve communication strategies to provide their patients with comprehensible, legally tenable information on dental implants and bridge information gaps in the future. © 2010 John Wiley & Sons A/S.

Technical reliability of geological disposal for high-level radioactive wastes in Japan. The second progress report. An extra issue: background of the geological disposal

International Nuclear Information System (INIS)

1999-11-01

Based on the Advisory Committee Report on Nuclear Fuel Cycle Backend Policy submitted to the Japanese Government in 1997, JNC documents the progress of research and development program in the form of the second progress report (the first one published in 1992). It summarizes an evaluation of the technical reliability and safety of the geological disposal concept for high-level radioactive wastes (HLW) in Japan. The present document, an extra issue of the progress report, was prepared for the expected readers of the report to have background information on the geological disposal. Thus it gives information about (1) generation of high-level radioactive wastes, (2) history of plans proposed for HLW disposal in Japan, and (3) procedure until the geological disposal plan is finally adopted and basic future schedules. It further discusses on such problems in HLW treatment and disposal, as for example a problem of reliable safety for a very long period. (Ohno, S.)

Progress on Plant-Level Components for Nuclear Fuel Recycling: Commonality

International Nuclear Information System (INIS)

De Almeida, Valmor F.

2011-01-01

Progress made in developing a common mathematical modeling framework for plant-level components of a simulation toolkit for nuclear fuel recycling is summarized. This ongoing work is performed under the DOE Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, which has an element focusing on safeguards and separations (SafeSeps). One goal of this element is to develop a modeling and simulation toolkit for used nuclear fuel recycling. The primary function of the SafeSeps simulation toolkit is to enable the time-dependent coupling of separation modules and safeguards tools (either native or third-party supplied) that simulate and/or monitor the individual separation processes in a separations plant. The toolkit integration environment will offer an interface for the modules to register in the toolkit domain based on the commonality of diverse unit operations. This report discusses the source of this commonality from a combined mathematical modeling and software design perspectives, and it defines the initial basic concepts needed for development of application modules and their integrated form, that is, an application software. A unifying mathematical theory of chemical thermomechanical network transport for physicochemical systems is proposed and outlined as the basis for developing advanced modules. A program for developing this theory from the underlying first-principles continuum thermomechanics will be needed in future developments; accomplishment of this task will enable the development of a modern modeling approach for plant-level models. Rigorous, advanced modeling approaches at the plant-level can only proceed from the development of reduced (or low-order) models based on a solid continuum field theory foundation. Such development will pave the way for future programmatic activities on software verification, simulation validation, and model uncertainty quantification on a scientific basis; currently, no satisfactory foundation exists for

Progress on Plant-Level Components for Nuclear Fuel Recycling: Commonality

Energy Technology Data Exchange (ETDEWEB)

de Almeida, Valmor F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2011-08-15

Progress made in developing a common mathematical modeling framework for plant-level components of a simulation toolkit for nuclear fuel recycling is summarized. This ongoing work is performed under the DOE Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, which has an element focusing on safeguards and separations (SafeSeps). One goal of this element is to develop a modeling and simulation toolkit for used nuclear fuel recycling. The primary function of the SafeSeps simulation toolkit is to enable the time-dependent coupling of separation modules and safeguards tools (either native or third-party supplied) that simulate and/or monitor the individual separation processes in a separations plant. The toolkit integration environment will offer an interface for the modules to register in the toolkit domain based on the commonality of diverse unit operations. This report discusses the source of this commonality from a combined mathematical modeling and software design perspectives, and it defines the initial basic concepts needed for development of application modules and their integrated form, that is, an application software. A unifying mathematical theory of chemical thermomechanical network transport for physicochemical systems is proposed and outlined as the basis for developing advanced modules. A program for developing this theory from the underlying first-principles continuum thermomechanics will be needed in future developments; accomplishment of this task will enable the development of a modern modeling approach for plant-level models. Rigorous, advanced modeling approaches at the plant-level can only proceed from the development of reduced (or low-order) models based on a solid continuum field theory foundation. Such development will pave the way for future programmatic activities on software verification, simulation validation, and model uncertainty quantification on a scientific basis; currently, no satisfactory foundation exists for

Geological disposal of high level radioactive waste in China: progress during 1985-2004

International Nuclear Information System (INIS)

Wang Ju; Xu Guoqing; Zheng Hualing; Fan Xianhua; Wang Chengzu; Fan Zhiwen

2005-01-01

Safe disposal of high level radioactive waste (HLW) is a challenging issue for the sustainable development of nuclear energy. The studies for the disposal of HLW in China started in 1985, the proposed goal was to build China's high level waste repository by mid-21st Century, while the waste to be disposed of will be vitrified waste, transuranic waste and small amount of spent fuel. The proposed repository was a shaft-tunnel-silo model hosted by granite in saturated zone. In the period of 1985 to 2004, progress was made in China's HLW disposal program. It was decided that 'deep geological disposal' will be used to dispose of China's HLW, while the technical strategy for the development of repository will a 3-step strategy, that includes steps of site selection and site evaluation, construction of underground research laboratory, and construction of repository. Based on nation wide screening, the Beishan area, Gansu Province, northwestern China, located in Gobi desert area with few inhabitants, integral crust structure and favorable geological and hydrogeological conditions, was selected as the most potential area for China's repository. In early 1990's, site selection for underground research laboratory was conducted, 2 sites in the suburb of Beijing were preliminarily selected as the potential sites for a 'generic underground research laboratory'. It was determined to use bentonite as backfill material for the repository, while the bentonite from Gaomiaozi deposit in Inner Mongolia was selected as potential buffer and backfill material for China's repository. The studies on the mineralogical, geotechnical, physico-mechanical and thermal properties of the Gaomiaozi bentonite have been conducting. Some parameters such as sorption radio, diffusion coefficient and dispersion coefficient of radionuclides (Np, Pu and Tc) in Beishan granite and bentonite have been obtained. A low-oxygen glove box and a device simulating the temperature, pressure and redox potential of

Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

Directory of Open Access Journals (Sweden)

Alam Hunain

2012-01-01

Full Text Available Abstract Background Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC. Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC. Methods To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131 using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients. Results Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041, increased lymph node metastasis (P = 0.001, less differentiation (P = 0.005, increased recurrence (P = 0.038 and shorter survival (P = 0.004 of the patients. Conclusion In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and

Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Alam, Hunain; Kannanl, Sadhna; Gude, Rajiv; Kane, Shubhada; Dalal, Sorab N; Vaidya, Milind M; Bhate, Amruta V; Gangadaran, Prakash; Sawant, Sharda S; Salot, Shimul; Sehgal, Lalit; Dange, Prerana P; Chaukar, Devendra A; D'cruz, Anil K

2012-01-01

Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC. To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients. Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041), increased lymph node metastasis (P = 0.001), less differentiation (P = 0.005), increased recurrence (P = 0.038) and shorter survival (P = 0.004) of the patients. In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC

LDL cholesterolemia as a novel risk factor for radiographic progression of rheumatoid arthritis: a single-center prospective study.

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Yune-Jung Park

Full Text Available Dyslipidemia has been implicated in various musculoskeletal diseases, including rheumatoid arthritis (RA. Evidence is emerging that there might be a pathogenic interaction among inflammation, dyslipidemia, and adipokines. We prospectively investigated the association of cumulative lipid levels with radiographic progression of RA. RA patients (n=242 underwent plasma cholesterol assessment at four visits. Disease activity parameters and X-rays of the hands and feet were also serially monitored in these patients. The cumulative inflammatory burden and lipid levels were estimated by time-integrated values. Serum leptin and adiponectin concentrations were determined by ELISA. When patients were divided into three groups according to time-integrated lipid levels, as expected, patients with LDL cholesterol and/or triglyceride levels in the third tertile had persistently higher ESR and CRP levels. In parallel, a more rapid radiographic progression over two years was observed in patients with higher LDL cholesterol and/or triglyceride levels. In multivariate analysis, time-integrated LDL cholesterol was independently associated with radiographic progression. Particularly, the risk of radiographic progression was 5.6-fold in a subgroup with both LDL cholesterol and triglyceride levels in the third tertile. Moreover, LDL cholesterol synergistically increased the adjusted probability of radiographic progression in patients with high serum leptin levels but not in those without. These results demonstrate that LDL cholesterolemia is a novel serum marker that can be used to predict radiographic progression of RA, which seems to be related to circulatory leptin levels. We suggest that personalized and more aggressive anti-rheumatic therapy is required for dyslipidemic subgroups in RA patients.

Serum Levels of Platelet Released CD40 Ligand Are Increased in Early Onset Occlusive Carotid Artery Disease

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József Balla

2006-01-01

Full Text Available Objective: Soluble CD40 ligand (sCD40L has been suggested as a key mediator between inflammation and atherosclerosis, and the CD40-CD40L interaction has a role in atherosclerotic lesion progression. We evaluated if platelet released serum sCD40L and sCD40 levels differ between patients with early onset occlusive carotid artery disease and age-matched controls.

α2-adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression

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Lamkin, Donald M.; Sung, Ha Yeon; Yang, Gyu Sik; David, John M.; Ma, Jeffrey C.Y.; Cole, Steve W.; Sloan, Erica K.

2014-01-01

Experimental studies in preclinical mouse models of breast cancer have shown that chronic restraint stress can enhance disease progression by increasing catecholamine levels and subsequent signaling of β-adrenergic receptors. Catecholamines also signal α-adrenergic receptors, and greater α-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of α-adrenergic receptors can result in elevated catecholamine levels, which may increase β-adrenergic signaling, because pre-synaptic α2-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of α-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective α-adrenergic blockade by phentolamine significantly inhibited those effects. However, under non-stress conditions, phentolamine increased primary tumor size and distant metastasis. Sympatho-neural gene expression for catecholamine biosynthesis enzymes was elevated by phentolamine under non-stress conditions, and the non-selective β-blocker propranolol inhibited the effect of phentolamine on breast cancer progression. Selective α2-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective α1-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that α2-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of β-adrenergic signaling on tumor progression-relevant biology. PMID:25462899

Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression

International Nuclear Information System (INIS)

Rodrigues dos Santos, Catarina; Fonseca, Isabel; Dias, Sérgio; Mendes de Almeida, JC

2014-01-01

Among women, breast cancer (BC) is the leading cancer and the most common cause of cancer-related death between 30 and 69 years. Although lifestyle and diet are considered to have a role in global BC incidence pattern, the specific influence of dyslipidemia in BC onset and progression is not yet completely understood. Fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) was prospectively assessed in 244 women with BC who were enrolled according to pre-set inclusion criteria: diagnosis of non-hereditary invasive ductal carcinoma; selection for surgery as first treatment, and no history of treatment with lipid-lowering or anti-diabetic drugs in the previous year. Pathological and clinical follow-up data were recorded for further inclusion in the statistical analysis. Univariate associations show that BC patients with higher levels of LDL-C at diagnosis have tumors that are larger, with higher differentiation grade, higher proliferative rate (assessed by Ki67 immunostaining), are more frequently Her2-neu positive and are diagnosed in more advanced stages. Cox regression model for disease-free survival (DFS), adjusted to tumor T and N stages of TNM classification, and immunohistochemical subtypes, revealed that high LDL-C at diagnosis is associated with poor DFS. At 25 months of follow up, DFS is 12% higher in BC patients within the third LDL-C tertile compared to those in the first tertile. This is a prospective study where LDL-C levels, at diagnosis, emerge as a prognostic factor; and this parameter can be useful in the identification and follow-up of high-risk groups. Our results further support a possible role for systemic cholesterol in BC progression and show that cholesterol metabolism may be an important therapeutic target in BC patients

Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression

Energy Technology Data Exchange (ETDEWEB)

Rodrigues dos Santos, Catarina [Gulbenkian Programme for Advanced Medical Education, Lisbon (Portugal); Department of Surgical Oncology, Instituto Português de Oncologia de Lisboa, Francisco Gentil, Lisbon (Portugal); Faculdade de Medicina de Lisboa, Lisbon (Portugal); Fonseca, Isabel [Department of Pathology, Instituto Português de Oncologia de Lisboa, Francisco Gentil, Lisbon (Portugal); Faculdade de Medicina de Lisboa, Lisbon (Portugal); Dias, Sérgio [Instituto de Medicina Molecular, Lisbon (Portugal); Faculdade de Medicina de Lisboa, Lisbon (Portugal); Mendes de Almeida, JC [Department of Surgical Oncology, Instituto Português de Oncologia de Lisboa, Francisco Gentil, Lisbon (Portugal); Faculdade de Medicina de Lisboa, Lisbon (Portugal)

2014-02-26

Among women, breast cancer (BC) is the leading cancer and the most common cause of cancer-related death between 30 and 69 years. Although lifestyle and diet are considered to have a role in global BC incidence pattern, the specific influence of dyslipidemia in BC onset and progression is not yet completely understood. Fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) was prospectively assessed in 244 women with BC who were enrolled according to pre-set inclusion criteria: diagnosis of non-hereditary invasive ductal carcinoma; selection for surgery as first treatment, and no history of treatment with lipid-lowering or anti-diabetic drugs in the previous year. Pathological and clinical follow-up data were recorded for further inclusion in the statistical analysis. Univariate associations show that BC patients with higher levels of LDL-C at diagnosis have tumors that are larger, with higher differentiation grade, higher proliferative rate (assessed by Ki67 immunostaining), are more frequently Her2-neu positive and are diagnosed in more advanced stages. Cox regression model for disease-free survival (DFS), adjusted to tumor T and N stages of TNM classification, and immunohistochemical subtypes, revealed that high LDL-C at diagnosis is associated with poor DFS. At 25 months of follow up, DFS is 12% higher in BC patients within the third LDL-C tertile compared to those in the first tertile. This is a prospective study where LDL-C levels, at diagnosis, emerge as a prognostic factor; and this parameter can be useful in the identification and follow-up of high-risk groups. Our results further support a possible role for systemic cholesterol in BC progression and show that cholesterol metabolism may be an important therapeutic target in BC patients.

Progress in evolving the state-level concept

International Nuclear Information System (INIS)

Cooley, J.N.

2013-01-01

The Department of Safeguards of the International Atomic Energy Agency has launched an important and ambitious project to further develop and implement the State-level concept. It means the development of State-level approaches that are customized for an individual State, meeting State-specific objectives. Further development of the State-level concept requires: 1) expanded use of State-specific factors and implementation of a structured acquisition path analysis to establish State-specific technical objectives and then prioritize them; 2) development of State-level approaches that specify and provide options for safeguards measures, both at Headquarters and in the field, for meeting these technical objectives; 3) identification of activities to be conducted over the course of a year in an annual implementation plan (AIP); and 4) ensuring the linkage between the State-evaluation process and the development and implementation of State-level approaches and AIPs. This project for evolving the State-level concept will result in safeguards implementation that is more objectives-based and information-driven. The paper is followed by the slides of the presentation. (A.C.)

Increased Blood-Reelin-Levels in First Episode Schizophrenia.

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Tobias Hornig

Full Text Available Reelin is an extracellular glycoprotein involved in several functions of brain development, synaptogenesis and dendritic proliferation. Numerous studies found perturbation in the reelin system and altered serum reelin levels in neuropsychiatric patients using the western blot procedure. In the international literature, this is the first study that made use of an enzyme-linked immunosorbent assay to analyze serum reelin protein concentration quantitatively.In order to study possible alterations in reelin blood levels in schizophrenia, we analyzed this signal in schizophrenic patients with a first episode hallucinatory and paranoid syndrome and control subjects in a pilot study design.We found increased blood reelin protein concentration in schizophrenic patients compared to healthy controls.Our findings point to a relevant role of reelin metabolism in the pathogenesis of schizophrenia.Reelin could be a biomarker for the course of disease or psychopharmacological treatment.We conclude that the reelin protein blood concentration might be a relevant signal with respect to the pathophysiology of schizophrenia.

Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels

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Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B.; Dong, Xiao; Wang, Hongjun

2015-01-01

Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

Exercise increases endostatin in circulation of healthy volunteers.

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Gu, Jian-Wei; Gadonski, Giovani; Wang, Julie; Makey, Ian; Adair, Thomas H

2004-01-16

Physical inactivity increases the risk of atherosclerosis. However, the molecular mechanisms of this relation are poorly understood. A recent report indicates that endostatin, an endogenous angiostatic factor, inhibits the progression of atherosclerosis, and suggests that reducing intimal and atherosclerotic plaque tissue neovascularization can inhibit the progression atherosclerosis in animal models. We hypothesize that exercise can elevate the circulatory endostatin level. Hence, exercise can protect against one of the mechanisms of atherosclerosis. We examined treadmill exercise tests in healthy volunteers to determine the effect of exercise on plasma levels of endostatin and other angiogenic regulators. Oxygen consumption (VO2) was calculated. Plasma levels of endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) were determined using ELISA. The total peak VO2 (L) in 7 male subjects was 29.5 +/- 17.8 over a 4-10 minute interval of exercise. Basal plasma levels of endostatin (immediately before exercise) were 20.3 +/- 3.2 pg/ml, the plasma levels increased to 29.3 +/- 4.2, 35.2 +/- 1.8, and 27.1 +/- 2.2 ng/ml, at 0.5, 2, and 6 h, respectively, after exercise. There was a strong linear correlation between increased plasma levels of endostatin (%) and the total peak VO2 (L) related to exercise (R2 = 0.9388; P < 0.01). Concurrently, VEGF levels decreased to 28.3 +/- 6.4, 17.6 +/- 2.4, and 26.5 +/- 12.5 pg/ml, at 0.5, 2, and 6 h, respectively, after exercise. There were no significant changes in plasma bFGF levels in those subjects before and after exercise. The results suggest that circulating endostatin can be significantly increased by exercise in proportion to the peak oxygen consumption under physiological conditions in healthy volunteers. These findings may provide new insights into the molecular links between physical inactivity and the risk of angiogenesis dependent diseases such as atherosclerosis.

Simulating the impact of inflation on the progressivity of personal income tax in Brazil

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Horacio Levy

2010-12-01

Full Text Available Income tax reform in Brazil has mainly stressed changes in rates, aiming at increasing its progressivity. One aspect frequently overlooked is that, in the absence of adjustments of the tax rules to inflation, the level and distribution of the income tax burden can be substantially affected. We use a microsimulation model to simulate the potential revenue and distributive effects of inflation on the income tax in Brazil. Our findings suggest that if the income tax is not adjusted for inflation, progressivity would decrease but redistribution would increase due to a larger tax burden, but income inequality would not substantially change.

Progress test utopia.

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van der Vleuten, Cees; Freeman, Adrian; Collares, Carlos Fernando

2018-04-01

This paper discusses the advantages of progress testing. A utopia is described where medical schools would work together to develop and administer progress testing. This would lead to a significant reduction of cost, an increase in the quality of measurement and phenomenal feedback to learner and school. Progress testing would also provide more freedom and resources for more creative in-school assessment. It would be an educationally attractive alternative for the creation of cognitive licensing exams. A utopia is always far away in the future, but by formulating a vision for that future we may engage in discussions on how to get there.

Metabolomic Biomarkers in the Progression to Type 1 Diabetes

DEFF Research Database (Denmark)

Overgaard, Anne Julie; Kaur, Simranjeet; Pociot, Flemming

2016-01-01

diabetes has been studied using this technique, although in relatively small cohorts and at limited time points. Overall, three observations have been consistently reported; phospholipids at birth are lower in children developing type 1 diabetes early in childhood, methionine levels are lower in children......Metabolomics is the snapshot of all detectable metabolites and lipids in biological materials and has potential in reflecting genetic and environmental factors contributing to the development of complex diseases, such as type 1 diabetes. The progression to seroconversion to development of type 1...... at seroconversion, and triglycerides are increased at seroconversion and associated to microbiome diversity, indicating an association between the metabolome and microbiome in type 1 diabetes progression....

The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxicity and Increase TDP-43 Levels.

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Salazar, Dominique A; Butler, Victoria J; Argouarch, Andrea R; Hsu, Tsung-Yuan; Mason, Amanda; Nakamura, Ayumi; McCurdy, Helen; Cox, David; Ng, Rachel; Pan, Gloria; Seeley, William W; Miller, Bruce L; Kao, Aimee W

2015-06-24

Mutations in the human progranulin gene resulting in protein haploinsufficiency cause frontotemporal lobar degeneration with TDP-43 inclusions. Although progress has been made in understanding the normal functions of progranulin and TDP-43, the molecular interactions between these proteins remain unclear. Progranulin is proteolytically processed into granulins, but the role of granulins in the pathogenesis of neurodegenerative disease is unknown. We used a Caenorhabditis elegans model of neuronal TDP-43 proteinopathy to specifically interrogate the contribution of granulins to the neurodegenerative process. Complete loss of the progranulin gene did not worsen TDP-43 toxicity, whereas progranulin heterozygosity did. Interestingly, expression of individual granulins alone had little effect on behavior. In contrast, when granulins were coexpressed with TDP-43, they exacerbated its toxicity in a variety of behaviors including motor coordination. These same granulins increased TDP-43 levels via a post-translational mechanism. We further found that in human neurodegenerative disease subjects, granulin fragments accumulated specifically in diseased regions of brain. To our knowledge, this is the first demonstration of a toxic role for granulin fragments in a neurodegenerative disease model. These studies suggest that presence of cleaved granulins, rather than or in addition to loss of full-length progranulin, may contribute to disease in TDP-43 proteinopathies. Copyright © 2015 the authors 0270-6474/15/359315-14$15.00/0.

Benefits and costs of increased levels of corticosterone in seabird chicks

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Kitaysky, A.S.; Kitaiskaia, E.V.; Piatt, John F.; Wingfield, J.C.

2003-01-01

Seabird chicks respond to food shortages by increasing corticosterone (cort) secretion, which is probably associated with fitness benefits and costs. To examine this, we experimentally increased levels of circulating cort in captive black-legged kittiwake chicks fed ad libitum. We found that cort-implanted chicks begged more frequently and were more aggressive compared to controls. These behavioral modifications must be beneficial to chicks as they facilitate acquisition of food from the parents and might trigger brood reduction and reduced competition for food. Cort-implanted chicks also increased food intake; however, their growth rates were similar to controls. To examine the costs of chronically increased circulating levels of cort, we removed cort implants and, after a 10-day recovery period, tested cognitive abilities of young kittiwakes. We found that the ability of kittiwakes to associate a visual cue with the presence of food in a choice situation was compromised by the experimental elevation of cort during development. To examine the long-term costs of increased levels of cort, 8 months later we tested the performance of the same individuals in a spatial task requiring them to make a detour around a barrier in order to escape from an enclosure. Individuals treated with cort during development took significantly more time to solve this task compared to controls. The results of this study suggest that the adrenocortical response of a developing bird to environmental stressors is associated with both benefits (increased food intake, foraging behavior, and aggression) and costs (low growth efficiency and compromised cognitive abilities later in life). This provides an evolutionary framework for relating juvenile physiological traits to fitness of birds in subsequent life-history stages. ?? 2003 Elsevier Science (USA). All rights reserved.

Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model

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Lunt Sarah

2008-05-01

Full Text Available Abstract Background Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model. Methods To address this issue, we determined the effects of 6 week in vivo acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG lesions in the transgenic polyomavirus middle T (PyMT breast cancer mouse model. Results We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the in vivo exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs, demonstrating a relationship between hypoxia and macrophages in an experimental model. Conclusion These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.

Monitoring the progressive increase of the longest episode of spontaneous movements in Guinea pig fetus

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Sekulić S.

2013-01-01

Full Text Available The aim of this work was to determine the changes in the duration of spontaneous movements in the guinea pig fetus after the appearance of its first movements. Every day from the 25th to the 35th gestation day, one fetus from each of twenty pregnant animals was examined by ultrasound. Fetal movements were observed for 5 min. The episode with the longest period of movement was taken into consideration and was recorded as: 3 s. Days 25 and 26 were characterized by episodes lasting 3 s (χ2 = 140.51 p <0.05. Tracking the dynamics of progressive increases in the longest episode of spontaneous movement could be a useful factor in estimating the maturity and condition of a fetus. [Projekat Ministarstva nauke Republike Srbije, br. 175006/2011

Geomorphic Response of a Low-Gradient Channel to Modern, Progressive Base-Level Lowering: Nahal HaArava, the Dead Sea

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Dente, Elad; Lensky, Nadav G.; Morin, Efrat; Grodek, Tamir; Sheffer, Nathan A.; Enzel, Yehouda

2017-12-01

The geomorphic response of channels to base-level fall is an important factor in landscape evolution. To better understand the complex interactions between the factors controlling channel evolution in an emerging continental shelf setting, we use an extensive data set (high-resolution digital elevation models, aerial photographs, and Landsat imagery) of a newly incising, perennial segment of Nahal (Wadi) HaArava, Israel. This channel responds to the rapid and progressive lowering of its base-level, the Dead Sea (>30 m in 35 years; 0.5-1.3 m yr-1). Progressively evolving longitudinal profiles, channel width, sinuosity, and knickpoint retreat during the last few decades were documented or reconstructed. The results indicate that even under fast base-level fall, rapid delta progradation on top of the shelf and shelf edge can moderate channel mouth slopes and, therefore, largely inhibit channel incision and knickpoint propagation. This channel elongation stage ends when the delta reaches an extended accommodation within the receiving basin and fails to keep the channel mouth slopes as low as the channel bed slopes. Then, processes of incision, narrowing, and meandering begin to shape the channel and expand upstream. When the down-cutting channel encounters a more resistant stratum within the channel substrate, these processes are restricted to a downstream reach by formation of a retreating vertical knickpoint. When the knickpoint and the channel incise to a level below this stratum, a spatially continuous, diffusion-like evolution characterizes the channel's response and source-to-sink transport can be implemented. These results emphasize the mouth slope and channel substrate resistance as the governing factors over long-term channel evolution, whereas flash floods have only local and short-lived impacts in a confined, continuously incising channel. The documented channel response applies to eustatic base-level fall under steepening basin bathymetry, rapid delta

Bicuspid aortic valves are associated with increased wall and turbulence shear stress levels compared to trileaflet aortic valves.

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Saikrishnan, Neelakantan; Mirabella, Lucia; Yoganathan, Ajit P

2015-06-01

Congenital bicuspid aortic valves (BAVs) are associated with accelerated disease progression, such as leaflet calcification and ascending aorta dilatation. Although common underlying genetic factors have been implicated in accelerated disease in BAV patients, several studies have suggested that altered hemodynamics also play a role in this disease process. The present study compares turbulence and wall shear stress (WSS) measurements between various BAV and trileaflet aortic valve (TAV) models to provide information for mechanobiological models of BAV disease. BAV and TAV models were constructed from excised porcine aortic valves to simulate parametric variations in BAV stenosis, hemodynamics and geometry. Particle image velocimetry experiments were conducted at physiological pressure conditions to characterize velocity fields in the ascending aorta. The velocity fields were post-processed to calculate turbulence, viscous and wall shear stresses in the ascending aorta. Stenosed BAV models showed the presence of eccentric systolic jets, causing increased WSS. Lower cardiac output resulted in a narrower jet, lower turbulence and lower viscous shear stress (VSS). The specific severe stenosis BAV model studied here showed reduced WSS due to reduction in non-fused leaflet mobility. Dilation of the aorta did not affect any turbulence or VSS, but reduced the WSS. In comparison with BAVs, TAVs have similar VSS values, but much smaller WSS and turbulence levels. These increased turbulence  and WSS levels in BAVs may play a key role in amplifying the biological responses of the ascending aorta wall and valvular leaflets, and support the hemodynamic underpinnings of BAV disease processes.

Idea Bank: Progress through Incentives: How One Music Program Helps Students Progress to Higher Levels of Musicianship

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Boyd, Joshua

2013-01-01

Students are motivated when they have a constant system of rewards. They have a desire to please others and be recognized. It was with this idea in mind that the Smokey Road Middle School Band in Newman, Georgia, started using the "Power in the Progress System" in 2011. This system, created by H. Dwight Satterwhite, a professor of music…

Progressive Increase in Telomerase Activity From Benign Melanocytic Conditions to Malignant Melanoma

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Ruben D. Ramirez

1999-04-01

Full Text Available The expression of telomerase activity and the in situ localization of the human telomerase RNA component (hTR in melanocytic skin lesions was evaluated in specimens from sixty-three patients. Specimens of melanocytic nevi, primary melanomas and subcutaneous metastases of melanoma were obtained from fifty-eight patients, whereas metastasized lymph nodes were obtained from five patients. Telomerase activity was determined in these specimens by using a Polymerase Chain Reaction—based assay (TRAP. High relative mean telomerase activity levels were detected in metastatic melanoma (subcutaneous metastasess = 54.5, lymph node metastasess = 56.5. Much lower levels were detected in primary melanomas, which increased with advancing levels of tumor cell penetration (Clark II = 0.02, Clark III = 1.1, and Clark IV = 1.9. Twenty-six formalin-fixed, paraffin-embedded melanocytic lesions were sectioned and analyzed for telomerase RNA with a radioactive in situ hybridization assay. In situ hybridization studies with a probe to the template RNA component of telomerase confirmed that expression was almost exclusively confined to tumor cells and not infiltrating lymphocytes. These results indicate that levels of telomerase activity and telomerase RNA in melanocytic lesions correlate well with clinical stage and could potentially assist in the diagnosis of borderline lesions.

Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice.

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Mateus Milani

Full Text Available Current monitoring of acute lymphoblastic leukemia (ALL in living mice is based on FACS analysis of blood hCD45+ cells. In this work, we evaluated the use of human IGFBP2, B2M or Hsp90 as soluble markers of leukemia. ELISA for B2M and IGFBP2 resulted in high background levels in healthy animals, precluding its use. Conversely, plasma levels of Hsp90 showed low background and linear correlation to FACS results. In another experiment, we compared Hsp90 levels with percentage of hCD45+ cells in blood, bone marrow, liver and spleen of animals weekly sacrificed. Hsp90 levels proved to be a superior method for the earlier detection of ALL engraftment and correlated linearly to ALL burden and progression in all compartments, even at minimal residual disease levels. Importantly, the Hsp90/hCD45+ ratio was not altered when animals were treated with dexamethasone or a PI3K inhibitor, indicating that chemotherapy does not directly interfere with leukemia production of Hsp90. In conclusion, plasma Hsp90 was validated as a soluble biomarker of ALL, useful for earlier detection of leukemia engraftment, monitoring leukemia kinetics at residual disease levels, and pre-clinical or mouse avatar evaluations of anti-leukemic drugs.

Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice

Science.gov (United States)

de Vasconcellos, Jaíra Ferreira; Brandalise, Silvia Regina; Nowill, Alexandre Eduardo; Yunes, José Andrés

2015-01-01

Current monitoring of acute lymphoblastic leukemia (ALL) in living mice is based on FACS analysis of blood hCD45+ cells. In this work, we evaluated the use of human IGFBP2, B2M or Hsp90 as soluble markers of leukemia. ELISA for B2M and IGFBP2 resulted in high background levels in healthy animals, precluding its use. Conversely, plasma levels of Hsp90 showed low background and linear correlation to FACS results. In another experiment, we compared Hsp90 levels with percentage of hCD45+ cells in blood, bone marrow, liver and spleen of animals weekly sacrificed. Hsp90 levels proved to be a superior method for the earlier detection of ALL engraftment and correlated linearly to ALL burden and progression in all compartments, even at minimal residual disease levels. Importantly, the Hsp90/hCD45+ ratio was not altered when animals were treated with dexamethasone or a PI3K inhibitor, indicating that chemotherapy does not directly interfere with leukemia production of Hsp90. In conclusion, plasma Hsp90 was validated as a soluble biomarker of ALL, useful for earlier detection of leukemia engraftment, monitoring leukemia kinetics at residual disease levels, and pre-clinical or mouse avatar evaluations of anti-leukemic drugs. PMID:26068922

High Circulating Adrenaline Levels at Admission Predict Increased Mortality After Trauma

DEFF Research Database (Denmark)

Johansson, Pär Ingemar; Stensballe, Jakob; Rasmussen, Lars Simon

2012-01-01

partial thromboplastin time, international normalized ratio, hematology, biochemistry, circulating adrenaline and noradrenaline, 11 biomarkers of tissue and endothelial damage, glycocalyx degradation, natural anticoagulation and fibrinolysis (histone-complexed DNA fragments, high-mobility group box 1......:: The adrenaline level was increased in nonsurvivors (p = 0.026), it was independently associated with increased activated partial thromboplastin time (p = 0.034) and syndecan-1 (p = 0.007), a marker of glycocalyx degradation, and it correlated with biomarkers of tissue and endothelial damage (histone......-complexed DNA, high-mobility group box 1, soluble thrombomodulin) and hyperfibrinolysis (tissue-type plasminogen activator, d-dimer). Furthermore, nonsurvivors had higher syndecan-1, tissue factor pathway inhibitor, and d-dimer levels (all p adrenaline was independently associated with 30...

Progressive hypoxia decouples activity and aerobic performance of skate embryos.

Science.gov (United States)

Di Santo, Valentina; Tran, Anna H; Svendsen, Jon C

2016-01-01

Although fish population size is strongly affected by survival during embryonic stages, our understanding of physiological responses to environmental stressors is based primarily on studies of post-hatch fishes. Embryonic responses to acute exposure to changes in abiotic conditions, including increase in hypoxia, could be particularly important in species exhibiting long developmental time, as embryos are unable to select a different environment behaviourally. Given that oxygen is key to metabolic processes in fishes and aquatic hypoxia is becoming more severe and frequent worldwide, organisms are expected to reduce their aerobic performance. Here, we examined the metabolic and behavioural responses of embryos of a benthic elasmobranch fish, the little skate (Leucoraja erinacea), to acute progressive hypoxia, by measuring oxygen consumption and movement (tail-beat) rates inside the egg case. Oxygen consumption rates were not significantly affected by ambient oxygen levels until reaching 45% air saturation (critical oxygen saturation, S crit). Below S crit, oxygen consumption rates declined rapidly, revealing an oxygen conformity response. Surprisingly, we observed a decoupling of aerobic performance and activity, as tail-beat rates increased, rather than matching the declining metabolic rates, at air saturation levels of 55% and below. These results suggest a significantly divergent response at the physiological and behavioural levels. While skate embryos depressed their metabolic rates in response to progressive hypoxia, they increased water circulation inside the egg case, presumably to restore normoxic conditions, until activity ceased abruptly around 9.8% air saturation.

Ghrelin administered spinally increases the blood glucose level in mice.

Science.gov (United States)

Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

2014-04-01

Ghrelin is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of ghrelin located in the spinal cord in the regulation of the blood glucose level were investigated in ICR mice. We found that intrathecal (i.t.) injection with ghrelin (from 1 to 10 μg) caused an elevation of the blood glucose level. In addition, i.t. pretreatment with YIL781 (ghrelin receptor antagonist; from 0.1 to 5 μg) markedly attenuated ghrelin-induced hyperglycemic effect. The plasma insulin level was increased by ghrelin. The enhanced plasma insulin level by ghrelin was reduced by i.t. pretreatment with YIL781. However, i.t. pretreatment with glucagon-like peptide-1 (GLP-1; 5 μg) did not affect the ghrelin-induced hyperglycemia. Furthermore, i.t. administration with ghrelin also elevated the blood glucose level, but in an additive manner, in d-glucose-fed model. Our results suggest that the activation of ghrelin receptors located in the spinal cord plays important roles for the elevation of the blood glucose level. Copyright © 2014 Elsevier Inc. All rights reserved.

Sunlight exposure and sun sensitivity associated with disability progression in multiple sclerosis.

Science.gov (United States)

D'hooghe, M B; Haentjens, P; Nagels, G; Garmyn, M; De Keyser, J

2012-04-01

Sunlight and vitamin D have been inversely associated with the risk of multiple sclerosis (MS). We investigated sunlight exposure and sun sensitivity in relation to disability progression in MS. We conducted a survey among persons with MS, registered by the Flemish MS society, Belgium, and stratified data according to relapsing-onset and progressive-onset MS. We used Kaplan-Meier survival and Cox proportional hazard regression analyses with time to Expanded Disability Status Scale (EDSS) 6 as outcome measure. Hazard ratios for the time from onset and from birth were calculated for the potentially predictive variables, adjusting for age at onset, gender and immunomodulatory treatment. 704 (51.3%) of the 1372 respondents had reached EDSS 6. In relapsing-onset MS, respondents reporting equal or higher levels of sun exposure than persons of the same age in the last 10 years had a decreased risk of reaching EDSS 6. In progressive-onset MS, increased sun sensitivity was associated with an increased hazard of reaching EDSS 6. The association of higher sun exposure with a better outcome in relapsing-onset MS may be explained by either a protective effect or reverse causality. Mechanisms underlying sun sensitivity might influence progression in progressive-onset MS.

Testosterone increases circulating dehydroepiandrosterone sulfate levels in the male rhesus macaque

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Krystina eSorwell

2014-06-01

Full Text Available The adrenal steroid dehydroepiandrosterone (DHEA and its sulfate (DHEAS are two of the most abundant hormones in the human circulation. Furthermore, they are released in a circadian pattern and show a marked age-associated decline. Adult levels of DHEA and DHEAS are significantly higher in males than in females, but the reason for this sexual dimorphism is unclear. In the present study, we administered supplementary androgens (DHEA, testosterone and 5α-dihydrotestosterone [DHT] to aged male rhesus macaques (Macaca mulatta. While this paradigm increased circulating DHEAS immediately after DHEA administration, an increase was also observed following either testosterone or DHT administration, resulting in hormonal profile resembling levels observed in young males in terms of both amplitude and circadian pattern. This stimulatory effect was limited to DHEAS, as an increase in circulating cortisol was not observed. Taken together, these data demonstrate an influence of the hypothalamo-pituitary-testicular axis on adrenal function in males, possibly by sensitizing the zona reticularis to the stimulating action of adrenocorticopic hormone. This represents a plausible mechanism to explain sex differences in circulating DHEA and DHEAS levels, and may have important implications in the development of hormone therapies designed for elderly men and women.

Increasing Resilience Through Engagement In Sea Level Rise Community Science Initiatives.

Science.gov (United States)

Chilton, L. A.; Rindge, H.

2017-12-01

Science literate and engaged members of the public, including students, are critical to building climate resilient communities. USC Sea Grant facilitates programs that work to build and strengthen these connections. The Urban Tides Community Science Initiative (Urban Tides) and the Youth Exploring Sea Level Rise Science Program (YESS) engage communities across the boundaries of public engagement, K-12 education, and informal education. YESS is an experiential sea level rise education program that combines classroom learning, field investigations and public presentations. Students explore sea level rise using a new curricula, collect their own data on sea level rise, develop communication products, and present their findings to city governments, researchers, and others. Urban Tides engages community members, informal education centers, K-12 students, and local government leaders in a citizen science program photo- documenting extreme high tides, erosion and coastal flooding in Southern California. Images provide critical information to help calibrate scientific models used to identify locations vulnerable to damage from future sea level rise. These tools and information enable community leaders and local governments to set priorities, guidelines, and update policies as they plan strategies that will help the region adapt. The program includes a mobile app for data collection, an open database to view photos, a lesson plan, and community beach walks. Urban Tides has led to an increase in data and data-gathering capacity for regional scientists, an increase in public participation in science, and an increase in ocean and climate literacy among initiative participants. Both of these programs bring informed and diverse voices into the discussion of how to adapt and build climate resilient communities. USC Sea Grant will share impacts and lessons learned from these two unique programs.

Pregnancy-induced progression of keratoconus.

Science.gov (United States)

Bilgihan, Kamil; Hondur, Ahmet; Sul, Sabahattin; Ozturk, Sertac

2011-09-01

To report eyes with keratoconus that progressed during pregnancy. Seven eyes of 4 patients with progression of keratoconus during pregnancy were included in this study. The mean age of patients and the mean follow-up duration were 29.3 years and 39 months, respectively. Progressive keratoconus was documented with changes in refraction, corneal topography, and rigid gas-permeable lens fitting pattern. Patients with accompanying systemic and ocular diseases associated with keratoconus, uncontrolled atopic disease, and eye rubbing were excluded. Mean increase in spherical equivalent refraction and simulated keratometry values were 1.4 ± 1.1 and 1.1 ± 0.8 diopters, respectively. In eyes wearing rigid gas-permeable lenses, increase in corneal apical touch and decrease in the base curve radius of the best-fitting contact lens were observed. Hormonal changes during pregnancy may affect corneal biomechanics negatively, and pregnancy may be a previously unrecognized risk factor for progression of keratoconus. To our knowledge, this is the first study showing pregnancy-induced keratoconus progression in patients with no accompanying disease.

Extensive Atrophic Gastritis Increases Intraduodenal Hydrogen Gas

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Yoshihisa Urita

2008-01-01

Full Text Available Objective. Gastric acid plays an important part in the prevention of bacterial colonization of the gastrointestinal tract. If these bacteria have an ability of hydrogen (H2 fermentation, intraluminal H2 gas might be detected. We attempted to measure the intraluminal H2 concentrations to determine the bacterial overgrowth in the gastrointestinal tract. Patients and methods. Studies were performed in 647 consecutive patients undergoing upper endoscopy. At the time of endoscopic examination, we intubated the stomach and the descending part of the duodenum without inflation by air, and 20 mL of intraluminal gas samples of both sites was collected through the biopsy channel. Intraluminal H2 concentrations were measured by gas chromatography. Results. Intragastric and intraduodenal H2 gas was detected in 566 (87.5% and 524 (81.0% patients, respectively. The mean values of intragastric and intraduodenal H2 gas were 8.5±15.9 and 13.2±58.0 ppm, respectively. The intraduodenal H2 level was increased with the progression of atrophic gastritis, whereas the intragastric H2 level was the highest in patients without atrophic gastritis. Conclusions. The intraduodenal hydrogen levels were increased with the progression of atrophic gastritis. It is likely that the influence of hypochlorhydria on bacterial overgrowth in the proximal small intestine is more pronounced, compared to that in the stomach.

MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis

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Yasmina Bauer

2017-03-01

Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease. Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7, Fas death receptor ligand, osteopontin and procollagen type I C-peptide, to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF. In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4. MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression.

Association of ficolin-3 with abdominal aortic aneurysm presence and progression

DEFF Research Database (Denmark)

Fernandez-García, C-E; Burillo, E; Lindholt, J S

2017-01-01

Essentials Abdominal aortic aneurysm (AAA) is asymptomatic and its evolution unpredictable. To find novel potential biomarkers of AAA, microvesicles are an excellent source of biomarkers. Ficolin-3 is increased in microvesicles obtained from activated platelets and AAA tissue. Increased ficolin-3...... plasma levels are associated with AAA presence and progression. SUMMARY: Background Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA...... pathophysiology. Objectives To define extra-hepatic sources of ficolin-3 in AAA and investigate the role of ficolin-3 as a biomarker of the presence and progression of AAA. Methods Microvesicles (exosomes and microparticles) were isolated from culture-conditioned medium of ADP-activated platelets, as well as from...

Grapevine rootstock effects on scion sap phenolic levels, resistance to Xylella fastidiosa infection, and progression of Pierce’s disease

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Christopher Michael Wallis

2013-12-01

Full Text Available The xylem-limited bacterium Xylella fastidiosa (Xf causes Pierce’s disease (PD, an important disease of grapevine, Vitis vinifera L.. Grapevine rootstocks were developed to provide increased resistance to root disease, but rootstock effects on cane and vine diseases remain unclear. Grapevines that consisted of Cabernet Sauvignon or Chardonnay grafted to 13 different rootstocks were inoculated with Xf and evaluated for PD severity and Xf titer after six months. A subset of six rootstock/scion combinations had xylem sap phenolic levels assessed in non-infected and Xf-infected grapevines. Vigor also was analyzed by measuring root lengths and masses. Cabernet Sauvignon grafted to 101-14MG, 1103P, 420A, or Schwarzmann had reduced PD severity compared to Cabernet Sauvignon grafted to 110R, 5BB, or SO4. Chardonnay grafted to Salt Creek or Freedom had reduced PD severity compared to Chardonnay grafted to RS3 or Schwarzmann. Chardonnay grafted to RS3 had greater Xf titer than Chardonnay grafted to 101-14MG, Freedom, or Salt Creek. No other differences in Xf titer among rootstocks were observed. Of the six scion/rootstock combinations which had xylem sap phenolics analyzed, Chardonnay/ RS3 had the highest levels of most phenolics whereas Cabernet Sauvignon/101-14MG had the lowest phenolic levels. However, Chardonnay/101-14MG, which had mild PD symptoms, had greater sap levels of caftaric acid than other scion/rootstock combinations. Sap levels of caftaric acid, methyl salicylate, a procyanidin trimer, and quinic acid were greater in Xf-infected versus non-infected grapevines. Chardonnay on 101-14MG or Salt Creek had greater root mass than Chardonnay on RS3. Cabernet Sauvignon on 101-14MG had greater root mass than Cabernet Sauvignon on 110R. These results identified rootstocks with the capacity for reducing PD symptom progression. Rootstocks also were shown to affect Xf titer, xylem sap phenolic levels, and plant vigor.

Impact of HIV Type 1 DNA Levels on Spontaneous Disease Progression: A Meta-Analysis

DEFF Research Database (Denmark)

Tsiara, Chrissa G; Nikolopoulos, Georgios K; Bagos, Pantelis G

2012-01-01

Abstract Several studies have reported the prognostic strength of HIV-1 DNA with variable results however. The aims of the current study were to estimate more accurately the ability of HIV-1 DNA to predict progression of HIV-1 disease toward acquired immunodeficiency syndrome (AIDS) or death...... of primary studies indicated that HIV-1 DNA was a significantly better predictor than HIV-1 RNA of either AIDS alone (ratio of RRs=1.47, 95% CI: 1.05-2.07) or of combined (AIDS or death) progression outcomes (ratio of RRs=1.51, 95% CI: 1.11-2.05). HIV-1 DNA is a strong predictor of HIV-1 disease progression...

Female Progress and Discrimination. An Economic Perspective

OpenAIRE

Sandra E. Black

2005-01-01

In the last 20 years, women’s economic progress has been staggering; this progress is particularly startling given that this has also been a period of marked increases in income inequality overall, declining relative wages of blacks, and declining real wages of low-skilled workers. Recent work has proposed a number of possible explanations for the progress of women, including changing social norms (in part facilitated by technological/pharmaceutical advances), increasing skill acquisition, ch...

Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

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Janaína Garcia Gonçalves

Full Text Available Despite a significant improvement in the management of chronic kidney disease (CKD, its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1. Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD.Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI; and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR; gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages, type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy, increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.Through inflammatory

Light ion ignitors for inertial confinement fusion: progress toward proof-of-principle

International Nuclear Information System (INIS)

Quintenz, J.P.; Kuswa, G.W.

1981-01-01

From the inception of the REB effort, it was recognized that light ion beams offered substantial advantages as an ICF driver, and as the pulse power driver program progressed the possibilities of using light ion beams became increasingly evident. Because of the rapid progress made in the available power in these light ion beams, their superior target deposition characteristics, the fact that nonrelativistic ion beams can readily be bunched by a factor of 2 to 4, and the favorable scaling relations leading toward reactor levels, Sandia shifted its ICF emphasis from electrons to ions in 1979. The progress which has been made toward proof-of-principle using light ion ignitors, as well as the remaining problems, will be detailed in this paper

Surgical resident technical skill self-evaluation: increased precision with training progression.

Science.gov (United States)

Quick, Jacob A; Kudav, Vishal; Doty, Jennifer; Crane, Megan; Bukoski, Alex D; Bennett, Bethany J; Barnes, Stephen L

2017-10-01

Surgical resident ability to accurately evaluate one's own skill level is an important part of educational growth. We aimed to determine if differences exist between self and observer technical skill evaluation of surgical residents performing a single procedure. We prospectively enrolled 14 categorical general surgery residents (six post-graduate year [PGY] 1-2, three PGY 3, and five PGY 4-5). Over a 6-month period, following each laparoscopic cholecystectomy, residents and seven faculty each completed the Objective Structured Assessment of Technical Skills (OSATS). Spearman's coefficient was calculated for three groups: senior (PGY 4-5), PGY3, and junior (PGY 1-2). Rho (ρ) values greater than 0.8 were considered well correlated. Of the 125 paired assessments (resident-faculty each evaluating the same case), 58 were completed for senior residents, 54 for PGY3 residents, and 13 for junior residents. Using the mean from all OSATS categories, trainee self-evaluations correlated well to faculty (senior ρ 0.97, PGY3 ρ 0.9, junior ρ 0.9). When specific OSATS categories were analyzed, junior residents exhibited poor correlation in categories of respect for tissue (ρ -0.5), instrument handling (ρ 0.71), operative flow (ρ 0.41), use of assistants (ρ 0.05), procedural knowledge (ρ 0.32), and overall comfort with the procedure (ρ 0.73). PGY3 residents lacked correlation in two OSATS categories, operative flow (ρ 0.7) and procedural knowledge (ρ 0.2). Senior resident self-evaluations exhibited strong correlations to observers in all areas. Surgical residents improve technical skill self-awareness with progressive training. Less-experienced trainees have a tendency to over-or-underestimate technical skill. Copyright © 2017 Elsevier Inc. All rights reserved.

Progress Toward Single-Photon-Level Nonlinear Optics in Crystalline Microcavities

Science.gov (United States)

Kowligy, Abijith S.

Over the last two decades, the emergence of quantum information science has uncovered many practical applications in areas such as communications, imaging, and sensing where harnessing quantum features of Nature provides tremendous benefits over existing methods exploiting classical physical phenomena. In this effort, one of the frontiers of research has been to identify and utilize quantum phenomena that are not susceptible to environmental and parasitic noise processes. Quantum photonics has been at the forefront of these studies because it allows room-temperature access to its inherently quantum-mechanical features, and allows leveraging the mature telecommunication industry. Accompanying the weak environmental influence, however, are also weak optical nonlinearities. Efficient nonlinear optical interactions are indispensible for many of the existing protocols for quantum optical computation and communication, e.g. high-fidelity entangling quantum logic gates rely on large nonlinear responses at the one- or few-photon-level. While this has been addressed to a great extent by interfacing photons with single quantum emitters and cold atomic gases, scalability has remained elusive. In this work, we identify the macroscopic second-order nonlinear polarization as a robust platform to address this challenge, and utilize the recent advances in the burgeoning field of optical microcavities to enhance this nonlinear response. In particular, we show theoretically that by using the quantum Zeno effect, low-noise, single-photon-level optical nonlinearities can be realized in lithium niobate whispering-gallery-mode microcavities, and present experimental progress toward this goal. Using the measured strength of the second-order nonlinear response in lithium niobate, we modeled the nonlinear system in the strong coupling regime using the Schrodinger picture framework and theoretically demonstrated that the single-photon-level operation can be observed for cavity lifetimes in

Enteral nutrition increases interstitial brain glucose levels in poor-grade subarachnoid hemorrhage patients.

Science.gov (United States)

Kofler, Mario; Schiefecker, Alois J; Beer, Ronny; Gaasch, Maxime; Rhomberg, Paul; Stover, John; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

2018-03-01

Low brain tissue glucose levels after acute brain injury are associated with poor outcome. Whether enteral nutrition (EN) reliably increases cerebral glucose levels remains unclear. In this retrospective analysis of prospectively collected observational data, we investigate the effect of EN on brain metabolism in 17 poor-grade subarachnoid hemorrhage (SAH) patients undergoing cerebral microdialysis (CMD) monitoring. CMD-values were obtained hourly. A nutritional intervention was defined as the clinical routine administration of EN without supplemental parenteral nutrition. Sixty-three interventions were analyzed. The mean amount of EN per intervention was 472.4 ± 10.7 kcal. CMD-glucose levels significantly increased from 1.59 ± 0.13 mmol/l at baseline to a maximum of 2.03 ± 0.2 mmol/l after 5 h (p  40) and the microdialysis probe location. The increase in CMD-glucose was directly dependent on the magnitude of increase of serum glucose levels (p = 0.007). No change in CMD-lactate, CMD-pyruvate, CMD-LPR, or CMD-glutamate (p > 0.4) was observed. Routine EN also increased CMD-glucose even if baseline concentrations were critically low ( < 0.7 mmol/l, neuroglucopenia; p < 0.001). These results may have treatment implications regarding glucose management of poor-grade aneurysmal SAH patients.

Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms

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Miroslava Bilecova-Rabajdova

2014-01-01

Full Text Available Background. In the last few years, the cancer research had tried to identify and characterize new biochemical and molecular pathways in which the inhibition induces prosurvival mechanisms. Our work describes the expression of two different members of apoptotic regulatory pathway and their relationship with a progression of breast carcinoma. Materials and Methods. We compared expression of genes related to apoptosis (DR6 and Gpm6B in the blood of patients suffering from stage I of breast cancer in different grades (I–IV, with healthy controls. After isolation of mRNA, transcription of mRNA into the cDNA was performed. The quantification of gene expression changes in DR6 and Gpm6B was detected by RT-PCR method. Analysis at the protein level was performed by the Western blot.Results. In statistical analysis of Dr6 mRNA level changes we detected significant increase starting in Grading 1 (G1 and reached maximal level in G3.This expression on mRNA levels was similar to protein levels, which copy rising tendency with maximal value in G3. The results of Gpm6B were significantly lower.Conclusion. This result showed that antiapoptotic signalling during neovascularization is increased significantly. It would be advisable in the future to study the influence of cytostatic treatment on the expression of genes related to apoptotic pathways and their relationship with progression of breast cancer tumours.

Performance-assessment progress for the Rozan low-level waste disposal facility

Energy Technology Data Exchange (ETDEWEB)

Smietanski, L.; Mitrega, J.; Frankowski, Z. [Polish Geological Institute, Warsaw (Poland)] [and others

1995-12-31

The paper presents a condensed progress report on the performance assessment of Poland`s low-level waste disposal facility which is operating since 1961. The Rozan repository is of near-surface type with facilities which are the concrete fortifications built about 1910. Site characterization activities supplied information on regional geology, geohydrology, climatic and hydrologic conditions and terrain surface evolution due to geodynamic processes. Field surveys enabled to decode lithological, hydrogeological and geochemical site specific conditions. From the laboratory tests the data on groundwater chemistry and soil geochemical and hydraulic characteristics were obtained. The site geohydrologic main vulnerable element is the upmost directly endangered unconfined aquifer which is perched in relation to the region-wide hydraulic system. Heterogeneity of this system reflects in a wide range of hydraulic conductivity and thickness variations. It strongly affects velocity and flow directions. The chemistry of groundwater is unstable due to large sensitivity to external impacts. Modeling of the migration of the critical long-lived radionuclides Tc-99, U-238 and Pu-239 showed that the nearly 20 m thick unsaturated zone plays crucial role as an effective protective barrier. These radionuclides constitute minor part of the total inventory. Modeling of the development of the H-3 plume pointed out the role the macrodispersion plays in the unsaturated zone beneath the repository.

Circulating Endothelial Microparticles: A Key Hallmark of Atherosclerosis Progression

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Keshav Raj Paudel

2016-01-01

Full Text Available The levels of circulating microparticles (MPs are raised in various cardiovascular diseases. Their increased level in plasma is regarded as a biomarker of alteration in vascular function. The prominent MPs present in blood are endothelial microparticles (EMPs described as complex submicron (0.1 to 1.0 μm vesicles like structure, released in response to endothelium cell activation or apoptosis. EMPs possess both physiological and pathological effects and may promote oxidative stress and vascular inflammation. EMPs release is triggered by inducer like angiotensin II, lipopolysaccharide, and hydrogen peroxide leading to the progression of atherosclerosis. However, there are multiple physiological pathways for EMPs generation like NADPH oxidase derived endothelial ROS formation, Rho kinase pathway, and mitogen-activated protein kinases. Endothelial dysfunction is a key initiating event in atherosclerotic plaque formation. Atheroemboli, resulting from ruptured carotid plaques, is a major cause of stroke. Increasing evidence suggests that EMPs play an important role in the pathogenesis of cardiovascular disease, acting as a marker of damage, either exacerbating disease progression or triggering a repair response. In this regard, it has been suggested that EMPs have the potential to act as biomarkers of disease status. This review aims to provide updated information of EMPs in relation to atherosclerosis pathogenesis.

SUMO-modified insulin-like growth factor 1 receptor (IGF-1R) increases cell cycle progression and cell proliferation.

Science.gov (United States)

Lin, Yingbo; Liu, Hongyu; Waraky, Ahmed; Haglund, Felix; Agarwal, Prasoon; Jernberg-Wiklund, Helena; Warsito, Dudi; Larsson, Olle

2017-10-01

Increasing number of studies have shown nuclear localization of the insulin-like growth factor 1 receptor (nIGF-1R) in tumor cells and its links to adverse clinical outcome in various cancers. Any obvious cell physiological roles of nIGF-1R have, however, still not been disclosed. Previously, we reported that IGF-1R translocates to cell nucleus and modulates gene expression by binding to enhancers, provided that the receptor is SUMOylated. In this study, we constructed stable transfectants of wild type IGF1R (WT) and triple-SUMO-site-mutated IGF1R (TSM) using igf1r knockout mouse fibroblasts (R-). Cell clones (R-WT and R-TSM) expressing equal amounts of IGF-1R were selected for experiments. Phosphorylation of IGF-1R, Akt, and Erk upon IGF-1 stimulation was equal in R-WT and R-TSM. WT was confirmed to enter nuclei. TSM did also undergo nuclear translocation, although to a lesser extent. This may be explained by that TSM heterodimerizes with insulin receptor, which is known to translocate to cell nuclei. R-WT proliferated substantially faster than R-TSM, which did not differ significantly from the empty vector control. Upon IGF-1 stimulation G1-S-phase progression of R-WT increased from 12 to 38%, compared to 13 to 20% of R-TSM. The G1-S progression of R-WT correlated with increased expression of cyclin D1, A, and CDK2, as well as downregulation of p27. This suggests that SUMO-IGF-1R affects upstream mechanisms that control and coordinate expression of cell cycle regulators. Further studies to identify such SUMO-IGF-1R dependent mechanisms seem important. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc.

Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

DEFF Research Database (Denmark)

Romme Christensen, Jeppe; Börnsen, Lars; Ratzer, Rikke

2013-01-01

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...... 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...

Systems-level organization of non-alcoholic fatty liver disease progression network

Directory of Open Access Journals (Sweden)

K. Shubham

2017-10-01

Full Text Available Non-Alcoholic Fatty Liver Disease (NAFLD is a hepatic metabolic disorder that is commonly associated with sedentary lifestyle and high fat diets. NAFLD is prevalent in individuals with obesity, insulin resistance and Type 2 Diabetes (T2D. The clinical spectrum of NAFLD ranges from simple steatosis to Non-Alcoholic Steatohepatitis (NASH with fibrosis, which can progress to cirrhosis and hepatocellular carcinoma.The pathogenesis of NAFLD is complex, involving crosstalk between multiple organs, cell-types, and environmental and genetic factors. Dysfunction of White Adipose Tissue (WAT plays a central role in the development of NAFLD and other metabolic disorders. WAT is an active endocrine organ that regulates whole-body energy homeostasis, lipid metabolism, insulin sensitivity and food intake by secreting biologically active molecules (lipokines, adipokines and cytokines. WAT dynamically reacts to nutrient excess or deprivation by remodelling the number (called hyperplasia and/or size (called hypertrophy of adipocytes to store fat or supply nutrients to other tissues by lipolysis, respectively. Adipose tissue remodelling is also accompanied by changes in the composition or function of stromal vascular cells and ECM. The major objective of our study was to identify and characterize the metabolic and signaling modules associated with the progression of NAFLD in the VAT. We performed Weighted Gene Co-expression Network Analysis (WGCNA to organize microarray data obtained from the VAT of patients at different stages of NAFLD into functional modules. In order to obtain insights into the metabolism and its regulation at the genome scale, a co-expression network of metabolic genes in the Human Metabolic Network (HMR2 was constructed and compared with the co-expression network constructed based on all the varying genes. We also used the prior network information on adipocyte metabolism (GEM to verify and extract reporter metabolites. Our analysis revealed

Sex Differences in the Relationship of IL-6 Signaling to Cancer Cachexia Progression

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Hetzler, Kimbell L.; Hardee, Justin P.; Puppa, Melissa J.; Narsale, Aditi A.; Sato, Shuichi; Davis, J. Mark; Carson, James A.

2015-01-01

A devastating aspect of cancer cachexia is severe loss of muscle and fat mass. Though cachexia occurs in both sexes, it is not well-defined in the female. The Apc Min/+ mouse is genetically predisposed to develop intestinal tumors; circulating IL-6 is a critical regulator of cancer cachexia in the male Apc Min/+ mouse. The purpose of this study was to examine the relationship between IL-6 signaling and cachexia progression in the female Apc Min/+ mouse. Male and female Apc Min/+ mice were examined during the initiation and progression of cachexia. Another group of females had IL-6 overexpressed between 12-14 weeks or 15-18 weeks of age to determine whether IL-6 could induce cachexia. Cachectic female Apc Min/+ mice lost body weight, muscle mass, and fat mass; increased muscle IL-6 mRNA expression was associated with these changes, but circulating IL-6 levels were not. Circulating IL-6 levels did not correlate with downstream signaling in muscle in the female. Muscle IL-6r mRNA expression and SOCS3 mRNA expression as well as muscle IL-6r protein and STAT3 phosphorylation increased with severe cachexia in both sexes. Muscle SOCS3 protein increased in cachectic females but decreased in cachectic males. IL-6 overexpression did not affect cachexia progression in female Apc Min/+ mice. Our results indicate that female Apc Min/+ mice undergo cachexia progression that is at least initially IL-6-independent. Future studies in the female will need to determine mechanisms underlying regulation of IL-6 response and cachexia induction. PMID:25555992

Myoclonic epilepsy with ragged-red fibers without increased lactate levels.

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Kimura, Shigemi; Ozasa, Shiro; Nakamura, Kyoko; Nomura, Keiko; Kosuge, Hirofumi

2009-07-01

Myoclonic epilepsy associated with ragged-red fibers is one of the mitochondrial encephalomyopathies. Pathogenic mitochondrial DNA mutations have been identified in the mitochondrial transfer RNA (tRNA)(Lys) at positions 8344 and 8356. Characteristics of myoclonic epilepsy associated with ragged-red fibers include myoclonic epilepsy, generalized epilepsy, hearing loss, exercise intolerance, lactic acidosis, and ragged-red fibers. The elevated lactate level is one of the most important symptoms needed to make a diagnosis of mitochondrial encephalomyopathy. In the present case, however, myoclonic epilepsy was associated with ragged-red fibers but without increased lactate levels. Therefore, myoclonic epilepsy associated with ragged-red fibers should be suspected in a patient who has myoclonic epilepsy that is difficult to control with antiepileptic medications and who has other symptoms of mitochondrial disease, such as mental retardation, even if the patient's lactate level is normal.

Serum Survivin Levels and Outcome of Chemotherapy in Patients with Malignant Mesothelioma

Directory of Open Access Journals (Sweden)

Katja Goričar

2015-01-01

Full Text Available Background. Survivin is an inhibitor of apoptosis protein involved in the regulation of cell proliferation that could be used as a marker for cancer diagnosis or prognosis. Our aim was to evaluate whether serum survivin levels influence the outcome of cisplatin-based chemotherapy in patients with malignant mesothelioma (MM. Methods. Serum survivin levels were determined using human survivin enzyme-linked immunosorbent assay in 78 MM patients before chemotherapy, after chemotherapy, and at disease progression. The influence on tumor response and survival was evaluated using nonparametric tests and Cox regression. Results. A median serum survivin level at diagnosis was 4.1 (0–217.5 pg/mL. Patients with a progressive disease had significantly higher survivin levels before chemotherapy (p = 0.041. A median serum survivin level after chemotherapy was 73.1 (0–346.2 pg/mL. If survivin levels increased after chemotherapy, patients had, conversely, better response (p = 0.001, OR = 5.40, 95% CI = 1.98–14.72. Unexpectedly, patients with increased survivin levels after chemotherapy also had longer progression-free (p < 0.001, HR = 0.33, 95% CI = 0.20–0.57 and overall survival (p = 0.001, HR = 0.29, 95% CI = 0.14–0.58. Conclusions. These results suggest that serum survivin levels before and during chemotherapy could serve as a biomarker predicting MM treatment response.

A Progressive Approach to Content Generation

DEFF Research Database (Denmark)

Shaker, Mohammad; Shaker, Noor; Togelius, Julian

2015-01-01

and the associated level design. The framework first generates timelines following the search-based paradigm. Timelines are game-independent and they reflect the rhythmic feel of the levels. A progressive, constructive-based approach is then implemented to evaluate timelines by mapping them into level designs...

Correlation between Gene Expression and Osteoarthritis Progression in Human.

Science.gov (United States)

Zhong, Leilei; Huang, Xiaobin; Karperien, Marcel; Post, Janine N

2016-07-14

Osteoarthritis (OA) is a multifactorial disease characterized by gradual degradation of joint cartilage. This study aimed to quantify major pathogenetic factors during OA progression in human cartilage. Cartilage specimens were isolated from OA patients and scored 0-5 according to the Osteoarthritis Research Society International (OARSI) guidelines. Protein and gene expressions were measured by immunohistochemistry and qPCR, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to detect apoptotic cells. Cartilage degeneration in OA is a gradual progress accompanied with gradual loss of collagen type II and a gradual decrease in mRNA expression of SOX9, ACAN and COL2A1. Expression of WNT antagonists DKK1 and FRZB was lost, while hypertrophic markers (RUNX2, COL10A1 and IHH) increased during OA progression. Moreover, DKK1 and FRZB negatively correlated with OA grading, while RUNX2 and IHH showed a significantly positive correlation with OA grading. The number of apoptotic cells was increased with the severity of OA. Taken together, our results suggested that genetic profiling of the gene expression could be used as markers for staging OA at the molecular level. This helps to understand the molecular pathology of OA and may lead to the development of therapies based on OA stage.

Progressive cerebral atrophy in neuromyelitis optica.

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Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

2015-12-01

We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients. © The Author(s), 2015.

Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.

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Papaspyridonos, Marianna; Matei, Irina; Huang, Yujie; do Rosario Andre, Maria; Brazier-Mitouart, Helene; Waite, Janelle C; Chan, April S; Kalter, Julie; Ramos, Ilyssa; Wu, Qi; Williams, Caitlin; Wolchok, Jedd D; Chapman, Paul B; Peinado, Hector; Anandasabapathy, Niroshana; Ocean, Allyson J; Kaplan, Rosandra N; Greenfield, Jeffrey P; Bromberg, Jacqueline; Skokos, Dimitris; Lyden, David

2015-04-29

A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.

Progress in the High Level Trigger Integration

CERN Multimedia

Cristobal Padilla

2007-01-01

During the week from March 19th to March 23rd, the DAQ/HLT group performed another of its technical runs. On this occasion the focus was on integrating the Level 2 and Event Filter triggers, with a much fuller integration of HLT components than had been done previously. For the first time this included complete trigger slices, with a menu to run the selection algorithms for muons, electrons, jets and taus at the Level-2 and Event Filter levels. This Technical run again used the "Pre-Series" system (a vertical slice prototype of the DAQ/HLT system, see the ATLAS e-news January issue for details). Simulated events, provided by our colleagues working in the streaming tests, were pre-loaded into the ROS (Read Out System) nodes. These are the PC's where the data from the detector is stored after coming out of the front-end electronics, the "first part of the TDAQ system" and the interface to the detectors. These events used a realistic beam interaction mixture and had been subjected to a Level-1 selection. The...

Progressive taxation as a tool for providing the budget system stability

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Margarita A. Vakhtina

2016-01-01

Full Text Available Objective to consider the alternative additional sources of income of the state budget in the framework of the action plan of the Russian government to provide socioeconomic stability of the country in 2016. Methods comparative and dynamic analysis classification and typology description and measurements including using the tools of institutional Economics the data were interpreted using tables. Results it is shown that due to the lack of financial resources the government has to make unpopular decisions that reduce the level of social support of the population for the near future. The adopted laws stipulating the principles of address character and needs when providing regional measures of social support increase the risks of poverty and inequality. The analysis has been made of the ranking position of Russia and member countries of the Organization for Economic Cooperation and Development in terms of GDP per capita human development index and quality of life index. The article grounds the need for institutional change to facilitate transition to progressive taxation and redistribution of the tax burden from the poor and middle classes to the super rich. The flat personal income tax rate has not led to the desired results of growing tax revenues in the budget. Russia is still among the top ten states with the largest tax evasion losses. The weak redistributive mechanisms including a flat scale of personal income tax regressive social security contributions and low property taxes lead to stagnation inequality underfunding of education and health. Scientific novelty the article proves the conclusion about need of institutional transformations associated with changing the current tax policy priorities. The transition to a progressive scale of income and wealth taxation promotes the transfer of tax burden from the middle and poor to the rich. These measures can provide a double economic effect. On the one hand the principle of effective taxation

Increased fibulin-1 plasma levels in polycystic ovary syndrome (PCOS) patients: possible contribution to the link between PCOS and cardiovascular risk.

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Scarinci, E; Tropea, A; Russo, G; Notaristefano, G; Messana, C; Alesiani, O; Fabozzi, S M; Lanzone, A; Apa, R

2018-04-21

To investigate a possible relation between fibulin-1 plasma levels and PCOS. ELISA quantitative determination of human fibulin-1. 50 women with PCOS and 40 control patients who attended the Unit of Human Reproductive Pathophysiology, Università Cattolica del Sacro Cuore, Rome, were enrolled. Ultrasonographic pelvic examinations, hormonal profile assays, oral tolerance test OGTT, lipid profile and ELISA quantitative determination of human fibulin-1 were performed. Fibulin-1 levels were found to be statistically significantly higher in PCOS patients than in matched control women. No statistically significant positive correlation was found between fibulin-1 and AUCi, HOMA-IR, total cholesterol, LDL, AMH, androstenedione and FAI, whereas a statistically significant positive correlation was found between fibulin-1 and 17OHP (p = 0.016) in the PCOS group. However, multivariable linear regression analysis showed that 17 OH P did not independently predict fibulin-1 levels (p = 0.089). Our data could contribute to explain the hypothesized increased cardiovascular risk and vascular damage in patients with PCOS. A better understanding of the cellular and molecular mechanisms involved in cardiometabolic disorders associated with PCOS is mandatory to identify new therapeutic strategies to eventually prevent the progression of cardiovascular diseases in these patients.

Topical Loperamide-Encapsulated Liposomal Gel Increases the Severity of Inflammation and Accelerates Disease Progression in the Adjuvant-Induced Model of Experimental Rheumatoid Arthritis

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Susan Hua

2017-08-01

Full Text Available This study evaluates the prophylactic effect of the peripherally-selective mu-opioid receptor agonist, loperamide, administered topically in a liposomal gel formulation on pain, inflammation, and disease progression in the adjuvant-induced model of experimental rheumatoid arthritis in female Lewis rats. In a randomized, blinded and controlled animal trial, AIA rats were divided into six groups consisting of eleven rats per group based on the following treatments: loperamide liposomal gel, free loperamide gel, empty liposomal gel, diclofenac gel (Voltaren®, no treatment, and naive control. Topical formulations were applied daily for a maximum of 17 days—starting from day 0 at the same time as immunization. The time course of the effect of the treatments on antinocieption and inflammation was assessed using a paw pressure analgesiometer and plethysmometer, respectively. Arthritis progression was scored daily using an established scoring protocol. At the end of the study, hind paws were processed for histological analysis. Administration of loperamide liposomal gel daily across the duration of the study produced significant peripheral antinociception as expected; however, increased the severity of inflammation and accelerated arthritis progression. This was indicated by an increase in paw volume, behavioral and observational scoring, and histological analysis compared to the control groups. In particular, histology results showed an increase in pannus formation and synovial inflammation, as well as an upregulation of markers of inflammation and angiogenesis. These findings may have implications for the use of loperamide and other opioids in arthritis and potentially other chronic inflammatory diseases.

Countdown to 2015 country case studies: what have we learned about processes and progress towards MDGs 4 and 5?

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Moucheraud, Corrina; Owen, Helen; Singh, Neha S; Ng, Courtney Kuonin; Requejo, Jennifer; Lawn, Joy E; Berman, Peter

2016-09-12

Countdown to 2015 was a multi-institution consortium tracking progress towards Millennium Development Goals (MDGs) 4 and 5. Case studies to explore factors contributing to progress (or lack of progress) in reproductive, maternal, newborn and child health (RMNCH) were undertaken in: Afghanistan, Bangladesh, China, Ethiopia, Kenya, Malawi, Niger, Pakistan, Peru, and Tanzania. This paper aims to identify cross-cutting themes on how and why these countries achieved or did not achieve MDG progress. Applying a standard evaluation framework, analyses of impact, coverage and equity were undertaken, including a mixed methods analysis of how these were influenced by national context and coverage determinants (including health systems, policies and financing). The majority (7/10) of case study countries met MDG-4 with over two-thirds reduction in child mortality, but none met MDG-5a for 75 % reduction in maternal mortality, although six countries achieved >75 % of this target. None achieved MDG-5b regarding reproductive health. Rates of reduction in neonatal mortality were half or less that for post-neonatal child mortality. Coverage increased most for interventions administered at lower levels of the health system (e.g., immunisation, insecticide treated nets), and these experienced substantial political and financial support. These interventions were associated with ~30-40 % of child lives saved in 2012 compared to 2000, in Ethiopia, Malawi, Peru and Tanzania. Intrapartum care for mothers and newborns -- which require higher-level health workers, more infrastructure, and increased community engagement -- showed variable increases in coverage, and persistent equity gaps. Countries have explored different approaches to address these problems, including shifting interventions to the community setting and tasks to lower-level health workers. These Countdown case studies underline the importance of consistent national investment and global attention for achieving improvements

Progressive mobility program and technology to increase the level of physical activity and its benefits in respiratory, muscular system, and functionality of ICU patients: study protocol for a randomized controlled trial.

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Schujmann, Debora Stripari; Lunardi, Adriana Claudia; Fu, Carolina

2018-05-10

Enhanced mobility in the Intensive Care Unit (ICU) could minimize the negative effects of critical illness, such as declines in cognitive, muscular, respiratory, and functional capacity. We aim to compare the functional status at ICU discharge of patients who underwent a progressive mobilization protocol versus patients who received conventional physiotherapy. We also examine the level of physical activity in the ICU, the degree of pulmonary and muscle function, and the length of stay to analyze correlations between these variables. This is a protocol for a randomized controlled trial with blind evaluation. Ninety-six ICU patients will be recruited from a single center and randomly assigned to a control group or an intervention group. To determine the level of protocol activity the patient will receive, the patients' ability to participate actively and their muscle strength will be considered. The protocol consists of five phases, ranging from passive therapies to walking and climbing stairs. The primary outcome will be the functional status at ICU discharge, measured with the Barthel Index and the ICU Mobility Scale (IMS). Measured secondary outcomes will include the level of physical activity, maximal inspiratory and expiratory pressures, forced expiratory volume in 1 second, maximum voluntary ventilation, handgrip strength, surface electromyography of the lower limb muscles, and results of the Timed Up and Go and 2-Minute Walk tests. Evaluations will be made within 2 days of ICU discharge except for the level of activity, which will be evaluated daily. Physiological variables and activity level will be analyzed by chi-square and t tests, according to the intention-to-treat paradigm. Mobility and exercise in the ICU should be undertaken with intensity, quantity, duration, and frequency adjusted according to the patients' status. The results of this study may contribute to new knowledge of early mobility in the ICU, activity level, and varying benefits in critical

Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.

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Chen, Zhe; Zhang, Yu-Xue; Fu, Dong-Wei; Gao, Qing-Feng; Ge, Feng-Xia; Liu, Wei-Hua

2016-08-01

Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p brucellosis (r = 0.707, p brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.

PSA Level 2:Scope And Method Of PSA Level 2 For Nuclear Power Plant

International Nuclear Information System (INIS)

Widodo, Surip; Antariksawan, Anhar R.

2001-01-01

A study of scope and method of PSA Level 2 had been conducted. The background of the study is the need to gain the capability to well perform PSA Level 2 for nuclear facilities. This study is a literature survey. The scope of PSA Level 2 consists of generating plant damage states, accident progression analysis, and grouping source terms. Concerning accident progression analysis, several methods are used, among others event tree method, named accident progression event tree (APET) or containment event tree (CET), and fault tree method. The end result of PSA Level 2 is release end states which is grouped into release bins. The results will be used for PSA Level 3

Experimental study of changes of skin blister fluid NPY, IL-12, sICAM-1 and GM-CSF levels in patients with vitiligo in progressive stage

International Nuclear Information System (INIS)

Bi Mingye; Huang Haifen

2011-01-01

Objective: To explore the significance of changes of skin blister fluid NPY, IL-12, sICAM-1 and GM-CSF levels in patients with vitiligo in progressive stage. Methods: 80 patients with vitiligo in progressive stage were divided into two groups (vulgaris vitiligo groups : n=54, segmental vitiligo groups : n=26) Their blister fluid levels of NPY and GM-CSF were determined by radioimmunoassay(RIA), and IL-12 and sICAM-1 were determined by enzyme immunoassay. Results: The levels of skin blister fluid NPY were definitely higher in vitiliginous skin than those in non-vitiliginous patches in segmental vitiligo groups (P 0.05). The levels of skin blister fluid IL-12, sICAM-1 and GM-CSF were all obviously higher in vitiliginous skin than that in non-vitiliginous patches in vulgaris vitiligo groups (P 0.05). Conclusion: The changes of skin blister fluid NPY, IL-12, sICAM-1 and GM-CSF levels in vitiliginous skin may be closely related to development of difference type vitiligo patients with vitiligo, determination of 4 indexes might be helpful for studying the pathogenesis and clinical diagnosis of vitiligo. (authors)

Plasma insulin levels are increased by sertraline in rats under oral glucose overload

Directory of Open Access Journals (Sweden)

Gomez R.

2001-01-01

Full Text Available Recognition and control of depression symptoms are important to increase patient compliance with treatment and to improve the quality of life of diabetic patients. Clinical studies indicate that selective serotonin reuptake inhibitors (SSRI are better antidepressants for diabetic patients than other drugs. However, preclinical trials have demonstrated that not all SSRI reduce plasma glucose levels. In fact, fluoxetine increases and sertraline decreases glycemia in diabetic and non-diabetic rats. In the present study we evaluated plasma insulin levels during fasting and after glucose overload after treatment with sertraline. Adult male Wistar rats were fasted and treated with saline or 30 mg/kg sertraline and submitted or not to glucose overload (N = 10. Blood was collected and plasma insulin was measured. The mean insulin levels were: fasting group: 25.9 ± 3.86, sertraline + fasting group: 31.10 ± 2.48, overload group: 34.1 ± 3.40, and overload + sertraline group: 43.73 ± 5.14 µU/ml. Insulinemia was significantly increased in the overload + sertraline group. There were no differences between the other groups. No difference in glucose/insulin ratios could be detected between groups. The overload + sertraline group was the only one in which a significant number of individuals exceeded the upper confidence limit of insulin levels. This study demonstrates that sertraline increases glucose-stimulated insulin secretion without any change in peripheral insulin sensitivity.

Blood parameters in growing pigs fed increasing levels of bacterial protein meal

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Tauson Anne-Helene

2007-11-01

Full Text Available Abstract The experiment investigated the effects of increasing dietary levels of bacterial protein meal (BPM on various blood parameters reflecting protein and fat metabolism, liver function, and purine base metabolism in growing pigs. Sixteen barrows were allocated to four different experimental diets. The control diet was based on soybean meal. In the other three diets soybean meal was replaced with increasing levels of BPM, approximately 17%, 35%, and 50% of the nitrogen being derived from BPM. Blood samples from the jugular vein were taken when the body weights of the pigs were approximately 10 kg, 21 kg, 45 kg, and 77 kg. The blood parameters reflecting fat metabolism and liver function were not affected by diet. Both the plasma albumin and uric acid concentrations tended to decrease (P = 0.07 and 0.01, respectively with increasing dietary BPM content, whereas the plasma glucose concentration tended to increase (P = 0.07 with increasing dietary BPM content. It was concluded that up to 50% of the nitrogen could be derived from BPM without affecting metabolic function, as reflected in the measured blood parameters.

Association of increased triglyceride levels in metabolic syndrome with coronary artery disease

International Nuclear Information System (INIS)

Helvaci, M.R.; Kaya, H.; Gundogdu, M.

2010-01-01

Objective: We tried to understand significance of increased triglyceride (TG) values in metabolic syndrome and coronary artery disease (CAD). Methodology: Check up cases with a TG value lower than 60 mg/dL were collected into the first, between 60 and 99 mg/dL into the second, between 100 and 149 mg/dL into the third, between 150 and 199 into the fourth, and 200 mg/dL and greater into the fifth groups. Results: Study included 478 cases. Values of the mean age, weight, body mass index, TG, and low density lipoprotein cholesterol (LDL-C) and prevalence of smoking, white coat hypertension (WCH), hypertension (HT), type 2 diabetes mellitus (DM), and CAD increased gradually and significantly nearly in all steps from the first towards the fifth groups. Conclusion: Metabolic syndrome may be a progression step between complete physical health and irreversible end points, such as obesity, type 2 DM, HT, CAD, and stroke. Hypertriglyceridemia and White Coat Hypertension (WCH) may be the most significant reversible parameters of the syndrome, and it is better to have the lowest TG value as much as possible. The most significant increase was seen after the value of 100 mg/dL. The overweight, smoking, hypertriglyceridemia, hyperbetalipoproteinemia, and WCH may only be one of hundreds of parameters of the syndrome. Therefore, it is advisable that underlying etiologies rather than reversible parameters of the syndrome should be targeted for treatment. For example, increased TG and LDL-C values, and prevalence of WCH by aging may be secondary to decreased physical and mental stresses in elderly. (author)

MicroRNA-124 slows down the progression of Huntington′s disease by promoting neurogenesis in the striatum

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Tian Liu

2015-01-01

Full Text Available MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington′s disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington′s disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Huntington′s disease transgenic mouse in the rotarod test. 5-Bromo-2′-deoxyuridine (BrdU staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was decreased. These findings suggest that microRNA-124 slows down the progression of Huntington′s disease possibly through its important role in neuronal differentiation and survival.

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

Science.gov (United States)

Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

2017-06-01

Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.

Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis

Energy Technology Data Exchange (ETDEWEB)

Cunha, Elizabeth S.; Kawahara, Rebeca [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Kadowaki, Marina K. [Universidade Estadual do Oeste do Parana, Cascavel, PR (Brazil); Amstalden, Hudson G.; Noleto, Guilhermina R.; Cadena, Silvia Maria S.C.; Winnischofer, Sheila M.B. [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Martinez, Glaucia R., E-mail: grmartinez@ufpr.br [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil)

2012-09-10

Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT-qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. -- Highlights: Black-Right-Pointing-Pointer Melanogenesis stimulation by L-tyrosine+NH{sub 4}Cl in B16-F10 melanoma cells increases ROS levels. Black-Right-Pointing-Pointer Melanogenesis inhibits cell proliferation, and induced cell cycle arrest in the G1 phase. Black-Right-Pointing-Pointer Proteomic analysis showed alterations in proteins of the cell cycle and glucose metabolism. Black-Right-Pointing-Pointer RT-qPCR analysis confirmed alterations of metabolic targets after melanogenesis stimulation.

Blood parameters in growing pigs fed increasing levels of bacterial protein meal

DEFF Research Database (Denmark)

Hellwing, Anne Louise Frydendahl; Tauson, Anne-Helene; Skrede, Anders

2007-01-01

The experiment investigated the effects of increasing dietary levels of bacterial protein meal (BPM) on various blood parameters reflecting protein and fat metabolism, liver function, and purine base metabolism in growing pigs. Sixteen barrows were allocated to four different experimental diets....... The control diet was based on soybean meal. In the other three diets soybean meal was replaced with increasing levels of BPM, approximately 17%, 35%, and 50% of the nitrogen being derived from BPM. Blood samples from the jugular vein were taken when the body weights of the pigs were approximately 10 kg, 21 kg......, 45 kg, and 77 kg. The blood parameters reflecting fat metabolism and liver funtion were not affected by diet. Both the plasma albumin and uric acid concentrations tended to decrease (P = 0.07 and 0.01, respectively) with increasing dietary BPM content, whereas the plasma glucose concentration tended...

A mouse model of familial ALS has increased CNS levels of endogenous ubiquinol9/10 and does not benefit from exogenous administration of ubiquinol10.

Directory of Open Access Journals (Sweden)

Jacopo Lucchetti

Full Text Available Oxidative stress and mitochondrial impairment are the main pathogenic mechanisms of Amyotrophic Lateral Sclerosis (ALS, a severe neurodegenerative disease still lacking of effective therapy. Recently, the coenzyme-Q (CoQ complex, a key component of mitochondrial function and redox-state modulator, has raised interest for ALS treatment. However, while the oxidized form ubiquinone10 was ineffective in ALS patients and modestly effective in mouse models of ALS, no evidence was reported on the effect of the reduced form ubiquinol10, which has better bioavailability and antioxidant properties. In this study we compared the effects of ubiquinone10 and a new stabilized formulation of ubiquinol10 on the disease course of SOD1(G93A transgenic mice, an experimental model of fALS. Chronic treatments (800 mg/kg/day orally started from the onset of disease until death, to mimic the clinical trials that only include patients with definite ALS symptoms. Although the plasma levels of CoQ10 were significantly increased by both treatments (from <0.20 to 3.0-3.4 µg/mL, no effect was found on the disease progression and survival of SOD1(G93A mice. The levels of CoQ10 in the brain and spinal cord of ubiquinone10- or ubiquinol10-treated mice were only slightly higher (≤10% than the endogenous levels in vehicle-treated mice, indicating poor CNS availability after oral dosing and possibly explaining the lack of pharmacological effects. To further examine this issue, we measured the oxidized and reduced forms of CoQ9/10 in the plasma, brain and spinal cord of symptomatic SOD1(G93A mice, in comparison with age-matched SOD1(WT. Levels of ubiquinol9/10, but not ubiquinone9/10, were significantly higher in the CNS, but not in plasma, of SOD1(G93A mice, suggesting that CoQ redox system might participate in the mechanisms trying to counteract the pathology progression. Therefore, the very low increases of CoQ10 induced by oral treatments in CNS might be not sufficient to

Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.

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Masato Furuhashi

Full Text Available Fatty acid-binding protein 4 (FABP4/A-FABP/aP2 is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP. Sodium-glucose cotransporter 2 (SGLT2 inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level.Canagliflozin (100 mg/day was administered to type 2 diabetic patients (n = 39 for 12 weeks. Serum FABP4 level was measured before and after treatment.At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008, though elevation of FABP4 level after treatment was observed in 26 (66.7% out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044, HbA1c (r = 0.329, P = 0.044 and noradrenaline (r = 0.329, P = 0.041 but was not significantly correlated with change in adiposity or other variables.Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2.UMIN-CTR Clinical Trial UMIN000018151.

Slowing Menthol's Progress: Differential Impact of a Tobacco Tax Increase on Cigarette Sales.

Science.gov (United States)

Amato, Michael S; D'Silva, Joanne; Boyle, Raymond G

2016-05-01

The proportion of smokers who use menthol cigarettes has increased nationally since 2004, while use of non-menthol cigarettes is declining, suggesting that menthol may be undermining the effectiveness of population level tobacco control efforts. In 2013 Minnesota passed a $1.75 cigarette tax increase. We investigated whether sales of menthol and non-menthol cigarettes were differentially affected by the price increase. Cigarette sales data from convenience stores in the Minneapolis, Minnesota, metro area from January 2012, through May 2015, were obtained. Proportion of sales accounted for by menthol cigarettes was analyzed with segmented regression. Before the price increase, menthol cigarettes gained 2.21% (1.17, 3.12) of market share annually. Following the price increase, the trend slowed to 0.26% (-0.78, 1.56) annually. The slope before the price increase was significantly positive; the slope following the price increase did not significantly differ from zero. Sales of menthol cigarettes declined less rapidly than non-menthol cigarettes before the price increase. Sales of menthol and non-menthol cigarettes declined at more comparable rates after the price increase. Increasing the price of tobacco may help ensure declines in consumption are more evenly distributed across menthol and non-menthol cigarettes. Using sales data, we found that a trend of increasing market share for menthol cigarettes was significantly reduced by a $1.75 cigarette price increase. These results suggest that cigarette price increases, a core tobacco control policy, may have a greater effect on menthol smokers than non-menthol smokers. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Increased Sclerostin Levels after Further Ablation of Remnant Estrogen by Aromatase Inhibitors

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Wonjin Kim

2015-03-01

Full Text Available BackgroundSclerostin is a secreted Wnt inhibitor produced almost exclusively by osteocytes, which inhibits bone formation. Aromatase inhibitors (AIs, which reduce the conversion of steroids to estrogen, are used to treat endocrine-responsive breast cancer. As AIs lower estrogen levels, they increase bone turnover and lower bone mass. We analyzed changes in serum sclerostin levels in Korean women with breast cancer who were treated with an AI.MethodsWe included postmenopausal women with endocrine-responsive breast cancer (n=90; mean age, 57.7 years treated with an AI, and compared them to healthy premenopausal women (n=36; mean age, 28.0 years. The subjects were randomly assigned to take either 5 mg alendronate with 0.5 µg calcitriol (n=46, or placebo (n=44 for 6 months.ResultsPostmenopausal women with breast cancer had significantly higher sclerostin levels compared to those in premenopausal women (27.8±13.6 pmol/L vs. 23.1±4.8 pmol/L, P0.05.ConclusionSerum sclerostin levels increased with absolute deficiency of residual estrogens in postmenopausal women with endocrine-responsive breast cancer who underwent AI therapy with concurrent bone loss.

Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

International Nuclear Information System (INIS)

Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

2013-01-01

Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

Energy Technology Data Exchange (ETDEWEB)

Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

2013-04-15

Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

Transgenic cells with increased plastoquinone levels and methods of use

Energy Technology Data Exchange (ETDEWEB)

Sayre, Richard T.; Subramanian, Sowmya; Cahoon, Edgar

2016-12-27

Disclosed herein are transgenic cells expressing a heterologous nucleic acid encoding a prephenate dehydrogenase (PDH) protein, a heterologous nucleic acid encoding a homogentisate solanesyl transferase (HST) protein, a heterologous nucleic acid encoding a deoxyxylulose phosphate synthase (DXS) protein, or a combination of two or more thereof. In particular examples, the disclosed transgenic cells have increased plastoquinone levels. Also disclosed are methods of increasing cell growth rates or production of biomass by cultivating transgenic cells expressing a heterologous nucleic acid encoding a PDH protein, a heterologous nucleic acid encoding an HST protein, a heterologous nucleic acid encoding a DXS protein, or a combination of two or more thereof under conditions sufficient to produce cell growth or biomass.

Multiscale assessment of progress of electrification in Indonesia based on brightness level derived from nighttime satellite imagery.

Science.gov (United States)

Ramdani, Fatwa; Setiani, Putri

2017-06-01

Availability of electricity can be used as an indicator to proximate parameters related to human well-being. Overall, the electrification process in Indonesia has been accelerating in the past two decades. Unfortunately, monitoring the country's progress on its effort to provide wider access to electricity poses challenges due to inconsistency of data provided by each national bureau, and limited availability of information. This study attempts to provide a reliable measure by employing nighttime satellite imagery to observe and to map the progress of electrification within a duration of 20 years, from 1993 to 2013. Brightness of 67,021 settlement-size points in 1993, 2003, and 2013 was assessed using data from DMSP/OLS instruments to study the electrification progress in the three service regions (Sumatera, Java-Bali, and East Indonesia) of the country's public electricity company, PLN. Observation of all service areas shows that the increase in brightness, which correspond with higher electricity development and consumption, has positive correlation with both population density (R 2  = 0.70) and urban change (R 2  = 0.79). Moreover, urban change has a stronger correlation with brightness, which is probably due to the high energy consumption in urban area per capita. This study also found that the brightness in Java-Bali region is very dominant, while the brightness in other areas has been lagging during the period of analysis. The slow development of electricity infrastructure, particularly in major parts of East Indonesia region, affects the low economic growth in some areas and formed vicious cycle.

Correlation between Gene Expression and Osteoarthritis Progression in Human

Directory of Open Access Journals (Sweden)

Leilei Zhong

2016-07-01

Full Text Available Osteoarthritis (OA is a multifactorial disease characterized by gradual degradation of joint cartilage. This study aimed to quantify major pathogenetic factors during OA progression in human cartilage. Cartilage specimens were isolated from OA patients and scored 0–5 according to the Osteoarthritis Research Society International (OARSI guidelines. Protein and gene expressions were measured by immunohistochemistry and qPCR, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assays were used to detect apoptotic cells. Cartilage degeneration in OA is a gradual progress accompanied with gradual loss of collagen type II and a gradual decrease in mRNA expression of SOX9, ACAN and COL2A1. Expression of WNT antagonists DKK1 and FRZB was lost, while hypertrophic markers (RUNX2, COL10A1 and IHH increased during OA progression. Moreover, DKK1 and FRZB negatively correlated with OA grading, while RUNX2 and IHH showed a significantly positive correlation with OA grading. The number of apoptotic cells was increased with the severity of OA. Taken together, our results suggested that genetic profiling of the gene expression could be used as markers for staging OA at the molecular level. This helps to understand the molecular pathology of OA and may lead to the development of therapies based on OA stage.

Progress in Childhood Vaccination Data in Immunization Information Systems - United States, 2013-2016.

Science.gov (United States)

Murthy, Neil; Rodgers, Loren; Pabst, Laura; Fiebelkorn, Amy Parker; Ng, Terence

2017-11-03

In 2016, 55 jurisdictions in 49 states and six cities in the United States* used immunization information systems (IISs) to collect and manage immunization data and support vaccination providers and immunization programs. To monitor progress toward achieving IIS program goals, CDC surveys jurisdictions through an annual self-administered IIS Annual Report (IISAR). Data from the 2013-2016 IISARs were analyzed to assess progress made in four priority areas: 1) data completeness, 2) bidirectional exchange of data with electronic health record systems, 3) clinical decision support for immunizations, and 4) ability to generate childhood vaccination coverage estimates. IIS participation among children aged 4 months through 5 years increased from 90% in 2013 to 94% in 2016, and 33 jurisdictions reported ≥95% of children aged 4 months through 5 years participating in their IIS in 2016. Bidirectional messaging capacity in IISs increased from 25 jurisdictions in 2013 to 37 in 2016. In 2016, nearly all jurisdictions (52 of 55) could provide automated provider-level coverage reports, and 32 jurisdictions reported that their IISs could send vaccine forecasts to providers via Health Level 7 (HL7) messaging, up from 17 in 2013. Incremental progress was made in each area since 2013, but continued effort is needed to implement these critical functionalities among all IISs. Success in these priority areas, as defined by the IIS Functional Standards (1), bolsters clinicians' and public health practitioners' ability to attain high vaccination coverage in pediatric populations, and prepares IISs to develop more advanced functionalities to support state/local immunization services. Success in these priority areas also supports the achievement of federal immunization objectives, including the use of IISs as supplemental sampling frames for vaccination coverage surveys like the National Immunization Survey (NIS)-Child, reducing data collection costs, and supporting increased precision

Content layer progressive coding of digital maps

DEFF Research Database (Denmark)

Forchhammer, Søren; Jensen, Ole Riis

2000-01-01

A new lossless context based method is presented for content progressive coding of limited bits/pixel images, such as maps, company logos, etc., common on the WWW. Progressive encoding is achieved by separating the image into content layers based on other predefined information. Information from...... already coded layers are used when coding subsequent layers. This approach is combined with efficient template based context bi-level coding, context collapsing methods for multi-level images and arithmetic coding. Relative pixel patterns are used to collapse contexts. The number of contexts are analyzed....... The new methods outperform existing coding schemes coding digital maps and in addition provide progressive coding. Compared to the state-of-the-art PWC coder, the compressed size is reduced to 60-70% on our layered test images....

Nondestructive Evaluation Program: Progress in 1986

International Nuclear Information System (INIS)

1987-07-01

The increasing cost of equipment for power generating plants and the potential increases in productivity and safety available through rapidly developing Nondestructive Evaluation (NDE) technology led EPRI to initiate a Nondestructive Evaluation Program in 1974. To date, the major focus has been on light water reactor inspection problems; however, increased application to other systems is now under way. This report presents a comprehensive review of the EPRI effort in the NDE area. Most of the report consists of contractor-supplied progress reports on each current project. An organizational plan of the program is presented in overview. In addition, organization from several viewpoints is presented, e.g., in-service inspection operators, R and D personnel, and utility representatives. The report summarizes significant progress made since the previous EPRI Special Report NP-4315-SR was issued in May 1986. Section 1 contains information about the program organization, and the sections that follow contain contractor-supplied progress reports of each current project. The progress reports are grouped by plant components - pipe, pressure vessel, steam generator and boiler tubes, and turbine. In addition, Part 6 is devoted to discussions of technology transfer

Childhood maltreatment is associated with increased body mass index and increased C-reactive protein levels in first-episode psychosis patients.

Science.gov (United States)

Hepgul, N; Pariante, C M; Dipasquale, S; DiForti, M; Taylor, H; Marques, T R; Morgan, C; Dazzan, P; Murray, R M; Mondelli, V

2012-09-01

The high incidence of the metabolic syndrome in patients with psychosis is mainly attributed to antipsychotic treatment. However, it is also possible that psychological stress plays a role, inducing a chronic inflammatory process that may predispose to the development of metabolic abnormalities. We investigated the association between childhood maltreatment and inflammatory and metabolic biomarkers in subjects with first-episode psychosis and healthy controls. Body mass index (BMI), weight and waist circumference were measured in 95 first-episode psychosis patients and 97 healthy controls. Inflammatory and metabolic markers were measured in a subsample of 28 patients and 45 controls. In all the subjects we collected information on childhood maltreatment and recent stressors. Patients with childhood maltreatment had higher BMI [25.0 (S.E.=0.6) kg/m2] and C-reactive protein (CRP) levels [1.1 (S.E.=0.6) mg/dl] when compared with healthy controls [23.4 (S.E.=0.4) kg/m2, p=0.030 and 0.2 (S.E.=0.1) mg/dl, p=0.009, respectively]. In contrast, patients without childhood maltreatment were not significantly different from healthy controls for either BMI [24.7 (S.E.=0.6) kg/m2, p=0.07] or CRP levels [0.5 (S.E.=0.2) mg/dl, p=0.25]. After controlling for the effect of BMI, the difference in CRP levels across the three groups remained significant (F 2,58=3.6, p=0.035), suggesting that the increase in inflammation was not driven by an increase in adipose tissue. Childhood maltreatment is associated with higher BMI, and increased CRP levels, in patients with a first-episode psychosis. Further studies need to confirm the mechanisms underlying the putative causal relationship between childhood maltreatment and higher BMI, and whether this is indeed mediated by increased inflammation.

Modeling Caspian Sea water level oscillations under different scenarios of increasing atmospheric carbon dioxide concentrations

Directory of Open Access Journals (Sweden)

Roshan GholamReza

2012-12-01

Full Text Available Abstract The rapid rise of Caspian Sea water level (about 2.25 meters since 1978 has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in the coastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was simulated. Variations in environmental parameters such as temperature, precipitation, evaporation, atmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for both past (1951-2006 and future (2025-2100 time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software (version 5.3. The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site has increased by ca. 0.17°C per decade under the impacts of atmospheric carbon dioxide changes (r=0.21. The Caspian Sea water level has increased by ca. +36cm per decade (r=0.82 between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64°C and precipitation will decrease by ca. 10% (182 mm over the Caspian Sea, whilst in the Volga river basin, temperatures are projected to increase by ca. 4.78°C and precipitation increase by ca. 12% (58 mm by the year 2100. Finally, statistical modeling of the Caspian Sea water levels project future water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively.

Modeling Caspian Sea water level oscillations under different scenarios of increasing atmospheric carbon dioxide concentrations.

Science.gov (United States)

Roshan, Gholamreza; Moghbel, Masumeh; Grab, Stefan

2012-12-12

The rapid rise of Caspian Sea water level (about 2.25 meters since 1978) has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in the coastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was simulated. Variations in environmental parameters such as temperature, precipitation, evaporation, atmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for both past (1951-2006) and future (2025-2100) time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software (version 5.3). The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site) has increased by ca. 0.17°C per decade under the impacts of atmospheric carbon dioxide changes (r=0.21). The Caspian Sea water level has increased by ca. +36cm per decade (r=0.82) between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64°C and precipitation will decrease by ca. 10% (182 mm) over the Caspian Sea, whilst in the Volga river basin, temperatures are projected to increase by ca. 4.78°C and precipitation increase by ca. 12% (58 mm) by the year 2100. Finally, statistical modeling of the Caspian Sea water levels project future water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively.

"A case report of Pott’s disease with unusual involvement of two separate levels of spine and delayed progressive Kyphosis "

OpenAIRE

Rahimi Movaghar V

2001-01-01

In Pott’s disease (tuberculous spondylitis), involvement of two separate levels of spine is rare. Attention to stability of spine prevents delayed progressive kyphosis. A 12-year-old girl presented with neck pain, tenderness and swelling Imaging showed Cl—C2 and T9-T10 and destruction. Mild spastic paraparesis was noticed. Preoperative diagnosis was metastasis. T9, T10 and T11 laminectomy and cervical operations were done in 2 sessions. Both pathologic examinations confirmed tuberculosis. Alt...

Elevated fasting insulin levels increase the risk of abdominal obesity in Korean men.

Science.gov (United States)

Park, Sung Keun; Oh, Chang-Mo; Jung, Taegi; Choi, Young-Jun; Chung, Ju Youn; Ryoo, Jae-Hong

2017-04-01

This study was designed to investigate whether an elevated fasting insulin level predicts abdominal obesity. A cohort study was conducted with 13,707 non-obese Korean men. They were categorized into 4 groups according to the quartile of fasting insulin level, and followed up from 2005 to 2010. Incidence rates of obesity were compared among the 4 groups during follow-up, and a Cox proportional hazards model was used to calculate hazard ratios (HRs) for abdominal obesity according to fasting insulin level. The overall incidence rate of obesity was 16.2%, but the rate increased in proportion to the fasting insulin level (quartiles 1-4: 9.8%, 12.4%, 16.9%, 25.5%, Pobesity increased proportionally to baseline fasting insulin level in an unadjusted model. However, after adjustment for covariates, including baseline waist circumference (WC), only in the quartile 4 group was the statistical significance of the association maintained [quartile 2-4; abdominal obesity: 0.89 (0.76-1.02), 1.00 (0.86-1.14) and 1.24 (1.08-1.43), P for trend obesity was highest in the group with the highest fasting insulin levels, an overall proportional relationship between fasting insulin level and incident abdominal obesity was not found. Additionally, this association was largely accounted for by baseline WC. Copyright © 2017 Elsevier B.V. All rights reserved.

Antibodies to elastin peptides in sera of Belgian Draught horses with chronic progressive lymphoedema.

Science.gov (United States)

van Brantegem, L; de Cock, H E V; Affolter, V K; Duchateau, L; Hoogewijs, M K; Govaere, J; Ferraro, G L; Ducatelle, R

2007-09-01

Chronic progressive lymphoedema (CPL) is a recently recognised disease of the lymphatic system characterised by lesions in the skin of the lower legs in several draught horse breeds, including the Belgian Draught hourse. Clinical signs slowly progress and result in severe disfigurement of the limbs. Ideally, supportive treatment should be started early in the disease process. However early diagnosis and monitoring progression of CPL is still a challenge. Elastin changes, characterised by morphological alterations as well as increased desmosine levels, in the skin of the distal limbs of horses affected with CPL are probably associated with a marked release of elastin degradation products, which elicit production of circulating anti-elastin antibodies (AEAbs) in the serum. An enzyme-linked immunosorbent assay (ELISA) for detection of serum AEAbs may document elastin breakdown. An ELISA technique was used to evaluate levels of AEAbs in sera of 97 affected Belgian Draught horses that were clinically healthy except for possible skin lesions, associated with CPL in their distal limbs. The horses were divided into 5 groups according to the severity of these skin lesions: normal horses (Group 1, n = 36), horses with mild lesions (Group 2, n = 43), horses with moderate lesions (Group 3, n = 8), horses with severe lesions (Group 4, n = 10) and, as a control, healthy Warmblood horses, unaffected by the disease (Group 5, n = 83). Horses with clinical signs of CPL had significantly higher AEAb levels compared to clinically normal Belgian Draught horses and to healthy Warmblood horses. These levels correlated with severity of lesions. CPL in draught horses is associated with an increase of serum AEAbs. Evaluation of serum levels of AEAbs by ELISA might be a useful diagnostic aid for CPL. Pathological degradation of elastic fibres, resulting in deficient support of the distal lymphatics, is proposed as a contributing factor for CPL in Belgian Draught horses.

Increased levels of circulating arginase I in overweight compared to normal weight adolescents.

Science.gov (United States)

Jung, Christian; Figulla, Hans R; Lichtenauer, Michael; Franz, Marcus; Pernow, John

2014-02-01

Overweight and the metabolic syndrome have become major problems, especially in children and adolescents. Obesity at a young age increases the risk for cardiovascular diseases and diabetes mellitus later in life. An early event in the development of cardiovascular disease is endothelial dysfunction which is found in obese young individuals. Increased activity of the enzyme arginase has been described as a central mechanism for endothelial dysfunction, especially in patients with diabetes mellitus. The aim of the study was to determine plasma levels of arginase in overweight adolescents. Sixty-six male German adolescents (age: 15.2 ± 1.1 years old) were included. Thirty-one of them were overweight (>90th age-specific weight percentile). Plasma arginase I and tumor necrosis factor alpha (TNFα) were determined. In addition, clinical data were recorded and anthropometrical measurements of obesity were performed. Overweight adolescents had a higher systolic blood pressure, lower high-density lipoprotein and increased levels of high-sensitive C-reactive protein (CRP). Circulating arginase I was elevated in overweight adolescents (95.8 ± 68.2 ng/ml) compared to normal weight adolescents (39.3 ± 26.9 ng/ml, p obesity. There was no difference between the two groups regarding TNFα. We demonstrate that arginase I levels are increased in obese adolescents. Knowing the important role for arginase in endothelial dysfunction, elevated levels of arginase I may represent a link between obesity, endothelial dysfunction and related comorbidities. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Increased prolactin levels are associated with impaired processing speed in subjects with early psychosis.

Science.gov (United States)

Montalvo, Itziar; Gutiérrez-Zotes, Alfonso; Creus, Marta; Monseny, Rosa; Ortega, Laura; Franch, Joan; Lawrie, Stephen M; Reynolds, Rebecca M; Vilella, Elisabet; Labad, Javier

2014-01-01

Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders with levels were determined as well as total cortisol levels in plasma. Psychopathological status was assessed and the use of psychopharmacological treatments (antipsychotics, antidepressants, benzodiazepines) recorded. Prolactin levels were negatively associated with cognitive performance in processing speed, in patients with a psychotic disorder and high-risk subjects. In the latter group, increased prolactin levels were also associated with impaired reasoning and problem solving and poorer general cognition. In a multiple linear regression analysis conducted in both high-risk and psychotic patients, controlling for potential confounders, prolactin and benzodiazepines were independently related to poorer cognitive performance in the speed of processing domain. A mediation analysis showed that both prolactin and benzodiazepine treatment act as mediators of the relationship between risperidone/paliperidone treatment and speed of processing. These results suggest that increased prolactin levels are associated with impaired processing speed in early psychosis. If these results are confirmed in future studies, strategies targeting reduction of prolactin levels may improve cognition in this population.

Serum apolipoprotein e level is not increased in Alzheimer's disease : The Rotterdam study

NARCIS (Netherlands)

Slooter, A.J.C.; Knijff, P. de; Hofman, A.; Cruts, M.; Breteler, M.M.B.; Broeckhoven, C. van; Havekes, L.M.; Duijn, C.M. van

1998-01-01

The APOE*4 allele of the apolipoprotein E gene (APOE) is an important risk factor for Alzheimer's disease. It has been suggested that levels of apolipoprotein E (apoE) in plasma are increased in Alzheimer's disease. In this population-based study, we found that serum apoE levels were lower in

Effect of increasing levels of apparent metabolizable energy on laying hens in barn system.

Science.gov (United States)

Kang, Hwan Ku; Park, Seong Bok; Jeon, Jin Joo; Kim, Hyun Soo; Park, Ki Tae; Kim, Sang Ho; Hong, Eui Chul; Kim, Chan Ho

2018-04-12

This experiment was to investigate the effect of increasing levels of apparent metabolizable energy (AMEn) on the laying performance, egg quality, blood parameter, blood biochemistry, intestinal morphology, and apparent total tract digestibility (ATTD) of energy and nutrients in diets fed to laying hens. A total of three-hundred twenty 33-week-old Hy-Line Brown laying hens (Gallus domesticus) were evenly assigned to four experimental diets of 2,750, 2,850, 2,950, and 3,050 kcal AMEn/kg in floor with deep litter of rice hulls. There were four replicates of each treatment, each consisting of 20 birds in a pen. AMEn intake was increased (linear, p Feed intake and feed conversion ratio were improved (linear, p hen-day egg production tended to be increased as increasing level of AMEn in diets increased. During the experiment, leukocyte concentration and blood biochemistry (total cholesterol, triglyceride, glucose, total protein, calcium, asparate aminotransferase (AST), and alanine transferase (ALT) were not influenced by increasing level of AMEn in diets. Gross energy and ether extract were increased (linear, p hens fed high AMEn diet (i.e., 3,050 kcal/kg in the current experiment) tended to overconsume energy with a positive effect on feed intake, feed conversion ratio, nutrient digestibility, and intestinal morphology but not in egg production and egg mass.

Countdown to 2015 country case studies: what have we learned about processes and progress towards MDGs 4 and 5?

Directory of Open Access Journals (Sweden)

Corrina Moucheraud

2016-09-01

Full Text Available Abstract Background Countdown to 2015 was a multi-institution consortium tracking progress towards Millennium Development Goals (MDGs 4 and 5. Case studies to explore factors contributing to progress (or lack of progress in reproductive, maternal, newborn and child health (RMNCH were undertaken in: Afghanistan, Bangladesh, China, Ethiopia, Kenya, Malawi, Niger, Pakistan, Peru, and Tanzania. This paper aims to identify cross-cutting themes on how and why these countries achieved or did not achieve MDG progress. Methods Applying a standard evaluation framework, analyses of impact, coverage and equity were undertaken, including a mixed methods analysis of how these were influenced by national context and coverage determinants (including health systems, policies and financing. Results The majority (7/10 of case study countries met MDG-4 with over two-thirds reduction in child mortality, but none met MDG-5a for 75 % reduction in maternal mortality, although six countries achieved >75 % of this target. None achieved MDG-5b regarding reproductive health. Rates of reduction in neonatal mortality were half or less that for post-neonatal child mortality. Coverage increased most for interventions administered at lower levels of the health system (e.g., immunisation, insecticide treated nets, and these experienced substantial political and financial support. These interventions were associated with ~30–40 % of child lives saved in 2012 compared to 2000, in Ethiopia, Malawi, Peru and Tanzania. Intrapartum care for mothers and newborns -- which require higher-level health workers, more infrastructure, and increased community engagement -- showed variable increases in coverage, and persistent equity gaps. Countries have explored different approaches to address these problems, including shifting interventions to the community setting and tasks to lower-level health workers. Conclusions These Countdown case studies underline the importance of consistent

Ingestive behavior of grazing steers fed increasing levels of concentrate supplementation with different crude protein contents.

Science.gov (United States)

Mendes, Fabrício Bacelar Lima; Silva, Robério Rodrigues; de Carvalho, Gleidson Giordano Pinto; da Silva, Fabiano Ferreira; Lins, Túlio Otávio Jardim D Almeida; da Silva, Anderson Luiz Nascimento; Macedo, Venício; Abreu Filho, George; de Souza, Sinvaldo Oliveira; Guimarães, Joanderson Oliveira

2015-02-01

This study aimed to evaluate the ingestive behavior of steers on Brachiaria brizantha pasture fed diets with increasing levels of concentrate supplementation. Thirty-two crossbred steers in the finishing phase with average weight of 420 ± 8 kg were distributed in a completely randomized design with four treatments and eight replicates per treatment. Their behavior was assessed every 5 min for 24 h, in the middle of the experimental period. Variance and regression analyses at 0.05 % probability were adopted. The times spent grazing and ruminating reduced linearly (P <0.05), whereas the times spent at the trough (eating) and on other activities increased linearly (P <0.05) as the supplementation levels were elevated. The total feeding and chewing times decreased linearly (P <0.05) as the concentrate levels in the diet were elevated. By increasing the supplementation levels, the number of bites per day decreased linearly (P <0.05), and the feed efficiency of dry matter increased quadratically. Rumination efficiency of dry matter increased linearly (P <0.05) with increasing levels of concentrate supplementation. Grazing and rumination activities are reduced when the time devoted to other activities and at the trough are increased, as a result of the substitution effect.

Widespread recent increases in county-level heart disease mortality across age groups.

Science.gov (United States)

Vaughan, Adam S; Ritchey, Matthew D; Hannan, Judy; Kramer, Michael R; Casper, Michele

2017-12-01

Recent national trends show decelerating declines in heart disease mortality, especially among younger adults. National trends may mask variation by geography and age. We examined recent county-level trends in heart disease mortality by age group. Using a Bayesian statistical model and National Vital Statistics Systems data, we estimated overall rates and percent change in heart disease mortality from 2010 through 2015 for four age groups (35-44, 45-54, 55-64, and 65-74 years) in 3098 US counties. Nationally, heart disease mortality declined in every age group except ages 55-64 years. County-level trends by age group showed geographically widespread increases, with 52.3%, 58.5%, 69.1%, and 42.0% of counties experiencing increases with median percent changes of 0.6%, 2.2%, 4.6%, and -1.5% for ages 35-44, 45-54, 55-64, and 65-74 years, respectively. Increases were more likely in counties with initially high heart disease mortality and outside large metropolitan areas. Recent national trends have masked local increases in heart disease mortality. These increases, especially among adults younger than age 65 years, represent challenges to communities across the country. Reversing these trends may require intensification of primary and secondary prevention-focusing policies, strategies, and interventions on younger populations, especially those living in less urban counties. Published by Elsevier Inc.

Lake-level increasing under the climate cryoaridization conditions during the Last Glacial Maximum

Science.gov (United States)

Amosov, Mikhail; Strelkov, Ivan

2017-04-01

A lake genesis and lake-level increasing during the Last Glacial Maximum (LGM) are the paramount issues in paleoclimatology. Investigating these problems reveals the regularities of lake development and figures out an arid territory conditions at the LGM stage. Pluvial theory is the most prevalent conception of lake formation during the LGM. This theory is based on a fact that the water bodies emerged and their level increased due to torrential rainfalls. In this study, it is paid attention to an alternative assumption of lake genesis at the LGM stage, which is called climate cryoaridization. In accordance with this hypothesis, the endorheic water basins had their level enlarged because of a simultaneous climate aridity and temperature decrease. In this research, a lake-level increasing in endorheic regions of Central Asia and South American Altiplano of the Andes is described. The lake investigation is related to its conditions during the LGM. The study also includes a lake catalogue clearly presenting the basin conditions at the LGM stage and nowadays. The data compilation partly consists of information from an earlier work of Mikhail Amosov, Lake-levels, Vegetation And Climate In Central Asia During The Last Glacial Maximum (EGU2014-3015). According to the investigation, a lake catalogue on 27 lakes showed that most of the water bodies had higher level. This feature could be mentioned for the biggest lakes of the Aral Sea, Lake Balkhash, Issyk-Kul etc. and for the small ones located in the mountains, such as Pamir, Tian-Shan and Tibet. Yet some lakes that are situated in Central Asian periphery (Lake Qinghai and lakes in Inner Mongolia) used to be lower than nowadays. Also, the lake-level increasing of Altiplano turned to be a significant feature during the LGM in accordance with the data of 5 lakes, such as Titicaca, Coipasa-Uyuni, Lejia, Miscanti and Santa-Maria. Most of the current endorheic basins at the LGM stage were filled with water due to abundant

Investigation of New Morpholino Oligomers to Increase Survival Motor Neuron Protein Levels in Spinal Muscular Atrophy.

Science.gov (United States)

Ramirez, Agnese; Crisafulli, Sebastiano G; Rizzuti, Mafalda; Bresolin, Nereo; Comi, Giacomo P; Corti, Stefania; Nizzardo, Monica

2018-01-06

Spinal muscular atrophy (SMA) is an autosomal-recessive childhood motor neuron disease and the main genetic cause of infant mortality. SMA is caused by deletions or mutations in the survival motor neuron 1 ( SMN1 ) gene, which results in SMN protein deficiency. Only one approved drug has recently become available and allows for the correction of aberrant splicing of the paralogous SMN2 gene by antisense oligonucleotides (ASOs), leading to production of full-length SMN protein. We have already demonstrated that a sequence of an ASO variant, Morpholino (MO), is particularly suitable because of its safety and efficacy profile and is both able to increase SMN levels and rescue the murine SMA phenotype. Here, we optimized this strategy by testing the efficacy of four new MO sequences targeting SMN2 . Two out of the four new MO sequences showed better efficacy in terms of SMN protein production both in SMA induced pluripotent stem cells (iPSCs) and SMAΔ7 mice. Further, the effect was enhanced when different MO sequences were administered in combination. Our data provide an important insight for MO-based treatment for SMA. Optimization of the target sequence and validation of a treatment based on a combination of different MO sequences could support further pre-clinical studies and the progression toward future clinical trials.

Low oxygen level increases proliferation and metabolic changes in bovine granulosa cells.

Science.gov (United States)

Shiratsuki, Shogo; Hara, Tomotaka; Munakata, Yasuhisa; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

2016-12-05

The present study addresses molecular backgrounds underlying low oxygen induced metabolic changes and 1.2-fold change in bovine granulosa cell (GCs) proliferation. RNA-seq revealed that low oxygen (5%) upregulated genes associated with HIF-1 and glycolysis and downregulated genes associated with mitochondrial respiration than that in high oxygen level (21%). Low oxygen level induced high glycolytic activity and low mitochondrial function and biogenesis. Low oxygen level enhanced GC proliferation with high expression levels of HIF-1, VEGF, AKT, mTOR, and S6RP, whereas addition of anti-VEGF antibody decreased cellular proliferation with low phosphorylated AKT and mTOR expression levels. Low oxygen level reduced SIRT1, whereas activation of SIRT1 by resveratrol increased mitochondrial replication and decreased cellular proliferation with reduction of phosphorylated mTOR. These results suggest that low oxygen level stimulates the HIF1-VEGF-AKT-mTOR pathway and up-regulates glycolysis, which contributes to GC proliferation, and downregulation of SIRT1 contributes to hypoxia-associated reduction of mitochondria and cellular proliferation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Increased Cord Blood Betatrophin Levels in the Offspring of Mothers with Gestational Diabetes

Science.gov (United States)

Wu, Shimin; Zhao, Yue; Du, Caiqi; Yuan, Guandou; Ning, Qin; McCormick, Kenneth; Luo, Xiaoping

2016-01-01

Aim Exposing a fetus to hyperglycemia can increase the risk for later-life metabolic disorders. Betatrophin has been proposed as a key regulator of pancreatic beta cell proliferation and lipid regulation. Highly responsive to nutritional signals, serum betatrophin concentrations have been found to be altered by various physiological and pathological conditions. We hypothesized that betatrophin levels are increased in the cord blood in offspring exposed to intrauterine hyperglycemia. Methods This was a cross-sectional study including 54 mothers who underwent uncomplicated Cesarean delivery in a university hospital. Maternal gestational glucose concentration was determined at 24–48 weeks gestation after a 75-g OGTT. Cord blood and placental tissue was collected immediately post delivery. Metabolic parameters were determined in the Clinical Laboratory. Cord blood betatrophin levels were assayed using a commercially available ELISA kit. Placental mitochondrial content was determined by real-time PCR. Results Cord blood betatrophin levels were increased in the gestational diabetes mellitus (GDM) group compared with the normoglycemic group. Furthermore, betatrophin levels were positively correlated with maternal gestational 2h post-OGTT glucose, cord blood insulin, HOMA-IR, and inversely correlated with placental mitochondrial content. Conclusions Cord blood betatrophin may function as a potential biomarker of maternal intrauterine hyperglycemia and fetal insulin resistance, which may presage for long-term metabolic impact of GDM on offspring. PMID:27196053

Lysyl oxidase enzymatic function increases stiffness to drive colorectal cancer progression through FAK

DEFF Research Database (Denmark)

Baker, A-M; Bird, D; Lang, G

2013-01-01

The extracellular, matrix-modifying enzyme lysyl oxidase (LOX) has recently been linked to colorectal cancer (CRC) progression, in particular to the stages of invasion and metastasis. In this report, we use cell lines expressing a catalytically inactive mutant form of LOX to show that catalytic a...... for patients with metastatic CRC.Oncogene advance online publication, 28 May 2012; doi:10.1038/onc.2012.202....

Developing a low-level radioactive waste disposal facility in Connecticut: Update on progress and new directions

Energy Technology Data Exchange (ETDEWEB)

Gingerich, R.E. [Connecticut Hazardous Waste Management Service, Hartford, CT (United States)

1993-03-01

Connecticut is a member of the Northeast Interstate Low-Level Radioactive Waste Management Compact (Northeast LLRW Compact). The other member of the Northeast LLRW Compact is New Jersey. The Northeast Interstate Low-Level Radioactive Waste Commission (Northeast Compact Commission), the Northeast LLRW Compact`s governing body, has designated both Connecticut and New Jersey as host states for disposal facilities. The Northeast Compact Commission has recommended that, for purposes of planning for each state`s facility, the siting agency for the state should use projected volumes and characteristics of the LLW generated in its own state. In 1987 Connecticut enacted legislation that assigns major responsibilities for developing a LLW disposal facility in Connecticut to the Connecticut Hazardous Waste Management Service (CHWMS). The CHWMS is required to: prepare and revise, as necessary, a LLW Management Plan for the state; select a site for a LLW disposal facility; select a disposal technology to be used at the site; select a firm to obtain the necessary approvals for the facility and to develop and operate it; and serve as the custodial agency for the facility. This paper discusses progress in developing a facility.

Increased Arousal Levels and Decreased Sleep by Brain Music in Rats

Institute of Scientific and Technical Information of China (English)

Guang-Zhan Fang; Chun-Peng Zhang; Dan Wu; Yang Xia; Yong-Xiu Lai; De-Zhong Yao

2009-01-01

More and more studies have been reported on whether music and other types of auditory stimulation would improve the quality of sleep.Many of these studies have found significant results,but others argue that music is not significantly better than the tones or control conditions in improving sleep.For further understanding the relationship between music and sleep or music and arousal,the present study therefore examines the effects of brain music on sleep and arousal by means of biofeedback.The music is from the transformation of rapid eye movement (REM) sleep electroencephalogram (EEG) of rats using an algorithm in the Chengdu Brain Music (CBM) system.When the brain music was played back to rats,EEG data were recorded to assess the efficacy of music to induce or improve sleep,or increase arousal levels by sleep staging,etc.Our results demonstrate that exposure to the brain music increases arousal levels and decreases sleep in rats,and the underlying mechanism of decreased non-rapid eye movement (NREM) and REM sleep may be different.

Lifestyle modification and progressive renal failure.

Science.gov (United States)

Ritz, Eberhard; Schwenger, Vedat

2005-08-01

There is increasing evidence that lifestyle factors impact on the risk of developing chronic kidney disease (CKD) and the risk of progression of CKD. Equally important is the consideration that patients with CKD are more likely to die from cardiovascular disease than to reach the stage of end-stage renal failure. It is advantageous that manoeuvres that interfere with progression at the same time also reduce the risk of cardiovascular events. Lifestyle factors that aggravate progression include, among others, smoking, obesity and dietary salt intake. Alcohol consumption, according to some preliminary information, has a bimodal relationship to cardiovascular risk and progression, with moderate consumption being protective.

Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination.

Directory of Open Access Journals (Sweden)

Henning Hagmann

Full Text Available RATIONALE: Preeclampsia is a devastating medical complication of pregnancy which leads to maternal and fetal morbidity and mortality. While the etiology of preeclampsia is unclear, human and animal studies suggest that excessive circulating levels of soluble fms-like tyrosine-kinase-1 (sFlt-1, an alternatively spliced variant of VEGF-receptor1, contribute to the signs and symptoms of preeclampsia. Since sFlt-1 binds to heparin and heparan sulfate proteoglycans, we hypothesized that the anticoagulant heparin, which is often used in pregnancy, may interfere with the levels, distribution and elimination of sFlt-1 in vivo. OBJECTIVE: We systematically determined serum and urine levels of angiogenic factors in preeclamptic women before and after administration of low molecular weight heparin and further characterized the interaction with heparin in biochemical studies. METHODS AND RESULTS: Serum and urine samples were used to measure sFlt-1 levels before and after heparin administration. Serum levels of sFlt-1 increased by 25% after heparin administration in pregnant women. The magnitude of the increase in circulating sFlt-1 correlated with initial sFlt-1 serum levels. Urinary sFlt-1 levels were also elevated following heparin administration and levels of elimination were dependent on the underlying integrity of the glomerular filtration barrier. Biochemical binding studies employing cation exchange chromatography revealed that heparin bound sFlt-1 had decreased affinity to negatively charged surfaces when compared to sFlt-1 alone. CONCLUSION: Low molecular weight heparin administration increased circulating sFlt1 levels and enhanced renal elimination. We provide evidence that both effects may be due to heparin binding to sFlt1 and masking the positive charges on sFlt1 protein.

Regional level approach for increasing energy efficiency

International Nuclear Information System (INIS)

Viholainen, Juha; Luoranen, Mika; Väisänen, Sanni; Niskanen, Antti; Horttanainen, Mika; Soukka, Risto

2016-01-01

Highlights: • Comprehensive snapshot of regional energy system for decision makers. • Connecting regional sustainability targets and energy planning. • Involving local players in energy planning. - Abstract: Actions for increasing the renewable share in the energy supply and improving both production and end-use energy efficiency are often built into the regional level sustainability targets. Because of this, many local stakeholders such as local governments, energy producers and distributors, industry, and public and private sector operators require information on the current state and development aspects of the regional energy efficiency. The drawback is that an overall view on the focal energy system operators, their energy interests, and future energy service needs in the region is often not available for the stakeholders. To support the local energy planning and management of the regional energy services, an approach for increasing the regional energy efficiency is being introduced. The presented approach can be seen as a solid framework for gathering the required data for energy efficiency analysis and also evaluating the energy system development, planned improvement actions, and the required energy services at the region. This study defines the theoretical structure of the energy efficiency approach and the required steps for revealing such energy system improvement actions that support the regional energy plan. To demonstrate the use of the approach, a case study of a Finnish small-town of Lohja is presented. In the case example, possible actions linked to the regional energy targets were evaluated with energy efficiency analysis. The results of the case example are system specific, but the conducted study can be seen as a justified example of generating easily attainable and transparent information on the impacts of different improvement actions on the regional energy system.

Diabetes mellitus type 2 is associated with higher levels of myeloperoxidase

NARCIS (Netherlands)

Wiersma, Jacobijne J.; Meuwese, Marijn C.; van Miert, Joram N. I.; Kastelein, Arnoud; Tijssen, Jan G. P.; Piek, Jan J.; Trip, Mieke D.

2008-01-01

BACKGROUND: Diabetes mellitus type 2 is linked to augmented endothelial dysfunction and accelerated atherosclerosis. Myeloperoxidase plays an important role in the initiation, progression, and the complications of atherosclerosis. We investigated whether myeloperoxidase levels are increased in

Plasma lactoferrin levels in pregnancy and cystic fibrosis

International Nuclear Information System (INIS)

Sykes, J.A.C.; Thomas, M.J.; Goldie, D.J.; Turner, G.M.

1982-01-01

Plasma lactoferrin levels have been determined by radioimmunoassay for the different weeks of normal pregnancy, in normal healthy adults and in children with and without cystic fibrosis. The lactoferrin levels were higher in pregnancy than in both male and female normal adults and showed a slight progressive increase up to week 29 and thereafter remained high. Five out of seven children with cystic fibrosis had markedly raised plasma lactoferrin levels from six to 16 times higher than the mean of a control group of children. (Auth.)

Increased cortisol levels in hair of recent Ecstasy/MDMA users.

Science.gov (United States)

Parrott, A C; Sands, H R; Jones, L; Clow, A; Evans, P; Downey, L A; Stalder, T

2014-03-01

Previous research has revealed an acute 8-fold increase in salivary cortisol following self-administrated Ecstasy/MDMA in dance clubbers. It is currently not known to what extent repeated usage impacts upon activity of the hypothalamic-pituitary-adrenal axis over a more prolonged period of time. This study investigated the integrated cortisol levels in 3-month hair samples from recent Ecstasy/MDMA users and non-user controls. One hundred and one unpaid participants (53 males, 48 females; mean age 21.75 years) completed the University of East London recreational drug use questionnaire, modified to cover the past 3-months of usage. They comprised 32 light recent Ecstasy/MDMA users (1-4 times in last 3 months), 23 recent heavy MDMA users (+5 times in last 3 months), and 54 non-user controls. Volunteers provided 3 cm hair samples for cortisol analysis. Hair cortisol levels were observed to be significantly higher in recent heavy MDMA users (mean = 55.0 ± 80.1 pg/mg), compared to recent light MDMA users (19.4 ± 16.0 pg/mg; p=0.015), and to non-users (13.8 ± 6.1 pg/mg; pEcstasy/MDMA was associated with almost 4-fold raised hair cortisol levels, in comparison with non-user controls. The present results are consistent with the bio-energetic stress model for Ecstasy/MDMA, which predicts that repeated stimulant drug use may increase cortisol production acutely, and result in greater deposits of the hormone in hair. These data may also help explain the neurocognitive, psychiatric, and other psychobiological problems of some abstinent users. Future study design and directions for research concerning the psychoneuroendocrinological impact of MDMA are also discussed. © 2013 Published by Elsevier B.V. and ECNP.

Progesterone receptor expression during prostate cancer progression suggests a role of this receptor in stromal cell differentiation.

Science.gov (United States)

Yu, Yue; Yang, Ou; Fazli, Ladan; Rennie, Paul S; Gleave, Martin E; Dong, Xuesen

2015-07-01

The progesterone receptor, like the androgen receptor, belongs to the steroid receptor superfamily. Our previous studies have reported that the PR is expressed specifically in prostate stroma. PR inhibits proliferation of, and regulates cytokine secretion by stromal cells. However, PR protein expression in cancer-associated stroma during prostate cancer progression has not been profiled. Since the phenotypes of prostate stromal cells change dynamically as tumors progress, whether the PR plays a role in regulating stromal cell differentiation needs to be investigated. Immunohistochemistry assays measured PR protein levels on human prostate tissue microarrays containing 367 tissue cores from benign prostate, prostate tumors with different Gleason scores, tumors under various durations of castration therapy, and tumors at the castration-resistant stage. Immunoblotting assays determined whether PR regulated the expression of alpha smooth muscle actin (α-SMA), vimentin, and fibroblast specific protein (FSP) in human prostate stromal cells. PR protein levels decreased in cancer-associated stroma when compared with that in benign prostate stroma. This reduction in PR expression was not correlated with Gleason scores. PR protein levels were elevated by castration therapy, but reduced to pre-castration levels when tumors progressed to the castration-resistant stage. Enhanced PR expression in human prostate stromal cells increased α-SMA, but decreased vimentin and FSP protein levels ligand-independently. These results suggest that PR plays an active role in regulating stromal cell phenotypes during prostate cancer progression. © 2015 Wiley Periodicals, Inc.

Trans fatty acids increase nitric oxide levels and pancreatic beta-cell necrosis in rats

Directory of Open Access Journals (Sweden)

Kusmiyati Tjahjono DK

2013-04-01

Full Text Available Background The prevalence of diabetes in Indonesia is increasing due to various factors, including life style changes such as trans fatty acid (TFA intake. High TFA intake is known to be related to blood lipid profile changes resulting in cardiovascular disorders. This study was to identify the effect of TFA on nitric oxide (NO production and on necrosis of pancreatic beta cells. Methods A study of randomized pre-test post–test design with control group. Thirty Sprague Dawley rats were divided into 3 groups, i.e. group K (control, group P1 receiving a diet with 5% TFA, and P2 receiving 10% TFA. The intervention was performed for 8 weeks. NO level and pancreatic beta-cell necrosis were analyzed using Pearson’s chi square test. Results After 4 weeks of treatment there was no change in NO levels in group K, but increased NO in P2 (2.6-3.8 ìM. At 8 weeks after treatment, NO levels in groups P1 and P2 increased to 2.6-3.4 ìM and 4.2-14.3 ìM, respectively, while in group K only 2 rats had increased NO levels of 2.8-2.9 ìM. With Pearson’s chi-square test, there was a signifant difference in the proportions of necrotic pancreatic beta cells after 4 weeks and 8 weeks (p=0.000. No necrosis of beta cells was found in group K, mild necrosis in group P1 (1-25% and moderate necrosis in group P2 (26-50%. Conclusion TFA consumption significantly increases NO levels in Sprague Dawley rats and also results in moderate grades of necrosis of pancreatic beta cells.

Trans fatty acids increase nitric oxide levels and pancreatic beta-cell necrosis in rats

Directory of Open Access Journals (Sweden)

Kusmiyati Tjahjono DK

2015-12-01

Full Text Available BACKGROUND The prevalence of diabetes in Indonesia is increasing due to various factors, including life style changes such as trans fatty acid (TFA intake. High TFA intake is known to be related to blood lipid profile changes resulting in cardiovascular disorders. This study was to identify the effect of TFA on nitric oxide (NO production and on necrosis of pancreatic beta cells. METHODS A study of randomized pre-test post–test design with control group. Thirty Sprague Dawley rats were divided into 3 groups, i.e. group K (control, group P1 receiving a diet with 5% TFA, and P2 receiving 10% TFA. The intervention was performed for 8 weeks. NO level and pancreatic beta-cell necrosis were analyzed using Pearson’s chi square test. RESULTS After 4 weeks of treatment there was no change in NO levels in group K, but increased NO in P2 (2.6-3.8 ìM. At 8 weeks after treatment, NO levels in groups P1 and P2 increased to 2.6-3.4 ìM and 4.2-14.3 ìM, respectively, while in group K only 2 rats had increased NO levels of 2.8-2.9 ìM. With Pearson’s chi-square test, there was a signifant difference in the proportions of necrotic pancreatic beta cells after 4 weeks and 8 weeks (p= 0.000. No necrosis of beta cells was found in group K, mild necrosis in group P1 (1-25% and moderate necrosis in group P2 (26-50%. CONCLUSION TFA consumption significantly increases NO levels in Sprague Dawley rats and also results in moderate grades of necrosis of pancreatic beta cells

Increased levels of unscheduled DNA synthesis in UV-irradiated human fibroblasts pretreated with sodium butyrate

International Nuclear Information System (INIS)

Williams, J.I.; Friedberg, E.C.

1982-01-01

Pretreatment of growing normal and xeroderma pigmentosum (XP) human fibroblasts with sodium butyrate at concentrations of 5-20 mM results in increased levels of DNA repair synthesis measured by autoradiography after exposure of the cells to 254 nm UV radiation in the fluence range 0-25 J/m 2 . The phenomenon manifests as an increased extent and an increased initial rate of unscheduled DNA synthesis (UDS). This experimental result is not due to an artifact of autoradiography related to cell size. Xeroderma pigmentosum cells from complementation groups A, C, D and E and XP variant cells all exhibit increases in the levels of UV-induced UDS in response to sodium butyrate proportional to those observed with normal cells. These UDS increases associated with butyrate pretreatment correlate with demonstrable changes in intracellular thymidine pool size and suggest that sodium butyrate enhances uptake of exogenous radiolabeled thymidine during UV-induced repair synthesis by reducing endogenous levels of thymidine. (author)

Apelin-13 increased food intake with serum ghrelin and leptin levels in male rats.

Science.gov (United States)

Saral, S; Alkanat, M; Sumer, A; Canpolat, S

2018-01-01

In this study, we aimed to explain the role of apelin-13 on body weight, food and water intake with serum leptin, ghrelin, neuropeptid Y (NPY) and peptid YY (PYY) levels in male rat. Thirty-two Sprague-Dawley male rats were used for the study. The rats were injected SP (0.9 %) intraperitoneally (i.p) in the control group and 30 (AP30), 100 (AP100) and 300 (AP300) µg/kg apelin-13 in the study groups, respectively, 10 min before the transition to dark period, for 10 days. During the experimental period, with light and dark periods of food and water intake, body weights were recorded in rats. Rats were euthanized and serum samples were obtained. In serum samples leptin, ghrelin, NPY and PYY levels were measured with specific ELISA kit. Apelin-13 was increased body weights in all three (AP30, AP100 and AP300) groups compared with the control group. AP100 and AP300 groups had increased food intake in the dark and the cumulative period, but in the light period food intake values were not significantly increased (p > 0.05). As for the value of water intake, compared with the control group, all dose of apelin-13 increased water intake during the dark and the cumulative period. There was no significant change in water intake in the light period. On the other hand, compared with the control group, serum leptin levels were found to increase in the groups administered 100 and 300 µg/kg of apelin-13 (p Ghrelin levels were found high in all groups treated with apelin-13. Serum levels of NPY decreased only in the 300 µg/kg apelin-13 treated group (p 0.05). Apelin-13 increases body weight in rats as well as food and water intake (dark and cumulative period). Additionally, ghrelin can mediate the orexigenic effect of apelin-13 in the regulation of food intake (Fig. 4, Ref. 37).

Erythropoetin treatment can increase 2,3-diphosphoglycerate levels in red blood cells.

Science.gov (United States)

Birgegård, G; Sandhagen, B

2001-01-01

Some patients experience an improved well-being during treatment with recombinant human erythropoietin even with an unchanged Hb level. We have hypothesized that this may not be only a placebo effect. 2,3-diphosphoglycerate (2,3-DPG) in red blood cells increases in response to anaemia/hypoxia and causes a shift of the oxygen dissociation curve, allowing a more effective oxygen delivery. We have investigated red cell 2,3-DPG concentrations during erythropoietin treatment in healthy volunteers as a mediator of a possible physiological explanation. Thirteen healthy subjects with no iron deficiency were recruited and randomly assigned to a treatment group comprising five males and three females and a control group including three males and two females. The treatment group was treated with erythropoietin (Recormon), 20 IE/kg subcutaneously three times/week for 4 weeks. Blood samples were collected at each injection day and 10 days after the last injection and at corresponding times in the control group. B-Hb, red cell 2,3-DPG and P50 were measured by standard techniques and oxygen-releasing capacity was calculated. due to the sampling (26 ml each time, three times/week) the mean Hb level was lowered from 140.5 +/- 5.9 to 128.6 +/- 10.4 g/L in the control group whereas the erythropoietin treatment group maintained a mean Hb level of about 142 g/L (plevel curve as well as that for oxygen releasing capacity also differed significantly between the two groups (p levels. treatment with erythropoietin causes an increase in red cell 2,3-DPG levels.

Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer.

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Jae-Kyung Myung

Full Text Available Androgen receptor (AR is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD. Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD.

Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo.

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Rehan M Baqri

Full Text Available Mutations in mitochondrial DNA polymerase (pol gamma cause several progressive human diseases including Parkinson's disease, Alper's syndrome, and progressive external ophthalmoplegia. At the cellular level, disruption of pol gamma leads to depletion of mtDNA, disrupts the mitochondrial respiratory chain, and increases susceptibility to oxidative stress. Although recent studies have intensified focus on the role of mtDNA in neuronal diseases, the changes that take place in mitochondrial biogenesis and mitochondrial axonal transport when mtDNA replication is disrupted are unknown. Using high-speed confocal microscopy, electron microscopy and biochemical approaches, we report that mutations in pol gamma deplete mtDNA levels and lead to an increase in mitochondrial density in Drosophila proximal nerves and muscles, without a noticeable increase in mitochondrial fragmentation. Furthermore, there is a rise in flux of bidirectional mitochondrial axonal transport, albeit with slower kinesin-based anterograde transport. In contrast, flux of synaptic vesicle precursors was modestly decreased in pol gamma-alpha mutants. Our data indicate that disruption of mtDNA replication does not hinder mitochondrial biogenesis, increases mitochondrial axonal transport, and raises the question of whether high levels of circulating mtDNA-deficient mitochondria are beneficial or deleterious in mtDNA diseases.

Biomarkers of evasive resistance predict disease progression in cancer patients treated with antiangiogenic therapies

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Pircher, Andreas; Jöhrer, Karin; Kocher, Florian; Steiner, Normann; Graziadei, Ivo; Heidegger, Isabel; Pichler, Renate; Leonhartsberger, Nicolai; Kremser, Christian; Kern, Johann; Untergasser, Gerold; Gunsilius, Eberhard; Hilbe, Wolfgang

2016-01-01

Numerous antiangiogenic agents are approved for the treatment of oncological diseases. However, almost all patients develop evasive resistance mechanisms against antiangiogenic therapies. Currently no predictive biomarker for therapy resistance or response has been established. Therefore, the aim of our study was to identify biomarkers predicting the development of therapy resistance in patients with hepatocellular cancer (n = 11), renal cell cancer (n = 7) and non-small cell lung cancer (n = 2). Thereby we measured levels of angiogenic growth factors, tumor perfusion, circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEP) and tumor endothelial markers (TEM) in patients during the course of therapy with antiangiogenic agents, and correlated them with the time to antiangiogenic progression (aTTP). Importantly, at disease progression, we observed an increase of proangiogenic factors, upregulation of CEC/CEP levels and downregulation of TEMs, such as Robo4 and endothelial cell-specific chemotaxis regulator (ECSCR), reflecting the formation of torturous tumor vessels. Increased TEM expression levels tended to correlate with prolonged aTTP (ECSCR high = 275 days vs. ECSCR low = 92.5 days; p = 0.07 and for Robo4 high = 387 days vs. Robo4 low = 90.0 days; p = 0.08). This indicates that loss of vascular stabilization factors aggravates the development of antiangiogenic resistance. Thus, our observations confirm that CEP/CEC populations, proangiogenic cytokines and TEMs contribute to evasive resistance in antiangiogenic treated patients. Higher TEM expression during disease progression may have clinical and pathophysiological implications, however, validation of our results is warranted for further biomarker development. PMID:26956051

Coagulation Parameters and Risk of Progressive Hemorrhagic Injury after Traumatic Brain Injury: A Systematic Review and Meta-Analysis

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Danfeng Zhang

2015-01-01

Full Text Available Intracranial hemorrhage (ICH after traumatic brain injury (TBI commonly increases in size and coagulopathy has been implicated in such progression. Our aim is to perform a meta-analysis to assess their relationship. Cochrane library, PubMed, and EMBASE were searched for literatures. Pooled effect sizes and 95% confidential intervals (CIs were calculated using random-effects model. We included six studies, involving 1700 participants with 540 progressive hemorrhagic injuries (PHIs. Our findings indicate that PT, D-dimer level, and INR value are positively associated with the risk of PHI. Higher level of PLT and Fg seemed to suggest a lower risk of PHI. Among these parameters, higher D-dimer level and INR value would possess more powerful strength in predicting PHI.

Increased expression of EZH2 in Merkel cell carcinoma is associated with disease progression and poorer prognosis.

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Harms, Kelly L; Chubb, Heather; Zhao, Lili; Fullen, Douglas R; Bichakjian, Christopher K; Johnson, Timothy M; Carskadon, Shannon; Palanisamy, Nallasivam; Harms, Paul W

2017-09-01

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that has a high risk of disease progression with nodal and distant metastases. Here, we evaluated EZH2 expression by immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph node metastases, 13 in-transit metastases, and 2 distant metastases) with clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors. Importantly, weak expression of EZH2 in the primary tumor, but not nodal metastases, correlated with improved prognosis compared to moderate/strong EZH2 expression (5-year MCC-specific survival of 68% versus 22%, respectively, P=.024). In addition, EZH2 was expressed at higher levels in nodal metastases compared to primary tumors (P=.005). Our data demonstrate that EZH2 has prognostic value and may play an oncogenic role in MCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of increased CO{sub 2} levels on monsoons

Energy Technology Data Exchange (ETDEWEB)

Cherchi, Annalisa; Masina, Simona; Navarra, Antonio [Centro Euro-Mediterraneo per i Cambiamenti Climatici and Istituto Nazionale di Geofisica e Vulcanologia, Bologna (Italy); Alessandri, Andrea [Centro Euro-Mediterraneo per i Cambiamenti Climatici, Bologna (Italy)

2011-07-15

Increased atmospheric carbon dioxide concentration provided warmer atmospheric temperature and higher atmospheric water vapor content, but not necessarily more precipitation. A set of experiments performed with a state-of-the-art coupled general circulation model forced with increased atmospheric CO{sub 2} concentration (2, 4 and 16 times the present-day mean value) were analyzed and compared with a control experiment to evaluate the effect of increased CO{sub 2} levels on monsoons. Generally, the monsoon precipitation responses to CO{sub 2} forcing are largest if extreme concentrations of carbon dioxide are used, but they are not necessarily proportional to the forcing applied. In fact, despite a common response in terms of an atmospheric water vapor increase to the atmospheric warming, two out of the six monsoons studied simulate less or equal summer mean precipitation in the 16 x CO{sub 2} experiment compared to the intermediate sensitivity experiments. The precipitation differences between CO{sub 2} sensitivity experiments and CTRL have been investigated specifying the contribution of thermodynamic and purely dynamic processes. As a general rule, the differences depending on the atmospheric moisture content changes (thermodynamic component) are large and positive, and they tend to be damped by the dynamic component associated with the changes in the vertical velocity. However, differences are observed among monsoons in terms of the role played by other terms (like moisture advection and evaporation) in shaping the precipitation changes in warmer climates. The precipitation increase, even if weak, occurs despite a weakening of the mean circulation in the monsoon regions (''precipitation-wind paradox''). In particular, the tropical east-west Walker circulation is reduced, as found from velocity potential analysis. The meridional component of the monsoon circulation is changed as well, with larger (smaller) meridional (vertical) scales. (orig.)

Low uric acid level increases the risk of infectious mononucleosis and this effect is more pronounced in women

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Zhang, Li; Zhou, Pingping; Meng, Zhaowei; Gong, Lu; Pang, Chongjie; Li, Xue; Jia, Qiang; Tan, Jian; Liu, Na; Hu, Tianpeng; Zhang, Qing; Jia, Qiyu; Song, Kun

2017-01-01

Infectious mononucleosis (IM) due to Epstein-Barr virus infection is common. Uric acid (UA) is an important endogenous antioxidant. To the best of our knowledge, the association between UA and IM has not been comprehensively investigated to date. The aim of the present study was to investigate this association in Chinese patients. A total of 95 patients (47 men and 48 women) with IM were recruited, along with 95 healthy controls. Clinical data were classified by patient sex. Receiver operating characteristic (ROC) curve analysis was adopted to determine the cut-off values of UA for IM diagnosis and prediction. Crude and adjusted odds ratios (ORs) of UA for IM were analyzed by binary logistic regression. The UA levels were significantly lower in IM patients compared with those in controls. In addition, UA levels in men were significantly higher compared with those in women. The ROC curve demonstrated good diagnostic and predictive values of UA for IM in both sexes. The UA cut-off values were 326.00 and 243.50 µmol/l for diagnosing IM in men and women, respectively, with a diagnostic accuracy of 76.596 and 80.208%, respectively. Binary logistic regression analysis revealed a significant risk of IM in the low UA quartiles in both sexes. Following adjustments, the ORs even increased. Women with low UA levels appeared to be more susceptible to IM. For example, the crude ORs in quartile 1 were 24.000 and 52.500 for men and women, respectively, and the respective adjusted ORs were 31.437 and 301.746 (all P<0.01). To the best of our knowledge, the present study is the first to demonstrate the inverse association between UA and IM, suggesting a progressive decrease of antioxidant reserve in IM. Moreover, low UA was suggestive of IM, particularly in women. PMID:29285370

Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

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Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

2018-01-01

The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

Current hemoglobin levels are more predictive of disease progression than hemoglobin measured at baseline in patients receiving antiretroviral treatment for HIV type 1 infection

DEFF Research Database (Denmark)

Kowalska, Justyna D; Mocroft, Amanda; Blaxhult, Anders

2007-01-01

The role of hemoglobin levels as an independent prognostic marker of progression to AIDS and/or death in HIV-infected patients starting combination antiretroviral therapy (cART) was investigated. A total of 2,579 patients from the EuroSIDA cohort with hemoglobin, CD4 cell count, and HIV RNA viral...

Physical water scarcity metrics for monitoring progress towards SDG target 6.4 : An evaluation of indicator 6.4.2 “Level of water stress”

NARCIS (Netherlands)

Vanham, D.; Hoekstra, A. Y.; Wada, Y.; Bouraoui, F.; de Roo, A.; Mekonnen, M. M.; van de Bund, W. J.; Batelaan, O.; Pavelic, P.; Bastiaanssen, Wim G M; Kummu, M.; Rockström, J.; Liu, J.; Bisselink, B.; Ronco, P.; Pistocchi, A.; Bidoglio, G.

2018-01-01

Target 6.4 of the recently adopted Sustainable Development Goals (SDGs) deals with the reduction of water scarcity. To monitor progress towards this target, two indicators are used: Indicator 6.4.1 measuring water use efficiency and 6.4.2 measuring the level of water stress (WS). This paper aims to

Increased level of miRNA 30b-3p in patients with prostatic hyperplasia and testosterone with high-level of prostate-specific antigen

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Wasnaa Jumaa Mohammad

2018-01-01

Full Text Available Background: Prostate cancer (PCa is the most common causing cancer-related in death in men and lack of reliable diagnostic tool. MicroRNAs are small molecules single-stranded RNA that affecting protein expression at the level of translation and dysregulation can dramatically affect cell metabolism. However, the using of circulating miRNAs as diagnostic biomarkers for diagnosis of PCa is still unknown. Methods: Ten patients with prostatic hyperplasia with high-level of PSA and 10 healthy controls were conducted in this study. The reverse transcription of miRNA based on quantitative polymerase chain reaction (qPCR were used for evaluating the dysregulation of miRNA 30b-3p and using of ELISA to evaluate the level of prostate-specific antigen (PSA and testosterone hormone. Results: Circulating miRNA 30b-3p level was increased in patients with prostatic hyperplasia with higher level of PSA as compared with healthy controls. Also, the testosterone hormone was increased in those patients as compared with normal level of testosterone in healthy individuals. Conclusion: The serum miRNA 30b-3p level increased in patients with hyperplasia in prostate and may be one of potential biomarker for diagnosis of PCa.

Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy.

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Maojing Liu

Full Text Available After activation, the complement system is involved in the pathogenesis of Immunoglobulin A nephropathy (IgAN. Complement factor H (CFH is a crucial inhibitory factor of the alternative pathway of the complement system. The study investigated the effects of urinary CFH levels on IgAN progression.A total of 351 patients with IgAN participated in this study. They were followed up for an average of 51.8 ± 26.6 months. Renal outcome was defined as a composite endpoint, that included instances of end-stage renal disease (ESRD, ≥ 50% decline in estimated glomerular filtration rate (eGFR or doubling of plasma creatinine levels. Urinary CFH levels were measured by enzyme-linked immunosorbent assay and calculated as the ratio of urinary CFH over creatinine (uCFH/uCr.In the whole cohort, uCFH/uCr values were associated with disease progression either as continuous [log(uCFH/uCr] or categorical traits (dichotomous and quartile variables after adjusting for eGFR, proteinuria, mean arterial blood pressure, histological grading and immunosuppressive therapy in the Cox proportional hazard model. Kaplan-Meier analysis showed that higher uCFH/uCr values at baseline predicted worse renal outcome during follow-up (log-rank, P < 0.001. Receiver operating characteristic curve (ROC analysis showed that log(uCFH/uCr had predictive value for renal outcome (area under curve [AUC] = 0.745, and the AUC increased to 0.805 after being incorporated into baseline eGFR and proteinuria. In subgroup analysis with eGFR ≥ 60 mL/min/1.73 m2, log(uCFH/uCr had better predictive value (AUC = 0.724, P = 0.002 for renal outcome compared to eGFR (AUC = 0.582, P = 0.259 and proteinuria (AUC = 0.615, P = 0.114.Urinary CFH levels are associated with renal function decline and increased urinary CFH levels are a risk factor for progression of IgA nephropathy.

Increased prolactin levels are associated with impaired processing speed in subjects with early psychosis.

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Itziar Montalvo

Full Text Available Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders with <3 years of illness, 23 high-risk subjects. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery, and prolactin levels were determined as well as total cortisol levels in plasma. Psychopathological status was assessed and the use of psychopharmacological treatments (antipsychotics, antidepressants, benzodiazepines recorded. Prolactin levels were negatively associated with cognitive performance in processing speed, in patients with a psychotic disorder and high-risk subjects. In the latter group, increased prolactin levels were also associated with impaired reasoning and problem solving and poorer general cognition. In a multiple linear regression analysis conducted in both high-risk and psychotic patients, controlling for potential confounders, prolactin and benzodiazepines were independently related to poorer cognitive performance in the speed of processing domain. A mediation analysis showed that both prolactin and benzodiazepine treatment act as mediators of the relationship between risperidone/paliperidone treatment and speed of processing. These results suggest that increased prolactin levels are associated with impaired processing speed in early psychosis. If these results are confirmed in future studies, strategies targeting reduction of prolactin levels may improve cognition in this population.

Inhibition of 5-Lipoxygenase inhibitor zileuton in high-fat diet-induced nonalcoholic fatty liver disease progression model

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Kuifen Ma

2017-11-01

Full Text Available Objective(s: Arachidonic Acid/5-lipoxygenase (AA/5-LOX pathway connects lipid metabolism and proinflammatory cytokine, which are both related to the development and progression of nonalcoholic fatty liver disease (NAFLD. Therefore, the present study was designed to investigate the role of AA/5-LOX pathway in progression of NAFLD, and the effect of zileuton, an inhibitor of 5-LOX, in this model. Materials and Methods: Animal model for progression of NAFLD was established via feeding high saturated fat diet (HFD. Liver function, HE staining, NAFLD activity score (NAS were used to evaluate NAFLD progression. We detected the lipid metabolism substrates: free fatty acids (FFA and AA, products: cysteinyl-leukotrienes (CysLTs, and changes in gene and protein level of key enzyme in AA/5-LOX pathway including PLA2 and 5-LOX. Furthermore, we determined whether NAFLD progression pathway was delayed or reversed when zileuton (1-[1-(1-benzothiophen-2-ylethyl]-1-hydroxyurea was administrated. Results: Rat model for progression of NAFLD was well established as analyzed by liver transaminase activities, hematoxylin-eosin (HE staining and NAS. The concentrations of substrates and products in AA/5-LOX pathway were increased with the progression of NAFLD. mRNA and protein expression of PLA2 and 5-LOX were all enhanced. Moreover, administration of zileuton inhibited AA/5-LOX pathway and reversed the increased transamine activities and NAS. Conclusion: AA/5-LOX pathway promotes the progression of NAFLD, which can be reversed by zileuton.

Absence of systemic oxidative stress and increased CSF prostaglandin F2α in progressive MS

DEFF Research Database (Denmark)

Lam, Magda A.; Maghzal, Ghassan J.; Khademi, Mohsen

2016-01-01

Objective: We aimed to investigate the role of oxidative stress in the progression of multiple sclerosis (MS).  Methods: We determined by liquid chromatography-tandem mass spectrometry nonenzymatic (F2-isoprostanes) and enzymatic oxidation products of arachidonic acid (prostaglandin F2α [PGF2α......]) in plasma and CSF of 45 controls (other neurologic disease [OND] with no signs of inflammation) and 62 patients with MS. Oxidation products were correlated with disease severity and validated biomarkers of inflammation (chemokine ligand 13; matrix metalloproteinase-9; osteopontin) and axonal damage...... with natalizumab and methylprednisolone treatment and was unaffected by the use of nonsteroidal anti-inflammatory drug in secondary progressive MS. CSF PGF2α did not associate with validated CSF markers of inflammation and axonal damage that themselves did not associate with the Expanded Disability Status Scale...

The degree of acceptability of swine blood values at increasing levels of hemolysis evaluated through visual inspection versus automated quantification.

Science.gov (United States)

Di Martino, Guido; Stefani, Anna Lisa; Lippi, Giuseppe; Gagliazzo, Laura; McCormick, Wanda; Gabai, Gianfranco; Bonfanti, Lebana

2015-05-01

The pronounced fragility that characterizes swine erythrocytes is likely to produce a variable degree of hemolysis during blood sampling, and the free hemoglobin may then unpredictably bias the quantification of several analytes. The aim of this study was to evaluate the degree of acceptability of values obtained for several biochemical parameters at different levels of hemolysis. Progressively increased degrees of physical hemolysis were induced in 3 aliquots of 30 nonhemolytic sera, and the relative effects on the test results were assessed. To define the level of hemolysis, we used both visual estimation (on a scale of 0 to 3+) and analytical assessment (hemolytic index) and identified the best analytical cutoff values for discriminating the visual levels of hemolysis. Hemolysis led to a variable and dose-dependent effect on the test results that was specific for each analyte tested. In mildly hemolyzed specimens, C-reactive protein, haptoglobin, β1-globulin, β2-globulin, α1-globulin, γ-globulin, sodium, calcium, and alkaline phosphatase were not significantly biased, whereas α2-globulin, albumin, urea, creatinine, glucose, total cholesterol, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, nonesterified fatty acids, bilirubin, phosphorus, magnesium, iron, zinc, copper, lipase, triglycerides, lactate dehydrogenase, unbound iron-binding capacity, and uric acid were significantly biased. Chloride and total protein were unbiased even in markedly hemolyzed samples. Analytical interference was hypothesized to be the main source of this bias, leading to a nonlinear trend that confirmed the difficulty in establishing reliable coefficients of correction for adjusting the test results. © 2015 The Author(s).

The lack of eye care preventive services in public health leads to an increase of progressive blindness

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Clecilene Gomes CARVALHO

2012-01-01

Full Text Available Blindness is a serious public health problem. In Brazil, it is estimated that there are 1 million 100 thousandblind and about four million visually impaired, 80% of blindness in the world are predictable causes and / or treatable.Considering the epidemiological importance of eye diseases and magnitude of blindness in Brazil, saw the need for aliterature review in order to understand the problem for future interventions. The survey results showed that: the maincauses of blindness are diabetic retinopathy, macular degeneration, cataracts, glaucoma, and an alarming number ofchildhood blindness due to various causes, the progressive increase of blindness is attributed to several factors, inparticular, the lack eye care, lack of infrastructure, organization, financial resources, which are aggravated by poverty,misinformation, inequality of the population and the absence / lack of educational efforts, despite the alarming statisticsand the gradual increase in blindness, has no effective measure to control it. The model of care in ophthalmologycurative until then, highlights the need for urgent action to ensure eye care in primary health care, thus allowing toensure the completeness, quality, equity in service of disease prevention, promotion, recovery and rehabilitation of eyehealth .

Modelling the increased frequency of extreme sea levels in the Ganges-Brahmaputra-Meghna delta due to sea level rise and other effects of climate change.

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Kay, S; Caesar, J; Wolf, J; Bricheno, L; Nicholls, R J; Saiful Islam, A K M; Haque, A; Pardaens, A; Lowe, J A

2015-07-01

Coastal flooding due to storm surge and high tides is a serious risk for inhabitants of the Ganges-Brahmaputra-Meghna (GBM) delta, as much of the land is close to sea level. Climate change could lead to large areas of land being subject to increased flooding, salinization and ultimate abandonment in West Bengal, India, and Bangladesh. IPCC 5th assessment modelling of sea level rise and estimates of subsidence rates from the EU IMPACT2C project suggest that sea level in the GBM delta region may rise by 0.63 to 0.88 m by 2090, with some studies suggesting this could be up to 0.5 m higher if potential substantial melting of the West Antarctic ice sheet is included. These sea level rise scenarios lead to increased frequency of high water coastal events. Any effect of climate change on the frequency and severity of storms can also have an effect on extreme sea levels. A shelf-sea model of the Bay of Bengal has been used to investigate how the combined effect of sea level rise and changes in other environmental conditions under climate change may alter the frequency of extreme sea level events for the period 1971 to 2099. The model was forced using atmospheric and oceanic boundary conditions derived from climate model projections and the future scenario increase in sea level was applied at its ocean boundary. The model results show an increased likelihood of extreme sea level events through the 21st century, with the frequency of events increasing greatly in the second half of the century: water levels that occurred at decadal time intervals under present-day model conditions occurred in most years by the middle of the 21st century and 3-15 times per year by 2100. The heights of the most extreme events tend to increase more in the first half of the century than the second. The modelled scenarios provide a case study of how sea level rise and other effects of climate change may combine to produce a greatly increased threat to life and property in the GBM delta by the end

Comparing Canadian and American cybersecurity awareness levels: Educational strategies to increase public awareness

Science.gov (United States)

Hoggard, Amy

Cybersecurity awareness is an important issue that affects everyone who uses a computer or a mobile device. Canada and the United States both recognize the value of mitigating cybersecurity risks in terms of national safety, economic stability and protection of their citizens. The research performed compared the levels of cybersecurity awareness in Canadian and American Internet users. Canadian and American users were equally aware of cybersecurity measures, but were not implementing best practices to keep themselves safe. The research suggested users needed to understand why a cybersecurity measure was important before being motivated to implement it. Educational strategies were reviewed in both Canada and the United States and it was determined that although there were significant resources available, they were not being utilized by both the educators and the public. In order to increase cybersecurity awareness levels, nations should focus on increasing the public's awareness by using various types of messaging, such as cartoons, in media. One possible consideration is a compulsory awareness model before accessing the Internet. Cybersecurity topics should be included in the curriculum for students at all levels of education and a focus on providing training and resources to teachers will help increase the cybersecurity knowledge of children and youth.

Beneficial effects of hydrogen-rich saline on early burn-wound progression in rats.

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Song Xue Guo

Full Text Available Deep burn wounds undergo a dynamic process known as wound progression that results in a deepening and extension of the initial burn area. The zone of stasis is more likely to develop more severe during wound progression in the presence of hypoperfusion. Hydrogen has been reported to alleviate injury triggered by ischaemia/reperfusion and burns in various organs by selectively quenching oxygen free radicals. The aim of this study was to investigate the possible protective effects of hydrogen against early burn-wound progression.Deep-burn models were established through contact with a boiled, rectangular, brass comb for 20 s. Fifty-six Sprague-Dawley rats were randomly divided into sham, burn plus saline, and burn plus hydrogen-rich saline (HS groups with sacrifice and analysis at various time windows (6 h, 24 h, 48 h post burn. Indexes of oxidative stress, apoptosis and autophagy were measured in each group. The zone of stasis was evaluated using immunofluorescence staining, ELISA, and Western blot to explore the underlying effects and mechanisms post burn.The burn-induced increase in malondialdehyde was markedly reduced with HS, while the activities of endogenous antioxidant enzymes were significantly increased. Moreover, HS treatment attenuated increases in apoptosis and autophagy postburn in wounds, according to the TUNEL staining results and the expression analysis of Bax, Bcl-2, caspase-3, Beclin-1 and Atg-5 proteins. Additionally, HS lowered the level of myeloperoxidase and expression of TNF-α, IL-1β, and IL-6 in the zone of stasis while augmenting IL-10. The elevated levels of Akt phosphorylation and NF-κB p65 expression post burn were also downregulated by HS management.Hydrogen can attenuate early wound progression following deep burn injury. The beneficial effect of hydrogen was mediated by attenuating oxidative stress, which inhibited apoptosis and inflammation, and the Akt/NF-κB signalling pathway may be involved in regulating the

Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression in mice.

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Gu, Jian-Wei; Young, Emily; Patterson, Sharla G; Makey, Kristina L; Wells, Jeremy; Huang, Min; Tucker, Kevan B; Miele, Lucio

2011-05-15

Obese postmenopausal women have a 50% higher risk of breast cancer than non-obese women. There is not an animal model that mimics postmenopausal obesity related to breast cancer progression. Using age-relevant C57BL/6 mice, this study determined whether postmenopausal obesity increases VEGF expression, tumor angiogenesis, and breast tumor growth. Ovariectomy (OVX) was performed in 12 sixty week-old female mice, then followed by a low-fat (5%, LF, n=6) or a high-fat (60%, HF, n=6) diet for 12 weeks. In the eighth week of the dietary program, 10(6) E0771 (mouse breast cancer) cells were injected in the left fourth mammary gland. Tumor size was monitored for 4 weeks. Body weights were monitored weekly. At the end of the experiment, blood samples, visceral fat and tumors were collected for measuring VEGF expression using ELISA and intratumoral microvessel density (IMD) using CD31 immunochemistry. Body weight was significantly increased in OVX/HF mice, compared to OVX/LF group (55.3±1.7 vs. 41.5±1.5 g; p < 0.01). There was a two-fold increase in the ratio of visceral fat/BW in OVX/HF mice, compared to those in OVX/LF group (0.062±0.005 vs. 0.032±0.003; p < 0.01). Postmenopausal obesity significantly increased breast tumor weight over the control (4.62±0.63 vs. 1.98±0.27 g; p < 0.01) and IMD (173±3.7 vs. 139±4.3 IM#/mm^2; p < 0.01). Tumor VEGF levels were higher in OVX/HF mice, compared to OVX/LF group (73.3±3.8 vs. 49.5±4.3 pg/mg protein; p < 0.01). Plasma VEGF levels (69±7.1 vs. 48±3.5 pg/ml) and visceral fat VEGF levels (424.4±39.5 vs. 208.5±22.4 pg/mg protein) were significantly increased in OVX/HF mice, compared to OVX/LF group, respectively (n=6; p < 0.01). Interestingly, adipose tissue primary culture showed that subcutaneous fat released more VEGF, compared to visceral fat (6.77±1.14 vs. 0.94±0.16 pg/mg tissue; n=6; p < 0.01). These findings support the hypothesis that postmenopausal obesity promotes tumor angiogenesis and breast cancer

Effect of fluoxetine on disease progression in a mouse model of ALS

Science.gov (United States)

Koschnitzky, J. E.; Quinlan, K. A.; Lukas, T. J.; Kajtaz, E.; Kocevar, E. J.; Mayers, W. F.; Siddique, T.

2014-01-01

Selective serotonin reuptake inhibitors (SSRIs) and other antidepressants are often prescribed to amyotrophic lateral sclerosis (ALS) patients; however, the impact of these prescriptions on ALS disease progression has not been systematically tested. To determine whether SSRIs impact disease progression, fluoxetine (Prozac, 5 or 10 mg/kg) was administered to mutant superoxide dismutase 1 (SOD1) mice during one of three age ranges: neonatal [postnatal day (P)5–11], adult presymptomatic (P30 to end stage), and adult symptomatic (P70 to end stage). Long-term adult fluoxetine treatment (started at either P30 or P70 and continuing until end stage) had no significant effect on disease progression. In contrast, neonatal fluoxetine treatment (P5-11) had two effects. First, all animals (mutant SOD1G93A and control: nontransgenic and SOD1WT) receiving the highest dose (10 mg/kg) had a sustained decrease in weight from P30 onward. Second, the high-dose SOD1G93A mice reached end stage ∼8 days (∼6% decrease in life span) sooner than vehicle and low-dose animals because of an increased rate of motor impairment. Fluoxetine increases synaptic serotonin (5-HT) levels, which is known to increase spinal motoneuron excitability. We confirmed that 5-HT increases spinal motoneuron excitability during this neonatal time period and therefore hypothesized that antagonizing 5-HT receptors during the same time period would improve disease outcome. However, cyproheptadine (1 or 5 mg/kg), a 5-HT receptor antagonist, had no effect on disease progression. These results show that a brief period of antidepressant treatment during a critical time window (the transition from neonatal to juvenile states) can be detrimental in ALS mouse models. PMID:24598527

Once-weekly 22microg subcutaneous IFN-beta-1a in secondary progressive MS: a 3-year follow-up study on brain MRI measurements and serum MMP-9 levels

DEFF Research Database (Denmark)

Wu, X; Kuusisto, H; Dastidar, P

2007-01-01

: There was no obvious effect on the number of contrast medium-enhancing lesions, the volume of T1 or T2 lesions or level of serum MMP-9, nor was any effect detected on the relapse rate and the Expanded Disability Status Scale (EDSS). Brain atrophy progression was not affected by the treatment. CONCLUSION: The lack......OBJECTIVE: To study the effect of weekly injected subcutaneous interferon (IFN)-beta-1a 22 microg on the extent of brain lesions on magnetic resonance imaging (MRI) and the level of serum matrix metalloproteinase (MMP)-9 in patients with secondary progressive multiple sclerosis (SPMS). SUBJECTS...... of effect on MRI, clinical outcomes or the levels of MMP-9 indicates that subcutaneous administration of low-dose low-frequency IFN-beta-1a is insufficient in controlling either the inflammatory constitutes or the neurodegenerative changes of advanced SPMS. Udgivelsesdato: 2007-Jul...

Superpulsed low-level laser therapy protects skeletal muscle of mdx mice against damage, inflammation and morphological changes delaying dystrophy progression.

Science.gov (United States)

Leal-Junior, Ernesto Cesar Pinto; de Almeida, Patrícia; Tomazoni, Shaiane Silva; de Carvalho, Paulo de Tarso Camillo; Lopes-Martins, Rodrigo Álvaro Brandão; Frigo, Lucio; Joensen, Jon; Johnson, Mark I; Bjordal, Jan Magnus

2014-01-01

To evaluate the effects of preventive treatment with low-level laser therapy (LLLT) on progression of dystrophy in mdx mice. Ten animals were randomly divided into 2 experimental groups treated with superpulsed LLLT (904 nm, 15 mW, 700 Hz, 1 J) or placebo-LLLT at one point overlying the tibialis anterior muscle (bilaterally) 5 times per week for 14 weeks (from 6th to 20th week of age). Morphological changes, creatine kinase (CK) activity and mRNA gene expression were assessed in animals at 20th week of age. Animals treated with LLLT showed very few morphological changes in skeletal muscle, with less atrophy and fibrosis than animals treated with placebo-LLLT. CK was significantly lower (p=0.0203) in animals treated with LLLT (864.70 U.l-1, SEM 226.10) than placebo (1708.00 U.l-1, SEM 184.60). mRNA gene expression of inflammatory markers was significantly decreased by treatment with LLLT (pmuscle damage and inflammation in mdx mice. This indicates that LLLT has potential to decrease progression of Duchenne muscular dystrophy.

Autism and increased paternal age related changes in global levels of gene expression regulation.

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Mark D Alter

2011-02-01

Full Text Available A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL of children with autism (n = 82 and controls (n = 64. Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other

Fed levels of amino acids are required for the somatotropin-induced increase in muscle protein synthesis.

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Wilson, Fiona A; Suryawan, Agus; Orellana, Renán A; Nguyen, Hanh V; Jeyapalan, Asumthia S; Gazzaneo, Maria C; Davis, Teresa A

2008-10-01

Chronic somatotropin (pST) treatment in pigs increases muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin could not account for the pST-induced increase in muscle protein synthesis when amino acids were maintained at fasting levels. This study aimed to determine whether the pST-induced increase in insulin promotes skeletal muscle protein synthesis when amino acids are provided at fed levels and whether the response is associated with enhanced translation initiation factor activation. Growing pigs were treated with pST (0 or 180 microg x kg(-1) x day(-1)) for 7 days, and then pancreatic-glucose-amino acid clamps were performed. Amino acids were raised to fed levels in the presence of either fasted or fed insulin concentrations; glucose was maintained at fasting throughout. Muscle protein synthesis was increased by pST treatment and by amino acids (with or without insulin) (P<0.001). In pST-treated pigs, fed, but not fasting, amino acid concentrations further increased muscle protein synthesis rates irrespective of insulin level (P<0.02). Fed amino acids, with or without raised insulin concentrations, increased the phosphorylation of S6 kinase (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1), decreased inactive 4EBP1.eIF4E complex association, and increased active eIF4E.eIF4G complex formation (P<0.02). pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of muscle protein synthesis requires fed amino acid levels, but not fed insulin levels. However, under the current conditions, the response to amino acids is not mediated by the activation of translation initiation factors that regulate mRNA binding to the ribosomal complex.

Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis.

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Petra Steinacker

Full Text Available BACKGROUND: Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPα and sAPPß correlated with clinical subtypes of ALS and were of prognostic value. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study including patients with ALS (N = 68 with clinical follow-up data over 6 months, Parkinson's disease (PD, N = 20, and age-matched controls (N = 40, cerebrospinal fluid (CSF levels of sAPPα a, sAPPß and neurofilaments (NfH(SMI35 were measured by multiplex assay, Progranulin by ELISA. CSF sAPPα and sAPPß levels were lower in ALS with a rapidly-progressive disease course (p = 0.03, and p = 0.02 and with longer disease duration (p = 0.01 and p = 0.01, respectively. CSF NfH(SMI35 was elevated in ALS compared to PD and controls, with highest concentrations found in patients with rapid disease progression (p<0.01. High CSF NfH(SMI3 was linked to low CSF sAPPα and sAPPß (p = 0.001, and p = 0.007, respectively. The ratios CSF NfH(SMI35/CSF sAPPα,-ß were elevated in patients with fast progression of disease (p = 0.002 each. CSF Progranulin decreased with ongoing disease (p = 0.04. CONCLUSIONS: This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggest that a deficiency of cellular neuroprotective mechanisms (decrease of sAPP is linked to progressive neuro-axonal damage (increase of NfH(SMI35 and to progression of disease.

Prospects for reconciling the conflict between economic growth and biodiversity conservation with technological progress.

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Czech, Brian

2008-12-01

The conflict between economic growth and biodiversity conservation is understood in portions of academia and sometimes acknowledged in political circles. Nevertheless, there is not a unified response. In political and policy circles, the environmental Kuznets curve (EKC) is posited to solve the conflict between economic growth and environmental protection. In academia, however, the EKC has been deemed fallacious in macroeconomic scenarios and largely irrelevant to biodiversity. A more compelling response to the conflict is that it may be resolved with technological progress. Herein I review the conflict between economic growth and biodiversity conservation in the absence of technological progress, explore the prospects for technological progress to reconcile that conflict, and provide linguistic suggestions for describing the relationships among economic growth, technological progress, and biodiversity conservation. The conflict between economic growth and biodiversity conservation is based on the first two laws of thermodynamics and principles of ecology such as trophic levels and competitive exclusion. In this biophysical context, the human economy grows at the competitive exclusion of nonhuman species in the aggregate. Reconciling the conflict via technological progress has not occurred and is infeasible because of the tight linkage between technological progress and economic growth at current levels of technology. Surplus production in existing economic sectors is required for conducting the research and development necessary for bringing new technologies to market. Technological regimes also reflect macroeconomic goals, and if the goal is economic growth, reconciliatory technologies are less likely to be developed. As the economy grows, the loss of biodiversity may be partly mitigated with end-use innovation that increases technical efficiency, but this type of technological progress requires policies that are unlikely if the conflict between economic growth

A Forest Tent Caterpillar Outbreak Increased Resource Levels and Seedling Growth in a Northern Hardwood Forest.

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Danaë M A Rozendaal

Full Text Available In closed-canopy forests, gap formation and closure are thought to be major drivers of forest dynamics. Crown defoliation by insects, however, may also influence understory resource levels and thus forest dynamics. We evaluate the effect of a forest tent caterpillar outbreak on understory light availability, soil nutrient levels and tree seedling height growth in six sites with contrasting levels of canopy defoliation in a hardwood forest in northern lower Michigan. We compared resource levels and seedling growth of six hardwood species before, during and in the three years after the outbreak (2008-2012. Canopy openness increased strongly during the forest tent caterpillar outbreak in the four moderately and severely defoliated sites, but not in lightly defoliated sites. Total inorganic soil nitrogen concentrations increased in response to the outbreak in moderately and severely defoliated sites. The increase in total inorganic soil nitrogen was driven by a strong increase in soil nitrate, and tended to become stronger with increasing site defoliation. Seedling height growth increased for all species in the moderately and severely defoliated sites, but not in lightly defoliated sites, either during the outbreak year or in the year after the outbreak. Growth increases did not become stronger with increasing site defoliation, but were strongest in a moderately defoliated site with high soil nutrient levels. Growth increases tended to be strongest for the shade intolerant species Fraxinus americana and Prunus serotina, and the shade tolerant species Ostrya virginiana. The strong growth response of F. americana and P. serotina suggests that recurring forest tent caterpillar outbreaks may facilitate the persistence of shade intolerant species in the understory in the absence of canopy gaps. Overall, our results suggest that recurrent canopy defoliation resulting from cyclical forest insect outbreaks may be an additional driver of dynamics in

A Forest Tent Caterpillar Outbreak Increased Resource Levels and Seedling Growth in a Northern Hardwood Forest.

Science.gov (United States)

Rozendaal, Danaë M A; Kobe, Richard K

2016-01-01

In closed-canopy forests, gap formation and closure are thought to be major drivers of forest dynamics. Crown defoliation by insects, however, may also influence understory resource levels and thus forest dynamics. We evaluate the effect of a forest tent caterpillar outbreak on understory light availability, soil nutrient levels and tree seedling height growth in six sites with contrasting levels of canopy defoliation in a hardwood forest in northern lower Michigan. We compared resource levels and seedling growth of six hardwood species before, during and in the three years after the outbreak (2008-2012). Canopy openness increased strongly during the forest tent caterpillar outbreak in the four moderately and severely defoliated sites, but not in lightly defoliated sites. Total inorganic soil nitrogen concentrations increased in response to the outbreak in moderately and severely defoliated sites. The increase in total inorganic soil nitrogen was driven by a strong increase in soil nitrate, and tended to become stronger with increasing site defoliation. Seedling height growth increased for all species in the moderately and severely defoliated sites, but not in lightly defoliated sites, either during the outbreak year or in the year after the outbreak. Growth increases did not become stronger with increasing site defoliation, but were strongest in a moderately defoliated site with high soil nutrient levels. Growth increases tended to be strongest for the shade intolerant species Fraxinus americana and Prunus serotina, and the shade tolerant species Ostrya virginiana. The strong growth response of F. americana and P. serotina suggests that recurring forest tent caterpillar outbreaks may facilitate the persistence of shade intolerant species in the understory in the absence of canopy gaps. Overall, our results suggest that recurrent canopy defoliation resulting from cyclical forest insect outbreaks may be an additional driver of dynamics in temperate closed

Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.

Science.gov (United States)

Zampieri, Sandra; Mammucari, Cristina; Romanello, Vanina; Barberi, Laura; Pietrangelo, Laura; Fusella, Aurora; Mosole, Simone; Gherardi, Gaia; Höfer, Christian; Löfler, Stefan; Sarabon, Nejc; Cvecka, Jan; Krenn, Matthias; Carraro, Ugo; Kern, Helmut; Protasi, Feliciano; Musarò, Antonio; Sandri, Marco; Rizzuto, Rosario

2016-12-01

Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca 2+ homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU-dependent mitochondrial Ca 2+ uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70-year-old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES-trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES-dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial-related proteins involved in Ca 2+ homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria-related proteins as potential pharmacological targets to counteract age-related muscle loss. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Chronic lithium treatment increased intracellular S100ß levels in rat primary neuronal culture.

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Masoumeh Emamghoreishi

2015-02-01

Full Text Available S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100β in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM or vehicle for 1day (acute or 7 days (chronic. RT-PCR and ELISA determined S100β mRNA and intra- and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100β in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05. Acute and chronic lithium treatments exerted no significant effects on intracellular S100β protein levels in astrocytes, and extracellular S100β protein levels in three studied cultures as compared to control cultures. Acute and chronic lithium treatments did not significantly alter S100β mRNA levels in three studied cultures, compared to control cultures. Chronic lithium treatment increased intracellular S100ß protein levels in a cell-type specific manner which may favor its neuroprotective action. The findings of this study suggest that lithium may exert its neuroprotective action, at least partly, by increasing neuronal S100ß level, with no effect on astrocytes or interaction between neurons and astrocytes.

Primary progressive aphasia and apraxia of speech.

Science.gov (United States)

Jung, Youngsin; Duffy, Joseph R; Josephs, Keith A

2013-09-01

Primary progressive aphasia is a neurodegenerative syndrome characterized by progressive language dysfunction. The majority of primary progressive aphasia cases can be classified into three subtypes: nonfluent/agrammatic, semantic, and logopenic variants. Each variant presents with unique clinical features, and is associated with distinctive underlying pathology and neuroimaging findings. Unlike primary progressive aphasia, apraxia of speech is a disorder that involves inaccurate production of sounds secondary to impaired planning or programming of speech movements. Primary progressive apraxia of speech is a neurodegenerative form of apraxia of speech, and it should be distinguished from primary progressive aphasia given its discrete clinicopathological presentation. Recently, there have been substantial advances in our understanding of these speech and language disorders. The clinical, neuroimaging, and histopathological features of primary progressive aphasia and apraxia of speech are reviewed in this article. The distinctions among these disorders for accurate diagnosis are increasingly important from a prognostic and therapeutic standpoint. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Mixing processes in high-level waste tanks. 1998 annual progress report

International Nuclear Information System (INIS)

Peterson, P.F.

1998-01-01

Flammable gases can be generated in DOE high-level waste tanks, including radiolytic hydrogen, and during cesium precipitation from salt solutions, benzene. Under normal operating conditions the potential for deflagration or detonation from these gases is precluded by purging and ventilation systems, which remove the flammable gases and maintain a well-mixed condition in the tanks. Upon failure of the ventilation system, due to seismic or other events, however, it has proven more difficult to make strong arguments for well-mixed conditions, due to the potential for density-induced stratification which can potentially sequester fuel or oxidizer at concentrations significantly higher than average. This has complicated the task of defining the safety basis for tank operation. Waste-tank mixing processes have considerable overlap with similar large-enclosure mixing processes that occur in enclosure fires and nuclear reactor containments. Significant differences also exist, so that modeling techniques that have been developed previously can not be directly applied to waste tanks. In particular, mixing of air introduced through tank roof penetrations by buoyancy and pressure driven exchange flows, mixed convection induced by an injected high-velocity purge jet interacting with buoyancy driven flow, and onset and breakdown of stable stratification under the influence of an injected jet have not been adequately studied but are important in assessing the potential for accumulation of high-concentration pockets of fuel and oxygen. Treating these phenomena requires a combination of experiments and the development of new, more general computational models than those that have been developed for enclosure fires. U.C. Berkeley is now completing the second year of its three-year project that started in September, 1996. Excellent progress has been made in several important areas related to waste-tank ventilation and mixing processes.'

On the increase of predictive performance with high-level data fusion

International Nuclear Information System (INIS)

Doeswijk, T.G.; Smilde, A.K.; Hageman, J.A.; Westerhuis, J.A.; Eeuwijk, F.A. van

2011-01-01

The combination of the different data sources for classification purposes, also called data fusion, can be done at different levels: low-level, i.e. concatenating data matrices, medium-level, i.e. concatenating data matrices after feature selection and high-level, i.e. combining model outputs. In this paper the predictive performance of high-level data fusion is investigated. Partial least squares is used on each of the data sets and dummy variables representing the classes are used as response variables. Based on the estimated responses y-hat j for data set j and class k, a Gaussian distribution p(g k |y-hat j ) is fitted. A simulation study is performed that shows the theoretical performance of high-level data fusion for two classes and two data sets. Within group correlations of the predicted responses of the two models and differences between the predictive ability of each of the separate models and the fused models are studied. Results show that the error rate is always less than or equal to the best performing subset and can theoretically approach zero. Negative within group correlations always improve the predictive performance. However, if the data sets have a joint basis, as with metabolomics data, this is not likely to happen. For equally performing individual classifiers the best results are expected for small within group correlations. Fusion of a non-predictive classifier with a classifier that exhibits discriminative ability lead to increased predictive performance if the within group correlations are strong. An example with real life data shows the applicability of the simulation results.

Monitoring Progression of Amyotrophic Lateral Sclerosis Using Ultrasound Morpho-Textural Muscle Biomarkers: A Pilot Study.

Science.gov (United States)

Martínez-Payá, Jacinto J; Ríos-Díaz, José; Medina-Mirapeix, Francesc; Vázquez-Costa, Juan F; Del Baño-Aledo, María Elena

2018-01-01

The need is increasing for progression biomarkers that allow the loss of motor neurons in amyotrophic lateral sclerosis (ALS) to be monitored in clinical trials. In this prospective longitudinal study, muscle thickness, echointensity, echovariation and gray level co-occurrence matrix textural features are examined as possible progression ultrasound biomarkers in ALS patients during a 5-mo follow-up period. We subjected 13 patients to 3 measurements for 20 wk. They showed a significant loss of muscle, an evident tendency to loss of thickness and increased echointensity and echovariation. In regard to textural parameters, muscle heterogeneity tended to increase as a result of the neoformation of non-contractile tissue through denervation. Considering some limitations of the study, the quantitative muscle ultrasound biomarkers evaluated showed a promising ability to monitor patients affected by ALS. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Toxoplasma gondii infection specifically increases the levels of key host microRNAs.

Directory of Open Access Journals (Sweden)

Gusti M Zeiner

2010-01-01

Full Text Available The apicomplexan parasite Toxoplasma gondii can infect and replicate in virtually any nucleated cell in many species of warm-blooded animals; thus, it has evolved the ability to exploit well-conserved biological processes common to its diverse hosts. Here we have investigated whether Toxoplasma modulates the levels of host microRNAs (miRNAs during infection.Using microarray profiling and a combination of conventional molecular approaches we report that Toxoplasma specifically modulates the expression of important host microRNAs during infection. We show that both the primary transcripts for miR-17 approximately 92 and miR-106b approximately 25 and the pivotal miRNAs that are derived from miR-17 approximately 92 display increased abundance in Toxoplasma-infected primary human cells; a Toxoplasma-dependent up-regulation of the miR-17 approximately 92 promoter is at least partly responsible for this increase. The abundance of mature miR-17 family members, which are derived from these two miRNA clusters, remains unchanged in host cells infected with the closely related apicomplexan Neospora caninum; thus, the Toxoplasma-induced increase in their abundance is a highly directed process rather than a general host response to infection.Altered levels of miR-17 approximately 92 and miR-106b approximately 25 are known to play crucial roles in mammalian cell regulation and have been implicated in numerous hyperproliferative diseases although the mechanisms driving their altered expression are unknown. Hence, in addition to the implications of these findings on the host-pathogen interaction, Toxoplasma may represent a powerful probe for understanding the normal mechanisms that regulate the levels of key host miRNAs.

Increased abdominal fat levels measured by bioelectrical impedance are associated with histological lesions of nonalcoholic steatohepatitis.

Science.gov (United States)

Margariti, Aikaterini; Kontogianni, Meropi D; Tileli, Nafsika; Georgoulis, Michael; Deutsch, Melanie; Zafeiropoulou, Rodessa; Tiniakos, Dina; Manios, Yannis; Pectasides, Dimitrios; Papatheodoridis, George V

2015-08-01

Abdominal fat is considered to play an important role in nonalcoholic fatty liver disease (NAFLD), although it is not adequately studied because abdominal fat levels cannot be estimated easily. In this study, associations between abdominal obesity, as assessed by abdominal bioelectrical impedance analysis (BIA), and the characteristics of patients with NAFLD were explored. Seventy-four consecutive NAFLD patients who underwent measurement of abdominal fat levels by BIA were included. Levels of abdominal fat 12.5 or less and more than 12.5 were considered to be average and increased, respectively. The mean±SD BMI was 30±4 kg/m and the mean abdominal fat levels were 16±5, whereas 26% of patients had average abdominal fat levels. Patients with average compared with those with increased abdominal fat levels were more frequently women (50 vs. 12%, P=0.001), had lower BMI (27±3 vs. 31±4 kg/m, Pabdominal fat levels (78 vs. 38%, P=0.030) and in patients with BMI 30 or more compared with less than 30 kg/m (87 vs. 48%, P=0.033), but similar in patients with increased or normal waist circumference (67 vs. 56%, P=0.693). Average levels of abdominal fat, as assessed by abdominal BIA, are mainly present in female patients with NAFLD and are associated with a lower degree of insulin resistance. Increased abdominal fat as assessed by BIA and obesity seem to represent strong risk factors for histological steatohepatitis.

Risk factors for the progression of periodontal disease in a Greek adult population.

Science.gov (United States)

Chrysanthakopoulos, Nikolaos A

2017-05-01

The purpose of the present study was to investigate the progression risk factors of periodontal disease by individual characteristics at baseline in a Greek adult population. The study sample consisted of 854 individuals. All participants were clinically examined and answered questions regarding sex, smoking status, socioeconomic status, low educational level, frequency of dental follow up, and oral hygiene habits. Serum levels of disease markers were investigated, and attachment levels were clinically recorded. For the assessment of periodontal disease progression, additional clinical attachment loss (CAL) was used if one or more sites showed a 3 mm or more increase in probing attachment level over a 2-year period. Statistical analysis was performed by using a modified multiple Poisson's analysis model. A total of 74% of the participants exhibited additional CAL over a 2-year period. Significant associations were observed between additional CAL and smoking (relative risk [RR] = 0.78, 95% confidence level [CI] = 0.65-0.92), attachment level of 5 mm or more at baseline (RR = 0.89, 95% CI = 0.75-1.05), educational level (RR = 0.90, 95% CI = 0.76-1.07), socioeconomic status (RR = 0.86, 95% CI = 0.59-1.14), and irregular dental follow up (RR = 1.23, 95% CI = 1.04-1.45). Smoking, baseline attachment level of 5 mm or more, low educational level, low socioeconomic status, and irregular dental follow up could be considered risk factors for further CAL. © 2015 Wiley Publishing Asia Pty Ltd.

Heparin-induced increase in serum levels of aminotranferases. A controlled clinical trial.

Science.gov (United States)

Nielsen, H K; Husted, S E; Koopmann, H D; Fasting, H; Simonsen, O; Andersen, K; Husegaard, H C; Petersen, T K

1984-01-01

Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.

Music stimuli lead to increased levels of nitrite in unstimulated mixed saliva.

Science.gov (United States)

Jin, Luyuan; Zhang, Mengbi; Xu, Junji; Xia, Dengsheng; Zhang, Chunmei; Wang, Jingsong; Wang, Songlin

2018-06-15

Concentration of salivary nitrate is approximately 10-fold to that of serum. Many circumstances such as acute stress could promote salivary nitrate secretion and nitrite formation. However, whether other conditions can also be used as regulators of salivary nitrate/nitrite has not yet been explored. The present study was designed to determine the influence of exposure to different music on the salivary flow rate and nitrate secretion and nitrite formation. Twenty-four undergraduate students (12 females and 12 males) were exposed to silence, rock music, classical music or white noise respectively on four consecutive mornings. The unstimulated salivary flow rate and stimulated salivary flow rate were measured. Salivary ionic (Na + , Ca 2+ Cl - , and PO 4 3- ) content and nitrate/nitrite levels were detected. The unstimulated salivary flow rate was significantly increased after classical music exposure compared to that after silence. Salivary nitrite levels were significantly higher upon classical music and white noise stimulation than those under silence in females. However, males were more sensitive only to white noise with regard to the nitrite increase. In conclusion, this study demonstrated that classical music stimulation promotes salivary nitrite formation and an increase in saliva volume was observed. These observations may play an important role in regulating oral function.

Taking stock of Myanmar's progress toward the health-related Millennium Development Goals: current roadblocks, paths ahead.

Science.gov (United States)

Saw, Yu Mon; Win, Khine Lae; Shiao, Laura Wen-Shuan; Thandar, Moe Moe; Amiya, Rachel M; Shibanuma, Akira; Tun, Soe; Jimba, Masamine

2013-09-11

Myanmar is a developing country with considerable humanitarian needs, rendering its pursuit of the Millennium Development Goals (MDGs) an especially high priority. Yet progress to date remains under-examined on key fronts. Particularly within the three health-related MDGs (MDGs 4, 5, and 6), the limited data reported point to patchy levels of achievement. This study was undertaken to provide an overview and assessment of Myanmar's progress toward the health-related MDGs, along with possible solutions for accelerating health-related development into 2015 and beyond. The review highlights off-track progress in the spheres of maternal and child health (MDGs 4 and 5). It also shows Myanmar's achievements toward MDG 6 targets--in the areas of HIV/AIDS, malaria, and tuberculosis. Such achievements are especially notable in that Myanmar has been receiving the lowest level of official development assistance among all of the least developed countries in Asia. However, to make similar progress in MDGs 4 and 5, Myanmar needs increased investment and commitment in health. Toward moving forward with the post-2015 development agenda, Myanmar's government also needs to take the lead in calling for attention from the World Health Organization and its global development partners to address the stagnation in health-related development progress within the country. In particular, Myanmar's government should invest greater efforts into health system strengthening to pave the road to universal health coverage.

Decreased serum level of HMGB1 and MyD88 during human aging progress in healthy individuals.

Science.gov (United States)

Fu, Guo-Xiang; Chen, Alex F; Zhong, Yuan; Zhao, Jian; Gu, Ying-Jia

2016-04-01

Previous studies have suggested that high mobility group box-1 protein (HMGB1) binds to the toll-like receptor 4 (TLR4) signaling mediates the progression of various inflammatory diseases. But the roles of HMGB1 and TLR4 in aging remain poorly unknown. In this study, we aimed to investigate the serum levels of HMGB1 and myeloid differentiation factor 88 (MyD88), which is one of TLR4's intracellular adaptor proteins during human aging process and their relevance with cathepsin B (CTSB). This research was conducted using the blood samples provided by healthy people (n = 90, 63 men and 27 women). Subjects were subdivided into groups with respect to age: young (about 25 years old, n = 30), middle age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of HMGB1, MyD88 and CTSB were measured using an enzyme-linked immunosorbent assay. The serum levels of HMGB1 and MyD88 were significantly decreased in the aged group compared with those in the young group. Linear regression analysis showed that HMGB1 and MyD88 positively correlated with CTSB among the whole healthy people. A negative correlation was determined between MyD88 and age. The serum levels of HMGB1 and MyD88 significantly decreased with age. MyD88, but not HMGB1, was negatively correlated with age.

Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression

DEFF Research Database (Denmark)

Wang, Qian; Bailey, Charles G; Ng, Cynthia

2011-01-01

was sufficient to decrease cell growth and mTORC1 signaling in prostate cancer cells. These cells maintained levels of amino acid influx through androgen receptor-mediated regulation of LAT3 expression and ATF4 regulation of LAT1 expression after amino acid deprivation. These responses remained intact in primary......L-Type amino acid transporters such as LAT1 and LAT3 mediate the uptake of essential amino acids. Here, we report that prostate cancer cells coordinate the expression of LAT1 and LAT3 to maintain sufficient levels of leucine needed for mTORC1 signaling and cell growth. Inhibiting LAT function...... prostate cancer, as indicated by high levels of LAT3 in primary disease, and by increased levels of LAT1 after hormone ablation and in metastatic lesions. Taken together, our results show how prostate cancer cells respond to demands for increased essential amino acids by coordinately activating amino acid...

Technical reliability of geological disposal for high-level radioactive wastes in Japan. The second progress report. Part 3. Safety assessment for geological disposal systems

International Nuclear Information System (INIS)

1999-11-01

Based on the Advisory Committee Report on Nuclear Fuel Cycle Backend Policy submitted to the Japanese Government in 1997, JNC documents the progress of research and development program in the form of the second progress report (the first one published in 1992). It summarizes an evaluation of the technical reliability and safety of the geological disposal concept for high-level radioactive wastes (HLW) in Japan. The present document, the part 3 of the progress report, concerns safety assessment for geological disposal systems definitely introduced in part 1 and 2 of this series and consists of 9 chapters. Chapter I concerns the methodology for safety assessment while Chapter II deals with diversity and uncertainty about the scenario, the adequate model and the required data of the systems above. Chapter III summarizes the components of the geological disposal system. Chapter IV refers to the relationship between radioactive wastes and human life through groundwater, i.e. nuclide migration. In Chapter V is made a reference case which characterizes the geological environmental data using artificial barrier specifications. (Ohno. S.)

Increasing Safety and Reducing Environmental Damage Risk from Aging High-Level Radioactive Waste Tanks - 2005 Report

International Nuclear Information System (INIS)

Eric D. Steffler; Eric D. Steffler; Mark M. Rashid; Frank A. McClintock; Richard L Williamson; Mili Selimotic

2005-01-01

Cracks of various shapes and sizes exist in large high-level waste (HLW) tanks at several DOE sites. There is justifiable concern that these cracks could grow to become unstable causing a substantial release of liquid contaminants to the environment. Accurate prediction of crack growth behavior in the tanks, especially during accident scenarios, is not possible with existing analysis methodologies. This research project responds to this problem by developing an improved ability to predict crack growth in material-structure combinations that are ductile. This new model not only addresses the problem for these tanks, but also has applicability to any crack in any ductile structure. This report summarizes work progress through the fourth quarter of FY-05 (year 1 of a second 3-year funding period)

A progressive methodology for seismic safety evaluation of gravity dams

International Nuclear Information System (INIS)

Ghrib, F.; Leger, P.; Tinawi, R.; Lupien, R.; Veilleux, M.

1995-01-01

A progressive methodology for the seismic safety evaluation of existing concrete gravity dams was described. The methodology was based on five structural analysis levels with increasing complexity to represent inertia forces, dam-foundation and dam-interaction mechanisms, as well as concrete cracking. The five levels were (1) preliminary screening, (2) pseudo-static method, (3) pseudo-dynamic method, (4) linear time history analysis, and (5) non-linear history analysis. The first four levels of analysis were applied for the seismic safety evaluation of Paugan gravity dam (Quebec). Results showed that internal forces from pseudo-dynamic, response spectra and transient finite element analyses could be used to interpret the dynamic stability of dams from familiar strength-based criteria. However, as soon as the base was cracked, the seismically induced forces were modified, and level IV analyses proved more suitable to handle rationally these complexities. 8 refs., 7 figs., 1 tab

Hypergravity-induced increase in plasma catecholamine and corticosterone levels in telemetrically collected blood of rats during centrifugation.

Science.gov (United States)

Petrak, Juraj; Mravec, Boris; Jurani, Marian; Baranovska, Magda; Tillinger, Andrej; Hapala, Ivan; Frollo, Ivan; Kvetnanský, Richard

2008-12-01

Rats subjected to various accelerations (+G) exhibited increased levels of plasma epinephrine (EPI), norepinephrine (NE), and corticosterone. However, the collection of blood was performed after a centrifugation finished, and therefore the levels could be affected by the process of deceleration. The aim of this study was to evaluate plasma EPI, NE, and corticosterone levels in blood collected directly during centrifugation after reaching different G (2-6), using newly developed remote-controlled equipment. Animals placed into the centrifuge cabins had inserted polyethylene tubing in the tail artery, which was connected with a preprogrammed device for blood withdrawals. Plasma EPI, NE, and corticosterone levels were measured at different time intervals of hypergravity of 2-6G. Plasma EPI levels showed a huge, hypergravity-level-dependent increase. After the last blood collection was completed during hypergravity, the centrifuge was turned off and another blood sampling was performed immediately after the centrifuge stopped (10 min). In these samples, plasma EPI showed significantly lower levels compared to centrifugation intervals. Plasma NE levels were significantly increased after 6G only. The increase in plasma corticosterone was dependent on level of G, however after the centrifuge stopped, corticosterone levels remained elevated. Thus, our data show that hypergravity highly activates the adrenomedullary and hypothalamo-pituitary-adrenocortical systems, whereas the sympathoneural system is activated only at high hypergravity. Immediately after centrifugation is over, EPI levels quickly return to control values. Our technique of blood collection during centrifugation allows assessment of the real hormonal levels at the particular hypergravity value.

Rapidly Progressive Quadriplegia and Encephalopathy.

Science.gov (United States)

Wynn, DonRaphael; McCorquodale, Donald; Peters, Angela; Juster-Switlyk, Kelsey; Smith, Gordon; Ansari, Safdar

2016-11-01

A woman aged 77 years was transferred to our neurocritical care unit for evaluation and treatment of rapidly progressive motor weakness and encephalopathy. Examination revealed an ability to follow simple commands only and abnormal movements, including myoclonus, tongue and orofacial dyskinesias, and opsoclonus. Imaging study findings were initially unremarkable, but when repeated, they demonstrated enhancement of the cauda equina nerve roots, trigeminal nerve, and pachymeninges. Cerebrospinal fluid examination revealed mildly elevated white blood cell count and protein levels. Serial electrodiagnostic testing demonstrated a rapidly progressive diffuse sensory motor axonopathy, and electroencephalogram findings progressed from generalized slowing to bilateral periodic lateralized epileptiform discharges. Critical details of her recent history prompted a diagnostic biopsy. Over time, the patient became completely unresponsive with no further abnormal movements and ultimately died. The differential diagnosis, pathological findings, and diagnosis are discussed with a brief review of a well-known yet rare diagnosis.

World progress toward fusion energy

International Nuclear Information System (INIS)

Davies, N.A.

1989-01-01

The author discusses international progress in fusion research during the last three years. Much of the technical progress has been achieved through international collaboration in magnetic fusion research. This progress has stimulated political interest in a multinational effort, aimed at designing and possibly constructing the world's first experimental fusion reactor. This interest was reflected in recent summit-level discussions involving President Mitterand, General Secretary Gorbachev, and President Reagan. Most recently, the European Community (EC), Japan, the United States, and the U.S.S.R. have decided to begin serious preparation for taking the next step toward practical fusion energy. These parties have agreed to begin the design and supporting R and D for an International Thermonuclear Experimental Reactor (ITER) under the auspices of the International Atomic Energy Agency (IAEA). The initiation of this international program to prepare for a fusion test reactor is discussed

Progressive behavioral changes in rats after exposure to low levels of ionizing radiation in utero

International Nuclear Information System (INIS)

Norton, S.; Kimler, B.F.; Mullenix, P.J.

1991-01-01

The deleterious effects of ionizing radiation on the developing brain may be not only prolonged but progressive. Fetuses were exposed to 0.75 Gy of ionizing radiation on gestational day 15 through whole body exposure of the pregnant rat. Three behavioral tests (gait analysis, continuous corridor activity and photographic analysis of sequences of behavioral acts) were performed at 1 and 3 months, postnatally. Body weight and thickness of the cerebral cortex of irradiated rats were 10-15 percent below controls throughout the period of study. Behavior in all tests was more affected at 3 months than at 1 month of age. Gait of control rats, as measured by the angle of advanced of hind feet, widened about 20 percent for males and 40 percent for females from 1 to 3 months, as expected, while, in irradiated rats, the angle widened only about 10 percent. Continuous corridor activity increased less than 10 percent in controls and about 35 percent in irradiated rats over the same period. In photographic analysis of behavior, controls increased their time spent standing by about 50 percent in males and 20 percent in females from 1 to 3 months of age. Irradiated males increased time standing only about 10 percent and irradiated females decreased about 30 percent over the same period. The data obtained in these experiments support other evidence that some behavioral alterations from perinatal exposure to radiation become more marked with maturation

Nuclear structure from radioactive decay. Annual progress report

International Nuclear Information System (INIS)

Wood, J.L.

1982-01-01

The most exciting development during this year has been the formulation of a unified description of shape coexistence in nuclei. The picture is built on the idea that deformation in nuclei is due to an attractive proton-neutron force acting in the valence shell model space. The excitation of nucleon pairs across closed shells effectively increases the number of valence nucleons, giving rise to a set of coexisting states with larger deformation. The major area of activity is the study of neutron-deficient nuclei around the Z = 82 shell closure, with special emphasis on the levels of the odd-mass Pt, Au, Hg and Tl isotopes. Progress is reported

Modeling caspian sea water level oscilLations Under Diffrent Scenarioes of Increasing Atmospheric Carbon Dioxide Concentrations

Directory of Open Access Journals (Sweden)

GholamReza Roshan

2012-12-01

Full Text Available The rapid rise of Caspian Sea water level (about 2.25 meters since 1978 has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in thecoastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was stimulated. Variations in environmentalparameters such as temperature, precipitation, evaporation, tmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for bothpast (1951-2006 and future (2025-2100 time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software(version 5.3. The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site has increased by ca. 0.17ºC per decade under the impacts of atmospheric carbon dioxide changes (r=0.21. The Caspian Sea water level has increasedby ca. +36 mm per decade (r=0.82 between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64ºC and precipitation will decrease by ca. 10% (182 mm over the Caspian Sea, whilst in the Volga river basin,temperatures are projected to increase by ca. 4.78ºC and precipitation increase by ca. 12% (58 mm by the year 2100. Finally, statistical modeling of the Caspian Sea water levels projectfuture water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively.

Bmi-1 expression modulates non-small cell lung cancer progression

Science.gov (United States)

Xiong, Dan; Ye, Yunlin; Fu, Yujie; Wang, Jinglong; Kuang, Bohua; Wang, Hongbo; Wang, Xiumin; Zu, Lidong; Xiao, Gang; Hao, Mingang; Wang, Jianhua

2015-01-01

Previous studies indicate that the role of B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is responsible for multiple cancer progression. However, Bmi-1 in controlling gene expression in non-small cell lung cancer (NSCLC) development is not well explored. Here we report that the Bmi-1 level is highly increased in primary NSCLC tissues compared to matched adjacent non-cancerous tissues and required for lung tumor growth in xenograft model. Furthermore, we also demonstrate that Bmi-1 level is lower in matched involved lymph node cancerous tissues than the respective primary NSCLC tissues. We find that Bmi-1 does not affect cell cycle and apoptosis in lung cancer cell lines as it does not affect the expression of p16/p19, Pten, AKT and P-AKT. Mechanistic analyses note that reduction of Bmi-1 expression inversely regulates invasion and metastasis of NSCLC cells in vitro and in vivo, followed by induction of epithelial-mesenchymal transition (EMT). Using genome microarray assays, we find that RNAi-mediated silence of Bmi-1 modulates some important molecular genetics or signaling pathways, potentially associated with NSCLC development. Taken together, our findings disclose for the first time that Bmi-1 level accumulates strongly in early stage and then declines in late stage, which is potentially important for NSCLC cell invasion and metastasis during progression. PMID:25880371

Environmental Sciences semiannual progress report, July-December 1980

International Nuclear Information System (INIS)

Hurley, J.D.; Hunt, D.C.

1981-01-01

Four major areas of research effort are reported: dust transport, distribution of transuranics in sediments, evaluation of critical ecological pathways for radionuclides, and terrestrial ecosystem compartmentalization of transuranics. Progress also is described in programs dealing with Rocky Flats Plant land management, a differential alpha emitter analysis project, quality control procedures, the effects of chlorine addition on biological oxygen measurements, and evaluation of Plant-related incident response involving wounded wildlife. In the dust transport project, data continued to be collected on transuranic airborne concentrations and surface-soil activity levels for a field known to have above-back-ground levels of transuranics. The data show principal airborne activity resides on nonrespirable (> 3-μm aerodynamic diameter) particles. Progress in the sediment sampling program included fitting and modification of the sampling platform; taking of preliminary cores, dredges, and pond-side samples from Lindsay Pond (a near background water body); and acquisition of required sample preparation and storage facilities. The critical pathways project continued, and data were obtained on transuranic levels in garden vegetables grown in soil (with excess transuranic levels) within and outside a greenhouse. Progress in studies of terrestrial ecological distributions of transuranics included collection for radionuclide analysis of approximately 70 rodents on two study plots east of the Plant's security fence

Progress on the Level-1 Calorimeter Trigger

CERN Multimedia

Eric Eisenhandler

The Level-1 Calorimeter Trigger (L1Calo) has recently passed a number of major hurdles. The various electronic modules that make up the trigger are either in full production or are about to be, and preparations in the ATLAS pit are well advanced. L1Calo has three main subsystems. The PreProcessor converts analogue calorimeter signals to digital, associates the rather broad trigger pulses with the correct proton-proton bunch crossing, and does a final calibration in transverse energy before sending digital data streams to the two algorithmic trigger processors. The Cluster Processor identifies and counts electrons, photons and taus, and the Jet/Energy-sum Processor looks for jets and also sums missing and total transverse energy. Readout drivers allow the performance of the trigger to be monitored online and offline, and also send region-of-interest information to the Level-2 Trigger. The PreProcessor (Heidelberg) is the L1Calo subsystem with the largest number of electronic modules (124), and most of its fu...

[Severely increased serum lipid levels in diabetic ketoacidosis - case report].

Science.gov (United States)

Stefansson, Hrafnkell; Sigvaldason, Kristinn; Kjartansson, Hilmar; Sigurjonsdottir, Helga Águsta

2017-01-01

Severe hypertriglyceridemia is a known, but uncommon complication of diabetic ketoacidosis. We discuss the case of a 23-year-old, previously healthy, woman who initially presented to the emergency department with abdominal pain. Grossly lipemic serum due to extremely high triglyceride (38.6 mmol/L) and cholesterol (23.2 mmol/L) levels were observed with a high blood glucose (23 mmol/L) and a low pH of 7.06 on a venous blood gas. She was treated successfully with fluids and insulin and had no sequale of pancreatitis or cerebral edema. Her triglycerides and cholesterol was normalized in three days and she was discharged home on insulin therapy after five days. Further history revealed a recent change in diet with no meat, fish or poultry consumption in the last 12 months and concomitantly an increase in carbohydrate intake which might have contributed to her extremely high serum lipid levels. This case demonstrates that clinicians should be mindful of the different presentations of diabetic ketoacidosis. Key words: diabetic ketoacidosis, hypertriglyceridemia, hyperlipidemia, vegan diet, carbohydrate diet. Correspondence: Hrafnkell Stefansson, hrafnkell.stefans@gmail.com.

Research progress in roles of gut microbiota and bile acid metabolism in development and progression of NAFLD

Directory of Open Access Journals (Sweden)

LU Xu

2014-11-01

Full Text Available With the prevalence of obesity and metabolic syndrome, the incidence of nonalcoholic fatty liver disease (NAFLD is increasing year by year. Studies have uncovered the important roles of gut microbiota and bile acid metabolism in the development and progression of NAFLD. The roles of gut microbiota, as well bile acid and bile acid receptors, in the development and progression of NAFLD are highlighted.

Increased CSF levels of phosphorylated neurofilament heavy protein following bout in amateur boxers.

Directory of Open Access Journals (Sweden)

Sanna Neselius

Full Text Available INTRODUCTION: Diagnosis of mild TBI is hampered by the lack of imaging or biochemical measurements for identifying or quantifying mild TBI in a clinical setting. We have previously shown increased biomarker levels of protein reflecting axonal (neurofilament light protein and tau and glial (GFAP and S-100B damage in cerebrospinal fluid (CSF after a boxing bout. The aims of this study were to find other biomarkers of mild TBI, which may help clinicians diagnose and monitor mild TBI, and to calculate the role of APOE ε4 allele genotype which has been associated with poor outcome after TBI. MATERIALS AND METHODS: Thirty amateur boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in a prospective cohort study. CSF and blood were collected at one occasion between 1 and 6 days after a bout, and after a rest period for at least 14 days (follow up. The controls were tested once. CSF levels of neurofilament heavy (pNFH, amyloid precursor proteins (sAPPα and sAPPβ, ApoE and ApoA1 were analyzed. In blood, plasma levels of Aβ42 and ApoE genotype were analyzed. RESULTS: CSF levels of pNFH were significantly increased between 1 and 6 days after boxing as compared with controls (p<0.001. The concentrations decreased at follow up but were still significantly increased compared to controls (p = 0.018. CSF pNFH concentrations correlated with NFL (r =  0.57 after bout and 0.64 at follow up, p<0.001. No significant change was found in the other biomarkers, as compared to controls. Boxers carrying the APOE ε4 allele had similar biomarker concentrations as non-carriers. CONCLUSIONS: Subconcussive repetitive trauma in amateur boxing causes a mild TBI that may be diagnosed by CSF analysis of pNFH, even without unconsciousness or concussion symptoms. Possession of the APOE ε4 allele was not found to influence biomarker levels after acute TBI.

The evolution of primary progressive apraxia of speech.

Science.gov (United States)

Josephs, Keith A; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Gunter, Jeffrey L; Schwarz, Christopher G; Reid, Robert I; Spychalla, Anthony J; Lowe, Val J; Jack, Clifford R; Whitwell, Jennifer L

2014-10-01

Primary progressive apraxia of speech is a recently described neurodegenerative disorder in which patients present with an isolated apraxia of speech and show focal degeneration of superior premotor cortex. Little is known about how these individuals progress over time, making it difficult to provide prognostic estimates. Thirteen subjects with primary progressive apraxia of speech underwent two serial comprehensive clinical and neuroimaging evaluations 2.4 years apart [median age of onset = 67 years (range: 49-76), seven females]. All underwent detailed speech and language, neurological and neuropsychological assessments, and magnetic resonance imaging, diffusion tensor imaging and (18)F-fluorodeoxyglucose positron emission tomography at both baseline and follow-up. Rates of change of whole brain, ventricle, and midbrain volumes were calculated using the boundary-shift integral and atlas-based parcellation, and rates of regional grey matter atrophy were assessed using tensor-based morphometry. White matter tract degeneration was assessed on diffusion-tensor imaging at each time-point. Patterns of hypometabolism were assessed at the single subject-level. Neuroimaging findings were compared with a cohort of 20 age, gender, and scan-interval matched healthy controls. All subjects developed extrapyramidal signs. In eight subjects the apraxia of speech remained the predominant feature. In the other five there was a striking progression of symptoms that had evolved into a progressive supranuclear palsy-like syndrome; they showed a combination of severe parkinsonism, near mutism, dysphagia with choking, vertical supranuclear gaze palsy or slowing, balance difficulties with falls and urinary incontinence, and one was wheelchair bound. Rates of whole brain atrophy (1.5% per year; controls = 0.4% per year), ventricular expansion (8.0% per year; controls = 3.3% per year) and midbrain atrophy (1.5% per year; controls = 0.1% per year) were elevated (P ≤ 0.001) in all 13

Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Mazière, Cécile, E-mail: maziere.cecile@chu-amiens.fr [Biochemistry Laboratory, South Hospital University, René Laennec Avenue, Amiens 80000 (France); Salle, Valéry [Internal Medicine, North Hospital University, Place Victor Pauchet, Amiens 80000 (France); INSERM U1088 (EA 4292), SFR CAP-Santé (FED 4231), University of Picardie – Jules Verne (France); Gomila, Cathy; Mazière, Jean-Claude [Biochemistry Laboratory, South Hospital University, René Laennec Avenue, Amiens 80000 (France)

2013-10-18

Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

Exploring Wellness Interventions in Progressive Multiple Sclerosis: an Evidence-Based Review.

Science.gov (United States)

Venasse, Myriam; Edwards, Thomas; Pilutti, Lara A

2018-04-10

There has been recent interest in the role of lifestyle and wellness-based approaches in the treatment and management of multiple sclerosis (MS). These approaches may be particularly relevant for patients with progressive MS, considering limited therapeutic options currently available. The purpose of this review is to examine the role of wellness-based interventions including exercise training, emotional well-being therapies, and dietary modification in patients with progressive MS. We conducted a literature search on the efficacy of wellness-based interventions in patients with progressive MS published between 1985 and July 2017. The level of evidence for each trial was evaluated using the American Academy of Neurology criteria. Overall, 21 articles reporting on 16 wellness-based interventions were identified: ten trials involved exercise training, three involved emotional wellness therapies, two involved dietary modification, and one was a combined wellness intervention. There is level C evidence (possibly effective; one class II study) for the efficacy of aerobic exercise training on cardiorespiratory fitness in patients with progressive MS. There is level B evidence (probably effective; one class I study) for the efficacy of mindfulness training on psychological distress, depression, anxiety, pain, and quality of life in patients with progressive MS. There is inadequate evidence (level U) for efficacy of dietary modification (one class III study and one class IV study) and combined wellness interventions involving exercise training, meditation, and dietary modification (one class IV study). High-quality research is needed to provide evidence-based recommendations for wellness behaviors and lifestyle change in patients with progressive MS.

Progressive taxation, income inequality, and happiness.

Science.gov (United States)

Oishi, Shigehiro; Kushlev, Kostadin; Schimmack, Ulrich

2018-01-01

Income inequality has become one of the more widely debated social issues today. The current article explores the role of progressive taxation in income inequality and happiness. Using historical data in the United States from 1962 to 2014, we found that income inequality was substantially smaller in years when the income tax was more progressive (i.e., a higher tax rate for higher income brackets), even when controlling for variables like stock market performance and unemployment rate. Time lag analyses further showed that higher progressive taxation predicted increasingly lower income inequality up to 5 years later. Data from the General Social Survey (1972-2014; N = 59,599) with U.S. residents (hereafter referred to as "Americans") showed that during years with higher progressive taxation rates, less wealthy Americans-those in the lowest 40% of the income distribution-tended to be happier, whereas the richest 20% were not significantly less happy. Mediational analyses confirmed that the association of progressive taxation with the happiness of less wealthy Americans can be explained by lower income inequality in years with higher progressive taxation. A separate sample of Americans polled online (N = 373) correctly predicted the positive association between progressive taxation and the happiness of poorer Americans but incorrectly expected a strong negative association between progressive taxation and the happiness of richer Americans. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

Energy Technology Data Exchange (ETDEWEB)

Bajenova, Olga, E-mail: o.bazhenova@spbu.ru [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Chaika, Nina [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Tolkunova, Elena; Davydov-Sinitsyn, Alexander [Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064 (Russian Federation); Gapon, Svetlana [Boston Children' s Hospital, Boston, MA 02115 (United States); Thomas, Peter [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); O’Brien, Stephen [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation)

2014-06-10

Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.

Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

International Nuclear Information System (INIS)

Bajenova, Olga; Chaika, Nina; Tolkunova, Elena; Davydov-Sinitsyn, Alexander; Gapon, Svetlana; Thomas, Peter; O’Brien, Stephen

2014-01-01

Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein

Association between iron level, glucose impairment and increased DNA damage during pregnancy.

Science.gov (United States)

Zein, Salam; Rachidi, Samar; Shami, Nadine; Sharara, Iman; Cheikh-Ali, Khawla; Gauchez, Anne-Sophie; Moulis, Jean-Marc; Ayoubi, Jean-Marc; Salameh, Pascale; Hininger-Favier, Isabelle

2017-09-01

Elevated circulating ferritin has been reported to increase the risk of gestational diabetes mellitus (GDM). When high ferritin translates into high iron stores, iron excess is also a condition leading to free radical damage. We aimed to evaluate the relationship between oxidative stress (OS) induced by iron status and GDM risk in non iron-supplemented pregnant women. This was a pilot observational study conducted on 93 non-anemic pregnant women. Iron status was assessed at the first trimester of gestation. Blood sampling was done at 24-28 weeks' gestation for oral glucose tolerance test (OGTT), insulin and biological markers of oxidative damage tests. A significant increase in DNA damage was found in patients who developed GDM. Women with elevated DNA damage had a six-fold increased risk of developing GDM (Exp (B)=6.851, P=0.038; 95% CI [1.108-42.375]). The serum ferritin levels at first trimester were significantly correlated to lipid peroxidation (rho=0.24, p=0.012). The stratified analysis suggests that ferritin is a modifying factor for the correlation of oxidative stress (OS) and glucose intolerance. Moderate ferritin levels due to iron intake without iron-supplement, at early pregnancy is a modifying factor for the correlation of oxidative damage and glucose intolerance in pregnant women. Larger studies to evaluate the risk of food iron intake induced increased oxidative damage in offspring are warranted to propose nutrition advice regarding iron intake in women with a high risk of GDM. Copyright © 2016 Elsevier GmbH. All rights reserved.

Autonomy Level Specification for Intelligent Autonomous Vehicles

Science.gov (United States)

2003-09-01

Autonomy Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report Hui-Min Huang, Elena Messina, James Albus...Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

Periodontal profile classes predict periodontal disease progression and tooth loss.

Science.gov (United States)

Morelli, Thiago; Moss, Kevin L; Preisser, John S; Beck, James D; Divaris, Kimon; Wu, Di; Offenbacher, Steven

2018-02-01

Current periodontal disease taxonomies have limited utility for predicting disease progression and tooth loss; in fact, tooth loss itself can undermine precise person-level periodontal disease classifications. To overcome this limitation, the current group recently introduced a novel patient stratification system using latent class analyses of clinical parameters, including patterns of missing teeth. This investigation sought to determine the clinical utility of the Periodontal Profile Classes and Tooth Profile Classes (PPC/TPC) taxonomy for risk assessment, specifically for predicting periodontal disease progression and incident tooth loss. The analytic sample comprised 4,682 adult participants of two prospective cohort studies (Dental Atherosclerosis Risk in Communities Study and Piedmont Dental Study) with information on periodontal disease progression and incident tooth loss. The PPC/TPC taxonomy includes seven distinct PPCs (person-level disease pattern and severity) and seven TPCs (tooth-level disease). Logistic regression modeling was used to estimate relative risks (RR) and 95% confidence intervals (CI) for the association of these latent classes with disease progression and incident tooth loss, adjusting for examination center, race, sex, age, diabetes, and smoking. To obtain personalized outcome propensities, risk estimates associated with each participant's PPC and TPC were combined into person-level composite risk scores (Index of Periodontal Risk [IPR]). Individuals in two PPCs (PPC-G: Severe Disease and PPC-D: Tooth Loss) had the highest tooth loss risk (RR = 3.6; 95% CI = 2.6 to 5.0 and RR = 3.8; 95% CI = 2.9 to 5.1, respectively). PPC-G also had the highest risk for periodontitis progression (RR = 5.7; 95% CI = 2.2 to 14.7). Personalized IPR scores were positively associated with both periodontitis progression and tooth loss. These findings, upon additional validation, suggest that the periodontal/tooth profile classes and the derived

Progress Report 2004-2005

Energy Technology Data Exchange (ETDEWEB)

NONE

2005-11-01

The Faculty of Electrical Engineering and Computing (FER) as a part of University of Zagreb, has its roots in the Technical Faculty Zagreb, founded in 1919, which evolved into the Faculty of Electrical Engineering in 1956 and was upgraded into the Faculty of Electrical Engineering and Computing in 1994. Due to the increasing progress and advances in electrical and electronic engineering as well as in computer science and information technologies, the Faculty has become the largest technical faculty and the leading educational and R and D institution in the fields of electrical engineering and computing in Croatia. More than 13000 graduate students, more than 1900 postgraduate students who received the Master degree and more than 540 students with PhD degree, are today's total numbers, which highlights our highly spirited activities in teaching. Additional to this number are also 3800 undergraduate students as well as about 500 graduates each year. Organised in 11 departments, the present educational staff comprises 130 professors and 200 teaching assistants and researchers operating in more than 60 laboratories and area of more than 35000 m{sup 2}. Education and research is the crucial factor determining the economic and social progress and equality of opportunity in our societies. It becomes even more so in the digital age in order to ensure life-long-learning and the emergence of new generations of creators, researchers and entrepreneurs and to empower playing an active role in the knowledge society. The experiences at the university level should be transferred to the others. We can help to do that, as a chain the global challenge. The Faculty offers a broad spectrum of services to business and industry, from research and consultancy to conference facilities, training and postgraduate recruitment. The Faculty is a leading research-led institution and undertakes research at the highest levels of international standing. The Faculty is an integral part of the

Progress Report 2004-2005

International Nuclear Information System (INIS)

2005-11-01

The Faculty of Electrical Engineering and Computing (FER) as a part of University of Zagreb, has its roots in the Technical Faculty Zagreb, founded in 1919, which evolved into the Faculty of Electrical Engineering in 1956 and was upgraded into the Faculty of Electrical Engineering and Computing in 1994. Due to the increasing progress and advances in electrical and electronic engineering as well as in computer science and information technologies, the Faculty has become the largest technical faculty and the leading educational and R and D institution in the fields of electrical engineering and computing in Croatia. More than 13000 graduate students, more than 1900 postgraduate students who received the Master degree and more than 540 students with PhD degree, are today's total numbers, which highlights our highly spirited activities in teaching. Additional to this number are also 3800 undergraduate students as well as about 500 graduates each year. Organised in 11 departments, the present educational staff comprises 130 professors and 200 teaching assistants and researchers operating in more than 60 laboratories and area of more than 35000 m 2 . Education and research is the crucial factor determining the economic and social progress and equality of opportunity in our societies. It becomes even more so in the digital age in order to ensure life-long-learning and the emergence of new generations of creators, researchers and entrepreneurs and to empower playing an active role in the knowledge society. The experiences at the university level should be transferred to the others. We can help to do that, as a chain the global challenge. The Faculty offers a broad spectrum of services to business and industry, from research and consultancy to conference facilities, training and postgraduate recruitment. The Faculty is a leading research-led institution and undertakes research at the highest levels of international standing. The Faculty is an integral part of the community

Cigarette smoking increases radon working level exposures to all occupants of the smoker's home

International Nuclear Information System (INIS)

Johnson, R.H. Jr.; Rosario, A. Jr.

1990-01-01

This paper reports that the 1988 National Academy of Sciences report on radon health risks evaluated the combined effects of radon exposures and cigarettes on the lung cancer risk to smokers. This report showed that the risk of lung cancer is about 10 times greater for smokers than for nonsmokers at the same Working Level exposures. In 1986, the Surgeon General reported that 106,000 lung cancer deaths occurred among smokers. Therefore, the health risks of cigarettes alone or in combination with radon exposures are well recognized. What has not been studied is the effect of cigarette smoke on the Working Levels in homes that increases the exposure to radon decay products to all occupants, both smokers and nonsmokers. Preliminary studies in a radon chamber at Radon QC showed that the smoke from a single cigarette increased the Working Levels by a factor of five within four hours. Furthermore, the Working Levels remained at an elevated level for more than 24 hours. The equilibrium ratio of radon decay products to radon gas also went from about 14% up to 71%, with a slow decrease over 24 hours. Similar studies in the homes of a smoker and nonsmoker confirmed the laboratory observations. The studies in homes also showed the effects of thoron decay products

Unequal Error Protected JPEG 2000 Broadcast Scheme with Progressive Fountain Codes

OpenAIRE

Chen, Zhao; Xu, Mai; Yin, Luiguo; Lu, Jianhua

2012-01-01

This paper proposes a novel scheme, based on progressive fountain codes, for broadcasting JPEG 2000 multimedia. In such a broadcast scheme, progressive resolution levels of images/video have been unequally protected when transmitted using the proposed progressive fountain codes. With progressive fountain codes applied in the broadcast scheme, the resolutions of images (JPEG 2000) or videos (MJPEG 2000) received by different users can be automatically adaptive to their channel qualities, i.e. ...

Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

Science.gov (United States)

Hurabielle, Charlotte; Pillebout, Evangéline; Stehlé, Thomas; Pagès, Cécile; Roux, Jennifer; Schneider, Pierre; Chevret, Sylvie; Chaffaut, Cendrine; Boutten, Anne; Mourah, Samia; Basset-Seguin, Nicole; Vidal-Petiot, Emmanuelle; Lebbé, Céleste; Flamant, Martin

2016-01-01

Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective. PMID:26930506

Does Participation in Sports Affect Osteoarthritic Progression After Periacetabular Osteotomy?

Science.gov (United States)

Hara, Daisuke; Hamai, Satoshi; Fukushi, Jun-Ichi; Kawaguchi, Ken-Ichi; Motomura, Goro; Ikemura, Satoshi; Komiyama, Keisuke; Nakashima, Yasuharu

2017-09-01

Periacetabular osteotomy (PAO) is an effective treatment for symptomatic acetabular dysplasia. However, whether postoperative participation in sports leads to progression of the Kellgren-Lawrence (KL) grade of osteoarthritis (OA) in these patients is unclear. To investigate (1) participation in sports before and after PAO and (2) whether postoperative participation in sports leads to progression of the KL grade. Case-control study; Level of evidence, 3. The authors retrospectively reviewed data on 161 patients (183 hips) who underwent PAO for symptomatic acetabular dysplasia with preoperative KL grade 1 or 2 between 1998 and 2011. The mean age at the time of surgery was 42.0 ± 10.9 years (range, 12-64 years), and the mean follow-up duration was 100 months (range, 13-180 months). Data included participation in sports, the University of California, Los Angeles (UCLA) activity scale score, age at the time of surgery, body mass index, follow-up duration, history of treatment for developmental hip dislocations, Merle d'Aubigné-Postel score, Oxford Hip Score, center-edge angle, and KL grade. Univariate and multivariate analyses were applied to determine which factors were associated with progression to KL grade 3 or 4 after PAO. The number of patients who participated in sports significantly increased from 50 (31.1%) preoperatively to 89 (55.3%) postoperatively. The mean UCLA score significantly increased from 4.7 ± 2.1 preoperatively to 5.5 ± 2.0 postoperatively. The KL grade progressed to grade 3 or 4 in 16 hips, including 4 hips that underwent conversion to total hip arthroplasty. No significant differences were found in postoperative participation in sports (89 hips [53.3%] vs 11 hips [68.8%], respectively; P = .24) and the UCLA score (5.6 ± 2.0 vs 5.1 ± 2.0, respectively; P = .30) between hips with KL grade 1 or 2 and KL grade 3 or 4. A multivariate analysis revealed that no factors, including postoperative participation in sports, were significantly

Myocardial infarction increases progressive visual field defects in well treated early primary open angle glaucoma--a prospective case control study.

Science.gov (United States)

Mondal, Lakshmikanta; Baidya, Krishnapada; Choudhury, Himadri; Roy, Rupam

2013-06-01

The purpose of the study was to evaluate the progression of glaucomatous field damage in patients with stable primary open angle glaucoma after an attack of myocardial infarction. In this case control study, 62 open angle glaucoma patients were selected and regularly followed up. Among 62 patients, 9 had an attack of myocardial infarction. The intra-ocular pressure and visual field progression of both the groups (myocardial infarction versus no myocardial infarction) were analysed. Three (33.3%) out of 9 patients who had suffered from myocardial infarction showed progressive visual field loss whereas only 9 (16.9%) out of 53 patients who did not suffer from myocardial infarction, showed progressive field changes. Both the groups had stable target intra-ocular pressure between 14 and 16 mm Hg. Myocardial infarction may adversely influence the progression of primary open angle glaucoma which is suspected to result from ischaemia induced neuronal loss and only control of intraocular pressure is not the only solution. We have to look for other drugs that prevents ischaemia induced neuronal damage.

The increasing of beta-defensin-2 level in saliva after probiotic Lactobacillus reuteri administration

Directory of Open Access Journals (Sweden)

Tuti Kusumaningsih

2015-03-01

Full Text Available Background: Commesal bacteria is an excellent inducer for beta defensin-2 (BD-2. Probiotics bacteria Lactobacillus reuteri (L. reuteri as commensal bacteria may play the same role as an excellent inducer for BD-2. Beta defensin is natural antimicrobial peptides widely expressed in oral cavity, including in epithelium salivary gland. Streptococcus mutans (S. mutans as the main of bacteria causing caries are sensitive to BD-2. Purpose: This research was aimed to determine whether administration of probiotic L. reuteri can increase salivary BD-2 level in Wistar rats. Methods: This research can be considered as a laboratory experimental research with a randomized control group post test only design. Twenty-four male Rattus norvegicus Wistar strain rats aged 3 months were used. They were randomly divided into four groups, namely two control groups (negative control group that was not induced and positive control group induced with S. mutans, and two treatment groups (K1: induced with L. reuteri for 14 days and S. mutans for 7 days, and K2: induced with L. reuteri and S. mutans simultaneously for 14 days. L. reuteri culture at a concentration of 108 CFU/ml and S. mutans culture at a concentration of 1010CFU/ml were induced into the oral cavity of Wistar rats. An examination of BD-2 level was then conducted by using Elisa techniques. results: There was significant difference of salivary BD-2 level among those treatment groups (p=0.001. BD-2 level in saliva was increased after the administration of L. reuteri. Conclusion: L. reuteri probiotic can increase salivary BD-2 level in Wistar rats.

Chemical speciation of strontium, americium, and curium in high level waste: Predictive modeling of phase partitioning during tank processing. Annual progress report, October 1996--September 1997

International Nuclear Information System (INIS)

Choppin, G.; Felmy, A.R.

1997-01-01

'The program at Florida State University was funded to collaborate with Dr. A. Felmy (PNNL) on speciation in high level wastes and with Dr. D. Rai (PNNL) on redox of Pu under high level waste conditions. The funding provided support for 3 research associates (postdoctoral researchers) under Professor G. R. Choppin as P.I. Dr. Kath Morris from U. Manchester (Great Britain), Dr. Dean Peterman and Dr. Amy Irwin (both from U. Cincinnati) joined the laboratory in the latter part of 1996. After an initial training period to become familiar with basic actinide chemistry and radiochemical techniques, they began their research. Dr. Peterman was assigned the task of measuring Th-EDTA complexation prior to measuring Pu(IV)-EDTA complexation. These studies are associated with the speciation program with Dr. Felmy. Drs. Morris and Irwin initiated research on redox of plutonium with agents present in the Hanford Tanks as a result of radiolysis or from use in separations. The preliminary results obtained thus far are described in this report. It is expected that the rate of progress will continue to increase significantly as the researchers gain more experience with plutonium chemistry.'

A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression

Directory of Open Access Journals (Sweden)

Todd D. Levine

2012-01-01

Full Text Available Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators. Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30 mg/d and tretinoin 10 mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs were performed to measure cerebrospinal fluid (CSF biomarker levels. Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of −1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of -.86 (P=.18. Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression. Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline.

A sub-threshold dose of pilocarpine increases glutamine synthetase in reactive astrocytes and enhances the progression of amygdaloid-kindling epilepsy in rats.

Science.gov (United States)

Sun, Hong-Liu; Deng, Da-Ping; Pan, Xiao-Hong; Wang, Chao-Yun; Zhang, Xiu-Li; Chen, Xiang-Ming; Wang, Chun-Hua; Liu, Yu-Xia; Li, Shu-Cui; Bai, Xian-Yong; Zhu, Wei

2016-03-02

The prognosis of patients exposed to a sub-threshold dose of a proconvulsant is difficult to establish. In this study, we investigated the effect of a single sub-threshold dose of the proconvulsant pilocarpine (PILO) on the progression of seizures that were subsequently induced by daily electrical stimulation (kindling) of the amygdaloid formation. Male Sprague–Dawley rats were each implanted with an electrode in the right basolateral amygdala and an indwelling cannula in the right ventricle. The animals were randomized into groups and were administered one of the following treatments: saline, PILO, saline+L-α-aminoadipic acid (L-AAA; one dosage tested), PILO+L-AAA, or PILO+L-methionine sulfoximine (three dosages tested). Amygdaloid stimulation and electroencephalography were performed once daily. We performed immunohistochemistry and western blot for glial fibrillary acidic protein and glutamine synthetase (GS). We also assayed the enzymic activity of GS in discrete brain regions. An intraperitoneal injection of a sub-threshold PILO dose enhanced the progression of amygdaloid-kindling seizures and was accompanied by an increase in reactive-astrocyte and GS (content and activity) in the hippocampus and piriform cortex. L-AAA and L-methionine sulfoximine, inhibitors of astrocytic and GS function, respectively, abolished the effect of PILO on amygdaloid-kindling seizures. We conclude that one sub-threshold dose of a proconvulsant may enhance the progression of subsequent epilepsy and astrocytic GS may play a role in this phenomenon. Thus, a future therapy for epilepsy could be inhibition of astrocytes and/or GS.

Ten-year weight gain is associated with elevated fasting insulin levels and precedes glucose elevation.

Science.gov (United States)

Pennings, Nicholas; Jaber, Johnny; Ahiawodzi, Peter

2018-05-01

Numerous studies have examined the relationship between endogenous insulin and weight change with mixed results. This study examined the relationship between fasting insulin levels, insulin resistance (IR), and 10-year weight change by glycaemic stage. Using data from the US National Health and Nutrition Examination Survey 2011-2014, 3840 participants were divided into 6 groups based on fasting glucose and fasting insulin levels. Fasting insulin concentrations were dichotomized into <25th percentile (normal) and ≥25th percentile (elevated). Ten-year weight change associated with fasting insulin was assessed by glycaemic stage. Average weight change over a 10-year period was higher in individuals with elevated insulin levels compared to the first quartile (1.40 lbs. vs 11.12 lbs, P < .0001). Across all groups, a 1 μU increase in fasting insulin levels resulted in a 0.52-pound increase in weight (P < .0001). Similarly, an increase in HOMA-IR was associated with increase in weight (1.32 lbs per IR unit, P < .0001). Marginal increases in weight were most pronounced in the normal insulin groups compared to elevated insulin groups and diminished as glycaemic stage progressed. Elevated fasting insulin level was positively associated with weight gain. The impact of fasting insulin and IR on weight gain preceded hyperglycaemia and diminished as glycaemic stage progressed. Copyright © 2018 John Wiley & Sons, Ltd.

Progression of motor symptoms in Parkinson's disease

Institute of Scientific and Technical Information of China (English)

Ruiping Xia; Zhi-Hong Mao

2012-01-01

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity,bradykinesia and tremor - due to loss of dopaminergic neurons.The motor symptoms of PD become progressively worse as the disease advances.PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others.In recent years,many studies have investigated the progression of the hallmark symptoms over time,and the cardinal motor symptoms have different rates of progression,with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor.The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability.Increasing the dosage of dopaminergic medication is commonly used to combat the worsenirtg symptoms.However,the drug-induced involuntary body movements and motor comphcations can significantly contribute to overall disability.Further,none of the currently-available therapies can slow or halt the disease progression.Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression.In this article,the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer

DEFF Research Database (Denmark)

Bryce, A H; Alumkal, J J; Armstrong, A

2017-01-01

monitoring alone to determine disease status on therapy. This approach has not been adequately tested. METHODS: Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide......BACKGROUND: Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA...... treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant...

Increased osteopontin plasma levels in multiple sclerosis patients correlate with bone-specific markers

NARCIS (Netherlands)

Vogt, M.H.J.; ten Kate, J.; Drent, R.J.M.; Polman, C.H.; Hupperts, R.

2010-01-01

The pro-inflammatory cytokine osteopontin has been found to be highly expressed in multiple sclerosis lesions and plasma levels are increased during relapses in relapse-onset multiple sclerosis patients. The objective was to determine the relationship between osteopontin plasma and cerebrospinal

Progress on Chinese evaluated nuclear parameters library (CENPL). Pt. 3

International Nuclear Information System (INIS)

Su Zongdi; Ge Zhigang; Zhou Chunmei

1994-01-01

The progress on Chinese evaluated nuclear parameters library (CENPL) is introduced. The setting up work of each sub-library of CENPL has got some new progresses at the past period. These sub-libraries are atomic mass and characteristic constant for nuclear ground state sub-library, discrete level scheme and batch ratio of γ decay sub-library, level density parameter sub-library, giant dipole resonance parameter for γ-ray strength function sub-library and optical model parameter sub-library

Cell-based multi-parametric model of cleft progression during submandibular salivary gland branching morphogenesis.

Directory of Open Access Journals (Sweden)

Shayoni Ray

Full Text Available Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ. Previous experimental studies indicated requirements for several epithelial cellular processes, such as proliferation, migration, cell-cell adhesion, cell-extracellular matrix (matrix adhesion, and cellular contraction in cleft formation; however, the relative contribution of each of these processes is not fully understood since it is not possible to experimentally manipulate each factor independently. We present here a comprehensive analysis of several cellular parameters regulating cleft progression during branching morphogenesis in the epithelial tissue of an early embryonic salivary gland at a local scale using an on lattice Monte-Carlo simulation model, the Glazier-Graner-Hogeweg model. We utilized measurements from time-lapse images of mouse submandibular gland organ explants to construct a temporally and spatially relevant cell-based 2D model. Our model simulates the effect of cellular proliferation, actomyosin contractility, cell-cell and cell-matrix adhesions on cleft progression, and it was used to test specific hypotheses regarding the function of these parameters in branching morphogenesis. We use innovative features capturing several aspects of cleft morphology and quantitatively analyze clefts formed during functional modification of the cellular parameters. Our simulations predict that a low epithelial mitosis rate and moderate level of actomyosin contractility in the cleft cells promote cleft progression. Raising or lowering levels of contractility and mitosis rate resulted in non-progressive clefts. We also show that lowered cell-cell adhesion in the cleft region and increased cleft cell-matrix adhesions are required for cleft progression. Using a classifier-based analysis, the relative importance of these four contributing cellular factors for effective cleft

The Dynamics of Platelet Activation during the Progression of Streptococcal Sepsis.

Directory of Open Access Journals (Sweden)

Sinead M Hurley

Full Text Available Platelets contribute to inflammation however, the role of platelet activation during the pathophysiological response to invasive bacterial infection and sepsis is not clear. Herein, we have investigated platelet activation in a mouse model of invasive Streptococcus pyogenes infection at 5, 12, and 18 hours post infection and correlated this to parameters of infection. The platelet population in ex-vivo blood samples showed no increased integrin activation or surface presentation of CD62P, however platelet-neutrophil complex formation and plasma levels of CD62P were increased during bacterial dissemination and the progression of sepsis, indicating that platelet activation had occurred in vivo. Platelet-neutrophil complex formation was the most discriminatory marker of platelet activation. Platelet-neutrophil complexes were increased above baseline levels during early sepsis but decreased to significantly lower levels than baseline during late sepsis. The removal of these complexes from the circulation coincided with a significant increase in organ damage and the accumulation of platelets in the liver sinusoids, suggesting that platelet activation in the circulation precedes accumulation of platelets in damaged organs. The results demonstrate that monitoring platelet activation using complementary methods may provide prognostic information during the pathogenesis of invasive S. pyogenes infection.

Evaluation of aldosterone-and cortisol levels in blood plasma in normal conditions of ingestion of sodium and potassium, after saline-increase and depletion, in regard to position, and after stimulation with ACTH and angiotensin II

International Nuclear Information System (INIS)

Okada, H.

1979-01-01

Methods for the determination of plasma aldosterone and cortisol, by radioimmunoassay, were performed utilizing highly specific antisera. With this methodology it was possible to evaluate cortisol and aldosterone secretion, in six normal subjects, submitted to a basal rice diet on standing and recumbent positions, the effects of exogenous cortrosyn (β1-24 ACTH) and angiotensin II and the same manoevres with progressively increased Na + content of the diet. Aldosterone basal levels decreased with the increase of Na + content in the diet. However, there were no significant differences between the relative increments observed on the recumbent position, at the three levels of sodium intake. The relative increase of plasma aldosterone after ACTH was similar for each basal level of aldosterone induced by different sodium intakes. The responsiveness of aldosterone secretion to cortrosyn and standing position was similar, with no relation to the sodium intake. The infusion of angiotensin II induced an increase in plasma aldosterone, and the relative increment in the levels of the hormone were higher with high sodium than on the rice diet. The average basal cortisol value at the different levels of sodium intake was significantly different being greater on the basal, rice diet, and there was a decrease in cortisol level after recumbency, with the theree diets. The injection of ACTH induced similar cortisol secretion with no relation to the sodium intake. The infusion of non-hypertensive doses of angiotensin II resulted in an anomalous fall in cortisol level, probably because of 'shunt' of substrates to biosynthesis with the added effect of cortisol diurnal rhythmycity. (Author) [pt

Optimal tax progressivity in imperfect labour markets

DEFF Research Database (Denmark)

Sørensen, Peter Birch

1999-01-01

that there may be an optimal degree of tax progressivity where the marginal welfare gain from reduced involuntary unemployment is just offset by the marginal welfare loss from lower productivity. This paper sets up four different models of an imperfect labour market in order to identify the degree of tax......All modern labour market theories capable of explaining involuntary unemployment as an equilibrium phenomenon imply that increased income tax progressivity reduces unemployment, but they also imply that higher progressivity tends to reduce work effort and labour productivity. This suggests...

The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo.

Science.gov (United States)

Xie, Zhongcong; Culley, Deborah J; Dong, Yuanlin; Zhang, Guohua; Zhang, Bin; Moir, Robert D; Frosch, Matthew P; Crosby, Gregory; Tanzi, Rudolph E

2008-12-01

An estimated 200 million patients worldwide have surgery each year. Anesthesia and surgery have been reported to facilitate emergence of Alzheimer's disease. The commonly used inhalation anesthetic isoflurane has previously been reported to induce apoptosis, and to increase levels and aggregation of Alzheimer's disease-associated amyloid beta-protein (Abeta) in cultured cells. However, the in vivo relevance has not been addressed. We therefore set out to determine effects of isoflurane on caspase activation and levels of beta-site amyloid precursor protein-cleaving enzyme (BACE) and Abeta in naive mice, using Western blot, immunohistochemistry, and reverse transcriptase polymerase chain reaction. Here we show for the first time that a clinically relevant isoflurane anesthesia (1.4% isoflurane for 2 hours) leads to caspase activation and modest increases in levels of BACE 6 hours after anesthesia in mouse brain. Isoflurane anesthesia induces caspase activation, and increases levels of BACE and Abeta up to 24 hours after anesthesia. Isoflurane may increase BACE levels by reducing BACE degradation. Moreover, the Abeta aggregation inhibitor, clioquinol, was able to attenuate isoflurane-induced caspase-3 activation in vivo. Given that transient insults to brain may lead to long-term brain damage, these findings suggest that isoflurane may promote Alzheimer's disease neuropathogenesis and, as such, have implications for use of isoflurane in humans, pending human study confirmation.

The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

International Nuclear Information System (INIS)

Arrieta, Oscar; Cacho, Bernardo; Morales-Espinosa, Daniela; Ruelas-Villavicencio, Ana; Flores-Estrada, Diana; Hernández-Pedro, Norma

2007-01-01

Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng/mL. Prospective studies are required to

One-year progression of diabetic subclinical macular edema in eyes with mild nonproliferative diabetic retinopathy

DEFF Research Database (Denmark)

Tejerina, Amparo Navea; Vujosevic, Stela; Varano, Monica

2015-01-01

PURPOSE: To characterize the 1-year progression of retinal thickness (RT) increase occurring in eyes with subclinical macular edema in type 2 diabetes. METHODS: Forty-eight type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (NPDR; levels 20 and 35 in the Early Treatment...... Diabetic Retinopathy Study) classified as presenting subclinical macular edema at baseline completed the 1-year follow-up period, from a sample of 194 followed in a 12-month observational and prospective study (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers...... in these eyes was performed, followed by verification and correction by a human grader. RESULTS: The highest increase in RT over the 1-year follow-up period for the 48 eyes/patients with subclinical macular edema was found in the inner nuclear layer (INL). Progression to clinical macular edema was also...

Increased complement C1q level marks active disease in human tuberculosis.

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Yi Cai

Full Text Available BACKGROUND: Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. METHODS: Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. RESULTS: C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. CONCLUSIONS: C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy.

High circulating levels of tumor necrosis factor-alpha in centenarians are not associated with increased production in T lymphocytes

DEFF Research Database (Denmark)

Sandmand, Marie; Bruunsgaard, Helle; Kemp, Kåre

2003-01-01

BACKGROUND: Aging is characterized by increased inflammatory activity reflected by increased plasma levels of proinflammatory cytokines, concomitant with an altered cytokine profile of T lymphocytes. High plasma levels of tumor necrosis factor (TNF)-alpha are strongly associated with morbidity...... and mortality in elderly humans. However, the cellular source and mechanisms for the increased circulating TNF-alpha levels are unknown. OBJECTIVE: The aim of the present study was to investigate if high plasma levels of TNF-alpha are associated with increased production of TNF-alpha by T lymphocytes in elderly...... humans. METHODS: TNF-alpha production by CD4+ and CD8+ T lymphocytes was measured by flow cytometry following stimulation with phorbol 12-myristate 13-acetate and ionomycin in 28 young controls, 14, 81-year-olds and 25 centenarians. RESULTS: Plasma levels of TNF-alpha increased with increasing age...

Increased circulating miR-21 levels are associated with kidney fibrosis.

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François Glowacki

Full Text Available MicroRNAs (miRNAs are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA. Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001. By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03, and between miR-21 levels and aMDRD (ß = -0.398, p = 0.006. Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis.

Visit-to-visit cholesterol variability correlates with coronary atheroma progression and clinical outcomes.

Science.gov (United States)

Clark, Donald; Nicholls, Stephen J; St John, Julie; Elshazly, Mohamed B; Kapadia, Samir R; Tuzcu, E Murat; Nissen, Steven E; Puri, Rishi

2018-04-21

Utilizing serial intravascular ultrasonography (IVUS), we aimed to exam the association of intra-individual lipid variability, coronary atheroma progression, and clinical outcomes. We performed a post hoc patient-level analysis of nine clinical trials involving 4976 patients with coronary artery disease who underwent serial coronary IVUS in the setting of a range of medical therapies. We assessed the associations between progression in percent atheroma volume (ΔPAV), clinical outcomes, and visit-to-visit lipid variability including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC)/HDL-C, and apolipoprotein B (ApoB). Variability of lipid parameters was measured using intra-individual standard deviation over 3, 6, 12, 18, and 24 months. Atherogenic lipoprotein variability significantly associated with ΔPAV [odds ratio (95% confidence interval; P-value), LDL-C: 1.09 (1.02, 1.17, P = 0.01); non-HDL-C: 1.10 (1.02, 1.18, P = 0.01); TC/HDL-C: 1.14 (1.06, 1.24, P = 0.001); ApoB: 1.13 (1.03, 1.24, P = 0.01)]. Survival curves revealed significant stepwise relationships between cumulative major adverse cardiovascular events and increasing quartiles of atherogenic lipoprotein variability at 24-months follow-up (log-rank P C). Stronger associations were noted between achieved lipoprotein levels and ΔPAV [LDL-C: 1.27 (1.17, 1.39; P C: 1.32 (1.21, 1.45; P C: 1.31 (1.19, 1.45; P < 0.001); ApoB: 1.20 (1.07, 1.35; P = 0.003)]. Greater visit-to-visit variability in atherogenic lipoprotein levels significantly associates with coronary atheroma progression and clinical outcomes, although the association between achieved atherogenic lipoproteins and atheroma progression appears stronger. These data highlight the importance of achieving low and consistent atherogenic lipoprotein levels to promote plaque regression and improve clinical outcomes.

Increased level and interferon-γ production of circulating natural killer cells in patients with scrub typhus.

Science.gov (United States)

Kang, Seung-Ji; Jin, Hye-Mi; Cho, Young-Nan; Kim, Seong Eun; Kim, Uh Jin; Park, Kyung-Hwa; Jang, Hee-Chang; Jung, Sook-In; Kee, Seung-Jung; Park, Yong-Wook

2017-07-01

Natural killer (NK) cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK cells in patients with scrub typhus. This study enrolled fifty-six scrub typhus patients and 56 health controls (HCs). The patients were divided into subgroups according to their disease severity. A flow cytometry measured NK cell level and function in peripheral blood. Circulating NK cell levels and CD69 expressions were significantly increased in scrub typhus patients. Increased NK cell levels reflected disease severity. In scrub typhus patients, tests showed their NK cells produced higher amounts of interferon (IFN)-γ after stimulation with interleukin (IL)-12 and IL-18 relative to those of HCs. Meanwhile, between scrub typhus patients and HCs, the cytotoxicity and degranulation of NK cells against K562 were comparable. CD69 expressions were recovered to the normal levels in the remission phase. This study shows that circulating NK cells are activated and numerically increased, and they produced more IFN-γ in scrub typhus patients.

Increased level and interferon-γ production of circulating natural killer cells in patients with scrub typhus.

Directory of Open Access Journals (Sweden)

Seung-Ji Kang

2017-07-01

Full Text Available Natural killer (NK cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK cells in patients with scrub typhus.This study enrolled fifty-six scrub typhus patients and 56 health controls (HCs. The patients were divided into subgroups according to their disease severity. A flow cytometry measured NK cell level and function in peripheral blood. Circulating NK cell levels and CD69 expressions were significantly increased in scrub typhus patients. Increased NK cell levels reflected disease severity. In scrub typhus patients, tests showed their NK cells produced higher amounts of interferon (IFN-γ after stimulation with interleukin (IL-12 and IL-18 relative to those of HCs. Meanwhile, between scrub typhus patients and HCs, the cytotoxicity and degranulation of NK cells against K562 were comparable. CD69 expressions were recovered to the normal levels in the remission phase.This study shows that circulating NK cells are activated and numerically increased, and they produced more IFN-γ in scrub typhus patients.

The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

Energy Technology Data Exchange (ETDEWEB)

Conde, Vanessa R. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Oliveira, Pedro F. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto – UMIB/ICBAS/UP (Portugal); Nunes, Ana R.; Rocha, Cátia S. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Ramalhosa, Elsa; Pereira, José A. [Mountain Research Centre (CIMO), School of Agriculture, Polytechnic Institute of Bragança (Portugal); Alves, Marco G., E-mail: alvesmarc@gmail.com [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Silva, Branca M., E-mail: bmcms@ubi.pt [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal)

2015-07-01

Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.

John Woolman and Ethical Progress in Kitcher's Pragmatic Naturalism.

Science.gov (United States)

Barresi, John

2017-01-01

The development of John Woolman’s views on slavery plays an important evidentiary role in Philip Kitcher’s recent book, The ethical project (Kitcher 2011). In this work Kitcher takes what he calls a “pragmatic naturalist” approach to ethics and claims that the discovery of ethical truth plays no role in the emergence of ethical progress. To support his view, he argues that Woolman’s contribution was not due to his discovery of an ethical truth about slavery, not previously known, but due to his sensitivity to slavery and his influence on others, which contributed to collective progressive change in moral norms involving slavery. While not disputing Kitcher’s ethical theory, I argue that personal discoveries of a moral psychological nature made by Woolman served both as insights and motivations for his contribution. Thus, even if there are no such things as independent ethical truths that can be discovered by individuals, a fully naturalistic approach to ethical progress requires that we make room not only for group-level progressive evolution of norms, but also for individual discoveries of a moral psychological nature that can sometimes cause an individual to play a significant initiating role in progressive ethical transitions that occur at a group level.

Technical reliability of geological disposal for high-level radioactive wastes in Japan. The second progress report. Part 2. Engineering technology for geological disposal

International Nuclear Information System (INIS)

1999-11-01

Based on the Advisory Committee Report on Nuclear Fuel Cycle Backend Policy submitted to the Japanese Government in 1997, JNC documents the progress of research and development program in the form of the second progress report (the first one published in 1992). It summarizes an evaluation of the technical reliability and safety of the deep geological disposal concept for high-level radioactive wastes (HLW) in Japan. The present document, part 2 of the progress report, concerns engineering aspect with reference to Japanese geological disposal plan, according to which the vitrified HLW will be disposed of into a deep, stable rock mass with thick containers and surrounding buffer materials at the depth of several hundred meters. It discusses on multi-barrier systems consisting of a series of engineered and natural barriers that will isolate radioactive nuclides effectively and retard their migrations to the biosphere environment. Performance of repository components, including specifications of containers for vitrified HLW and their overpacks under design as well as buffer material such as Japanese bentonite to be placed in between are described referring also to such possible problems as corrosion arising from the supposed system. It also presents plans and designs for underground disposal facilities, and the presumed management of the underground facilities. (Ohno, S.)

Risk management of biosimilars in oncology: each medicine is a work in progress

OpenAIRE

Vulto, Arnold G.; Crow, Stacy A.

2012-01-01

textabstractDrug licensing and drug safety monitoring for standard chemical entities have been established and are routinely used. These have resulted in a solid foundation of knowledge from which confident therapeutic decisions can be made. For many chemical entities, this advanced level of experience is also present for the generic products. The expertise surrounding the development of biosimilar competitor versions is increasing and progress is encouraging. To address the re-engineering an...

Androgen receptor variation affects prostate cancer progression and drug resistance.

Science.gov (United States)

McCrea, Edel; Sissung, Tristan M; Price, Douglas K; Chau, Cindy H; Figg, William D

2016-12-01

Significant therapeutic progress has been made in treating prostate cancer in recent years. Drugs such as enzalutamide, abiraterone, and cabazitaxel have expanded the treatment armamentarium, although it is not completely clear which of these drugs are the most-effective option for individual patients. Moreover, such advances have been tempered by the development of therapeutic resistance. The purpose of this review is to summarize the current literature pertaining to the biochemical effects of AR variants and their consequences on prostate cancer therapies at both the molecular level and in clinical treatment. We address how these AR splice variants and mutations affect tumor progression and therapeutic resistance and discuss potential novel therapeutic strategies under development. It is hoped that these therapies can be administered with increasing precision as tumor genotyping methods become more sophisticated, thereby lending clinicians a better understanding of the underlying biology of prostate tumors in individual patients. Published by Elsevier Ltd.

Rho/ROCK signaling in regulation of corneal epithelial cell cycle progression.

Science.gov (United States)

Chen, Jian; Guerriero, Emily; Lathrop, Kira; SundarRaj, Nirmala

2008-01-01

The authors' previous study showed that the expression of a Rho-associated serine/threonine kinase (ROCK) is regulated during cell cycle progression in corneal epithelial cells. The present study was conducted to determine whether and how Rho/ROCK signaling regulates cell cycle progression. Rabbit corneal epithelial cells (RCECs) in culture were arrested in the G(0) phase of the cell cycle by serum deprivation and then allowed to re-enter the cell cycle in the presence or absence of the ROCK inhibitor (Y27632) in serum-supplemented medium. The number of cells in the S phase, the relative levels of specific cyclins and CDKs and their intracellular distribution, and the relative levels of mRNAs were determined by BrdU labeling, Western blot and immunocytochemical analyses, and real-time RT-PCR, respectively. ROCK inhibition delayed the progression of G(1) to S phase and led to a decrease in the number of RCECs entering the S phase between 12 and 24 hours from 31.5% +/- 4.5% to 8.1% +/- 2.6%. During the cell cycle progression, protein and mRNA levels of cyclin-D1 and -D3 and cyclin-dependent kinases CDK4 and CDK6 were significantly lower, whereas the protein levels of the CDK inhibitor p27(Kip1) were higher in ROCK-inhibited cells. Intracellular mRNA or protein levels of cyclin-E and protein levels of CDK2 were not significantly affected, but their nuclear translocation was delayed by ROCK inhibition. ROCK signaling is involved in cell cycle progression in RCECs, possibly by upregulation of cyclin-D1 and -D3 and CDK4, -6, and -2; nuclear translocation of CDK2 and cyclin-E; and downregulation of p27(Kip1).