Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of PGC-1α expression

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

Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf

The present investigation was carried out to elucidate a possible molecular mechanism related to the effects of aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of Peroxisome proliferator activated receptor gamma co-activator 1α (PGC-1α) and its downstream targets i.e. Nuclear respiratory factor-1(NRF-1), Nuclear respiratory factor-2(NRF-2) and Mitochondrial transcription factor A (Tfam) in mitochondrial biogenesis. Aluminium lactate (10 mg/kg b.wt./day) was administered intragastrically to rats for 12 weeks. After 12 weeks of exposure, we found an increase in ROS levels, mitochondrial DNA oxidation and decrease in citrate synthase activity in the Hippocampus (HC) andmore » Corpus striatum (CS) regions of rat brain. On the other hand, there was a decrease in the mRNA levels of the mitochondrial encoded subunits–NADH dehydrogenase (ND) subunits i.e. ND1, ND2, ND3, Cytochrome b (Cytb), Cytochrome oxidase (COX) subunits i.e. COX1, COX3, ATP synthase (ATPase) subunit 6 along with reduced expression of nuclear encoded subunits COX4, COX5A, COX5B of Electron transport chain (ETC). Besides, a decrease in mitochondrial DNA copy number and mitochondrial content in both regions of rat brain was observed. The PGC-1α was down-regulated in aluminium treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1α in aluminium treated rats. Electron microscopy results revealed a significant increase in the mitochondrial swelling, loss of cristae, chromatin condensation and decreases in mitochondrial number in case of aluminium treated rats as compared to control. So, PGC-1α seems to be a potent target for aluminium neurotoxicity, which makes it an almost ideal target to control or limit the damage that has been associated with the defective mitochondrial function seen in neurodegenerative diseases. - Highlights: • Aluminium decreases the mRNA levels of mitochondrial and nuclear

Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients.

PubMed

Karatas, Fatih; Erdem, Gokmen Umut; Sahin, Suleyman; Aytekin, Aydin; Yuce, Deniz; Sever, Ali R; Babacan, Taner; Ates, Ozturk; Ozisik, Yavuz; Altundag, Kadri

2017-04-01

�= 40%; P = 0.06 respectively). Median RFS was significantly higher in N/U group compared to OB patients (150 vs. 76 months respectively, P = 0.03) and was also higher in pCR group compared to non-pCR patients (151 vs. 77 months P = 0.004). Median OS was significantly higher in N/U patients compared to OB patients (N/U = not reached, OW = 211 and OB = 114 months; P = 0.01) and was also higher in pCR group compared to non-pCR patients (not reached vs. 211 months P = 0.04). In Cox regression analysis; pCR, histopathological grade and TNBC were found as independent prognostic factors on OS (HR, 0.29; 95% CI, 0.11 to 0.79, P = 0.015, HR, 2.09; 95% CI, 1.14 to 3.83, P = 0.017, HR, 1.95; 95% CI, 1.01 to 3.77, P = 0.046, respectively). It was observed that obesity was an important independent prognostic factor which has an adverse effect on pCR. Moreover it causes decreasing RFS and OS in BC patients who had received NAC. The probability of inefficient treatment in obese patients should be considered. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dietary overload lithium decreases the adipogenesis in abdominal adipose tissue of broiler chickens.

PubMed

Bai, Shiping; Pan, Shuqin; Zhang, Keying; Ding, Xuemei; Wang, Jianping; Zeng, Qiufeng; Xuan, Yue; Su, Zuowei

2017-01-01

To investigate the toxic effects of dietary overload lithium on the adipogenesis in adipose tissue of chicken and the role of hypothalamic neuropeptide Y (NPY) in this process, one-day-old male chicks were fed with the basal diet added with 0 (control) or 100mg lithium/kg diet from lithium chloride (overload lithium) for 35days. Abdominal adipose tissue and hypothalamus were collected at day 6, 14, and 35. As a percentage of body weight, abdominal fat decreased (p<0.001) at day 6, 14, and 35, and feed intake and body weight gain decreased during day 7-14, and day 15-35 in overload lithium treated broilers as compared to control. Adipocyte diameter and DNA content in abdominal adipose tissue were significantly lower in overload-lithium treatment than control at day 35, although no significant differences were observed at day 6 and 14. Dietary overload lithium decreased (p<0.01) transcriptional expression of preadipocyte proliferation makers ki-67 (KI67), microtubule-associated protein homolog (TPX2), and topoisomerase 2-alpha (TOP2A), and preadipocyte differentiation transcriptional factors peroxisome proliferator-activated receptor-γ (PPARγ), and CCAAT/enhancer binding protein (C/EBP) α mRNA abundance in abdominal adipose tissue. In hypothalamus, dietary overload lithium influenced (p<0.001) NPY, and NPY receptor (NPYR) 6 mRNA abundance at day 6 and 14, but not at day 35. In conclusion, dietary overload lithium decreased the adipogenesis in abdominal adipose tissue of chicken, which was accompanied by depressing transcriptional expression of adipogenesis-associated factors. Hypothalamic NPY had a potential role in the adipogenesis in abdominal adipose tissue of broilers with a short-term overload lithium treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Higher thermostability of l-lactate dehydrogenases is a key factor in decreasing the optical purity of d-lactic acid produced from Lactobacillus coryniformis.

PubMed

Gu, Sol-A; Jun, Chanha; Joo, Jeong Chan; Kim, Seil; Lee, Seung Hwan; Kim, Yong Hwan

2014-05-10

Lactobacillus coryniformis is known to produce d-lactic acid as a dominant fermentation product at a cultivation temperature of approximately 30°C. However, the considerable production of l-lactic acid is observed when the fermentation temperature is greater than 40°C. Because optically pure lactates are synthesized from pyruvate by the catalysis of chiral-specific d- or l-lactate dehydrogenase, the higher thermostability of l-LDHs is assumed to be one of the key factors decreasing the optical purity of d-lactic acid produced from L. coryniformis at high temperature. To verify this hypothesis, two types of d-ldh genes and six types of l-ldh genes based on the genomic information of L. coryniformis were synthesized and expressed in Escherichia coli. Among the LDHs tested, five LDHs showed activity and were used to construct polyclonal antibodies. d-LDH1, l-LDH2, and l-LDH3 were found to be expressed in L. coryniformis by Western blotting analysis. The half-life values (t1/2) of the LDHs at 40°C were estimated to be 10.50, 41.76, and 2311min, and the T50(10) values were 39.50, 39.90, and 58.60°C, respectively. In addition, the Tm values were 36.0, 41.0, and 62.4°C, respectively, which indicates that l-LDH has greater thermostability than d-LDH. The higher thermostability of l-LDHs compared with that of d-LDH1 may be a major reason why the enantiopurity of d-lactic acid is decreased at high fermentation temperatures. The key enzymes characterized will suggest a direction for the design of genetically modified lactic acid bacteria to produce optically pure d-lactic acid. Copyright © 2014 Elsevier Inc. All rights reserved.

Dramatic decreases in brain reward function during nicotine withdrawal.

PubMed

Epping-Jordan, M P; Watkins, S S; Koob, G F; Markou, A

1998-05-07

Tobacco smoking is a worldwide public health problem. In the United States alone, over 400,000 deaths and $50 billion in medical costs annually are directly attributed to smoking. Accumulated evidence indicates that nicotine is the component of tobacco smoke that leads to addiction, but the means by which nicotine produces addiction remain unclear. Nicotine is less effective as a positive reinforcer than other drugs of abuse in non-dependent animals. Nevertheless, nicotine-withdrawal symptoms, including depressed mood, anxiety, irritability and craving in dependent subjects may contribute to the addictive liability of nicotine. We show here that spontaneous nicotine withdrawal in rats resulted in a significant decrease in brain reward function, as measured by elevations in brain reward thresholds, which persisted for four days. Further, systemic injections of a competitive nicotinic-receptor antagonist led to a dose-dependent increase in brain reward thresholds in chronic nicotine-treated rats. The decreased function in brain reward systems during nicotine withdrawal is comparable in magnitude and duration to that of other major drugs of abuse, and may constitute an important motivational factor that contributes to craving, relapse and continued tobacco consumption in humans.

Decreased Central Nervous System Grey Matter Volume (GMV) in Smokers Affects Cognitive Abilities: A Systematic Review.

PubMed

Vňuková, Martina; Ptáček, Radek; Raboch, Jiří; Stefano, George B

2017-04-20

Although cigarette smoking is a leading cause of preventable mortality, tobacco is consumed by approximately 22% of the adult population worldwide. Smoking is also a risk factor for cardiovascular disease, affects brain processing, and is a recognized risk factor for Alzheimer disease (AD). Tobacco toxins (e.g., nicotine at high levels) inhaled in smoke may cause disorders resulting in preclinical brain changes. Researchers suggest that there are differences in brain volume between smokers and non-smokers. This review examines these differences in brain grey matter volume (GMV). In March/April 2015, MedLine, Embase, and PsycINFO were searched using the terms: "grey matter" AND "voxel-based" AND "smoking" AND "cigarette". The 4 studies analyzed found brain GMV decreases in smokers compared to non-smokers. Furthermore, sex-specific differences were found; while the thalamus and cerebellum were affected in both sexes, decreased GMV in the olfactory gyrus was found only in male smokers. Age-group differences were also found, and these may suggest pre-existing abnormalities that lead to nicotine dependence in younger individuals. Only 1 study found a positive correlation between number of pack-years smoked and GMV. Smoking decreases GMV in most brain areas. This decrease may be responsible for the cognitive impairment and difficulties with emotional regulation found in smokers compared with non-smokers.

Decreased Central Nervous System Grey Matter Volume (GMV) in Smokers Affects Cognitive Abilities: A Systematic Review

PubMed Central

Vňuková, Martina; Ptáček, Radek; Raboch, Jiří; Stefano, George B.

2017-01-01

Although cigarette smoking is a leading cause of preventable mortality, tobacco is consumed by approximately 22% of the adult population worldwide. Smoking is also a risk factor for cardiovascular disease, affects brain processing, and is a recognized risk factor for Alzheimer disease (AD). Tobacco toxins (e.g., nicotine at high levels) inhaled in smoke may cause disorders resulting in preclinical brain changes. Researchers suggest that there are differences in brain volume between smokers and non-smokers. This review examines these differences in brain grey matter volume (GMV). In March/April 2015, MedLine, Embase, and PsycINFO were searched using the terms: “grey matter” AND “voxel-based” AND “smoking” AND “cigarette”. The 4 studies analyzed found brain GMV decreases in smokers compared to non-smokers. Furthermore, sex-specific differences were found; while the thalamus and cerebellum were affected in both sexes, decreased GMV in the olfactory gyrus was found only in male smokers. Age-group differences were also found, and these may suggest pre-existing abnormalities that lead to nicotine dependence in younger individuals. Only 1 study found a positive correlation between number of pack-years smoked and GMV. Smoking decreases GMV in most brain areas. This decrease may be responsible for the cognitive impairment and difficulties with emotional regulation found in smokers compared with non-smokers. PMID:28426638

Deterioration of the anammox process at decreasing temperatures and long SRTs.

PubMed

Hoekstra, Maaike; de Weerd, Florence A; Kleerebezem, Robbert; van Loosdrecht, Mark C M

2018-03-01

The implementation of autotrophic nitrogen removal in the mainstream of a municipal wastewater treatment plant is currently pursued. Among the crucial unknown factors are the kinetic properties of anaerobic ammonium oxidising (anammox) bacteria at low temperatures. In this study we investigated the adaptation of a fast-growing anammox culture to a lower temperature. In a membrane bioreactor a highly enriched anammox community was obtained at 30°C, 25°C and 20°C. This culture was exposed to long- and short-term temperature changes. In short-term experiments the decrease in biomass-specific activity due to decrease in temperature can be described by an activation energy of 64 ± 28 kJ mol -1 . Prolonged cultivation (months) implies that cultivation at low temperatures resulted in deterioration of biomass-specific activity (Ea LT 239 kJ mol -1 ). The growth rate and specific anammox activity in the system decreased from 0.33 d -1 and 4.47 g NO 2 -N g VSS -1  d -1 at 30°C to 0.0011 d -1 and 0.037 g NO 2 -N g VSS -1  d -1 at 20°C. The reason for the deterioration of the system was related to the required long SRT in the system. The long SRT leads to an increase of non-active and non-anammox cells in the reactor, thereby decreasing the biomass-specific activity.

Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of PGC-1α expression.

PubMed

Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf; Sharma, Reeta Kumari; Kandimalla, Ramesh J L; Bal, Amanjit; Gill, Kiran Dip

2013-12-01

The present investigation was carried out to elucidate a possible molecular mechanism related to the effects of aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of Peroxisome proliferator activated receptor gamma co-activator 1α (PGC-1α) and its downstream targets i.e. Nuclear respiratory factor-1(NRF-1), Nuclear respiratory factor-2(NRF-2) and Mitochondrial transcription factor A (Tfam) in mitochondrial biogenesis. Aluminium lactate (10mg/kgb.wt./day) was administered intragastrically to rats for 12 weeks. After 12 weeks of exposure, we found an increase in ROS levels, mitochondrial DNA oxidation and decrease in citrate synthase activity in the Hippocampus (HC) and Corpus striatum (CS) regions of rat brain. On the other hand, there was a decrease in the mRNA levels of the mitochondrial encoded subunits-NADH dehydrogenase (ND) subunits i.e. ND1, ND2, ND3, Cytochrome b (Cytb), Cytochrome oxidase (COX) subunits i.e. COX1, COX3, ATP synthase (ATPase) subunit 6 along with reduced expression of nuclear encoded subunits COX4, COX5A, COX5B of Electron transport chain (ETC). Besides, a decrease in mitochondrial DNA copy number and mitochondrial content in both regions of rat brain was observed. The PGC-1α was down-regulated in aluminium treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1α in aluminium treated rats. Electron microscopy results revealed a significant increase in the mitochondrial swelling, loss of cristae, chromatin condensation and decreases in mitochondrial number in case of aluminium treated rats as compared to control. So, PGC-1α seems to be a potent target for aluminium neurotoxicity, which makes it an almost ideal target to control or limit the damage that has been associated with the defective mitochondrial function seen in neurodegenerative diseases. © 2013.

Calorically restricted diets decrease PCSK9 in overweight adolescents.

PubMed

Levenson, A E; Milliren, C E; Biddinger, S B; Ebbeling, C B; Feldman, H A; Ludwig, D S; de Ferranti, S D

2017-04-01

Nutritional therapy is the first line approach to treatment of hyperlipidemia in childhood. Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of plasma cholesterol levels and a target of novel lipid-lowering pharmacotherapies. We examined the effects of an intensive nutritional intervention on PCSK9 levels in overweight adolescents with cardiovascular disease (CVD) risk factors. Twenty seven obese and overweight adolescents with CVD risk factors were assigned to either a low fat or low glycemic load diet. During an 8-week "Intensive Phase," assigned meals were delivered to the home, and all participants received weekly in-person home nutrition counseling and phone calls. The subjects then underwent a 4-month "Maintenance Phase" without food provision and with no in-person contact. Anthropometric measurements, laboratory data, and serum PCSK9 protein levels were measured at baseline, 8 weeks, and 6 months. PCSK9 decreased by 16.5% at 8 weeks (201.2 ± 56.3 vs 165.6 ± 58.4 ng/mL; p < 0.001); PCSK9 levels returned to baseline levels at 6 months, after the Maintenance Phase. Change in PCSK9 was associated with change in fasting insulin, HOMA-IR, and AUC insulin, independent of weight loss. PCSK9 decreased in youth participating in an intensive dietary intervention. Change in HOMA-IR was associated with change in PCSK9, independent of weight loss, suggesting an important relationship with insulin sensitivity. ClinicalTrials.gov Identifier: NCT01080339. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Observed decrease in atmospheric mercury explained by global decline in anthropogenic emissions.

PubMed

Zhang, Yanxu; Jacob, Daniel J; Horowitz, Hannah M; Chen, Long; Amos, Helen M; Krabbenhoft, David P; Slemr, Franz; St Louis, Vincent L; Sunderland, Elsie M

2016-01-19

Observations of elemental mercury (Hg(0)) at sites in North America and Europe show large decreases (∼ 1-2% y(-1)) from 1990 to present. Observations in background northern hemisphere air, including Mauna Loa Observatory (Hawaii) and CARIBIC (Civil Aircraft for the Regular Investigation of the atmosphere Based on an Instrument Container) aircraft flights, show weaker decreases (<1% y(-1)). These decreases are inconsistent with current global emission inventories indicating flat or increasing emissions over that period. However, the inventories have three major flaws: (i) they do not account for the decline in atmospheric release of Hg from commercial products; (ii) they are biased in their estimate of artisanal and small-scale gold mining emissions; and (iii) they do not properly account for the change in Hg(0)/Hg(II) speciation of emissions from coal-fired utilities after implementation of emission controls targeted at SO2 and NOx. We construct an improved global emission inventory for the period 1990 to 2010 accounting for the above factors and find a 20% decrease in total Hg emissions and a 30% decrease in anthropogenic Hg(0) emissions, with much larger decreases in North America and Europe offsetting the effect of increasing emissions in Asia. Implementation of our inventory in a global 3D atmospheric Hg simulation [GEOS-Chem (Goddard Earth Observing System-Chemistry)] coupled to land and ocean reservoirs reproduces the observed large-scale trends in atmospheric Hg(0) concentrations and in Hg(II) wet deposition. The large trends observed in North America and Europe reflect the phase-out of Hg from commercial products as well as the cobenefit from SO2 and NOx emission controls on coal-fired utilities.

Cholinergic Basal Forebrain Lesion Decreases Neurotrophin Signaling without Affecting Tau Hyperphosphorylation in Genetically Susceptible Mice.

PubMed

Turnbull, Marion T; Coulson, Elizabeth J

2017-01-01

Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation. Our results reveal that the loss of BFCNs in pre-symptomatic pR5 (P301L) tau transgenic mice results in a decrease in hippocampal brain-derived neurotrophic factor levels and reduced TrkB receptor activation. However, there was no exacerbation of the levels of phosphorylated tau or its aggregation in the hippocampus of susceptible mice. Furthermore the animals' performance in a hippocampal-dependent learning and memory task was unaltered, and no changes in hippocampal synaptic markers were observed. This suggests that tau pathology is likely to be regulated independently of BFCN degeneration and the corresponding decrease in hippocampal neurotrophin levels, although these features may still contribute to disease etiology.

Serum vascular endothelial growth factor B is elevated in women with polycystic ovary syndrome and can be decreased with metformin treatment.

PubMed

Cheng, Feifei; Zhao, Lu; Wu, Yuanyuan; Huang, Tiantian; Yang, Gangyi; Zhang, Zhanyu; Wu, Yijia; Jia, Fang; Wu, Jinlin; Chen, Chen; Liu, Dongfang

2016-03-01

To determine serum vascular endothelial growth factor B (VEGF-B) levels in polycystic ovary syndrome, their association with insulin resistance and β-cell dysfunction, and the effect of metformin on serum VEGF-B levels. A cross-sectional, interventional study. We recruited 103 women with polycystic ovary syndrome and 96 age-matched healthy controls. Serum VEGF-B levels were determined in all participants, and 44 polycystic ovary syndrome patients randomly received metformin. We measured VEGF-B levels in healthy controls and women with polycystic ovary syndrome before and after metformin treatment. Women with polycystic ovary syndrome had higher serum VEGF-B levels, which decreased with metformin treatment. In the lean and overweight/obese groups, patients with polycystic ovary syndrome had higher plasma VEGF-B levels than did healthy controls (P < 0·05). VEGF-B levels were correlated with body mass index, body fat percentage, M values, homeostasis model assessment of insulin resistance and β-cell function indices. A multiple linear regression analysis showed that VEGF-B level was associated with M values after adjusting for age, body mass index, serum sex hormones and serum lipids in women with polycystic ovary syndrome. Serum VEGF-B is significantly higher in women with polycystic ovary syndrome and is closely and positively related to insulin resistance. Metformin treatment reduces VEGF-B levels and ameliorates insulin resistance. © 2015 John Wiley & Sons Ltd.

Placental telomere length decreases with gestational age and is influenced by parity: a study of third trimester live-born twins.

PubMed

Gielen, M; Hageman, G; Pachen, D; Derom, C; Vlietinck, R; Zeegers, M P

2014-10-01

In contrast to the postnatal period, little is known about telomere length (TL) during prenatal life. The decrease in placental TL remains unknown, although intra uterine growth retardation and preeclampsia are associated with shorter placental TL. The aim of this study is to assess the decrease of placental TL during the third trimester of gestation and to explore the role of potential "growth influencing factors". The study sample consisted of 329 live-born twins from the East Flanders Prospective Twin Survey. TL was determined using a multiplex quantitative PCR method. Gestational age, sex, birth order, placental characteristics, parity, maternal and paternal age, diabetes, hypertension, smoking, alcohol use, and socio economic status (SES) were considered "growth influencing factors". Bivariable multilevel regression analysis with "growth influencing factors" was performed. Placental TL ranged from 4.3 kbp to 84.4 kbp with a median of 10.8 kbp. Ln(TL) decreased in a linear fashion with an estimated TL decreasing from 13.98 kbp at 28 weeks to 10.56 kbp at 42 weeks. The regression coefficient of gestational age became smaller if considered together with SES (b = -0.017; p = 0.08) or diabetes (b = -0.018; p = 0.07) and bigger if considered together with parity (b = -0.022; p = 0.02), indicating that part of the association between gestational age and telomere length is explained by these three confounding factors. Placental TL decreases during the third trimester of gestation of live-born twins with approximately 25% indicating that telomere shortening may play a role in aging of the placenta. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetic Factors That Increase Male Facial Masculinity Decrease Facial Attractiveness of Female Relatives

PubMed Central

Lee, Anthony J.; Mitchem, Dorian G.; Wright, Margaret J.; Martin, Nicholas G.; Keller, Matthew C.; Zietsch, Brendan P.

2014-01-01

For women, choosing a facially masculine man as a mate is thought to confer genetic benefits to offspring. Crucial assumptions of this hypothesis have not been adequately tested. It has been assumed that variation in facial masculinity is due to genetic variation and that genetic factors that increase male facial masculinity do not increase facial masculinity in female relatives. We objectively quantified the facial masculinity in photos of identical (n = 411) and nonidentical (n = 782) twins and their siblings (n = 106). Using biometrical modeling, we found that much of the variation in male and female facial masculinity is genetic. However, we also found that masculinity of male faces is unrelated to their attractiveness and that facially masculine men tend to have facially masculine, less-attractive sisters. These findings challenge the idea that facially masculine men provide net genetic benefits to offspring and call into question this popular theoretical framework. PMID:24379153

Genetic factors that increase male facial masculinity decrease facial attractiveness of female relatives.

PubMed

Lee, Anthony J; Mitchem, Dorian G; Wright, Margaret J; Martin, Nicholas G; Keller, Matthew C; Zietsch, Brendan P

2014-02-01

For women, choosing a facially masculine man as a mate is thought to confer genetic benefits to offspring. Crucial assumptions of this hypothesis have not been adequately tested. It has been assumed that variation in facial masculinity is due to genetic variation and that genetic factors that increase male facial masculinity do not increase facial masculinity in female relatives. We objectively quantified the facial masculinity in photos of identical (n = 411) and nonidentical (n = 782) twins and their siblings (n = 106). Using biometrical modeling, we found that much of the variation in male and female facial masculinity is genetic. However, we also found that masculinity of male faces is unrelated to their attractiveness and that facially masculine men tend to have facially masculine, less-attractive sisters. These findings challenge the idea that facially masculine men provide net genetic benefits to offspring and call into question this popular theoretical framework.

Nocturnal polyuria and decreased serum testosterone: is there an association in men with lower urinary tract symptoms?

PubMed

Kim, Jin Wook; Oh, Mi Mi; Yoon, Cheol Yong; Bae, Jae Hyun; Kim, Je Jong; Moon, Du Geon

2014-05-01

To investigate the putative association between nocturia and decreased serum testosterone in men with lower urinary tract symptoms. Frequency volume charts and serum testosterone levels of patients visiting the outpatient clinic for lower urinary tract symptoms were collected and analyzed. Age, prostate volume, body mass index and the presence of comorbidities were accounted for. Frequency volume charts were analyzed for pathophysiological components of nocturnal polyuria, global polyuria, decreased nocturnal bladder capacity and increased frequency to identify associated risks. Frequency volume charts were also used to chart 8-h changes of volume, frequency and capacity to identify time diurnal interactions with risk factors based on serum testosterone levels. A total of 2180 patients were enrolled in the study. Multivariate analysis showed testosterone decreased 0.142 ng/mL for every increase in nocturia, independent of other factors. Logistic regression analysis showed a significant difference between pathophysiological components. Decreased testosterone was shown to carry a significant independent risk for overall nocturia (odds ratio 1.60, 95% confidence interval 1.013-2.527, P = 0.044), and particularly nocturnal polyuria (odds ratio 1.934, 95% confidence interval 1.001-3.737, P = 0.027). Repeated measurement models showed patients with serum testosterone below 2.50 ng/mL to have a paradoxical increase in nocturnal urine volume at night. Nocturia, especially nocturnal polyuria, is associated with decreased serum testosterone. Patients with low serum testosterone show increased nocturnal urine output. © 2013 The Japanese Urological Association.

Projections of increased and decreased dengue incidence under climate change.

PubMed

Williams, C R; Mincham, G; Faddy, H; Viennet, E; Ritchie, S A; Harley, D

2016-10-01

Dengue is the world's most prevalent mosquito-borne disease, with more than 200 million people each year becoming infected. We used a mechanistic virus transmission model to determine whether climate warming would change dengue transmission in Australia. Using two climate models each with two carbon emission scenarios, we calculated future dengue epidemic potential for the period 2046-2064. Using the ECHAM5 model, decreased dengue transmission was predicted under the A2 carbon emission scenario, whereas some increases are likely under the B1 scenario. Dengue epidemic potential may decrease under climate warming due to mosquito breeding sites becoming drier and mosquito survivorship declining. These results contradict most previous studies that use correlative models to show increased dengue transmission under climate warming. Dengue epidemiology is determined by a complex interplay between climatic, human host, and pathogen factors. It is therefore naive to assume a simple relationship between climate and incidence, and incorrect to state that climate warming will uniformly increase dengue transmission, although in general the health impacts of climate change will be negative.

Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior.

PubMed

Chourbaji, Sabine; Hellweg, Rainer; Brandis, Dorothee; Zörner, Björn; Zacher, Christiane; Lang, Undine E; Henn, Fritz A; Hörtnagl, Heide; Gass, Peter

2004-02-05

The "neurotrophin hypothesis" of depression predicts that depressive disorders in humans coincide with a decreased activity and/or expression of brain-derived neurotrophic factor (BDNF) in the brain. Therefore, we investigated whether mice with a reduced BDNF expression due to heterozygous gene disruption demonstrate depression-like neurochemical changes or behavioral symptoms. BNDF protein levels of adult BDNF(+/-) mice were reduced to about 60% in several brain areas investigated, including the hippocampus, frontal cortex, striatum, and hypothalamus. The content of monoamines (serotonin, norepinephrine, and dopamine) as well as of serotonin and dopamine degradation products was unchanged in these brain regions. By contrast, choline acetyltransferase activity was significantly reduced by 19% in the hippocampus of BDNF(+/-) mice, indicating that the cholinergic system of the basal forebrain is critically dependent on sufficient endogenous BDNF levels in adulthood. Moreover, BDNF(+/-) mice exhibited normal corticosterone and adrenocorticotropic hormone (ACTH) serum levels under baseline conditions and following immobilization stress. In a panel of behavioral tests investigating locomotor activity, exploration, anxiety, fear-associated learning, and behavioral despair, BDNF(+/-) mice were indistinguishable from wild-type littermates. Thus, a chronic reduction of BDNF protein content in adult mice is not sufficient to induce neurochemical or behavioral alterations that are reminiscent of depressive symptoms in humans.

Upregulation of PEDF expression by PARP inhibition contributes to the decrease in hyperglycemia-induced apoptosis in HUVECs

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

Chen Haibing; Department of Ophthalmology, Anhui Provincial Hospital, Hefei; Jia Weiping

2008-05-02

Poly(ADP-ribose)polymerase (PARP) inhibitors decrease angiogenesis through reducing vascular endothelium growth factor (VEGF) induced proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). In contrast to VEGF, pigment epithelium-derived factor (PEDF) has been demonstrated to act as a strong endogenous inhibitor of angiogenesis. Here, we show that PARP inhibition with a specific inhibitor PJ-34 or specific PARP antisense oligonucleotide upregulates hyperglycemia-induced PEDF expression in HUVECs in a dose-dependent manner. This results in the retard of activation of p38 MAP kinase and the concomitant decrease in cell apoptosis. These results give the first direct demonstration that PEDF might representmore » a target for PARP inhibition treatment and the effects of PEDF on endothelial cells growth are context dependent.« less

Influence of Terraced area DEM Resolution on RUSLE LS Factor

NASA Astrophysics Data System (ADS)

Zhang, Hongming; Baartman, Jantiene E. M.; Yang, Xiaomei; Gai, Lingtong; Geissen, Viollette

2017-04-01

Topography has a large impact on the erosion of soil by water. Slope steepness and slope length are combined (the LS factor) in the universal soil-loss equation (USLE) and its revised version (RUSLE) for predicting soil erosion. The LS factor is usually extracted from a digital elevation model (DEM). The grid size of the DEM will thus influence the LS factor and the subsequent calculation of soil loss. Terracing is considered as a support practice factor (P) in the USLE/RUSLE equations, which is multiplied with the other USLE/RUSLE factors. However, as terraces change the slope length and steepness, they also affect the LS factor. The effect of DEM grid size on the LS factor has not been investigated for a terraced area. We obtained a high-resolution DEM by unmanned aerial vehicles (UAVs) photogrammetry, from which the slope steepness, slope length, and LS factor were extracted. The changes in these parameters at various DEM resolutions were then analysed. The DEM produced detailed LS-factor maps, particularly for low LS factors. High (small valleys, gullies, and terrace ridges) and low (flats and terrace fields) spatial frequencies were both sensitive to changes in resolution, so the areas of higher and lower slope steepness both decreased with increasing grid size. Average slope steepness decreased and average slope length increased with grid size. Slope length, however, had a larger effect than slope steepness on the LS factor as the grid size varied. The LS factor increased when the grid size increased from 0.5 to 30-m and increased significantly at grid sizes >5-m. The LS factor was increasingly overestimated as grid size decreased. The LS factor decreased from grid sizes of 30 to 100-m, because the details of the terraced terrain were gradually lost, but the factor was still overestimated.

Social-ecological factors and preventive actions decrease the risk of dengue infection at the household-level: Results from a prospective dengue surveillance study in Machala, Ecuador

PubMed Central

Kenneson, Aileen; Beltrán-Ayala, Efraín; Borbor-Cordova, Mercy J.; Polhemus, Mark E.; Ryan, Sadie J.; Endy, Timothy P.

2017-01-01

Background In Ecuador, dengue virus (DENV) infections transmitted by the Aedes aegypti mosquito are among the greatest public health concerns in urban coastal communities. Community- and household-level vector control is the principal means of controlling disease outbreaks. This study aimed to assess the impact of knowledge, attitudes, and practices (KAPs) and social-ecological factors on the presence or absence of DENV infections in the household. Methods In 2014 and 2015, individuals with DENV infections from sentinel clinics in Machala, Ecuador, were invited to participate in the study, as well as members of their household and members of four neighboring households located within 200 meters. We conducted diagnostic testing for DENV on all study participants; we surveyed heads of households (HOHs) regarding demographics, housing conditions and KAPs. We compared KAPs and social-ecological factors between households with (n = 139) versus without (n = 80) DENV infections, using bivariate analyses and multivariate logistic regression models with and without interactions. Results Significant risk factors in multivariate models included proximity to abandoned properties, interruptions in piped water, and shaded patios (p<0.05). Significant protective factors included the use of mosquito bed nets, fumigation inside the home, and piped water inside the home (p<0.05). In bivariate analyses (but not multivariate modeling), DENV infections were positively associated with HOHs who were male, employed, and of younger age than households without infections (p<0.05). DENV infections were not associated with knowledge, attitude, or reported barriers to prevention activities. Discussion Specific actions that can be considered to decrease the risk of DENV infections in the household include targeting vector control in highly shaded properties, fumigating inside the home, and use of mosquito bed nets. Community-level interventions include cleanup of abandoned properties, daily

Exercise-induced decrease in insular cortex rCBF during postexercise hypotension.

PubMed

Lamb, Kala; Gallagher, Kevin; McColl, Roderick; Mathews, Dana; Querry, Ross; Williamson, Jon W

2007-04-01

The insular cortex (IC), a region of the brain involved in blood pressure (BP) modulation, shows decreases in regional cerebral blood flow (rCBF) during postexercise hypotension (PEH). To determine whether changes in IC neural activity were caused by prior exercise or by changes in BP, this investigation compared patterns of rCBF during periods of hypotension, which was induced by prior exercise (i.e., PEH) and sodium nitroprusside (SNP) infusion and a cold pressor (CP), to restore BP. Ten subjects were studied on three different days with randomly assigned conditions: i) resting baseline; ii) PEH; and iii) SNP-induced hypotension (matched to the PEH BP decrease). Data were collected for heart rate (HR) and mean BP, and rCBF was assessed using single-photon emission computed tomography (SPECT) as an index of brain activation. Using ANOVA across conditions, there were differences (P<0.05; mean +/- SD) from baseline during PEH for HR (+12 +/- 3 bpm) and mean BP (-8 +/- 2 mm Hg) and during SNP-induced hypotension (HR = +15 +/- 4 bpm; MBP = -9 +/- 2 mm Hg), with no differences between PEH and SNP. After exercise, there were decreases (P<0.05) in the leg sensorimotor area, anterior cingulate, and the right and left inferior thalamus, right inferior insula, and left anterior insular regions. During SNP-induced hypotension, there were significant increases in the right and left inferior thalamus and the right and left inferior anterior IC. CP during PEH increased BP and IC activity. Data show that reductions in IC neural activity are not caused by acute BP decreases. Findings suggest that exercise can lead to a temporary decrease in IC neural activity, which may be a significant neural factor contributing to PEH.

Observed decrease in atmospheric mercury explained by global decline in anthropogenic emissions

PubMed Central

Zhang, Yanxu; Jacob, Daniel J.; Horowitz, Hannah M.; Chen, Long; Amos, Helen M.; Krabbenhoft, David P.; Slemr, Franz; St. Louis, Vincent L.; Sunderland, Elsie M.

2016-01-01

Observations of elemental mercury (Hg0) at sites in North America and Europe show large decreases (∼1–2% y−1) from 1990 to present. Observations in background northern hemisphere air, including Mauna Loa Observatory (Hawaii) and CARIBIC (Civil Aircraft for the Regular Investigation of the atmosphere Based on an Instrument Container) aircraft flights, show weaker decreases (<1% y−1). These decreases are inconsistent with current global emission inventories indicating flat or increasing emissions over that period. However, the inventories have three major flaws: (i) they do not account for the decline in atmospheric release of Hg from commercial products; (ii) they are biased in their estimate of artisanal and small-scale gold mining emissions; and (iii) they do not properly account for the change in Hg0/HgII speciation of emissions from coal-fired utilities after implementation of emission controls targeted at SO2 and NOx. We construct an improved global emission inventory for the period 1990 to 2010 accounting for the above factors and find a 20% decrease in total Hg emissions and a 30% decrease in anthropogenic Hg0 emissions, with much larger decreases in North America and Europe offsetting the effect of increasing emissions in Asia. Implementation of our inventory in a global 3D atmospheric Hg simulation [GEOS-Chem (Goddard Earth Observing System-Chemistry)] coupled to land and ocean reservoirs reproduces the observed large-scale trends in atmospheric Hg0 concentrations and in HgII wet deposition. The large trends observed in North America and Europe reflect the phase-out of Hg from commercial products as well as the cobenefit from SO2 and NOx emission controls on coal-fired utilities. PMID:26729866

Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures

PubMed Central

LaFrance, W.C.; Leaver, K.; Stopa, E.G.; Papandonatos, G.D.; Blum, A.S.

2010-01-01

Objective: Neurotrophins promote neurogenesis and help regulate synaptic reorganization. Their dysregulation has been implicated in a number of neurologic and psychiatric disorders. Previous studies have shown decreased levels of brain-derived neurotrophic factor (BDNF) in the serum of patients with psychiatric disorders such as major depressive disorder (MDD) and conversion disorder (CD). In human patients with temporal lobe epilepsy, there is an increase in both BDNF mRNA and protein levels in surgically resected hippocampi compared to controls. One study of children with epilepsy has found normal to increased serum BDNF levels compared to controls. Serum BDNF levels have not been investigated in adult patients with epileptic seizures (ES). We hypothesized that BDNF would differentiate between ES and psychogenic nonepileptic seizures (PNES). Methods: We assessed serum BDNF immunoreactivity in 15 patients with ES, 12 patients with PNES, and 17 healthy volunteers. Serum BDNF levels were measured using an enzyme-linked immunoassay. Results: Healthy controls showed higher BDNF levels (4,289 ± 1,810 pg/mL) compared to patients with PNES (1,033 ± 435 pg/mL) (p < 0.001). However, unexpectedly, healthy controls also showed higher levels of BDNF compared to patients with ES without comorbid MDD (977 ± 565 pg/mL) (p < 0.001). Conclusions: Unlike children, adults with epilepsy appear to have decreased levels of serum BDNF. Reduced serum BDNF levels can be used to differentiate adult patients with ES or PNES from healthy controls. Further human studies are needed to better understand the pathophysiology explaining the decreased serum BDNF levels found in epilepsy and in PNES. GLOSSARY AED = antiepileptic drug; BDI-II = Beck Depression Inventory II; BDNF = brain-derived neurotrophic factor; CD = conversion disorder; ECS = electroconvulsive seizure; ES = epileptic seizure; GTC = generalized tonic-clonic seizure; HC = healthy control; MDD = major depressive disorder; PNES

Decreased muscle mass is not an independent risk factor for metabolic syndrome in Korean population aged 70 or older.

PubMed

Koo, Hyung Suk; Kim, Moon Jong; Kim, Kwang-Min; Kim, Young-Sang

2015-04-01

The association of low muscle mass with cardiometabolic risks is still controversial. The aim of this study was to investigate the relationship between low muscle mass and metabolic syndrome (MetS) according to the various muscle mass indices and to evaluate the influence of muscle mass on MetS independent of fat mass. Cross-sectional study About 841 men and 1106 women aged 70 or older from Korea National Health and Nutrition Examination Survey 2008-2010 MEASUREMENTS: We used various muscle mass indices: appendicular skeletal muscle mass (ASM) divided by height squared (ASM/Ht(2) ), ASM divided by body weight (ASM/Wt) and ASM adjusted for height and fat mass (residual). Low muscle mass is defined as ASM/Ht(2) and ASM/Wt below 2 SD of the sex-specific mean for healthy young adults. The sex-specific lowest quintile of the distribution of the residual was regarded as low muscle mass. The prevalence of MetS was higher in the population with low muscle mass defined by ASM/Wt, but lower in those defined by ASM/Ht(2) . However, after stratification according to the central obesity, low muscle mass was barely related with MetS. Meanwhile, when both ASM and fat mass were included in a logistic regression model, the odds ratios of 1 SD change of ASM for MetS were 1·07 (0·85-1·34) for men and 1·24 (1·04-1·47) for women, respectively. The relationship between low muscle mass and MetS was different according to the various muscle mass indices. After controlling the influence of fat mass, decreased muscle mass was not an independent risk factor for MetS. © 2014 John Wiley & Sons Ltd.

Using Bayes factors for multi-factor, biometric authentication

NASA Astrophysics Data System (ADS)

Giffin, A.; Skufca, J. D.; Lao, P. A.

2015-01-01

Multi-factor/multi-modal authentication systems are becoming the de facto industry standard. Traditional methods typically use rates that are point estimates and lack a good measure of uncertainty. Additionally, multiple factors are typically fused together in an ad hoc manner. To be consistent, as well as to establish and make proper use of uncertainties, we use a Bayesian method that will update our estimates and uncertainties as new information presents itself. Our algorithm compares competing classes (such as genuine vs. imposter) using Bayes Factors (BF). The importance of this approach is that we not only accept or reject one model (class), but compare it to others to make a decision. We show using a Receiver Operating Characteristic (ROC) curve that using BF for determining class will always perform at least as well as the traditional combining of factors, such as a voting algorithm. As the uncertainty decreases, the BF result continues to exceed the traditional methods result.

A proactive outreach intervention that decreases readmission after hepatectomy.

PubMed

Narula, Nisha; Kim, Bradford J; Davis, Catherine H; Dewhurst, Whitney L; Samp, Leigh A; Aloia, Thomas A

2018-04-01

After hepatectomy, 7%-19% of patients are readmitted within 30 days, accounting for substantial cost and poor patient experience. The purpose of this study was to analyze the impact of a proactive outreach intervention on readmissions. Consecutive patients undergoing hepatectomy by a single surgeon 2012-2016 were identified in a prospectively maintained database. In August 2013 a postoperative intervention was implemented; an advanced practice provider called each patient within 72 hours of discharge. Readmission rates were compared pre- and postintervention using standard statistics. Two hundred thirty-one patients met the inclusion criteria and major hepatectomy was performed in 45.5% of patients. Although the complication rate was similar (25.0% preintervention and 19.4% postintervention, P = .324), readmissions within 30 days of operation decreased from 14.5% pre- to 6.5% postintervention (P = .046). Approximately 30% of outreach interactions required outpatient intervention. Factors associated with readmission on univariate analysis included increased operative time (P = .007), major hepatectomy (P = .012), hemi or extended hepatectomy (P = .032), second stage operation (P = .031), bile leak (P = 0.022), and any complication/modified Accordion complication ≥ 3 within 30 days (P <.0001). On multivariate analysis, lack of post-discharge intervention (P = .012) and bile leak (P = .031) were independently associated with readmission. These data demonstrate the efficacy of a proactive communication intervention after discharge to decrease readmissions after hepatectomy. The additional work created by the intervention is likely offset by decreased inpatient care needs and costs. Identification of high-risk populations and application of technology are likely to lead to further improvements. Copyright © 2017 Elsevier Inc. All rights reserved.

Calcitriol decreases TGF-β1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats.

PubMed

Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Liou, Hung-Hsiang; Hsu, Bang-Gee

2014-01-01

Peritoneal fibrosis is a major complication of peritoneal dialysis that can lead to ultrafiltration failure. This study investigates the protective effects of calcitriol on chlorhexidine digluconate-induced peritoneal fibrosis in rats. Peritoneal fibrosis was induced in Sprague-Dawley rats by daily administration of 0.5mL 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis for 1week. Rats received daily intravenous injections of calcitriol (low-dose, 10ng/kg; or high-dose, 100ng/kg) for 1week. After 7days, conventional 4.25% Dianeal (30mL) was administered via peritoneal dialysis over 4h. Peritoneal solute transport was calculated from the dialysate concentration relative to its concentration in the initial infused dialysis solution (D4/D0 glucose) for glucose, and the dialysate-to-plasma concentration ratio (D4/P4 urea) at 4h for urea. Rats were then sacrificed and the liver peritoneum was harvested for immunohistochemical analysis via microscopy. After dialysis, the D4/P4 Urea level was reduced; increases were observed in the D4/D0 glucose level and the levels of active transforming growth factor-β1 and angiotensin II in serum and dialysate; the liver peritoneum and muscle peritoneum was markedly thickened, and the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and phosphorylated Smad2/3 (P-Smad2/3)-positive cells in the liver peritoneum was elevated in the peritoneal fibrosis group compared with the vehicle group. Calcitriol decreased the serum and dialysate active transforming growth factor-β1 and angiotensin II level, decreased the thickness of the liver peritoneum and muscle peritoneum, and decreased the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and P-Smad2/3-positive cells in liver peritoneum cells. High-dose calcitriol exhibited better protective effects against

Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

PubMed Central

Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian

2013-01-01

Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the decrease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance. PMID:25206547

Decreased tongue pressure is associated with sarcopenia and sarcopenic dysphagia in the elderly.

PubMed

Maeda, Keisuke; Akagi, Junji

2015-02-01

The aim of this study was to clarify the association between tongue pressure and factors related to sarcopenia such as aging, activities of daily living, nutritional state, and dysphagia. One-hundred-and-four patients without a history of treatment of stroke and without a diagnosis of neurodegenerative disease (36 men and 68 women), with a mean age of 84.1 ± 5.6 years, hospitalized from May 2013 to June 2013 were included in this study. Maximum voluntary tongue pressure against the palate (MTP) was measured by a device consisting of a disposable oral balloon probe. Nutritional and anthropometric parameters such as serum albumin concentration, Mini-Nutritional Assessment short form (MNA-SF), body mass index, arm muscle area (AMA), and others and presence of sarcopenia and dysphagia were analyzed to evaluate their relationships. Correlation analysis and univariate or multivariate analysis were performed. Simple correlation analysis showed that MTP correlated with Barthel index (BI), MNA-SF, serum albumin concentration, body mass index, and AMA. Univariate and multivariate analysis showed that sarcopenia, BI, MNA-SF, and age were the independent explanatory factors for decreased MTP, and the propensity score for dysphagia, including causes of primary or secondary sarcopenia, and the presence of sarcopenia were significantly associated with the presence of dysphagia. Decreased MTP and dysphagia were related to sarcopenia or the causes of sarcopenia in the studied population. Furthermore, the clinical condition of sarcopenic dysphagia may be partially interpreted as the presence of sarcopenia and causal factors for sarcopenia.

Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis.

PubMed

Meier, Remo; Lutz, Christian; Cosín-Roger, Jesus; Fagagnini, Stefania; Bollmann, Gabi; Hünerwadel, Anouk; Mamie, Celine; Lang, Silvia; Tchouboukov, Alexander; Weber, Franz E; Weber, Achim; Rogler, Gerhard; Hausmann, Martin

2016-03-01

Fibrosis as a common problem in patients with Crohn's disease is a result of an imbalance toward excessive tissue repair. At present, there is no specific treatment option. Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis with both antifibrotic and anti-inflammatory effects. We subsequently investigated the impact of pirfenidone treatment on development of fibrosis in a new mouse model of intestinal fibrosis. Small bowel resections from donor mice were transplanted subcutaneously into the neck of recipients. Animals received either pirfenidone (100 mg/kg, three times daily, orally) or vehicle. After administration of pirfenidone, a significantly decreased collagen layer thickness was revealed as compared to vehicle (9.7 ± 1.0 versus 13.5 ± 1.5 µm, respectively, **P < 0.001). Transforming growth factor-β and matrix metalloproteinase-9 were significantly decreased after treatment with pirfenidone as confirmed by real-time PCR (0.42 ± 0.13 versus 1.00 ± 0.21 and 0.46 ± 0.24 versus 1.00 ± 0.62 mRNA expression level relative to GAPDH, respectively, *P < 0.05). Significantly decreased transforming growth factor-β after administration of pirfenidone was confirmed by Western blotting. In our mouse model, intestinal fibrosis can be reliably induced and is developed within 7 days. Pirfenidone partially prevented the development of fibrosis, making it a potential treatment option against Crohn's disease-associated fibrosis.

Mediators and Treatment Factors in Intervention for Children Exposed to Interparental Violence.

PubMed

Overbeek, Mathilde M; De Schipper, J Clasien; Willemen, Agnes M; Lamers-Winkelman, Francien; Schuengel, Carlo

2017-01-01

Changes in children's emotion differentiation, coping skills, parenting stress, parental psychopathology, and parent-child interaction were explored as mediators of treatment factors in two selective preventive group interventions for children exposed to interparental violence (IPV) and their parents. One hundred thirty-four IPV-exposed children (ages 6-12 years, 52% boys) and their parents were randomized to an IPV-focused or common factors community-based group intervention and completed baseline, posttest, and follow-up assessments for posttraumatic stress (PTS). A multilevel model tested mediators that included children's ability to differentiate emotions and coping skills, parenting stress, parental psychopathology, and parent-child interactions. In both conditions, exposure to nonspecific factors, specific factors unrelated to IPV and trauma-specific intervention factors was coded from videotaped child and parent sessions. Improved parental mental health mediated the link between greater exposure to nonspecific treatment factors and decreases in PTS symptoms. In addition, an increase in emotion differentiation and a decrease in parenting stress were associated with a decrease in PTS symptoms. Greater exposure to trauma-specific factors in child sessions was associated with a small decrease in emotion differentiation, an increase in coping skills, and a decrease in PTS symptoms over time. Greater exposure to nonspecific treatment factors in child and parent sessions was associated with more positive parent-child interaction. Parental mental health appears to be an important mechanism of change that can be promoted through exposure to nonspecific factors in parent intervention. For children, the effect of greater exposure to trauma-specific factors in intervention is less clear and may not have clear benefits.

Dark septate endophyte decreases stress on rice plants.

PubMed

Santos, Silvana Gomes Dos; Silva, Paula Renata Alves da; Garcia, Andres Calderin; Zilli, Jerri Édson; Berbara, Ricardo Luis Louro

Abiotic stress is one of the major limiting factors for plant development and productivity, which makes it important to identify microorganisms capable of increasing plant tolerance to stress. Dark septate endophytes can be symbionts of plants. In the present study, we evaluated the ability of dark septate endophytes isolates to reduce the effects of water stress in the rice varieties Nipponbare and Piauí. The experiments were performed under gnotobiotic conditions, and the water stress was induced with PEG. Four dark septate endophytes were isolated from the roots of wild rice (Oryza glumaepatula) collected from the Brazilian Amazon. Plant height as well as shoot and root fresh and dry matter were measured. Leaf protein concentrations and antioxidant enzyme activity were also estimated. The dark septate endophytes were grown in vitro in Petri dishes containing culture medium; they exhibited different levels of tolerance to salinity and water stress. The two rice varieties tested responded differently to inoculation with dark septate endophytes. Endophytes promoted rice plant growth both in the presence and in the absence of a water deficit. Decreased oxidative stress in plants in response to inoculation was observed in nearly all inoculated treatments, as indicated by the decrease in antioxidant enzyme activity. Dark septate endophytes fungi were shown to increase the tolerance of rice plants to stress caused by water deficiency. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Decreasing age at first anal intercourse among men who have sex with men in China: a multicentre cross-sectional survey

PubMed Central

Zou, Huachun; Xu, Junjie; Hu, Qinghai; Yu, Yanqiu; Fu, Gengfeng; Wang, Zhe; Lu, Lin; Zhuang, Minghua; Chen, Xi; Fu, Jihua; Zhou, Zhenhai; Geng, Wenqing; Jiang, Yongjun; Shang, Hong

2016-01-01

Introduction Literature on the age at first anal intercourse (AFAI) among men who have sex with men (MSM) is limited. We aimed to elucidate the evolution of AFAI and the factors associated with early AFAI, based on a large sample of MSM in China. Methods We collected information on the demographics and sexual behaviours of MSM from seven large cities in China from 2012 to 2013. Blood samples were collected for HIV serology. AFAI was calculated for MSM born in different time periods. Linear regression models were used to explore factors associated with younger AFAI. Results A total of 4491 MSM (median age: 27 years, median AFAI: 21 years) were recruited. Median AFAI decreased steadily from 33 years of age among MSM born from 1940 to 1959 to 18 years of age among MSM born from 1990 to 1996. Factors significantly associated with younger AFAI included more recent birth cohort, being unmarried or living with a male partner, being a student or industry worker, the gender of the first partner being male, and using Rush or Ecstasy in the past six months (p for all <0.05). Conclusions AFAI among MSM in China has considerably decreased over the past few decades. The decreasing AFAI and factors associated with younger AFAI point to the necessity of early sex education and control of recreational drug use among MSM in China. PMID:27515018

Green tea extract-induced lethal toxicity in fasted but not in nonfasted dogs.

PubMed

Wu, Kuei-Meng; Yao, Jiaqin; Boring, Daniel

2011-02-01

Recent chronic toxicity studies performed on green tea extracts in fasted dogs have revealed some unique dose-limiting lethal liver, gastrointestinal, and renal toxicities. Key findings included necrosis of hepatic cells, gastrointestinal epithelia and renal tubules, atrophy of reproductive organs, atrophy and necrosis of hematopoietic tissues, and associated hematological changes. The polyphenol cachetins (a mixture of primarily epigallocatechin gallate [≥55%]; plus up to 10% each of epigallocatechin, epicatechin, and epigallocatechin gallate) appeared to be the causative agents for the observed toxicities because they are the active ingredients of green tea extract studied. Conduct of the study in nonfasted dogs under the same testing conditions and dose levels showed unremarkable results. Assuming both studies were valid, at the identified no observed adverse effect levels (NOAEL) of each study, systemic exposures (based on area under the curve [AUC]) were actually lower in fasted than nonfasted dogs, suggesting that fasting may have rendered the target organ systems potentially more vulnerable to the effects of green tea extract. The toxicity mechanisms that produced lethality are not known, but the results are scientifically intriguing. Because tea drinking has become more popular in the United States and abroad, the mode of action and site of action of green tea extract-induced lethal toxicities during fasting and the role of other phytochemical components of Folia Camellia sinensis (including nonpolyphenol fractions, which are often consumed when whole-leaf products are presented) warrant further investigation.

Effects of Nuclear Factor-E2-related factor 2/Heme Oxygenase 1 on splanchnic hemodynamics in experimental cirrhosis with portal hypertension.

PubMed

Qin, Jun; He, Yue; Duan, Ming; Luo, Meng

2017-05-01

We explored the effects of Nuclear Factor-E2-related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1) on splanchnic hemodynamics in portal hypertensive rats. Experimental cirrhosis with portal hypertension was induced by intraperitoneal injection of carbon tetrachloride. The expression of proteins was examined by immunoblotting. Hemodynamic studies were performed by radioactive microspheres. The vascular perfusion system was used to measure the contractile response of mesentery arterioles in rats. Nrf2 expression in the nucleus and HO-1 expression in cytoplasm was significantly enhanced in portal hypertensive rats. Portal pressure, as well as regional blood flow, increased significantly in portal hypertension and can be blocked by tin protoporphyrin IX. The expression of endogenous nitric oxide synthase and vascular endothelial growth factors increased significantly compared to normal rats, while HO-1 inhibition decreased the expression of these proteins significantly. The contractile response of mesenteric arteries decreased in portal hypertension, but can be partially recovered through tin protoporphyrin IX treatment. The expression of Nrf2/HO-1 increased in mesenteric arteries of portal hypertensive rats, which was related to oxidative stress. HO-1was involved in increased portal pressure and anomaly splanchnic hemodynamics in portal hypertensive rats. Copyright © 2016 Elsevier Inc. All rights reserved.

The anti-fibrotic effect of liver growth factor is associated with decreased intrahepatic levels of matrix metalloproteinases 2 and 9 and transforming growth factor beta 1 in bile duct-ligated rats.

PubMed

Díaz-Gil, Juan J; García-Monzón, Carmelo; Rúa, Carmen; Martín-Sanz, Paloma; Cereceda, Rosa M; Miquilena-Colina, María E; Machín, Celia; Fernández-Martínez, Amalia; García-Cañero, Rarael

2008-05-01

Liver growth factor (LGF), a mitogen for liver cells, behaves as an anti-fibrotic agent even in extrahepatic sites, but its mechanistic basis is unknown. We aimed to determine the intrahepatic expression pattern of key modulators of liver fibrosis in bile duct-ligated rats (BDL) after injection of LGF. BDL rats received either LGF (4.5 microg/ratXdose, two doses/week, at time 0 or 2 or 5w after operation, depending on the group (BDL+LGF groups, n=20) or saline (BDL+S groups, n=20). Groups were compared in terms of fibrosis (histomorphometry), liver function (aminopyrine breath test), matrix metalloproteinases MMP-2 and MMP-9, transforming growth factor beta 1 (TGF-beta1) and liver endoglin content (Western blotting), and serum tissue inhibitor of metalloproteinases 1 (TIMP-1) levels (ELISA). In BDL+LGF rats, the fibrotic index was significantly lower at 5w, p=0.006, and at 8w, p=0.04, than in BDL+S rats. Liver function values in BDL+LGF rats were higher than those obtained in BDL+S rats (80% at 5w and 79% at 8w, versus 38% and 29%, p<0.01, taking healthy controls as 100%). Notably, in BDL+LGF rats the intrahepatic expression levels of both MMPs were lower at 2w (MMP-2, p=0.03; MMP-9, p=0.05) and 5w (MMP-2, p=0.05, MMP-9, p=0.04). In addition, the hepatic TGF-beta1 level in BDL+LGF rats was lower at 2w (36%, p=0.008), 5w (50%) and 8wk (37%), whereas intrahepatic endoglin expression remained constant in all BDL rats studied. LGF ameliorates liver fibrosis and improves liver function in BDL rats. The LGF-induced anti-fibrotic effect is associated with a decreased hepatic level of MMP-2, MMP-9 and TGF-beta1 in fibrotic rats.

Low Oxygen Modulates Multiple Signaling Pathways, Increasing Self-Renewal, While Decreasing Differentiation, Senescence, and Apoptosis in Stromal MIAMI Cells

PubMed Central

Rios, Carmen; D'Ippolito, Gianluca; Curtis, Kevin M.; Delcroix, Gaëtan J.-R.; Gomez, Lourdes A.; El Hokayem, Jimmy; Rieger, Megan; Parrondo, Ricardo; de las Pozas, Alicia; Perez-Stable, Carlos; Howard, Guy A.

2016-01-01

Human bone marrow multipotent mesenchymal stromal cell (hMSC) number decreases with aging. Subpopulations of hMSCs can differentiate into cells found in bone, vasculature, cartilage, gut, and other tissues and participate in their repair. Maintaining throughout adult life such cell subpopulations should help prevent or delay the onset of age-related degenerative conditions. Low oxygen tension, the physiological environment in progenitor cell-rich regions of the bone marrow microarchitecture, stimulates the self-renewal of marrow-isolated adult multilineage inducible (MIAMI) cells and expression of Sox2, Nanog, Oct4a nuclear accumulation, Notch intracellular domain, notch target genes, neuronal transcriptional repressor element 1 (RE1)-silencing transcription factor (REST), and hypoxia-inducible factor-1 alpha (HIF-1α), and additionally, by decreasing the expression of (i) the proapoptotic proteins, apoptosis-inducing factor (AIF) and Bak, and (ii) senescence-associated p53 expression and β-galactosidase activity. Furthermore, low oxygen increases canonical Wnt pathway signaling coreceptor Lrp5 expression, and PI3K/Akt pathway activation. Lrp5 inhibition decreases self-renewal marker Sox2 mRNA, Oct4a nuclear accumulation, and cell numbers. Wortmannin-mediated PI3K/Akt pathway inhibition leads to increased osteoblastic differentiation at both low and high oxygen tension. We demonstrate that low oxygen stimulates a complex signaling network involving PI3K/Akt, Notch, and canonical Wnt pathways, which mediate the observed increase in nuclear Oct4a and REST, with simultaneous decrease in p53, AIF, and Bak. Collectively, these pathway activations contribute to increased self-renewal with concomitant decreased differentiation, cell cycle arrest, apoptosis, and/or senescence in MIAMI cells. Importantly, the PI3K/Akt pathway plays a central mechanistic role in the oxygen tension-regulated self-renewal versus osteoblastic differentiation of progenitor cells. PMID:27059084

[Why is bread consumption decreasing?].

PubMed

Rolland, M F; Chabert, C; Serville, Y

1977-01-01

In France bread plays a very special and ambivalent role among our foodstuffs because of the considerable drop in its consumption, its alleged harmful effects on our health and the respect in which it is traditionally held. More than half the 1 089 adults interviewed in this study say they have decreased their consumption of bread in the last 10 years. The reasons given vary according to age, body weight and urbanization level. The main reasons given for this restriction are the desire to prevent or reduce obesity, the decrease in physical activity, the general reduction in food consumption and the possibility of diversifying foods even further. Moreover, the decreasing appeal of bread in relation to other foods, as well as a modification in the structure of meals, in which bread becomes less useful to accompany other food, accentuate this loss of attraction. However, the respect for bread as part of the staple diet remains very acute as 95 p. 100 of those interviewed express a reluctance to throw bread away, more for cultural than economic reasons. Mechanization and urbanization having brought about a decrease in energy needs, the most common alimentary adaptation is general caloric restriction by which glucids, and especially bread, are curtailed.

Decreased expression of connective tissue growth factor in non-small cell lung cancer is associated with clinicopathological variables and can be restored by epigenetic modifiers.

PubMed

Drzewiecka, Hanna; Gałęcki, Bartłomiej; Jarmołowska-Jurczyszyn, Donata; Kluk, Andrzej; Dyszkiewicz, Wojciech; Jagodziński, Paweł P

2016-09-01

Recent studies indicated undisputed contribution of connective tissue growth factor (CTGF) in the development of many cancers, including non-small cell lung cancer (NSCLC). However, the functional role and regulation of CTGF expression during tumorigenesis remain elusive. Our goal was to determine CTGF transcript and protein levels in tumoral and matched control tissues from 98 NSCLC patients, to correlate the results with clinicopathological features and to investigate whether the CTGF expression can be epigenetically regulated in NSCLC. We used quantitative PCR, Western blotting and immunohistochemistry to evaluate CTGF expression in lung cancerous and histopathologically unchanged tissues. We tested the impact of 5-Aza-2'-deoxycytidine (5-dAzaC) and trichostatin A (TSA) on CTGF transcript and protein levels in NSCLC cells (A549, Calu-1). DNA methylation status of the CTGF regulatory region was evaluated by bisulfite sequencing. The influence of 5-dAzaC and TSA on NSCLC cells viability and proliferation was monitored by the trypan blue assay. We found significantly decreased levels of CTGF mRNA and protein (both p < 0.0000001) in cancerous tissues of NSCLC patients. Down-regulation of CTGF occurred regardless of gender in all histological subtypes of NSCLC. Moreover, we showed that 5-dAzaC and TSA were able to restore CTGF mRNA and protein contents in NSCLC cells. However, no methylation within CTGF regulatory region was detected. Both compounds significantly reduced NSCLC cells proliferation. Decreased expression of CTGF is a common feature in NSCLC; however, it can be restored by the chromatin-modifying agents such as 5-dAzaC or TSA and consequently restrain cancer development.

A Teacher-Focused Intervention to Decrease PE Students' Amotivation by Increasing Need Satisfaction and Decreasing Need Frustration.

PubMed

Cheon, Sung Hyeon; Reeve, Johnmarshall; Song, Yong-Gwan

2016-06-01

Intervention-induced gains in need satisfaction decrease PE students' amotivation. The present study adopted a dual-process model to test whether an intervention could also decrease need frustration and hence provide a second supplemental source to further decrease students' PE amotivation. Using an experimental, longitudinal research design, 19 experienced PE teachers (9 experimental, 10 control) and their 1,017 students participated in an intervention program to help teachers become both more autonomy supportive and less controlling. Multilevel repeated measures analyses showed that students of teachers in the experimental group reported greater T2, T3, and T4 perceived autonomy support, need satisfaction, and engagement and lesser T2, T3, and T4 perceived teacher control, need frustration, and amotivation than did students of teachers in the control group. Multilevel structural equation modeling analyses confirmed the hypothesized dual-process model in which both intervention-induced increases in need satisfaction and intervention-induced decreases need frustration decreased students' end-of-semester amotivation. We discuss the theoretical and practical implications of this new finding on the dual antecedents of diminished amotivation.

T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFβ dosage.

PubMed Central

Talebian, Laleh; Li, Zhe; Guo, Yalin; Gaudet, Justin; Speck, Maren E.; Sugiyama, Daisuke; Kaur, Prabhjot; Pear, Warren S.; Maillard, Ivan; Speck, Nancy A.

2007-01-01

The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non–DNA-binding partner CBFβ. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFβ levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFβ levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFβ levels, and were virtually absent when CBFβ levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4−CD8− double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFβ threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development. PMID:16940420

Repeated Habitat Disturbances by Fire Decrease Local Effective Population Size

PubMed Central

Ragsdale, Alexandria K.; McCoy, Earl D.; Mushinsky, Henry R.

2016-01-01

Effective population size is a fundamental parameter in population genetics, and factors that alter effective population size will shape the genetic characteristics of populations. Habitat disturbance may have a large effect on genetic characteristics of populations by influencing immigration and gene flow, particularly in fragmented habitats. We used the Florida Sand Skink (Plestiodon reynoldsi) to investigate the effect of fire-based habitat disturbances on the effective population size in the highly threatened, severely fragmented, and fire dependent Florida scrub habitat. We screened 7 microsatellite loci in 604 individuals collected from 12 locations at Archbold Biological Station. Archbold Biological Station has an active fire management plan and detailed records of fires dating to 1967. Our objective was to determine how the timing, number, and intervals between fires affect effective population size, focusing on multiple fires in the same location. Effective population size was higher in areas that had not been burned for more than 10 years and decreased with number of fires and shorter time between fires. A similar pattern was observed in abundance: increasing abundance with time-since-fire and decreasing abundance with number of fires. The ratio of effective population size to census size was higher at sites with more recent fires and tended to decrease with time-since-last-fire. These results suggest that habitat disturbances, such as fire, may have a large effect in the genetic characteristics of local populations and that Florida Sand Skinks are well adapted to the natural fire dynamics required to maintain Florida scrub. PMID:26976940

Natriuretic factor, a lasting enigma.

PubMed

Licht, A; Fine, L G; Bourgoignie, J J

1978-01-01

A gel filtration fraction of urine from patients with chronic uremia (natriuretic factor) decreases potential difference, net sodium flux and lumen to peritubular flux of sodium across the isolated rabbit cortical collecting tubule. These effects are consistent with the possibility that natriuretic factor represents a modulator of sodium excretion in the mammalian nephron. Natriuretic factor induces a dose-dependent inhibition of short-circuit current in the isolated toad bladder. By comparing the effects of natriuretic factor to those of a standard unit of reference, it may be possible to develop a quantitative assay for natriuretic factor. The acidic nature of natriuretic factor was confirmed by cation exchange column in a high pressure liquid chromatography system.

Liposomal gene transfer of keratinocyte growth factor improves wound healing by altering growth factor and collagen expression.

PubMed

Pereira, Clifford T; Herndon, David N; Rocker, Roland; Jeschke, Marc G

2007-05-15

Growth factors affect the complex cascade of wound healing; however, interaction between different growth factors during dermal and epidermal regeneration are still not entirely defined. In the present study, we thought to determine the interaction between keratinocyte growth factor (KGF) administered as liposomal cDNA with other dermal and epidermal growth factors and collagen synthesis in an acute wound. Rats received an acute wound and were divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and Lac-Z gene (0.22 microg). Histological and immunohistochemical techniques were used to determine growth factor, collagen expression, and dermal and epidermal structure. KGF cDNA increased insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and fibroblast growth factor (FGF), decreased transforming growth factor-beta (TGF-beta), while it had no effect on platelet-derived growth factor (PDGF) levels in the wound. KGF cDNA significantly increased collagen Type IV at both the wound edge as well as the wound bed, while it had no effect on collagen Type I and III. KGF cDNA increased re-epithelialization, improved dermal regeneration, and increased neovascularization. Exogenous administered KGF cDNA causes increases in IGF-I, IGF-BP3, FGF, and collagen IV and decreases TGF-beta concentration. KGF gene transfer accelerates wound healing without causing an increase in collagen I or III.

Factoring vs linear modeling in rate estimation: a simulation study of relative accuracy.

PubMed

Maldonado, G; Greenland, S

1998-07-01

A common strategy for modeling dose-response in epidemiology is to transform ordered exposures and covariates into sets of dichotomous indicator variables (that is, to factor the variables). Factoring tends to increase estimation variance, but it also tends to decrease bias and thus may increase or decrease total accuracy. We conducted a simulation study to examine the impact of factoring on the accuracy of rate estimation. Factored and unfactored Poisson regression models were fit to follow-up study datasets that were randomly generated from 37,500 population model forms that ranged from subadditive to supramultiplicative. In the situations we examined, factoring sometimes substantially improved accuracy relative to fitting the corresponding unfactored model, sometimes substantially decreased accuracy, and sometimes made little difference. The difference in accuracy between factored and unfactored models depended in a complicated fashion on the difference between the true and fitted model forms, the strength of exposure and covariate effects in the population, and the study size. It may be difficult in practice to predict when factoring is increasing or decreasing accuracy. We recommend, therefore, that the strategy of factoring variables be supplemented with other strategies for modeling dose-response.

BMP signaling and podocyte markers are decreased in human diabetic nephropathy in association with CTGF overexpression.

PubMed

Turk, Tamara; Leeuwis, Jan Willem; Gray, Julia; Torti, Suzy V; Lyons, Karen M; Nguyen, Tri Q; Goldschmeding, Roel

2009-07-01

Diabetic nephropathy is characterized by decreased expression of bone morphogenetic protein-7 (BMP-7) and decreased podocyte number and differentiation. Extracellular antagonists such as connective tissue growth factor (CTGF; CCN-2) and sclerostin domain-containing-1 (SOSTDC1; USAG-1) are important determinants of BMP signaling activity in glomeruli. We studied BMP signaling activity in glomeruli from diabetic patients and non-diabetic individuals and from control and diabetic CTGF(+/+) and CTGF(+/-) mice. BMP signaling activity was visualized by phosphorylated Smad1, -5, and -8 (pSmad1/5/8) immunostaining, and related to expression of CTGF, SOSTDC1, and the podocyte differentiation markers WT1, synaptopodin, and nephrin. In control and diabetic glomeruli, pSmad1/5/8 was mainly localized in podocytes, but both number of positive cells and staining intensity were decreased in diabetes. Nephrin and synaptopodin were decreased in diabetic glomeruli. Decrease of pSmad1/5/8 was only partially explained by decrease in podocyte number. SOSTDC1 and CTGF were expressed exclusively in podocytes. In diabetic glomeruli, SOSTDC1 decreased in parallel with podocyte number, whereas CTGF was strongly increased. In diabetic CTGF(+/-) mice, pSmad1/5/8 was preserved, compared with diabetic CTGF(+/+) mice. In conclusion, in human diabetic nephropathy, BMP signaling activity is diminished, together with reduction of podocyte markers. This might relate to concomitant overexpression of CTGF but not SOSTDC1.

Angiotensin II Moderately Decreases Plasmodium Infection and Experimental Cerebral Malaria in Mice.

PubMed

Gallego-Delgado, Julio; Baravian, Charlotte; Edagha, Innocent; Ty, Maureen C; Ruiz-Ortega, Marta; Xu, Wenyue; Rodriguez, Ana

2015-01-01

Angiotensin II, a peptide hormone that regulates blood pressure, has been proposed as a protective factor against cerebral malaria based on a genetic analysis. In vitro studies have documented an inhibitory effect of angiotensin II on Plasmodium growth, while studies using chemical inhibitors of angiotensin II in mice showed protection against experimental cerebral malaria but not major effects on parasite growth. To determine whether the level of angiotensin II affects Plasmodium growth and/or disease outcome in malaria, elevated levels of angiotensin II were induced in mice by intradermal implantation of osmotic mini-pumps providing constant release of this hormone. Mice were then infected with P. berghei and monitored for parasitemia and incidence of cerebral malaria. Mice infused with angiotensin II showed decreased parasitemia seven days after infection. The development of experimental cerebral malaria was delayed and a moderate increase in survival was observed in mice with elevated angiotensin II, as confirmed by decreased number of cerebral hemorrhages compared to controls. The results presented here show for the first time the effect of elevated levels of angiotensin II in an in vivo model of malaria. The decreased pathogenesis observed in mice complements a previous human genetic study, reinforcing the hypothesis of a beneficial effect of angiotensin II in malaria.

Emodin up-regulates glucose metabolism, decreases lipolysis, and attenuates inflammation in vitro.

PubMed

Zhang, Xiaoyan; Zhang, Rong; Lv, Pengfei; Yang, Jian; Deng, Yujie; Xu, Jun; Zhu, Rongfeng; Zhang, Di; Yang, Ying

2015-05-01

Emodin, the major bioactive component of Rheum palmatum, has many different activities, including antitumor, anti-inflammatory, and antidiabetes effects. Recently, emodin was reported to regulate energy metabolism. In the present study, we further explored the effects of emodin on glucose and lipid metabolism. Differentiated C2C12 myotubes and 3T3-L1 adipocytes were treated with or without different concentrations of emodin (6.25, 12.5, 25 or 50 μmol/L) for different time (1 h, 3 h, 12 h, 24 h or 48 h). Glucose metabolism, oxygen consumption, lactic acid levels, glycerol levels, and inflammation pathways were then evaluated. Cells were collected for quantitative polymerase chain reaction (PCR) and western blot analysis. Emodin upregulated glucose uptake and consumption in both C2C12 myotubes and 3T3-L1 adipocytes, with glycolysis increased. Furthermore, emodin inhibited lipolysis under basal conditions (as well as in the presence of 10 ng/ml tumor necrosis factor (TNF-)-α in 3T3-L1 adipocytes) and significantly decreased phosphorylated perilipin. Moreover, emodin inhibited the nuclear factor-κB and extracellular signal-regulated kinase pathways in C2C12 myotubes and 3T3-L1 adipocytes. Emodin upregulates glucose metabolism, decreases lipolysis, and inhibits inflammation in C2C12 myotubes and 3T3-L1 adipocytes. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Involvement of Difference in Decrease of Hemoglobin Level in Poor Prognosis of Stage I and II Nasopharyngeal Carcinoma: Implication in Outcome of Radiotherapy

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

Gao Jin; State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University, Guangzhou; Department of Radiation Oncology, Anhui provincial hospital, Hefei

2012-03-15

Purpose: To investigate the effect of hemoglobin (Hb) concentration and the difference in its decrease during treatment on outcome of radiotherapy (RT) alone for patients with Stage I and II nasopharyngeal carcinoma. Methods and Materials: A total of 572 patients with Stage I-II nasopharyngeal carcinoma with RT alone between January 2001 and December 2004 were retrospectively analyzed. Patient characteristics, tumor variables, and Hb level, including pre-RT Hb, mid-RT Hb, and dynamic change of Hb between pre- and post- RT and its difference in decrease ( White-Up-Pointing-Small-Triangle Hb) were subjected to univariate and multivariable analysis to identify factors that predict disease-specificmore » survival (DSS), local regional recurrence-free survival (LRFS), and metastases-free survival (MFS). Results: The 5-year DSS was poorer in the Hb continuous decrease group than in the Hb noncontinuous decrease group (84% vs. 89%; p = 0.008). There was poorer 5-year DSS in patients with White-Up-Pointing-Small-Triangle Hb of >11.5 g/L than in those with White-Up-Pointing-Small-Triangle Hb of {<=}11.5 g/L (82% vs. 89%; p = 0.001), and poorer LRFS (79% vs. 83%; p = 0.035). Univariate and multivariate analysis showed that Hb decrease difference with greater than 11.5 g/L was an independent prognostic factor for DSS and LRFS. Conclusions: The difference in decrease of Hb level during the course of radiation treatment appeared as a poor prognostic factor in Stage I and II nasopharyngeal carcinoma patients.« less

The Developmental Decrease in REM Sleep: The Role of Transmitters and Electrical Coupling

PubMed Central

Garcia-Rill, Edgar; Charlesworth, Amanda; Heister, David; Ye, Meijun; Hayar, Abdallah

2008-01-01

Study Objectives: This mini-review considers certain factors related to the developmental decrease in rapid eye movement (REM) sleep, which occurs in favor of additional waking time, and its relationship to developmental factors that may influence its potential role in brain development. Design: Specifically, we discuss some of the theories proposed for the occurrence of REM sleep and agree with the classic notion that REM sleep is, at the least, a mechanism that may play a role in the maturation of thalamocortical pathways. The developmental decrease in REM sleep occurs gradually from birth until close to puberty in the human, and in other mammals it is brief and coincides with eye and ear opening and the beginning of massive exogenous activation. Therefore, the purported role for REM sleep may change to involve a number of other functions with age. Measurements and Results: We describe recent findings showing that morphologic and physiologic properties as well as cholinergic, gamma amino-butyric acid, kainic acid, n-methyl-d-aspartic acid, noradrenergic, and serotonergic synaptic inputs to mesopontine cholinergic neurons, as well as the degree of electrical coupling between mostly noncholinergic mesopontine neurons and levels of the neuronal gap-junction protein connexin 36, change dramatically during this critical period in development. A novel mechanism for sleep-wake control based on well-known transmitter interactions, as well as electrical coupling, is described. Conclusion: We hypothesize that a dysregulation of this process could result in life-long disturbances in arousal and REM sleep drive, leading to hypervigilance or hypovigilance such as that observed in a number of disorders that have a mostly postpubertal age of onset. Citation: Garcia-Rill E; Charlesworth A; Heister D; Ye Y; Hayar A. The developmental decrease in REM sleep: the role of transmitters and electrical coupling. SLEEP 2008;31(5):673–690. PMID:18517037

Decrease of VOC emissions from vehicular emissions in Hong Kong from 2003 to 2015: Results from a tunnel study

NASA Astrophysics Data System (ADS)

Cui, Long; Wang, Xiao Liang; Ho, Kin Fai; Gao, Yuan; Liu, Chang; Hang Ho, Steven Sai; Li, Hai Wei; Lee, Shun Cheng; Wang, Xin Ming; Jiang, Bo Qiong; Huang, Yu; Chow, Judith C.; Watson, John G.; Chen, Lung-Wen

2018-03-01

Vehicular emissions are one of major anthropogenic sources of ambient volatile organic compounds (VOCs) in Hong Kong. During the past twelve years, the government of the Hong Kong Special Administrative Region has undertaken a series of air pollution control measures to reduce vehicular emissions in Hong Kong. Vehicular emissions were characterized by repeated measurement in the same roadway tunnel in 2003 and 2015. The total net concentration of measured VOCs decreased by 44.7% from 2003 to 2015. The fleet-average VOC emission factor decreased from 107.1 ± 44.8 mg veh-1 km-1 in 2003 to 58.8 ± 50.7 mg veh-1 km-1 in 2015, and the total ozone (O3) formation potential of measured VOCs decreased from 474.1 mg O3 veh-1 km-1 to 190.8 mg O3 veh-1 km-1. The emission factor of ethene, which is one of the key tracers for diesel vehicular emissions, decreased by 67.3% from 2003 to 2015 as a result of the strict control measures on diesel vehicular emissions. Total road transport VOC emissions is estimated to be reduced by 40% as compared with 2010 by 2020, which will be an important contributor to achieve the goal of total VOC emission reduction in the Pearl River Delta region. The large decrease of VOC emissions from on-road vehicles demonstrates the effectiveness of past multi-vehicular emission control strategy in Hong Kong.

Understanding Decreases in Land Relative Humidity with Global Warming: Conceptual Model and GCM Simulations

NASA Astrophysics Data System (ADS)

Byrne, Michael P.; O'Gorman, Paul A.

2016-12-01

Climate models simulate a strong land-ocean contrast in the response of near-surface relative humidity to global warming: relative humidity tends to increase slightly over oceans but decrease substantially over land. Surface energy balance arguments have been used to understand the response over ocean but are difficult to apply over more complex land surfaces. Here, a conceptual box model is introduced, involving moisture transport between the land and ocean boundary layers and evapotranspiration, to investigate the decreases in land relative humidity as the climate warms. The box model is applied to idealized and full-complexity (CMIP5) general circulation model simulations, and it is found to capture many of the features of the simulated changes in land relative humidity. The box model suggests there is a strong link between fractional changes in specific humidity over land and ocean, and the greater warming over land than ocean then implies a decrease in land relative humidity. Evapotranspiration is of secondary importance for the increase in specific humidity over land, but it matters more for the decrease in relative humidity. Further analysis shows there is a strong feedback between changes in surface-air temperature and relative humidity, and this can amplify the influence on relative humidity of factors such as stomatal conductance and soil moisture.

SU-E-T-469: A Practical Approach for the Determination of Small Field Output Factors Using Published Monte Carlo Derived Correction Factors

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

Calderon, E; Siergiej, D

2014-06-01

Purpose: Output factor determination for small fields (less than 20 mm) presents significant challenges due to ion chamber volume averaging and diode over-response. Measured output factor values between detectors are known to have large deviations as field sizes are decreased. No set standard to resolve this difference in measurement exists. We observed differences between measured output factors of up to 14% using two different detectors. Published Monte Carlo derived correction factors were used to address this challenge and decrease the output factor deviation between detectors. Methods: Output factors for Elekta's linac-based stereotactic cone system were measured using the EDGE detectormore » (Sun Nuclear) and the A16 ion chamber (Standard Imaging). Measurements conditions were 100 cm SSD (source to surface distance) and 1.5 cm depth. Output factors were first normalized to a 10.4 cm × 10.4 cm field size using a daisy-chaining technique to minimize the dependence of field size on detector response. An equation expressing the relation between published Monte Carlo correction factors as a function of field size for each detector was derived. The measured output factors were then multiplied by the calculated correction factors. EBT3 gafchromic film dosimetry was used to independently validate the corrected output factors. Results: Without correction, the deviation in output factors between the EDGE and A16 detectors ranged from 1.3 to 14.8%, depending on cone size. After applying the calculated correction factors, this deviation fell to 0 to 3.4%. Output factors determined with film agree within 3.5% of the corrected output factors. Conclusion: We present a practical approach to applying published Monte Carlo derived correction factors to measured small field output factors for the EDGE and A16 detectors. Using this method, we were able to decrease the percent deviation between both detectors from 14.8% to 3.4% agreement.« less

Nursing role model for computed tomography contrast injection decreases extravasation rates.

PubMed

Kadom, Nadja; Hashim, Hayder D; Olsen, Cara; Cefaratti, Marjean; Bulas, Dorothy; Shalaby-Rana, Eglal

2012-04-01

Extravasation of intravenous contrast administered for computed tomography remains of concern in pediatric patients. It is of great interest to any pediatric radiology department to decrease extravasation events in an effort to reduce even small adverse outcomes and improve the overall patient experience in the radiology department. Here, a total of 17 extravasation events, as reported and documented in departmental quality assurance at our institution over 4 years, were retrospectively reviewed for factors contributing to the number of adverse extravasation events. We found that pediatric nursing plays a central role in both achieving and maintaining a low extravasation rate at our institution. Copyright © 2012 Elsevier Inc. All rights reserved.

Common cold decreases lung function in infants with recurrent wheezing.

PubMed

Mallol, J; Aguirre, V; Wandalsen, G

2010-01-01

Common acute viral respiratory infections (colds) are the most frequent cause of exacerbations in infants with recurrent wheezing (RW). However, there is no quantitative information about the effect of colds on the lung function of infants with RW. This study was undertaken to determine the effect of common cold on forced expiratory parameters measured from raised lung volume in infants with RW. Spirometric lung function (expiratory flows from raised lung volume) was randomly assessed in 28 infants with RW while they had a common cold and when asymptomatic. It was found that during colds there was a significant decrease in all forced expiratory parameters and this was much more evident for flows (FEF(50%), FEF(75%) and FEF(25-75%)) which were definitively abnormal (less than -1.65 z-score) in the majority of infants. There was not association between family asthma, tobacco exposure, and other factors, with the extent of lung function decrease during colds. Tobacco during pregnancy but not a history of family asthma was significantly associated to lower expiratory flows; however, the association was significant only when infants were asymptomatic. This study shows that common colds cause a marked reduction of lung function in infants with RW. 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Valsartan decreases TGF-β1 production and protects against chlorhexidine digluconate-induced liver peritoneal fibrosis in rats.

PubMed

Subeq, Yi-Maun; Ke, Chen-Yen; Lin, Nien-Tsung; Lee, Chung-Jen; Chiu, Yi-Han; Hsu, Bang-Gee

2011-02-01

Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of valsartan on chlorhexidine digluconate-induced PF by decreasing TGF-β1 production in rats. PF was induced in Sprague-Dawley rats by daily administration of 0.5 ml 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis (PD) tube for 1 week. Rats received daily intravenous injections of low dose valsartan (1 mg/kg) or high dose valsartan (3 mg/kg) for 1 week. After 7 days, conventional 4.25% Dianeal (30 ml) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D₄/P(4Urea) level was reduced, the D₄/D₀ glucose level, serum and dialysate transforming growth factor-β1 (TGF-β1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-β1, alpha-smooth muscle actin (α-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PF group compared with the vehicle group. High dose of valsartan decreased the serum and dialysate TGF-β1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-β1, α-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. The low dose of valsartan did not protect against chlorhexidine digluconate-induced PF in rat. Valsartan protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-β1 production. Copyright © 2010 Elsevier Ltd. All rights reserved.

Decreased Rac1 Cardiac Expression in Nitrofen-Induced Diaphragmatic Hernia.

PubMed

Nakamura, Hiroki; Zimmer, Julia; Puri, Prem

2018-02-01

 The high incidence of cardiac malformations in humans and animal models with congenital diaphragmatic hernia (CDH) is well known. The hypoplasia of left heart is common among fetuses with CDH and has been identified as a poor prognostic factor. However, the precise mechanisms underlying cardiac maldevelopment in CDH are not fully understood. Ras-related C3 botulinum toxin substrate 1 (Rac1) plays a key role in cardiomyocyte polarity and embryonic heart development. Deficiency of Rac1 is reported to impair elongation and cytoskeletal organization of cardiomyocytes, resulting in congenital cardiac defects. We designed this study to test the hypothesis that Rac1 expression is downregulated in the developing hearts of rats with nitrofen-induced CDH.  Following ethical approval (REC1103), time-pregnant Sprague Dawley rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D18 and D21 and divided into CDH and control (CTRL) ( n  = 6 for each group and time point). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and confocal-immunofluorescence microscopy were performed to detect cardiac gene and protein expression of Rac1.  qRT-PCR and Western blot analysis revealed that Rac1 expression was significantly decreased in the CDH group compared with controls ( p  < 0.05). Confocal-immunofluorescence microscopy revealed that Rac1 cardiac expression was markedly decreased in the CDH group compared with controls.  Decreased cardiac Rac1 expression in the nitrofen-induced CDH suggests that Rac1 deficiency during morphogenesis may impair structural cardiac remodeling, resulting in congenital cardiac defects. Georg Thieme Verlag KG Stuttgart · New York.

Repeated Habitat Disturbances by Fire Decrease Local Effective Population Size.

PubMed

Schrey, Aaron W; Ragsdale, Alexandria K; McCoy, Earl D; Mushinsky, Henry R

2016-07-01

Effective population size is a fundamental parameter in population genetics, and factors that alter effective population size will shape the genetic characteristics of populations. Habitat disturbance may have a large effect on genetic characteristics of populations by influencing immigration and gene flow, particularly in fragmented habitats. We used the Florida Sand Skink (Plestiodon reynoldsi) to investigate the effect of fire-based habitat disturbances on the effective population size in the highly threatened, severely fragmented, and fire dependent Florida scrub habitat. We screened 7 microsatellite loci in 604 individuals collected from 12 locations at Archbold Biological Station. Archbold Biological Station has an active fire management plan and detailed records of fires dating to 1967. Our objective was to determine how the timing, number, and intervals between fires affect effective population size, focusing on multiple fires in the same location. Effective population size was higher in areas that had not been burned for more than 10 years and decreased with number of fires and shorter time between fires. A similar pattern was observed in abundance: increasing abundance with time-since-fire and decreasing abundance with number of fires. The ratio of effective population size to census size was higher at sites with more recent fires and tended to decrease with time-since-last-fire. These results suggest that habitat disturbances, such as fire, may have a large effect in the genetic characteristics of local populations and that Florida Sand Skinks are well adapted to the natural fire dynamics required to maintain Florida scrub. © The American Genetic Association. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hypokalemia decreases testosterone production in male mice by altering luteinizing hormone secretion.

PubMed

Sánchez-Capelo, A; Castells, M T; Cremades, A; Peñafiel, R

1996-09-01

Potassium deficiency produced by feeding mice a low potassium diet caused a marked decrease in plasma and testicular testosterone concentrations and a concomitant fall in the weight of seminal vesicles and in renal ornithine decarboxylase activity. All of these parameters were rapidly restored when potassium supply was normalized. Immunocytochemical analysis of gonadotropes and plasma LH values suggested that the pulsatile liberation of LH by the pituitary was impaired in the potassium-deficient male mice. Because the synthesis of testosterone in the potassium-deficient mice was stimulated by exogenous LH, hCG, or GnRH, one can conclude that alteration of the transcellular potassium gradient could affect the regulation of the hypothalamo-hypophyseal-testicular axis by affecting the pulsatile release of GnRH. Our results showing that the stimulation of LH secretion after castration was similar in control and potassium-deficient male mice suggest that a testicular factor(s) different from testosterone could be implicated in the abnormal regulation of LH secretion in potassium-deficient mice. We conclude that plasma potassium concentration is an important factor in the regulation of gonadotropin secretion and testicular functions.

BMP Signaling and Podocyte Markers Are Decreased in Human Diabetic Nephropathy in Association With CTGF Overexpression

PubMed Central

Turk, Tamara; Leeuwis, Jan Willem; Gray, Julia; Torti, Suzy V.; Lyons, Karen M.; Nguyen, Tri Q.; Goldschmeding, Roel

2009-01-01

Diabetic nephropathy is characterized by decreased expression of bone morphogenetic protein-7 (BMP-7) and decreased podocyte number and differentiation. Extracellular antagonists such as connective tissue growth factor (CTGF; CCN-2) and sclerostin domain-containing-1 (SOSTDC1; USAG-1) are important determinants of BMP signaling activity in glomeruli. We studied BMP signaling activity in glomeruli from diabetic patients and non-diabetic individuals and from control and diabetic CTGF+/+ and CTGF+/− mice. BMP signaling activity was visualized by phosphorylated Smad1, -5, and -8 (pSmad1/5/8) immunostaining, and related to expression of CTGF, SOSTDC1, and the podocyte differentiation markers WT1, synaptopodin, and nephrin. In control and diabetic glomeruli, pSmad1/5/8 was mainly localized in podocytes, but both number of positive cells and staining intensity were decreased in diabetes. Nephrin and synaptopodin were decreased in diabetic glomeruli. Decrease of pSmad1/5/8 was only partially explained by decrease in podocyte number. SOSTDC1 and CTGF were expressed exclusively in podocytes. In diabetic glomeruli, SOSTDC1 decreased in parallel with podocyte number, whereas CTGF was strongly increased. In diabetic CTGF+/− mice, pSmad1/5/8 was preserved, compared with diabetic CTGF+/+ mice. In conclusion, in human diabetic nephropathy, BMP signaling activity is diminished, together with reduction of podocyte markers. This might relate to concomitant overexpression of CTGF but not SOSTDC1. (J Histochem Cytochem 57:623–631, 2009) PMID:19255250

Age independency of mobility decrease assessed using the Locomotive Syndrome Risk Test in elderly with disability: a cross-sectional study.

PubMed

Yamada, Keiko; Muranaga, Shingo; Shinozaki, Tomohiro; Nakamura, Kozo; Tanaka, Sakae; Ogata, Toru

2018-01-26

Mobility decrease is reportedly age-dependent in community dwelling elderly, and a major factor of disability in the geriatric population. The purpose of this study is to examine whether mobility decrease, as assessed using a set of tests, is similarly age-dependent in elderly adults who already have disability. One hundred thirty-five community-dwelling elderly (54 men, 81 women) with disability and 1469 independent community dwellers (1009 men, 460 women) were analyzed. Disability was defined having a certified need for care under the long-term care insurance system in Japan. Lower extremity mobility decrease was quantified using the Locomotive Syndrome Risk Test, which comprises the two-step test, stand-up test, and 25-Question Geriatric Locomotive Function Scale (GLFS-25). Multivariable regression analyses indicated no age-related decrease in the three test scores among elderly with disability, whereas these scores all decreased with age among independent community dwellers. All the test scores decreased as care level increased. Mobility decrease among elderly adults with disability is unrelated to age. However, the severity of care level is associated with mobility decrease.

Chronic stress and decreased physical exercise: impact on weight for African American women.

PubMed

Moore-Greene, Gracie M; Gross, Susan M; Silver, Kristi D; Perrino, Carrol S

2012-01-01

African American women continue to have the highest prevalence of obesity in the United States and in the state of Maryland they are disproportionately affected by overweight and obesity. There are many contributing factors including chronic stress and the use of health behaviors such as physical exercise that play a role in increased weight for African American women. We examined the relationship of stress to weight and the role of physical exercise in African American paraprofessional women. Cross-sectional study African American paraprofessionals were asked about their perspectives regarding association with chronic stress and physical exercise. The three most salient stressors for the women were finances (33%), work (28%) and family/friends (19%). Ninety percent of the women were overweight or obese. Significant predictors of increased BMI were lack of physical exercise (P = .004) and health compared to others (P = .006). Ethnic discrimination was a form of chronic stress (r = .319) but was not correlated with BMI (r = .095). Decreased physical exercise (P = .02) mediated the relationship between chronic stress and BMI. Findings regarding finance and work stress suggest the need for employers to consider the impact of job strain when implementing employee health programs to decrease stress and improve health. A focus on decreased physical exercise, unhealthy eating habits and misperceptions regarding increased risk for obesity related diseases with health status may be helpful to include in intervention strategies to decrease obesity for this population.

Acutely Decreased Thermoregulatory Energy Expenditure or Decreased Activity Energy Expenditure Both Acutely Reduce Food Intake in Mice

PubMed Central

Kaiyala, Karl J.; Morton, Gregory J.; Thaler, Joshua P.; Meek, Thomas H.; Tylee, Tracy; Ogimoto, Kayoko; Wisse, Brent E.

2012-01-01

Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1) increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2) exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21°C to 28°C) rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40±1%) and dark cycle energy expenditure (15±3%) at normal ambient temperature (21°C). Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65±7%), thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14±2% at 21°C; 21±4% at 28°C), while food intake was reduced during the dark cycle (0.9±0.1 g) in mice housed at 28°C, but during the light cycle (0.3±0.1 g) in mice housed at 21°C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R2 = 0.51, p<0.01). We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure. PMID:22936977

Lithium-induced neuroprotection in stroke involves increased miR-124 expression, reduced RE1-silencing transcription factor abundance and decreased protein deubiquitination by GSK3β inhibition-independent pathways.

PubMed

Doeppner, Thorsten R; Kaltwasser, Britta; Sanchez-Mendoza, Eduardo H; Caglayan, Ahmet B; Bähr, Mathias; Hermann, Dirk M

2017-03-01

Lithium promotes acute poststroke neuronal survival, which includes mechanisms that are not limited to GSK3β inhibition. However, whether lithium induces long-term neuroprotection and enhanced brain remodeling is unclear. Therefore, mice were exposed to transient middle cerebral artery occlusion and lithium (1 mg/kg bolus followed by 2 mg/kg/day over up to 7 days) was intraperitoneally administered starting 0-9 h after reperfusion onset. Delivery of lithium no later than 6 h reduced infarct volume on day 2 and decreased brain edema, leukocyte infiltration, and microglial activation, as shown by histochemistry and flow cytometry. Lithium-induced neuroprotection persisted throughout the observation period of 56 days and was associated with enhanced neurological recovery. Poststroke angioneurogenesis and axonal plasticity were also enhanced by lithium. On the molecular level, lithium increased miR-124 expression, reduced RE1-silencing transcription factor abundance, and decreased protein deubiquitination in cultivated cortical neurons exposed to oxygen-glucose deprivation and in brains of mice exposed to cerebral ischemia. Notably, this effect was not mimicked by pharmacological GSK3β inhibition. This study for the first time provides efficacy data for lithium in the postacute ischemic phase, reporting a novel mechanism of action, i.e. increased miR-124 expression facilitating REST degradation by which lithium promotes postischemic neuroplasticity and angiogenesis.

Lithium-induced neuroprotection in stroke involves increased miR-124 expression, reduced RE1-silencing transcription factor abundance and decreased protein deubiquitination by GSK3β inhibition-independent pathways

PubMed Central

Kaltwasser, Britta; Sanchez-Mendoza, Eduardo H; Caglayan, Ahmet B; Bähr, Mathias; Hermann, Dirk M

2016-01-01

Lithium promotes acute poststroke neuronal survival, which includes mechanisms that are not limited to GSK3β inhibition. However, whether lithium induces long-term neuroprotection and enhanced brain remodeling is unclear. Therefore, mice were exposed to transient middle cerebral artery occlusion and lithium (1 mg/kg bolus followed by 2 mg/kg/day over up to 7 days) was intraperitoneally administered starting 0–9 h after reperfusion onset. Delivery of lithium no later than 6 h reduced infarct volume on day 2 and decreased brain edema, leukocyte infiltration, and microglial activation, as shown by histochemistry and flow cytometry. Lithium-induced neuroprotection persisted throughout the observation period of 56 days and was associated with enhanced neurological recovery. Poststroke angioneurogenesis and axonal plasticity were also enhanced by lithium. On the molecular level, lithium increased miR-124 expression, reduced RE1-silencing transcription factor abundance, and decreased protein deubiquitination in cultivated cortical neurons exposed to oxygen–glucose deprivation and in brains of mice exposed to cerebral ischemia. Notably, this effect was not mimicked by pharmacological GSK3β inhibition. This study for the first time provides efficacy data for lithium in the postacute ischemic phase, reporting a novel mechanism of action, i.e. increased miR-124 expression facilitating REST degradation by which lithium promotes postischemic neuroplasticity and angiogenesis. PMID:27126323

Valproic acid inhibits epithelial‑mesenchymal transition in renal cell carcinoma by decreasing SMAD4 expression.

PubMed

Mao, Shaowei; Lu, Guoliang; Lan, Xiaopeng; Yuan, Chuanwei; Jiang, Wei; Chen, Yougen; Jin, Xunbo; Xia, Qinghua

2017-11-01

Renal cell carcinoma (RCC) is the most common malignancy in urogenital neoplasms worldwide. According to previous studies, valproic acid (VPA), an anticonvulsant drug, can suppress tumor metastasis and decrease the expression level of Mothers against decapentaplegic homolog 4 (SMAD4) and therefore may inhibit epithelial‑mesenchymal transition (EMT), which is responsible for cancer metastasis. However, the association between VPA, EMT and SMAD4 in RCC metastasis remains obscure. In the present study, it was demonstrated that in the RCC cell lines 786‑O and Caki‑1 treated with VPA, the neural (N)‑cadherin, vimentin and SMAD4 protein and mRNA levels were decreased, accompanied with an increase in expression of epithelial (E)‑cadherin. Silencing SMAD4 expression decreased the expression of EMT markers, including N‑cadherin and simultaneously upregulated E‑cadherin in RCC cell lines. SMAD4 overexpression counteracted the VPA‑mediated EMT‑inhibitory effect (P<0.05). The present study demonstrates that VPA inhibited EMT in RCC cells via altering SMAD4 expression. In addition, immunohistochemical staining demonstrated that transforming growth factor‑β (TGF‑β) and low expression of SMAD4 was associated with a lower Fuhrman grade and low expression of transcription intermediary factor 1‑γ was associated with a higher tumor Fuhrman grade (P<0.05), Therefore, based on the regulatory effect of SMAD4 on EMT‑associated transcription factors, SMAD4 which can form a SMAD3/SMAD4 complex induced by TGF‑β, could be a potential anticancer drug target inhibiting tumor invasion and metastasis in RCC.

Invasiveness is associated with metastasis and decreased survival in hemangiopericytoma of the central nervous system.

PubMed

Kinslow, Connor J; Rajpara, Raj S; Wu, Cheng-Chia; Bruce, Samuel S; Canoll, Peter D; Wang, Shih-Hsiu; Sonabend, Adam M; Sheth, Sameer A; McKhann, Guy M; Sisti, Michael B; Bruce, Jeffrey N; Wang, Tony J C

2017-06-01

Meningeal hemangiopericytoma (m-HPC) is a rare tumor of the central nervous system (CNS), which is distinguished clinically from meningioma by its tendency to recur and metastasize. The histological classification and grading scheme for m-HPC is still evolving and few studies have identified tumor features that are associated with metastasis. All patients at our institution with m-HPC were assessed for patient, tumor, and treatment characteristics associated with survival, recurrence, and metastasis. New findings were validated using the SEER database. Twenty-seven patients were identified in our institutional records with m-HPC with a median follow-up time of 85 months. Invasiveness was the strongest predictor of decreased overall survival (OS) and decreased metastasis-free survival (MFS) (p = 0.004 and 0.001). On subgroup analysis, bone invasion trended towards decreased OS (p = 0.056). Bone invasion and soft tissue invasion were significantly associated with decreased MFS (p = 0.001 and 0.012). An additional 315 patients with m-HPC were identified in the SEER database that had information on tumor invasion and 263 with information on distant metastasis. Invasion was significantly associated with decreased survival (HR = 5.769, p = 0.007) and metastasis (OR 134, p = 0.000) in the SEER data. In this study, the authors identified a previously unreported tumor characteristic, invasiveness, as the strongest factor associated with decreased survival and metastasis. The association of invasion with decreased survival and metastasis was confirmed in a separate, larger, publicly available database. Invasion may be a useful parameter in the histological grading and clinical management of hemangiopericytoma of the CNS.

Increasing platelet concentrations in leukocyte-reduced platelet-rich plasma decrease collagen gene synthesis in tendons.

PubMed

Boswell, Stacie G; Schnabel, Lauren V; Mohammed, Hussni O; Sundman, Emily A; Minas, Tom; Fortier, Lisa A

2014-01-01

Platelet-rich plasma (PRP) is used for the treatment of tendinopathy. There are numerous PRP preparations, and the optimal combination of platelets and leukocytes is not known. Within leukocyte-reduced PRP (lrPRP), there is a plateau effect of platelet concentration, with increasing platelet concentrations being detrimental to extracellular matrix synthesis. Controlled laboratory study. Different formulations of lrPRP with respect to the platelet:leukocyte ratio were generated from venous blood of 8 horses. Explants of the superficial digital flexor tendon were cultured in lrPRP products for 96 hours. Platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and interleukin-1β (IL-1β) concentrations were determined in the media by enzyme-linked immunosorbent assay. Gene expression in tendon tissue for collagen type I and III (COL1A1 and COL3A1, respectively), matrix metalloproteinase-3 and -13 (MMP-3 and MMP-13, respectively), cartilage oligomeric matrix protein (COMP), and IL-1β was determined. Data were divided into 3 groups of lrPRP based on the ratio of platelets:leukocytes and evaluated to determine the effect of platelet concentration. Complete blood counts verified leukocyte reduction and platelet enrichment in all PRP preparations. In the lrPRP preparation, the anabolic growth factors PDGF-BB and TGF-β1 were increased with increasing platelet concentrations, and the catabolic cytokine IL-1β was decreased with increasing platelet concentrations. Increasing the platelet concentration resulted in a significant reduction in COL1A1 and COL3A1 synthesis in tendons. Increasing the platelet concentration within lrPRP preparations results in the delivery of more anabolic growth factors and less proinflammatory cytokines, but the biological effect on tendons is diminished metabolism as indicated by a decrease in the synthesis of both COL1A1 and COL3A1. Together, this information suggests that

Postsurgical Acute Phase Reaction is Associated with Decreased Levels of Circulating Myostatin.

PubMed

Åkerfeldt, Torbjörn; Helmersson-Karlqvist, Johanna; Gunningberg, Lena; Swenne, Christine Leo; Larsson, Anders

2015-08-01

Muscle strength is of importance for postsurgical rehabilitation. Myostatin is a growth factor that regulates the size of muscles and could thus influence muscle mass and function in the postsurgical period. The aim of the present study was to study the changes in myostatin levels during the postsurgical inflammatory period. Myostatin was analysed in serum samples from two elective surgery groups, orthopaedic surgery (n = 24) and coronary bypass patients (n = 21). The samples were collected prior to surgery and 4 and 30 days after surgery. In the orthopaedic group, the median myostatin levels decreased from 3582 ng/L prior to surgery to 774 ng/L at day 4 (p < 0.001) and to 2016 ng/L at day 30 (p < 0.001). Median CRP increased from 2.35 mg/L preoperatively to 117 mg/L at day 4 and decreased to 5.5 mg/L at day 30 in the same group. The coronary bypass group showed a similar pattern with a decrease in myostatin from 4212 ng/L to 2574 ng/L at day 4 (p < 0.001) and to 2808 ng/L at day 30 (p = 0.002). Median CRP increased from 1.80 mg/L preoperatively to 136 mg/L at day 4 and returned to 6.12 mg/L at day 30 in the coronary bypass group. There was a significant decrease in myostatin concentrations both in the early and late postsurgical period. The lowest myostatin concentration time point coincided with the highest CRP concentration time point.

Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

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

Mercado, Nicolas; Thimmulappa, Rajesh; Thomas, Catherine M.R.

2011-03-11

Research highlights: {yields} Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. {yields} HDAC inhibition decreases Nrf2 protein stability. {yields} HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. {yields} HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show thatmore » down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H{sub 2}O{sub 2}) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H{sub 2}O{sub 2}-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.« less

Elevated serum α-linolenic acid levels are associated with decreased chance of pregnancy after in vitro fertilization.

PubMed

Jungheim, Emily S; Macones, George A; Odem, Randall R; Patterson, Bruce W; Moley, Kelle H

2011-10-01

To analyze relationships between serum free fatty acid (FFA) concentrations and pregnancy. Prospective cohort. University hospital. Ninety-one women undergoing IVF. Serum was analyzed for total and specific serum FFAs, including myristic, palmitic, stearic, oleic, linoleic, and α-linolenic acids. Univariate analyses were used to identify specific FFAs and other factors associated with pregnancy after IVF. Logistic regression was performed modeling relationships between identified factors and chance of pregnancy. In unadjusted analyses, women with elevated serum α-linolenic acid (ALA) levels (highest quartile) demonstrated a decreased chance of pregnancy compared with women with the lowest levels (odds ratio 0.24, 95% confidence interval 0.052-0.792). No associations between other FFAs and pregnancy were identified. In a multivariable regression model, associations between elevated serum ALA levels and decreased chance of pregnancy remained after adjusting for patient age, body mass index, and history of endometriosis or previous live birth (adjusted odds ratio 0.139, 95% confidence interval 0.028-0.686). Elevated serum ALA levels are associated with decreased chance of pregnancy in women undergoing IVF. Further work is needed to determine whether ALA is involved in early reproductive processes and whether the relationship between ALA and pregnancy is associated with excess ALA intake, impaired ALA metabolism, or both. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

TauFactor: An open-source application for calculating tortuosity factors from tomographic data

NASA Astrophysics Data System (ADS)

Cooper, S. J.; Bertei, A.; Shearing, P. R.; Kilner, J. A.; Brandon, N. P.

TauFactor is a MatLab application for efficiently calculating the tortuosity factor, as well as volume fractions, surface areas and triple phase boundary densities, from image based microstructural data. The tortuosity factor quantifies the apparent decrease in diffusive transport resulting from convolutions of the flow paths through porous media. TauFactor was originally developed to improve the understanding of electrode microstructures for batteries and fuel cells; however, the tortuosity factor has been of interest to a wide range of disciplines for over a century, including geoscience, biology and optics. It is still common practice to use correlations, such as that developed by Bruggeman, to approximate the tortuosity factor, but in recent years the increasing availability of 3D imaging techniques has spurred interest in calculating this quantity more directly. This tool provides a fast and accurate computational platform applicable to the big datasets (>108 voxels) typical of modern tomography, without requiring high computational power.

Expression of a transmembrane phosphotyrosine phosphatase inhibits cellular response to platelet-derived growth factor and insulin-like growth factor-1.

PubMed

Mooney, R A; Freund, G G; Way, B A; Bordwell, K L

1992-11-25

Tyrosine phosphorylation is a mechanism of signal transduction shared by many growth factor receptors and oncogene products. Phosphotyrosine phosphatases (PTPases) potentially modulate or counter-regulate these signaling pathways. To test this hypothesis, the transmembrane PTPase CD45 (leukocyte common antigen) was expressed in the murine cell line C127. Hormone-dependent autophosphorylation of the platelet-derived growth factor (PDGF) and insulin-like growth factor-1 (IGF-1) receptors was markedly reduced in cells expressing the transmembrane PTPase. Tyrosine phosphorylation of other PDGF-dependent phosphoproteins (160, 140, and 55 kDa) and IGF-1-dependent phosphoproteins (145 kDa) was similarly decreased. Interestingly, the pattern of growth factor-independent tyrosine phosphorylations was comparable in cells expressing the PTPase and control cells. This suggests a selectivity or accessibility of the PTPase limited to a subset of cellular phosphotyrosyl proteins. The maximum mitogenic response to PDGF and IGF-1 in cells expressing the PTPase was decreased by 67 and 71%, respectively. These results demonstrate that a transmembrane PTPase can both affect the tyrosine phosphorylation state of growth factor receptors and modulate proximal and distal cellular responses to the growth factors.

Image-guidance in endoscopic sinus surgery: is it associated with decreased medicolegal liability?

PubMed

Eloy, Jean Anderson; Svider, Peter F; D'Aguillo, Christine M; Baredes, Soly; Setzen, Michael; Folbe, Adam J

2013-12-01

The use of image-guidance (IG) in endoscopic sinus surgery (ESS) has escalated over the last decade despite a lack of consensus that its use improves outcomes or decreases complications. One theoretical reason for using IG in ESS is its potential to minimize legal liability should an adverse outcome occur. In this study, we aimed to characterize the role of IG in ESS litigation, and further detail other factors in pertinent cases. A secondary objective was to characterize recent malpractice litigation for other relevant factors. Relevant cases from Westlaw were examined to determine whether the use of IG played a role in initiating litigation in ESS malpractice suits. Factors such as patient demographics and alleged cause(s) of malpractice litigation were examined. Out of 30 malpractice cases from 2004 to April 2013, 4 (13.3%) mentioned the use of IG during ESS, although this did not appear to be a factor affecting the plaintiff's decision to initiate litigation, nor the case outcomes. In the 26 cases (86.7%) in which IG was not used, its non-use was not specified as an alleged cause of negligence. Eleven (36.7%) cases were resolved in the defendant's favor. Frequently-cited factors included iatrogenic injury (83.3%), permanent deficits (66.7%), needing additional surgery (63.3%), orbital and intracranial injury, and perceived deficits in informed consent (40.0%). The use of IG was not found to be a factor in ESS litigation. This suggests that not using IG does not necessarily make one more vulnerable to malpractice litigation. © 2013 ARS-AAOA, LLC.

Calbindins decreased after space flight

NASA Technical Reports Server (NTRS)

Sergeev, I. N.; Rhoten, W. B.; Carney, M. D.

1996-01-01

Exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to analyze the expression of calbindin-D28k and calbindin-D9k in kidneys, small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, modeled weightlessness animals (tail suspension), and their controls. Exposure to microgravity resulted in a significant and sustained decrease in calbindin-D28k content in the kidney and calbindin-D9k in the small intestine of flight animals, as measured by enzyme-linked immunosorbent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestine, and the expression of insulin in pancreas. There was a large decrease of immunoreactivity in renal distal tubular cell-associated calbindin-D28k and in intestinal absorptive cell-associated calbindin-D9k of space flight and modeled weightlessness animals compared with matched controls. No consistent difference in pancreatic insulin immunoreactivity between space flight, modeled weightlessness, and controls was observed. Regression analysis of results obtained by quantitative ICC and ELISA for space flight, modeled weightlessness animals, and their controls demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins

Altered Gravity Simulated by Parabolic Flight and Water Immersion Leads to Decreased Trunk Motion

PubMed Central

Tian, Yu; Li, Fan; Zhang, Shaoyao; Zhang, Lin; Guo, Yaoyu; Liu, Weibo; Wang, Chunhui; Chen, Shanguang; Guo, Jinhu

2015-01-01

Gravity is one of the important environmental factors that influence the physiologies and behaviors of animals and humans, and changes in gravity elicit a variety of physiological and behavioral alterations that include impaired movement coordination, vertigo, spatial disorientation, and perceptual illusions. To elucidate the effects of gravity on human physiology and behavior, we examined changes in wrist and trunk activities and heart rate during parabolic flight and the activity of wrist and trunk in water immersion experiments. Data from 195 person-time parabolas performed by eight subjects revealed that the trunk motion counts decreased by approximately half during ascending legs (hypergravity), relative to the data acquired before the parabolic flights. In contrast, the wrist activity remained unchanged. The results from the water immersion experiments demonstrated that in the underwater condition, both the wrist and trunk activities were significantly decreased but the latter decreased to a much lower level. Together, these data suggest that gravitational alterations can result in differential influences on the motions of the wrist and the trunk. These findings might be important for understanding the degeneration of skeleton and muscular system and performance of astronauts in microgravity. PMID:26208253

Modeling Ability Differentiation in the Second-Order Factor Model

ERIC Educational Resources Information Center

Molenaar, Dylan; Dolan, Conor V.; van der Maas, Han L. J.

2011-01-01

In this article we present factor models to test for ability differentiation. Ability differentiation predicts that the size of IQ subtest correlations decreases as a function of the general intelligence factor. In the Schmid-Leiman decomposition of the second-order factor model, we model differentiation by introducing heteroscedastic residuals,…

Brain glycogen decreases during prolonged exercise

PubMed Central

Matsui, Takashi; Soya, Shingo; Okamoto, Masahiro; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki

2011-01-01

Abstract Brain glycogen could be a critical energy source for brain activity when the glucose supply from the blood is inadequate (hypoglycaemia). Although untested, it is hypothesized that during prolonged exhaustive exercise that induces hypoglycaemia and muscular glycogen depletion, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here, we tested this hypothesis and also investigated the possible involvement of brain monoamines with the reduced levels of brain glycogen. For this purpose, we exercised male Wistar rats on a treadmill for different durations (30–120 min) at moderate intensity (20 m min−1) and measured their brain glycogen levels using high-power microwave irradiation (10 kW). At the end of 30 and 60 min of running, the brain glycogen levels remained unchanged from resting levels, but liver and muscle glycogen decreased. After 120 min of running, the glycogen levels decreased significantly by ∼37–60% in five discrete brain loci (the cerebellum 60%, cortex 48%, hippocampus 43%, brainstem 37% and hypothalamus 34%) compared to those of the sedentary control. The brain glycogen levels in all five regions after running were positively correlated with the respective blood and brain glucose levels. Further, in the cortex, the levels of methoxyhydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), potential involved in degradation of the brain glycogen, increased during prolonged exercise and negatively correlated with the glycogen levels. These results support the hypothesis that brain glycogen could decrease with prolonged exhaustive exercise. Increased monoamines together with hypoglycaemia should be associated with the development of decreased brain glycogen, suggesting a new clue towards the understanding of central fatigue during prolonged exercise. PMID:21521757

Cognitive, personality, and social factors associated with adolescents' online personal information disclosure.

PubMed

Liu, Cong; Ang, Rebecca P; Lwin, May O

2013-08-01

The current study aims to understand the factors that influence adolescents' disclosure of personally identifiable information (PII) on social networking sites (SNSs). A survey was conducted among 780 adolescent participants (between 13 and 18) who were Facebook users. Structural equation modeling was used for analyzing the data and obtaining an overarching model that include cognitive, personality, and social factors that influence adolescents' PII disclosure. Results showed privacy concern as the cognitive factor reduces adolescents' PII disclosure and it serves as a potential mediator for personality and social factors. Amongst personality factors, narcissism was found to directly increase PII disclosure, and social anxiety indirectly decreases PII disclosure by increasing privacy concern. Amongst social factors, active parental mediation decreases PII disclosure directly and indirectly by increasing privacy concern. Restrictive parental mediation decreases PII disclosure only indirectly by increasing privacy concern. Implications of the findings to parents, educators, and policy makers were discussed. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Scutellaria barbata attenuates diabetic retinopathy by preventing retinal inflammation and the decreased expression of tight junction protein

PubMed Central

Mei, Xi-Yu; Zhou, Ling-Yu; Zhang, Tian-Yu; Lu, Bin; Ji, Li-Li

2017-01-01

AIM To observe the attenuation of ethanol extract of Herba Scutellaria barbata (SE) against diabetic retinopathy (DR) and its engaged mechanism. METHODS C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ, 55 mg/kg) for 5 consecutive days to induce diabetes. The diabetic mice were orally given with SE (100, 200 mg/kg) for 1mo at 1mo after STZ injection. Blood-retinal barrier (BRB) breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence staining were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. RESULTS SE (100, 200 mg/kg) reversed the breakdown of BRB in STZ-induced diabetic mice. The decreased expression of retinal claudin-1 and claudin-19, which are both tight junction (TJ) proteins, was reversed by SE. SE decreased the increased serum contents and retinal mRNA expression of TNF-α and IL-1β. SE also decreased the increased retinal expression of intercellular cell adhesion molecule-1 (ICAM-1). SE reduced the increased phosphorylation of nuclear factor kappa B (NFκB) p65 and its subsequent nuclear translocation in retinas from STZ-induced diabetic mice. Results of Western blot and retinal immunofluorescence staining of ionized calcium-binding adapter molecule 1 (Iba1) demonstrated that SE abrogated the activation of microglia cells in STZ-induced diabetic mice. CONCLUSION SE attenuates the development of DR by inhibiting retinal inflammation and restoring the decreased expression of TJ proteins including claudin-1 and claudin-19. PMID:28730076

Magical thinking decreases across adulthood.

PubMed

Brashier, Nadia M; Multhaup, Kristi S

2017-12-01

Magical thinking, or illogical causal reasoning such as superstitions, decreases across childhood, but almost no data speak to whether this developmental trajectory continues across the life span. In four experiments, magical thinking decreased across adulthood. This pattern replicated across two judgment domains and could not be explained by age-related differences in tolerance of ambiguity, domain-specific knowledge, or search for meaning. These data complement and extend findings that experience, accumulated over decades, guides older adults' judgments so that they match, or even exceed, young adults' performance. They also counter participants' expectations, and cultural sayings (e.g., "old wives' tales"), that suggest that older adults are especially superstitious. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Correlates and geographic patterns of knowledge that physical activity decreases cancer risk.

PubMed

Ramírez, A Susana; Finney Rutten, Lila J; Vanderpool, Robin C; Moser, Richard P; Hesse, Bradford W

2013-04-01

While many lifestyle-related cancer risk factors including tobacco use, poor diet, and sun exposure are well recognized by the general public, the role of physical activity in decreasing cancer risk is less recognized. Studies have demonstrated gender-, race/ethnicity-, and age-based disparities in cancer risk factor knowledge; however, beliefs and geographic factors that may be related to knowledge are under-examined. In this study, we analyzed data from the 2008 Health Information National Trends Survey to determine correlates of knowledge of the relationship between physical activity and reduced cancer risk in the adult US population. We generated geographic information system maps to examine the geographic distribution of this knowledge. Results revealed that there is confusion among US adults about the relationship between physical activity and cancer risk: Respondents who believed that cancer is not preventable had significantly lower odds of knowing that physical activity reduces cancer risk (p < .001) whereas respondents who believed that cancer is caused by one's behavior had almost two times the odds of knowing that physical activity reduces cancer risk (p < .001). Those who were aware of current physical activity guidelines were also significantly more likely to know that physical activity reduces cancer risk (p < .01). Observed geographic variability in knowledge was consistent with geographic trends in obesity and physical inactivity. Correlates of cancer risk factor knowledge point to opportunities for targeted interventions.

Decreased frequencies and impaired functions of the CD31+ subpopulation in Treg cells associated with decreased FoxP3 expression and enhanced Treg cell defects in patients with coronary heart disease.

PubMed

Huang, L; Zheng, Y; Yuan, X; Ma, Y; Xie, G; Wang, W; Chen, H; Shen, L

2017-03-01

Coronary heart disease (CHD) is one of the most common types of organ lesions caused by atherosclerosis, in which CD4 + CD25 + forkhead box protein 3 (FoxP3 + ) regulatory T cells (T reg ) play an atheroprotective role. However, T reg cell numbers are decreased and their functions are impaired in atherosclerosis; the underlying mechanisms remain unclear. CD31 plays an important part in T cell response and contributes to maintaining T cell tolerance. The immunomodulatory effects of CD31 are also implicated in atherosclerosis. In this study, we found that decreased frequencies of the CD31 + subpopulation in T reg cells (CD31 + Tr cells) correlated positively with decreased FoxP3 expression in CHD patients. Cell culture in vitro demonstrated CD31 + Tr cells maintaining stable FoxP3 expression after activation and exhibited enhanced proliferation and immunosuppression compared with the CD31 - subpopulation in T reg cells (CD31 - Tr cells). We also confirmed impaired secretion of transforming growth factor (TGF)-β1 and interleukin (IL)-10 in CD31 + Tr cells of CHD patients. Further analysis revealed reduced phospho-SHP2 (associated with CD31 activation) and phospho-signal transducer and activator of transcription-5 (STAT-5) (associated with FoxP3 transcription) levels in CD31 + Tr cells of CHD patients, suggesting that decreased FoxP3 expression in CD31 + Tr cells might be because of attenuated SHP2 and STAT-5 activation. These data indicate that decreased frequencies and impaired functions of the CD31 + Tr subpopulation associated with decreased FoxP3 expression give rise, at least in part, to T reg cell defects in CHD patients. Our findings emphasize the important role of the CD31 + Tr subpopulation in maintaining T reg cell normal function and may provide a novel explanation for impaired immunoregulation of T reg cells in CHD. © 2016 British Society for Immunology.

Radiolarians decreased silicification as an evolutionary response to reduced Cenozoic ocean silica availability

PubMed Central

Lazarus, David B.; Kotrc, Benjamin; Wulf, Gerwin; Schmidt, Daniela N.

2009-01-01

It has been hypothesized that increased water column stratification has been an abiotic “universal driver” affecting average cell size in Cenozoic marine plankton. Gradually decreasing Cenozoic radiolarian shell weight, by contrast, suggests that competition for dissolved silica, a shared nutrient, resulted in biologic coevolution between radiolaria and marine diatoms, which expanded dramatically in the Cenozoic. We present data on the 2 components of shell weight change—size and silicification—of Cenozoic radiolarians. In low latitudes, increasing Cenozoic export of silica to deep waters by diatoms and decreasing nutrient upwelling from increased water column stratification have created modern silica-poor surface waters. Here, radiolarian silicification decreases significantly (r = 0.91, P < 0.001), from ≈0.18 (shell volume fraction) in the basal Cenozoic to modern values of ≈0.06. A third of the total change occurred rapidly at 35 Ma, in correlation to major increases in water column stratification and abundance of diatoms. In high southern latitudes, Southern Ocean circulation, present since the late Eocene, maintains significant surface water silica availability. Here, radiolarian silicification decreased insignificantly (r = 0.58, P = 0.1), from ≈0.13 at 35 Ma to 0.11 today. Trends in shell size in both time series are statistically insignificant and are not correlated with each other. We conclude that there is no universal driver changing cell size in Cenozoic marine plankton. Furthermore, biologic and physical factors have, in concert, by reducing silica availability in surface waters, forced macroevolutionary changes in Cenozoic low-latitude radiolarians. PMID:19458255

Radiolarians decreased silicification as an evolutionary response to reduced Cenozoic ocean silica availability.

PubMed

Lazarus, David B; Kotrc, Benjamin; Wulf, Gerwin; Schmidt, Daniela N

2009-06-09

It has been hypothesized that increased water column stratification has been an abiotic "universal driver" affecting average cell size in Cenozoic marine plankton. Gradually decreasing Cenozoic radiolarian shell weight, by contrast, suggests that competition for dissolved silica, a shared nutrient, resulted in biologic coevolution between radiolaria and marine diatoms, which expanded dramatically in the Cenozoic. We present data on the 2 components of shell weight change--size and silicification--of Cenozoic radiolarians. In low latitudes, increasing Cenozoic export of silica to deep waters by diatoms and decreasing nutrient upwelling from increased water column stratification have created modern silica-poor surface waters. Here, radiolarian silicification decreases significantly (r = 0.91, P < 0.001), from approximately 0.18 (shell volume fraction) in the basal Cenozoic to modern values of approximately 0.06. A third of the total change occurred rapidly at 35 Ma, in correlation to major increases in water column stratification and abundance of diatoms. In high southern latitudes, Southern Ocean circulation, present since the late Eocene, maintains significant surface water silica availability. Here, radiolarian silicification decreased insignificantly (r = 0.58, P = 0.1), from approximately 0.13 at 35 Ma to 0.11 today. Trends in shell size in both time series are statistically insignificant and are not correlated with each other. We conclude that there is no universal driver changing cell size in Cenozoic marine plankton. Furthermore, biologic and physical factors have, in concert, by reducing silica availability in surface waters, forced macroevolutionary changes in Cenozoic low-latitude radiolarians.

[Interaction of human factor X with thromboplastin].

PubMed

Kiselev, S V; Zubairov, D M; Timarbaev, V N

2003-01-01

The binding of 125I-labeled human factor X to native and papaine-treated tissue tromboplastin in the presence of CaCl2 or EDTA was studied. The Scatchard analysis suggests the existence of high (Kd=l,8 x10(-9) M) and low affinity binding sites on the thromboplastin surface. The removal of Ca2+ reduced affinity of factor X to the high affinity sites. This was accompanied by some increase of their number. Proteolysis by papaine decreased affinity of high affinity sites and caused the increase of their number in the presence of Ca2+. In the absence of Ca2+ the affinity remained unchanged, but the number of sites decreased. At low concentrations of factor X positive cooperativity for high affinity binding sites was observed. It did not depend on the presence of Ca2+. The results indirectly confirm the role of hydrophobic interactons in Ca2+ dependent binding of factor X to thromboplastin and the fact that heterogeneity of this binding is determined by mesophase structure of the thromboplastin phospholipids.

[Chronic renal disease as cardiovascular risk factor].

PubMed

Hermans, M M H; Kooman, J P; Stehouwer, C D A

2008-07-19

A lowering of the glomerular filtration rate (GFR) and/or the presence of albuminuria are signs of chronic renal disease. Both variables are for the most part independently associated with an increased risk of cardiovascular morbidity and mortality. Albuminuria is a marker of endothelial dysfunction. A decrease of the GFR is associated with non-traditional risk factors, e.g. renal anaemia, uraemic toxins due to a decrease of the renal clearance, hyperhomocysteinaemia caused by a diminished homocysteine metabolism, excessive activation of the sympathetic nervous system which is related to sleep apnoea syndrome, oxidative stress and dyslipidaemia associated with the formation of vasotoxic, oxidised LDL cholesterol. These non-traditional risk factors may, alone or in combination with traditional atherogenic risk factors (e.g. age, male gender, smoking, hypercholesterolaemia, hypertension, obesity, positive family history and diabetes mellitus), partially via endothelial dysfunction, result in harmful effects on arterial function, increasing cardiovascular morbidity and mortality. Different stages of chronic kidney disease are associated with specific risk factors, making a specific therapeutic approach essential.

Decreased levels of serum fibroblast growth factor-2 in children with autism spectrum disorder.

PubMed

Esnafoglu, Erman; Ayyıldız, Sema Nur

2017-11-01

The neurodevelopment and functioning of the central nervous system, and especially the cerebral cortex, have basic importance to understand neuropsychiatric disorders like autism. Fibroblast growth factor-2 (FGF-2) plays a very important role in the development and functioning of the cortex. FGF-2 is related to developmental processes in the central nervous system such as neurogenesis, migration, differentiation and survival. This study researched the serum FGF-2 levels in children with autism spectrum disorder (ASD). With this aim, 60 ASD children and 40 healthy controls were compared. We applied a sociodemographic form and the Childhood Autism Rating Scale (CARS) to each subject with their family to assess the severity of autism. Additionally, all subjects had routine laboratory tests performed. Serum samples were studied with ELISA. The results found that serum FGF-2 levels were statistically significantly low in the patient group compared to the healthy control group (p value 0.003). Additionally there was a statistically significant negative correlation identified between serum FGF-2 levels and CARS score for all subjects (r = -0.300; p = 0.02). In conclusion, FGF-2 may contribute to the etiopathogenesis of ASD. Copyright © 2017 Elsevier B.V. All rights reserved.

CDODA-Me decreases specificity protein transcription factors and induces apoptosis in bladder cancer cells through induction of reactive oxygen species.

PubMed

Takeuchi, Hisashi; Taoka, Rikiya; Mmeje, Chinedu O; Jinesh, Goodwin G; Safe, Stephen; Kamat, Ashish M

2016-08-01

The objective is to determine whether methyl 2-cyano-3,11-dioxo-18b-olean-1,12-dien-30-oate (CDODA-Me) has therapeutic potential in bladder cancer. We investigated the effects of CDODA-Me on the growth and survival of bladder cancer cells, and expression of specificity protein (Sp) transcription factors that regulate genes associated with cancer cell proliferation and survival. J82, RT4P, and 253JB-V bladder cancer cell lines were treated with vehicle alone or with CDODA-Me with or without the antioxidant l-glutathione. Cell viability and DNA fragmentation were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide-fluorescence-activated cell sorting (FACS) analysis, respectively. Intracellular reactive oxygen species (ROS) were measured by 2',7'-dichlorofluorescin diacetate-FACS analysis. We assessed CDODA's effects on the levels of Sp and Sp-regulated proteins and induction of apoptosis in bladder cancer cells by Western blotting. We also assessed the anticancer effects of CDODA-Me in nude mice bearing RT4v6 bladder cancer. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and FACS analysis revealed that CDODA-Me inhibited the proliferation and survival of the 3 bladder cancer cell lines in a dose-dependent manner. FACS analysis also indicated that CDODA-Me-induced intracellular ROS, and Western blot analysis indicated that CDODA-Me decreased levels of Sp and Sp-regulated proteins and induced apoptosis in a dose-dependent and time-dependent manner. l-Glutathione attenuated CDODA-Me's down-regulation of Sp and Sp-regulated proteins. Compared with the control treatment, CDODA-Me substantially inhibited tumor growth in vivo. CDODA-Me has antineoplastic activity in bladder cancer cells by inducing ROS, which down-regulate Sp and Sp-regulated proteins. Thus, CDODA-Me has therapeutic potential in bladder cancer, and additional studies of the agent's efficacy and mode of action are warranted. Copyright �

Factors potentially influencing aminoglycoside use and expenditure

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

DiPiro, J.T.; Kilsdonk, G.F.; Amerson, A.B.

1982-07-01

Factors that may have influenced aminoglycoside use and expenditure in one hospital were examined. Factors that were evaluated as to their influence on aminoglycoside-use patterns were: (1) formulary status; (2) bacterial susceptibility patterns; (3) identified or perceived differences in toxicity; (4) changes in patient population; (5) price paid by the hospital for aminoglycosides; (6) distribution of newsletters or memoranda; (7) advertising and detailing; and (8) pharmacy policies. For FY 1976-77 to 1979-80, the largest proportion of aminoglycoside expense was for gentamicin. During FY 1980-81, the expenditure for gentamicin decreased and tobramycin accounted for the largest proportion of total expenditure. Monthlymore » gentamicin use decreased 20% during FY 1980-81 from the previous year. Tobramycin use increased from January 1979 to November 1980 and decreased from December 1980 to June 1981. Kanamycin use and amikacin use were fairly constant during the study period. Based on temporal relationships, the following factors appeared to influence aminoglycoside use and expenditure: (1) a study conducted at the institution from June 1977 to June 1979 comparing gentamicin and tobramycin nephrotoxicity; (2) a comparative nephrotoxicity study published in a widely circulated medical journal in May 1980; and (3) an intramural newsletter and memorandum distributed in March 1981 encouraging selective aminoglycoside use. The identification of factors that potentially influenced aminoglycoside use can be used to anticipate the future impact of similar events and to devise strategies to influence antimicrobial use.« less

Decreasing trend of groundwater in Turkey

NASA Astrophysics Data System (ADS)

Sarachi, S.; Moghim, S.; Famiglietti, J. S.

2010-12-01

In these days the increasing demand for water has created problems for availability of its resources. Some recent issues like population growth, global warming and inefficient methods of water consumption, generated the need to find sources of water other than surface water such as ground water. Excess using of groundwater in most parts of the world causes depletion of ground water in those areas. Scientists are trying to find efficient means to quantify these trends. GRACE (Gravity Recovery and Climate Experiment) including two satellites launched in March 2002, is making measurements of the Earth's gravity field which is used to display the change of storage of the water on the Earth. GRACE makes it possible to find the trend of the change of storage all over the world.It can show specific areas in the world that have dramatic decreasing trend of water storage. One of these regions that have been considered in this study is Turkey in western Asia, as one of the countries deeply affected by global warming. Turkey is identified as one of the first places where desertification will start in Europe, according to estimates by the UN Environment Program (UNEP). Turkey has 25 underground water tables and they had a decrease in level of 27 meters in the past 25 years (Turkey water report 2009). In this paper the change of the ground water is evaluated by applying the GRACE storage anomalies and the mass conservation equation that concludes the reduction trend in groundwater. The results clarify that decreasing trend of groundwater is more noticeable during recent years, particularly since 2006. Our results show that in recent years the average decrease in ground water level is 2.5 cm per year and the maximum decrease occurred in May 2007 with the value of about 7.9 cm. KEY WORDS: water resources; Ground water; Turkey; GRACE

Decrease in artificial tanning by French teenagers: 2011-2016.

PubMed

Say, Matthieu; Beauchet, Alain; Vouldoukis, Ioannis; Beauchet, Pascale; Boudet, Monique; Tella, Emilie; Mahé, Emmanuel

2018-03-13

The major risk factor for skin cancers is exposure to solar and artificial ultraviolet radiation, in particular during childhood and adolescence. In France, a law was restricted for tanning-bed access to adults (≥18 years) since 1997. To evaluate teenagers' artificial tanning behaviour in 2016 and to compare results with those obtained in a similar survey performed in 2011. The SOLADO 2011 and 2016 surveys were conducted in a general school in Antony and a technical school in Fontenay-aux-Roses (Paris suburb). In 2016, 630 teenagers (mean age: 14.2 ± 1.9 y: Males/Females: 301/329) completed the questionnaire, 1.3% of teenagers reported using tanning beds, 1.1% tanning pills and 8.9% tanning creams. Between 2011 and 2016, the use of tanning beds decreased from 1.4% to 0.7% in Antony (P = .26) and from 9.5% to 4.8% in Fontenay-aux-Roses (P = .01), and the use of tanning creams from 39.8% to 17.6% in Fontenay-aux-Rose (P = .0007). The incidence of sunburn decreased from 60.5% to 54.0% in Antony (P = .02) and from 55.4% to 42.4% in Fontenay-aux-Roses (P = .05). As compared to 2011, teenagers used artificial tanning methods less frequently in 2016. In particular, they used tanning beds less frequently, suggesting that the new stricter legislation has been effective. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Increased vulnerability to depressive-like behavior of mice with decreased expression of VGLUT1.

PubMed

Garcia-Garcia, Alvaro L; Elizalde, Natalia; Matrov, Denis; Harro, Jaanus; Wojcik, Sonja M; Venzala, Elisabet; Ramírez, Maria J; Del Rio, Joaquin; Tordera, Rosa M

2009-08-01

Many studies link depression to an increase in the excitatory-inhibitory ratio in the forebrain. Presynaptic alterations in a shared pathway of the glutamate/gamma-aminobutyric acid (GABA) cycle may account for this imbalance. Evidence suggests that decreased vesicular glutamate transporter 1 (VGLUT1) levels in the forebrain affect the glutamate/GABA cycle and induce helpless behavior. We studied decreased VGLUT1 as a potential factor enhancing a depressive-like phenotype in an animal model. Glutamate and GABA synthesis as well as oxidative metabolism were studied in heterozygous mice for the VGLUT1+/- and wildtype. The regulation of neurotransmitter levels, proteins involved in the glutamate/GABA cycle, and behavior by both genotype and chronic mild stress (CMS) were studied. Finally, the effect of chronic imipramine on VGLUT1 control and CMS mice was studied. VGLUT1+/- mice showed increased neuronal synthesis of glutamate; decreased cortical and hippocampal GABA, VGLUT1, and excitatory amino acid transporter 1 (EAAT1) as well as helplessness and anhedonia. CMS induced an increase of glutamate and a decrease of GABA, the vesicular GABA transporter (VGAT), and glutamic acid decarboxylase 65 (GAD65) in both areas and led to upregulation of EAAT1 in the hippocampus. Moreover, CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory. VGLUT1+/- CMS mice showed a combined phenotype (genotype plus stress) and specific alterations, such as an upregulation of VGLUT2 and hyperlocomotion. Moreover, an increased vulnerability to anhedonia and helplessness reversible by chronic imipramine was shown. These studies highlight a crucial role for decreased VGLUT1 in the forebrain as a biological mediator of increased vulnerability to chronic mild stress.

Temporal Decrease in Upper Atmospheric Chlorine

NASA Technical Reports Server (NTRS)

Froidevaux, L.; Livesey, N. J.; Read, W. G.; Salawitch, R. J.; Waters, J. W.; Drouin, B.; MacKenzie, I. A.; Pumphrey, H. C.; Bernath, P.; Boone, C.;

Anemia--prevalence and risk factors in pregnancy.

PubMed

Bencaiova, Gabriela; Burkhardt, Tilo; Breymann, Christian

2012-09-01

To assess the prevalence of decreased iron stores and anemia in pregnant women. To determine whether the risk factors: socio-demographic background, age, BMI, and parity are associated with abnormal hemoglobin concentrations and/or abnormal iron status. A longitudinal study was carried out at the Department of Obstetrics, University Hospital of Zurich to establish the risk factors and prevalence of the decreased iron stores and anemia in early pregnancy. In order to determine the hematological parameters and ferritin levels, venous blood samples of 470 singleton pregnancies between 16 and 20 pregnancy weeks were collected. According to hemoglobin and iron status, the patients were divided into four groups: patients with iron deficiency anemia, patients with decreased iron stores, patients with anemia for other reasons and normal patients. The determinants socio-demographic background, age, BMI and parity were explored using multiple logistic regression analysis. The prevalence of decreased iron stores (ferritin<20 μg/l) was observed in 31.8% of subjects (149/470) and anemia (Hb<110 g/l) in 18.5% (87/470). The prevalence of iron deficiency anemia was higher among women coming from former Yugoslavia and developing countries (p=0.004 and p=0.012). In patients coming from developing countries, a significant increase of anemia for other reasons was observed (p=0.027) and in patients older than 30 years, a significant increase of decreased iron stores (p=0.018). In our study population with low parity, the prevalence of abnormal hemoglobin and abnormal iron status was 50.2% (236/470), and socio-demographic background was the most important risk factor of anemia. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Morris Water Maze Training in Mice Elevates Hippocampal Levels of Transcription Factors Nuclear Factor (Erythroid-derived 2)-like 2 and Nuclear Factor Kappa B p65

PubMed Central

Snow, Wanda M.; Pahlavan, Payam S.; Djordjevic, Jelena; McAllister, Danielle; Platt, Eric E.; Alashmali, Shoug; Bernstein, Michael J.; Suh, Miyoung; Albensi, Benedict C.

2015-01-01

Research has identified several transcription factors that regulate activity-dependent plasticity and memory, with cAMP-response element binding protein (CREB) being the most well-studied. In neurons, CREB activation is influenced by the transcription factor nuclear factor kappa B (NF-κB), considered central to immunity but more recently implicated in memory. The transcription factor early growth response-2 (Egr-2), an NF-κB gene target, is also associated with learning and memory. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcription factor linked to NF-κB in pathological conditions, has not been studied in normal memory. Given that numerous transcription factors implicated in activity-dependent plasticity demonstrate connections to NF-κB, this study simultaneously evaluated protein levels of NF-κB, CREB, Egr-2, Nrf2, and actin in hippocampi from young (1 month-old) weanling CD1 mice after training in the Morris water maze, a hippocampal-dependent spatial memory task. After a 6-day acquisition period, time to locate the hidden platform decreased in the Morris water maze. Mice spent more time in the target vs. non-target quadrants of the maze, suggestive of recall of the platform location. Western blot data revealed a decrease in NF-κB p50 protein after training relative to controls, whereas NF-κB p65, Nrf2 and actin increased. Nrf2 levels were correlated with platform crosses in nearly all tested animals. These data demonstrate that training in a spatial memory task results in alterations in and associations with particular transcription factors in the hippocampus, including upregulation of NF-κB p65 and Nrf2. Training-induced increases in actin protein levels caution against its use as a loading control in immunoblot studies examining activity-dependent plasticity, learning, and memory. PMID:26635523

Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

PubMed

Kartal, Ömer; Aydınöz, Seçil; Kartal, Ayşe Tuğba; Kelestemur, Taha; Caglayan, Ahmet Burak; Beker, Mustafa Caglar; Karademir, Ferhan; Süleymanoğlu, Selami; Kul, Mustafa; Yulug, Burak; Kilic, Ertugrul

2016-08-01

Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival.

Combined Functional and Immunochemical Analysis of Normal and Abnormal Human Factor X

PubMed Central

Fair, Daryl S.; Plow, Edward F.; Edgington, Thomas S.

1979-01-01

Human Factor X was isolated from Cohn fraction III and characterized by polyacrylamide gel electrophoresis, amino acid composition, and isoelectric focusing. Two molecular forms with biological activity were observed at isoelectric points of 4.8 and 5.0. Antisera generated to Factor X was monospecific and used to establish an equilibrium competitive inhibition radioimmunoassay. This assay was specific for human Factor X and did not cross-react with human prothrombin or bovine Factor X within the sensitivity range of 6-300 ng Factor X antigen/ml. The mean concentration of Factor X based on the antigen was 11.9 μg/ml, whereas concentration values based on coagulant activity was 7.8 μg/ml. This 30% difference in measurement appears to result from the presence of a subpopulation of Factor X molecules devoid of coagulant activity. The radioimmunoassay was used to qualitatively and quantitatively compare purified Factor X to plasmic Factor X obtained from normal, warfarintreated, acquired Factor X-deficient, and congenitaldeficient patients. In all but one case, the Factor X present in these plasmas was immunochemically identical to the purified Factor X and permitted precise quantitation of these abnormal Factor X molecules. Factor X procoagulant activity was analyzed relative to Factor X antigen and the specific activities were used to characterize normal and abnormal Factor X molecules. Reduced Factor X activity in plasmas from warfarin-treated and acquired Factor X-deficient patients was attributed to both decreases in Factor X antigen and decreased function of the Factor X molecules. Congenitally deficient patients, in general, showed a reduction in Factor X antigen in parallel with Factor X procoagulant activities resulting from comparable decreases in specific biological activity of the molecules. Images PMID:90058

IGF-1 decreases collagen degradation in diabetic NOD mesangial cells: implications for diabetic nephropathy.

PubMed

Lupia, E; Elliot, S J; Lenz, O; Zheng, F; Hattori, M; Striker, G E; Striker, L J

1999-08-01

Nonobese diabetic (NOD) mice develop glomerulosclerosis shortly after the onset of diabetes. We showed that mesangial cells (MCs) from diabetic mice exhibited a stable phenotypic switch, consisting of both increased IGF-1 synthesis and proliferation (Elliot SJ, Striker LJ, Hattori M, Yang CW, He CJ, Peten EP, Striker GE: Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I. Endocrinology 133:1783-1788, 1993). Because the extracellular matrix (ECM) accumulation in diabetic glomerulosclerosis may be partly due to decreased degradation, we examined the effect of excess IGF-1 on collagen turnover and the activity of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in diabetic and nondiabetic NOD-MC. Total collagen degradation was reduced by 58 +/- 18% in diabetic NOD-MCs, which correlated with a constitutive decrease in MMP-2 activity and mRNA levels, and nearly undetectable MMP-9 activity and mRNA. TIMP levels were slightly decreased in diabetic NOD-MC. The addition of recombinant IGF-1 to nondiabetic NOD-MC resulted in a decrease in MMP-2 and TIMP activity. Furthermore, treatment of diabetic NOD-MC with a neutralizing antibody against IGF-1 increased the latent form, and restored the active form, of MMP-2. In conclusion, the excessive production of IGF-1 contributes to the altered ECM turnover in diabetic NOD-MC, largely through a reduction of MMP-2 activity. These data suggest that IGF-1 could be a major contributor to the development of diabetic glomerulosclerosis.

Decreased non-MHC-restricted (CD56+) killer cell cytotoxicity after spaceflight

NASA Technical Reports Server (NTRS)

Mehta, S. K.; Kaur, I.; Grimm, E. A.; Smid, C.; Feeback, D. L.; Pierson, D. L.

2001-01-01

Cytotoxic activity of non-major histocompatibility complex-restricted (CD56+) (NMHC) killer cells and cell surface marker expression of peripheral blood mononuclear cells were determined before and after spaceflight. Ten astronauts (9 men, 1 woman) from two space shuttle missions (9- and 10-day duration) participated in the study. Blood samples were collected 10 days before launch, within 3 h after landing, and 3 days after landing. All peripheral blood mononuclear cell preparations were cryopreserved and analyzed simultaneously in a 4-h cytotoxicity (51)Cr release assay using K562 target cells. NMHC killer cell lytic activity was normalized per 1,000 CD56+ cells. When all 10 subjects were considered as one study group, NMHC killer cell numbers did not change significantly during the three sampling periods, but at landing lytic activity had decreased by approximately 40% (P < 0.05) from preflight values. Nine of ten astronauts had decreased lytic activity immediately after flight. NMHC killer cell cytotoxicity of only three astronauts returned toward preflight values by 3 days after landing. Consistent with decreased NMHC killer cell cytotoxicity, urinary cortisol significantly increased after landing compared with preflight levels. Plasma cortisol and ACTH levels at landing were not significantly different from preflight values. No correlation of changes in NMHC killer cell function or hormone levels with factors such as age, gender, mission, or spaceflight experience was found. After landing, expression of the major lymphocyte surface markers (CD3, CD4, CD8, CD14, CD16, CD56), as determined by flow cytometric analysis, did not show any consistent changes from measurements made before flight.

Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice.

PubMed

Yamada, Yosuke; Tomaru, Utano; Ishizu, Akihiro; Ito, Tomoki; Kiuchi, Takayuki; Ono, Ayako; Miyajima, Syota; Nagai, Katsura; Higashi, Tsunehito; Matsuno, Yoshihiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu; Miwa, Soichi; Kasahara, Masanori

2015-06-01

Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

Orbital Metastasis Is Associated With Decreased Survival in Stage M Neuroblastoma.

PubMed

Harreld, Julie H; Bratton, Emily M; Federico, Sara M; Li, Xingyu; Grover, William; Li, Yimei; Kerr, Natalie C; Wilson, Matthew W; Hoehn, Mary E

2016-04-01

Approximately 30% of patients with metastatic (stage M) neuroblastoma present with periorbital ecchymosis from orbital osseous disease. Though locoregional disease is staged by imaging, the prognostic significance of metastatic site in stage M disease is unknown. We hypothesize that, compared to nonorbital metastasis, orbital metastasis is associated with decreased survival in patients with stage M neuroblastoma, and that periorbital ecchymosis reflects location and extent of orbital disease. Medical records and imaging from 222 patients with stage M neuroblastoma seen at St. Jude Children's Research Hospital between January 1995 and May 2009 were reviewed. Thirty-seven patients were <18 months of age at diagnosis and 185 were ≥18 months of age. Overall survival (OS) and 5-year survival (5YS) were compared for patients with and without orbital, calvarial and nonorbital osseous metastasis, and with and without periorbital ecchymosis (log-rank test). Associations of periorbital ecchymosis with orbital metastasis location/extent were explored (Fisher's exact test, t-test). In patients ≥18 months of age, only orbital metastasis was associated with decreased 5YS (P = 0.0323) and OS (P = 0.0288). In patients <18 months of age, neither orbital, calvarial, or nonorbital bone metastasis was associated with OS or 5YS. Periorbital ecchymosis was associated with higher number of involved orbital bones (P = 0.0135), but not location or survival. In patients ≥ 18 months of age with stage M neuroblastoma, orbital metastatic disease is associated with decreased 5YS and OS. In future clinical trials, orbital disease may be useful as an imaging-based risk factor for substratification of stage M neuroblastoma. © 2015 Wiley Periodicals, Inc.

Arabidopsis Reduces Growth Under Osmotic Stress by Decreasing SPEECHLESS Protein

PubMed Central

Kumari, Archana; Jewaria, Pawan K.; Bergmann, Dominique C.; Kakimoto, Tatsuo

2014-01-01

Plants, which are sessile unlike most animals, have evolved a system to reduce growth under stress; however, the molecular mechanisms of this stress response are not well known. During programmed development, a fraction of the leaf epidermal precursor cells become meristemoid mother cells (MMCs), which are stem cells that produce both stomatal guard cells and epidermal pavement cells. Here we report that Arabidopsis plants, in response to osmotic stress, post-transcriptionally decrease the protein level of SPEECHLESS, the transcription factor promoting MMC identity, through the action of a mitogen-activated protein kinase (MAPK) cascade. The growth reduction under osmotic stress was lessened by inhibition of the MAPK cascade or by a mutation that disrupted the MAPK target amino acids in SPEECHLESS, indicating that Arabidopsis reduces growth under stress by integrating the osmotic stress signal into the MAPK–SPEECHLESS core developmental pathway. PMID:25381317

Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine

PubMed Central

Weerachayaphorn, Jittima; Mennone, Albert; Soroka, Carol J.; Harry, Kathy; Hagey, Lee R.; Kensler, Thomas W.

2012-01-01

The transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a key regulator for induction of hepatic detoxification and antioxidant mechanisms, as well as for certain hepatobiliary transporters. To examine the role of Nrf2 in bile acid homeostasis and cholestasis, we assessed the determinants of bile secretion and bile acid synthesis and transport before and after bile duct ligation (BDL) in Nrf2−/− mice. Our findings indicate reduced rates of biliary bile acid and GSH excretion, higher levels of intrahepatic bile acids, and decreased expression of regulators of bile acid synthesis, Cyp7a1 and Cyp8b1, in Nrf2−/− compared with wild-type control mice. The mRNA expression of the bile acid transporters bile salt export pump (Bsep) and organic solute transporter (Ostα) were increased in the face of impaired expression of the multidrug resistance-associated proteins Mrp3 and Mrp4. Deletion of Nrf2 also decreased ileal apical sodium-dependent bile acid transporter (Asbt) expression, leading to reduced bile acid reabsorption and increased loss of bile acid in feces. Finally, when cholestasis is induced by BDL, liver injury was not different from that in wild-type BDL mice. These Nrf2−/− mice also had increased pregnane X receptor (Pxr) and Cyp3a11 mRNA expression in association with enhanced hepatic bile acid hydroxylation. In conclusion, this study finds that Nrf2 plays a major role in the regulation of bile acid homeostasis in the liver and intestine. Deletion of Nrf2 results in a cholestatic phenotype but does not augment liver injury following BDL. PMID:22345550

Loss of calreticulin function decreases NFκB activity by stabilizing IκB protein.

PubMed

Massaeli, Hamid; Jalali, Shahrzad; Viswanathan, Divya; Mesaeli, Nasrin

2014-11-01

Transcription factor NFκB is activated by several processes including inflammation, endoplasmic-reticulum (ER) stress, increase in Akt signaling and enhanced proteasomal degradation. Calreticulin (CRT) is an ER Ca(2+)-binding chaperone that regulates many cellular processes. Gene-targeted deletion of CRT has been shown to induce ER stress that is accompanied with a significant increase in the proteasome activity. Loss of CRT function increases the resistance of CRT-deficient (crt-/-) cells to UV- and drug-induced apoptosis. Based on these reports we hypothesized that loss of CRT will activate NFκB signaling thus contributing to enhanced resistance to apoptosis. In contrast to our hypothesis, we observed a significant decrease in the basal transcriptional activity of NFκB in CRT-deficient cells. Treatment with lipopolysaccharide failed to increase the transcriptional activity of NFκB in the crt-/- cells to the same level as in the wt cells. Our data illustrate that the mechanism of decreased NFκB activity in CRT-deficient cells is mediated by a significant increase in IκB protein expression. Furthermore, we showed a significant increase in protein phosphatase 2A activity inhibition which resulted in decreased IκBα protein level in CRT-deficient cells. Based on our data we concluded that loss of CRT increases the stability of IκB protein thus reducing NFκB activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Decreased activation and subsyndromal manic symptoms predict lower remission rates in bipolar depression.

PubMed

Caldieraro, Marco Antonio; Walsh, Samantha; Deckersbach, Thilo; Bobo, William V; Gao, Keming; Ketter, Terence A; Shelton, Richard C; Reilly-Harrington, Noreen A; Tohen, Mauricio; Calabrese, Joseph R; Thase, Michael E; Kocsis, James H; Sylvia, Louisa G; Nierenberg, Andrew A

2017-11-01

Activation encompasses energy and activity and is a central feature of bipolar disorder. However, the impact of activation on treatment response of bipolar depression requires further exploration. The aims of this study were to assess the association of decreased activation and sustained remission in bipolar depression and test for factors that could affect this association. We assessed participants with Diagnostic and Statistical Manual of Mental Disorders (4th ed) bipolar depression ( n = 303) included in a comparative effectiveness study of lithium- and quetiapine-based treatments (the Bipolar CHOICE study). Activation was evaluated using items from the Bipolar Inventory of Symptoms Scale. The selection of these items was based on a dimension of energy and interest symptoms associated with poorer treatment response in major depression. Decreased activation was associated with lower remission rates in the raw analyses and in a logistic regression model adjusted for baseline severity and subsyndromal manic symptoms (odds ratio = 0.899; p = 0.015). The manic features also predicted lower remission (odds ratio = 0.934; p < 0.001). Remission rates were similar in the two treatment groups. Decreased activation and subsyndromal manic symptoms predict lower remission rates in bipolar depression. Patients with these features may require specific treatment approaches, but new studies are necessary to identify treatments that could improve outcomes in this population.

Ore grade decrease as life cycle impact indicator for metal scarcity: the case of copper.

PubMed

Vieira, Marisa D M; Goedkoop, Mark J; Storm, Per; Huijbregts, Mark A J

2012-12-04

In the life cycle assessment (LCA) of products, the increasing scarcity of metal resources is currently addressed in a preliminary way. Here, we propose a new method on the basis of global ore grade information to assess the importance of the extraction of metal resources in the life cycle of products. It is shown how characterization factors, reflecting the decrease in ore grade due to an increase in metal extraction, can be derived from cumulative ore grade-tonnage relationships. CFs were derived for three different types of copper deposits (porphyry, sediment-hosted, and volcanogenic massive sulfide). We tested the influence of the CF model (marginal vs average), mathematical distribution (loglogistic vs loglinear), and reserve estimate (ultimate reserve vs reserve base). For the marginal CFs, the statistical distribution choice and the estimate of the copper reserves introduce a difference of a factor of 1.0-5.0 and a factor of 1.2-1.7, respectively. For the average CFs, the differences are larger for these two choices, i.e. respectively a factor of 5.7-43 and a factor of 2.1-3.8. Comparing the marginal CFs with the average CFs, the differences are higher (a factor 1.7-94). This paper demonstrates that cumulative grade-tonnage relationships for metal extraction can be used in LCA to assess the relative importance of metal extractions.

Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice

PubMed Central

Pineton de Chambrun, G; Body-Malapel, M; Frey-Wagner, I; Djouina, M; Deknuydt, F; Atrott, K; Esquerre, N; Altare, F; Neut, C; Arrieta, M C; Kanneganti, T-D; Rogler, G; Colombel, J-F; Cortot, A; Desreumaux, P; Vignal, C

2014-01-01

The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10−/−) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor. PMID:24129165

Distraction decreases prefrontal oxygenation: A NIRS study.

PubMed

Ozawa, Sachiyo; Hiraki, Kazuo

2017-04-01

When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks. Copyright © 2017 Elsevier Inc. All rights reserved.

Decreased plasma levels of ceruloplasmin after diet-induced weight loss in obese women.

PubMed

Tajik, N; Golpaie, A; Keshavarz, S A; Djalali, M; Sehat, M; Masoudkabir, F; Ahmadivand, Z; Fatehi, F; Zare, M; Yazdani, T

2012-06-01

Plasma ceruloplasmin (Cp) has been shown to be a risk factor for cardiovascular disease and also to be associated with obesity. However, it is not known whether weight loss could decrease the plasma Cp levels. To investigate the effect of diet-induced weight loss on plasma Cp in obese women. Sixty-seven healthy obese women [age =33.4±8.7 yr, body mass index (BMI) =36.0±4.8 kg/m2] were entered into a medically supervised program aimed at reducing body weight by 10% or more. Weight loss was achieved through a diet providing a daily energy deficit of 500-1000 kcal/day. In addition, all patients were prescribed to use 50 g of a fiber supplement per day. For all subjects, assessment of dietary intake, anthropometric indices, and plasma levels of C-reactive protein and Cp was performed at the first visit and repeated at 12th week of follow-up. By completing the program, weight (Δ=-9.5%, p<0.0001), BMI (Δ=-9.7%, p<0.0001), waist-circumference (Δ=-6.1%, p<0.0001), and triceps skinfold thickness (Δ=-14.9%, p<0.0001) significantly decreased. Plasma Cp significantly decreased after 12 weeks of dietary intervention (33.6±5.6 mg/dl vs 25.2±5.8 mg/dl, p<0.0001). Percent change in Cp was correlated with percent change in waist-circumference (r=446, p=0.015). Our study suggests that an improved body composition induced by restriction of energy intake is associated with decreased serum concentrations of Cp in obese women which in turn might have reduced the subjects' risk of developing cardiovascular disease.

Decrease in Urinary Incontinence Management Costs in Women Enrolled in a Clinical Trial of Weight Loss to Treat Urinary Incontinence

PubMed Central

Subak, Leslee L.; Pinto, Angela Marinilli; Wing, Rena R.; Nakagawa, Sanae; Kusek, John W.; Herman, William H.; Kuppermann, Miriam

2012-01-01

Objective To estimate the effect of a decrease in urinary incontinence frequency on urinary incontinence management costs among women enrolled in a clinical trial of a weight loss intervention and to identify factors that predict change in cost. Methods This is a secondary cohort analysis of 338 obese and overweight women with ≥ 10 weekly episodes of urinary incontinence enrolled in an 18-month randomized clinical trial of a weight loss intervention compared to a structured education program to treat urinary incontinence. Quantities of resources used for incontinence management, including pads, additional laundry, and dry cleaning were reported by participants. Direct costs for urinary incontinence management (“cost”) were calculated by multiplying resources used by national resource costs (in 2006 U.S. dollars). Randomized groups were combined to examine the effects of change in incontinence frequency on cost. Possible predictors of change in cost were examined using generalized estimating equations controlling for factors associated with change in cost in univariable analyses. Results Mean (±SD) age was 53±10 years and baseline weight was 97+17 kg. Mean weekly urinary incontinence frequency was 24+18 at baseline and decreased by 37% at 6 months and 60% at 18 months follow-up (both P<0.001). At baseline, adjusted mean cost was $7.76±$14 per week, with costs increasing significantly with greater incontinence frequency. Mean cost decreased by 54% at 6 months and 81% at 18 months (both P<0.001). In multivariable analyses, cost independently decreased by 23% for each decrease of seven urinary incontinence episodes per week and 21% for each 5 kg of weight lost (P<0.001 for both). Conclusion In obese and overweight women enrolled in a clinical trial of weight loss for urinary incontinence, incontinence management cost decreased by 81% at 18 months ($327 per woman per year) and was strongly and independently associated with decreasing incontinence frequency

Regulatory T cells decrease invariant natural killer T cell-mediated pregnancy loss in mice.

PubMed

Li, L; Tu, J; Jiang, Y; Zhou, J; Schust, D J

2017-05-01

Pregnancy loss is the commonest complication of pregnancy. The causes of pregnancy loss are poorly understood. It has been reported that stimulation of invariant natural killer T (iNKT) cells using α-galactosylceramide (αGC) induces pregnancy loss in mice. Here we investigated the mechanisms, especially the role of regulatory T (Treg) cells, in iNKT cell-mediated pregnancy loss. We found that injection of αGC rapidly induced fetal resorption, activated decidual iNKT cells, decreased the percentage of decidual Treg cells and their interleukin (IL)-10 and transforming growth factor (TGF)-β production, and upregulated the levels of interferon (IFN)-γ, tumor necrosis factor-α, IL-4, and IL-10 in serum. Adoptive transfer of iNKT cells from wild-type (WT) and IL-4 -/- mice but not IFN-γ -/- mice into αGC-treated iNKT cell-deficient Jα18 -/- mice restored αGC-induced pregnancy loss. Adoptive transfer of Treg cells downregulated α-GC-induced pregnancy loss in WT mice. Finally, co-culture with αGC-stimulated decidual iNKT cells decreased the production of IL-10 and TGF-β in decidual Treg cells and inhibited their suppressive activity. These findings suggest that activation of iNKT cells induces pregnancy loss in mice in an IFN-γ-dependent manner. In addition, inhibition of the function of decidual Treg cells has an important role in iNKT cell-mediated pregnancy loss.

Dexamethasone treatment decreases replication of viral hemorrhagic septicemia virus in Epithelioma papulosum cyprini cells.

PubMed

Kim, Min Sun; Lee, Su Jin; Choi, Seung Hyuk; Kang, Yue Jai; Kim, Ki Hong

2017-05-01

The expression of Mx1 in EPC cells after treatment with poly(I:C) or infection with viral hemorrhagic septicemia virus (VHSV) was significantly suppressed by treatment with dexamethasone. However, the titer of VHSV did not increase but instead decreased after dexamethasone treatment. This suggests that dexamethasone not only downregulates type I IFN but also affects certain factors that are necessary for VHSV replication. An important effect of HSP90 on replication of RNA viruses and downregulation of HSP90 by glucocorticoids have been reported. In this study, dexamethasone downregulated HSP90α expression in EPC cells that were stimulated with poly(I:C) or infected with VHSV. Furthermore, cells treated with an HSP90 inhibitor, geldanamycin, showed significantly decreased titers of VHSV, suggesting that HSP90 may be an important host component involved in VHSV replication, and HSP90 inhibition might be one of the causes for the observed reduction in viral titer caused by dexamethasone treatment.

Decreasing child mortality, spatial clustering and decreasing disparity in North-Western Burkina Faso.

PubMed

Becher, Heiko; Müller, Olaf; Dambach, Peter; Gabrysch, Sabine; Niamba, Louis; Sankoh, Osman; Simboro, Seraphin; Schoeps, Anja; Stieglbauer, Gabriele; Yé, Yazoume; Sié, Ali

2016-04-01

Within relatively small areas, there exist high spatial variations of mortality between villages. In rural Burkina Faso, with data from 1993 to 1998, clusters of particularly high child mortality were identified in the population of the Nouna Health and Demographic Surveillance System (HDSS), a member of the INDEPTH Network. In this paper, we report child mortality with respect to temporal trends, spatial clustering and disparity in this HDSS from 1993 to 2012. Poisson regression was used to describe village-specific child mortality rates and time trends in mortality. The spatial scan statistic was used to identify villages or village clusters with higher child mortality. Clustering of mortality in the area is still present, but not as strong as before. The disparity of child mortality between villages has decreased. The decrease occurred in the context of an overall halving of child mortality in the rural area of Nouna HDSS between 1993 and 2012. Extrapolated to the Millennium Development Goals target period 1990-2015, this yields an estimated reduction of 54%, which is not too far off the aim of a two-thirds reduction. © 2016 John Wiley & Sons Ltd.

Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells.

PubMed

Sbaraglini, María Laura; Molinuevo, María Silvina; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond

2014-03-15

Diabetes mellitus is associated with a decrease in bone quality and an increase in fracture incidence. Additionally, treatment with anti-diabetic drugs can either adversely or positively affect bone metabolism. In this study we evaluated: the effect of a 3-week oral treatment with saxagliptin on femoral microarchitecture in young male non-type-2-diabetic Sprague Dawley rats; and the in vitro effect of saxagliptin and/or fetal bovine serum (FBS), insulin or insulin-like growth factor-1 (IGF1), on the proliferation, differentiation (Runx2 and PPAR-gamma expression, type-1 collagen production, osteocalcin expression, mineralization) and extracellular-regulated kinase (ERK) activation, in bone marrow stromal cells (MSC) obtained from control (untreated) rats and in MC3T3E1 osteoblast-like cells. In vivo, oral saxagliptin treatment induced a significant decrease in the femoral osteocytic and osteoblastic density of metaphyseal trabecular bone and in the average height of the proximal cartilage growth plate; and an increase in osteoclastic tartrate-resistant acid phosphatase (TRAP) activity of the primary spongiosa. In vitro, saxagliptin inhibited FBS-, insulin- and IGF1-induced ERK phosphorylation and cell proliferation, in both MSC and MC3T3E1 preosteoblasts. In the absence of growth factors, saxagliptin had no effect on ERK activation or cell proliferation. In both MSC and MC3T3E1 cells, saxagliptin in the presence of FBS inhibited Runx2 and osteocalcin expression, type-1 collagen production and mineralization, while increasing PPAR-gamma expression. In conclusion, orally administered saxagliptin induced alterations in long-bone microarchitecture that could be related to its in vitro down-regulation of the ERK signaling pathway for insulin and IGF1 in MSC, thus decreasing the osteogenic potential of these cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Changing perception: facial reanimation surgery improves attractiveness and decreases negative facial perception.

PubMed

Dey, Jacob K; Ishii, Masaru; Boahene, Kofi D O; Byrne, Patrick J; Ishii, Lisa E

2014-01-01

Determine the effect of facial reanimation surgery on observer-graded attractiveness and negative facial perception of patients with facial paralysis. Randomized controlled experiment. Ninety observers viewed images of paralyzed faces, smiling and in repose, before and after reanimation surgery, as well as normal comparison faces. Observers rated the attractiveness of each face and characterized the paralyzed faces by rating severity, disfigured/bothersome, and importance to repair. Iterated factor analysis indicated these highly correlated variables measure a common domain, so they were combined to create the disfigured, important to repair, bothersome, severity (DIBS) factor score. Mixed effects linear regression determined the effect of facial reanimation surgery on attractiveness and DIBS score. Facial paralysis induces an attractiveness penalty of 2.51 on a 10-point scale for faces in repose and 3.38 for smiling faces. Mixed effects linear regression showed that reanimation surgery improved attractiveness for faces both in repose and smiling by 0.84 (95% confidence interval [CI]: 0.67, 1.01) and 1.24 (95% CI: 1.07, 1.42) respectively. Planned hypothesis tests confirmed statistically significant differences in attractiveness ratings between postoperative and normal faces, indicating attractiveness was not completely normalized. Regression analysis also showed that reanimation surgery decreased DIBS by 0.807 (95% CI: 0.704, 0.911) for faces in repose and 0.989 (95% CI: 0.886, 1.093), an entire standard deviation, for smiling faces. Facial reanimation surgery increases attractiveness and decreases negative facial perception of patients with facial paralysis. These data emphasize the need to optimize reanimation surgery to restore not only function, but also symmetry and cosmesis to improve facial perception and patient quality of life. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

A school-based resilience intervention to decrease tobacco, alcohol and marijuana use in high school students.

PubMed

Hodder, Rebecca K; Daly, Justine; Freund, Megan; Bowman, Jenny; Hazell, Trevor; Wiggers, John

2011-09-24

Despite schools theoretically being an ideal setting for accessing adolescents and preventing initiation of substance use, there is limited evidence of effective interventions in this setting. Resilience theory provides one approach to achieving such an outcome through improving adolescent mental well-being and resilience. A study was undertaken to examine the potential effectiveness of such an intervention approach in improving adolescent resilience and protective factor scores; and reducing the prevalence of adolescent tobacco, alcohol and marijuana use in three high schools. A non-controlled before and after study was undertaken. Data regarding student resilience and protective factors, and measures of tobacco, alcohol and marijuana use were collected from grade 7 to 10 students at baseline (n = 1449) and one year following a three year intervention (n = 1205). Significantly higher resilience and protective factors scores, and significantly lower prevalence of substance use were evident at follow up. The results suggest that the intervention has the potential to increase resilience and protective factors, and to decrease the use of tobacco, alcohol and marijuana by adolescents. Further more rigorous research is required to confirm this potential.

Correlations between metabolic syndrome, serologic factors, and gallstones

PubMed Central

Sang, Jae Hong; Ki, Nam Kyun; Cho, Jae Hwan; Ahn, Jae Ouk; Sunwoo, Jae Gun

2016-01-01

[Purpose] This study investigated the serologic factors associated with metabolic syndrome and gallstones. [Subjects and Methods] The study evaluated subjects who visited a health promotion center in Seoul from March 2, 2013 to February 28, 2014, and had undergone abdominal ultrasonography. Height, weight, and blood pressure were measured. Blood sampling was performed for high-density lipoprotein cholesterol, triglyceride, fasting blood glucose, total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, uric acid, total cholesterol, low-density lipoprotein cholesterol, thyroid stimulating hormone, and red and white blood cell counts. We conducted logistic regression analysis to assess the risk factors associated with metabolic syndrome. [Results] The risk factors for metabolic syndrome in men, in order of decreasing weight, were red blood cell count, body mass index, maximum size of gallstones, white blood cell count, waist circumference, and uric acid level. The factors in women, in order of decreasing weight, were red blood cell count, presence/absence of gallstones, uric acid level, body mass index, fasting blood glucose, and waist circumference. [Conclusion] Most serum biochemical factors and gallstone occurrence could be used to indicate the presence or absence of metabolic syndrome, independent of gender. PMID:27630427

Alcohol consumption decreases the protection efficiency of the antioxidant network and increases the risk of sunburn in human skin.

PubMed

Darvin, M E; Sterry, W; Lademann, J; Patzelt, A

2013-01-01

In recent years, epidemiological data has demonstrated that alcohol consumption is a risk factor for sunburn, melanoma and nonmelanoma skin cancer. We hypothesized that if the concentration of the antioxidants in the skin has already decreased due to alcohol consumption, then an adequate neutralization of the free radicals induced by ultraviolet light cannot be performed. Based on this hypothesis, we determined the carotenoid concentration in the skin and the minimal erythema dose (MED) of 6 male human volunteers before and after consumption of alcohol or alcohol and orange juice combined. The results showed a significant decrease in the carotenoid concentration in the skin and the MED after alcohol consumption, but no significant decrease after a combined intake of alcohol and orange juice. Copyright © 2012 S. Karger AG, Basel.

Vildagliptin, a DPP4 inhibitor, alleviates diabetes-associated cognitive deficits by decreasing the levels of apoptosis-related proteins in the rat hippocampus.

PubMed

Zhang, Dan-Dan; Shi, Nan; Fang, Hui; Ma, Liang; Wu, Wei-Ping; Zhang, Ya-Zhong; Tian, Jin-Li; Tian, Luo-Bing; Kang, Kang; Chen, Si

2018-06-01

Cognitive impairment is a prevalent but underestimated complication of diabetes, which can cause spatial memory and learning deficits. In the present study, a streptozotocin-induced type 2 diabetic rat model was employed to investigate the effects of vildagliptin, a new oral hypoglycemic agent that acts by inhibiting dipeptidyl peptidase-4, on diabetes-associated cognitive impairments, as well as the molecular mechanisms involved. The present findings demonstrated that vildagliptin treatment prevented memory impairment and decreased the apoptosis of hippocampal neurons. It also attenuated the abnormal expression of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein in the diabetic model. Vildagliptin treatment also reversed diabetes-induced decreases in phosphorylated (p)-protein kinase B (Akt) and p-glycogen synthase kinase 3β (GSK3β), brain-derived neurotrophic factor and nerve growth factor expression levels. The results indicated that the administration of vildagliptin exerts a protective effect against cognitive deficits by decreasing the expression of apoptosis-related proteins in the hippocampus and that this protective effect was mediated via the Akt/GSK3β signaling pathway.

Vildagliptin, a DPP4 inhibitor, alleviates diabetes-associated cognitive deficits by decreasing the levels of apoptosis-related proteins in the rat hippocampus

PubMed Central

Zhang, Dan-Dan; Shi, Nan; Fang, Hui; Ma, Liang; Wu, Wei-Ping; Zhang, Ya-Zhong; Tian, Jin-Li; Tian, Luo-Bing; Kang, Kang; Chen, Si

2018-01-01

Cognitive impairment is a prevalent but underestimated complication of diabetes, which can cause spatial memory and learning deficits. In the present study, a streptozotocin-induced type 2 diabetic rat model was employed to investigate the effects of vildagliptin, a new oral hypoglycemic agent that acts by inhibiting dipeptidyl peptidase-4, on diabetes-associated cognitive impairments, as well as the molecular mechanisms involved. The present findings demonstrated that vildagliptin treatment prevented memory impairment and decreased the apoptosis of hippocampal neurons. It also attenuated the abnormal expression of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein in the diabetic model. Vildagliptin treatment also reversed diabetes-induced decreases in phosphorylated (p)-protein kinase B (Akt) and p-glycogen synthase kinase 3β (GSK3β), brain-derived neurotrophic factor and nerve growth factor expression levels. The results indicated that the administration of vildagliptin exerts a protective effect against cognitive deficits by decreasing the expression of apoptosis-related proteins in the hippocampus and that this protective effect was mediated via the Akt/GSK3β signaling pathway.

Cessation of Alcohol Consumption Decreases Rate of Nicotine Metabolism In Male Alcohol-Dependent Smokers#

PubMed Central

Gubner, Noah R.; Kozar-Konieczna, Aleksandra; Szoltysek-Boldys, Izabela; Slodczyk-Mankowska, Ewa; Goniewicz, Jerzy; Sobczak, Andrzej; Jacob, Peyton; Benowitz, Neal L.; Goniewicz, Maciej L.

2016-01-01

Background Rate of nicotine metabolism is an important factor influencing cigarette smoking behavior, dependence, and efficacy of nicotine replacement therapy. The current study examined the hypothesis that chronic alcohol abuse can accelerate the rate of nicotine metabolism. Nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism) and patterns of nicotine metabolites were assessed at three time points after alcohol cessation. Methods Participants were 22 Caucasian men randomly selected from a sample of 165 smokers entering a 7-week alcohol dependence treatment program in Poland. Data were collected at three time points: baseline (week 1, after acute alcohol detoxification), week 4, and week 7. Urine was analyzed for nicotine and metabolites and used to determine the nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism), and total nicotine equivalents (TNE, a biomarker for total daily nicotine exposure). Results and conclusions There was a significant decrease in urine NMR over the 7 weeks after alcohol abstinence (F(2,42)=18.83, p<0.001), indicating a decrease in rate of nicotine metabolism. On average NMR decreased 50.0% from baseline to week 7 (9.6 ± 1.3 vs. 4.1 ± 0.6). There was no change in urine TNE across the three sessions, indicating no change daily nicotine intake. The results support the idea that chronic alcohol abuse may increases the rate of nicotine metabolism, which then decreases over time after alcohol cessation. This information may help to inform future smoking cessation interventions in this population. PMID:27107849

Cessation of alcohol consumption decreases rate of nicotine metabolism in male alcohol-dependent smokers.

PubMed

Gubner, Noah R; Kozar-Konieczna, Aleksandra; Szoltysek-Boldys, Izabela; Slodczyk-Mankowska, Ewa; Goniewicz, Jerzy; Sobczak, Andrzej; Jacob, Peyton; Benowitz, Neal L; Goniewicz, Maciej L

2016-06-01

Rate of nicotine metabolism is an important factor influencing cigarette smoking behavior, dependence, and efficacy of nicotine replacement therapy. The current study examined the hypothesis that chronic alcohol abuse can accelerate the rate of nicotine metabolism. Nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism) and patterns of nicotine metabolites were assessed at three time points after alcohol cessation. Participants were 22 Caucasian men randomly selected from a sample of 165 smokers entering a 7-week alcohol dependence treatment program in Poland. Data were collected at three time points: baseline (week 1, after acute alcohol detoxification), week 4, and week 7. Urine was analyzed for nicotine and metabolites and used to determine the nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism), and total nicotine equivalents (TNE, a biomarker for total daily nicotine exposure). There was a significant decrease in urine NMR over the 7 weeks after alcohol abstinence (F(2,42)=18.83, p<0.001), indicating a decrease in rate of nicotine metabolism. On average NMR decreased 50.0% from baseline to week 7 (9.6±1.3 vs 4.1±0.6). There was no change in urine TNE across the three sessions, indicating no change daily nicotine intake. The results support the idea that chronic alcohol abuse may increase the rate of nicotine metabolism, which then decreases over time after alcohol cessation. This information may help to inform future smoking cessation interventions in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer.

PubMed

Ide, Hisamitsu; Lu, Yan; Noguchi, Takahiro; Muto, Satoru; Okada, Hiroshi; Kawato, Suguru; Horie, Shigeo

2018-04-01

Intratumoral androgen biosynthesis has been recognized as an essential factor of castration-resistant prostate cancer. The present study investigated the effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated with or without curcumin after which cell proliferation was measured at 0, 24, 48 and 72 hours, respectively. Prostate tissues from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model were obtained after 1-month oral administration of 200 mg/kg/d curcumin. Testosterone and dihydrotestosterone concentrations in LNCaP prostate cancer cells were determined through LC-MS/MS assay. Curcumin inhibited cell proliferation and induced apoptosis of prostate cancer cells in a dose-dependent manner. Curcumin decreased the expression of steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 in prostate cancer cell lines, supporting the decrease of testosterone production. After 1-month oral administration of curcumin, Aldo-Keto reductase 1C2 (AKR1C2) expression was elevated. Simultaneously, decreased testosterone levels in the prostate tissues were observed in the TRAMP mice. Meanwhile, curcumin treatments considerably increased the expression of AKR1C2 in prostate cancer cell lines, supporting the decrease of dihydrotestosterone. Taken together, these results suggest that curcumin's natural bioactive compounds could have potent anticancer properties due to suppression of androgen production, and this could have therapeutic effects on prostate cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury.

PubMed

Husain, Kareem D; Stromberg, Paul E; Woolsey, Cheryl A; Turnbull, Isaiah R; Dunne, W Michael; Javadi, Pardis; Buchman, Timothy G; Karl, Irene E; Hotchkiss, Richard S; Coopersmith, Craig M

2005-10-01

The aim of this study was to determine the effects of acute lung injury on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. Randomized, controlled study. University research laboratory. Genetically inbred mice. Following induction of acute lung injury, gut epithelial proliferation and apoptosis were assessed in a) C3H/HeN wild-type and C3H/HeJ mice, which lack functional Toll-like receptor 4 (n = 17); b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-alpha or control antibody (n = 22); and c) C57Bl/6 wild-type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n = 21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n = 24) as well as in a time course analysis following a fixed injury (n = 18). Acute lung injury caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-tumor necrosis factor-alpha antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe acute lung injury. Changes in both gut epithelial proliferation and death were apparent within 12 hrs, but proliferation was decreased 36 hrs following acute lung injury while apoptosis returned to normal. Acute lung injury causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving Toll-like receptor 4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the

Exercise Decreases and Smoking Increases Bladder Cancer Mortality

PubMed Central

Liss, Michael A.; White, Martha; Natarajan, Loki; Parsons, J. Kellogg

2018-01-01

Modifiable lifestyle factors play an important role regarding the development and outcomes in solid tumors. Whereas smoking has been attributed to bladder cancer and cessation leads to better outcome, we show that exercise may provide similar benefits regarding bladder cancer mortality Background The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. Patients and Methods We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as “did no exercise” vs. “light, moderate, or vigorous exercise in ≥ 10-minute bouts”), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Results Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HRadj], 0.53; 95% confidence interval [CI], 0.29–0.96; P = .038) to die of bladder cancer than “no exercise”. Compared with never-smokers, current (HRadj, 4.24; 95% CI, 1.89–9.65; P = .001) and former (HRadj, 2.95; 95% CI, 1.50–5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Conclusion Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death. PMID:28007367

Recollection, not familiarity, decreases in healthy aging: Converging evidence from four estimation methods

PubMed Central

Koen, Joshua D.; Yonelinas, Andrew P.

2014-01-01

Although it is generally accepted that aging is associated with recollection impairments, there is considerable disagreement surrounding how healthy aging influences familiarity-based recognition. One factor that might contribute to the mixed findings regarding age differences in familiarity is the estimation method used to quantify the two mnemonic processes. Here, this issue is examined by having a group of older adults (N = 39) between 40 and 81 years of age complete Remember/Know (RK), receiver operating characteristic (ROC), and process dissociation (PD) recognition tests. Estimates of recollection, but not familiarity, showed a significant negative correlation with chronological age. Inconsistent with previous findings, the estimation method did not moderate the relationship between age and estimations of recollection and familiarity. In a final analysis, recollection and familiarity were estimated as latent factors in a confirmatory factor analysis (CFA) that modeled the covariance between measures of free recall and recognition, and the results converged with the results from the RK, PD, and ROC tasks. These results are consistent with the hypothesis that episodic memory declines in older adults are primary driven by recollection deficits, and also suggest that the estimation method plays little to no role in age-related decreases in familiarity. PMID:25485974

Blockade of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling for therapy of metastatic human pancreatic cancer.

PubMed

Baker, Cheryl H; Solorzano, Carmen C; Fidler, Isaiah J

2002-04-01

We determined whether concurrent blockage of vascular endothelial growth factor (VEGF) receptor and epidermal growth factor (EGF) receptor signaling by two novel tyrosine kinase inhibitors, PTK 787 and PKI 166, respectively, can inhibit angiogenesis and, hence, the growth and metastasis of human pancreatic carcinoma in nude mice. Highly metastatic human pancreatic carcinoma L3.6pl cells were injected into the pancreas of nude mice. Seven days later, groups of mice began receiving oral doses of PTK 787 and PKI 166 three times weekly. Some groups of mice also received i.p. injections of gemcitabine twice a week. The mice were necropsied when the control mice became moribund. Treatment with PTK 787 and PKI 166, with gemcitabine alone, or with the combination of PTK 787, PKI 166, and gemcitabine produced 69, 50, and 97% reduction in the volume of pancreatic tumors, respectively. Administration of protein tyrosine kinase inhibitors and gemcitabine also significantly decreased the incidence of lymph node and liver metastasis. The therapeutic efficacy directly correlated with a decrease in circulating proangiogenic molecules (VEGF, interleukin-8), a decrease in microvessel density, a decrease in proliferating cell nuclear antigen staining, and an increase in apoptosis of tumor cells and endothelial cells. Therapies produced by combining gemcitabine with either PKI 166 or PTK 787 were similar to those produced by combining gemcitabine with both PKI 166 and PTK 787. These results suggest that blockade of either epidermal growth factor receptor or VEGF receptor signaling combined with chemotherapy provides an effective approach to the therapy of pancreatic cancer.

HO-1 and CO decrease platelet-derived growth factor-induced vascular smooth muscle cell migration via inhibition of Nox1

PubMed Central

Rodriguez, Andres I.; Gangopadhyay, Archana; Kelley, Eric E.; Pagano, Patrick J.; Zuckerbraun, Brian S.; Bauer, Philip M.

2009-01-01

Objective Heme oxygenase-1 (HO-1), via its enzymatic degradation products, exhibits cell and tissue protective effects in models of vascular injury and disease. The migration of vascular smooth muscle cells (VSMC) from the medial to the intimal layer of blood vessels plays an integral role in the development of a neointima in these models. Despite this, there are no studies addressing the effect of increased HO-1 expression on VSMC migration. Results and Methods The effects of increased HO-1 expression as well as biliverdin, bilirubin, and carbon monoxide (CO), were studied in in vitro models of VSMC migration. Induction of HO-1 or CO, but not biliverdin or bilirubin, inhibited VSMC migration. This effect was mediated by the inhibition of Nox1 as determined by a range of approaches including detection of intracellular superoxide, NADPH oxidase activity measurements, and siRNA experiments. Furthermore, CO decreased PDGF-stimulated, redox-sensitive signaling pathways. Conclusion Herein we demonstrate that increased HO-1 expression and CO decreases PDGF-stimulated VSMC migration via inhibition of Nox1 enzymatic activity. These studies reveal a novel mechanism by which HO-1 and CO may mediate their beneficial effects in arterial inflammation and injury. PMID:19875720

Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection.

PubMed

Lang, Charles H; Frost, Robert A

2002-05-01

The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.

Forbush Decrease Prediction Based on Remote Solar Observations

NASA Astrophysics Data System (ADS)

Dumbovic, Mateja; Vrsnak, Bojan; Calogovic, Jasa

2016-04-01

We study the relation between remote observations of coronal mass ejections (CMEs), their associated solar flares and short-term depressions in the galactic cosmic-ray flux (so called Forbush decreases). Statistical relations between Forbush decrease magnitude and several CME/flare parameters are examined. In general we find that Forbush decrease magnitude is larger for faster CMEs with larger apparent width, which is associated with stronger flares that originate close to the center of the solar disk and are (possibly) involved in a CME-CME interaction. The statistical relations are quantified and employed to forecast expected Forbush decrease magnitude range based on the selected remote solar observations of the CME and associated solar flare. Several verification measures are used to evaluate the forecast method. We find that the forecast is most reliable in predicting whether or not a CME will produce a Forbush decrease with a magnitude >3 %. The main advantage of the method is that it provides an early prediction, 1-4 days in advance. Based on the presented research, an online forecast tool was developed (Forbush Decrease Forecast Tool, FDFT) available at Hvar Observatory web page: http://oh.geof.unizg.hr/FDFT/fdft.php. We acknowledge the support of Croatian Science Foundation under the project 6212 "Solar and Stellar Variability" and of European social fond under the project "PoKRet".

Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression

PubMed Central

Lu, Xiaoming; Zoller, Erin E.; Weirauch, Matthew T.; Wu, Zhiguo; Namjou, Bahram; Williams, Adrienne H.; Ziegler, Julie T.; Comeau, Mary E.; Marion, Miranda C.; Glenn, Stuart B.; Adler, Adam; Shen, Nan; Nath, Swapan K.; Stevens, Anne M.; Freedman, Barry I.; Tsao, Betty P.; Jacob, Chaim O.; Kamen, Diane L.; Brown, Elizabeth E.; Gilkeson, Gary S.; Alarcón, Graciela S.; Reveille, John D.; Anaya, Juan-Manuel; James, Judith A.; Sivils, Kathy L.; Criswell, Lindsey A.; Vilá, Luis M.; Alarcón-Riquelme, Marta E.; Petri, Michelle; Scofield, R. Hal; Kimberly, Robert P.; Ramsey-Goldman, Rosalind; Joo, Young Bin; Choi, Jeongim; Bae, Sang-Cheol; Boackle, Susan A.; Graham, Deborah Cunninghame; Vyse, Timothy J.; Guthridge, Joel M.; Gaffney, Patrick M.; Langefeld, Carl D.; Kelly, Jennifer A.; Greis, Kenneth D.; Kaufman, Kenneth M.; Harley, John B.; Kottyan, Leah C.

2015-01-01

Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been associated with systemic lupus erythematosus (SLE), or lupus, in independent cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a critical driver of immune cell function and differentiation, and mice deficient in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of 14,551 subjects from multi-ancestral cohorts by starting with genotyped variants and imputing to all common variants spanning ETS1. By constructing genetic models via frequentist and Bayesian association methods, we identified 16 variants that are statistically likely to be causal. We functionally assessed each of these variants on the basis of their likelihood of affecting transcription factor binding, miRNA binding, or chromatin state. Of the four variants that we experimentally examined, only rs6590330 differentially binds lysate from B cells. Using mass spectrometry, we found more binding of the transcription factor signal transducer and activator of transcription 1 (STAT1) to DNA near the risk allele of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed that the risk allele increased binding to the active form of STAT1. Analysis with expression quantitative trait loci indicated that the risk allele of rs6590330 is associated with decreased ETS1 expression in Han Chinese, but not other ancestral cohorts. We propose a model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1. PMID:25865496

Modulatory effect of silymarin on nuclear factor-erythroid-2-related factor 2 regulated redox status, nuclear factor-κB mediated inflammation and apoptosis in experimental gastric ulcer.

PubMed

Arafa Keshk, Walaa; Zahran, Samer Mahmoud; Katary, Mohamed Alaa; Abd-Elaziz Ali, Darin

2017-08-01

Non-steroidal anti-inflammatory drugs (NSAIDs) consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Silymarin (SM) is a flavonoid mixture with anti-oxidant and anti-inflammatory activities which explain its protective role against hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus we went further to investigate the potential protective effects of SM against indomethacin-induced gastric injury in rats. Pretreatment with SM (50 mg/kg orally) attenuated the severity of gastric mucosal damage as evidenced by decreasing ulcer index (UI) and ulcer score, improvement of disturbed histopathologicl features to be insignificant with those induced by the reference anti-ulcer drug. Pretreatment with SM also suppressed gastric inflammation by decreasing myeloperoxidase activity, tumer necrosis factor-α (TNF- α) and interleukin 6 (IL6) levels along with nuclear factor kappa B p65 (NF-κB) expression. Meanwhile, SM prevent gastric oxidative stress via inhibition of lipid peroxides formation, enhancement of glutathione peroxidase, superoxide dismutase activities and up-regulation of nuclear factor-erythroid-2-related factor 2 (Nrf2), the redox-sensitive master regulator of oxidative stress signaling. In conclusion, the results herein revealed that SM has a gastro-protective effect which is mediated via suppression of gastric inflammation, oxidative stress, increased the anti-oxidant and the cyto-protective defense mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Three Days of Intermittent Fasting: Repeated-Sprint Performance Decreased by Vertical-Stiffness Impairment.

PubMed

Cherif, Anissa; Meeusen, Romain; Farooq, Abdulaziz; Ryu, Joong; Fenneni, Mohamed Amine; Nikolovski, Zoran; Elshafie, Sittana; Chamari, Karim; Roelands, Bart

2017-03-01

To examine the effects of 3 d of intermittent fasting (3d-IF: abstaining from eating/drinking from dawn to sunset) on physical performance and metabolic responses to repeated sprints (RSs). Twenty-one active males performed an RS test (2 sets: 5 × 5-s maximal sprints with 25 s of recovery between and 3 min of recovery between sets on an instrumented treadmill) in 2 conditions: counterbalanced fed/control session (CS) and fasting session (FS). Biomechanical and biochemical markers were assessed preexercise and postexercise. Significant main effects of IF were observed for sprints: maximal speed (P = .016), mean speed (P = .015), maximal power (P = .035), mean power (P = .049), vertical stiffness (P = .032), and vertical center-of-mass displacement (P = .047). Sprint speed and vertical stiffness decreased during the 1st (P = .003 and P = .005) and 2nd sprints (P = .046 and P = .048) of set 2, respectively. Postexercise insulin decreased in CS (P = .023) but not in FS (P = .230). Free-fatty-acid levels were higher in FS than in CS at preexercise (P < .001) and at postexercise (P = .009). High-density lipoprotein cholesterol (HDL-C) was higher at postexercise in FS (1.32 ± 0.22 mmol/L) than in CS (1.26 ± 0.21 mmol/L, P = .039). The triglyceride (TG) concentration was decreased in FS (P < .05) compared with CS. 3d-IF impaired speed and power through a decrease in vertical stiffness during the initial runs of the 2nd set of RS. The findings of the current study confirmed the benefits of 3d-IF: improved HDL-C and TG profiles while maintaining total cholesterol and low-density lipoprotein cholesterol levels. Moreover, improving muscle power might be a key factor to retain a higher vertical stiffness and to partly counteract the negative effects of intermittent fasting.

Ethylene and pollination decrease transcript abundance of an ethylene receptor gene in Dendrobium petals.

PubMed

Thongkum, Monthathip; Burns, Parichart; Bhunchoth, Anjana; Warin, Nuchnard; Chatchawankanphanich, Orawan; van Doorn, Wouter G

2015-03-15

We studied the expression of a gene encoding an ethylene receptor, called Ethylene Response Sensor 1 (Den-ERS1), in the petals of Dendrobium orchid flowers. Transcripts accumulated during the young floral bud stage and declined by the time the flowers had been open for several days. Pollination or exposure to exogenous ethylene resulted in earlier flower senescence, an increase in ethylene production and a lower Den-ERS1 transcript abundance. Treatment with 1-methylcyclopropene (1-MCP), an inhibitor of the ethylene receptor, decreased ethylene production and resulted in high transcript abundance. The literature indicates two kinds of ethylene receptor genes with regard to the effects of ethylene. One group shows ethylene-induced down-regulated transcription, while the other has ethylene-induced up-regulation. The present gene is an example of the first group. The 5' flanking region showed binding sites for Myb and myb-like, homeodomain, MADS domain, NAC, TCP, bHLH and EIN3-like transcription factors. The binding site for the EIN3-like factor might explain the ethylene effect on transcription. A few other transcription factors (RAV1 and NAC) seem also related to ethylene effects. Copyright © 2015 Elsevier GmbH. All rights reserved.

Embryonic and postnatal telomere length decrease with ovulation order within clutches

PubMed Central

Noguera, José C.; Metcalfe, Neil B.; Reichert, Sophie; Monaghan, Pat

2016-01-01

Telomere length (TL) in early life has been found to be predictive of subsequent lifespan. Factors such as parental TL, parental age and environmental conditions during development have been shown to contribute to the observed variation in TL among individuals. One factor that has not hitherto been considered is ovulation order, although it is well established that the last hatched/born offspring in a brood or litter often show relatively poor subsequent performance. We examined the within- and across-clutch effect of ovulation order on TL in embryos of zebra finches experiencing the same controlled incubation conditions (N = 151), and tested whether any such ovulation order effects remained detectable in adults (N = 122). Irrespective of clutch and egg size, TL in early-stage embryos (72 h incubation) markedly decreased with within-clutch ovulation order; the difference in TL of first and last-laid embryos was equivalent to the average within-individual telomere loss over the entire period of nestling and juvenile life. This ovulation-order effect occurred only within but not across clutches, and was still evident in adults. Given that TL in early life predicts lifespan, our results suggest that parental effects on telomere length could contribute to the known poor performance of later-ovulated family members. PMID:27174767

Decreased seroprevalence for Toxoplasma gondii in Seventh Day Adventists in Maryland.

PubMed

Roghmann, M C; Faulkner, C T; Lefkowitz, A; Patton, S; Zimmerman, J; Morris, J G

1999-05-01

Despite its widespread prevalence, uncertainties remain about the relative contribution of various routes of transmission to the overall rate of infection with Toxoplasma gondii, particularly in developed countries. To explore the hypothesis that meat consumption is an important risk factor for infection, a cross-sectional seroprevalence study was performed on healthy adults in one region in the state of Maryland. The population included Seventh Day Adventists who as a group follow a diet containing no meat, and control community volunteers who were not Seventh Day Adventists. Thirty-one percent of the population had serologic evidence of T. gondii infection. People with T. gondii infection were older (49 versus 42 years old; P < 0.01, by t-test) and less likely to be Seventh Day Adventists (24% versus 50%; P < 0.01, by chi-square test) than people without T. gondii infection. When adjustments were made for age and gender through multiple logistic regression, Seventh Day Adventists had a significantly decreased risk of T. gondii infection (odds ratio = 0.21, 95% confidence interval = 0.09-0.46, P = 0.0001) compared with the controls. While the basis for this effect remains to be determined, one possible protective factor is the general adherence of Seventh Day Adventists to a diet that does not contain meat.

Glucagon Decreases IGF-1 Bioactivity in Humans, Independently of Insulin, by Modulating Its Binding Proteins.

PubMed

Sarem, Zeinab; Bumke-Vogt, Christiane; Mahmoud, Ayman M; Assefa, Biruhalem; Weickert, Martin O; Adamidou, Aikatarini; Bähr, Volker; Frystyk, Jan; Möhlig, Matthias; Spranger, Joachim; Lieske, Stefanie; Birkenfeld, Andreas L; Pfeiffer, Andreas F H; Arafat, Ayman M

2017-09-01

Depending on its lipolytic activity, glucagon plays a promising role in obesity treatment. Glucagon-induced growth hormone (GH) release can promote its effect on lipid metabolism, although the underlying mechanisms have not been well-defined. The present study highlights the glucagon effect on the GH/insulinlike growth factor 1 (IGF-1)/IGF-binding protein (IGFBP) axis in vivo and in vitro, taking into consideration insulin as a confounding factor. In a double-blind, placebo-controlled study, we investigated changes in GH, IGFBP, and IGF-1 bioactivity after intramuscular glucagon administration in 13 lean controls, 11 obese participants, and 13 patients with type 1 diabetes mellitus (T1DM). The effect of glucagon on the transcription factor forkhead box protein O1 (FOXO1) translocation, the transcription of GH/IGF-1 system members, and phosphorylation of protein kinase B (Akt) was further investigated in vitro. Despite unchanged total IGF-1 and IGFBP-3 levels, glucagon decreased IGF-1 bioactivity in all study groups by increasing IGFBP-1 and IGFBP-2. The reduction in IGF-1 bioactivity occurred before the glucagon-induced surge in GH. In contrast to the transient increase in circulating insulin in obese and lean participants, no change was observed in those with T1DM. In vitro, glucagon dose dependently induced a substantial nuclear translocation of FOXO1 in human osteosarcoma cells and tended to increase IGFBP-1 and IGFBP-2 gene expression in mouse primary hepatocytes, despite absent Akt phosphorylation. Our data point to the glucagon-induced decrease in bioactive IGF-1 levels as a mechanism through which glucagon induces GH secretion. This insulin-independent reduction is related to increased IGFBP-1 and IGFBP-2 levels, which are most likely mediated via activation of the FOXO/mTOR (mechanistic target of rapamycin) pathway. Copyright © 2017 Endocrine Society

Environmentally persistent free radicals decrease cardiac function before and after ischemia/reperfusion injury in vivo

PubMed Central

Lord, Kevin; Moll, David; Lindsey, John K.; Mahne, Sarah; Raman, Girija; Dugas, Tammy; Cormier, Stephania; Troxlair, Dana; Lomnicki, Slawo; Dellinger, Barry; Varner, Kurt

2011-01-01

Exposure to airborne particles is associated with increased cardiovascular morbidity and mortality. During the combustion of chlorine-containing hazardous materials and fuels, chlorinated hydrocarbons chemisorb to the surface of transition metal-oxide-containing particles, reduce the metal, and form an organic free radical. These radical-particle systems can survive in the environment for days and are called environmentally persistent free radicals (EPFRs). This study determined whether EPFRs could decrease left ventricular function before and after ischemia and reperfusion (I/R) in vivo. Male Brown Norway rats were dosed (8 mg/kg, i.t.) 24 hr prior to testing with particles containing the EPFR of 1, 2-dichlorobenzene (DCB230). DCB230 treatment decreased systolic and diastolic function. DCB230 also produced pulmonary and cardiac inflammation. After ischemia, systolic, but not diastolic function was significantly decreased in DCB230-treated rats. Ventricular function was not affected by I/R in control rats. There was greater oxidative stress in the heart and increased 8-isoprostane (biomarker of oxidative stress) in the plasma of treated vs control rats after I/R. These data demonstrate for the first time that DCB230 can produce inflammation and significantly decrease cardiac function at baseline and after I/R in vivo. Furthermore, these data suggest that EPFRs may be a risk factor for cardiac toxicity in healthy individuals and individuals with ischemic heart disease. Potential mechanisms involving cytokines/chemokines and/or oxidative stress are discussed. PMID:21385100

Decreases in beetle body size linked to climate change and warming temperatures.

PubMed

Tseng, Michelle; Kaur, Katrina M; Soleimani Pari, Sina; Sarai, Karnjit; Chan, Denessa; Yao, Christine H; Porto, Paula; Toor, Anmol; Toor, Harpawantaj S; Fograscher, Katrina

2018-05-01

Body size is a fundamental ecological trait and is correlated with population dynamics, community structure and function, and ecosystem fluxes. Laboratory data from broad taxonomic groups suggest that a widespread response to a warming world may be an overall decrease in organism body size. However, given the myriad of biotic and abiotic factors that can also influence organism body size in the wild, it is unclear whether results from these laboratory assays hold in nature. Here we use datasets spanning 30 to 100 years to examine whether the body size of wild-caught beetles has changed over time, whether body size changes are correlated with increased temperatures, and we frame these results using predictions derived from a quantitative review of laboratory responses of 22 beetle species to temperature. We found that 95% of laboratory-reared beetles decreased in size with increased rearing temperature, with larger-bodied species shrinking disproportionately more than smaller-bodied beetles. In addition, the museum datasets revealed that larger-bodied beetle species have decreased in size over time, that mean beetle body size explains much of the interspecific variation in beetle responses to temperature, and that long-term beetle size changes are explained by increases in autumn temperature and decreases in spring temperature in this region. Our data demonstrate that the relationship between body size and temperature of wild-caught beetles matches relatively well with results from laboratory studies, and that variation in this relationship is largely explained by interspecific variation in mean beetle body size. This long-term beetle dataset is one of the most comprehensive arthropod body size datasets compiled to date, it improves predictions regarding the shrinking of organisms with global climate change, and together with the meta-analysis data, call for new hypotheses to explain why larger-bodied organisms may be more sensitive to temperature. © 2018 The

Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic condition.

PubMed

Yamazaki, Hiroki; Lai, Yu-Chang; Tateno, Morihiro; Setoguchi, Asuka; Goto-Koshino, Yuko; Endo, Yasuyuki; Nakaichi, Munekazu; Tsujimoto, Hajime; Miura, Naoki

2017-01-01

We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells. Additionally, TH-302 decreased the survival rate of the cells under hypoxic condition. Our studies suggest that hypoxic stimulation may advance the tumorigenicity of canine lymphoma cells, favoring malignant transformation. Therefore, the data presented may contribute to the development of TH-302-based hypoxia-targeting therapies for canine lymphoma.

Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy.

PubMed

Zhao, Yang; Dong, Daoyin; Reece, E Albert; Wang, Ashley R; Yang, Peixin

2018-01-01

Maternal diabetes induces neural tube defects, and oxidative stress is a causal factor for maternal diabetes-induced neural tube defects. The redox gene nuclear factor erythroid 2-related factor 2 is the master regulator of the cellular antioxidant system. In this study, we aimed to determine whether maternal diabetes inhibits nuclear factor erythroid 2-related factor 2 expression and nuclear factor erythroid 2-related factor 2-controlled antioxidant genes through the redox-sensitive miR-27a. We used a well-established type 1 diabetic embryopathy mouse model induced by streptozotocin for our in vivo studies. Embryos at embryonic day 8.5 were harvested for analysis of nuclear factor erythroid 2-related factor 2, nuclear factor erythroid 2-related factor 2-controlled antioxidant genes, and miR-27a expression. To determine if mitigating oxidative stress inhibits the increase of miR-27a and the decrease of nuclear factor erythroid 2-related factor 2 expression, we induced diabetic embryopathy in superoxide dismutase 2 (mitochondrial-associated antioxidant gene)-overexpressing mice. This model exhibits reduced mitochondria reactive oxygen species even in the presence of hyperglycemia. To investigate the causal relationship between miR-27a and nuclear factor erythroid 2-related factor 2 in vitro, we examined C17.2 neural stem cells under normal and high-glucose conditions. We observed that the messenger RNA and protein levels of nuclear factor erythroid 2-related factor 2 were significantly decreased in embryos on embryonic day 8.5 from diabetic dams compared to those from nondiabetic dams. High-glucose also significantly decreased nuclear factor erythroid 2-related factor 2 expression in a dose- and time-dependent manner in cultured neural stem cells. Our data revealed that miR-27a was up-regulated in embryos on embryonic day 8.5 exposed to diabetes, and that high glucose increased miR-27a levels in a dose- and time-dependent manner in cultured neural stem cells. In

Donepezil is associated with decreased in-hospital mortality as a result of pneumonia among older patients with dementia: A retrospective cohort study.

PubMed

Abe, Yasuko; Shimokado, Kentaro; Fushimi, Kiyohide

2018-02-01

Pneumonia is one of the major causes of mortality in older adults. As the average lifespan has extended and new modalities to prevent or treat pneumonia are developed, the factors that affect the length of hospital stay (LHS) and in-hospital mortality of older patients with pneumonia have changed. The object of the present study was to determine the factors associated with LHS and mortality as a result of pneumonia among older patients with dementia. With a retrospective cohort study design, we used the data derived from the Japanese Administrative Database and diagnosis procedure combination/per diem payment system (DPC/PDPS) database. There were 39 336 admissions of older patients for pneumonia between August 2010 and March 2012. Patients with incomplete data were excluded, leaving 25 602 patients for analysis. Having dementia decreased mortality (OR 0.71, P < 0.001) and increased LHS. Multiple logistic regression analysis identified donepezil as an independent factor that decreased mortality in patients with dementia (OR 0.36, P < 0.001). Donepezil was prescribed for 28.7% of these patients, and their mortality rate was significantly lower than those of patients with dementia who were not treated with donepezil and of patients without dementia. The mortality rate was higher for patients with dementia who were not treated with donepezil compared with patients who did not have dementia. All other factors that influenced LHS and mortality were similar to those reported by others. Donepezil seems to decrease in-hospital mortality as a result of pneumonia among older patients with dementia. Geriatr Gerontol Int 2018; 18: 269-275. © 2017 Japan Geriatrics Society.

Imatinib mesylate (STI571) decreases the vascular endothelial growth factor plasma concentration in patients with chronic myeloid leukemia.

PubMed

Legros, Laurence; Bourcier, Christine; Jacquel, Arnaud; Mahon, François-Xavier; Cassuto, Jill-Patrice; Auberger, Patrick; Pagès, Gilles

2004-07-15

Increased angiogenesis in bone marrow (BM) is one of the characteristics of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder that expresses a chimeric Bcr/Abl protein. Recently, the therapeutic strategy in CML has been totally modified with the development of a new drug: imatinib mesylate (STI571), a specific inhibitor of Bcr/Abl tyrosine kinase activity. The aim of our study was to determine, in patients with CML, the capacity of imatinib mesylate to modulate one of the most potent regulators of angiogenesis, the vascular endothelial growth factor (VEGF). In newly diagnosed CML, we observed significantly increased VEGF secretion by CML BM cells and significantly increased VEGF plasma concentrations. We showed that low plasma VEGF concentrations could be one of the characteristics of complete cytogenetic remission. To understand the molecular mechanisms leading to the inhibition of VEGF production by imatinib, we focused our experiments on the human cell line K562, which is Bcr/Abl positive. We demonstrated that imatinib inhibits VEGF gene transcription by targeting the Sp1 and Sp3 transcription factors. Taken together, our results highlight the potential prognostic value of VEGF concentrations in evaluating the evolution of CML patients treated with imatinib.

Exploring the determinants of secular decreases in dental caries among Korean children.

PubMed

Lee, Hye-Ju; Han, Dong-Hun

2015-08-01

The aim of this study was to determine the contributions of sealant and water fluoridation to the time trends in dental caries from 2003 to 2010. Data were from three waves of the Korean National Oral Health Surveys between 2003 and 2010, including a total of 23 059 children (11 889 boys and 11 170 girls) aged 8, 10, and 12 years. The impacts of sealant and water fluoridation on dental caries were obtained by logistic regression for each age group of children. The contributions of sealant and water fluoridation to the time trends in the prevalence of dental caries were examined by a series of logistic regression models, and changes in the adjusted odds ratios for each survey year were also calculated. Over the past 7 years, the prevalence of dental caries decreased dramatically. Although sealant had a significant impact on dental caries in each survey year, remarkable decreases in dental caries from 2003 to 2010 were not explained by the secular changes in the dental sealant or water fluoridation factor. We observed important population declines in dental caries in Korea in children aged 8-12 years; however, the likely causes for these secular trends remain to be determined. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Decreasing photobleaching by silver island films: application to muscle⋆

PubMed Central

Muthu, P.; Gryczynski, I.; Gryczynski, Z.; Talent, J.; Akopova, I.; Jain, K.; Borejdo, J.

2007-01-01

Recently it has become possible to study interactions between proteins at the level of single molecules. This requires collecting data from an extremely small volume, small enough to contain one molecule—typically of the order of attoliters (10−18 L). Collection of data from such a small volume with sufficiently high signal-to-noise ratio requires that the rate of photon detection per molecule be high. This calls for a large illuminating light flux, which in turn leads to rapid photobleaching of the fluorophores that are labeling the proteins. To decrease photobleaching, we measured fluorescence from a sample placed on coverslips coated with silver island films (SIF). SIF reduce photobleaching because they enhance fluorescence brightness and significantly decrease fluorescence lifetime. Increase in the brightness effectively decreases photobleaching because illumination can be attenuated to obtain the same fluorescence intensity. Decrease of lifetime decreases photobleaching because short lifetime minimizes the probability of oxygen attack while the fluorophore is in the excited state. The decrease of photobleaching was demonstrated in skeletal muscle. Myofibrils were labeled lightly with rhodamine–phalloidin, placed on coverslips coated with SIF, illuminated by total internal reflection, and observed through a confocal aperture. We show that SIF causes the intensity of phalloidin fluorescence to increase 4- to 5- fold and its fluorescence lifetime to decrease on average 23-fold. As a consequence, the rate of photobleaching of four or five molecules of actin of a myofibril on Olympus coverslips coated with SIF decreased at least 30-fold in comparison with photobleaching on an uncoated coverslip. Significant decrease of photobleaching makes the measurement of signal from a single cross-bridge of contracting muscle feasible. PMID:17531183

Effects of comprehensive education protocol in decreasing pre-hospital stroke delay among Chinese urban community population.

PubMed

Chen, Shengyun; Sun, Haixin; Zhao, Xingquan; Fu, Paul; Yan, Wang; Yilong, Wang; Hongyan, Jia; Yan, Zhang; Wenzhi, Wang

2013-06-01

Studies have shown that awareness of early stroke symptoms and the use of ambulances are two important factors in decreasing pre-hospital stroke delay. The purpose of this study is to evaluate a comprehensive educational stroke protocol in improving stroke response times. Two urban communities in Beijing (population ≍50 000), matched in economic status and geography, were enrolled in this study. A comprehensive educational protocol, which included public lectures and distribution of instructive material for the community and its medical staff, was implemented from August 2008 to December 2010. Surveillance of new onset stroke in both communities was carried out during the same period. Pre-hospital delay time and percentage of patients using emergency medical services (EMS) were compared between the two communities. After comprehensive educational protocol, we found that: (i) pre-hospital delay (time from stroke symptom onset to hospital arrival) decreased from 180 to 79 minutes, (ii) the proportion of patients arriving within three hours of stroke onset increased from 55·8% to 80·4%, (iii) pre-hospital delay of stroke patients with symptoms of paralysis, numbness, and speech impediments was decreased, and (iv) the proportion of stroke patients calling for EMS increased from 50·4% to 60·7%. The comprehensive educational stroke protocol was significantly effective in decreasing pre-hospital stroke delay.

Genetically decreased vitamin D and risk of Alzheimer disease.

PubMed

Mokry, Lauren E; Ross, Stephanie; Morris, John A; Manousaki, Despoina; Forgetta, Vincenzo; Richards, J Brent

2016-12-13

To test whether genetically decreased vitamin D levels are associated with Alzheimer disease (AD) using mendelian randomization (MR), a method that minimizes bias due to confounding or reverse causation. We selected single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels (p < 5 × 10 -8 ) from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) Consortium (N = 33,996) to act as instrumental variables for the MR study. We measured the effect of each of these SNPs on 25OHD levels in the Canadian Multicentre Osteoporosis Study (CaMos; N = 2,347) and obtained the corresponding effect estimates for each SNP on AD risk from the International Genomics of Alzheimer's Project (N = 17,008 AD cases and 37,154 controls). To produce MR estimates, we weighted the effect of each SNP on AD by its effect on 25OHD and meta-analyzed these estimates using a fixed-effects model to provide a summary effect estimate. The SUNLIGHT Consortium identified 4 SNPs to be genome-wide significant for 25OHD, which described 2.44% of the variance in 25OHD in CaMos. All 4 SNPs map to genes within the vitamin D metabolic pathway. MR analyses demonstrated that a 1-SD decrease in natural log-transformed 25OHD increased AD risk by 25% (odds ratio 1.25, 95% confidence interval 1.03-1.51, p = 0.021). After sensitivity analysis in which we removed SNPs possibly influenced by pleiotropy and population stratification, the results were largely unchanged. Our results provide evidence supporting 25OHD as a causal risk factor for AD. These findings provide further rationale to understand the effect of vitamin D supplementation on cognition and AD risk in randomized controlled trials. © 2016 American Academy of Neurology.

Recombinant activated factor VII in cardiac surgery: single-center experience.

PubMed

Singh, Sarvesh Pal; Chauhan, Sandeep; Choudhury, Minati; Malik, Vishwas; Choudhary, Shiv Kumar

2014-02-01

The widespread off-label use of recombinant activated factor VII for the control of refractory postoperative hemorrhage continues despite a warning from the Food and Drug Administration. Although effective in reducing the need for transfusion of blood and blood products, safety concerns still prevail. To compare the dosing and efficacy of recombinant activated factor VII between pediatric and adult patients, and in the operating room and intensive care unit. The records of 69 patients (33 children and 36 adults) who underwent cardiovascular surgery and received recombinant activated factor VII were reviewed retrospectively. The dose of recombinant activated factor VII, mediastinal drainage, use of blood and blood products, incidence of thrombosis, and 28-day mortality were studied. the efficacy of recombinant activated factor VII was comparable in adults and children, despite the lower dose in adults. Prophylactic use of recombinant activated factor VII decreased the incidence of mediastinal exploration and the duration of intensive care unit stay. A 4.3% incidence of thrombotic complications was observed in this study. The efficacious dose of recombinant activated factor VII is much less in adults compared to children. Prophylactic use of recombinant activated factor VII decreases the dose required, the incidence of mediastinal exploration, and intensive care unit stay, with no survival benefit.

Identifying and overcoming the effect of mass transfer limitation on decreased yield in enzymatic hydrolysis of lignocellulose at high solid concentrations.

PubMed

Du, Jian; Cao, Yuan; Liu, Guodong; Zhao, Jian; Li, Xuezhi; Qu, Yinbo

2017-04-01

Cellulose conversion decreases significantly with increasing solid concentrations during enzymatic hydrolysis of insoluble lignocellulosic materials. Here, mass transfer limitation was identified as a significant determining factor of this decrease by studying the hydrolysis of delignified corncob residue in shake flask, the most used reaction vessel in bench scale. Two mass transfer efficiency-related factors, mixing speed and flask filling, were shown to correlate closely with cellulose conversion at solid loadings higher than 15% DM. The role of substrate characteristics in mass transfer performance was also significant, which was revealed by the saccharification of two corn stover substrates with different pretreatment methods at the same solid loading. Several approaches including premix, fed-batch operation, and particularly the use of horizontal rotating reactor were shown to be valid in facilitating cellulose conversion via improving mass transfer efficiency at solid concentrations higher than 15% DM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Krüppel-like factor 4, a novel transcription factor regulates microglial activation and subsequent neuroinflammation.

PubMed

Kaushik, Deepak K; Gupta, Malvika; Das, Sulagna; Basu, Anirban

2010-10-15

Activation of microglia, the resident macrophages of the central nervous system (CNS), is the hallmark of neuroinflammation in neurodegenerative diseases and other pathological conditions associated with CNS infection. The activation of microglia is often associated with bystander neuronal death. Nuclear factor-κB (NF-κB) is one of the important transcription factors known to be associated with microglial activation which upregulates the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (Cox-2) and other pro-inflammatory cytokines. Recent studies have focused on the role of Krüppel-like factor 4 (Klf4), one of the zinc-finger transcription factors, in mediating inflammation. However, these studies were limited to peripheral system and its role in CNS is not understood. Our studies focused on the possible role of Klf4 in mediating CNS inflammation. For in vitro studies, mouse microglial BV-2 cell lines were treated with 500 ng/ml Salmonella enterica lipopolysacchride (LPS). Brain tissues were isolated from BALB/c mice administered with 5 mg/kg body weight of LPS. Expressions of Klf4, Cox-2, iNOS and pNF-κB were evaluated using western blotting, quantitative real time PCR, and reverse transcriptase polymerase chain reactions (RT-PCRs). Klf4 knockdown was carried out using SiRNA specific for Klf4 mRNA and luciferase assays and electromobility shift assay (EMSA) were performed to study the interaction of Klf4 to iNOS promoter elements in vitro. Co-immunoprecipitation of Klf4 and pNF-κB was done in order to study a possible interaction between the two transcription factors. LPS stimulation increased Klf4 expression in microglial cells in a time- and dose-dependent manner. Knockdown of Klf4 resulted in decreased levels of the pro-inflammatory cytokines TNF-α, MCP-1 and IL-6, along with a significant decrease in iNOS and Cox-2 expression. NO production also decreased as a result of Klf4 knockdown. We found that Klf4 can potentially interact with

Deciphering the relative weights of demographic transition and vaccination in the decrease of measles incidence in Italy.

PubMed

Merler, Stefano; Ajelli, Marco

2014-02-22

In Italy, during the course of the past century to the present-day, measles incidence underwent a remarkable decreasing trend that started well before the introduction of the national immunization programme. In this work, we aim at examining to what extent both the demographic transition, characterized by declining mortality and fertility rates over time, and the vaccination programme are responsible for the observed epidemiological pattern. Making use of a non-stationary, age-structured disease transmission model, we show that in the pre-vaccination era, from 1901 to 1982, the decline in birth rates has resulted in a drastic decrease in the effective transmission rate, which in turn has determined a declining trend of measles incidence (from 25.2 to 10.3 infections per 1000 individuals). However, since 1983, vaccination appears to have become the major contributing factor in the decrease of measles incidence, which otherwise would have remained stable as a consequence of the nearly constant birth rates. This led to a remarkable decrease in the effective transmission rate, to a level well below the critical threshold for disease persistence. These findings call for the adoption of epidemiological models, which deviate the age structure from stationary equilibrium solutions, to better understand the biology of infectious diseases and evaluate immunization programmes.

On the origin of the decrease in stability of the DNA hairpin d(GCGAAGC) on complexation with aromatic drugs.

PubMed

Kostjukov, V V; Lantushenko, A O; Davies, D B; Evstigneev, M P

2007-08-01

Molecular dynamics simulations of drug-DNA complexes have been carried out in order to explain the experimentally observed decrease in thermal stability of the DNA hairpin d(GCGAAGC) on binding the aromatic drug molecules, daunomycin, ethidium bromide, novantrone and proflavine. This complexation behavior is in contrast to the stabilizing effect of the same aromatic drug molecules on DNA duplexes. Analysis of the energy parameters and the hydration properties of the complexes shows that the main factor correlating with the decrease in melting temperatures of the drug-hairpin complexes is the number of water bridges, with a reduction of at least 40% on ligand binding.

Factors associated with intern fatigue.

PubMed

Friesen, Lindsay D; Vidyarthi, Arpana R; Baron, Robert B; Katz, Patricia P

2008-12-01

Prior data suggest that fatigue adversely affects patient safety and resident well-being. ACGME duty hour limitations were intended, in part, to reduce resident fatigue, but the factors that affect intern fatigue are unknown. To identify factors associated with intern fatigue following implementation of duty hour limitations. Cross-sectional confidential survey of validated questions related to fatigue, sleep, and stress, as well as author-developed teamwork questions. Interns in cognitive specialties at the University of California, San Francisco. Univariate statistics characterized the distribution of responses. Pearson correlations elucidated bivariate relationships between fatigue and other variables. Multivariate linear regression models identified factors independently associated with fatigue, sleep, and stress. Of 111 eligible interns, 66 responded (59%). In a regression analysis including gender, hours worked in the previous week, sleep quality, perceived stress, and teamwork, only poorer quality of sleep and greater perceived stress were significantly associated with fatigue (p < 0.001 and p = 0.02, respectively). To identify factors that may affect sleep, specifically duty hours and stress, a secondary model was constructed. Only greater perceived stress was significantly associated with diminished sleep quality (p = 0.04), and only poorer teamwork was significantly associated with perceived stress (p < 0.001). Working >80 h was not significantly associated with perceived stress, quality of sleep, or fatigue. Simply decreasing the number of duty hours may be insufficient to reduce intern fatigue. Residency programs may need to incorporate programmatic changes to reduce stress, improve sleep quality, and foster teamwork in order to decrease intern fatigue and its deleterious consequences.

A school-based resilience intervention to decrease tobacco, alcohol and marijuana use in high school students

PubMed Central

2011-01-01

Background Despite schools theoretically being an ideal setting for accessing adolescents and preventing initiation of substance use, there is limited evidence of effective interventions in this setting. Resilience theory provides one approach to achieving such an outcome through improving adolescent mental well-being and resilience. A study was undertaken to examine the potential effectiveness of such an intervention approach in improving adolescent resilience and protective factor scores; and reducing the prevalence of adolescent tobacco, alcohol and marijuana use in three high schools. Methods A non-controlled before and after study was undertaken. Data regarding student resilience and protective factors, and measures of tobacco, alcohol and marijuana use were collected from grade 7 to 10 students at baseline (n = 1449) and one year following a three year intervention (n = 1205). Results Significantly higher resilience and protective factors scores, and significantly lower prevalence of substance use were evident at follow up. Conclusions The results suggest that the intervention has the potential to increase resilience and protective factors, and to decrease the use of tobacco, alcohol and marijuana by adolescents. Further more rigorous research is required to confirm this potential. PMID:21942951

Decreases in Human Semen Quality with Age Among Healthy Men

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

Eskenazi, B.; Wyrobek, A.J.; Kidd, S.A.

The objective of this report is to characterize the associations between age and semen quality among healthy active men after controlling for identified covariates. Ninety-seven healthy, nonsmoking men between 22 and 80 years without known fertility problems who worked for or retired from a large research laboratory. There was a gradual decrease in all semen parameters from 22-80 years of age. After adjusting for covariates, volume decreased 0.03 ml per year (p = 0.001); sperm concentration decreased 2.5% per year (p = 0.005); total count decreased 3.6% per year of age (p < 0.001); motility decreased 0.7% per year (Pmore » < 0.001); progressive motility decreased 3.1% per year (p < 0.001); and total progressively motile sperm decreased 4.8% per year (p < 0.001). In a group of healthy active men, semen volume, sperm concentration, total sperm count, and sperm motility decrease continuously between 22-80 years of age, with no evidence of a threshold.« less

Overexpression of a wheat (Triticum aestivum L.) bZIP transcription factor gene, TabZIP6, decreased the freezing tolerance of transgenic Arabidopsis seedlings by down-regulating the expression of CBFs.

PubMed

Cai, Wangting; Yang, Yaling; Wang, Weiwei; Guo, Guangyan; Liu, Wei; Bi, Caili

2018-03-01

The basic leucine zipper (bZIP) proteins play important roles against abiotic stress in plants, including cold stress. However, most bZIPs involved in plant freezing tolerance are positive regulators. Only a few bZIPs function negatively in cold stress response. In this study, TabZIP6, a Group C bZIP transcription factor gene from common wheat (Triticum aestivum L.), was cloned and characterized. The transcript of TabZIP6 was strongly induced by cold treatment (4 °C). TabZIP6 is a nuclear-localized protein with transcriptional activation activity. Arabidopsis plants overexpressing TabZIP6 showed decreased tolerance to freezing stress. Microarray as well as quantitative real-time PCR (qRT-PCR) analysis showed that CBFs and some key COR genes, including COR47 and COR15B, were down-regulated by cold treatment in TabZIP6-overexpressing Arabidopsis lines. TabZIP6 was capable of binding to the G-box motif and the CBF1 and CBF3 promoters in yeast cells. A yeast two-hybrid assay revealed that TabZIP6, as well as the other two Group S bZIP proteins involved in cold stress tolerance in wheat, Wlip19 and TaOBF1, can form homodimers by themselves and heterodimers with each other. These results suggest that TabZIP6 may function negatively in the cold stress response by binding to the promoters of CBFs, and thereby decreasing the expression of downstream COR genes in TabZIP6-overexpressing Arabidopsis seedlings. Copyright © 2018. Published by Elsevier Masson SAS.

Administration of Bifidobacterium breve Decreases the Production of TNF-α in Children with Celiac Disease.

PubMed

Klemenak, Martina; Dolinšek, Jernej; Langerholc, Tomaž; Di Gioia, Diana; Mičetić-Turk, Dušanka

2015-11-01

Increasing evidence suggests that not only genetics, but also environmental factors like gut microbiota dysbiosis play an important role in the pathogenesis of celiac disease (CD). The aim of our study was to investigate the effect of two probiotic strains Bifidobacterium breve BR03 and B. breve B632 on serum production of anti-inflammatory cytokine interleukin 10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in children with CD. The study was a double-blinded, placebo-controlled trial that included 49 children with CD on gluten-free diet (GFD) randomized into two groups and 18 healthy children in the control group. The first group (24 children with CD) daily received B. breve BR03 and B632 (2 × 10(9) colony-forming units) and the second group (25 children with CD) received placebo for 3 months. TNF-α levels were significantly decreased in the first group after receiving B. breve for 3 months. On follow-up, 3 months after receiving probiotics, TNF-α levels increased again. Children with CD who were on GFD for less than 1 year showed similar baseline TNF-α levels as children who were on GFD for more than 1 year. IL-10 levels were in all groups of patients below detection level. Probiotic intervention with B. breve strains has shown a positive effect on decreasing the production of pro-inflammatory cytokine TNF-α in children with CD on GFD.

Decreased sodium:potassium ratios in cats: 49 cases.

PubMed

Bell, Rory; Mellor, Dominic J; Ramsey, Ian; Knottenbelt, Clare

2005-06-01

Sodium:potassium (Na:K) ratios are often reported in feline biochemical panels, although the importance of this measurement has not been investigated. The aims of this study were to document the range of feline disease states associated with a decreased Na:K ratio, to determine the prevalence of this biochemical abnormality in a referral hospital population, and to identify any particular disease that was more likely to have a decreased Na:K ratio. A group of 49 cats with decreased Na:K ratios was compared with a group of 50 cats with normal Na:K ratios that were randomly selected from the same hospital population. Twelve of the 49 cats (24.5%) had gastrointestinal disease, 10 (20.4%) had urinary disease, 8 (16.3%) had endocrine disease, 8 (16.3%) had cardiorespiratory disease, and 5 (10.0%) had diseases affecting other body systems. Six (12.2%) had artifactually decreased Na:K ratios. No cat was identified with hypoadrenocorticism. Statistical analysis revealed that, although none of these disease states was significantly over- or under-represented in the affected group, a significantly higher proportion of cats with decreased Na:K ratio had body cavity effusions (P = .025). Serum potassium concentrations were significantly higher in the affected group (P < .0001), but there was no significant difference in mean sodium concentration between the 2 groups. Decreased Na:K ratios frequently occur in cats with diseases other than hypoadrenocorticism, including cats with effusions. These findings should be considered when evaluating cats with this biochemical abnormality.

Risk of iron overload is decreased in beating heart coronary artery surgery compared to conventional bypass.

PubMed

Mumby, S; Koh, T W; Pepper, J R; Gutteridge, J M

2001-11-29

Conventional cardiopulmonary bypass surgery (CCPB) increases the iron loading of plasma transferrin often to a state of plasma iron overload, with the presence of low molecular mass iron. Such iron is a potential risk factor for oxidative stress and microbial virulence. Here we assess 'off-pump' coronary artery surgery on the beating heart for changes in plasma iron chemistry. Seventeen patients undergoing cardiac surgery using the 'Octopus' myocardial wall stabilisation device were monitored at five time points for changes in plasma iron chemistry. This group was further divided into those (n=9) who had one- or two- (n=8) vessel grafts, and compared with eight patients undergoing conventional coronary artery surgery. Patients undergoing beating heart surgery had significantly lower levels of total plasma non-haem iron, and a decreased percentage saturation of their transferrin at all time points compared to conventional bypass patients. Plasma iron overload occurred in only one patient undergoing CCPB. Beating heart surgery appears to decrease red blood cell haemolysis, and tissue damage during the operative procedures and thereby significantly decreases the risk of plasma iron overload associated with conventional bypass.

Fermented Moringa oleifera Decreases Hepatic Adiposity and Ameliorates Glucose Intolerance in High-Fat Diet-Induced Obese Mice.

PubMed

Joung, Hyunchae; Kim, Bobae; Park, Hyunjoon; Lee, Kyuyeon; Kim, Hee-Hoon; Sim, Ho-Cheol; Do, Hyun-Jin; Hyun, Chang-Kee; Do, Myoung-Sool

2017-05-01

Metabolic diseases, such as glucose intolerance and nonalcoholic fatty-liver disease (NAFLD), are primary risk factors for life-threatening conditions such as diabetes, heart attack, stroke, and hepatic cancer. Extracts from the tropical tree Moringa oleifera show antidiabetic, antioxidant, anti-inflammatory, and anticancer effects. Fermentation can further improve the safety and nutritional value of certain foods. We investigated the efficacy of fermented M. oleifera extract (FM) against high-fat diet (HFD)-induced glucose intolerance and hepatic lipid accumulation and investigated the underlying mechanisms by analyzing expression of proteins and genes involved in glucose and lipid regulation. C57BL/6 mice were fed with normal chow diet (ND) or HFD supplemented with distilled water (DW, control), nonfermented M. oleifera extract (NFM), or FM for 10 weeks. Although body weights were similar among HFD-fed treatment groups, liver weight was decreased, and glucose tolerance test (GTT) results improved in the FM group compared with DW and NFM groups. Hepatic lipid accumulation was also lower in the FM group, and expressions of genes involved in liver lipid metabolism were upregulated. In addition, HFD-induced endoplasmic reticulum (ER) stress, oxidative stress, and lipotoxicity in quadriceps muscles were decreased by FM. Finally, proinflammatory cytokine mRNA expression was decreased by FM in the liver, epididymal adipose tissue, and quadriceps of HFD-fed mice. FMs may decrease glucose intolerance and NAFLD under HFD-induced obesity by decreasing ER stress, oxidative stress, and inflammation.

The epidemiology of infectious mononucleosis in Northern Scotland: a decreasing incidence and winter peak.

PubMed

Visser, Elizabeth; Milne, Denis; Collacott, Ian; McLernon, David; Counsell, Carl; Vickers, Mark

2014-03-20

Infection with Epstein-Barr virus (EBV) is almost ubiquitous in humans and generally occurs at two ages: infantile, which is usually asymptomatic and associated with poorer socioeconomic conditions, and adolescent, which causes infectious mononucleosis (IM) in ~25% cases. The determinants of whether the infection causes IM remain uncertain. We aimed to evaluate seasonality and temporal trends in IM. Data from all Monospot tests, used as a marker for IM, were collected from the Grampian population over 16 years. Positive Monospot test results peaked at 17 years in females and 19 in males. Females had 16% more diagnoses, although 55% more tests. IM was ~38% more common in winter than summer. The annual rate of positive tests decreased progressively over the study period, from 174/100 000 (95% CI 171-178) in 1997 to 67/100 000 (95% CI 65-69) in 2012. IM appears to be decreasing in incidence, which may be caused by changing environmental influences on immune systems. One such factor may be exposure to sunlight.Words 168. The Medical Research Council and NHS Grampian-MS endowments.

29 CFR 4043.22 - Amendment decreasing benefits payable.

Code of Federal Regulations, 2010 CFR

2010-07-01

... TERMINATIONS REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.22 Amendment decreasing benefits payable. (a) Reportable event. A reportable event occurs... contributions with respect to any participant may be decreased. (b) Waivers. Notice is waived for this event. ...

29 CFR 4043.22 - Amendment decreasing benefits payable.

Code of Federal Regulations, 2014 CFR

2014-07-01

... TERMINATIONS REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.22 Amendment decreasing benefits payable. (a) Reportable event. A reportable event occurs... contributions with respect to any participant may be decreased. (b) Waivers. Notice is waived for this event. ...

29 CFR 4043.22 - Amendment decreasing benefits payable.

Code of Federal Regulations, 2012 CFR

2012-07-01

... TERMINATIONS REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.22 Amendment decreasing benefits payable. (a) Reportable event. A reportable event occurs... contributions with respect to any participant may be decreased. (b) Waivers. Notice is waived for this event. ...

29 CFR 4043.22 - Amendment decreasing benefits payable.

Code of Federal Regulations, 2013 CFR

2013-07-01

... TERMINATIONS REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.22 Amendment decreasing benefits payable. (a) Reportable event. A reportable event occurs... contributions with respect to any participant may be decreased. (b) Waivers. Notice is waived for this event. ...

29 CFR 4043.22 - Amendment decreasing benefits payable.

Code of Federal Regulations, 2011 CFR

2011-07-01

... TERMINATIONS REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.22 Amendment decreasing benefits payable. (a) Reportable event. A reportable event occurs... contributions with respect to any participant may be decreased. (b) Waivers. Notice is waived for this event. ...

Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats.

PubMed

Napimoga, Marcelo H; Benatti, Bruno B; Lima, Flavia O; Alves, Polyanna M; Campos, Alline C; Pena-Dos-Santos, Diego R; Severino, Fernando P; Cunha, Fernando Q; Guimarães, Francisco S

2009-02-01

Cannabidiol (CBD) is a cannabinoid component from Cannabis sativa that does not induce psychotomimetic effects and possess anti-inflammatory properties. In the present study we tested the effects of CBD in a periodontitis experimental model in rats. We also investigated possible mechanisms underlying these effects. Periodontal disease was induced by a ligature placed around the mandible first molars of each animal. Male Wistar rats were divided into 3 groups: control animals; ligature-induced animals treated with vehicle and ligature-induced animals treated with CBD (5 mg/kg, daily). Thirty days after the induction of periodontal disease the animals were sacrificed and mandibles and gingival tissues removed for further analysis. Morphometrical analysis of alveolar bone loss demonstrated that CBD-treated animals presented a decreased alveolar bone loss and a lower expression of the activator of nuclear factor-kappaB ligand RANKL/RANK. Moreover, gingival tissues from the CBD-treated group showed decreased neutrophil migration (MPO assay) associated with lower interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha production. These results indicate that CBD may be useful to control bone resorption during progression of experimental periodontitis in rats.

Changes in the retrobulbar arterial circulation after decrease of the elevated intraocular pressure in men and women with primary open angle glaucoma.

PubMed

Marjanović, Ivan; Martinez, Antonio; Marjanović, Marija; Kontić, Djordje; Hentova-Senćanić, Paraskeva; Marković, Vujica; Bozić, Marija

2013-01-01

An altered perfusion of the optic nerve head has been proposed as a pathogenic factor of glaucoma. The aim of this study was to evaluate the changes of the hemodynamic parameters in the retrobulbar arterial circulation after decrease of the elevated intraocular pressure (IOP) in women and men with primary open angle glaucoma. The study included 60 patients (33 males and 27 females) older than 50 years, with diagnosed and treated primary open angle glaucoma (77 eyes of 39 patients had increased IOP, > 25 mm Hg).They were examined at the Clinic of Eye Diseases (complete ophthalmologic exam) and Clinic of Neurology, Clinical Center of Serbia, Belgrade, from December 2009 to December 2010. Imaging of hemodynamic parameters of three retrobulbar arterial vessels: ophthalmic, central retinal and posterior ciliary arteries with color Doppler was performed. Among women, hemodynamic arterial parameter of the peak-systolic velocity was increased in the central retinal artery and decreased in the ophthalmic artery and posterior ciliary arteries; end-diastolic velocity was increased in all three retrobulbar vascular levels; Pourcelot resistivity index was increased, but pulsatility index was decreased in all three vessels. Among men, peak-systolic velocity, end-diastolic velocity and pulsatility index were decreased in all three vessels; resistivity index was increased in the ophthalmic artery, but decreased in the central retinal artery and posterior ciliary arteries. There was a significant change of the ophthalmic artery pulsatility index in women, and the end-diastolic velocity of the ophthalmic artery in men. There was a difference of the retrobulbar arterial circulation between women and men with primary open angle glaucoma after decrease of the elevated intraocular pressure.The role of vascular factors in the supply of the optic disc neuroretinal rim is important.

Proton-pump inhibitors can decrease gastrointestinal bleeding after percutaneous coronary intervention.

PubMed

Jiang, Zongdan; Wu, Hailu; Duan, Zhaotao; Wang, Zhibing; Hu, Kewei; Ye, Fei; Zhang, Zhenyu

2013-12-01

Current medical therapies for patients who have an acute coronary syndrome (ACS) focus on the coagulation cascade and platelet inhibition. These, coupled with early use of cardiac catheterization and revascularization, have decreased morbidity and mortality rates in patients who have acute ischemic heart disease with risk of bleeding. The study aimed to determine the incidence of gastrointestinal bleeding after percutaneous coronary intervention (PCI). The effect of proton-pump inhibitor (PPI) treatment was also analyzed. This case-control study evaluated gastrointestinal bleeding within a year of PCI for stable angina and acute coronary syndromes at Nanjing First Hospital between 2008 and 2011. Cases were identified and outcomes assessed using linkage analysis of data from cardiology and gastroenterology department databases. Analysis of the case and control groups for both risk and protective factors was performed using independent two-sample Student's t-test with Fisher's exact P value and logistic regression. The incidence of gastrointestinal bleeding following PCI was 1.3% (35/2680 patients). The risk factors for gastrointestinal bleeding were advanced age, female gender, smoking, drinking, previous peptic ulcer and previous gastrointestinal bleeding. PPI use after PCI (P=0.000) was accompanied by a lower risk of gastrointestinal bleeding, with only a few cases of gastrointestinal bleeding events reported. The incidence of gastrointestinal bleeding associated with the combination of aspirin and clopidogrel therapy was estimated to be 1.3%. Advanced age, being female, smokers, drinkers, previous peptic ulcer and previous gastrointestinal bleeding were significant independent risk factors. PPI for the prevention and treatment of gastrointestinal bleeding induced by the combination of aspirin and clopidogrel in patients after PCI was safe and effective. Published by Elsevier Masson SAS.

Decreased natural killer cell activity in atopic eczema.

PubMed Central

Hall, T J; Rycroft, R; Brostoff, J

1985-01-01

We have studied NK cell activity in atopic and non-atopic subjects using a standard 51Cr-release assay and K562 target cells. In atopics (AT) with allergic rhinitis and/or asthma, NK cell activity was similar to that in non-atopic (N) subjects, whilst patients with severe atopic eczema (AE) had depressed NK cell activity compared to AT or N subjects. In addition, circulating T-cell numbers and Con A responsiveness was decreased in AE, although neither parameter was correlated with decreased NK cell activity. However, decreased NK cell activity in atopic eczema was positively correlated with decreased numbers of Fc gamma + lymphocytes (P = 0.01) and decreased effector: target cell binding (P = 0.05), and negatively correlated with increased monocytes in AE (P = 0.09). AE NK cell activity was equally or more sensitive to the inhibitory effects of drugs such as dibutyryl cyclic AMP, prostaglandins (PG) D2,E2 and histamine. The relative percentage increase in NK cell activity by the interferon inducer poly I:C was similar in AE patients and controls. The results suggest that reduced numbers of circulating NK cells and pre-NK cells account for the depressed level of NK cell activity in subjects with severe atopic eczema. PMID:3876984

Early Childhood Risk Factors for Decreased FEV1 at Age Six to Seven Years in Young Children with Cystic Fibrosis.

PubMed

Sanders, Don B; Emerson, Julia; Ren, Clement L; Schechter, Michael S; Gibson, Ronald L; Morgan, Wayne; Rosenfeld, Margaret

2015-08-01

There are limited objective measures of the severity of lung disease before children are able to routinely perform spirometry, generally at age 6 years. Identifying risk factors for reduced lung function at age 6 provides opportunities to intervene and slow the progression of cystic fibrosis (CF) lung disease. To evaluate early childhood predictors of lung function at age 6-7 in a large U.S. CF cohort in the current era of widespread early eradication therapy for Pseudomonas aeruginosa (P. aeruginosa). Participants were children with CF enrolled before age 4 in the Early Pseudomonas Infection Control (EPIC) Observational Study, a multicenter, longitudinal study that enrolled P. aeruginosa-negative children not exceeding 12 years of age. Linear regression was used to estimate the association between potential early childhood risk factors and the best FEV1% predicted at age 6-7 years. Four hundred and eighty-four children (of 1,797 enrolled in the EPIC Observational Study) met the eligibility criteria for this analysis. Mean (SD) age at enrollment was 2.0 (1.3) years. In a multivariable model adjusted for age at enrollment, the following risk factors were significantly associated with lower mean (95% confidence interval) FEV1% predicted at age 6-7: weight percentile less than 10% during the year of enrollment (-5.3 [-9.1, -1.5]), P. aeruginosa positive during the year of enrollment (-2.8 [-5.7, 0.0]), crackles or wheeze during the year of enrollment (-5.7 [-9.4, -1.9]), mother's education of high school or less (-4.2 [-7.3, -1.2]), and mother smoked during pregnancy (-4.4 [-8.8, 0.1]). In this large U.S. cohort, we identified several early childhood risk factors for lower FEV1 at age 6-7 years, most of which are modifiable. Clinical trial registered with www.clinicaltrials.gov (NCT00097773).

Decreasing Fires in Mediterranean Europe

PubMed Central

Turco, Marco; Bedia, Joaquín; Di Liberto, Fabrizio; Fiorucci, Paolo; von Hardenberg, Jost; Koutsias, Nikos; Llasat, Maria-Carmen; Xystrakis, Fotios; Provenzale, Antonello

2016-01-01

Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA) displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value). These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011) and a mixed trend in Portugal (1980-2011). Similar overall results were found for the annual number of fires (NF), which globally decreased by about 12600 in the study period (about -59%), except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980’s, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts. PMID:26982584

Decreasing Fires in Mediterranean Europe.

PubMed

Turco, Marco; Bedia, Joaquín; Di Liberto, Fabrizio; Fiorucci, Paolo; von Hardenberg, Jost; Koutsias, Nikos; Llasat, Maria-Carmen; Xystrakis, Fotios; Provenzale, Antonello

2016-01-01

Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA) displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value). These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011) and a mixed trend in Portugal (1980-2011). Similar overall results were found for the annual number of fires (NF), which globally decreased by about 12600 in the study period (about -59%), except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

Decreased NAA in gray matter is correlated with decreased availability of acetate in white matter in postmortem multiple sclerosis cortex.

PubMed

Li, S; Clements, R; Sulak, M; Gregory, R; Freeman, E; McDonough, J

2013-11-01

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) which leads to progressive neurological disability. Our previous studies have demonstrated mitochondrial involvement in MS cortical pathology and others have documented decreased levels of the neuronal mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is synthesized in neurons, it is broken down in oligodendrocytes into aspartate and acetate. The resulting acetate is incorporated into myelin lipids, linking neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin lipids in the CNS. In the present study we show that treating human SH-SY5Y neuroblastoma cells with the electron transport chain inhibitor antimycin A decreased levels of NAA as measured by HPLC. To better understand the significance of the relationship between mitochondrial function and levels of NAA and its breakdown product acetate on MS pathology we then quantitated the levels of NAA and acetate in MS and control postmortem tissue blocks. Regardless of lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray matter from parietal and motor cortex in MS, respectively, compared to controls. Acetate levels in adjacent white matter mirrored these decreases as evidenced by the 36 and 45 % reduction in acetate obtained from parietal and motor cortices. These data suggest a novel mechanism whereby mitochondrial dysfunction and reduced NAA levels in neurons may result in compromised myelination by oligodendrocytes due to decreased availability of acetate necessary for the synthesis of myelin lipids.

Intake of fish oil, oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive protein and reduces coronary heart disease risk factors in male patients in a cardiac rehabilitation program.

PubMed

Carrero, Juan Jesús; Fonollá, Juristo; Marti, José Luis; Jiménez, Jesús; Boza, Julio J; López-Huertas, Eduardo

2007-02-01

Certain nutrients have been shown to be effective in preventing coronary heart disease. We hypothesized that a daily intake of low amounts of a number of these nutrients would exert beneficial effects on risk factors and clinical variables in patients that suffered from myocardial infarction (MI) and were following a cardiac rehabilitation program. Forty male MI patients were randomly allocated into 2 groups. The supplemented group consumed 500 mL/d of a fortified dairy product containing eicosapentaenoic acid, docosahexaenoic acid, oleic acid, folic acid, and vitamins A, B-6, D, and E. The control group consumed 500 mL/d of semi-skimmed milk with added vitamins A and D. The patients received supervised exercise training, lifestyle and dietary recommendations, and they were instructed to consume the products in addition to their regular diet. Blood extractions and clinical examinations were performed after 0, 3, 6, 9, and 12 mo. Plasma concentrations of eicosapentaenoic acid, docosahexaenoic acid, oleic acid, folic acid, vitamin B-6, and vitamin E increased after supplementation (P<0.05). Plasma total and LDL-cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein concentrations decreased in the supplemented group (P<0.05), and plasma total homocysteine decreased in both groups. There were no changes in heart rate, blood pressure, or cardiac electrocardiographic parameters in either group. Therapeutic lifestyle changes, effected through a CR program comprising regular exercise and the intake of a combination of dietary nutrients, reduced a variety of risk factors in MI patients, which supports the rationale for nutritional programs in the secondary prevention of coronary heart disease.

Effective degradation of methylisothiazolone biocide using ozone: Kinetics, mechanisms, and decreases in toxicity.

PubMed

Li, Ang; Wu, Qian-Yuan; Tian, Gui-Peng; Hu, Hong-Ying

2016-12-01

Methylisothiazolone (MIT) is a common biocide that is widely used in water-desalination reverse-osmosis processes. The transformation of MIT during water treatment processes is poorly understood. The kinetics and mechanisms involved in the degradation of MIT during ozonation were investigated in this study. Ozonation was found to be a useful way of degrading MIT in water, and the degradation rate constant was 0.11 (±0.1) × 10 3  L/(mol·s). The degradation rate constant did not change when the pH was increased from 3 to 9. The pre-exponential factor A and the activation energy E a for the ozonation process were 7.564 × 10 13  L/(mol·s) and 66.74 kJ/mol, respectively. The decrease in the MIT concentration and the amount of ozone consumed were measured, and the stoichiometric factor α for the ozone consumption to MIT removal ratio was found to be 1.8. Several ozonation products were detected using time-of-flight mass spectrometry. Almost 32% of the organic sulfur in the MIT was oxidized to release sulfate ions, which caused a decrease in pH. Sulfur atoms were oxidized to sulfone species and then hydrolyzed to give sulfate during ozonation. Addition reactions involving carbon-carbon double bonds and the oxidation of α-carbon atoms also occurred. MIT was found to be lethal to Daphnia magna Straus (D. magna) with a median lethal concentration of 18.2 μmol/L. Even though the primary ozonation products of MIT still showed some toxicity to D. magna, ozone could minimize the toxic effect after a long reaction time. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum concentrations of brain-derived neurotrophic factor (BDNF) are decreased in colorectal cancer patients.

PubMed

Brierley, G V; Priebe, I K; Purins, L; Fung, K Y C; Tabor, B; Lockett, T; Nice, E; Gibbs, P; Tie, J; McMurrick, P; Moore, J; Ruszkiewicz, A; Burgess, A; Cosgrove, L J

2013-01-01

To determine the usefulness of brain-derived neurotrophic factor (BDNF) as a diagnostic biomarker for colorectal cancer (CRC). ELISA immunoassay was used to examine BDNF concentrations in the sera of two different retrospective cohorts consisting of CRC patients and age/gender matched controls. Cohort 1 consisted of 99 controls and 97 CRC patients, whereas cohort 2 consisted of 47 controls and 91 CRC patients. In cohort 1, the median concentration of BDNF was significantly (p< 0.0001) lower in CRC patient samples (18.8 ng/mL, range 4.0-56.5 ng/mL) than control samples (23.4 ng/mL, range 3.0-43.1 ng/mL). This finding was validated in an independent patient cohort (CRC patients: 23.0 ng/mL, range 6.0-45.9 ng/mL; control patients: 32.3 ng/mL, range 14.2-62.4 ng/mL). BDNF concentrations did not differ significantly between Dukes' staging in the patient cohort, however patients with Stages A, B, C and D (p< 0.01 for each stage) tumours had significantly reduced BDNF levels compared to healthy controls. Receiver operating characteristic analysis was performed to determine the ability of BDNF to discriminate between healthy controls and those with CRC. At 95% specificity, BDNF concentrations distinguished CRC patients with 25% and 18% sensitivity, respectively, in cohorts 1 and 2 (cohort 1: AUC=0.79, 95% CI 0.70-0.87; cohort 2: AUC =0.69, 95% CI 0.61-0.76). The serum levels of BDNF were significantly lower in colorectal cancer patients when compared to a control population, and this did not differ between different Dukes' stages.

Why is the gender gap in life expectancy decreasing? The impact of age- and cause-specific mortality in Sweden 1997-2014.

PubMed

Sundberg, Louise; Agahi, Neda; Fritzell, Johan; Fors, Stefan

2018-04-13

To enhance the understanding of the current increase in life expectancy and decreasing gender gap in life expectancy. We obtained data on underlying cause of death from the National Board of Health and Welfare in Sweden for 1997 and 2014 and used Arriaga's method to decompose life expectancy by age group and 24 causes of death. Decreased mortality from ischemic heart disease had the largest impact on the increased life expectancy of both men and women and on the decreased gender gap in life expectancy. Increased mortality from Alzheimer's disease negatively influenced overall life expectancy, but because of higher female mortality, it also served to decrease the gender gap in life expectancy. The impact of other causes of death, particularly smoking-related causes, decreased in men but increased in women, also reducing the gap in life expectancy. This study shows that a focus on overall changes in life expectancies may hide important differences in age- and cause-specific mortality. It also emphasizes the importance of addressing modifiable lifestyle factors to reduce avoidable mortality.

Foot and ankle risk factors for falls in older people: a prospective study.

PubMed

Menz, Hylton B; Morris, Meg E; Lord, Stephen R

2006-08-01

Foot problems are common in older people and are associated with impaired balance and functional ability. Few prospective studies, however, have been undertaken to determine whether foot problems are a risk factor for falls. One hundred seventy-six people (56 men and 120 women, mean age 80.1, standard deviation 6.4 years) residing in a retirement village underwent tests of foot and ankle characteristics (including foot posture, range of motion, strength, and deformity) and physiological falls risk factors (including vision, sensation, strength, reaction time, and balance) and were followed for 12 months to determine the incidence of falls. Seventy-one participants (41%) reported falling during the follow-up period. Compared to those who did not fall, fallers exhibited decreased ankle flexibility, more severe hallux valgus deformity, decreased plantar tactile sensitivity, and decreased toe plantarflexor strength; they were also more likely to have disabling foot pain. Discriminant function analysis revealed that decreased toe plantarflexor strength and disabling foot pain were significantly and independently associated with falls after accounting for physiological falls risk factors and age. Foot and ankle problems increase the risk of falls in older people. Interventions to address these factors may hold some promise as a falls prevention strategy.

Silicosis decreases bone mineral density in rats.

PubMed

Hui, Zhang; Dingjie, Xu; Yuan, Yuan; Zhongqiu, Wei; Na, Mao; Mingjian, Bei; Yu, Gou; Guangyuan, Liu; Xuemin, Gao; Shifeng, Li; Yucong, Geng; Fang, Yang; Summer, Ross; Hong, Xu

2018-06-01

Silicosis is the most common occupational lung disease in China, and is associated with a variety of complications, many of which are poorly understood. For example, recent data indicate that silicosis associates with the development of osteopenia, and in some cases this bone loss is severe, meeting criteria for osteoporosis. Although many factors are likely to contribute to this relationship, including a sedentary lifestyle in patients with advanced silicotic lung disease, we hypothesized that silica might directly reduce bone mineral density. In the present study, six Wistar rats were exposed to silica for 24 weeks in order to induce pulmonary silicosis and examine the relationship to bone mineral density. As expected, all rats exposed to silica developed severe pulmonary fibrosis, as manifested by the formation of innumerable silicotic nodules and the deposition of large amounts of interstitial collagen. Moreover, micro-CT results showed that bone mineral density (BMD) was also significantly reduced in rats exposed to silica when compared control animals and this associated with a modest reduction in serum calcium and 25-hydroxyvitamin D levels. In addition, we found that decreased BMD was also linked to increased osteoclast activity as well as fibrosis-like changes, and to the deposition of silica within bone marrow. In summary, our findings support the hypothesis that silicosis reduces bone mineral density and provide support for ongoing investigations into the mechanisms causing osteopenia in silicosis patients. Copyright © 2018. Published by Elsevier Inc.

Explaining the Decrease in Deaths from Cardiovascular Disease in Poland. The Top-Down Risk Assessment Approach, from Policy to Health Impact.

PubMed

Kobza, Joanna; Geremek, Mariusz

2016-04-13

The purpose of this paper was to assess the relations between policy and health outcome The CVD mortality rate in Poland over the past two decades has decreased by about 40%. It was the highest decrease among Central and Eastern European countries and also exceptional on a global scale. Key determinants which can account for these phenomena include CVD-related life style factors, better environmental indicators, and better access to medical technologies and to pharmacological treatment. Health policy played a vital role. The study was based on an extensive literature review, documentation analysis and questionnaire survey research. The top-down risk assessment approach model was implemented, which followed the logical pathway between the policy, health determinants, risk factors and health outcome. Several national public health programs have been implemented since the beginning of the 1990s. The National Health Fund has constantly increased the expenditures on cardiology treatment. The number of invasive cardiology units has increased, as has the number of coronarography and angioplasty procedures in the same period. The significant mortality decrease can indicate to policy makers that it is necessary to prioritize policies to manage effective, innovative medical interventions. Topdown policy risk assessment is a useful methodological tool to present the full chain of interactions.

Natural Decrease in Texas Counties.

ERIC Educational Resources Information Center

Koebernick, Thomas E.; Markides, Kyriakos S.

In replication of other studies, the natural decrease of Texas population was examined in terms of the effect of migration and fertility. Utilizing Texas and U.S. vital statistics and the 1970 U.S. Census of Population, Texas population trends were analyzed for the 1968-72 period by dividing the 254 Texas counties into: (1) 65 natural decrease…

Decreasing transobturator sling groin pain without decreasing efficacy using TVT-Abbrevo.

PubMed

Shaw, Jonathan S; Jeppson, Peter C; Rardin, Charles R

2015-09-01

Groin pain following a transobturator (TO) midurethral sling is not uncommon and can be difficult to manage. We sought to determine if decreasing the mesh burden in the groin would decrease pain. The primary objective was to compare the incidence of post-operative groin pain following placement of full-length TVT-Obturator versus the shorter TVT-Abbrevo. Secondarily, we aimed to compare the efficacy between both devices 6 months after surgery. This is a retrospective cohort study of all women who underwent a TO midurethral sling by the division of urogynecology at one institution between 1 January 2007 and 31 October 2013. Charts were reviewed and the incidence of post-operative groin pain in the two groups dichotomized as present or absent and compared using a Chi-squared test. Validated questionnaire scores of the groups were compared using t tests. There were 125 patients who received a TVT-Obturator and 100 patients who received a TVT-Abbrevo. No differences in demographic data were present between the groups. Twelve patients (9.6 %) in the TVT-Obturator group and 1 patient (1 %) in the TVT-Abbrevo group experienced bothersome groin pain (P value = 0.007). The complete pre- and 6-month post-operative ISI, UDI-6 and PFIQ-7 scores were available for 76 (61 %), 47 (38 %), and 45 (36 %) patients following TVT-Obturator and 57 (57 %), 30 (30 %), and 28 (28 %) following TVT-Abbrevo treatment. At 6 months the mean improvement in questionnaire scores for the TVT-Obturator and TVT-Abbrevo groups were as follows: 5.0 and 5.1 for ISI (P value = 0.9), 8.3 and 7.9 for UDI-6 (P value = 0.8), and 4.8 and 6.1 for PFIQ-7 (P value = 0.4). Use of TVT-Abbrevo reduces post-operative groin pain compared with the full-length TVT-Obturator, without any reduction in efficacy.

Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy

PubMed Central

Min, Xu; Xu, Xiaohong

2017-01-01

Diabetic nephropathy (DN) is manifested as increased urinary protein level, decreased glomerular filtration rate, and final renal dysfunction. DN is the leading cause of end-stage renal disease worldwide and causes a huge societal healthcare burden. Since satisfied treatments are still limited, exploring new strategies for the treatment of this disease is urgently needed. Oxidative stress takes part in the initiation and development of DN. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the treatment of DN. In current review, we discussed and summarized the therapeutic effects of Nrf2 activation on DN from both basic and clinical studies. PMID:28512642

SLAP deficiency decreases dsDNA autoantibody production

PubMed Central

Peterson, Lisa K.; Pennington, Luke F.; Shaw, Laura A.; Brown, Meredith; Treacy, Eric C.; Friend, Samantha F.; Hatlevik, Øyvind; Rubtsova, Kira; Rubtsov, Anatoly V.; Dragone, Leonard L.

2014-01-01

Src-like adaptor protein (SLAP) adapts c-Cbl, an E3 ubiquitin ligase, to activated components of the BCR signaling complex regulating BCR levels and signaling in developing B cells. Based on this function, we asked whether SLAP deficiency could decrease the threshold for tolerance and eliminate development of autoreactive B cells in two models of autoantibody production. First, we sensitized mice with a dsDNA mimetope that causes an anti-dsDNA response. Despite equivalent production of anti-peptide antibodies compared to BALB/c controls, SLAP−/− mice did not produce anti-dsDNA. Second, we used the 56R tolerance model. SLAP−/− 56R mice had decreased levels of dsDNA-reactive antibodies compared to 56R mice due to skewed light chain usage. Thus, SLAP is a critical regulator of B-cell development and function and its deficiency leads to decreased autoreactive B cells that are otherwise maintained by inefficient receptor editing or failed negative selection. PMID:24440645

SLAP deficiency decreases dsDNA autoantibody production.

PubMed

Peterson, Lisa K; Pennington, Luke F; Shaw, Laura A; Brown, Meredith; Treacy, Eric C; Friend, Samantha F; Hatlevik, Øyvind; Rubtsova, Kira; Rubtsov, Anatoly V; Dragone, Leonard L

2014-02-01

Src-like adaptor protein (SLAP) adapts c-Cbl, an E3 ubiquitin ligase, to activated components of the BCR signaling complex regulating BCR levels and signaling in developing B cells. Based on this function, we asked whether SLAP deficiency could decrease the threshold for tolerance and eliminate development of autoreactive B cells in two models of autoantibody production. First, we sensitized mice with a dsDNA mimetope that causes an anti-dsDNA response. Despite equivalent production of anti-peptide antibodies compared to BALB/c controls, SLAP(-/-) mice did not produce anti-dsDNA. Second, we used the 56R tolerance model. SLAP(-/-) 56R mice had decreased levels of dsDNA-reactive antibodies compared to 56R mice due to skewed light chain usage. Thus, SLAP is a critical regulator of B-cell development and function and its deficiency leads to decreased autoreactive B cells that are otherwise maintained by inefficient receptor editing or failed negative selection. Copyright © 2013 Elsevier Inc. All rights reserved.

The role of tumour necrosis factor-α and tumour necrosis factor receptor signalling in inflammation-associated systemic genotoxicity

PubMed Central

Westbrook, Aya M.; Wei, Bo; Hacke, Katrin; Xia, Menghang; Braun, Jonathan; Schiestl, Robert H.

2012-01-01

Chronic inflammatory diseases are characterised by systemically elevated levels of tumour necrosis factor (TNF)-α, a proinflammatory cytokine with pleiotropic downstream effects. We have previously demonstrated increased genotoxicity in peripheral leukocytes and various tissues in models of intestinal inflammation. In the present study, we asked whether TNF-α is sufficient to induce DNA damage systemically, as observed in intestinal inflammation, and whether tumour necrosis factor receptor (TNFR) signalling would be necessary for the resultant genotoxicity. In the wild-type mice, 500 ng per mouse of TNF-α was sufficient to induce DNA damage to multiple cell types and organs 1-h post-administration. Primary splenic T cells manifested TNF-α-induced DNA damage in the absence of other cell types. Furthermore, TNFR1−/−TNFR2−/− mice demonstrated decreased systemic DNA damage in a model of intestinal inflammation and after TNF-α injection versus wild-type mice, indicating the necessity of TNFR signalling. Nuclear factor (NF)-κB inhibitors were also able to decrease damage induced by TNF-α injection in wild-type mice. When TNF-α administration was combined with interleukin (IL)-1β, another proinflammatory cytokine, DNA damage persisted for up to 24 h. When combined with IL-10, an anti-inflammatory cytokine, decreased genotoxicity was observed in vivo and in vitro. TNF-α/TNFR-mediated signalling is therefore sufficient and plays a large role in mediating DNA damage to various cell types, subject to modulation by other cytokines and their mediators. PMID:21980144

43 CFR 4110.3-2 - Decreasing active use.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Decreasing active use. 4110.3-2 Section... Qualifications and Preference § 4110.3-2 Decreasing active use. (a) The authorized officer may suspend active use... site inventory, or other acceptable methods, the authorized officer will reduce active use, otherwise...

43 CFR 4110.3-2 - Decreasing active use.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Decreasing active use. 4110.3-2 Section... Qualifications and Preference § 4110.3-2 Decreasing active use. (a) The authorized officer may suspend active use... site inventory, or other acceptable methods, the authorized officer will reduce active use, otherwise...

43 CFR 4110.3-2 - Decreasing active use.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Decreasing active use. 4110.3-2 Section... Qualifications and Preference § 4110.3-2 Decreasing active use. (a) The authorized officer may suspend active use... site inventory, or other acceptable methods, the authorized officer will reduce active use, otherwise...

43 CFR 4110.3-2 - Decreasing active use.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Decreasing active use. 4110.3-2 Section... Qualifications and Preference § 4110.3-2 Decreasing active use. (a) The authorized officer may suspend active use... site inventory, or other acceptable methods, the authorized officer will reduce active use, otherwise...

Ammonia excretion increased and urea excretion decreased in urine of a new world nectarivorous bat with decreased nitrogen intake.

PubMed

Herrera M, L Gerardo; Ramirez P, Nicte; Miron M, Leticia

2006-01-01

We determined the effect of water and nitrogen intake on nitrogenous waste composition in the nectarivorous Pallas's long-tongued bat Glossophaga soricina (Phyllostomidae) to test the hypothesis that bats reduce excretion of urea nitrogen and increase the excretion of ammonia nitrogen as nitrogen intake decreases and water intake decreases. Because changes in urine nitrogen composition are expected only in animals whose natural diets are low in nitrogen and high in water content, we also measured maintenance nitrogen requirements (MNR). We hypothesized that, similar to other plant-eating vertebrates, nectarivorous bats have low MNR. Our nitrogen excretion hypothesis was partly proved correct. There was an increase in the proportion of N excreted as ammonia and a decrease in the proportion excreted as urea in low-nitrogen diets. The proportion of N excreted as ammonia and urea was independent of water intake. Most individuals were ureotelic (n = 28), and only a few were ureo-ammonotelic (n = 3) or ammonotelic (n = 2). According to our nitrogen requirement hypothesis, apparent MNR (60 mg kg(-0.75) d(-1)) and truly digestible MNR (54 mg N kg(-0.75) d(-1)) were low. A decrease in urea excretion in low-nitrogen diets may result from urea recycling from liver to the gut functioning as a nitrogen salvage system in nectarivorous bats. This mechanism probably contributes to the low MNR found in Pallas's long-tongued bats.

Grazing dairy cows had decreased interferon-γ, tumor necrosis factor, and interleukin-17, and increased expression of interleukin-10 during the first week after calving.

PubMed

Heiser, Axel; McCarthy, Allison; Wedlock, Neil; Meier, Susanne; Kay, Jane; Walker, Caroline; Crookenden, Mallory A; Mitchell, Murray D; Morgan, Stuart; Watkins, Kate; Loor, Juan J; Roche, John R

2015-02-01

Peripartum, and especially during the transition period, dairy cows undergo dramatic physiological changes. These coincide with an increased risk of disease during the first 2 wk after calving and have been linked to dairy cows failing to achieve production as well as reproductive targets. Previous evidence suggests that these physiological changes affect the immune system and that transition dairy cows experience some form of reduced immunocompetence. However, almost all of these studies were undertaken in high-production, housed dairy cows. Grazing cows have much lower levels of production and this study aimed to provide clarity whether or not the dysfunctional attributes of the peripartum immune system reported in high production housed cows are evident in these animals. Therefore, cell culture techniques, flow cytometry, and quantitative PCR were applied to analyze the cellular composition of peripheral blood mononuclear cells from transition dairy cows as well as the performance of these cells in an in vitro assay. First, a combination of in vitro stimulation and quantitative PCR for cytokines was validated as a quantifiable immunocompetence assay in 29 cattle and a correlation of quantitative PCR and ELISA demonstrated. Second, the relative number of T helper cells, cytotoxic T cells, B cells, γδ T cells, natural killer cells, and monocytes in peripheral blood was measured, of which B cells and natural killer cells increased in number postcalving (n=29) compared with precalving. Third, following in vitro stimulation cytokine profiles indicated decreased expression of IFNγ, tumor necrosis factor, and IL-17 and increased expression of IL-10 wk 1 after calving, which later all returned to precalving values (n=39). Additionally, treatment of transition cows with a nonsteroidal anti-inflammatory drug (i.e., carprofen) administered on d 1, 3, and 5 postcalving (n=19; untreated control n=20) did not affect the cytokine expression at any time point. In conclusion

Global and Regional Decreases in Tropospheric Oxidants from Photochemical Effects of Aerosols

NASA Technical Reports Server (NTRS)

Martin, Randall V.; Jacob, Daniel J.; Yantosca, Robert M.; Chin, Mian; Ginoux, Paul

2003-01-01

We evaluate the sensitivity of tropospheric OH, O3, and O3 precursors to photochemical effects of aerosols not usually included in global models: (1) aerosol scattering and absorption of ultraviolet radiation and (2) reactive uptake of HO', NO2, and NO3. Our approach is to couple a global 3-D model of tropospheric chemistry (GEOS- CHEM) with aerosol fields from a global 3-D aerosol model (GOCART). Reactive uptake by aerosols is computed using reaction probabilities from a recent review (gamma(sub HO2) = 0.2, gamma(sub NO2) = 10(exp -4), gamma(sub NO3) = l0(exp -3). Aerosols decrease the O3 - O((sup 1)D) photolysis frequency by 5-20% at the surface throughout the Northern Hemisphere (largely due to mineral dust) and by a factor of 2 in biomass burning regions (largely due to black carbon). Aerosol uptake of HO2 accounts for 10-40% of total HOx radical ((triple bonds)OH + peroxy) loss in the boundary layer over polluted continental regions (largely due to sulfate and organic carbon) and for more than 70% over tropical biomass burning regions (largely due to organic carbon). Uptake of NO2 and NO3 accounts for 10-20% of total HNO3 production over biomass burning regions and less elsewhere. Annual mean OH concentrations decrease by 9% globally and by 5-35% in the boundary layer over the Northern Hemisphere. Simulated CO increases by 5- 15 ppbv in the remote Northern Hemisphere, improving agreement with observations. Simulated boundary layer O3 decreases by 15- 45 ppbv over India during the biomass burning season in March and by 5-9 ppbv over northern Europe in August, again improving comparison with observations. We find that particulate matter controls would increase surface O3 over Europe and other industrial regions.

Decreased NAA in Gray Matter is Correlated with Decreased Availability of Acetate in White Matter in Postmortem Multiple Sclerosis Cortex

PubMed Central

Li, S.; Clements, R.; Sulak, M.; Gregory, R.; Freeman, E.; McDonough, J.

2013-01-01

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) which leads to progressive neurological disability. Our previous studies have demonstrated mitochondrial involvement in MS cortical pathology and others have documented decreased levels of the neuronal mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is synthesized in neurons, it is broken down in oligodendrocytes into aspartate and acetate. The resulting acetate is incorporated into myelin lipids, linking neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin lipids in the CNS. In the present study we show that treating human SH-SY5Y neuroblastoma cells with the electron transport chain inhibitor antimycin A decreased levels of NAA as measured by HPLC. To better understand the significance of the relationship between mitochondrial function and levels of NAA and its breakdown product acetate on MS pathology we then quantitated the levels of NAA and acetate in MS and control postmortem tissue blocks. Regardless of lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray matter from parietal and motor cortex in MS, respectively, compared to controls. Acetate levels in adjacent white matter mirrored these decreases as evidenced by the 36 and 45 % reduction in acetate obtained from parietal and motor cortices. These data suggest a novel mechanism whereby mitochondrial dysfunction and reduced NAA levels in neurons may result in compromised myelination by oligodendrocytes due to decreased availability of acetate necessary for the synthesis of myelin lipids. PMID:24078261

Curcumin decreases the expression of Pokemon by suppressing the binding activity of the Sp1 protein in human lung cancer cells.

PubMed

Cui, Jiajun; Meng, Xianfeng; Gao, Xudong; Tan, Guangxuan

2010-03-01

Pokemon, which stands for POK erythroid myeloid ontogenic factor, can regulate expression of many genes and plays an important role in tumorigenesis. Curcumin, a natural and non-toxic yellow compound, has capacity for antioxidant, free radical scavenger, anti-inflammatory properties. Recent studies shows it is a potential inhibitor of cell proliferation in a variety of tumour cells. To investigate whether curcumin can regulate the expression of Pokemon, a series of experiments were carried out. Transient transfection experiments demonstrated that curcumin could decrease the activity of the Pokemon promoter. Western blot analysis suggested that curcumin could significantly decrease the expression of the Pokemon. Overexpression of Sp1 could enhance the activity of the Pokemon promoter, whereas knockdown of Sp1 could decrease its activity. More important, we also found that curcumin could decrease the expression of the Pokemon by suppressing the stimulation of the Sp1 protein. Therefore, curcumin is a potential reagent for tumour therapy which may target Pokemon.

Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

PubMed

Cai, Qian-Ying; Zhang, Heng-Xin; Wang, Chen-Chen; Sun, Hao; Sun, Shu-Qiang; Wang, Yu-Huan; Yan, Hong-Tao; Yang, Xin-Jun

2017-08-01

To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P < 0.001), but not in macrosomic neonates. Cord blood BDNF was positively associated with placental BDNF relative expression (r s  = 0.245, P = 0.02) in the total group. Higher cord blood BDNF levels were independently associated with protection against nondiabetic macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

Decreased frequency and duration of tooth brushing is a risk factor for endothelial dysfunction.

PubMed

Matsui, Shogo; Kajikawa, Masato; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Oda, Nozomu; Kishimoto, Shinji; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Nakashima, Ayumu; Noma, Kensuke; Taguchi, Akira; Higashi, Yukihito

2017-08-15

Periodontal disease is associated with endothelial dysfunction, leading to cardiovascular disease. The effect of detailed tooth brushing behavior, not only frequency but also duration of tooth brushing, on endothelial function is unclear. The purpose of this study was to evaluate the relationships of detailed methods of tooth brushing with vascular function. We evaluated flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation, and frequency and duration of tooth brushing in 896 subjects. We divided the subjects into three groups according to the frequency and duration of tooth brushing: low frequency and short duration group (factors (OR: 2.25, 95% CI: 1.39-3.59; P<0.001). These findings suggest that low frequency and short duration of tooth brushing are associated with endothelial dysfunction. URL for clinical trial: http://UMIN; registration number for clinical trial: UMIN000003409. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Decreasing Use of Percutaneous Endoscopic Gastrostomy Tube Feeding in Japan.

PubMed

Komiya, Kosaku; Usagawa, Yuko; Kadota, Jun-Ichi; Ikegami, Naoki

2018-05-25

To identify trends in percutaneous endoscopic gastrostomy (PEG) tube placement and intravenous hyperalimentation (IVH) in nonhospital settings (as a potential alternative to tube feeding for nutrition) and to summarize published reports concerning the decision-making process for PEG placement. National survey and systematic review. Japan. All Japanese people. Data on numbers of individuals with a PEG tube and IVH were obtained from the website of the Japanese Ministry of Health, Labour, and Welfare and published reports concerning the decision-making process for PEG placement in Japan were summarized. The number of PEG tube placements peaked in 2007 and has been decreasing since Japan experienced the Great East Japan Earthquake in 2011. A further decline was seen in 2015 after the Japanese Ministry of Health, Labour and Welfare revised the fee schedule in 2014. More than half of individuals who had tubes were aged 80 and older during the years observed. In contrast, the number of individuals receiving IVH was lowest in the same year as PEG tube placement peaked and has been increasing ever since. Four studies reported that the decision-making process included consideration of not only the underlying disease, but also the individual's age and social barriers and the physician's personal philosophy. The number of PEG tube placements has been decreasing since its peak in 2007, and the number of individuals receiving IVH has been increasing. Many factors influence the decision-making process for PEG tube placement. Physicians in Japan may be realizing that there is little evidence to support the use of tube feeding in frail elderly adults. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Involvement of Brain-Derived Neurotrophic Factor in Late-Life Depression

PubMed Central

Dwivedi, Yogesh

2013-01-01

Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons, synaptic integrity, and synaptic plasticity. Evidence suggests that BDNF is involved in major depression, such that the level of BDNF is decreased in depressed patients and that antidepressants reverse this decrease. Stress, a major factor in depression, also modulates BDNF expression. These studies have led to the proposal of the neurotrophin hypothesis of depression. Late-life depression is associated with disturbances in structural and neural plasticity as well as impairments in cognitive behavior. Stress and aging also play a crucial role in late-life depression. Many recent studies have suggested that not only expression of BDNF is decreased in the serum/plasma of patients with late-life depression, but structural abnormalities in the brain of these patients may be associated with a polymorphism in the BDNF gene, and that there is a relationship between a BDNF polymorphism and antidepressant remission rates. This review provides a critical review of the involvement of BDNF in major depression, in general, and in late-life depression, in particular. PMID:23570887

Decreased Interleukin-20 Expression in Scleroderma Skin Contributes to Cutaneous Fibrosis

PubMed Central

Kudo, Hideo; Jinnin, Masatoshi; Asano, Yoshihide; Trojanowska, Maria; Nakayama, Wakana; Inoue, Kuniko; Honda, Noritoshi; Kajihara, Ikko; Makino, Katsunari; Fukushima, Satoshi; Ihn, Hironobu

2014-01-01

Objective To clarify the role of interleukin-20 (IL-20) in the regulatory mechanism of extracellular matrix expression and to determine the contribution of IL-20 to the phenotype of systemic sclerosis (SSc). Methods Protein and messenger RNA (mRNA) levels of collagen, Fli-1, IL-20, and IL-20 receptor (IL-20R) were analyzed using polymerase chain reaction (PCR) array, immunoblotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time PCR. Results PCR array revealed that IL-20 decreased gene expression of α2(I) collagen (0.03-fold), Smad3 (0.02-fold), and endoglin (0.05-fold) in cultured normal dermal fibroblasts. Fli-1 protein expression was induced by IL-20 (~2-fold). The inhibition of collagen by IL-20, the induction of Fli-1 by IL-20, and the reduction of Smad3 and endoglin by IL-20 were also observed in SSc fibroblasts. Serum IL-20 levels were reduced only slightly in SSc patients but were significantly decreased in patients with scleroderma spectrum disorders (the prodromal stage of SSc) compared with those in normal subjects (111.3 pg/ml versus 180.4 pg/ml; P < 0.05). On the other hand, IL-20 mRNA expression in SSc skin was decreased compared with that in normal skin (P < 0.05), which may result in the induction of collagen synthesis in SSc dermal fibroblasts. IL-20R was expressed in normal and SSc fibroblasts. Moreover, IL-20 supplementation by injection into the skin reversed skin fibrosis induced by bleomycin in mice (~0.5-fold). Conclusion IL-20 reduces basal collagen transcription via Fli-1 induction, while down-regulation of Smad3 and endoglin may cancel the effect of transforming growth factor β in SSc fibroblasts. To confirm the therapeutic value of IL-20 and IL-20R, their function and expression in vivo should be further studied. PMID:24470401

Decreased interleukin-20 expression in scleroderma skin contributes to cutaneous fibrosis.

PubMed

Kudo, Hideo; Jinnin, Masatoshi; Asano, Yoshihide; Trojanowska, Maria; Nakayama, Wakana; Inoue, Kuniko; Honda, Noritoshi; Kajihara, Ikko; Makino, Katsunari; Fukushima, Satoshi; Ihn, Hironobu

2014-06-01

To clarify the role of interleukin-20 (IL-20) in the regulatory mechanism of extracellular matrix expression and to determine the contribution of IL-20 to the phenotype of systemic sclerosis (SSc). Protein and messenger RNA (mRNA) levels of collagen, Fli-1, IL-20, and IL-20 receptor (IL-20R) were analyzed using polymerase chain reaction (PCR) array, immunoblotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time PCR. PCR array revealed that IL-20 decreased gene expression of α2(I) collagen (0.03-fold), Smad3 (0.02-fold), and endoglin (0.05-fold) in cultured normal dermal fibroblasts. Fli-1 protein expression was induced by IL-20 (~2-fold). The inhibition of collagen by IL-20, the induction of Fli-1 by IL-20, and the reduction of Smad3 and endoglin by IL-20 were also observed in SSc fibroblasts. Serum IL-20 levels were reduced only slightly in SSc patients but were significantly decreased in patients with scleroderma spectrum disorders (the prodromal stage of SSc) compared with those in normal subjects (111.3 pg/ml versus 180.4 pg/ml; P < 0.05). On the other hand, IL-20 mRNA expression in SSc skin was decreased compared with that in normal skin (P < 0.05), which may result in the induction of collagen synthesis in SSc dermal fibroblasts. IL-20R was expressed in normal and SSc fibroblasts. Moreover, IL-20 supplementation by injection into the skin reversed skin fibrosis induced by bleomycin in mice (~0.5-fold). IL-20 reduces basal collagen transcription via Fli-1 induction, while down-regulation of Smad3 and endoglin may cancel the effect of transforming growth factor β in SSc fibroblasts. To confirm the therapeutic value of IL-20 and IL-20R, their function and expression in vivo should be further studied. Copyright © 2014 by the American College of Rheumatology.

Can Diuretics Decrease Your Potassium Level?

MedlinePlus

... of low potassium? Can diuretics decrease your potassium level? Answers from Sheldon G. Sheps, M.D. Yes, ... your urine. This can lead to low potassium levels in your blood (hypokalemia). Signs and symptoms of ...

Progressive decrease of melatonin production over consecutive days of simulated night work.

PubMed

Dumont, Marie; Paquet, Jean

2014-12-01

decrease was larger in women using oral contraceptives. There was no difference between the three groups, and the magnitude of the decrease in melatonin production for nighttime and for the 24 h was not associated with the magnitude of the absolute circadian phase shift. As light intensity was relatively low and because the decrease in melatonin production was progressive, direct suppression by nighttime light exposure was probably not a significant factor. However, according to previous experimental observations, the decrease in melatonin production most likely reflects the circadian disruption associated with the process of re-entrainment. It remains to be determined whether reduced melatonin production can be harmful by itself, but long-term and repeated circadian disruption most probably is.

von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins

PubMed Central

Chauhan, Anil K.; Kisucka, Janka; Lamb, Colin B.; Bergmeier, Wolfgang

2007-01-01

von Willebrand factor (VWF) protects factor VIII (FVIII) from proteolysis and mediates the initial contact of platelets with the injured vessel wall, thus playing an important role in hemostasis and thrombosis. VWF is crucial for the formation of occlusive thrombi at arterial shear rates. However, with only a few conflicting studies published, the role of VWF in venous thrombosis is still unclear. Using gene-targeted mice, we show that in ferric chloride–injured veins platelet adhesion to subendothelium is decreased and thrombus growth is impaired in VWF−/− mice when compared with wild type (WT). We also observed increased embolization in the VWF−/− mice, which was due to lower FVIII levels in these mice as recombinant factor VIII (r-FVIII) restored thrombus stability. Despite normalization of blood clotting time and thrombus stability after r-FVIII infusion, the VWF−/− venules did not occlude. Transgenic platelets lacking the VWF receptor GPIbα extracellular domain showed decreased adhesion to injured veins. But, after a delay, all the injured venules occluded in these transgenic mice. Thus, VWF likely uses other adhesion receptors besides GPIbα in thrombus growth under venous shear conditions. Our studies document crucial roles for VWF and FVIII in experimental thrombosis under venous flow conditions in vivo. PMID:17119108

MDMA DECREASES THE EFFECTS OF SIMULATED SOCIAL REJECTION

PubMed Central

Frye, Charles G.; Wardle, Margaret C.; Norman, Greg J.; de Wit, Harriet

2014-01-01

3-4-methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N = 36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called “Cyberball” during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments. PMID

Apixaban decreases brain thrombin activity in a male mouse model of acute ischemic stroke.

PubMed

Bushi, Doron; Chapman, Joab; Wohl, Anton; Stein, Efrat Shavit; Feingold, Ekaterina; Tanne, David

2018-05-14

Factor Xa (FXa) plays a critical role in the coagulation cascade by generation of thrombin. During focal ischemia thrombin levels increase in the brain tissue and cause neural damage. This study examined the hypothesis that administration of the FXa inhibitor, apixaban, following focal ischemic stroke may have therapeutic potential by decreasing brain thrombin activity and infarct volume. Male mice were divided into a treated groups that received different doses of apixaban (2, 20, 100 mg/kg administered I.P.) or saline (controls) immediately after blocking the middle cerebral artery (MCA). Thrombin activity was measured by a fluorescence assay on fresh coronal slices taken from the mice brains 24 hr following the MCA occlusion. Infarct volume was assessed using triphenyltetrazolium chloride staining. A high dose of apixaban (100 mg/kg) significantly decreased thrombin activity levels in the ipsilateral hemisphere compared to the control group (Slice#5, p = .016; Slice#6, p = .016; Slice#7, p = .016; Slice#8, p = .036; by the nonparametric Mann-Whitney test). In addition, treatment with apixaban doses of both 100 mg/kg (32 ± 8% vs. 76 ± 7% in the treatment vs. control groups respectively; p = .005 by the nonparametric Mann-Whitney test) and 20 mg/kg (43 ± 7% vs. 76 ± 7% in the treatment vs. control groups respectively; p = .019 by the nonparametric Mann-Whitney test) decreased infarct volumes in areas surrounding the ischemic core (Slices #3 and #8). No brain hemorrhages were observed either in the treated or control groups. In summary, I.P. administration of high dose of apixaban immediately after MCA occlusion decreases brain thrombin activity and reduces infarct size. © 2018 Wiley Periodicals, Inc.

Observed Decrease of North American Winter Temperature Variability

NASA Astrophysics Data System (ADS)

Rhines, A. N.; Tingley, M.; McKinnon, K. A.; Huybers, P. J.

2015-12-01

There is considerable interest in determining whether temperature variability has changed in recent decades. Model ensembles project that extratropical land temperature variance will detectably decrease by 2070. We use quantile regression of station observations to show that decreasing variability is already robustly detectable for North American winter during 1979--2014. Pointwise trends from GHCND stations are mapped into a continuous spatial field using thin-plate spline regression, resolving small-scales while providing uncertainties accounting for spatial covariance and varying station density. We find that variability of daily temperatures, as measured by the difference between the 95th and 5th percentiles, has decreased markedly in winter for both daily minima and maxima. Composites indicate that the reduced spread of winter temperatures primarily results from Arctic amplification decreasing the meridional temperature gradient. Greater observed warming in the 5th relative to the 95th percentile stems from asymmetric effects of advection during cold versus warm days; cold air advection is generally from northerly regions that have experienced greater warming than western or southwestern regions that are generally sourced during warm days.

Growth/differentiation factor-11: an evolutionary conserved growth factor in vertebrates.

PubMed

Funkenstein, Bruria; Olekh, Elena

2010-11-01

Growth and differentiation factor-11 (GDF-11) is a member of the transforming growth factor-β superfamily and is thought to be derived together with myostatin (known also as GDF-8) from an ancestral gene. In the present study, we report the isolation and characterization of GDF-11 homolog from a marine teleost, the gilthead sea bream Sparus aurata, and show that this growth factor is highly conserved throughout vertebrates. Using bioinformatics, we identified GDF-11 in Tetraodon, Takifugu, medaka, and stickleback and found that they are highly conserved at the amino acid sequence as well as gene organization. Moreover, we found conservation of syntenic relationships among vertebrates in the GDF-11 locus. Transcripts for GDF-11 can be found in eggs and early embryos, albeit at low levels, while in post-hatching larvae expression levels are high and decreases as development progresses, suggesting that GDF-11 might have a role during early development of fish as found in tetrapods and zebrafish. Finally, GDF-11 is expressed in various tissues in the adult fish including muscle, brain, and eye.

Decreasing radiation exposure on pediatric portable chest radiographs.

PubMed

Hawking, Nancy G; Sharp, Ted D

2013-01-01

To determine whether additional shielding designed for pediatric patients during portable chest exams that ascertain endotracheal tube placement would significantly decrease the amount of scatter radiation. Children aged 24 months or younger were intubated and received daily morning chest radiographs to determine endotracheal tube placement. For each measurement, the amount of scatter radiation decreased by more than 20% from a nonshielded exposure to a shielded exposure. There was a significant decrease in scatter radiation when using the lead shielding device along with appropriate collimation vs appropriate collimation alone. These results suggest that applying additional shielding to appropriately collimated chest radiographs could significantly reduce scatter radiation and therefore the overall dose to young children.

Factors Associated with Intern Fatigue

PubMed Central

Vidyarthi, Arpana R.; Baron, Robert B.; Katz, Patricia P.

2008-01-01

ABSTRACT BACKGROUND Prior data suggest that fatigue adversely affects patient safety and resident well-being. ACGME duty hour limitations were intended, in part, to reduce resident fatigue, but the factors that affect intern fatigue are unknown. OBJECTIVE To identify factors associated with intern fatigue following implementation of duty hour limitations. DESIGN Cross-sectional confidential survey of validated questions related to fatigue, sleep, and stress, as well as author-developed teamwork questions. SUBJECTS Interns in cognitive specialties at the University of California, San Francisco. MEASUREMENTS Univariate statistics characterized the distribution of responses. Pearson correlations elucidated bivariate relationships between fatigue and other variables. Multivariate linear regression models identified factors independently associated with fatigue, sleep, and stress. RESULTS Of 111 eligible interns, 66 responded (59%). In a regression analysis including gender, hours worked in the previous week, sleep quality, perceived stress, and teamwork, only poorer quality of sleep and greater perceived stress were significantly associated with fatigue (p < 0.001 and p = 0.02, respectively). To identify factors that may affect sleep, specifically duty hours and stress, a secondary model was constructed. Only greater perceived stress was significantly associated with diminished sleep quality (p = 0.04), and only poorer teamwork was significantly associated with perceived stress (p < 0.001). Working >80 h was not significantly associated with perceived stress, quality of sleep, or fatigue. CONCLUSIONS Simply decreasing the number of duty hours may be insufficient to reduce intern fatigue. Residency programs may need to incorporate programmatic changes to reduce stress, improve sleep quality, and foster teamwork in order to decrease intern fatigue and its deleterious consequences. PMID:18807096

The high dosage of earthworm (Eisenia andrei) extract decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

PubMed Central

Yan, Bing Chun; Yoo, Ki-Yeon; Park, Joon Ha; Lee, Choong Hyun; Choi, Jung Hoon

2011-01-01

Earthworm extract has shown anticancer characteristics. In the present study, we examined the effect of chronic treatment with a high dose of earthworm (Eisenia andrei) extract (EE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of 3-week-old mice using 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 immunohistochemistry for cell proliferation and doublecortin (DCX) immunohistochemistry for neuroblast differentiation, respectively. BrdU-, Ki-67-, and DCX-immunoreactive cells were easily detected in the subgranular zone of the DG in vehicle (saline)-treated mice. However, BrdU-, Ki-67-, and DCX-immunoreactive cells in the 500 mg/kg EE-treated mice decreased distinctively compared to those in the vehicle-treated mice. In addition, brain-derived neurotrophic factor (BDNF) immunoreactivity and its protein level decreased markedly in the DG of the EE-treated group compared to those in the vehicle-treated group. These results indicate that chronic treatment with high dose EE decreased cell proliferation and neuroblast differentiation, and that BDNF immunoreactivity decreased in the DG of EE-treated mice. PMID:22025974

Baroreflex Sensitivity Decreases During 90-Day Bed Rest

NASA Technical Reports Server (NTRS)

Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

2008-01-01

Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (p<0.001) from pre- BR across BR days. High frequency in normalized units, a measure of parasympathetic activity, decreased with BR (p=0.027) and was lower (p=0.046) in men (0.39+/-0.02, mean+/-SEM) than women (0.48+/-0.02). The spontaneous baroreflex slope, our measure of BRS, increased with PE and decreased with SNP across BR (p<0.001). The percentage decrease in BRS from pre- to post-BR appeared to be larger in women (43.6+/-7.0%) than in men (31.3+/-3.9%, p=0.06). CONCLUSION: Parasympathetic activity and baroreflex sensitivity decrease during 90 days of BR, and BRS tends to diminish more in women than in men.

Factors Affecting Age at ASD Diagnosis in UK: No Evidence That Diagnosis Age Has Decreased between 2004 and 2014

ERIC Educational Resources Information Center

Brett, Denise; Warnell, Frances; McConachie, Helen; Parr, Jeremy R.

2016-01-01

Clinical initiatives have aimed to reduce the age at ASD diagnosis in the UK. This study investigated whether the median age at diagnosis in childhood has reduced in recent years, and identified the factors associated with earlier diagnosis in the UK. Data on 2,134 children with ASD came from two large family databases. Results showed that the age…

Dendrobium chrysotoxum Lindl. Alleviates Diabetic Retinopathy by Preventing Retinal Inflammation and Tight Junction Protein Decrease

PubMed Central

Yu, Zengyang; Gong, Chenyuan; Lu, Bin; Yang, Li; Sheng, Yuchen; Ji, Lili; Wang, Zhengtao

2015-01-01

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus. This study aimed to observe the alleviation of the ethanol extract of Dendrobium chrysotoxum Lindl. (DC), a traditional Chinese herbal medicine, on DR and its engaged mechanism. After DC (30 or 300 mg/kg) was orally administrated, the breakdown of blood retinal barrier (BRB) in streptozotocin- (STZ-) induced diabetic rats was attenuated by DC. Decreased retinal mRNA expression of tight junction proteins (including occludin and claudin-1) in diabetic rats was also reversed by DC. Western blot analysis and retinal immunofluorescence staining results further confirmed that DC reversed the decreased expression of occludin and claudin-1 proteins in diabetic rats. DC reduced the increased retinal mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor α (TNFα), interleukin- (IL-) 6, and IL-1β in diabetic rats. In addition, DC alleviated the increased 1 and phosphorylated p65, IκB, and IκB kinase (IKK) in diabetic rats. DC also reduced the increased serum levels of TNFα, interferon-γ (IFN-γ), IL-6, IL-1β, IL-8, IL-12, IL-2, IL-3, and IL-10 in diabetic rats. Therefore, DC can alleviate DR by inhibiting retinal inflammation and preventing the decrease of tight junction proteins, such as occludin and claudin-1. PMID:25685822

Chemical Feedback From Decreasing Carbon Monoxide Emissions

NASA Astrophysics Data System (ADS)

Gaubert, B.; Worden, H. M.; Arellano, A. F. J.; Emmons, L. K.; Tilmes, S.; Barré, J.; Martinez Alonso, S.; Vitt, F.; Anderson, J. L.; Alkemade, F.; Houweling, S.; Edwards, D. P.

2017-10-01

Understanding changes in the burden and growth rate of atmospheric methane (CH4) has been the focus of several recent studies but still lacks scientific consensus. Here we investigate the role of decreasing anthropogenic carbon monoxide (CO) emissions since 2002 on hydroxyl radical (OH) sinks and tropospheric CH4 loss. We quantify this impact by contrasting two model simulations for 2002-2013: (1) a Measurement of the Pollution in the Troposphere (MOPITT) CO reanalysis and (2) a Control-Run without CO assimilation. These simulations are performed with the Community Atmosphere Model with Chemistry of the Community Earth System Model fully coupled chemistry climate model with prescribed CH4 surface concentrations. The assimilation of MOPITT observations constrains the global CO burden, which significantly decreased over this period by 20%. We find that this decrease results to (a) increase in CO chemical production, (b) higher CH4 oxidation by OH, and (c) 8% shorter CH4 lifetime. We elucidate this coupling by a surrogate mechanism for CO-OH-CH4 that is quantified from the full chemistry simulations.

Decreasing luminescence lifetime of evaporating phosphorescent droplets

NASA Astrophysics Data System (ADS)

van der Voort, D. D.; Dam, N. J.; Sweep, A. M.; Kunnen, R. P. J.; van Heijst, G. J. F.; Clercx, H. J. H.; van de Water, W.

2016-12-01

Laser-induced phosphorescence has been used extensively to study spray dynamics. It is important to understand the influence of droplet evaporation in the interpretation of such measurements, as it increases luminescence quenching. By suspending a single evaporating n-heptane droplet in an acoustic levitator, the properties of lanthanide-complex europium-thenoyltrifluoroacetone-trioctylphosphine oxide (Eu-TTA-TOPO) phosphorescence are determined through high-speed imaging. A decrease was found in the measured phosphorescence decay coefficient (780 → 200 μs) with decreasing droplet volumes (10-9 → 10-11 m3) corresponding to increasing concentrations (10-4 → 10-2 M). This decrease continues up to the point of shell-formation at supersaturated concentrations. The diminished luminescence is shown not to be attributable to triplet-triplet annihilation, quenching between excited triplet-state molecules. Instead, the pure exponential decays found in the measurements show that a non-phosphorescent quencher, such as free TTA/TOPO, can be attributable to this decay. The concentration dependence of the phosphorescence lifetime can therefore be used as a diagnostic of evaporation in sprays.

Impact of an Early Decrease in Systolic Blood Pressure on The Risk of Contrast-Induced Nephropathy after Percutaneous Coronary Intervention.

PubMed

Li, Hualong; Huang, Shuijin; He, Yiting; Liu, Yong; Liu, Yuanhui; Chen, Jiyan; Zhou, Yingling; Tan, Ning; Duan, Chongyang; Chen, Pingyan

2016-02-01

The early postprocedural period was thought to be the rush hour of contrast media excretion, causing rapid and prolonged renal hypoperfusion, which was the critical time window for contrast-induced nephropathy (CIN). 349 consecutive patients were enrolled into the study. The relation between an early postprocedural decrease in systolic blood pressure (SBP) and the risk of CIN was assessed using multivariate logistic regression. A postprocedural decrease in SBP was observed in 63% of patients and CIN developed in 28 (8.0%) patients. The CIN group had a lower postprocedural SBP (114.5±13.5 vs. 123.7±15.6mmHg, P=0.003) and a greater postprocedural decrease in SBP (16.2±19.1 vs. 5.9±18.7mmHg, P=0.005) than the no-CIN group. ROC analysis revealed that the optimum cutoff value for the SBP decrease in detecting CIN was >10mmHg (sensitivity 60.7%, specificity 59.5%, AUC=0.66). Multivariate logistic regression analysis found that a postprocedural decrease in SBP >10mmHg was a significant independent predictor of CIN (OR 2.368, 95%CI: 1.043-5.379, P=0.039), after adjustment for other risk factors. An early moderate postprocedural decrease in SBP may increase the risk of CIN in patients undergoing PCI. Copyright © 2015. Published by Elsevier B.V.

Association of ABO blood groups with von Willebrand factor, factor VIII and ADAMTS-13 in patients with lung cancer.

PubMed

Liu, Xia; Chen, Xiaogang; Yang, Jiezuan; Guo, Renyong

2017-09-01

Coagulative and fibrinolytic disorders appear to be associated with the development of lung cancer. The aim of the present study was to determine plasma levels of von Willebrand factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif 13 (ADAMTS-13), and factor VIII (FVIII) activity, in association with O and non-O blood groups in patients with lung cancer. Plasma levels of VWF and ADAMTS-13, and FVIII activity were measured in 115 patients with lung cancer and 98 healthy subjects. Phenotyping of the ABO blood groups was also performed for the two groups. Significantly increased VWF levels and FVIII activity, as well as significantly decreased ADAMTS-13 levels, were observed in patients with distant metastasis as compared with those without distant metastasis and the healthy controls. Plasma VWF levels and FVIII activity were significantly increased in subjects with non-O type blood compared with those with type O blood in the two groups. However, a significant decrease in ADAMTS-13 levels was observed only in the control group among those with non-O type blood, compared with those with type O blood. The results of the present study indicate that increased VWF and decreased ADAMTS-13 levels facilitate the invasiveness and metastasis of lung cancer. Non-O blood groups constitute a risk factor for increased VWF and FVIII in plasma. Continued monitoring of VWF and ADAMTS-13 levels, and of FVIII activity in patients with lung cancer with distinct blood groups may help to minimize the incidence of thrombotic events and improve assessment of disease progression.

Experimental and Finite Element Modeling of Near-Threshold Fatigue Crack Growth for the K-Decreasing Test Method

NASA Technical Reports Server (NTRS)

Smith, Stephen W.; Seshadri, Banavara R.; Newman, John A.

2015-01-01

The experimental methods to determine near-threshold fatigue crack growth rate data are prescribed in ASTM standard E647. To produce near-threshold data at a constant stress ratio (R), the applied stress-intensity factor (K) is decreased as the crack grows based on a specified K-gradient. Consequently, as the fatigue crack growth rate threshold is approached and the crack tip opening displacement decreases, remote crack wake contact may occur due to the plastically deformed crack wake surfaces and shield the growing crack tip resulting in a reduced crack tip driving force and non-representative crack growth rate data. If such data are used to life a component, the evaluation could yield highly non-conservative predictions. Although this anomalous behavior has been shown to be affected by K-gradient, starting K level, residual stresses, environmental assisted cracking, specimen geometry, and material type, the specifications within the standard to avoid this effect are limited to a maximum fatigue crack growth rate and a suggestion for the K-gradient value. This paper provides parallel experimental and computational simulations for the K-decreasing method for two materials (an aluminum alloy, AA 2024-T3 and a titanium alloy, Ti 6-2-2-2-2) to aid in establishing clear understanding of appropriate testing requirements. These simulations investigate the effect of K-gradient, the maximum value of stress-intensity factor applied, and material type. A material independent term is developed to guide in the selection of appropriate test conditions for most engineering alloys. With the use of such a term, near-threshold fatigue crack growth rate tests can be performed at accelerated rates, near-threshold data can be acquired in days instead of weeks without having to establish testing criteria through trial and error, and these data can be acquired for most engineering materials, even those that are produced in relatively small product forms.

Type 2 Diabetes, Diabetes Genetic Score and Risk of Decreased Renal Function and Albuminuria: A Mendelian Randomization Study.

PubMed

Xu, Min; Bi, Yufang; Huang, Ya; Xie, Lan; Hao, Mingli; Zhao, Zhiyun; Xu, Yu; Lu, Jieli; Chen, Yuhong; Sun, Yimin; Qi, Lu; Wang, Weiqing; Ning, Guang

2016-04-01

Type 2 diabetes (T2D) is a risk factor for dysregulation of glomerular filtration rate (GFR) and albuminuria. However, whether the association is causal remains unestablished. We performed a Mendelian Randomization (MR) analysis in 11,502 participants aged 40 and above, from a well-defined community in Shanghai during 2011-2013, to explore the causal association between T2D and decreased estimated GFR (eGFR) and increased urinary albumin-to-creatinine ratio (uACR). We genotyped 34 established T2D common variants in East Asians, and created a T2D-genetic risk score (GRS). We defined decreased eGFR as eGFR<90ml/min/1.73m(2) and increased uACR as uACR≥30mg/g. We used the T2D_GRS as the instrumental variable (IV) to quantify the causal effect of T2D on decreased eGFR and increased uACR. Each 1-standard deviation (SD, 3.90 points) increment in T2D_GRS was associated with decreased eGFR: odds ratio (OR)=1.18 (95% confidence interval [CI]: 1.01, 1.30). In the MR analysis, we demonstrated a causal relationship between genetically determined T2D and decreased eGFR (OR=1.47, 95% CI: 1.15, 1.88, P=0.0003). When grouping the genetic loci according to their relations with either insulin secretion (IS) or insulin resistance (IR), we found both IS_GRS and IR_GRS were significantly related to decreased eGFR (both P<0.02). In addition, T2D_GRS and IS_GRS were significantly associated with Log-uACR (both P=0.04). Our results provide novel evidence for a causal association between T2D and decreased eGFR by using MR approach in a Chinese population. Copyright © 2016. Published by Elsevier B.V.

[On the mechanism of noopept action: decrease in activity of stress-induced kinases and increase in expression of neutrophines].

PubMed

Ostrovskaia, R U; Vakhitova, Iu V; Salimgareeva, M Kh; Iamidanov, R S; Sadovnikov, S V; Kapitsa, I G; Seredenin, S B

2010-12-01

The influence of noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111)--a drug combining the nootrope and neuroprotector properties--on the activity of mitogen-activated protein kinases (MAPKs) and the level of NGF and BDNF gene and protein expression in the frontal cortex, hippocampus, and hypothalamus has been studied in rats. Under conditions of chronic administration (28 days, 0.5 mg/day, i.p.), noopept decreased the activity of stress-induced kinases (SAPK/JNK 46/54 and pERK1/2) in rat hippocampus and increases the level of mRNA of the BDNF gene in both hypothalamus and hippocampus. The content of BDNF protein in the hypothalamus was also somewhat increased. In the context of notions about the activation of stress-induced kinases, as an important factor of amyloidogenesis and tau-protein deposition in brain tissue, and the role of deficiency of the neurotrophic factors in the development of neurodegenerative processes, the observed decrease in the activity of stress-activated MAPKs and increased expression of BDNF as a result of noopept administration suggest thatthis drug hasaspecific activity withrespect to some pathogenetic mechanisms involved in the Alzheimer disease.

The Development of the General Factor of Psychopathology 'p Factor' Through Childhood and Adolescence.

PubMed

Murray, Aja Louise; Eisner, Manuel; Ribeaud, Denis

2016-11-01

Recent studies have suggested that the structure of psychopathology may be usefully represented in terms of a general factor of psychopathology (p-factor) capturing variance common to a broad range of symptoms transcending diagnostic domains in addition to specific factors capturing variance common to smaller subsets of more closely related symptoms. Little is known about how the general co-morbidity captured by this p-factor develops and whether general co-morbidity increases or decreases over childhood and adolescence. We evaluated two competing hypotheses: 1) dynamic mutualism which predicts growth in general co-morbidity and associated p-factor strength over time and 2) p-differentiation which predicts that manifestations of liabilities towards psychopathology become increasingly specific over time. Data came from the Zurich Project on the Social Development of Children and Youths (z-proso), a longitudinal study of a normative sample (approx. 50 % male) measured at 8 time points from ages 7 to 15. We operationalised general co-morbidity as p-factor strength in a bi-factor model and used omega hierarchical to track how this changed over development. In contrast to the predictions of both dynamic mutualism and p-differentiation, p-factor strength remained relatively constant over the studied period suggesting that such processes do not govern the interplay between psychopathological symptoms during this phase of development. Future research should focus on earlier phases of development and on factors that maintain the consistency of symptom-general covariation across this period.

Decreasing but still significant facilitation effect of cold-season macrophytes on wetlands purification function during cold winter.

PubMed

Zou, Xiangxu; Zhang, Hui; Zuo, Jie; Wang, Penghe; Zhao, Dehua; An, Shuqing

2016-06-01

To identify the facilitation effect of a cool-season aquatic macrophyte (FEam) for use in effluent purification via constructed floating wetlands (CFWs) and to determine the possible pathways used during a winter period with an average temperature of less than 5 °C, pilot-scale CFWs were planted with the cold-season macrophyte Oenanthe clecumbens and were operated as batch systems. Although some leaves withered, the roots retained relatively high levels of activity during the winter, which had average air and water temperatures of 3.63 and 5.04 °C, respectively. The N and P removal efficiencies in CFWs decreased significantly in winter relative to those in late autumn. The presence of cool-season plants resulted in significant improvements in N and P removal, with a FEam of 15.23-25.86% in winter. Microbial N removal accounted for 71.57% of the total N removed in winter, and the decrease in plant uptake was the dominant factor in the wintertime decrease in N removal relative to that in late autumn. These results demonstrate the importance of cold-season plants in CFWs for the treatment of secondary effluent during cold winters.

Serum triglycerides, but not cholesterol or leptin, are decreased in suicide attempters with mood disorders.

PubMed

da Graça Cantarelli, Maria; Nardin, Patrícia; Buffon, Andréia; Eidt, Murilo Castilhos; Antônio Godoy, Luiz; Fernandes, Brisa S; Gonçalves, Carlos-Alberto

2015-02-01

Many peripheral biomarkers, including low cholesterol and its fractions, have been examined to identify suicidal behavior. Herein, we assessed serum lipid profile and some proteins putatively associated with suicidal behavior in subjects with mood disorder (bipolar disorder or major depressive disorder) with a recent suicide attempt and with no lifetime history of suicide attempts. Fifty subjects had presented an episode of attempted suicide during the last 15 days, and 36 subjects had no history of any suicide attempt. We measured total cholesterol, HDL, LDL and triglycerides as well as serum leptin, brain-derived neurotrophic factor (BDNF), S100B and C-reactive protein (CRP). Individuals that had attempted suicide presented decreased body mass index (BMI) and waist circumference. After adjusting for these confounders, we found that triglycerides were decreased in attempted suicide subjects. We found no differences among total cholesterol, LDL, and HDL or leptin, S100B, CRP and BDNF. This is a cross-sectional study, and we cannot therefore assess whether a decrease in triglycerides caused a mood episode with suicidal ideation that led to a suicide attempt or if the presence of a mood episode originated a loss of appetite and consequent loss of weight, therefore decreasing triglyceride levels. These results do not support the hypothesis that lower levels of cholesterol are associated with suicidal behavior in a mood disorder sample. However, our data support the idea that adiposity is differentiated in these patients (reduced BMI, waist circumference and serum triglycerides), which could lead to an altered communication between the adipose tissue and brain. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration.

PubMed

Wang, Jie; Zibetti, Cristina; Shang, Peng; Sripathi, Srinivasa R; Zhang, Pingwu; Cano, Marisol; Hoang, Thanh; Xia, Shuli; Ji, Hongkai; Merbs, Shannath L; Zack, Donald J; Handa, James T; Sinha, Debasish; Blackshaw, Seth; Qian, Jiang

2018-04-10

Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the retina and retinal pigmented epithelium (RPE) from AMD and control patients. Global decreases in chromatin accessibility occur in the RPE with early AMD, and in the retina of advanced disease, suggesting that dysfunction in the RPE drives disease onset. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates chromatin accessibility changes seen in AMD, providing an epigenetic link between a known risk factor for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the observed reduction in chromatin accessibility, suggesting that HDAC11 may be a potential new therapeutic target for AMD.

Pb inventory in an ombrotrophic bog decreases over time

NASA Astrophysics Data System (ADS)

Baumann, E.; Jeremiason, J.; Sebestyen, S.

2016-12-01

Peat cores were collected from the S2 ombrotrophic bog at the Marcell Experimental Forest (MEF) to determine if the Pb inventory in the bog has decreased over time. Pb concentrations in the outflow of the bog measured from 2009-2016 indicated continued mobilization and export of Pb out of the bog despite dramatic decreases in atmospheric deposition. A seminal study conducted by Urban et al. (1990) from 1981-1983 calculated a mass balance of Pb in the S2 watershed which included a Pb inventory in peat based on the approximate time frame of 1930 to 1983. We collected peat cores in 2016 to compare peat inventories of Pb over the same time range. We found that Pb inventories in the peat have decreased over time, consistent with Pb being mobilized by dissolved organic carbon (DOC) and gradually flushed out of the bog. Since 1983, DOC levels may have increased leading to further Pb mobilization and transport from the bog, but this trend is unclear. In contrast to Pb concentrations in the outflow water, upland runoff and the surface sphagnum moss layer have dramatically lower Pb concentrations compared to 1980s levels indicating fast ecosystem responses to a decrease in Pb inputs in these compartments. However, the deeper peat layers near the water table are responding more slowly to the decrease in Pb inputs and historical Pb inputs continue to be mobilized and transported from the bog. Our results would be applicable to other trace metals, such as Hg, that bind strongly to DOC. For example, a dramatic decrease in Hg deposition would not result in near-term decreases in Hg out of the bog.

[Significant decrease in factor VII activity by tissue thromboplastin derived from rabbit brain in a patient with congenital factor VII deficiency (FVII Padua)].

PubMed

Sekiya, Akiko; Morishita, Eriko; Maruyama, Keiko; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

2012-03-01

Congenital factor VII (FVII) deficiency is a bleeding disorder that requires optimal hemostatic management for each case due to its wide variety of bleeding symptoms. We experienced a patient with inherited FVII deficiency who demonstrated different FVII activities depending on tissue thromboplastins used for assays. An 82-year-old woman without any episodes of abnormal bleeding was found to have different FVII activities of 1.4% and 32% when assayed using thromboplastins from rabbit brain and human placenta, respectively. DNA sequencing analysis revealed a homozygous missense mutation of G10828A (FVII Padua) that caused an amino acid substitution of Arg304 to Gln (R304Q). Carriers of 304Q alleles are usually clinically asymptomatic and do not require FVII replacement therapies even in cases of homozygotes. In case a prolonged prothrombin time or reduced FVII activity is detected, re-examination using thromboplastins of other sources can be helpful for preliminary diagnosis of R304Q, in order to prevent unnecessary FVII replacement therapies.

Activation of phosphatidylinositol-3-kinase by platelet-derived growth factor and insulin-like growth factor-1 is inhibited by a transmembrane phosphotyrosine phosphatase.

PubMed

Way, B A; Mooney, R A

1993-12-15

Expression of the transmembrane phosphotyrosine phosphatase (PTPase) CD45 has been shown to inhibit hormone-dependent tyrosine phosphorylation and mitogenesis (Mooney, R. A., Freund, G. G., Way, B. A., and Bordwell, K. L. (1992) J. Biol. Chem. 267, 23443-23446). Here the impact of PTPase expression on insulin-like growth factor-1 (IGF-1) and platelet-derived growth factor- (PDGF) dependent activation of PI-3-K was investigated. In PTPase+ cells, IGF-1 and PDGF-dependent PI-3-K activity in antiphosphotyrosine immunoprecipitates was decreased by 62 +/- 13 and 46 +/- 17%, respectively, compared to control cells. Similar decreases in PI-3-K activity associated with anti-PDGF receptor and anti-insulin receptor substrate-1 (IRS-1) immunoprecipitates were also observed. Association of PI-3-K with the hormone-activated PDGF receptor decreased approximately 55%, paralleling its loss of activation in PTPase+ cells. Tyrosine phosphorylation of the 85-kDa subunit of PI-3-K was also inhibited. Similarly, IGF-1 dependent tyrosine phosphorylation of IRS-1 was decreased by 45%, and its association with PI-3-K was decreased by 65% in PTPase+ cells. Finally, PDGF-dependent tyrosine phosphorylation of phospholipase C-gamma 1 and GTPase-activating protein was reduced by 60-70% in the PTPase+ cells as was tyrosine phosphorylation of the PDGF receptor associated with these proteins. In summary, expression of a transmembrane PTPase decreased hormone-dependent PI-3-K activation, tyrosine phosphorylation of receptor substrates, and their association with signaling complexes. These data support a role for transmembrane PTPases in the regulation of receptor signal transduction pathways.

Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid

PubMed Central

Liu, Xudong; Zhang, Yuchao; Li, Jinquan; Wang, Dong; Wu, Yang; Li, Yan; Lu, Zhisong; Yu, Samuel CT; Li, Rui; Yang, Xu

2014-01-01

Single-walled carbon nanotubes (SWCNTs) have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test), brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH]), inflammation (nuclear factor κB, tumor necrosis factor α, interleukin-1β), and apoptosis (cysteine-aspartic acid protease 3) in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of ascorbic acid. This work suggests SWCNTs could induce cognitive deficits and decreased locomotor activity, and provides a strategy to avoid the adverse effects. PMID:24596461

Decreasing seagrass density negatively influences associated fauna

PubMed Central

McCloskey, Rosemary M.

2015-01-01

Seagrass meadows globally are disappearing at a rapid rate with physical disturbances being one of the major drivers of this habitat loss. Disturbance of seagrass can lead to fragmentation, a reduction in shoot density, canopy height and coverage, and potentially permanent loss of habitat. Despite being such a widespread issue, knowledge of how such small scale change affects the spatial distribution and abundances of motile fauna remains limited. The present study investigated fish and macro faunal community response patterns to a range of habitat variables (shoot length, cover and density), including individual species habitat preferences within a disturbed and patchy intertidal seagrass meadow. Multivariate analysis showed a measurable effect of variable seagrass cover on the abundance and distribution of the fauna, with species specific preferences to both high and low seagrass cover seagrass. The faunal community composition varied significantly with increasing/decreasing cover. The faunal species composition of low cover seagrass was more similar to sandy control plots than to higher cover seagrass. Shannon Wiener Diversity (H′) and species richness was significantly higher in high cover seagrass than in low cover seagrass, indicating increasing habitat value as density increases. The results of this study underline how the impacts of small scale disturbances from factors such as anchor damage, boat moorings and intertidal vehicle use on seagrass meadows that reduce shoot density and cover can impact upon associated fauna. These impacts have negative consequences for the delivery of ecosystem services such as the provision of nursery habitat. PMID:26137432

Decreased electrical excitability of peripheral nerves in demyelinating polyneuropathies.

PubMed Central

Meulstee, J; Darbas, A; van Doorn, P A; van Briemen, L; van der Meché, F G

1997-01-01

Not recognising the presence of decreased excitability may give rise to a seemingly low compound muscle action potential, which may lead erroneously to the conclusion of conduction block. To quantify decreased electrical excitability, stimulation-response curves and the current needed to achieve 90% of the maximal compound muscle action potential amplitude, i90, were obtained in 17 healthy controls, eight patients with Guillain-Barre syndrome, 14 with chronic inflammatory demyelinating polyneuropathy, and 10 with hereditary motor sensory neuropathy type I. Decreased electrical excitability was found in patients with chronic inflammatory demyelinating polyneuropathy and hereditary motor sensory neuropathy type I, by contrast with patients with Guillain-Barré syndrome. Recognising decreased excitability prevents the false assertion of conduction block and has electrodiagnostic importance for the differential diagnosis of demyelinating polyneuropathies. PMID:9120460

Which factors in raw cow's milk contribute to protection against allergies?

PubMed

van Neerven, R J Joost; Knol, Edward F; Heck, Jeroen M L; Savelkoul, Huub F J

2012-10-01

Several epidemiologic studies have shown that growing up in a farming environment is associated with a decreased risk of allergies. A factor that correlates strongly with this effect is the early ingestion of unheated cow's milk. Although, to date, no controlled studies on raw milk consumption have been performed to formally demonstrate this effect, several factors in bovine milk have been described that might explain how raw cow's milk consumption can decrease the risk of allergies. In addition, increasing knowledge on the immunologically active factors in breast milk have also contributed to our understanding of the effects of bovine milk in infants because many of the factors in bovine milk are expected to have functional effects in human subjects as well. Here we review these factors and their mechanisms of action and compare their presence in bovine milk and breast milk. A better understanding of these factors, as well as how to retain them, might ultimately lead to the development of mildly processed milk and infant nutrition products that could become a part of preventive strategies to reduce the incidence of allergic disease. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Proportion offered in the Dictator and Ultimatum Games decreases with amount and social distance.

PubMed

Bechler, Christopher; Green, Leonard; Myerson, Joel

2015-06-01

Behavior in both the Dictator Game and the Ultimatum Game is of special interest because proposers often violate the predictions of normative economic theory: On average, offers in both games are higher than what would be considered income-maximizing. In the present study, the initial amount provided to the proposer and the social distance between the proposer and the respondent were both varied across a wide range, and the effects of these manipulations on offers in the Dictator Game and the Ultimatum Game were examined in a broad sample of participants recruited via MTurk. Although the amount offered was consistently higher in the Ultimatum Game, the proportion of the amount offered decreased as the size of the initial amount increased in both games. Moreover, the proportion offered also decreased as a function of the social distance between the proposer and the responder. The present results extend our knowledge of the determinants of proposers' behavior in two-person economic games and emphasize the importance of social distance and the amount of money at stake as factors that affect people's economic decisions. Copyright © 2015 Elsevier B.V. All rights reserved.

The epidemiology of infectious mononucleosis in Northern Scotland: a decreasing incidence and winter peak

PubMed Central

2014-01-01

Background Infection with Epstein-Barr virus (EBV) is almost ubiquitous in humans and generally occurs at two ages: infantile, which is usually asymptomatic and associated with poorer socioeconomic conditions, and adolescent, which causes infectious mononucleosis (IM) in ~25% cases. The determinants of whether the infection causes IM remain uncertain. We aimed to evaluate seasonality and temporal trends in IM. Methods Data from all Monospot tests, used as a marker for IM, were collected from the Grampian population over 16 years. Results Positive Monospot test results peaked at 17 years in females and 19 in males. Females had 16% more diagnoses, although 55% more tests. IM was ~38% more common in winter than summer. The annual rate of positive tests decreased progressively over the study period, from 174/100 000 (95% CI 171–178) in 1997 to 67/100 000 (95% CI 65–69) in 2012. Conclusions IM appears to be decreasing in incidence, which may be caused by changing environmental influences on immune systems. One such factor may be exposure to sunlight. Words 168. Funding The Medical Research Council and NHS Grampian-MS endowments. PMID:24650116

Decreasing Physical Inactivity in the Veterans Health Administration Employee Population.

PubMed

Schult, Tamara M; Schmunk, Sandra K; Awosika, Ebi R

2016-12-01

The aim of this study was to describe a comprehensive approach to decrease physical inactivity in the Veterans Health Administration (VHA) employee population. The approach included (1) initiatives to decrease physical inactivity in the workplace; (2) two operational surveys to assess system-wide service provision; and (3) two national employee surveys. From 2010 to 2012, 86 employee fitness centers were completed in VA medical centers. A grants program (2010 to 2015) funded smaller projects designed to decrease physical inactivity in the workplace. Projects involved the provision of equipment to decrease sedentary behaviors, including stability balls, treadmill and sit-to-stand desks, stairwell projects, and funding for on-site fitness classes, bicycle racks, and outdoor par courses and walking paths among others. A comprehensive approach to decrease physical inactivity in VHA employees was successful. Overall, self-reported, age-adjusted physical inactivity in VHA employees decreased from 25.3% in 2010 to 16.1% in 2015.

Can Technology Decrease Sexual Risk Behaviors among Young People? Results of a Pilot Study Examining the Effectiveness of a Mobile Application Intervention

ERIC Educational Resources Information Center

Jackson, Dawnyéa D.; Ingram, Lucy Annang; Boyer, Cherrie B.; Robillard, Alyssa; Huhns, Michael N.

2016-01-01

College students represent an important population for studying and understanding factors that influence sexual risk given the populations' high risk of sexually transmitted infections and unintended pregnancies. Using a quasi-experimental design, the efficacy of a brief and theory-driven mobile application intervention designed to decrease sexual…

The influence of non-nociceptive factors on hot-plate latency in rats.

PubMed

Gunn, Amanda; Bobeck, Erin N; Weber, Ceri; Morgan, Michael M

2011-02-01

The hot plate is a widely used test to assess nociception. The effect of non-nociceptive factors (weight, sex, activity, habituation, and repeated testing) on hot-plate latency was examined. Comparison of body weight and hot-plate latency revealed a small but significant inverse correlation (light rats had longer latencies). Habituating rats to the test room for 1 hour prior to testing did not decrease hot-plate latency except for female rats tested on days 2 to 4. Hot-plate latency decreased with repeated daily testing, but this was not caused by a decrease in locomotor activity or learning to respond. Activity on the hot plate was consistent across all 4 trials, and prior exposure to a room-temperature plate caused a similar decrease in latency as rats tested repeatedly on the hot plate. Despite this decrease in baseline hot-plate latency, there was no difference in morphine antinociceptive potency. The present study shows that weight, habituation to the test room, and repeated testing can alter baseline hot-plate latency, but these effects are small and have relatively little impact on morphine antinociception. This manuscript shows that non-nociceptive factors such as body weight, habituation, and repeated testing can alter hot-plate latency, but these factors do not alter morphine potency. In sum, the hot-plate test is an easy to use and reliable method to assess supraspinally organized nociceptive responses. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Investigation into the mechanism(s) that leads to platelet decreases in cynomolgus monkeys during administration of ISIS-104838, a 2'-MOE-modified antisense oligonucleotide.

PubMed

Narayanan, P K; Shen, L; Curtis, B R; Bourdon, M; Nolan, J P; Zhou, F; Christian, B; Gupta, S; Schaubhut, J L; Greenlee, S; Hoffmaster, C; Burel, S; Witztum, J L; Engelhardt, J A; Henry, S P

2018-05-29

ISIS 104838, a 2'-O-methoxyethyl (2'-MOE)-modified antisense oligonucleotide (ASO), causes a moderate, reproducible, dose-dependent, but self-limiting decrease in platelet (PLT) counts in monkeys and humans. To determine the etiology of PLT decrease in cynomolgus monkeys, a 12-week repeat dose toxicology study in 5 cynomolgus monkeys given subcutaneous injections of ISIS 104838 (30 to 60 mg/kg/week). Monkeys were also injected intravenously with 111In-oxine-labeled PLTs to investigate PLT sequestration. In response to continued dosing, PLT counts were decreased by 50 to 90% by day 30 in all monkeys. PLT decreases were accompanied by 2- to 4.5-fold increases in immunoglobulin M(IgM), which were typified by a 2-to-5-fold increase in anti-platelet factor 4 (PF4) IgM and anti-PLT IgM, respectively. Monocyte chemotactic protein 1 (MCP-1) increased upon dosing of ISIS 104838, concomitant with a 2- to 6-fold increase in monocyte-derived extracellular vesicles (EVs), indicating monocyte activation but not PLT activation. Despite a 2- to- 3-fold increase in von Willebrand factor (VWF) antigen in all monkeys following ASO administration, only two monkeys showed a 2 to 4-fold increase in endothelial EVs. Additionally, a 25-45% increase in PLT sequestration in liver and spleen was also observed. Collectively, these results suggest the overall increase in total IgM, anti-PLT IgM and/or anti-PF4 IgM, in concert with monocyte activation contributed to increased PLT sequestration in spleen and liver, leading to decreased PLTs in peripheral blood.

Intestine-Specific Mttp Deletion Decreases Mortality and Prevents Sepsis-Induced Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia

PubMed Central

Dominguez, Jessica A.; Xie, Yan; Dunne, W. Michael; Yoseph, Benyam P.; Burd, Eileen M.; Coopersmith, Craig M.; Davidson, Nicholas O.

2012-01-01

Background The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the “motor” of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO), which exhibit a block in chylomicron assembly together with lipid malabsorption. Methodology/Principal Findings Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0%) dying compared to 5/17 (29%) control mice (p<0.05). This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL) levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice. Conclusions/Significance These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by

The farm cost of decreasing antimicrobial use in dairy production

PubMed Central

Tauer, Loren William; Gröhn, Yrjo Tapio

2018-01-01

Antimicrobials are used in animal agriculture to cure bacterial infectious diseases. However, antimicrobial use (AMU) inevitably leads to the selection of resistant bacteria, potentially infecting humans. As a global public threat, antimicrobial resistance has led policy makers to implement regulations supervising AMU. The objective of our research was to investigate the farm impact of several potential policies aimed at decreasing AMU. We modeled a dairy herd of 1000 cows with an average level of disease prevalence for the nine most frequent bacterial dairy diseases found in western countries. We calculated the farm net costs of AMU prohibition, as well as cost increases in antimicrobial treatments prices, and an increase in the milk withdrawal period after AMU. Sensitivity analyses were conducted to assess the impact of output and input prices, and disease prevalence. At a mean disease prevalence, the average net costs of not using antimicrobials were $61 per cow per year greater compared to a scenario modeling current farm AMU. The model predicted that the minimum and maximum increased costs associated with AMU prohibition were $46 and $73 per cow per year compared to current AMU. In each scenario, the cost difference increased with disease prevalence. Sensitivity analysis showed that the three stochastic variables which most significantly influenced the cost difference were respectively, cow replacement prices, cow slaughter price, and the milk price. Antimicrobial price increases of a factor of five, or extending the milk withdrawal period by 15 days, resulted in increasing the costs of diseases to a level where the farmer was better off not using antimicrobials. Our results suggest that the farm level costs of AMU prohibition in many cases might be minor, although the consequences of any policy instrument should be carefully evaluated to reach the ultimate goal of decreasing AMU without threatening the sustainability of milk production. PMID:29566103

Taking the Initiative: Risk-Reduction Strategies and Decreased Malpractice Costs.

PubMed

Raper, Steven E; Rose, Deborah; Nepps, Mary Ellen; Drebin, Jeffrey A

2017-11-01

To heighten awareness of attending and resident surgeons regarding strategies for defense against malpractice claims, a series of risk reduction initiatives have been carried out in our Department of Surgery. We hypothesized that emphasis on certain aspects of risk might be associated with decreased malpractice costs. The relative impact of Department of Surgery initiatives was assessed when compared with malpractice experience for the rest of the Clinical Practices of the University of Pennsylvania (CPUP). Surgery and CPUP malpractice claims, indemnity, and expenses were obtained from the Office of General Counsel. Malpractice premium data were obtained from CPUP finance. The Department of Surgery was assessed in comparison with all other CPUP departments. Cost data (yearly indemnity and expenses), and malpractice premiums (total and per physician) were expressed as a percentage of the 5-year mean value preceding implementation of the initiative program. Surgery implemented 38 risk reduction initiatives. Faculty participated in 27 initiatives; house staff participated in 10 initiatives; and advanced practitioners in 1 initiative. Department of Surgery claims were significantly less than CPUP (74.07% vs 81.07%; p < 0.05). The mean yearly indemnity paid by the Department of Surgery was significantly less than that of the other CPUP departments (84.08% vs 122.14%; p < 0.05). Department of Surgery-paid expenses were also significantly less (83.17% vs 104.96%; p < 0.05), and surgical malpractice premiums declined from baseline, but remained significantly higher than CPUP premiums. The data suggest that educating surgeons on malpractice and risk reduction may play a role in decreasing malpractice costs. Additional extrinsic factors may also affect cost data. Emphasis on risk reduction appears to be cumulative and should be part of an ongoing program. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Silencing vimentin expression decreases pulmonary metastases in a pre-diabetic mouse model of mammary tumor progression.

PubMed

Zelenko, Z; Gallagher, E J; Tobin-Hess, A; Belardi, V; Rostoker, R; Blank, J; Dina, Y; LeRoith, D

2017-03-01

Increased breast cancer risk and mortality has been associated with obesity and type 2 diabetes (T2D). Hyperinsulinemia, a key factor in obesity, pre-diabetes and T2D, has been associated with decreased breast cancer survival. In this study, a mouse model of pre-diabetes (MKR mouse) was used to investigate the mechanisms through which endogenous hyperinsulinemia promotes mammary tumor metastases. The MKR mice developed larger primary tumors and greater number of pulmonary metastases compared with wild-type (WT) mice after injection with c-Myc/Vegf overexpressing MVT-1 cells. Analysis of the primary tumors showed significant increase in vimentin protein expression in the MKR mice compared with WT. We hypothesized that vimentin was an important mediator in the effect of hyperinsulinemia on breast cancer metastasis. Lentiviral short hairpin RNA knockdown of vimentin led to a significant decrease in invasion of the MVT-1 cells and abrogated the increase in cell invasion in response to insulin. In the pre-diabetic MKR mouse, vimentin knockdown led to a decrease in pulmonary metastases. In vitro, we found that insulin increased pAKT, prevented caspase 3 activation, and increased vimentin. Inhibiting the phosphatidylinositol 3 kinase/AKT pathway, using NVP-BKM120, increased active caspase 3 and decreased vimentin levels. This study is the first to show that vimentin has an important role in tumor metastasis in vivo in the setting of pre-diabetes and endogenous hyperinsulinemia. Vimentin targeting may be an important therapeutic strategy to reduce metastases in patients with obesity, pre-diabetes or T2D.

Decreased seed oil production in FUSCA3 Brassica napus mutant plants.

PubMed

Elahi, Nosheen; Duncan, Robert W; Stasolla, Claudio

2015-11-01

Canola (Brassica napus L.) oil is extensively utilized for human consumption and industrial applications. Among the genes regulating seed development and participating in oil accumulation is FUSCA3 (FUS3), a member of the plant-specific B3-domain family of transcription factors. To evaluate the role of this gene during seed storage deposition, three BnFUSCA3 (BnFUS3) TILLING mutants were generated. Mutations occurring downstream of the B3 domain reduced silique number and repressed seed oil level resulting in increased protein content in developing seeds. BnFUS3 mutant seeds also had increased levels of linoleic acid, possibly due to the reduced expression of ω-3 FA DESATURASE (FAD3). These observed phenotypic alterations were accompanied by the decreased expression of genes encoding transcription factors stimulating fatty acid (FA) synthesis: LEAFY COTYLEDON1 and 2 (LEC1 and 2) ABSCISIC ACID-INSENSITIVE 3 (BnABI3) and WRINKLED1 (WRI1). Additionally, expression of genes encoding enzymes involved in sucrose metabolism, glycolysis, and FA modifications were down-regulated in developing seeds of the mutant plants. Collectively, these transcriptional changes support altered sucrose metabolism and reduced glycolytic activity, diminishing the carbon pool available for the synthesis of FA and ultimately seed oil production. Based on these observations, it is suggested that targeted manipulations of BnFUS3 can be used as a tool to influence oil accumulation in the economically important species B. napus. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Decreased knee adduction moment does not guarantee decreased medial contact force during gait.

PubMed

Walter, Jonathan P; D'Lima, Darryl D; Colwell, Clifford W; Fregly, Benjamin J

2010-10-01

Excessive contact force is believed to contribute to the development of medial compartment knee osteoarthritis. The external knee adduction moment (KAM) has been identified as a surrogate measure for medial contact force during gait, with an abnormally large peak value being linked to increased pain and rate of disease progression. This study used in vivo gait data collected from a subject with a force-measuring knee implant to assess whether KAM decreases accurately predict corresponding decreases in medial contact force. Changes in both quantities generated via gait modification were analyzed statistically relative to the subject's normal gait. The two gait modifications were a "medial thrust" gait involving knee medialization during stance phase and a "walking pole" gait involving use of bilateral walking poles. Reductions in the first (largest) peak of the KAM (32-33%) did not correspond to reductions in the first peak of the medial contact force. In contrast, reductions in the second peak and angular impulse of the KAM (15-47%) corresponded to reductions in the second peak and impulse of the medial contact force (12-42%). Calculated reductions in both KAM peaks were highly sensitive to rotation of the shank reference frame about the superior-inferior axis of the shank. Both peaks of medial contact force were best predicted by a combination of peak values of the external KAM and peak absolute values of the external knee flexion moment (R(2) = 0.93). Future studies that evaluate the effectiveness of gait modifications for offloading the medial compartment of the knee should consider the combined effect of these two knee moments. Published by Wiley Periodicals, Inc. J Orthop Res 28:1348-1354, 2010.

Selective angiographic embolization of blunt splenic traumatic injuries in adults decreases failure rate of nonoperative management.

PubMed

Bhullar, Indermeet S; Frykberg, Eric R; Siragusa, Daniel; Chesire, David; Paul, Julia; Tepas, Joseph J; Kerwin, Andrew J

2012-05-01

To determine whether angioembolization (AE) in hemodynamically stable adult patients with blunt splenic trauma (BST) at high risk for failure of nonoperative management (NOM) (contrast blush [CB] on computed tomography, high-grade IV-V injuries, or decreasing hemoglobin) results in lower failure rates than reported. The records of patients with BST from July 2000 to December 2010 at a Level I trauma center were retrospectively reviewed using National Trauma Registry of the American College of Surgeons. Failure of NOM (FNOM) occurred if splenic surgery was required after attempted NOM. Logistic regression analysis was used to identify factors associated with FNOM. A total of 1,039 patients with BST were found. Pediatric patients (age <17 years), those who died in the emergency department, and those requiring immediate surgery for hemodynamic instability were excluded. Of the 539 (64% of all BST) hemodynamically stable patients who underwent NOM, 104 (19%) underwent AE and 435 (81%) were observed without AE (NO-AE). FNOM for the various groups were as follows: overall NOM (4%), NO-AE (4%), and AE (4%). There was no significant difference in FNOM for NO-AE versus AE for grades I to III: grade I (1% vs. 0%, p = 1), grade II (2% vs. 0%, p = 0.318), and grade III (5% vs. 0%, p = 0.562); however, a significant decrease in FNOM was noted with the addition of AE for grades IV to V: grade IV (23% vs. 3%, p = 0.04) and grade V (63% vs. 9%, p = 0.03). Statistically significant independent risk factors for FNOM were grade IV to V injuries and CB. Application of strictly defined selection criteria for NOM and AE in patients with BST resulted in one of the lowest overall FNOM rates (4%). Hemodynamically stable BST patients are candidates for NOM with selective AE for high-risk patients with grade IV to V injuries, CB on initial computed tomography, and/or decreasing hemoglobin levels. III, therapeutic study.

Decreased IGF-1 concentration during the first trimester of pregnancy in women with normal somatotroph function.

PubMed

Persechini, Marie-Laure; Gennero, Isabelle; Grunenwald, Solange; Vezzosi, Delphine; Bennet, Antoine; Caron, Philippe

2015-08-01

A decrease of insulin-like growth factor-I levels (IGF-I) has been reported during the first trimester of pregnancy in women with acromegaly before the secretion of placental growth hormone (GH) progressively increases IGF-1 concentration. To evaluate variations of concentrations of IGF-1, insulin-like growth factor (IGF)-binding protein-3 (IGF-BP3) and GH during the first trimester of pregnancy in women with normal somatotroph function. Sixteen women (median age 31 years) with as who were followed for benign thyroid disorders (n = 15) or prolactin-secreting microadenoma (n = 1) were evaluated before and in the first trimester of pregnancy. Serum concentrations of GH, IGF-1, IGF-BP3, TSH and estradiol (E2) were measured before and in the first trimester (5.4 ± 2.2 weeks of gestation). Before pregnancy, somatotroph and thyroid functions (median TSH 1.2 mU/L) were normal in all women. At the first trimester IGF-1 levels decreased significantly (before = 210 ng/mL, first trimester = 145 ng/mL, p < 0.001) with no significant change in GH (before = 1.5 ng/mL, first trimester = 0.84 ng/mL) or IGF-BP3 levels (before = 2.3 ng/mL, first trimester = 2.2 ng/mL), while estradiol levels increased significantly (before = 46.5 pg/100 mL, first trimester = 448.5 pg/100 mL, p < 0.001). In women with normal somatotroph function, IGF-1 levels decrease in the first trimester of pregnancy without changes in GH or IGF-BP3 levels. These results confirm liver resistance to GH as a consequence of the physiological increase of estrogens during the first trimester.

Decrease of concentration and colloidal fraction of organic carbon and trace elements in response to the anomalously hot summer 2010 in a humic boreal lake.

PubMed

Shirokova, L S; Pokrovsky, O S; Moreva, O Yu; Chupakov, A V; Zabelina, S A; Klimov, S I; Shorina, N V; Vorobieva, T Ya

2013-10-01

The colloidal distribution and size fractionation of organic carbon (OC), major elements and trace elements (TE) were studied in a seasonally stratified, organic-rich boreal lake, Lake Svyatoe, located in the European subarctic zone (NW Russia, Arkhangelsk region). This study took place over the course of 4 years in both winter and summer periods using an in situ dialysis technique (1 kDa, 10 kDa and 50 kDa) and traditional frontal filtration and ultrafiltration (5, 0.22 and 0.025 μm). We observed a systematic difference in dissolved elements and colloidal fractions between summer and winter periods with the highest proportion of organic and organo-ferric colloids (1 kDa-0.22 μm) observed during winter periods. The anomalously hot summer of 2010 in European Russia produced surface water temperatures of approximately 30°C, which were 10° above the usual summer temperatures and brought about crucial changes in element speciation and size fractionation. In August 2010, the concentration of dissolved organic carbon (DOC) decreased by more than 30% compared to normal period, while the relative proportion of organic colloids decreased from 70-80% to only 20-30% over the full depth of the water column. Similarly, the proportion of colloidal Fe decreased from 90-98% in most summers and winters to approximately 60-70% in August 2010. During this hot summer, measurable and significant (>30% compared to other periods) decreases in the colloidal fractions of Ca, Mg, Sr, Ba, Al, Ti, Ni, As, V, Co, Y, all rare earth elements (REEs), Zr, Hf, Th and U were also observed. In addition, dissolved (<0.22 μm) TE concentrations decreased by a factor of 2 to 6 compared to previously investigated periods. The three processes most likely responsible for such a crucial change in element biogeochemistry with elevated water temperature are 1) massive phytoplankton bloom, 2) enhanced mineralization (respiration) of allochthonous dissolved organic matter by heterotrophic aerobic

Decrease in lean body mass in men with prostate cancer receiving androgen deprivation therapy: mechanism and biomarkers.

PubMed

Hara, Noboru; Ishizaki, Fumio; Saito, Toshihiro; Nishiyama, Tsutomu; Kawasaki, Takashi; Takahashi, Kota

2013-02-01

To elucidate the mechanism of the androgen deprivation therapy (ADT)-related decrease in lean body mass (LBM). The LBM and blood samples were studied before and after 6 months of ADT in 72 patients with localized prostate cancer. The LBM was assessed using a foot-to-foot bioelectrical impedance analyzer. Before ADT, the LBM correlated with none of the serum sex steroid levels; however, it correlated closely with serum 5α-androstane-3α,17β-diol glucuronide (Spearman's rank correlation coefficient = 0.409, P = .001) and insulin-like growth factor-1 (IGF-I, Spearman's rank correlation coefficient = 0.329, P = .005). After ADT, the LBM decreased by 0.9% (P = .036), and the serum testosterone and dihydrotestosterone had decreased by 96.8% and 94.3%, respectively (P <.001 for both), and the IGF-I had increased by 11.6% (from 19.9 to 22.2 nmol/L, P = .001). The serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels decreased after ADT by 9.8% (from 66.2 to 59.7 pg/mL, P = .008), and the post-treatment LBM correlated inversely with 1,25(OH)2D (Spearman's rank correlation coefficient = -0.343, P = .003). The post-treatment LBM was dissociated with 5α-androstane-3α,17β-diol glucuronide and IGF-I. The pretreatment and post-treatment LBMs both correlated inversely with serum sex hormone-binding globulin (P = .024 and P = .016, respectively). The deficiency in androgen levels was suggested to be a link to the ADT-related decrease in LBM; the androgen metabolite 5α-androstane-3α,17β-diol glucuronide has a potential value for assessing the LBM in untreated men. IGF-I also promotes muscle building and is positively regulated during ADT. Sex hormone-binding globulin possibly accelerates the ADT-related decrease in LBM. Although the mechanism for the decrease in 1,25(OH)2D and its inverse correlation with LBM during ADT is unclear, 1,25(OH)2D might be a biomarker reflecting the ADT-related decrease in LBM. Copyright © 2013 Elsevier Inc. All rights reserved.

Decreased concentration of serum melatonin in nighttime compared with daytime female medical technologists in South Korea.

PubMed

Song, GiSeon; Yoon, Kyong-Ah; Chi, HyunYoung; Roh, Jaehoon; Kim, Jin-Hee

2016-01-01

Working during the night can disrupt the normal circadian rhythm by altering the melatonin level. A low level of melatonin is associated with an increased risk of cancer, possibly by decreasing the expression of tumor-suppressor genes, such as p53. To determine whether nighttime work is associated with melatonin level in serum as well as the expression of related genetic markers, we enrolled 100 female nighttime medical technologists employed at a hospital in South Korea. Melatonin concentration and melatonin receptor 1 (MT1) expression were significantly lower in nighttime than in daytime workers (1.84 pg/mL versus 4.04 pg/mL; 1.16 versus 1.61, respectively). However, p53 expression showed no difference between the groups. In summary, nighttime work could be an important risk factor for circadian disruption, but not a direct risk factor for cancer in medical technologists in South Korea.

Does additional cone beam computed tomography decrease the risk of inferior alveolar nerve injury in high-risk cases undergoing third molar surgery?Does CBCT decrease the risk of IAN injury?

PubMed

Korkmaz, Y T; Kayıpmaz, S; Senel, F C; Atasoy, K T; Gumrukcu, Z

2017-05-01

The objectives of this study were to evaluate the efficacy of additional cone beam computed tomography (CBCT) imaging on decreasing the risk of inferior alveolar nerve (IAN) injury during third molar removal in patients at high risk and to assess the surgical outcomes. The study sample included patients considered at high risk for IAN injury based on panoramic radiography (PAN) evaluation. The primary predictor was the type of imaging method (PAN only or with additional CBCT). The other variables were demographic and anatomical/radiographic factors. The primary outcome variable was IAN injury. The secondary outcome variables were the preoperative surgical plan and surgical results including IAN exposure and duration of surgery. The sample comprised 122 patients (139 teeth) aged 18-48 years. Postoperative temporary IAN injury was present in three (4.2%) cases in the CBCT group and 11 (16.4%) in the PAN group at 7 days after surgery. However, none of the patients had a permanent IAN injury at the 6-month follow-up. Additional CBCT imaging was not superior to PAN in reducing IAN injury after third molar surgery during long-term follow-up. Nonetheless, CBCT may decrease the prevalence of temporary IAN injury and improve the surgical outcomes in high-risk patients. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

The regulation of trefoil factor 2 expression by the transcription factor Sp3.

PubMed

Liu, Jingjing; Wang, Xu; Cai, Yiling; Zhou, Jingping; Guleng, Bayasi; Shi, Huaxiu; Ren, Jianlin

2012-10-19

Trefoil factor family 2 (TFF2) participates in mucus stabilization and repair, apoptosis, and inflammatory responses. Previously published reports have indicated that several growth factors and basal transcription factors are associated with the expression of TFF2. However, the detailed mechanisms that regulate TFF2 expression are not fully understood. The present study was designed to assess the essential role of the transcription factor SP3 with respect to TFF2 expression. We first demonstrated that there was a negative correlation between the expression levels of SP3 and TFF2. Thus, in the examined cells, the overexpression of SP3 decreased the expression level of TFF2, whereas the inhibition of SP3 increased the expression level of TFF2. Moreover, we discovered two GC boxes in the TFF2 promoter and confirmed the specific binding of SP3 to this promoter. On the whole, this study indicated that Sp3 was a major regulator of TFF2 expression. This knowledge should contribute to our understanding of the role that is played by SP3 in the regulation of TFF2 expression. Copyright © 2012 Elsevier Inc. All rights reserved.

Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats.

PubMed

Gong, Meng-Juan; Han, Bin; Wang, Shu-mei; Liang, Sheng-wang; Zou, Zhong-jie

2016-05-10

Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

Hemistepsin A ameliorates acute inflammation in macrophages via inhibition of nuclear factor-κB and activation of nuclear factor erythroid 2-related factor 2.

PubMed

Kim, Jae Kwang; Lee, Ji Eun; Jung, Eun Hye; Jung, Ji Yun; Jung, Dae Hwa; Ku, Sae Kwang; Cho, Il Je; Kim, Sang Chan

2018-01-01

Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata (Bunge) Bunge. We investigated the anti-inflammatory effects of HsA and sought to determine its mechanisms of action in macrophages. HsA pretreatment inhibited nitric oxide production, and reduced the expression of iNOS and COX-2 in Toll-like receptor ligand-stimulated RAW 264.7 cells. Additionally, HsA decreased the secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated Kupffer cells as well as in RAW 264.7 cells. HsA inhibited phosphorylation of IKKα/β and degradation of IκBα, resulting in decreased nuclear translocation of nuclear factor-κB (NF-κB) and its transcriptional activity. Moreover, HsA phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2), increased expression levels of antioxidant genes, and attenuated LPS-stimulated H 2 O 2 production. Phosphorylation of p38 and c-Jun N-terminal kinase was required for HsA-mediated Nrf2 phosphorylation. In a D-galactosamine/LPS-induced liver injury model, HsA ameliorated D-galactosamine/LPS-induced hepatocyte degeneration and inflammatory cells infiltration. Moreover, immunohistochemical analyses using nitrotyrosine, 4-hydroxynonenal, and cleaved poly (ADP-ribose) polymerase antibodies revealed that HsA protected the liver from oxidative stress. Furthermore, HsA reduced the numbers of proinflammatory cytokine-positive cells in hepatic tissues. Thus, these results suggest HsA may be a promising natural product to manage inflammation-mediated tissue injuries through inhibition of NF-κB and activation of Nrf2. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Economic mechanisms in decreasing the level of hospitalizations].

PubMed

Kadyrov, F N

1997-01-01

Increase of the role of primary health care and decrease of hospitalizations is a pressing medical and economic problem. However, rather often it is beneficial for a medical institution to hospitalize a patient. In order to create stimuli for decreasing the level of hospitalization, medical institutions are to have a share in the economy due to non-hospitalization. Proper validation of the share of the resultant economy is needed to realize this principle.

Bee Venom Decreases LPS-Induced Inflammatory Responses in Bovine Mammary Epithelial Cells.

PubMed

Jeong, Chang Hee; Cheng, Wei Nee; Bae, Hyojin; Lee, Kyung Woo; Han, Sang Mi; Petriello, Michael C; Lee, Hong Gu; Seo, Han Geuk; Han, Sung Gu

2017-10-28

The world dairy industry has long been challenged by bovine mastitis, an inflammatory disease, which causes economic loss due to decreased milk production and quality. Attempts have been made to prevent or treat this disease with multiple approaches, primarily through increased abuse of antibiotics, but effective natural solutions remain elusive. Bee venom (BV) contains a variety of peptides ( e.g. , melittin) and shows multiple bioactivities, including prevention of inflammation. Thus, in the current study, it was hypothesized that BV can reduce inflammation in bovine mammary epithelial cells (MAC-T). To examine the hypothesis, cells were treated with LPS (1 μg/ml) to induce an inflammatory response and the anti-inflammatory effects of BV (2.5 and 5 μg/ml) were investigated. The cellular mechanisms of BV against LPS-induced inflammation were also investigated. Results showed that BV can attenuate expression of an inflammatory protein, COX2, and pro-inflammatory cytokines such as IL-6 and TNF-α. Activation of NF-κB, an inflammatory transcription factor, was significantly downregulated by BV in cells treated with LPS, through dephosphorylation of ERK1/2. Moreover, pretreatment of cells with BV attenuated LPS-induced production of intracellular reactive oxygen species ( e.g. , superoxide anion). These results support our hypothesis that BV can decrease LPS-induced inflammatory responses in bovine mammary epithelial cells through inhibition of oxidative stress, NF-κB, ERK1/2, and COX-2 signaling.

Mutation in the factor VII hepatocyte nuclear factor 4α-binding site contributes to factor VII deficiency.

PubMed

Zheng, Xing-Wu; Kudaravalli, Rama; Russell, Theresa T; DiMichele, Donna M; Gibb, Constance; Russell, J Eric; Margaritis, Paris; Pollak, Eleanor S

2011-10-01

Severe coagulant factor VII (FVII) deficiency in postpubertal dizygotic twin males results from two point mutations in the FVII gene, a promoter region T→C transition at -60 and a His-to-Arg substitution at amino acid 348; both mutations prevent persistence of plasma functional FVII. This report documents longitudinal laboratory measurements from infancy to adulthood of FVII coagulant activity (FVII:C) in the twin FVII-deficient patients; it also details specific biochemical analyses of the -60 T→C mutation. The results revealed FVII:C levels of less than 1% in infancy that remain severely decreased through puberty and into adulthood. In-vitro analyses utilizing hepatocyte nuclear factor 4α (HNF4α) co-transfection and a chromatin immunoprecipitation assay indicate that the -60 T→C mutation severely diminishes functional interaction between the FVII promoter and transcription factor HNF4α. The importance of interaction between the FVII gene and HNF4α in normal FVII expression provides an in-vivo illustration of the regulated expression of an autosomal gene encoding a coagulation protein. The constancy of FVII:C and peripubertal patient symptomatology reported here illustrates androgen-independent expression in contrast to expression with an analogous mutation in the promoter region of the gene encoding coagulation FIX.

Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

PubMed

Wang, Zhenzhi; Zhai, Dongxia; Zhang, Danying; Bai, Lingling; Yao, Ruipin; Yu, Jin; Cheng, Wen; Yu, Chaoqin

2017-05-01

Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

Respiratory syncytial virus nonstructural proteins decrease levels of multiple members of the cellular interferon pathways.

PubMed

Swedan, Samer; Musiyenko, Alla; Barik, Sailen

2009-10-01

Viruses of the Paramyxoviridae family, such as the respiratory syncytial virus (RSV), suppress cellular innate immunity represented by type I interferon (IFN) for optimal growth in their hosts. The two unique nonstructural (NS) proteins, NS1 and NS2, of RSV suppress IFN synthesis, as well as IFN function, but their exact targets are still uncharacterized. Here, we investigate if either or both of the NS proteins affect the steady-state levels of key members of the IFN pathway. We found that both NS1 and NS2 decreased the levels of TRAF3, a strategic integrator of multiple IFN-inducing signals, although NS1 was more efficient. Only NS1 reduced IKKepsilon, a key protein kinase that specifically phosphorylates and activates IFN regulatory factor 3. Loss of the TRAF3 and IKKepsilon proteins appeared to involve a nonproteasomal mechanism. Interestingly, NS2 modestly increased IKKepsilon levels. In the IFN response pathway, NS2 decreased the levels of STAT2, the essential transcription factor for IFN-inducible antiviral genes. Preliminary mapping revealed that the C-terminal 10 residues of NS1 were essential for reducing IKKepsilon levels and the C-terminal 10 residues of NS2 were essential for increasing and reducing IKKepsilon and STAT2, respectively. In contrast, deletion of up to 20 residues of the C termini of NS1 and NS2 did not diminish their TRAF3-reducing activity. Coimmunoprecipitation studies revealed that NS1 and NS2 form a heterodimer. Clearly, the NS proteins of RSV, working individually and together, regulate key signaling molecules of both the IFN activation and response pathways.

Health Benefits of Decreases in PM2.5 and Ozone in the United States from 1998 to 2016

NASA Astrophysics Data System (ADS)

Nawaz, O.; Zhang, Y.; Tong, D.; van Donkelaar, A.; Martin, R.; West, J. J.

2017-12-01

Between 1990 and 2015 the US average concentration of PM2.5 decreased by 37% and ozone decreased by 22%, driven by environmental regulations and technological advances. These decreases in pollutants are expected to have brought substantial benefits for public health in the US. Here we assess the effects of this decrease by estimating the total burden of PM2.5 and ozone on premature mortality, each year between 1998-2016. Two data sets of ambient concentration were implemented in the health impact analysis that included different subsets of the time period. First, we use data from the North American Chemical Reanalysis project, which uses OMI NO2 and MODIS AOD observations for data assimilation to constrain ozone and PM2.5 between 2009-2016. Second, we use satellite-derived estimates of ground-level PM2.5 using AOD retrievals from NASA satellites combined with the GEOS-Chem chemical transport model between 1998-2015; these estimates are calibrated to ground-based observations using a geographically weighted regression. Using yearly data on population and baseline mortality provided by the Centers for Disease Control (CDC), we assess how air pollution-related mortality has changed annually within the continental United States, and analyze trends to determine how effectively the health burden has been reduced by environmental regulations and other factors.

Are airbags effective in decreasing trauma in auto accidents?

PubMed

Williams, Regan F; Croce, Martin A

2009-01-01

Multiple studies have addressed the effect of airbags on injury and mortality after motor vehicle collision with discrepant results (Table 1). Although large, population-based studies have minimized the protective effect of airbags, the most recent studies examining airbags have shown a decrease in injury and death, with the greatest protective effect seen when they are used in conjunction with seatbelts. Optimal restraint use is also associated with a decrease in infectious morbidity and hospital resource utilization. The widespread use of seatbelts and airbags will continue to save lives and decrease morbidity after motor vehicle collision.

Ascorbic acid, but not dehydroascorbic acid increases intracellular vitamin C content to decrease Hypoxia Inducible Factor -1 alpha activity and reduce malignant potential in human melanoma.

PubMed

Fischer, Adam P; Miles, Sarah L

2017-02-01

Accumulation of hypoxia inducible factor-1 alpha (HIF-1α) in malignant tissue is known to contribute to oncogenic progression and is inversely associated with patient survival. Ascorbic acid (AA) depletion in malignant tissue may contribute to aberrant normoxic activity of HIF-1α. While AA supplementation has been shown to attenuate HIF-1α function in malignant melanoma, the use of dehydroascorbic acid (DHA) as a therapeutic means to increase intracellular AA and modulate HIF-1α function is yet to be evaluated. Here we compared the ability of AA and DHA to increase intracellular vitamin C content and decrease the malignant potential of human melanoma by reducing the activity of HIF-1α. HIF-1α protein accumulation was evaluated by western blot and transcriptional activity was evaluated by reporter gene assay using a HIF-1 HRE-luciferase plasmid. Protein expressions and subcellular localizations of vitamin C transporters were evaluated by western blot and confocal imaging. Intracellular vitamin C content following AA, ascorbate 2-phosphate (A2P), or DHA supplementation was determined using a vitamin C assay. Malignant potential was accessed using a 3D spheroid Matrigel invasion assay. Data was analyzed by One or Two-way ANOVA with Tukey's multiple comparisons test as appropriate with p<0.05 considered significant. Melanoma cells expressed both sodium dependent vitamin C (SVCT) and glucose (GLUT) transporters for AA and DHA transport respectively, however advanced melanomas responded favorably to AA, but not DHA. Physiological glucose conditions significantly impaired intracellular vitamin C accumulation following DHA treatment. Consequently, A2P and AA, but not DHA treated cells demonstrated lower HIF-1α protein expression and activity, and reduced malignant potential. The ability of AA to regulate HIF-1α was dependent on SVCT2 function and SVCT2 was not significantly inhibited at pH representative of the tumor microenvironment. The use of ascorbic acid as an

The 'donations for decreased ALT (D4D)' prosocial behavior incentive scheme for NAFLD patients.

PubMed

Sumida, Yoshio; Yoshikawa, Toshikazu; Tanaka, Saiyu; Taketani, Hiroyoshi; Kanemasa, Kazuyuki; Nishimura, Tekeshi; Yamaguchi, Kanji; Mitsuyoshi, Hironori; Yasui, Kohichiroh; Minami, Masahito; Naito, Yuji; Itoh, Yoshito

2014-12-01

Physicians often experience difficulties in motivating patients with non-alcoholic fatty liver disease (NAFLD) to undergo lifestyle changes. The aim of this study is to examine whether 'Donations for Decreased alanine aminotransferase (ALT)' (D4D) prosocial behavior incentive can serve as an effective intrinsic motivational factor in comparison with conventional dietary and exercise intervention alone for NAFLD patients. Twenty-five NAFLD patients with elevated ALT were randomly assigned to a control group that received conventional dietary and exercise intervention alone, or a donation group whereby, as an incentive, we would make a monetary donation to the United Nations World Food Programme (WFP) based on the decrease in their ALT levels achieved over 12 weeks, in addition to receiving control intervention. In a donation group, we would donate US$1 to the WFP for every 1 IU/l of decrease in their ALT levels. There were no differences of pre-treatment clinical characteristics between the two groups. Significant reductions of ALT levels were achieved only in a donation group, although post-treatment ALT levels were not different between the two groups. These patients raised a total of $316 for the WFP. Promoting patients' intrinsic motivation by incorporating 'D4D' prosocial behavior incentive into conventional dietary and exercise intervention may provide a means to improve NAFLD. © The Author 2013. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Glial cell-derived neurotrophic factor alleviates sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nicotinic acetylcholine receptors in an experimental rat model of neuromyopathy.

PubMed

Wang, Xin; Min, Su; Xie, Fei; Yang, Jun; Li, Liang; Chen, Jingyuan

2018-02-05

Sepsis-induced neuromuscular dysfunction results from up-regulation of the expression of γ- and α7-nicotinic acetylcholine receptors (nAChR). Although glial cell derived neurotrophic factor (GDNF) has been implicated in repairing and supporting neurons, little is known about the effects of GDNF on demyelination of nerves in sepsis. In this study, we tested the hypothesis that GDNF could alleviate sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nAChR in an experimental rat model of neuromyopathy. Rats were randomly divided into a sham group and a sepsis group. Levels of inflammatory factors, muscle function, and nicotinic acetylcholine receptors were tested in rats after cecal ligation and puncture (CLP). At 24 h after CLP, GDNF was injected around the sciatic nerve of sepsis rats, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining was used to detect the expression of nAChRs. GDNF and its downstream effector (Erk1/2 and GFR-α), neuregulin-1 (NRG-1) and γ- and α7-nAChR were measured using Western blot analysis. The expression of GDNF reached a minimum at 24 h after CLP. Compared with the sham group, the release of cytokines and the expression of γ- and α7-nAChR were significantly increased in the sepsis group. The administration of GDNF significantly alleviated sepsis-induced neuromuscular dysfunction, as well as reducing the expression of γ- and α7-nAChR. In addition, the expression of Erk1/2, GFR-α, NRG-1 were significantly increased after GDNF treatment. GDNF administration may improve patient outcomes by reducing the demyelination of nerves and the expression of γ- and α7-nAChR. Copyright © 2018. Published by Elsevier Inc.

Music decreases aortic stiffness and wave reflections.

PubMed

Vlachopoulos, Charalambos; Aggelakas, Angelos; Ioakeimidis, Nikolaos; Xaplanteris, Panagiotis; Terentes-Printzios, Dimitrios; Abdelrasoul, Mahmoud; Lazaros, George; Tousoulis, Dimitris

2015-05-01

Music has been related to cardiovascular health and used as adjunct therapy in patients with cardiovascular disease. Aortic stiffness and wave reflections are predictors of cardiovascular risk. We investigated the short-term effect of classical and rock music on arterial stiffness and wave reflections. Twenty healthy individuals (22.5±2.5 years) were studied on three different occasions and listened to a 30-min music track compilation (classical, rock, or no music for the sham procedure). Both classical and rock music resulted in a decrease of carotid-femoral pulse wave velocity (PWV) immediately after the end of music listening (all p<0.01). Augmentation index (AIx) decreased with either classical or rock music in a more sustained way (nadir by 6.0% and 5.8%, respectively, at time zero post-music listening, all p<0.01). When music preference was taken into consideration, both classical and rock music had a more potent effect on PWV in classical aficionados (by 0.20 m/s, p=0.003 and 0.13 m/s, p=0.015, respectively), whereas there was no effect in rock aficionados (all p=NS). Regarding wave reflections, classical music led to a more potent response in classical aficionados (AIx decrease by 9.45%), whereas rock led to a more potent response to rock aficionados (by 10.7%, all p<0.01). Music, both classical and rock, decreases aortic stiffness and wave reflections. Effect on aortic stiffness lasts for as long as music is listened to, while classical music has a sustained effect on wave reflections. These findings may have important implications, extending the spectrum of lifestyle modifications that can ameliorate arterial function. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Microglial numbers attain adult levels after undergoing a rapid decrease in cell number in the third postnatal week.

PubMed

Nikodemova, Maria; Kimyon, Rebecca S; De, Ishani; Small, Alissa L; Collier, Lara S; Watters, Jyoti J

2015-01-15

During postnatal development, microglia, CNS resident innate immune cells, are essential for synaptic pruning, neuronal apoptosis and remodeling. During this period microglia undergo morphological and phenotypic transformations; however, little is known about how microglial number and density is regulated during postnatal CNS development. We found that after an initial increase during the first 14 postnatal days, microglial numbers in mouse brain began declining in the third postnatal week and were reduced by 50% by 6weeks of age; these "adult" levels were maintained until at least 9months of age. Microglial CD11b levels increased, whereas CD45 and ER-MP58 declined between P10 and adulthood, consistent with a maturing microglial phenotype. Our data indicate that both increased microglial apoptosis and a decreased proliferative capacity contribute to the developmental reduction in microglial numbers. We found no correlation between developmental reductions in microglial numbers and brain mRNA levels of Cd200, Cx3Cl1, M-Csf or Il-34. We tested the ability of M-Csf-overexpression, a key growth factor promoting microglial proliferation and survival, to prevent microglial loss in the third postnatal week. Mice overexpressing M-Csf in astrocytes had higher numbers of microglia at all ages tested. However, the developmental decline in microglial numbers still occurred, suggesting that chronically elevated M-CSF is unable to overcome the developmental decrease in microglial numbers. Whereas the identity of the factor(s) regulating microglial number and density during development remains to be determined, it is likely that microglia respond to a "maturation" signal since the reduction in microglial numbers coincides with CNS maturation. Copyright © 2014 Elsevier B.V. All rights reserved.

Trends in population blood pressure and determinant factors for population blood pressure.

PubMed

Andersen, Ulla Overgaard

2017-03-01

Strategies to reduce the burden of blood pressure attributable diseases require knowledge of secular trend in PBP and its determinants. The issues were investigated in the Copenhagen City Heart Study. The design of CCHS is a repeated measures study. Such designs are uniquely suited to studying changes of an outcome and what risk factors may be associated with that outcome. Repeated measures studies are very well suited for trend analysis by using mixed effect analyses. SBP decreased about 2 mmHg in 25 years. The risk factors age, gender and BMI were found valid as determinant factors for secular trends in SBP. In addition, the following factors were identified: household income and the interactions ''gender*age'' and ''survey*age''. The interaction ''gender*age'' stated that the difference between SBP in the two genders was great in the young individuals and diminished by age. The interaction ''survey*age'' stated that SBP in the young individuals decreased more with survey than SBP in the older individuals. Thus, the 20 years old subjects in survey 2, 3 and 4 have lower SBP than the 20 years old subjects in preceding surveys. The slopes were less steep in higher ages. In the group of elderly and old subjects the trend is partly explained by treatment bias because more and more subjects leave the untreated group and start treatment. The factor ''household income'' was significant only in the female population and stated that high-income women had lower SBP and a more beneficial secular trend in SBP than low-income women. Marital status, self-reported physical exercise and alcohol intake were not significant factors. A number of factors, that are interesting in relation to SBP, were not included in the CCHS and therefore not investigated. Among them are salt intake, childhood factors, genetic factors and the DASH diet. A survival study was performed to investigate the mortality rate in relation to SBP changes during the observation period. A Cox regression analysis

Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies

PubMed Central

Tan, Jiangning; Tedrow, John R.; Dutta, Justin A.; Juan-Guardela, Brenda; Nouraie, Mehdi; Chu, Yanxia; Trejo Bittar, Humberto; Ramani, Kritika; Biswas, Partha S.; Veraldi, Kristen L.; Kaminski, Naftali; Zhang, Yingze

2016-01-01

Rationale: Relaxin is a hormone that has been considered as a potential therapy for patients with fibrotic diseases. Objectives: To gauge the potential efficacy of relaxin-based therapies in idiopathic pulmonary fibrosis (IPF), we studied gene expression for relaxin/insulin-like family peptide receptor 1 (RXFP1) in IPF lungs and controls. Methods: We analyzed gene expression data obtained from the Lung Tissue Research Consortium and correlated RXFP1 gene expression data with cross-sectional clinical and demographic data. We also employed ex vivo donor and IPF lung fibroblasts to test RXFP1 expression in vitro. We tested CGEN25009, a relaxin-like peptide, in lung fibroblasts and in bleomycin injury. Measurements and Main Results: We found that RXFP1 is significantly decreased in IPF. In patients with IPF, the magnitude of RXFP1 gene expression correlated directly with diffusing capacity of the lung for carbon monoxide (P < 0.0001). Significantly less RXFP1 was detected in vitro in IPF fibroblasts than in donor controls. Transforming growth factor-β decreased RXFP1 in both donor and IPF lung fibroblasts. CGEN25009 was effective at decreasing bleomycin-induced, acid-soluble collagen deposition in vivo. The relaxin-like actions of CGEN25009 were abrogated by RXFP1 silencing in vitro, and, in comparison with donor lung fibroblasts, IPF lung fibroblasts exhibited decreased sensitivity to the relaxin-like effects of CGEN25009. Conclusions: IPF is characterized by the loss of RXFP1 expression. RXFP1 expression is directly associated with pulmonary function in patients with IPF. The relaxin-like effects of CGEN25009 in vitro are dependent on expression of RXFP1. Our data suggest that patients with IPF with the highest RXFP1 expression would be predicted to be most sensitive to relaxin-based therapies. PMID:27310652

Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies.

PubMed

Tan, Jiangning; Tedrow, John R; Dutta, Justin A; Juan-Guardela, Brenda; Nouraie, Mehdi; Chu, Yanxia; Trejo Bittar, Humberto; Ramani, Kritika; Biswas, Partha S; Veraldi, Kristen L; Kaminski, Naftali; Zhang, Yingze; Kass, Daniel J

2016-12-01

Relaxin is a hormone that has been considered as a potential therapy for patients with fibrotic diseases. To gauge the potential efficacy of relaxin-based therapies in idiopathic pulmonary fibrosis (IPF), we studied gene expression for relaxin/insulin-like family peptide receptor 1 (RXFP1) in IPF lungs and controls. We analyzed gene expression data obtained from the Lung Tissue Research Consortium and correlated RXFP1 gene expression data with cross-sectional clinical and demographic data. We also employed ex vivo donor and IPF lung fibroblasts to test RXFP1 expression in vitro. We tested CGEN25009, a relaxin-like peptide, in lung fibroblasts and in bleomycin injury. We found that RXFP1 is significantly decreased in IPF. In patients with IPF, the magnitude of RXFP1 gene expression correlated directly with diffusing capacity of the lung for carbon monoxide (P < 0.0001). Significantly less RXFP1 was detected in vitro in IPF fibroblasts than in donor controls. Transforming growth factor-β decreased RXFP1 in both donor and IPF lung fibroblasts. CGEN25009 was effective at decreasing bleomycin-induced, acid-soluble collagen deposition in vivo. The relaxin-like actions of CGEN25009 were abrogated by RXFP1 silencing in vitro, and, in comparison with donor lung fibroblasts, IPF lung fibroblasts exhibited decreased sensitivity to the relaxin-like effects of CGEN25009. IPF is characterized by the loss of RXFP1 expression. RXFP1 expression is directly associated with pulmonary function in patients with IPF. The relaxin-like effects of CGEN25009 in vitro are dependent on expression of RXFP1. Our data suggest that patients with IPF with the highest RXFP1 expression would be predicted to be most sensitive to relaxin-based therapies.

Pre-operative patient education is associated with decreased risk of arthrofibrosis after total knee arthroplasty: a case control study.

PubMed

Livbjerg, Anna Emilie; Froekjaer, Sara; Simonsen, Ole; Rathleff, Michael S

2013-09-01

The purpose was to investigate risk factors for postoperative stiffness and long-term outcome following manipulation under anaesthesia (MUA). In one of the five Danish regions, all patients in a 4-year period who received MUA following total knee arthroplasty (N=36) were included in two case-control studies. Data on potential risk factors were extracted from the Danish Knee arthroplasty Register and from a postal questionnaire including long-term outcome measures regarding pain, function and quality of life (Oxford Knee Score and EQ-5D). Previous knee surgery and a high preoperative Knee Society Function Score were significant risk factors, whereas attending a preoperative information meeting was associated with a significantly decreased risk of postoperative stiffness requiring MUA (P<0.001). The long-term results following MUA (1-5 years) were equivalent to patients without postoperative stiffness. Copyright © 2013 Elsevier Inc. All rights reserved.

[Risk factors associated to preclampsia].

PubMed

López-Carbajal, Mario Joaquín; Manríquez-Moreno, María Esther; Gálvez-Camargo, Daniela; Ramírez-Jiménez, Evelia

2012-01-01

preeclampsia constitutes one of the main causes of maternal and perinatal morbidity and mortality. The aim was to identify the risk factors associated to the developmental of preeclampsia mild-moderate and severe, as well as the force of association of these factors in a hospital of second-level medical care. study of cases and controls, a relation 1:1, in women withdrawn of the Service of Gynecology and Obstetrics during 2004 to 2007. Pregnant women with more than 20 weeks gestation were included. In the cases group we included patients with diagnosis of preeclampsia mild-moderate or severe (corroborated clinical and laboratory). In the controls group that had a normal childbirth without pathology during the pregnancy. 42 cases and 42 controls. The average age was of 27 years. The associated risk factors were overweight, obesity, irregular prenatal control, short or long intergenesic period, history of caesarean or preeclampsia in previous pregnancies. the knowledge of the risk factors will allow the accomplishment of preventive measures and decrease the fetal and maternal morbidity and mortality due to preeclampsia.

Estrogenic compounds decrease growth hormone receptor abundance and alter osmoregulation in Atlantic salmon

USGS Publications Warehouse

Lerner, Darren T.; Sheridan, Mark A.; McCormick, Stephen D.

2012-01-01

Exposure of Atlantic salmon smolts to estrogenic compounds is shown to compromise several aspects of smolt development. We sought to determine the underlying endocrine mechanisms of estrogen impacts on the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. Smolts in freshwater (FW) were either injected 3 times over 10 days with 2 μg g−1 17β-estradiol (E2) or 150 μg g−1 4-nonylphenol (NP). Seawater (SW)-acclimated fish received intraperitoneal implants of 30 μg g−1 E2 over two weeks. Treatment with these estrogenic compounds increased hepatosomatic index and total plasma calcium. E2 and NP reduced maximum growth hormone binding by 30–60% in hepatic and branchial membranes in FW and SW, but did not alter the dissociation constant. E2 and NP treatment decreased plasma levels of IGF-I levels in both FW and SW. In FW E2 and NP decreased plasma GH whereas in SW plasma GH increased after E2 treatment. Compared to controls, plasma chloride concentrations of E2-treated fish were decreased 5.5 mM in FW and increased 10.5 mM in SW. There was no effect of NP or E2 on gill sodium–potassium adenosine triphosphatase (Na+/K+-ATPase) activity in FW smolts, whereas E2 treatment in SW reduced gill Na+/K+-ATPase activity and altered the number and size of ionocytes. Our data indicate that E2 downregulates the GH/IGF-I-axis and SW tolerance which may be part of its normal function for reproduction and movement into FW. We conclude that the mechanism of endocrine disruption of smolt development by NP is in part through alteration of the GH/IGF-I axis via reduced GH receptor abundance.

Response of microbial communities to experimental warming and precipitation decrease in Rzecin peatland (Poland)

NASA Astrophysics Data System (ADS)

Basińska, Anna M.; Gąbka, Maciej; Reczuga, Monika; Łuców, Dominika; Stróżecki, Marcin; Samson, Mateusz; Józefczyk, Damian; Chojnicki, Bogdan; Urbaniak, Marek; Leśny, Jacek; Olejnik, Janusz; Gilbert, Daniel; Silvennoinen, Hanna; Juszczak, Radosław; Lamentowicz, Mariusz

2017-04-01

In the last decade researchers are intensively testing the consequences of different climate change scenarios. Due to high biodiversity, huge amount of stored carbon and their sensitivity to environmental changes, peatlands became important for the temperature increase and drought experiments. Analyses showed that mosses, vascular plants and microbial communities were affected by warming or drought, but still not all effects are clear. Studying the response of microbial groups and indicators (e.g. mixotrophic species of testate amoeba) to warming in combination with decrease of precipitation will allow to better understand the future environmental changes. To recognize the inflow of organic matter and the carbon fixing processes in disturbed environment, we need to analyse the structure and biomass of main groups living in peatlands and the response of those groups to disturbances. The Polish - Norway "WETMAN" project was designed to recognize biotic and abiotic components of ecosystem response to active warming and decrease of precipitation. In this study we present the response of microbial communities and chosen testate amoeba species (TA) to different treatments: warming, warming and decreased precipitation and only decreased precipitation, in relation to control plots. The microbial biomass of upper and lower Sphagnum segments were analysed separately. Particular microbial groups were positively correlated with manipulations e. g. microalgae and rotifers, and other were negatively affected by combination of drought and warming e.g. cyanobacteria and testate amoeba. The structure of community was modified by manipulations, and differed in the case of upper and lower segment of Sphagnum. RDA analyses showed that different factors were crucial for the biomass of microbial groups in upper (conductivity, temperature and phosphorus) and lower (nitrates and sodium) segment. Considering higher taxonomic resolution we found that at the beginning of the experiment TA

Bradykinin-induced growth inhibition of normal rat kidney (NRK) cells is paralleled by a decrease in epidermal-growth-factor receptor expression.

PubMed Central

Van Zoelen, E J; Peters, P H; Afink, G B; Van Genesen, S; De Roos, D G; Van Rotterdam, W; Theuvenet, A P

1994-01-01

Normal rat kidney fibroblasts, grown to density arrest in the presence of epidermal growth factor (EGF), can be induced to undergo phenotypic transformation by treatment with transforming growth factor beta or retinoic acid. Here we show that bradykinin blocks this growth-stimulus-induced loss of density-dependent growth arrest by a specific receptor-mediated mechanism. The effects of bradykinin are specific, and are not mimicked by other phosphoinositide-mobilizing agents such as prostaglandin F2 alpha. Northern-blot analysis and receptor-binding studies demonstrate that bradykinin also inhibits the retinoic acid-induced increase in EGF receptor levels in these cells. These studies provide additional evidence that EGF receptor levels modulate EGF-induced expression of the transformed phenotype in these cells. Images Figure 5 PMID:8135739

Factors That Affect Success in Nursing. Research Report No. 89-28R.

ERIC Educational Resources Information Center

Belcher, Marcia J.

In response to decreasing nursing program enrollments, less qualified enrollees, and decreasing scores on the national licensing board exams, a study was conducted at Miami-Dade Community College (MDCC) to examine factors that might contribute to success or failure among students entering the nursing program. In order to identify "high risk"…

Decrease in Urinary Creatinine Excretion in Early Stage Chronic Kidney Disease

PubMed Central

Tynkevich, Elena; Flamant, Martin; Haymann, Jean-Philippe; Metzger, Marie; Thervet, Eric; Boffa, Jean-Jacques; Vrtovsnik, François; Houillier, Pascal; Froissart, Marc; Stengel, Bénédicte

2014-01-01

Background Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population. Methods We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by 51Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time. Results Baseline mean urinary creatinine excretion decreased from 15.3±3.1 to 12.1±3.3 mmol/24 h (0.20±0.03 to 0.15±0.04 mmol/kg/24 h) in men, with mGFR falling from ≥60 to <15 mL/min/1.73 m2, and from 9.6±1.9 to 7.6±2.5 (0.16±0.03 to 0.12±0.03) in women. In addition to mGFR, an older age, diabetes, and lower levels of body mass index, proteinuria, and protein intake assessed by urinary urea were associated with lower mean urinary creatinine excretion at baseline. Mean annual decline in mGFR was 1.53±0.12 mL/min/1.73 m2 per year and that of urinary creatinine excretion rate, 0.28±0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m2 had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass. Conclusions Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass. PMID:25401694

Global mortality from storm surges is decreasing

NASA Astrophysics Data System (ADS)

Bouwer, Laurens M.; Jonkman, Sebastiaan N.

2018-01-01

Changes in society’s vulnerability to natural hazards are important to understand, as they determine current and future risks, and the need to improve protection. Very large impacts including high numbers of fatalities occur due to single storm surge flood events. Here, we report on impacts of global coastal storm surge events since the year 1900, based on a compilation of events and data on loss of life. We find that over the past, more than eight thousand people are killed and 1.5 million people are affected annually by storm surges. The occurrence of very substantial loss of life (>10 000 persons) from single events has however decreased over time. Moreover, there is a consistent decrease in event mortality, measured by the fraction of exposed people that are killed, for all global regions, except South East Asia. Average mortality for storm surges is slightly higher than for river floods, but lower than for flash floods. We also find that for the same coastal surge water level, mortality has decreased over time. This indicates that risk reduction efforts have been successful, but need to be continued with projected climate change, increased rates of sea-level rise and urbanisation in coastal zones.

Inhibition of CDK-mediated phosphorylation of Smad3 results in decreased oncogenesis in triple negative breast cancer cells

PubMed Central

Tarasewicz, Elizabeth; Rivas, Lisbi; Hamdan, Randala; Dokic, Danijela; Parimi, Vamsi; Bernabe, Beatriz Penalver; Thomas, Alexandra; Shea, Lonnie D; Jeruss, Jacqueline S

2014-01-01

Breast cancer onset and disease progression have been linked to members of the TGFβ superfamily and their downstream signaling components, the Smads. Alterations in Smad3 signaling are associated with the dichotomous role of TGFβ in malignancy, mediating both tumor suppressant and pro-metastatic behaviors. Overexpression of cell cycle regulators, cyclins D and E, renders cyclin-dependent kinases (CDKs) 4/2 hyperactive. Noncanonical phosphorylation of Smad3 by CDK4/2 inhibits tumor suppressant actions of Smad3. We hypothesized that CDK inhibition (CDKi) would restore Smad3 action and help promote cancer cell regression. Treatment of triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-436, Hs578T) with CDK2i or CDK4i resulted in increased Smad3 activity and decreased cell migration. Transfection with a 5M Smad3 construct containing inhibitory mutations in 5 CDK phosphorylation sites also resulted in decreased TNBC cell migration and invasion. MDA-MB-231 cells treated with CDK2i or CDK4i resulted in decreased Smad3 protein phosphorylation at the CDK phosphorylation T179 site, decreased MMP2 and c-myc expression, and increased p15 and p21 expression. Using a novel transfected cell array, we found that CDK2i treatment decreased activity of the epithelial-to-mesenchymal transition related transcription factors Snail and Twist. In vivo studies in an MDA-MB-231 tumor model showed that individual and combination treatment with paclitaxel and CDK2i resulted in decreased tumor volume and Ki67 staining. Collectively, these data support further investigation of targeted CDK inhibitors as a promising therapeutic strategy for TNBC, a breast cancer subtype with limited treatment options. PMID:25485498

Decreased GFR estimated by MDRD or Cockcroft-Gault equation predicts incident CVD: the strong heart study.

PubMed

Shara, Nawar M; Resnick, Helaine E; Lu, Li; Xu, Jiaqiong; Vupputuri, Suma; Howard, Barbara V; Umans, Jason G

2009-01-01

Kidney function, expressed as glomerular filtration rate (GFR), is commonly estimated from serum creatinine (Scr) and, when decreased, may serve as a nonclassical risk factor for incident cardiovascular disease (CVD). The ability of estimated GFR (eGFR) to predict CVD events during 5-10 years of follow-up is assessed using data from the Strong Heart Study (SHS), a large cohort with a high prevalence of diabetes. eGFRs were calculated with the abbreviated Modification of Diet in Renal Disease study (MDRD) and the Cockcroft-Gault (CG) equations. These estimates were compared in participants with normal and abnormal Scr. The association between eGFR and incident CVD was assessed. More subjects were labeled as having low eGFR (<60 ml/min per 1.73 m2) by the MDRD or CG equation, than by Scr alone. When Scr was in the normal range, both equations labeled similar numbers of participants as having low eGFRs, although concordance between the equations was poor. However, when Scr was elevated, the MDRD equation labeled more subjects as having low eGFR. Persons with low eGFR had increased risk of CVD. The MDRD and CG equations labeled more participants as having decreased GFR than did Scr alone. Decreased eGFR was predictive of CVD in this American Indian population with a high prevalence of obesity and type 2 diabetes mellitus.

On a decrease of high-latitude corona temperature of the Sun in the last 50 years

NASA Astrophysics Data System (ADS)

Makarov, V. I.; Tlatov, A. G.

2002-03-01

The ground-based observations of the green Fe XIV 5303 Å and red Fe X 6374 Å corona forbidden lines obtained at the Kislovodsk Solar Station since 1952 are used to determine the temperature variations of the solar corona. The observations of the solar corona at the Arosa, Pic du Midi, Kislovodsk, Norikura, Kanzelhöhe, Wendelstein and Lomnický Stit have been used to receive the Kislovodsk series of the green K I5303 and red K I6374 corona intensities for 1947-2000. Comparison of the K I5303 with the Wolf numbers W(t) shows high correlation factor 0.91. The mean monthly corona intensity has been calculated in the sunspot (0° - 45°) and at the high-latitude (45° - 90°) zones. We found a decrease of the K I5303 in 1.5 times at the high-latitudes in this period. It was shown that the ratio K I6374/K I5303 increased more than two times. We have found a decrease of temperature in polar zones of the Sun of order 0.1×106 during the last 50 years. It is supposed that a decrease of polar corona temperature connected with an increase of magnetic flux from high-latitude regions of the Sun during the last 120 years.

Study Looking at End Expiratory Pressure for Altitude Illness Decrease (SLEEP-AID).

PubMed

Lipman, Grant S; Kanaan, Nicholas C; Phillips, Caleb; Pomeranz, Dave; Cain, Patrick; Fontes, Kristin; Higbee, Becky; Meyer, Carolyn; Shaheen, Michael; Wentworth, Sean; Walsh, Diane

2015-06-01

Lipman, Grant S., Nicholas C. Kanaan, Caleb Phillips, Dave Pomeranz, Patrick Cain, Kristin Fontes, Becky Higbee, Carolyn Meyer, Michael Shaheen, Sean Wentworth, and Diane Walsh. Study Looking at End Expiratory Pressure for Altitude Illness Decrease (SLEEP-AID). High Alt Med Biol 16:154-161, 2015.--Acute mountain sickness (AMS) affects 25%-70% of the tens of millions of high altitude travelers annually, with hypoxia and nocturnal desaturations as major contributing factors. This is the first double blind randomized placebo controlled trial to assess expiratory positive airway pressure (EPAP) for AMS prevention and nocturnal hypoxic events. Healthy adult participants trekking in the Khumbu region of the Himalayas were randomized to a single-use EPAP nasal strip, or a visually identical sham device (placebo) prior to first night sleeping between 4371-4530 m (14,340-14,800 ft). The primary outcome was AMS incidence, measured by Lake Louise Questionnaire (LLQ), with secondary outcomes of AMS severity (by LLQ) and physiologic sleep indices measured by continuous sleep monitor. Intent-to-treat analysis included 219 participants with comparable demographic characteristics, of which 115 received EPAP and 104 placebo. There was no decrease in AMS with EPAP intervention (14% EPAP vs. 17% placebo; p=0.65; risk difference (-)3.15%, 95% CI (-)12.85%-6.56%). While overall AMS severity was not different between groups, EPAP reported decreased incidence of headache (64% vs. 76%; p<0.05, OR 0.51, 95% CI 0.27-0.95) and dizziness (81% vs. 98%; p<0.03, OR 0.29, 95% CI 0.09-0.78). During sleep, EPAP resulted in significant improvements in average peripheral oxygenation (Spo(2)) (80% versus 78%; p<0.01, mean difference=2, 95% CI 0.58-3.63) and a reduced percentage of time below 80% Spo(2) (31% vs. 46%; p<0.03, median difference=16, 95% CI 2.22-28.18). This lightweight and inexpensive EPAP device did not prevent acute mountain sickness, but did reduce the subgroup incidence of

Decrease in toe pinch force in male type 2 diabetic patients with diabetic nephropathy.

PubMed

Kataoka, Hiroaki; Miyatake, Nobuyuki; Kitayama, Naomi; Murao, Satoshi; Tanaka, Satoshi

2018-06-01

The purpose of this cross-sectional study was to investigate the toe pinch force (TPF) of type 2 diabetic patients with diabetic nephropathy by disease stage, and to clarify the factors affecting the TPF. Seventy-four men with diabetic nephropathy (age: 62.7 ± 8.9 years, duration of diabetes: 14.2 ± 8.6 years) were enrolled. According to the staging of diabetic nephropathy, TPF and knee extension force (KEF) were compared among three groups: normoalbuminuria, microalbuminuria, and overt nephropathy. In addition, we investigated factors influencing TPF and KEF by performing multiple regression analysis. Normoalbuminuria group, microalbuminuria group, and overt nephropathy group included 26, 25, and 23 patients, respectively. The TPF of the overt nephropathy group (3.15 ± 0.75 kg) was significantly lower than that of the normoalbuminuria (4.2 ± 0.7 kg, p < 0.001) and microalbuminuria groups (3.65 ± 0.81 kg, p = 0.022). The KEF of the overt nephropathy group (37.1 ± 8.3 kgf) was significantly lower than that of the normoalbuminuria group (44.8 ± 8.3 kgf, p = 0.010). Multiple regression analysis revealed that diabetic polyneuropathy (DPN) and diabetic nephropathy were determinant factors of the TPF; and age, body mass index, and diabetic nephropathy were determinant factors of the KEF. We found in male patients with diabetic nephropathy, the TPF and KEF decreased with progression of diabetic nephropathy. Furthermore, our findings suggest diabetic nephropathy and DPN are critically involved in the reduction of TPF and KEF.

Maternal intrapartum antibiotics and decreased vertical transmission of Lactobacillus to neonates during birth.

PubMed

Keski-Nisula, Leea; Kyynäräinen, Hanna-Reetta; Kärkkäinen, Ulla; Karhukorpi, Jari; Heinonen, Seppo; Pekkanen, Juha

2013-05-01

To estimate the transmission of maternal vaginal microbiota to neonates during term delivery, focusing on Lactobacillus flora in relation to various obstetric clinical factors. Fifty consecutive pregnant healthy women with singleton term pregnancies and their newborn infants. Vertical transmission of Lactobacillus flora to the newborn during delivery was evaluated in 45 mother-newborn pairs. Lactobacillus-dominant mixed flora was detected in 90% (N = 45) of vaginal samples, but only in 28% (N = 14) of neonatal cultures (transmission rate 31%). All neonates with Lactobacillus-dominant mixed flora had findings similar to those in maternal cultures. Cocci-dominant flora was the most common finding in neonates. Administration of antibiotics to the mother during the intrapartum period before birth and duration of rupture of membranes (ROM), regardless of maternal antibiotic treatment, were associated significantly with a decreased transmission rate of Lactobacillus-dominant mixed flora to neonates. Maternal intrapartum antibiotics and prolonged expectant management after ROM were associated with decreased transmission rate of vaginal Lactobacillus flora to the neonate during birth. As early colonization of Lactobacillus flora may have a preventive role in the development of allergic diseases later, the significance of intrapartum prophylactic antibiotics needs to be highlighted in forthcoming studies, especially as regards immunological development of the offspring. ©2013 The Author(s)/Acta Paediatrica ©2013 Foundation Acta Paediatrica.

Decreased bone mineral density in experimental myasthenia gravis in C57BL/6 mice.

PubMed

Oshima, Minako; Iida-Klein, Akiko; Maruta, Takahiro; Deitiker, Philip R; Atassi, M Zouhair

2017-09-01

Experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia gravis (MG), can be induced in C57BL/6 (B6, H-2  b ) mice by 2-3 injections with Torpedo californica AChR (tAChR) in complete Freund's adjuvant. Some EAMG mice exhibit weight loss with muscle weakness. The loss in body weight, which is closely associated with bone structure, is particularly evident in EAMG mice with severe muscle weakness. However, the relationship between muscle weakness and bone loss in EAMG has not been studied before. Recent investigations on bone have shed light on association of bone health and immunological states. It is possible that muscle weakness in EAMG developed by anti-tAChR immune responses might accompany bone loss. We determined whether reduced muscle strength associates with decreased bone mineral density (BMD) in EAMG mice. EAMG was induced by two injections at 4-week interval of tAChR and adjuvants in two different age groups. The first tAChR injection was either at age 8 weeks or at 15 weeks. We measured BMD at three skeletal sites, including femur, tibia, and lumbar vertebrae, using dual energy X-ray absorptiometry. Among these bone areas, femur of EAMG mice in both age groups showed a significant decrease in BMD compared to control adjuvant-injected and to non-immunized mice. Reduction in BMD in induced EAMG at a later-age appears to parallel the severity of the disease. The results indicate that anti-tAChR autoimmune response alone can reduce bone density in EAMG mice. BMD reduction was also observed in adjuvant-injected mice in comparison to normal un-injected mice, suggesting that BMD decrease can occur even when muscle activity is normal. Decreased BMD observed in both tAChR-injected and adjuvant-injected mice groups were discussed in relation to innate immunity and bone-related immunology involving activated T cells and tumour necrosis factor-related cytokines that trigger osteoclastogenesis and bone loss.

Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

PubMed

Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

2014-06-01

Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.

Correlation between polymerization shrinkage stress and C-factor depends upon cavity compliance.

PubMed

Wang, Zhengzhi; Chiang, Martin Y M

2016-03-01

The literature reports inconsistent results regarding using configuration factor (C-factor) as an indicator to reflect the generation of polymerization shrinkage stress (PS) from dental restorative composites due to the constraint of cavity configuration. The current study aimed at unraveling the complex effects of C-factor on PS based on analytical and experimental approaches together, such that the reported inconsistency can be explained and a significance of C-factor in clinic can be comprehensively provided. Analytical models based on linear elasticity were established to predict PS measured in instruments (testing systems) with different compliances, and complex effects of C-factor on PS were derived. The analyses were validated by experiments using a cantilever beam-based instrument and systematic variation of instrumental compliance. For a general trend, PS decreased with increasing C-factor when measured by instruments with high compliance. However, this trend gradually diminished and eventually reversed (PS became increased with increasing C-factor) by decreasing the system compliance. Our study indicates that the correlation between PS and C-factor are highly dependent on the compliance of testing instrument for PS measurement. This suggests that the current concept on the role of C-factor in the stress development and transmission to tooth structures, higher C-factor produces higher PS due to reduced flow capacity of more confined materials, can be misleading. Thus, the compliance of the prepared tooth (cavity) structure should also be considered in the effect of C-factor on PS. Published by Elsevier Ltd.

Nitrogen deposition and management practices increase soil microbial biomass carbon but decrease diversity in Moso bamboo plantations

PubMed Central

Li, Quan; Song, Xinzhang; Gu, Honghao; Gao, Fei

2016-01-01

Because microbial communities play a key role in carbon (C) and nitrogen (N) cycling, changes in the soil microbial community may directly affect ecosystem functioning. However, the effects of N deposition and management practices on soil microbes are still poorly understood. We studied the effects of these two factors on soil microbial biomass carbon (MBC) and community composition in Moso bamboo plantations using high-throughput sequencing of the 16S rRNA gene. Plantations under conventional (CM) or intensive management (IM) were subjected to one of four N treatments for 30 months. IM and N addition, both separately and in combination, significantly increased soil MBC while decreasing bacterial diversity. However, increases in soil MBC were inhibited when N addition exceeded 60 kg N∙ha−1∙yr−1. IM increased the relative abundances of Actinobacteria and Crenarchaeota but decreased that of Acidobacteria. N addition increased the relative abundances of Acidobacteria, Crenarchaeota, and Actinobacteria but decreased that of Proteobacteria. Soil bacterial diversity was significantly related to soil pH, C/N ratio, and nitrogen and available phosphorus content. Management practices exerted a greater influence over regulation of the soil MBC and microbial diversity compared to that of N deposition in Moso bamboo plantations. PMID:27302857

Consumption of Acidic Water Alters the Gut Microbiome and Decreases the Risk of Diabetes in NOD Mice

PubMed Central

Wolf, Kyle J.; Daft, Joseph G.; Tanner, Scott M.; Hartmann, Riley; Khafipour, Ehsan

2014-01-01

Infant formula and breastfeeding are environmental factors that influence the incidence of Type 1 Diabetes (T1D) as well as the acidity of newborn diets. To determine if altering the intestinal microbiome is one mechanism through which an acidic liquid plays a role in T1D, we placed non-obese diabetic (NOD)/ShiLtJt mice on neutral (N) or acidified H2O and monitored the impact on microbial composition and diabetes incidence. NOD-N mice showed an increased development of diabetes, while exhibiting a decrease in Firmicutes and an increase in Bacteroidetes, Actinobacteria, and Proteobacteria from as early as 2 weeks of age. NOD-N mice had a decrease in the levels of Foxp3 expression in CD4+Foxp3+ cells, as well as decreased CD4+IL17+ cells, and a lower ratio of IL17/IFNγ CD4+ T-cells. Our data clearly indicates that a change in the acidity of liquids consumed dramatically alters the intestinal microbiome, the presence of protective Th17 and Treg cells, and the incidence of diabetes. This data suggests that early dietary manipulation of intestinal microbiota may be a novel mechanism to delay T1D onset in genetically pre-disposed individuals. PMID:24453191

Consumption of acidic water alters the gut microbiome and decreases the risk of diabetes in NOD mice.

PubMed

Wolf, Kyle J; Daft, Joseph G; Tanner, Scott M; Hartmann, Riley; Khafipour, Ehsan; Lorenz, Robin G

2014-04-01

Infant formula and breastfeeding are environmental factors that influence the incidence of Type 1 Diabetes (T1D) as well as the acidity of newborn diets. To determine if altering the intestinal microbiome is one mechanism through which an acidic liquid plays a role in T1D, we placed non-obese diabetic (NOD)/ShiLtJt mice on neutral (N) or acidified H2O and monitored the impact on microbial composition and diabetes incidence. NOD-N mice showed an increased development of diabetes, while exhibiting a decrease in Firmicutes and an increase in Bacteroidetes, Actinobacteria, and Proteobacteria from as early as 2 weeks of age. NOD-N mice had a decrease in the levels of Foxp3 expression in CD4(+)Foxp3(+) cells, as well as decreased CD4(+)IL17(+) cells, and a lower ratio of IL17/IFNγ CD4+ T-cells. Our data clearly indicates that a change in the acidity of liquids consumed dramatically alters the intestinal microbiome, the presence of protective Th17 and Treg cells, and the incidence of diabetes. This data suggests that early dietary manipulation of intestinal microbiota may be a novel mechanism to delay T1D onset in genetically pre-disposed individuals.

Cellular and soluble components decrease the viable pathogen counts in milk from dairy cows with subclinical mastitis.

PubMed

Koshiishi, Tomoko; Watanabe, Masako; Miyake, Hajime; Hisaeda, Keiichi; Isobe, Naoki

2017-08-10

The present study was undertaken to clarify the factors that reduce the viable pathogen count in milk collected from the udders of subclinical mastitic cows during preservation. Milk was centrifuged to divide somatic cells (cellular components, precipitates) and antimicrobial peptides (soluble components, supernatants without fat layer); each fraction was cultured with bacteria, and the number of viable bacteria was assessed prior to and after culture. In 28.8% of milk samples, we noted no viable bacteria immediately after collection; this value increased significantly after a 5-hr incubation of milk with cellular components but not with soluble components (48.1 and 28.8%, respectively). After culture with cellular components, the numbers of bacteria (excluding Staphylococcus aureus and Streptococcus uberis) and yeast decreased dramatically, although the differences were not statistically significant. After cultivation with soluble components, only yeasts showed a tendency toward decreased mean viability, whereas the mean bacterial counts of S. uberis and T. pyogenes tended to increase after 5-hr preservation with soluble components. These results suggest that most pathogens in high somatic cell count (SCC) milk decreased during preservation at 15 to 25°C, due to both the cellular components and antimicrobial components in the milk. Particularly, the cellular components more potently reduced bacterial counts during preservation.

Decreasing water availability across the globe improves the effectiveness of protective ant-plant mutualisms: a meta-analysis.

PubMed

Leal, Laura C; Peixoto, Paulo E C

2017-08-01

Abiotic conditions can increase the costs of services and/or the benefits of rewards provided by mutualistic partners. Consequently, in some situations, the outcome of mutualisms can move from beneficial to detrimental for at least one partner. In the case of protective mutualisms between ant bodyguards and plants bearing extrafloral nectaries (EFNs), plants from arid environments face a trade-off between EFN production and maintenance and water and carbon economy. This trade-off may increase EFN costs and decrease their value as a defensive strategy to plants in such environments. Despite this, the presence of EFNs is an ubiquitous trait in plants from arid environments, suggesting that they provide greater benefits to plants in these environments to compensate for their higher costs. We used a meta-analysis to investigate if such benefits do increase with decreasing water availability and the possible underlying causes (such as ant behaviour or ant diversity). As predicted, ant effect on EFN plants performance increased as mean annual precipitation decreased. We also found that the frequency of dominant ants on EFN plants increased in drier areas. Due to the more aggressive behaviour of dominant ants, we suggest that they represent an important factor shaping the adaptive value of EFNs to plants in arid environments. © 2016 Cambridge Philosophical Society.

Nitrogen deposition and management practices increase soil microbial biomass carbon but decrease diversity in Moso bamboo plantations

NASA Astrophysics Data System (ADS)

Li, Quan; Song, Xinzhang; Gu, Honghao; Gao, Fei

2016-06-01

Because microbial communities play a key role in carbon (C) and nitrogen (N) cycling, changes in the soil microbial community may directly affect ecosystem functioning. However, the effects of N deposition and management practices on soil microbes are still poorly understood. We studied the effects of these two factors on soil microbial biomass carbon (MBC) and community composition in Moso bamboo plantations using high-throughput sequencing of the 16S rRNA gene. Plantations under conventional (CM) or intensive management (IM) were subjected to one of four N treatments for 30 months. IM and N addition, both separately and in combination, significantly increased soil MBC while decreasing bacterial diversity. However, increases in soil MBC were inhibited when N addition exceeded 60 kg N•ha-1•yr-1. IM increased the relative abundances of Actinobacteria and Crenarchaeota but decreased that of Acidobacteria. N addition increased the relative abundances of Acidobacteria, Crenarchaeota, and Actinobacteria but decreased that of Proteobacteria. Soil bacterial diversity was significantly related to soil pH, C/N ratio, and nitrogen and available phosphorus content. Management practices exerted a greater influence over regulation of the soil MBC and microbial diversity compared to that of N deposition in Moso bamboo plantations.

Decreased "ineffective erythropoiesis" preserves polycythemia in mice under long-term hypoxia.

PubMed

Harada, Tomonori; Tsuboi, Isao; Hirabayashi, Yukio; Kosaku, Kazuhiro; Naito, Michiko; Hara, Hiroyuki; Inoue, Tohru; Aizawa, Shin

2015-05-01

Hypoxia induces innumerable changes in humans and other animals, including an increase in peripheral red blood cells (polycythemia) caused by the activation of erythropoiesis mediated by increased erythropoietin (EPO) production. However, the elevation of EPO is limited and levels return to normal ranges under normoxia within 5-7 days of exposure to hypoxia, whereas polycythemia continues for as long as hypoxia persists. We investigated erythropoiesis in bone marrow and spleens from mouse models of long-term normobaric hypoxia (10 % O2) to clarify the mechanism of prolonged polycythemia in chronic hypoxia. The numbers of erythroid colony-forming units (CFU-E) in the spleen remarkably increased along with elevated serum EPO levels indicating the activation of erythropoiesis during the first 7 days of hypoxia. After 14 days of hypoxia, the numbers of CFU-E returned to normoxic levels, whereas polycythemia persisted for >140 days. Flow cytometry revealed a prolonged increase in the numbers of TER119-positive cells (erythroid cells derived from pro-erythroblasts through mature erythrocyte stages), especially the TER119 (high) CD71 (high) population, in bone marrow. The numbers of annexin-V-positive cells among the TER119-positive cells particularly declined under chronic hypoxia, suggesting that the numbers of apoptotic cells decrease during erythroid cell maturation. Furthermore, RT-PCR analysis showed that the RNA expression of BMP-4 and stem cell factor that reduces apoptotic changes during erythroid cell proliferation and maturation was increased in bone marrow under hypoxia. These findings indicated that decreased apoptosis of erythroid cells during erythropoiesis contributes to polycythemia in mice during chronic exposure to long-term hypoxia.

Arctigenin improves vascular tone and decreases inflammation in human saphenous vein.

PubMed

Daci, Armond; Neziri, Burim; Krasniqi, Shaip; Cavolli, Raif; Alaj, Rame; Norata, Giuseppe Danilo; Beretta, Giangiacomo

2017-09-05

The goal of this study was to test the effects of bioactive phenylpropanoid dibenzylbutyrolactone lignan arctigenin (ATG) in vascular tone. Human bypass graft vessel, from a saphenous vein (SV), were set up in organ bath system and contracted with potassium chloride (KCl, 40mM). Two concentration-response curves of noradrenaline (NE) (10nM-100μM) separated with an incubation period of 30min without (Control) or with ATG (3-100μM) were established. Inhibitors of nitric oxide, prostaglandins, K + related channels or calcium influx were used to delineate the molecular mechanisms beyond ATG effects. To investigate anti-inflammatory actions, SV were treated with 10μM or 100μM ATG and incubated for 18h in the absence or presence of both interleukin-1beta (IL-1β) and lipopolysaccharide (LPS) to mimic the physiological or inflamed tissue conditions. Proatherogenic and inflammatory mediators İnterleukine-1 beta (IL-1β), Monocyte Chemoattractant Proteine-1 (MCP-1), Tumor Necrosis Factor- α (TNF-α), İnterleukine-6 (IL-6), Prostaglandin E 2 (PGE 2 ) and İnterleukine-8 (IL-8) in the supernatant were measured. ATG significantly decreased vascular contractile response to NE. Moreover, it reduced contractions induced by KCl and cumulative addition of CaCl 2. The mediators were significantly increased in inflammatory conditions compared to normal conditions, an effect which was inhibited by ATG (10 and 100µM). ATG reduces contractions in SV and decreases the production of proinflammatory-proatherogenic mediators, setting the stage for further evaluating the effect of ATG in cardiovascular diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Positive Feedback Loops for Factor V and Factor VII Activation Supply Sensitivity to Local Surface Tissue Factor Density During Blood Coagulation

PubMed Central

Balandina, A.N.; Shibeko, A.M.; Kireev, D.A.; Novikova, A.A.; Shmirev, I.I.; Panteleev, M.A.; Ataullakhanov, F.I.

2011-01-01

Blood coagulation is triggered not only by surface tissue factor (TF) density but also by surface TF distribution. We investigated recognition of surface TF distribution patterns during blood coagulation and identified the underlying molecular mechanisms. For these investigations, we employed 1), an in vitro reaction-diffusion experimental model of coagulation; and 2), numerical simulations using a mathematical model of coagulation in a three-dimensional space. When TF was uniformly immobilized over the activating surface, the clotting initiation time in normal plasma increased from 4 min to >120 min, with a decrease in TF density from 100 to 0.7 pmol/m2. In contrast, surface-immobilized fibroblasts initiated clotting within 3–7 min, independently of fibroblast quantity and despite a change in average surface TF density from 0.5 to 130 pmol/m2. Experiments using factor V-, VII-, and VIII-deficient plasma and computer simulations demonstrated that different responses to these two TF distributions are caused by two positive feedback loops in the blood coagulation network: activation of the TF–VII complex by factor Xa, and activation of factor V by thrombin. This finding suggests a new role for these reactions: to supply sensitivity to local TF density during blood coagulation. PMID:22004734

Development of the National Transplant Program Has Significantly Decreased but Not Ended Transplant Tourism in Montenegro.

PubMed

Ratkovic, M; Basic Jukic, N; Kastelan, Z; Radunovic, D; Kavaric, P; Brezak, J; Topalovic Grkovic, M; Hudolin, T; Prelevic, V

2018-06-01

Organ transplantation has prolonged and improved the lives of many patients around the world. However, a widespread shortage of donors remains the main factor that has led to organ trafficking and transplant tourism. To stop transplant tourism and to provide optimal treatment for its citizens with end-stage renal disease, Montenegro started performing renal transplantations in September 2012. Thirty-five transplantations have been performed since that time, 34 from living donors and only 1 from a deceased donor. This practice has significantly decreased but not ended transplant tourism in Montenegro. Copyright © 2018 Elsevier Inc. All rights reserved.

Characteristics of Factors of Protozoa Blastocystis hominis Persistence.

PubMed

Potaturkina-Nesterova, N I; Il'ina, N A; Bugero, N V; Nesterov, A S

2016-10-01

Persistence activity manifested in the expression of anti-lysozyme, anti-lactoferrin, and antihistone factors promoting inactivation of natural anti-infection resistance factors in the body was revealed in Blastocystis hominis protozoa. Activities of these factors were ranged. The frequency of these factors in clinical isolates of blastocyst decreased in the following order: anti-lactoferrin activity (84.5±3.7%)→anti-lysozyme activity (64.8±5.7%)→anti-histone activity (48.1±2.3%). In healthy humans, the corresponding parameters were 7.3±1.3, 5.3±0.9, and 3.3±0.4%, respectively (p<0.05). It was shown that the studied activities in highly virulent blastocysts were higher than in groups of medium-, low-, and avirulent protozoa.