Assessment of postmenopausal women and significant risk factors for osteoporosis.

PubMed

Schnatz, Peter F; Marakovits, Kimberly A; O'Sullivan, David M

2010-09-01

The assessment of osteoporosis risk factors can help guide early intervention. The objective of this study was to analyze numerous potential risk factors to see which were associated with postmenopausal osteoporosis. Women aged 49 or greater presenting for dual-energy x-ray absorptiometry bone scans were recruited from radiology sites in the Hartford, Connecticut, area between January 2007 and March 2009, inclusive. Information was collected regarding primary and secondary risk factors for osteoporosis development, as well as family history and history of pregnancy and breast-feeding. Survey results were subsequently correlated with each woman's dual-energy x-ray absorptiometry scan results. In a sample of 619 women, history of fracture (odds ratio [OR], 12.49), weight less than 127 pounds (OR, 3.50), and use of anticoagulants (OR, 5.40) increased the chance of developing osteoporosis. In contrast, multiparity (OR, 0.45) and history of breast-feeding (OR, 0.38) decreased the development of osteoporosis in postmenopausal women. In women aged 49 to 54, breast-feeding was significantly protective, while low body mass index was most indicative of osteoporosis in women ages 55 to 64. Both previous fracture and low body mass index were associated with osteoporosis in women over age 64. The current results are consistent with other studies suggesting that previous fracture, low body weight, and use of anticoagulants increase the risk of osteoporosis. Our results also suggest that a history of pregnancy and breast-feeding protects against the development of postmenopausal osteoporosis, especially in women aged 49 to 54.

Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition

PubMed Central

Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

2017-01-01

Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown. Therefore, we examined the effects of TBT on the activity of transcription factors that control GluR2 expression. Exposure of primary cortical neurons to 20 nM TBT for 3 h to 9 days resulted in a decrease in GluR2 mRNA expression. Moreover, TBT inhibited the DNA binding activity of nuclear respiratory factor-1 (NRF-1), a transcription factor that positively regulates the GluR2. This result indicates that TBT inhibits the activity of NRF-1 and subsequently decreases GluR2 expression. In addition, 20 nM TBT decreased the expression of genes such as cytochrome c, cytochrome c oxidase (COX) 4, and COX 6c, which are downstream of NRF-1. Our results suggest that NRF-1 inhibition is an important molecular action of the neurotoxicity induced by low-concentration TBT. PMID:28800112

Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition.

PubMed

Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

2017-08-11

Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 ( GluR2 ) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown. Therefore, we examined the effects of TBT on the activity of transcription factors that control GluR2 expression. Exposure of primary cortical neurons to 20 nM TBT for 3 h to 9 days resulted in a decrease in GluR2 mRNA expression. Moreover, TBT inhibited the DNA binding activity of nuclear respiratory factor-1 (NRF-1), a transcription factor that positively regulates the GluR2 . This result indicates that TBT inhibits the activity of NRF-1 and subsequently decreases GluR2 expression. In addition, 20 nM TBT decreased the expression of genes such as cytochrome c, cytochrome c oxidase (COX) 4, and COX 6c, which are downstream of NRF-1. Our results suggest that NRF-1 inhibition is an important molecular action of the neurotoxicity induced by low-concentration TBT.

Frequent plateletpheresis does not clinically significantly decrease platelet counts in donors.

PubMed

Katz, Louis; Palmer, Kim; McDonnell, Emily; Kabat, Andy

2007-09-01

In October 2005, the US Food and Drug Administration (FDA) issued draft guidance on collecting platelets (PLTs) by automated methods. The FDA proposed limiting collections to 24 components, rather than 24 procedures, annually with up to 3 components per procedure. The rationale was from literature suggesting frequent PLT collection resulted in significant declines in donor PLT counts. Additional requirements for minimal interdonation intervals were proposed. Plateletpheresis records at a regional blood center with predonation PLT counts were used to assess the impact of the restriction on PLT collections. They were reviewed to demonstrate the effects of collection frequency, number of products collected, and interdonation interval on donor PLT counts. Total protein and albumin levels were compared in a subset of 24-times-per-year PLT donors and control whole-blood donors. A limit of 24 components would require replacement of approximately 20 percent of the donor base to recover lost components. No clinically important decrease in PLT counts before donation was seen in donors donating multiple PLT components up to 24 times per year, regardless of interdonation interval. No frequent donor was deferred for a PLT count less than 150 x 10(9) per L. Short interdonation intervals were associated with statistically but not clinically important decreases in PLT counts. Protein levels were not distinguishable between PLT donors and controls. The proposed restrictions are not required to prevent thrombocytopenia in frequent PLT donors and would adversely impact the supply of apheresis PLTs. Protein levels are maintained in these high-frequency donors.

Spleen stiffness is positively correlated with HVPG and decreases significantly after TIPS implantation.

PubMed

Buechter, Matthias; Manka, Paul; Theysohn, Jens M; Reinboldt, Marcus; Canbay, Ali; Kahraman, Alisan

2018-01-01

Transjugular intrahepatic portosystemic shunt (TIPS) is indicated in patients with decompensated portal hypertension (PH). Hepatic venous pressure gradient (HVPG) is considered gold standard for assessment of PH. Because HVPG measurement is invasive, non-invasive methods for evaluating severity of PH are warranted. We retrospectively correlated spleen stiffness as measured by FibroScan with HVPG in patients who underwent TIPS. Twenty-four patients with spleen stiffness measurement (SSM) one day before (D-1), one day after (D+1) and 28 days after TIPS (D+28) were included. SSM was positively correlated with pre-TIPS HVPG (HVPG <13mmHg, median SSM: 19.7±8.6kPa; HVPG 13-24mmHg, median SSM: 45.0±15.7kPa; HVPG >24mmHg, median SSM: 75.0±6.2kPa; p<0.05]; r 2 =0.72; p<0.001) and decreased significantly after TIPS implantation (D-1, median SSM: 67.1±17.3kPa; D+1, median SSM: 44.7±18.5kPa; D+28, median SSM: 35.6±17.0kPa; p<0.05), while liver stiffness measurement decrease was not statistically significant. Our study highlights the utility of SSM as non-invasive tool in patients with chronic liver disease in evaluating degree of PH potentially offering a confirmable additional parameter in surveillance of patients undergoing TIPS procedure. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice

PubMed Central

2011-01-01

Exogenous administration of insulin-like growth factor (IGF)-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF) while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng) was administered intracerebroventricularly (i.c.v.) to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng). Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST). Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß), tumor necrosis factor-(TNF)α, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP). Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior. PMID:21306618

Implementation of a Multidisciplinary Bleeding and Transfusion Protocol Significantly Decreases Perioperative Blood Product Utilization and Improves Some Bleeding Outcomes.

PubMed

Timpa, Joseph G; O'Meara, L Carlisle; Goldberg, Kellen G; Phillips, Jay P; Crawford, Jack H; Jackson, Kimberly W; Alten, Jeffrey A

2016-03-01

Perioperative transfusion of blood products is associated with increased morbidity and mortality after pediatric cardiac surgery. We report the results of a quality improvement project aimed at decreasing perioperative blood product administration and bleeding after pediatric cardiopulmonary bypass (CPB) surgery. A multidisciplinary team evaluated baseline data from 99 consecutive CPB patients, focusing on the variability in transfusion management and bleeding outcomes, to create a standardized bleeding and transfusion management protocol. A total of 62 subsequent patients were evaluated after implementation of the protocol: 17 with single pass hemoconcentrated (SPHC) blood transfusion and 45 with modified ultrafiltration (MUF). Implementation of the protocol with SPHC blood led to significant decrease in transfusion of every blood product in the cardiovascular operating room and first 6 hours in cardiovascular intensive care unit ([CVICU] p < .05). Addition of MUF to the protocol led to further decrease in transfusion of all blood products compared to preprotocol. Patients <2 months old had 49% decrease in total blood product administration: 155 mL/kg preprotocol, 117 mL/kg protocol plus SPHC, and 79 mL/kg protocol plus MUF (p < .01). There were significant decreases in postoperative bleeding in the first hour after CVICU admission: 6 mL/kg preprotocol, 3.8 mL/kg protocol plus SPHC, and 2 mL/kg protocol plusMUF (p = .02). There was also significantly decreased incidence of severe postoperative bleeding (>10 mL/kg) in the first CVICU hour for protocol plus MUF patients (p < .01). Implementation of a multidisciplinary bleeding and transfusion protocol significantly decreases perioperative blood product transfusion and improves some bleeding outcomes.

Change in kidney function after unilateral adrenalectomy in patients with primary aldosteronism: identification of risk factors for decreased kidney function.

PubMed

Kim, Il Young; Park, In Seong; Kim, Min Jeong; Han, Miyeun; Rhee, Harin; Seong, Eun Young; Lee, Dong Won; Lee, Soo Bong; Kwak, Ihm Soo; Song, Sang Heon; Chung, Hyun Chul

2018-05-19

Glomerular filtration rate (GFR) has been reported to decrease after unilateral adrenalectomy in patients with primary aldosteronism (PA). The aim of this study was to identify clinical predictors for decreased GFR after adrenalectomy in patients with PA. The records of 187 patients (98 patients with PA and 89 with non-PA adrenal disease) who were followed up for at least 6 months after unilateral adrenalectomy were retrospectively analyzed. Estimated GFR (eGFR) was investigated at 1, 3, and 6 months postoperatively. Preoperative risk factors for eGFR% decline at 1 month ([preoperative eGFR-eGFR at 1 month]/preoperative eGFR × 100) and postoperative CKD development were investigated. The eGFR decreased significantly at 1 month and remained stable in the PA group. However, there were no significant changes in eGFR in the non-PA group over the 6-month period. In the PA group, a high preoperative eGFR and high aldosterone to renin ratio (ARR) were independently associated with eGFR% decline at 1 month. In patients with PA but without preoperative CKD (n = 68), a low preoperative eGFR and high ARR were independent risk factors for developing postoperative CKD. The best preoperative cut-off values of eGFR and ARR for predicting the development of postoperative CKD were ≤ 102 ml/min/1.73 m 2 and ≥ 448 ng/dl:ng/ml/h, respectively. Renal function deteriorated significantly after unilateral adrenalectomy in patients with PA. Clinicians must pay attention to postoperative renal function in PA patients at elevated risk of developing decreased kidney function.

Decreased importance of environmental risk factors for childhood asthma from 1996 to 2006.

PubMed

Bjerg, A; Hedman, L; Perzanowski, M; Wennergren, G; Lundbäck, B; Rönmark, E

2015-01-01

The large increase in asthma prevalence continues in several, but not all areas. Despite the individual risk factors that have been identified, the reasons for the observed trends in prevalence are largely unknown. This study sought to characterize what trends in risk factors accompanied trends in asthma prevalence. Two population-based cohorts of 7- to 8-year-old children from the same Swedish study areas examined by expanded International Study of Asthma and Allergy in Childhood questionnaires were compared 10 years apart. In 1996 and 2006, 3430 (97% participation) and 2585 (96% participation) questionnaires were completed, respectively. A subset was skin-prick-tested: in 1996 and 2006, 2148 (88% participation) and 1700 (90% participation) children, respectively. The adjusted population-attributable fraction (aPAF) was calculated using the prevalence and multivariate odds ratio of each risk factor. The prevalence of current asthma and wheeze was similar in 1996 and 2006. Allergic sensitization, however, increased from 21% to 30%. The prevalence of parental asthma increased from 17% to 24%, while respiratory infections and maternal smoking decreased (60% to 29% and 32% to 16%, respectively). The aPAFs of non-environmental risk factors for current asthma increased in 1996-2006: allergic sensitization from 35% to 41%, parental asthma from 27% to 45% and male sex from 20% to 25%. Conversely, the aPAFs of environmental risk factors decreased: respiratory infections from 36% to 32% and damp home and maternal smoking from 14% and 19%, respectively, to near zero in 2006. From 1996 to 2006, the non-environmental risk factors parental asthma, allergic sensitization and male sex had an increasing or constant importance for current asthma in 7- to 8-year-old children. The importance of the environmental exposures damp home, respiratory infections and maternal smoking decreased. This counterbalancing in risk factors may explain the level of prevalence of current asthma. �

L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells.

PubMed

Mobarak, Halimeh; Fathi, Ezzatollah; Farahzadi, Raheleh; Zarghami, Nosratollah; Javanmardi, Sara

2017-03-01

Mesenchymal stem cells are undifferentiated cells that have the ability to divide continuously and tissue regeneration potential during the transplantation. Aging and loss of cell survival, is one of the main problems in cell therapy. Since the production of free radicals in the aging process is effective, the use of antioxidant compounds can help in scavenging free radicals and prevent the aging of cells. The aim of this study is evaluate the effects of L-carnitine (LC) on proliferation and aging of rat adipose tissue-derived mesenchymal stem cells (rADSC). rADSCs were isolated from inguinal region of 5 male Rattus rats. Oil red-O, alizarin red-S and toluidine blue staining were performed to evaluate the adipogenic, osteogenic and chondrogenic differentiation of rADSCs, respectively. Flow cytometric analysis was done for investigating the cell surface markers. The methyl thiazol tetrazolium (MTT) method was used to determine the cell proliferation of rADSCs following exposure to different concentrations of LC. rADSCs aging was evaluated by beta-galactosidase staining. The results showed significant proliferation of rADSCs 48 h after treatment with concentrations of 0.2 mM LC. In addition, in the presence of 0.2 mM LC, rADSCs appeared to be growing faster than control group and 0.2 mM LC supplementation could significantly decrease the population doubling time and aging of rADSCs. It seems that LC would be a good antioxidant to improve lifespan of rADSCs due to the decrease in aging.

Psoriasis is associated with decreased plasma adiponectin levels independently of cardiometabolic risk factors

PubMed Central

Li, R. C.; Krishnamoorthy, P.; DerOhannessian, S.; Doveikis, J.; Wilcox, M.; Thomas, P.; Rader, D. J.; Reilly, M. P.; Voorhees, A. Van; Gelfand, J. M.; Mehta, N. N.

2013-01-01

Summary Background Psoriasis is an inflammatory skin disease that may be associated with an adverse cardiometabolic profile including modulated plasma adiponectin and leptin levels. Whether these levels are independent of cardiometabolic risk factors, which are also prevalent in psoriasis, is not known. Methods A consecutive sample of 122 participants with varying degrees of psoriasis severity, and a random sample of 134 participants without psoriasis were recruited for this case–control study. Cardiometabolic risk factors including traditional cardiovascular risk factors, waist circumference, insulin resistance, and total plasma adiponectin and leptin were measured. Total plasma adiponectin and leptin levels were compared in unadjusted and adjusted analyses by psoriasis status. Results Participants with psoriasis had mostly mild disease and were mainly on topical therapies, but still had a more adverse cardiometabolic profile compared with those without psoriasis. Furthermore, plasma adiponectin levels were significantly lower in participants with psoriasis than those without {7.13 µg/mL [interquartile range (IQR) 4.9–11.3) vs. 14.5 µg/mL (IQR 8.4–24.1); P < 0.001]}. Plasma leptin (ng/mL) levels were higher in the psoriasis group but this did not reach statistical significance [11.3 (IQR 6.4–21.8) vs. 9.8 (IQR 4.9–20.5); P = 0.07]. In multivariable modelling, plasma adiponectin levels were still negatively associated with psoriasis status after adjusting for waist size (% difference = −41.2%, P < 0.001), insulin resistance (% difference = −39.5%, P < 0.001) and both waist size and insulin resistance (% difference = −38.5%, P < 0.001) Conclusion Plasma levels of adiponectin were lower in psoriasis, and this relationship persisted after adjusting for cardiometabolic risk factors known to decrease adiponectin levels. These findings suggest that inflammation present in psoriasis may be associated with adipose tissue dysfunction; however, direct

Bundling of Reimbursement for Inferior Vena Cava Filter Placement Resulted in Significantly Decreased Utilization between 2012 and 2014.

PubMed

Glocker, Roan J; TerBush, Matthew J; Hill, Elaine L; Guido, Joseph J; Doyle, Adam; Ellis, Jennifer L; Raman, Kathleen; Morrow, Gary R; Stoner, Michael C

2017-01-01

On January 1, 2012, reimbursement for inferior vena cava filters (IVCFs) became bundled by the Centers for Medicare and Medicaid Services. This resulted in ICVF placement (CPT code 37191) now yielding 4.71 relative value units (RVUs), a decrease from 15.6 RVUs for placement and associated procedures (CPT codes 37620, 36010, 75825-26, 75940-26). Our hypothesis was that IVCF utilization would decrease in response to this change as other procedures had done once they had become bundled. Including data from 2010 to 2011 (before bundling) and 2012 to 2014 (after bundling), we utilized 5% inpatient, outpatient, and carrier files of Medicare limited data sets and analyzed IVCF utilization before and after bundling across specialty types, controlling for total diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) (ICD-9 codes 453.xx and 415.xx, respectively) and placement location. In 2010 and 2011, the rates/10,000 DVT/PE diagnoses were 918 and 1,052, respectively (average 985). In 2012, 2013, and 2014, rates were 987, 877, and 605, respectively (average 823). Comparing each year individually, there is a significant difference (P < 0.0001) with 2012, 2013, and 2014 having lower rates of ICVF utilization. Comparing averages in the 2010-2011 and 2012-2014 groups, there is also a significant decrease in utilization after bundling (P < 0.0001). Following the bundling of reimbursement for IVCF placement, procedural utilization decreased significantly. More data from subsequent years will be needed to show if this decrease utilization continues to persist. Copyright © 2016 Elsevier Inc. All rights reserved.

Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Cross, Janet V; Engle, Randall; Aragón-Flores, Mariana; Gómez-Garza, Gilberto; Jewells, Valerie; Medina-Cortina, Humberto; Solorio, Edelmira; Chao, Chih-Kai; Zhu, Hongtu; Mukherjee, Partha S; Ferreira-Azevedo, Lara; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

2013-01-01

Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA) children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children). We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1) and/or inflammatory mediators in MCMA children. Thirty gram of dark cocoa with 680 mg of total flavonols were given daily for 10.11 ± 3.4 days (range 9-24 days) to 18 children (10.55 years, SD = 1.45; 11F/7M). Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p = 0.0002). Fifteen children (83%) showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter (PM) and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer's and Parkinson's diseases.

Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children

PubMed Central

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Cross, Janet V.; Engle, Randall; Aragón-Flores, Mariana; Gómez-Garza, Gilberto; Jewells, Valerie; Weili, Lin; Medina-Cortina, Humberto; Solorio, Edelmira; Chao, Chih-kai; Zhu, Hongtu; Mukherjee, Partha S.; Ferreira-Azevedo, Lara; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

2013-01-01

Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA) children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children). We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1) and/or inflammatory mediators in MCMA children. Thirty gram of dark cocoa with 680 mg of total flavonols were given daily for 10.11 ± 3.4 days (range 9–24 days) to 18 children (10.55 years, SD = 1.45; 11F/7M). Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p = 0.0002). Fifteen children (83%) showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter (PM) and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer's and Parkinson's diseases. PMID:23986703

Removal of the blue component of light significantly decreases retinal damage after high intensity exposure.

PubMed

Vicente-Tejedor, Javier; Marchena, Miguel; Ramírez, Laura; García-Ayuso, Diego; Gómez-Vicente, Violeta; Sánchez-Ramos, Celia; de la Villa, Pedro; Germain, Francisco

2018-01-01

Light causes damage to the retina (phototoxicity) and decreases photoreceptor responses to light. The most harmful component of visible light is the blue wavelength (400-500 nm). Different filters have been tested, but so far all of them allow passing a lot of this wavelength (70%). The aim of this work has been to prove that a filter that removes 94% of the blue component may protect the function and morphology of the retina significantly. Three experimental groups were designed. The first group was unexposed to light, the second one was exposed and the third one was exposed and protected by a blue-blocking filter. Light damage was induced in young albino mice (p30) by exposing them to white light of high intensity (5,000 lux) continuously for 7 days. Short wavelength light filters were used for light protection. The blue component was removed (94%) from the light source by our filter. Electroretinographical recordings were performed before and after light damage. Changes in retinal structure were studied using immunohistochemistry, and TUNEL labeling. Also, cells in the outer nuclear layer were counted and compared among the three different groups. Functional visual responses were significantly more conserved in protected animals (with the blue-blocking filter) than in unprotected animals. Also, retinal structure was better kept and photoreceptor survival was greater in protected animals, these differences were significant in central areas of the retina. Still, functional and morphological responses were significantly lower in protected than in unexposed groups. In conclusion, this blue-blocking filter decreases significantly photoreceptor damage after exposure to high intensity light. Actually, our eyes are exposed for a very long time to high levels of blue light (screens, artificial light LED, neons…). The potential damage caused by blue light can be palliated.

Neonatal manipulation of oxytocin prevents lipopolysaccharide-induced decrease in gene expression of growth factors in two developmental stages of the female rat.

PubMed

Bakos, Jan; Lestanova, Zuzana; Strbak, Vladimir; Havranek, Tomas; Bacova, Zuzana

2014-10-01

Oxytocin production and secretion is important for early development of the brain. Long-term consequences of manipulation of oxytocin system might include changes in markers of brain plasticity - cytoskeletal proteins and neurotrophins. The aim of the present study was (1) to determine whether neonatal oxytocin administration affects gene expression of nestin, microtubule-associated protein-2 (MAP-2), brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of two developmental stages of rat and (2) to evaluate whether neonatal oxytocin administration protects against lipopolysaccharide (LPS) induced inflammation. Neonatal oxytocin did not prevent a decrease of body weight in the LPS treated animals. Oxytocin significantly increased gene expression of BDNF in the right hippocampus in 21-day and 2-month old rats of both sexes. Gene expression of NGF and MAP-2 significantly increased in males treated with oxytocin. Both, growth factors and intermediate filament-nestin mRNA levels, were reduced in females exposed to LPS. Oxytocin treatment prevented a decrease in the gene expression of only growth factors. In conclusion, neonatal manipulation of oxytocin has developmental and sex-dependent effect on markers of brain plasticity. These results also indicate, that oxytocin may be protective against inflammation particularly in females. Copyright © 2014 Elsevier Ltd. All rights reserved.

Psychosocial factors and tooth wear with a significant component of attrition.

PubMed

da Silva, A M; Oakley, D A; Hemmings, K W; Newman, H N; Watkins, S

1997-06-01

Pathological tooth wear is often associated with bruxism, which appears in turn to be influenced by psychosocial factors. This study investigated putative relationships between psychosocial factors (total and average perceived stress, state and trait anxiety) and tooth wear, comparing 45 patients exhibiting tooth wear with a significant component of attrition to 45 controls. Groups were matched for gender and age. Subjects completed the Modified and Perceived Stress Scale and the State-Trait Anxiety Inventory. A between-groups multivariate analysis of variance indicated that the two groups did not differ significantly on the combined psychosocial factors, F(4,85) = 1.16, P > 0.05. However, a univariate F-test showed that tooth-wear patients presented significantly more trait anxiety than controls, F(1,88) = 4.15, P < 0.05. Further research is indicated to clarify the importance of trait anxiety and other psychosocial factors in the progression of tooth wear with a significant component of attrition.

Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.

PubMed

Lloyd, Steven A; Corkill, Beau; Bruster, Matthew C; Roberts, Rick L; Shanks, Ryan A

2017-07-01

Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Decreased serum fibroblast growth factor - 2 levels in pre- and post-treatment patients with major depressive disorder.

PubMed

He, Shen; Zhang, Tianhong; Hong, Bo; Peng, Daihui; Su, Hui; Lin, Zhiguang; Fang, Yiru; Jiang, Kaida; Liu, Xiaohua; Li, Huafang

2014-09-05

Increasing evidence indicates that neurotrophic factor dysfunction might be involved in the pathophysiology and treatment of major depressive disorder (MDD). Fibroblast growth factor (FGF)-2, one of the major neurotrophins, plays an important role in the central nervous system (CNS). The aim of this study was to explore whether the FGF-2 in serum was associated with MDD and to evaluate the effects of antidepressant treatment on serum FGF-2 levels. Serum FGF-2 levels were determined in 28 pre- and post-treatment MDD patients and 30 healthy controls using ELISA. The results of the current study revealed that serum FGF-2 levels in MDD patients were significantly lower than those in healthy controls (p=0.005), and the serum FGF-2 levels decreased significantly but marginally following treatment for 8 weeks (p=0.005). These findings demonstrate that the lower serum FGF-2 levels contribute to the pathophysiology of MDD and that FGF-2 may be used as a peripheral biological marker for MDD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Risk factors for decreased range of motion and poor outcomes in open periarticular elbow fractures.

PubMed

Dickens, Jonathan F; Wilson, Kevin W; Tintle, Scott M; Heckert, Reed; Gordon, Wade T; D'Alleyrand, Jean-Claude G; Potter, Benjamin K

2015-04-01

The purpose of this study was to identify risk factors present at the time of injury that predict poor functional outcomes and heterotopic ossification (HO) in open periarticular elbow fractures. We performed a retrospective review of 136 combat-related open elbow fractures from 2003 to 2010. Patient demographics, injury characteristics, treatment variables, and complications were recorded. Functional outcomes were analyzed to determine range of motion (ROM) and Mayo Elbow Performance Score (MEPS). Secondary outcome measures included the development of HO, return to duty, and revision operation. At a median 2.7 years from injury the median MEPS was 67.8 (range 30-100) with an average ulnohumeral arc motion of 89°. Bipolar fractures, with periarticular fractures on both sides of the elbow and at least one side containing intra-articular extension, were independently associated with decreased ulnohumeral motion (p=0.02) and decreased MEPS (p<0.004). Additional independent risk factors for decreased ROM included more severe osseous comminution (p=0.001), and increased time to definitive fixation (p=0.03) and HO (p=0.02). More severe soft tissue injury (Gustilo and Anderson fracture type, p=0.02), peripheral nerve injury (p=0.04), and HO (p=0.03) were independently associated with decreased MEPS. HO developed in 65% (89/136) of extremities and was associated with more severe Orthopaedic Trauma Association (OTA) fracture type (p=0.01) and escalating Gustilo and Anderson fracture classification (p=0.049). In the largest series of open elbow fractures, we identified risk factors that portend a poor clinical outcome and decreased ROM. Bipolar elbow fractures, which have not previously been associated with worse results, are particularly prone to decreased ROM and worse outcomes. Prognostic level IV. Published by Elsevier Ltd.

Factors associated with menstrual irregularities and decreased bone mineral density in female athletes.

PubMed

Fruth, S J; Worrell, T W

1995-07-01

Menstrual irregularities occur in some female athletes. The most extreme form of menstrual irregularity is amenorrhea, which has been linked to significant decreases in vertebral bone density and increases in injury prevalence. Many authors have sought to determine the causal factors of athletic amenorrhea, some of which include hormonal status, training and physical parameters, nutritional balance, and psychological stress. The purpose of this paper was to compare studies that have examined the relationship of these variables to menstrual irregularities and bone density. Controversy exists regarding the relative contribution of these variables. The etiology is likely multifactorial and should be evaluated as such. Clinicians treating female athletes must be knowledgeable about the negative consequences associated with menstrual irregularities. Furthermore, it is critical that clinicians provide thorough patient education in order to prevent injuries and the long-term loss of bone density. Appropriate medical and/or psychological referral of the athlete with menstrual irregularities may be necessary.

Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells

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

Liu, Yanlong; Department of Medicine, University of Louisville, Louisville, KY; Wang, Chunhong

2012-10-15

Fibroblast growth factor-21 (FGF21) is a potential metabolic regulator with multiple beneficial effects on metabolic diseases. FGF21 is mainly expressed in the liver, but is also found in other tissues including the intestine, which expresses β-klotho abundantly. The intestine is a unique organ that operates in a physiologically hypoxic environment, and is responsible for the fat absorption processes including triglyceride breakdown, re-synthesis and absorption into the portal circulation. In the present study, we investigated the effects of hypoxia and the chemical hypoxia inducer, cobalt chloride (CoCl{sub 2}), on FGF21 expression in Caco-2 cells and the consequence of fat accumulation. Physicalmore » hypoxia (1% oxygen) and CoCl{sub 2} treatment decreased both FGF21 mRNA and secreted protein levels. Gene silence and inhibition of hypoxia-inducible factor-α (HIFα) did not affect the reduction of FGF21 mRNA and protein levels by hypoxia. However, CoCl{sub 2} administration caused a significant increase in oxidative stress. The addition of n-acetylcysteine (NAC) suppressed CoCl{sub 2}-induced reactive oxygen species (ROS) formation and completely negated CoCl{sub 2}-induced FGF21 loss. mRNA stability analysis demonstrated that the CoCl{sub 2} administration caused a remarkable reduction in FGF21 mRNA stability. Furthermore, CoCl{sub 2} increased intracellular triglyceride (TG) accumulation, along with a reduction in mRNA levels of lipid lipase, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), and an increase of sterol regulatory element-binding protein-1c (SREBP1c) and stearoyl-coenzyme A (SCD1). Addition of both NAC and recombinant FGF21 significantly attenuated the CoCl{sub 2}-induced TG accumulation. In conclusion, the decrease of FGF21 in Caco-2 cells by chemical hypoxia is independent of HIFα, but dependent on an oxidative stress-mediated mechanism. The regulation of FGF21 by hypoxia may contribute to intestinal lipid metabolism and

Inhibition of Myocardin-Related Transcription Factor/Serum Response Factor Signaling Decreases Lung Fibrosis and Promotes Mesenchymal Cell Apoptosis

PubMed Central

Sisson, Thomas H.; Ajayi, Iyabode O.; Subbotina, Natalya; Dodi, Amos E.; Rodansky, Eva S.; Chibucos, Lauren N.; Kim, Kevin K.; Keshamouni, Venkateshwar G.; White, Eric S.; Zhou, Yong; Higgins, Peter D.R.; Larsen, Scott D.; Neubig, Richard R.; Horowitz, Jeffrey C.

2016-01-01

Myofibroblasts are crucial to the pathogenesis of tissue fibrosis. Their formation of stress fibers results in the release of myocardin-related transcription factor (MRTF), a transcriptional coactivator of serum response factor (SRF). MRTF-A (Mkl1)-deficient mice are protected from lung fibrosis. We hypothesized that the SRF/MRTF pathway inhibitor CCG-203971 would modulate myofibroblast function in vitro and limit lung fibrosis in vivo. Normal and idiopathic pulmonary fibrosis lung fibroblasts were treated with/without CCG-203971 (N-[4-chlorophenyl]-1-[3-(2-furanyl)benzoyl]-3-piperidine carboxamide) and/or Fas-activating antibody in the presence/absence of transforming growth factor (TGF)-β1, and apoptosis was assessed. In vivo studies examined the effect of therapeutically administered CCG-203971 on lung fibrosis in two distinct murine models of fibrosis induced by bleomycin or targeted type II alveolar epithelial injury. In vitro, CCG-203971 prevented nuclear localization of MRTF-A; increased the apoptotic susceptibility of normal and idiopathic pulmonary fibrosis fibroblasts; blocked TGF-β1–induced myofibroblast differentiation; and inhibited TGF-β1–induced expression of fibronectin, X-linked inhibitor of apoptosis, and plasminogen activator inhibitor-1. TGF-β1 did not protect fibroblasts or myofibroblasts from apoptosis in the presence of CCG-203971. In vivo, CCG-203971 significantly reduced lung collagen content in both murine models while decreasing alveolar plasminogen activator inhibitor-1 and promoting myofibroblast apoptosis. These data support a central role of the SRF/MRTF pathway in the pathobiology of lung fibrosis and suggest that its inhibition can help resolve lung fibrosis by promoting fibroblast apoptosis. PMID:25681733

Decreased Epidermal Growth Factor (EGF) Associated with HMGB1 and Increased Hyperactivity in Children with Autism

PubMed Central

Russo, Anthony J.

2013-01-01

Background Autism spectrum disorders (ASDs), characterized by impaired social interactions and deficits in verbal and nonverbal communication, are thought to affect 1 in 88 children in the United States. There is much support for the role of growth factors in the etiology of autism. Recent research has shown that epithelial growth factor (EGF) is decreased in young autistic children (2–4 years of age). This study was designed to determine plasma levels of EGF in an older group of autistic children (mean age 10.6 years) and to correlate these EGF levels with putative biomarkers HGF, uPA, uPAR, GAD2, MPO GABA, and HMGB1, as well as symptom severity of 19 different symptoms. Subjects and methods Plasma from 38 autistic children, 11 children with pervasive developmental disorder (PDD-NOS) and 40 neurotypical, age and gender similar controls was assessed for EGF concentration using ELISAs. Severity of 19 symptoms (awareness, expressive language, receptive language, (conversational) pragmatic language, focus/attention, hyperactivity, impulsivity, perseveration, fine motor skills, gross motor skills, hypotonia (low muscle tone), tiptoeing, rocking/pacing, stimming, obsessions/fixations, eye contact, sound sensitivity, light sensitivity, and tactile sensitivity) was assessed and then compared to EGF concentrations. Results In this study, we found EGF levels in autistic children and those with PDD-NOS to be significantly lower when compared with neurotypical controls. EGF levels correlated with HMGB1 levels but not the other tested putative biomarkers, and EGF correlated negatively with hyperactivity, gross motor skills, and tiptoeing but not other symptoms. Conclusions These results suggest an association between decreased plasma EGF levels and selected symptom severity. We also found a strong correlation between plasma EGF and HMGB1, suggesting inflammation is associated with decreased EGF. PMID:23645980

Significant Factors Related to Failed Pediatric Dental General Anesthesia Appointments at a Hospital-based Residency Program.

PubMed

Emhardt, John R; Yepes, Juan F; Vinson, LaQuia A; Jones, James E; Emhardt, John D; Kozlowski, Diana C; Eckert, George J; Maupome, Gerardo

2017-05-15

The purposes of this study were to: (1) evaluate the relationship between appointment failure and the factors of age, gender, race, insurance type, day of week, scheduled time of surgery, distance traveled, and weather; (2) investigate reasons for failure; and (3) explore the relationships between the factors and reasons for failure. Electronic medical records were accessed to obtain data for patients scheduled for dental care under general anesthesia from May 2012 to May 2015. Factors were analyzed for relation to appointment failure. Data from 3,513 appointments for 2,874 children were analyzed. Bivariate associations showed statistically significant (P<0.05) relationships between failed appointment and race, insurance type, scheduled time of surgery, distance traveled, snowfall, and temperature. Multinomial regression analysis showed the following associations between factors and the reason for failure (P<0.05): (1) decreased temperature and increased snowfall were associated with weather as reason for failure; (2) the African American population showed an association with family barriers; (3) Hispanic families were less likely to give advanced notice; and (4) the "additional races" category showed an association with fasting violation. Patients who have treatment under general anesthesia face specific barriers to care.

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients.

PubMed

Maruyama, Noriaki; Otsuki, Tomoyasu; Yoshida, Yoshinori; Nagura, Chinami; Kitai, Maki; Shibahara, Nami; Tomita, Hyoe; Maruyama, Takashi; Abe, Masanori

2018-06-06

Serum phosphate and vitamin D receptor activator regulate fibroblast growth factor 23 (FGF23), and iron may modulate FGF23 metabolism. The aim of the present study was to elucidate the effects of ferric citrate hydrate and lanthanum carbohydrate on serum FGF23 levels in hemodialysis patients. This prospective, open-label, multicenter study enrolled 60 patients on hemodialysis treated with lanthanum carbonate. Patients were randomly assigned to 2 groups: those switching from lanthanum carbonate to ferric citrate hydrate (ferric citrate group, n = 30) or those continuing lanthanum carbonate (control group, n = 30). Patients were monitored for 24 weeks. Endpoints included changes in FGF23, phosphate, and the dose of erythropoiesis stimulating agent (ESA), erythropoietin responsiveness index (ERI), and adverse events. FGF-23 levels were significantly lower in the ferric citrate group compared with the levels in the control group (change from baseline -6,160 vs. -1,118 pg/mL; p = 0.026). There were no significant changes in serum calcium, phosphate, and intact parathyroid hormone levels in either group. The ferric citrate group had significantly increased serum iron, ferritin, and transferrin saturation. Hemoglobin levels were significantly elevated, and the dose of ESA was significantly decreased in the ferric citrate group but not in the control group. ERI and the dose of intravenous saccharated ferric oxide were significantly lower in the ferric citrate group compared with those of the control group (p = 0.015 and p = 0.002). In patients on hemodialysis, 24-week treatment with ferric citrate hydrate resulted in significant reduction in FGF23 and ERI independently of serum phosphate level. © 2018 S. Karger AG, Basel.

48 CFR 815.304 - Evaluation factors and significant subfactors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Evaluation factors and significant subfactors. 815.304 Section 815.304 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Source Selection 815.304...

48 CFR 315.304 - Evaluation factors and significant subfactors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Evaluation factors and significant subfactors. 315.304 Section 315.304 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Source Selection 315.304...

48 CFR 15.304 - Evaluation factors and significant subfactors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Evaluation factors and significant subfactors. 15.304 Section 15.304 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Source Selection 15.304...

Cochlear Pericytes Are Capable of Reversibly Decreasing Capillary Diameter In Vivo After Tumor Necrosis Factor Exposure.

PubMed

Bertlich, Mattis; Ihler, Friedrich; Weiss, Bernhard G; Freytag, Saskia; Strupp, Michael; Canis, Martin

2017-12-01

The aim of this work was to evaluate the effect of tumor necrosis factor (TNF) and its neutralization with etanercept on the capability of cochlear pericytes to alter capillary diameter in the stria vascularis. Twelve Dunkin-Hartley guinea pigs were randomly assigned to one of three groups. Each group was treated either with placebo and then placebo, TNF and then placebo, or TNF and then etanercept. Cochlear pericytes were visualized using diaminofluorescein-2-diacetate and intravasal blood flow by fluorescein-dextrane. Vessel diameter at sites of pericyte somas and downstream controls were quantified by specialized software. Values were obtained before treatment, after first treatment with tumor necrosis factor or placebo and after second treatment with etanercept or placebo. Overall, 199 pericytes in 12 animals were visualized. After initial treatment with TNF, a significant decrease in vessel diameter at sites of pericyte somas (3.6 ±4.3%, n = 141) compared with placebo and downstream controls was observed. After initial treatment with TNF, the application of etanercept caused a significant increase (3.3 ±5.5%, n = 59) in vessel diameter at the sites of pericyte somata compared with placebo and downstream controls. We have been able to show that cochlear pericytes are capable of reducing capillary diameter after exposition to TNF. Moreover, the reduction in capillary diameter observed after the application of TNF is revertible after neutralization of tumor necrosis factor by the application of etanercept. It seems that contraction of cochlear pericytes contributes to the regulation of cochlear blood flow.

Sepsis-Induced Coagulation in the Baboon Lung Is Associated with Decreased Tissue Factor Pathway Inhibitor

PubMed Central

Tang, Haiwang; Ivanciu, Lacramioara; Popescu, Narcis; Peer, Glenn; Hack, Erik; Lupu, Cristina; Taylor, Fletcher B.; Lupu, Florea

2007-01-01

Increased tissue factor (TF)-dependent procoagulant activity in sepsis may be partly due to decreased expression or function of tissue factor pathway inhibitor (TFPI). To test this hypothesis, baboons were infused with live Escherichia coli and sacrificed after 2, 8, or 24 hours. Confocal and electron microscopy revealed increased leukocyte infiltration and fibrin deposition in the intravascular and interstitial compartments. Large amounts of TF were detected by immunostaining in leukocytes and platelet-rich microthrombi. TF induction was documented by quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and coagulation assays. Lung-associated TFPI antigen and mRNA decreased during sepsis, and TFPI activity diminished abruptly at 2 hours. Blocking antibodies against TFPI increased fibrin deposition in septic baboon lungs, suggesting that TF-dependent coagulation might be aggravated by reduced endothelial TFPI. Decreased TFPI activity coincided with the release of tissue plasminogen activator and the peak of plasmin generation, suggesting that TFPI could undergo proteolytic inactivation by plasmin. Enhanced plasmin produced in septic baboons by infusion of blocking antibodies against plasminogen activator inhibitor-1 led to decreased lung-associated TFPI and unforeseen massive fibrin deposition. We conclude that activation of TF-driven coagulation not adequately countered by TFPI may underlie the widespread thrombotic complications of sepsis. PMID:17640967

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

PubMed Central

Kicic, Anthony; Hallstrand, Teal S.; Sutanto, Erika N.; Stevens, Paul T.; Kobor, Michael S.; Taplin, Christopher; Paré, Peter D.; Beyer, Richard P.; Stick, Stephen M.; Knight, Darryl A.

2010-01-01

Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from children with asthma fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n = 36), healthy atopic control subjects (n = 23), and healthy nonatopic control subjects (n = 53) were investigated by microarray, gene expression and silencing, transcript regulation analysis, and ability to close mechanical wounds. Measurements and Main Results: Time to repair a mechanical wound in vitro by AEC from healthy and atopic children was not significantly different and both were faster than AEC from children with asthma. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by quantitative polymerase chain reaction and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in nonasthmatic AEC inhibited wound repair, whereas addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5′, 2′deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells. PMID:20110557

Foot-and-mouth disease virus leader proteinase inhibits dsRNA-induced type I interferon transcription by decreasing interferon regulatory factor 3/7 in protein levels

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

Wang, Dang; Fang, Liurong; Luo, Rui

2010-08-13

Research highlights: {yields} FMDV L{sup pro} inhibits poly(I:C)-induced IFN-{alpha}1/{beta} mRNA expression. {yields} L{sup pro} inhibits MDA5-mediated activation of the IFN-{alpha}1/{beta} promoter. {yields} L{sup pro} significantly reduced the transcription of multiple IRF-responsive genes. {yields} L{sup pro} inhibits IFN-{alpha}1/{beta} promoter activation by decreasing IRF-3/7 in protein levels. {yields} The ability to process eIF-4G of L{sup pro} is not necessary to inhibit IFN-{alpha}1/{beta} activation. -- Abstract: The leader proteinase (L{sup pro}) of foot-and-mouth disease virus (FMDV) has been identified as an interferon-{beta} (IFN-{beta}) antagonist that disrupts the integrity of transcription factor nuclear factor {kappa}B (NF-{kappa}B). In this study, we showed that the reductionmore » of double stranded RNA (dsRNA)-induced IFN-{alpha}1/{beta} expression caused by L{sup pro} was also associated with a decrease of interferon regulatory factor 3/7 (IRF-3/7) in protein levels, two critical transcription factors for activation of IFN-{alpha}/{beta}. Furthermore, overexpression of L{sup pro} significantly reduced the transcription of multiple IRF-responsive genes including 2',5'-OAS, ISG54, IP-10, and RANTES. Screening L{sup pro} mutants indicated that the ability to process eIF-4G of L{sup pro} is not required for suppressing dsRNA-induced activation of the IFN-{alpha}1/{beta} promoter and decreasing IRF-3/7 expression. Taken together, our results demonstrate that, in addition to disrupting NF-{kappa}B, L{sup pro} also decreases IRF-3/7 expression to suppress dsRNA-induced type I IFN production, suggesting multiple strategies used by FMDV to counteract the immune response to viral infection.« less

Epidermal growth factor treatment decreases mortality and is associated with improved gut integrity in sepsis.

PubMed

Clark, Jessica A; Clark, Andrew T; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

2008-07-01

Epidermal growth factor (EGF) is a cytoprotective peptide that has healing effects on the intestinal mucosa. We sought to determine whether systemic administration of EGF after the onset of sepsis improved intestinal integrity and decreased mortality. FVB/N mice were subjected to either sham laparotomy or 2 x 23 cecal ligation and puncture (CLP). Septic mice were further randomized to receive injection of either 150 microg kg(-1) d(-1) (i.p.) EGF or 0.9% saline (i.p.). Circulating EGF levels were decreased after CLP compared with sham animals but were unaffected by giving exogenous EGF treatment. In contrast, intestinal EGF levels increased after CLP and were further augmented by exogenous EGF treatment. Intestinal EGF receptor was increased after CLP, whether assayed by immunohistochemistry, real-time polymerase chain reaction, or Western blot, and exogenous EGF treatment decreased intestinal EGF receptor. Villus length decreased 2-fold between sham and septic animals, and EGF treatment resulted in near total restitution of villus length. Sepsis decreased intestinal proliferation and increased intestinal apoptosis. This was accompanied by increased expression of the proapoptotic proteins Bid and Fas-associated death domain, as well as the cyclin-dependent kinase inhibitor p21 cip1/waf Epidermal growth factor treatment after the onset of sepsis restored both proliferation and apoptosis to levels seen in sham animals and normalized expression of Bid, Fas-associated death domain, and p21 cip1/waf . To determine whether improvements in gut homeostasis were associated with a decrease in sepsis-induced mortality, septic mice with or without EGF treatment after CLP were followed 7 days for survival. Mortality decreased from 60% to 30% in mice treated with EGF after the onset of sepsis (P < 0.05). Thus, EGF may be a potential therapeutic agent for the treatment of sepsis in part due to its ability to protect intestinal integrity.

INCREASING AGE IS A RISK FACTOR FOR DECREASED POSTPARTUM PELVIC FLOOR STRENGTH

PubMed Central

Quiroz, Lieschen H.; Pickett, Stephanie D.; Peck, Jennifer D; Rostaminia, Ghazaleh; Stone, Daniel E.; Shobeiri, S. Abbas

2016-01-01

Objectives To determine factors associated with decreased pelvic floor strength (PFS) after the first vaginal delivery in a cohort of low risk women Methods This is a secondary analysis of a prospective study examining the risk of pelvic floor injury in a cohort of primiparous women. All recruited participants underwent an examination, 3D ultrasound and measurement of pelvic floor strength (PFS) in the third trimester and repeated at 4 weeks-6 months postpartum using a perineometer. Results There were 84 women recruited for the study, and 70 completed the postpartum assessment. Average age was 28.4 years (SD, 4.8). There were 46 (66%) subjects with a vaginal delivery (VD) and 24 (34%) with a cesarean delivery (CD) who labored. Decreased PFS was observed more frequently in the VD group compared to the CD group (68% vs. 42%, p=0.03). In modified Poisson regression models controlling for mode of delivery and time of postpartum assessment, women who were age 25-29 (RR=2.80, 95% CI 1.03-7.57) and >=30 (RR=2.53, 95% CI 0.93-6.86)) were over 2.5 times more likely to have decreased postpartum PFS compared to women < 25 yo. Conclusions In this population, women age 25 and older were more than twice as likely to have a decrease in postpartum PFS. PMID:28067746

Fingolimod (FTY-720) is Capable of Reversing Tumor Necrosis Factor Induced Decreases in Cochlear Blood Flow.

PubMed

Bertlich, Mattis; Ihler, Friedrich; Weiss, Bernhard G; Freytag, Saskia; Jakob, Mark; Strupp, Michael; Pellkofer, Hannah; Canis, Martin

2017-09-01

The potential of Fingolimod (FTY-720), a sphingosine-1-phosphate analogue, to revoke the changes in cochlear blood flow induced by tumor necrosis factor (TNF) was investigated. Impairment of cochlear blood flow has often been considered as the common final pathway of various inner ear pathologies. TNF, an ubiquitous cytokine, plays a major role in these pathologies, reducing cochlear blood flow via sphingosine-1-phosphate-signaling. Fifteen Dunkin-Hartley guinea pigs were randomly assigned to one of three groups (placebo/placebo, TNF/placebo, TNF/FTY-720). Cochlear microcirculation was quantified over 60 minutes by in vivo fluorescence microscopy before and after topical application of placebo or TNF (5 ng/ml) and after subsequent application of placebo or FTY-720 (200 μg/ml). Treatment with TNF led to a significant decrease of cochlear blood flow.Following this, application of placebo caused no significant changes while application of FTY-720 caused a significant rise in cochlear blood flow. FTY-720 is capable of reversing changes in cochlear blood flow induced by application of TNF. This makes FTY-720 a valid candidate for potential treatment of numerous inner ear pathologies.

Decreased placental and muscular expression of the fibroblast growth factor 19 in gestational diabetes mellitus.

PubMed

Wang, Dongyu; Xu, Shuqia; Ding, Wenjing; Zhu, Caixia; Deng, Songqing; Qiu, Xiwen; Wang, Zilian

2018-05-07

Fibroblast growth factor (FGF) 19 has been shown to improve glycaemic homeostasis and lipid metabolism in animal models. In humans, decreased FGF19 level has been described in diabetes. This study aimed to investigate the expression of FGF19 in gestational diabetes mellitus (GDM). Samples for measurement were obtained from 20 GDM women and 25 healthy controls. The mRNA and protein expression levels of FGF19, FGF21 and co-receptor β-klotho (KLB) in placenta, rectus muscle and subcutaneous fat tissues were quantified by real-time quantitative polymerase chain reaction, western-blot and immunohistochemistry, respectively. Women with GDM had significantly lower mRNA and protein expressions of FGF19 than control women had in placenta (mRNA: 0.33 ± 0.05 vs. 0.72 ± 0.09; protein: 0.34 ± 0.13 vs. 0.85 ± 0.20) and rectus muscle (mRNA: 0.83 ± 0.11 vs. 1.28 ± 0.19; protein: 0.78 ± 0.24 vs. 1.23 ± 0.39). However, there were no significant differences between GDM women and controls with respect to the expression levels of FGF21 and KLB in placenta and rectus muscle. There were almost no detectable FGF19 and FGF21 expressions in subcutaneous fat tissue. Moreover, KLB expression levels were not different between GDM and control group in subcutaneous fat. FGF19expressions are decreased in GDM women's placenta and rectus muscle. This may contribute to the pathophysiology or development of GDM. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Significant Effect of Acupressure in Elevating Blood Stem Cell Factor During Chemotherapy in Patients With Gynecologic Cancer.

PubMed

Shih, Ya-Wen; Yang, Shun-Fa; Chien, Ming-Hsien; Chang, Ching-Wen; Chang, Vincent H S; Tsai, Hsiu-Ting

2017-12-09

Chemotherapy is used mainly to treat and control the progression of gynecological cancer. Bone marrow suppression, one of the adverse side effects of chemotherapy, may decrease immune function, increasing the risk of serious, fatal infections. The aims of this study were to evaluate the effectiveness of noninvasive acupressure in preventing and diminishing chemotherapy-induced myelosuppression in patients with gynecologic cancer and to determine whether this effect is associated with the regulation of the expressions of granulocyte-macrophage colony-stimulating factor and stem cell factor (SCF). In total, 28 women with gynecological cancer were randomly assigned either to the experimental group (n = 10) or to the control group (n = 18). The experimental group received acupressure of 5-minute duration to the Hegu (LI4), Quchi (LI11), Xuehai (SP10), Sanyinjiao (SP6), Taixi (K3), Zusanli (ST36), Taichong (LR3), and Baihui (GV20) points, respectively, three times per day for 6 weeks. The control group did not receive the acupressure intervention. The blood count, including white blood cells, platelets, and hemoglobin, and serum levels for SCF and granulocyte-macrophage colony-stimulating factor were assessed before (pretest) and 6 weeks after (posttest) the participants' first course of chemotherapy. At posttest, blood hemoglobin had significantly decreased from (mean ± SD) 11.6 ± 2.2 to 10.8 ±1.6 mg/dl (p = .03) in the control group. However, no significant pretest-posttest difference in hemoglobin concentration (11.4 ± 1.0 vs. 10.9 ± 1.1 mg/dl) was detected in the experimental group. Levels of SCF increased significantly between pretest and posttest in both the control group (from 1196.10 ± 293.17 to 1325.05 ± 253.77 ng/ml; p = .01) and the acupressure group (from 1046.78 ± 469.52 to 1387.06 ± 310.00 ng/ml; p = .007). In addition, a borderline difference (p = .05) in mean pretest-posttest SCF increase was found between the acupressure group (340.28 ± 255

Is thermogenesis a significant causal factor in preventing the "globesity" epidemic?

PubMed

Hansen, Jens Carl; Gilman, Andrew P; Odland, Jon Øyvind

2010-08-01

During the last four decades the world has experienced an epidemic of overweight individuals in affluent as well as developing countries. The WHO has predicted a "globesity epidemic" with more than 1 billion adults being overweight and at least 300 million of these being clinically obese. Obesity among children and adolescents is of great significance. From a global population perspective, this epidemic in weight gain and its sequelae are the largest public health problems identified to date and have very significant adverse implications for population health, and have by now almost reached the proportion of a pandemic. While genetic changes have been discussed as a cause of the epidemic, there has been too little time since its start to enable enough genetic adaptation to take place for this to provide a valid explanation. Traditionally positive energy balance and sedentary life style have been regarded as the primary causal factors; however, these factors have so far failed to provide explanations for the entire problem. For these reasons it seems warranted to investigate other possible co-factors contributing to the "globesity epidemic" and to find efficient strategies to counteract further increases in the size and nature of the epidemic. The purpose of this paper is to discuss a potential preventive co-factor, thermogenesis. Special attention has been paid to the influence of ambient temperature as a grossly neglected factor in the debate. As most people today live and work at ambient temperatures close to their body temperature (the thermal neutral point), we hypothesise that this is an important causal co-factor in the "globesity" epidemic. The hypothesis: The null hypothesis that adaptive thermogenesis in brown adipose tissue in adult humans is not significant for weight loss is rejected. We propose the hypothesis that homoeothermic living conditions close to the thermogenic neutral level is an important causal co-factor in the "Globesity" Epidemic

Prognostic Significance of Selected Lifestyle Factors in Urinary Bladder Cancer

PubMed Central

Wakai, Kenji; Ohno, Yoshiyuki; Obata, Kohji; Aoki, Kunio

1993-01-01

To examine the prognostic significance of lifestyle factors in urinary bladder cancer, we conducted a follow‐up study of 258 incident bladder cancer patients, who were originally recruited in a case‐control study in metropolitan Nagoya. Information on individual survivals was obtained from the computer data‐file of the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate analyses revealed significant associations of 5‐year survivorship with educational attainment, marital status, drinking habits and consumption of green tea in males, and age at first consultation, histological type and grade of tumor, stage and distant metastasis in both sexes. After adjustment for age, stage, histology (histological type and grade) and distant metastasis by means of a proportional hazards model, drinking of alcoholic beverages was significantly associated with the prognosis of bladder cancer in males. Its adjusted hazard ratio was 0.46 (95% confidence interval: 0.26–0.79), favoring patients who had taken alcoholic beverages. In detailed analysis, ex‐drinkers and all levels of current drinkers demonstrated hazard ratios smaller than unity, although no clear dose‐response relationship was detected. No prognostic significance was found for such lifestyle factors as smoking habit, uses of artificial sweeteners and hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and cola. PMID:8294212

Prognostic significance of selected lifestyle factors in urinary bladder cancer.

PubMed

Wakai, K; Ohno, Y; Obata, K; Aoki, K

1993-12-01

To examine the prognostic significance of lifestyle factors in urinary bladder cancer, we conducted a follow-up study of 258 incident bladder cancer patients, who were originally recruited in a case-control study in metropolitan Nagoya. Information on individual survivals was obtained from the computer data-file of the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate analyses revealed significant associations of 5-year survivorship with educational attainment, marital status, drinking habits and consumption of green tea in males, and age at first consultation, histological type and grade of tumor, stage and distant metastasis in both sexes. After adjustment for age, stage, histology (histological type and grade) and distant metastasis by means of a proportional hazards model, drinking of alcoholic beverages was significantly associated with the prognosis of bladder cancer in males. Its adjusted hazard ratio was 0.46 (95% confidence interval: 0.26-0.79), favoring patients who had taken alcoholic beverages. In detailed analysis, ex-drinkers and all levels of current drinkers demonstrated hazard ratios smaller than unity, although no clear dose-response relationship was detected. No prognostic significance was found for such lifestyle factors as smoking habit, uses of artificial sweeteners and hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and cola.

[Preliminary study of clinical significance of decreased D(L)CO in patients with left ventricular heart failure].

PubMed

Tan, Xiao-yue; Sun, Xing-guo; Hu, Sheng-shou; Zhang, Jian; Huang, Jie; Chen, Zhi-gao; Ma, Li

2015-07-01

This study aimed to investigate the feature of D(L)CO (Diffusion Lung Capacity for Carbon Monoxide) in CHF (left ventricular heart failure) patients, underlying pathophysiological mechanism and clinical significance. We retrospectively studied the D(L)CO, pulmonary ventilation function, cardiopulmonary exercise testing and related clinical information in severer HF patients. Peak VO2 severely decreased to 34 ± 7 percentage of predicted(%pred) and anaerobic threshold to 48 ± 11%pred in all patients. D(L)CO moderately decreased to 63 ± 12%pred and there were 25 patients lower than 80%pred. FVC, FEV1, FEV1/FVC and TLC were 75 ± 14%pred, 71 ± 17%pred, 97 ± 11%pred, and 79 ± 13%pred, which indicated borderline or mild restrictive ventilatory dysfunction. The decrease of D(L)CO was more severe than those of TLC, FEV1 and FVC. For patients with severe CHF, cardiopulmonary exercise function is extremely limited, D(L)CO generally moderately declines and ventilation function is merely mildly limited. D(L)CO is the parameter for cardiopulmonary coupling, reflecting limitation of the cardiovascular dysfunction while without ventilatory limit.

Etanercept prevents decrease of cochlear blood flow dose-dependently caused by tumor necrosis factor alpha.

PubMed

Ihler, Friedrich; Sharaf, Kariem; Bertlich, Mattis; Strieth, Sebastian; Reichel, Christoph A; Berghaus, Alexander; Canis, Martin

2013-07-01

Tumor necrosis factor alpha (TNF-alpha) is a mediator of inflammation and microcirculation in the cochlea. This study aimed to quantify the effect of a local increase of TNF-alpha and study the effect of its interaction with etanercept on cochlear microcirculation. Cochlear lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. First, 24 animals were randomly distributed into 4 groups of 6 each. Exposed vessels were superfused repeatedly either with 1 of 3 different concentrations of TNF-alpha (5.0, 0.5, and 0.05 ng/mL) or with placebo (0.9% saline solution). Second, 12 animals were randomly distributed into 2 groups of 6 each. Vessels were pretreated with etanercept (1.0 microg/ mL) or placebo (0.9% saline solution), and then treated by repeated superfusion with TNF-alpha (5.0 ng/mL). TNF-alpha was shown to be effective in decreasing cochlear blood flow at a dose of 5.0 ng/mL (p < 0.01, analysis of variance on ranks). Lower concentrations or placebo treatment did not lead to significant changes. After pretreatment with etanercept, TNF-alpha at a dose of 5.0 ng/mL no longer led to a change in cochlear blood flow. The decreasing effect that TNF-alpha has on cochlear blood flow is dose-dependent. Etanercept abrogates this effect.

Depression as a modifiable factor to decrease the risk of dementia

PubMed Central

Almeida, O P; Hankey, G J; Yeap, B B; Golledge, J; Flicker, L

2017-01-01

Depression is an accepted risk factor for dementia, but it is unclear if this relationship is causal. This study investigated whether dementia associated with depression decreases with antidepressant use and is independent of the time between exposure to depression and the onset of dementia. We completed a 14-year longitudinal study of 4922 cognitively healthy men aged 71–89 years, and collected information about history of past depression, current depression and severity of depressive symptoms. Other measures included use of antidepressants, age, education, smoking and history of diabetes, hypertension, coronary heart disease, and stroke. The onset of dementia and death during follow-up was ascertained via the Western Australian Data Linkage System. A total of 682 men had past (n=388) or current (n=294) depression. During 8.9 years follow-up, 903 (18.3%) developed dementia and 1884 (38.3%) died free of dementia. The sub-hazard ratios (SHRs) of dementia for men with past and current depression were 1.3 (95% confidence interval (CI)=1.0, 1.6) and 1.5 (95% CI=1.2, 2.0). The use of antidepressants did not decrease this risk. Compared to men with no symptoms, the SHRs of dementia associated with questionable, mild-to-moderate and severe depressive symptoms were 1.2 (95% CI=1.0, 1.4), 1.7 (95% CI=1.4, 2.2) and 2.1 (95% CI=1.4, 3.2), respectively. The association between depression and dementia was only apparent during the initial 5 years of follow-up. Older men with history of depression are at increased risk of developing dementia, but depression is more likely to be a marker of incipient dementia than a truly modifiable risk factor. PMID:28463236

Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity.

PubMed

Tomlinson, Elizabeth; Fu, Ling; John, Linu; Hultgren, Bruce; Huang, Xiaojian; Renz, Mark; Stephan, Jean Philippe; Tsai, Saio Ping; Powell-Braxton, Lyn; French, Dorothy; Stewart, Timothy A

2002-05-01

The fibroblast growth factors (FGFs), and the corresponding receptors, are implicated in more than just the regulation of epithelial cell proliferation and differentiation. Specifically, FGF23 is a regulator of serum inorganic phosphate levels, and mice deficient in FGF receptor-4 have altered cholesterol metabolism. The recently described FGF19 is unusual in that it is nonmitogenic and appears to interact only with FGF receptor-4. Here, we report that FGF19 transgenic mice had a significant and specific reduction in fat mass that resulted from an increase in energy expenditure. Further, the FGF19 transgenic mice did not become obese or diabetic on a high fat diet. The FGF19 transgenic mice had increased brown adipose tissue mass and decreased liver expression of acetyl coenzyme A carboxylase 2, providing two mechanisms by which FGF19 may increase energy expenditure. Consistent with the reduction in expression of acetyl CoA carboxylase 2, liver triglyceride levels were reduced.

Emodin Decreases Hepatic Hypoxia-Inducible Factor-1[Formula: see text] by Inhibiting its Biosynthesis.

PubMed

Ma, Feifei; Hu, Lijuan; Yu, Ming; Wang, Feng

2016-01-01

Hypoxia-inducible factor-1 (HIF-1) is an [Formula: see text] dimeric transcription factor. Because HIF-1[Formula: see text] is instable with oxygen, HIF-1 is scarce in normal mammalian cells. However, HIF-1[Formula: see text] is expressed in pathological conditions such as cancer and obesity. Inhibiting HIF-1[Formula: see text] may be of therapeutic value for these pathologies. Here, we investigated whether emodin, derived from the herb of Rheum palmatum L, which is also known as Chinese rhubarb, and is native to China, regulates HIF-1[Formula: see text] expression. Male C57BL/6 mice without or with diet-induced obesity were treated with emodin for two weeks, while control mice were treated with vehicle. HIF-1[Formula: see text] expression was determined by Western blot. We found that emodin inhibited obesity-induced HIF-1[Formula: see text] expression in liver and skeletal muscle but did not regulate HIF-1[Formula: see text] expression in the kidneys or in intra-abdominal fat. In vitro, emodin inhibited HIF-1[Formula: see text] expression in human HepG2 hepatic cells and Y1 adrenocortical cells. Further, we investigated the mechanisms of HIF-1[Formula: see text] expression in emodin-treated HepG2 cells. First, we found that HIF-1[Formula: see text] had normal stability in the presence of emodin. Thus, emodin did not decrease HIF-1[Formula: see text] by stimulating its degradation. Importantly, emodin decreased the activity of the signaling pathways that led to HIF-1[Formula: see text] biosynthesis. Interestingly, emodin increased HIF-1[Formula: see text] mRNA in HepG2 cells. This may be a result of feedback in response to the emodin-induced decrease in the protein of HIF-1[Formula: see text]. In conclusion, emodin decreases hepatic HIF-1[Formula: see text] by inhibiting its biosynthesis.

Statewide ban on recreational fires resulted in a significant decrease in campfire-related summer burn center admissions.

PubMed

Hoang, David Manh; Reid, Dixie; Lentz, Christopher William

2013-01-01

Every summer, there is an increase in the number of burn injuries caused by accidents around campfires. Because of the prevalence of drought, high winds, and uncontrolled wild fires, a statewide ban on recreational fires was instituted in New Mexico from June to July 2011. We hypothesized that this legislation would have a significant impact on burn admissions caused by campfire-related injuries. A retrospective review of summer admissions to a state burn center was conducted to assess the effect of this ban on recreational fire injuries, and these data were compared with that of the previous summer when no ban was in effect. All burn admissions to a state burn center were reviewed from Memorial Day to Labor Day in 2010 and 2011. Data collected included cause, % TBSA, age, days of hospitalization, intensive care unit days, and total surface area grafted. Nonparametric statistical analysis was performed with Fisher exact test for dichotomous data and Mann-Whitney test for continuous data with significance at P < .05. There were 164 burn center admissions between Memorial Day and Labor Day in 2010 (n = 82) and 2011 (n = 82). Compared with all summer burn center admissions, patients injured by campfires were younger (18 vs 37 years; P = .002) with smaller total surface area burns (3.2 vs 6.2%; P = .41) and had shorter lengths of stay (10-11 vs 6-7 days; P = .62). There was more than a 3-fold decrease in burn admissions due to recreational fires during the study period (n = 14 [17%] in 2010 and 4 [5%] in 2011; P = .02). This resulted in a decrease in the number of patient-days from 91 in 2010 to 25 in 2011. Half of the camp fire admissions required skin grafts to definitively close the wounds (6/14 in 2010 and 2/4 in 2011). Recreational fire bans targeted at controlling wildfires during conditions favoring rapid spread were associated with a 3- to 4-fold decrease in campfire-related burn admissions. Compared with a summer when no fire ban was in effect, the number of

Early HIV Diagnosis Leads to Significantly Decreased Costs in the First 2 Years of HIV Care in an Urban Charity Hospital in New Orleans.

PubMed

Halperin, Jason; Katz, Morgan; Pathmanathan, Ishani; Myers, Leann; Van Sickels, Nicholas; Seal, Paula Sereebutra; Richey, Lauren E

We undertook a retrospective cohort study of patients with a positive HIV test in the emergency department who were then linked to care. Inpatient, outpatient, and emergency costs were collected for the first 2 years after HIV diagnosis. Fifty-six patients met the inclusion criteria; they were predominantly uninsured (73%) and African American (89%). The median total cost for a newly diagnosed patient over the first 2 years was US$36 808, driven predominantly by outpatient costs of US$17 512. Median inpatient and total costs were significantly different between the lowest (<200 cells/mm 3 ) and highest (>499 cells/mm 3 ) CD4 count categories (US$21 878 vs US$6607, P <.05; US$61 378 vs US$18 837, P <.05, respectively). Total costs were significantly different between viral load categories <100 000 HIV-RNA copies/mL and ≥100 000 HIV-RNA copies/mL (US$28 219 vs US$49 482, P <.05). Costs were significantly lower among patients diagnosed earlier in their disease. Decreased cost is another factor supporting early diagnosis and linkage to care for patients with HIV.

Significance of specificity of Tinetti B-POMA test and fall risk factor in third age of life.

PubMed

Avdić, Dijana; Pecar, Dzemal

2006-02-01

As for the third age, psychophysical abilities of humans gradually decrease, while the ability of adaptation to endogenous and exogenous burdens is going down. In 1987, "Harada" et al. (1) have found out that 9.5 million persons in USA have difficulties running daily activities, while 59% of them (which is 5.6 million) are older than 65 years in age. The study has encompassed 77 questioned persons of both sexes with their average age 71.73 +/- 5.63 (scope of 65-90 years in age), chosen by random sampling. Each patient has been questioned in his/her own home and familiar to great extent with the methodology and aims of the questionnaire. Percentage of questioned women was 64.94% (50 patients) while the percentage for men was 35.06% (27 patients). As for the value of risk factor score achieved conducting the questionnaire and B-POMA test, there are statistically significant differences between men and women, as well as between patients who fell and those who never did. As for the way of life (alone or in the community), there are no significant statistical differences. Average results gained through B-POMA test in this study are statistically significantly higher in men and patients who did not provide data about falling, while there was no statistically significant difference in the way of life. In relation to the percentage of maximum number of positive answers to particular questions, regarding gender, way of life and the data about falling, there were no statistically significant differences between the value of B-POMA test and the risk factor score (the questionnaire).

Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

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

Yasui, K.; Yamazaki, M.; Miyagawa, Y.

Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine (/sup 3/H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease ofmore » neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder.« less

Multipotent mesenchymal stromal cells decrease transforming growth factor β1 expression in microglia/macrophages and down-regulate plasminogen activator inhibitor 1 expression in astrocytes after stroke.

PubMed

Xin, Hongqi; Chopp, Michael; Shen, Li Hong; Zhang, Rui Lan; Zhang, Li; Zhang, Zheng Gang; Li, Yi

2013-05-10

Multipotent mesenchymal stromal cells (MSCs) decrease the expression of transforming growth factor β1 (TGFβ1) in astrocytes and subsequently decrease astrocytic plasminogen activator inhibitor 1 (PAI-1) level in an autocrine manner. Since activated microglia/macrophages are also a source of TGFβ1 after stroke, we therefore tested whether MSCs regulate TGFβ1 expression in microglia/macrophages and subsequently alters PAI-1 expression after ischemia. TGFβ1 and its downstream effector phosphorylated SMAD 2/3 (p-SMAD 2/3) were measured in mice subjected to middle cerebral artery occlusion (MCAo). MSC treatment significantly decreased TGFβ1 protein expression in both astrocytes and microglia/macrophages in the ischemic boundary zone (IBZ) at day 14 after stroke. However, the p-SMAD 2/3 was only detected in astrocytes and decreased after MSC treatment. In vitro, RT-PCR results showed that the TGFβ1 mRNA level was increased in both astrocytes and microglia/macrophages in an astrocyte-microglia/macrophage co-culture system after oxygen-glucose deprived (OGD) treatment. MSCs treatment significantly decreased the above TGFβ1 mRNA level under OGD conditions, respectively. OGD increased the PAI-1 mRNA in astrocytes in the astrocyte-microglia/macrophage co-culture system, and MSC administration significantly decreased this level. PAI-1 mRNA was very low in microglia/macrophages compared with that in astrocytes under different conditions. Western blot results also verified that MSC administration significantly decreased p-SMAD 2/3 and PAI-1 level in astrocytes in astrocyte-microglia/macrophage co-culture system under OGD conditions. Our in vivo and in vitro data, in concert, suggest that MSCs decrease TGFβ1 expression in microglia/macrophages in the IBZ which contribute to the down-regulation of PAI-1 level in astrocytes. Published by Elsevier Ireland Ltd.

Decreased Superoxide Production, Degranulation, Tumor Necrosis Factor Alpha Secretion, and CD11b/CD18 Receptor Expression by Adherent Monocytes from Preterm Infants

PubMed Central

Kaufman, David; Kilpatrick, Laurie; Hudson, R. Guy; Campbell, Donald E.; Kaufman, Ann; Douglas, Steven D.; Harris, Mary C.

1999-01-01

Preterm infants have an increased incidence of infection, which is principally due to deficiencies in neonatal host defense mechanisms. Monocyte adherence is important in localizing cells at sites of infection and is associated with enhanced antimicrobial functions. We isolated cord blood monocytes from preterm and full-term infants to study their adhesion and immune functions, including superoxide (O2−) generation, degranulation, and cytokine secretion and their adhesion receptors. O2− production and degranulation were significantly diminished, by 28 and 37%, respectively, in adherent monocytes from preterm infants compared to full-term infants (P < 0.05); however, these differences were not seen in freshly isolated cells. We also observed a significant decrease of 35% in tumor necrosis factor alpha secretion by lipopolysaccharide-stimulated adherent monocytes from preterm infants compared to full-term infants (P < 0.05); however, this difference was not observed in interleukin-1β or interleukin-6 production by the monocytes. The cell surface expression of the CD11b/CD18 adhesion receptor subunits was significantly decreased (by 60 and 52%, respectively) in monocytes from preterm infants compared to full-term infants (P < 0.01). The cascade of the immune response to infection involves monocyte upregulation and adherence via CD11b/CD18 receptors followed by cell activation and the release of cytokines and bactericidal products. We speculate that monocyte adherence factors may be important in the modulation of immune responses in preterm infants. PMID:10391855

Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

ERIC Educational Resources Information Center

Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

2011-01-01

Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

Significance Testing in Confirmatory Factor Analytic Models.

ERIC Educational Resources Information Center

Khattab, Ali-Maher; Hocevar, Dennis

Traditionally, confirmatory factor analytic models are tested against a null model of total independence. Using randomly generated factors in a matrix of 46 aptitude tests, this approach is shown to be unlikely to reject even random factors. An alternative null model, based on a single general factor, is suggested. In addition, an index of model…

Prognostic Factors and Significance of Gastrointestinal Leak After Cytoreductive Surgery (CRS) with Heated Intraperitoneal Chemotherapy (HIPEC).

PubMed

Chouliaras, Konstantinos; Levine, Edward A; Fino, Nora; Shen, Perry; Votanopoulos, Konstantinos I

2017-04-01

Gastrointestinal leak (GIL) after cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC) is associated with significant morbidity and mortality. This study aimed to identify GIL prognostic factors and its impact on overall survival. A retrospective analysis of a prospectively maintained database comprising 1270 CRS/HIPEC procedures was performed. Type of GIL, functional and resection status, morbidity, mortality, and survival were reviewed. Gastrointestinal leaks were identified in 8.7% (110/1270) of CRS/HIPEC procedures, including 53 anastomotic leaks (4.2%), 53 hollow viscus perforations (4.2%), and four leaks at unknown sites. The multivariate predictors of leak were Eastern Cooperative Oncology Group (ECOG) functional status (ECOG 1 vs. 0: odds ratio [OR] 2.12, p = 0.009; ECOG 2 vs. 0: OR 2.90, p = 0.004), and number of anastomoses (OR 5.34; p < 0.0001). The in-hospital mortality rate for the GIL cohort was 21.8% (24/110), with a 72% (80/110) reoperation rate. The leak cohort had a higher major morbidity rate (88.3 vs. 23.3%; p < 0.0001), a longer hospital stay (39.0 vs. 9.9 days; p < 0.0001), and a longer intensive care unit (ICU) stay (7.7 vs. 1.7 days; p = 0.0003). After surgical mortality was excluded, the overall survival periods for the leak and no-leak patients with complete cytoreduction were respectively 1.5 and 4.98 years (p = 0.0001). Clinically significant decreases in survival were observed for all primary malignancies. Gastrointestinal leak after CRS/HIPEC is a source of significant mortality, with a decrease in overall survival even after complete CRS. Preoperative functional status and number of anastomoses are predictors of leak for CRS/HIPEC patients.

[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.

Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma

PubMed Central

Arrieta, O; Guevara, P; Escobar, E; García-Navarrete, R; Pineda, B; Sotelo, J

2005-01-01

Angiotensin II (Ang II) is a main effector peptide in the renin–angiotensin system and participates in the regulation of vascular tone. It also has a role in the expression of growth factors that induce neovascularisation which is closely associated to the growth of malignant gliomas. We have shown that the selective blockage of the AT1 receptor of angiotensin inhibites tumour growth, cell proliferation and angiogenesis of C6 rat glioma. The aim of this study was to study the effects of the blockage of AT1 receptor on the synthesis of growth factors, and in the genesis of apoptosis in cultured C6 glioma cells and in rats with C6 glioma. Administration of losartan at doses of 40 or 80 mg kg−1 to rats with C6 glioma significantly decreased tumoral volume and production of platelet-derived growth factor, vascular endothelial growth factor and basic fibroblast growth factor. It also induced apoptosis in a dose-dependent manner. Administration of Ang II increased cell proliferation of cultured C6 cells which decreased by the administration of losartan. Our results suggest that the selective blockage of AT1 diminishes tumoral growth through inhibition of growth factors and promotion of apoptosis. PMID:15785746

First record of Anopheles minimus C and significant decrease of An. minimus A in central Vietnam.

PubMed

Garros, Claire; Marchand, Ron P; Quang, Nguyen Tuyen; Hai, Nguyen Son; Manguin, Sylvie

2005-06-01

Before August 1998, in the Khanh Phu commune (central Vietnam), Anopheles minimus s.l. individuals were identified as species A and showed the typical species A wing form. After a significant decrease over the 3 years 1999-2001, an increase in 2002 of An. minimus s.l. possessing a different wing pattern was observed. To determine the specific status of the An. minimus species collected in 2002 and to follow changes in the species composition, an allele-specific polymerase chain reaction was applied to samples collected from 1993 to 2002. This study reports the first record of An. minimus C in central Vietnam and, since 1998, a significant reduction of An. minimus A that coincided with the wide use of permethrin-treated bednets. This change in anopheline composition may have important consequences on malaria transmission. This work shows that the geographic distribution of malaria vectors in southeast Asia is only partially known and highlights the importance of species identification for understanding changes in the vector composition as a result of selective vector control.

Decreased expression of extracellular matrix proteins and trophic factors in the amygdala complex of depressed mice after chronic immobilization stress

PubMed Central

2012-01-01

Background The amygdala plays an essential role in controlling emotional behaviors and has numerous connections to other brain regions. The functional role of the amygdala has been highlighted by various studies of stress-induced behavioral changes. Here we investigated gene expression changes in the amygdala in the chronic immobilization stress (CIS)-induced depression model. Results Eight genes were decreased in the amygdala of CIS mice, including genes for neurotrophic factors and extracellular matrix proteins. Among these, osteoglycin, fibromodulin, insulin-like growth factor 2 (Igf2), and insulin-like growth factor binding protein 2 (Igfbp2) were further analyzed for histological expression changes. The expression of osteoglycin and fibromodulin simultaneously decreased in the medial, basolateral, and central amygdala regions. However, Igf2 and Igfbp2 decreased specifically in the central nucleus of the amygdala. Interestingly, this decrease was found only in the amygdala of mice showing higher immobility, but not in mice displaying lower immobility, although the CIS regimen was the same for both groups. Conclusions These results suggest that the responsiveness of the amygdala may play a role in the sensitivity of CIS-induced behavioral changes in mice. PMID:22672618

Increased cardiac alpha-myosin heavy chain in left atria and decreased myocardial insulin-like growth factor (Igf-I) expression accompany low heart rate in hibernating grizzly bears.

PubMed

Barrows, N D; Nelson, O L; Robbins, C T; Rourke, B C

2011-01-01

Grizzly bears (Ursus arctos horribilis) tolerate extended periods of extremely low heart rate during hibernation without developing congestive heart failure or cardiac chamber dilation. Left ventricular atrophy and decreased left ventricular compliance have been reported in this species during hibernation. We evaluated the myocardial response to significantly reduced heart rate during hibernation by measuring relative myosin heavy-chain (MyHC) isoform expression and expression of a set of genes important to muscle plasticity and mass regulation in the left atria and left ventricles of active and hibernating bears. We supplemented these data with measurements of systolic and diastolic function via echocardiography in unanesthetized grizzly bears. Atrial strain imaging revealed decreased atrial contractility, decreased expansion/reservoir function (increased atrial stiffness), and decreased passive-filling function (increased ventricular stiffness) in hibernating bears. Relative MyHC-α protein expression increased significantly in the atrium during hibernation. The left ventricle expressed 100% MyHC-β protein in both groups. Insulin-like growth factor (IGF-I) mRNA expression was reduced by ∼50% in both chambers during hibernation, consistent with the ventricular atrophy observed in these bears. Interestingly, mRNA expression of the atrophy-related ubiquitin ligases Muscle Atrophy F-box (MAFBx) and Muscle Ring Finger 1 did not increase, nor did expression of myostatin or hypoxia-inducible factor 1α (HIF-1α). We report atrium-specific decreases of 40% and 50%, respectively, in MAFBx and creatine kinase mRNA expression during hibernation. Decreased creatine kinase expression is consistent with lowered energy requirements and could relate to reduced atrial emptying function during hibernation. Taken together with our hemodynamic assessment, these data suggest a potential downregulation of atrial chamber function during hibernation to prevent fatigue and dilation

Tumor Necrosis Factor Inhibitor Primary Failure Predicts Decreased Ustekinumab Efficacy in Psoriasis Patients.

PubMed

Sorensen, Eric P; Fanucci, Kristina A; Saraiya, Ami; Volf, Eva; Au, Shiu-chung; Argobi, Yahya; Mansfield, Ryan; Gottlieb, Alice B

2015-08-01

Additional studies are needed to examine the efficacy of ustekinumab in psoriasis patients who have previously been exposed to tumor necrosis factor inhibitors (TNFi). To examine the predictive effect of TNFi primary failure and the number of TNFi exposures on the efficacy of ustekinumab in psoriasis treatment. This retrospective study examined 44 psoriasis patients treated at the Tufts Medical Center Department of Dermatology between January 2008 and July 2014. Patients were selected if they were treated with ustekinumab and had ≥ 1 previous TNFi exposure. The following subgroups were compared: patients with vs without a previous TNFi primary failure, and patients with one vs multiple previous TNFi exposures. The efficacy measure used was the previously validated Simple Measure for Assessing Psoriasis Activity (S-MAPA), which is calculated by the product of the body surface area and physician global assessment. The primary outcome was the percentage improvement S-MAPA from course baseline at week 12 of ustekinumab treatment. Secondary outcomes were the psoriasis clearance, primary failure, and secondary failure rates with ustekinumab treatment. Patients with a previous TNFi primary failure had a significantly lower percentage improvement in S-MAPA score at week 12 of ustekinumab treatment compared with patients without TNFi primary failure (36.2% vs 61.1%, P=.027). Multivariate analysis demonstrated that this relationship was independent of patient demographics and medical comorbidities. Patients with multiple TNFi exposures had a non-statistically significant lower percentage S-MAPA improvement at week 12 (40.5% vs 52.9%, P=.294) of ustekinumab treatment compared with patients with a single TNFi exposure. Among psoriasis patients previously exposed to TNFi, a history of a previous TNFi primary failure predicts a decreased response to ustekinumab independent of patient demographics and medical comorbidities.

Agavins Increase Neurotrophic Factors and Decrease Oxidative Stress in the Brains of High-Fat Diet-Induced Obese Mice.

PubMed

Franco-Robles, Elena; López, Mercedes G

2016-08-02

Fructans obtained from agave, called agavins, have recently shown significant benefits for human health including obesity. Therefore, we evaluated the potential of agavins as neuroprotectors and antioxidants by determining their effect on brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) as well as oxidative brain damage in of obese mice. Male C57BL/6J mice were fed a high-fat diet (HFD) and treated daily with 5% (HFD/A5) or 10% (HFD/A10) of agavins or a standard diet (SD) for 10 weeks. The levels of BDNF and GDNF were evaluated by ELISA. The oxidative stress was evaluated by lipid peroxidation (TBARS) and carbonyls. SCFAs were also measured with GC-FID. Differences between groups were assessed using ANOVA and by Tukey's test considering p < 0.05. The body weight gain and food intake of mice HFD/A10 group were significantly lower than those in the HFD group. Agavins restored BDNF levels in HFD/A5 group and GDNF levels of HFD/A5 and HFD/A10 groups in cerebellum. Interestingly, agavins decreased TBARS levels in HFD/A5 and HFD/A10 groups in the hippocampus, frontal cortex and cerebellum. Carbonyl levels were also lower in HFD/A5 and HFD/A10 for only the hippocampus and cerebellum. It was also found that agavins enhanced SCFAs production in feces. Agavins may act as bioactive ingredients with antioxidant and protective roles in the brain.

Biomaterials Transforming growth factor-beta 1 delivery from microporous scaffolds decreases inflammation post-implant and enhances function of transplanted islets

PubMed Central

Liu, JMH; Zhang, J; Zhang, X; Hlavaty, KA; Ricci, CF; Leonard, JN; Shea, LD; Gower, RM

2015-01-01

Biomaterial scaffolds are central to many regenerative strategies as they create a space for infiltration of host tissue and provide a platform to deliver growth factors and progenitor cells. However, biomaterial implantation results in an unavoidable inflammatory response, which can impair tissue regeneration and promote loss or dysfunction of transplanted cells. We investigated localized TGF-β1 delivery to modulate this immunological environment around scaffolds and transplanted cells. TGF-β1 was delivered from layered scaffolds, with protein entrapped within an inner layer and outer layers designed for cell seeding and host tissue integration. Scaffolds were implanted into the epididymal fat pad, a site frequently used for cell transplantation. Expression of cytokines TNF-a, IL-12, and MCP-1 were decreased by at least 40% for scaffolds releasing TGF-β1 relative to control scaffolds. This decrease in inflammatory cytokine production corresponded to a 60% decrease in leukocyte infiltration. Transplantation of islets into diabetic mice on TGF-β1 scaffolds significantly improved the ability of syngeneic islets to control blood glucose levels within the first week of transplant and delayed rejection of allogeneic islets. Together, these studies emphasize the ability of localized TGF-β1 delivery to modulate the immune response to biomaterial implants and enhance cell function in cell-based therapies. PMID:26701143

Can changes in psychosocial factors and residency explain the decrease in physical activity during the transition from high school to college or university?

PubMed

Van Dyck, Delfien; De Bourdeaudhuij, Ilse; Deliens, Tom; Deforche, Benedicte

2015-04-01

When students make the transition from high school to college or university, their physical activity (PA) levels decrease strongly. Consequently, it is of crucial importance to identify the determinants of this decline in PA. The study aims were to (1) examine changes in psychosocial factors in students during the transition from high school to college/university, (2) examine if changes in psychosocial factors and residency can predict changes in PA, and (3) investigate the moderating effects of residency on the relationship between changes in psychosocial factors and changes in PA. Between March 2008 and October 2010, 291 Flemish students participated in a longitudinal study, with baseline measurements during the final year of high school and follow-up measurements at the start of second year of college/university. At both time points, participants completed a questionnaire assessing demographics, active transportation, leisure-time sports, psychosocial variables, and residency. Repeated measures MANOVA analyses and multiple moderated hierarchic regression analyses were conducted. Modeling, self-efficacy, competition-related benefits, and health-related, external and social barriers decreased, while health-related benefits and time-related barriers increased from baseline to follow-up. Decreases in modeling and time-related barriers were associated with a decrease in active transportation (adjusted R(2) = 3.2%); residency, decreases in self-efficacy, competition-related benefits, and increases in health- and time-related barriers predicted a decrease in leisure-time sports (adjusted R(2) = 29.3%). Residency only moderated two associations between psychosocial factors and changes in PA. Residency and changes in psychosocial factors were mainly important to explain the decrease in leisure-time sports. Other factors such as distance to college/university are likely more important to explain the decrease in active transportation; these are worth exploring in

Identification of significant factors in fatal-injury highway crashes using genetic algorithm and neural network.

PubMed

Li, Yunjie; Ma, Dongfang; Zhu, Mengtao; Zeng, Ziqiang; Wang, Yinhai

2018-02-01

Identification of the significant factors of traffic crashes has been a primary concern of the transportation safety research community for many years. A fatal-injury crash is a comprehensive result influenced by multiple variables involved at the moment of the crash scenario, the main idea of this paper is to explore the process of significant factors identification from a multi-objective optimization (MOP) standpoint. It proposes a data-driven model which combines the Non-dominated Sorting Genetic Algorithm (NSGA-II) with the Neural Network (NN) architecture to efficiently search for optimal solutions. This paper also defines the index of Factor Significance (F s ) for quantitative evaluation of the significance of each factor. Based on a set of three year data of crash records collected from three main interstate highways in the Washington State, the proposed method reveals that the top five significant factors for a better Fatal-injury crash identification are 1) Driver Conduct, 2) Vehicle Action, 3) Roadway Surface Condition, 4) Driver Restraint and 5) Driver Age. The most sensitive factors from a spatiotemporal perspective are the Hour of Day, Most Severe Sobriety, and Roadway Characteristics. The method and results in this paper provide new insights into the injury pattern of highway crashes and may be used to improve the understanding of, prevention of, and other enforcement efforts related to injury crashes in the future. Copyright © 2017. Published by Elsevier Ltd.

Parenteral diclofenac infusion significantly decreases brain-tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage

PubMed Central

2013-01-01

Introduction Diclofenac, a nonsteroidal antiinflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis, including brain-tissue oxygen tension (PbtO2) and brain metabolism after aneurysmal subarachnoid hemorrhage (aSAH). Methods We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature, and PbtO2 were analyzed after parenteral diclofenac infusion administered over a 34-minute period (20 to 45 IQR). Data are given as mean ± standard error of mean and median with interquartile range (IQR), as appropriate. Time-series data were analyzed by using a general linear model extended by generalized estimation equations (GEEs). Results One-hundred twenty-three interventions were analyzed. Body temperature decreased from 38.3°C ± 0.05°C by 0.8°C ± 0.06°C (P < 0.001). A 10% decrease in MAP and CPP (P < 0.001) necessitated an increase of vasopressors in 26% (n = 32), colloids in 33% (n = 41), and crystalloids in 5% (n = 7) of interventions. PbtO2 decreased by 13% from a baseline value of 28.1 ± 2.2 mm Hg, resulting in brain-tissue hypoxia (PbtO2 <20 mm Hg) in 38% (n = 8) of patients and 35% (n = 43) of interventions. PbtO2 <30 mm Hg before intervention was associated with brain-tissue hypoxia after parenteral diclofenac infusion (likelihood ratio, 40; AUC, 93%; 95% confidence interval (CI), 87% to 99%; P < 0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion. Conclusions Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain-tissue hypoxia, which were both associated with poor outcome after aSAH. PMID:23663770

Inhibition of connective tissue growth factor (CTGF/CCN2) expression decreases the survival and myogenic differentiation of human rhabdomyosarcoma cells.

PubMed

Croci, Stefania; Landuzzi, Lorena; Astolfi, Annalisa; Nicoletti, Giordano; Rosolen, Angelo; Sartori, Francesca; Follo, Matilde Y; Oliver, Noelynn; De Giovanni, Carla; Nanni, Patrizia; Lollini, Pier-Luigi

2004-03-01

Connective tissue growth factor (CTGF/CCN2), a cysteine-rich protein of the CCN (Cyr61, CTGF, Nov) family of genes, emerged from a microarray screen of genes expressed by human rhabdomyosarcoma cells. Rhabdomyosarcoma is a soft tissue sarcoma of childhood deriving from skeletal muscle cells. In this study, we investigated the role of CTGF in rhabdomyosarcoma. Human rhabdomyosarcoma cells of the embryonal (RD/12, RD/18, CCA) and the alveolar histotype (RMZ-RC2, SJ-RH4, SJ-RH30), rhabdomyosarcoma tumor specimens, and normal skeletal muscle cells expressed CTGF. To determine the function of CTGF, we treated rhabdomyosarcoma cells with a CTGF antisense oligonucleotide or with a CTGF small interfering RNA (siRNA). Both treatments inhibited rhabdomyosarcoma cell growth, suggesting the existence of a new autocrine loop based on CTGF. CTGF antisense oligonucleotide-mediated growth inhibition was specifically due to a significant increase in apoptosis, whereas cell proliferation was unchanged. CTGF antisense oligonucleotide induced a strong decrease in the level of myogenic differentiation of rhabdomyosarcoma cells, whereas the addition of recombinant CTGF significantly increased the proportion of myosin-positive cells. CTGF emerges as a survival and differentiation factor and could be a new therapeutic target in human rhabdomyosarcoma.

Levothyroxine treatment restored the decreased circulating fibroblast growth factor 21 levels in patients with hypothyroidism.

PubMed

Wang, Guang; Liu, Jia; Yang, Ning; Hu, Yanjin; Zhang, Heng; Miao, Li; Yao, Zhi; Xu, Yuan

2016-06-01

Fibroblast growth factor 21 (FGF21) is an important endogenous regulator of energy metabolism. Thyroid hormone has been shown to regulate hepatic FGF21 expression in rodents. The goal of this study was to evaluate the plasma FGF21 levels in participants with normal thyroid function, subclinical hypothyroidism, or overt hypothyroidism and to investigate the change of plasma FGF21 levels in patients with overt hypothyroidism after levothyroxine treatment. A total of 473 drug-naive participants were recruited, including 250 healthy control subjects, 116 patients with subclinical hypothyroidism, and 107 patients with overt hypothyroidism. Thirty-eight patients with overt hypothyroidism were assigned to receive levothyroxine treatment. The overt hypothyroidism group had decreased FGF21 levels compared with the control and subclinical hypothyroidism groups (P<0.01). Levothyroxine treatment markedly attenuated the increased circulating levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hsCRP), and homeostasis model assessment index of insulin resistance (HOMA-IR) in patients with overt hypothyroidism. A significant increase in plasma FGF21 levels was observed after levothyroxine treatment (P<0.01). The change in FGF21 levels was correlated with the increase of FT3 and FT4 after levothyroxine treatment (FT3: r=0.44; FT4: r=0.53; all P<0.05). Levothyroxine treatment ameliorated metabolic disorders and restored the decreased circulating FGF21 levels in patients with overt hypothyroidism. The increase in FGF21 levels after levothyroxine treatment might be partly associated with the amelioration of metabolic disorders in patients with hypothyroidism. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Genetic sphingosine kinase 1 deficiency significantly decreases synovial inflammation and joint erosions in murine TNF-alpha-induced arthritis.

PubMed

Baker, DeAnna A; Barth, Jeremy; Chang, Raymond; Obeid, Lina M; Gilkeson, Gary S

2010-08-15

Sphingosine kinase 1 (SphK1) is an enzyme that converts sphingosine to bioactive sphingosine-1-phosphate. Recent in vitro data suggest a potential role of SphK1 in TNF-alpha-mediated inflammation. Our aims in this study were to determine the in vivo significance of SphK1 in TNF-alpha-mediated chronic inflammation and to define which pathogenic mechanisms induced by TNF-alpha are SphK1 dependent. To pursue these aims, we studied the effect of SphK1 deficiency in an in vivo model of TNF-alpha-induced chronic inflammatory arthritis. Transgenic hTNF-alpha mice, which develop spontaneous inflammatory erosive arthritis beginning at 14-16 wk, were crossed with SphK1 null mice (SphK1(-/-)), on the C57BL6 genetic background. Beginning at 4 mo of age, hTNF/SphK1(-/-) mice had significantly less severe clinically evident paw swelling and deformity, less synovial and periarticular inflammation, and markedly decreased bone erosions as measured quantitatively through micro-CT images. Mechanistically, the mice lacking SphK1 had less articular cyclooxygenase 2 protein and fewer synovial Th17 cells than did hTNF/SphK1(+/+) littermates. Microarray analysis and real-time RT-PCR of the ankle synovial tissue demonstrated that hTNF/SphK1(-/-) mice had increased transcript levels of suppressor of cytokine signaling 3 compared with hTNF/SphK1(+/+) mice, likely also contributing to the decreased inflammation in the SphK1-deficient mice. Finally, significantly fewer mature osteoclasts were detected in the ankle joints of hTNF/SphK1(-/-) mice compared with hTNF/SphK1(+/+) mice. These data indicate that SphK1 plays a key role in hTNF-alpha-induced inflammatory arthritis via impacting synovial inflammation and osteoclast number.

Epidermal growth factor treatment decreases mortality and is associated with improved gut integrity in sepsis

PubMed Central

Clark, Jessica A.; Clark, Andrew T.; Hotchkiss, Richard S.; Buchman, Timothy G.; Coopersmith, Craig M.

2007-01-01

Epidermal growth factor (EGF) is a cytoprotective peptide that has healing effects on the intestinal mucosa. We sought to determine whether systemic administration of EGF following the onset of sepsis improved intestinal integrity and decreased mortality. FVB/N mice were subjected to either sham laparotomy or 2×23 cecal ligation and puncture (CLP). Septic mice were further randomized to receive intraperitoneal injection of either 150 μg/kg/day EGF or 0.9% saline. Circulating EGF levels were decreased following CLP compared to sham animals but were unaffected by giving exogenous EGF treatment. In contrast, intestinal EGF levels increased following CLP, and were further augmented by exogenous EGF treatment. Intestinal EGF-receptor (EGF-R) was increased following CLP whether assayed by immunohistochemistry, real-time PCR or western blot, and exogenous EGF treatment decreased intestinal EGF-R. Villus length decreased 2-fold between sham and septic animals, and EGF treatment resulted in near total restitution of villus length. Sepsis decreased intestinal proliferation and increased intestinal apoptosis. This was accompanied by increased expression of the pro-apoptotic proteins Bid and FADD, as well as the cyclin-dependent kinase inhibitor p21cip1/waf. EGF treatment after the onset of sepsis restored both proliferation and apoptosis to levels seen in sham animals and normalized expression of Bid, FADD, and p21cip1/waf. To determine whether improvements in gut homeostasis were associated with a decrease in sepsis-induced mortality, septic mice with or without EGF treatment after CLP were followed seven days for survival. Mortality decreased from 60% to 30% in mice treated with EGF after the onset of sepsis (p<0.05). EGF may thus be a potential therapeutic agent for the treatment of sepsis, in part due to its ability to protect intestinal integrity. PMID:18004230

Decreased Phosphorylated Protein Kinase B (Akt) in Individuals with Autism Associated with High Epidermal Growth Factor Receptor (EGFR) and Low Gamma-Aminobutyric Acid (GABA).

PubMed

Russo, Anthony J

2015-01-01

Dysregulation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway could contribute to the pathogenesis of autism spectrum disorders. In this study, phosphorylated Akt concentration was measured in 37 autistic children and 12, gender and age similar neurotypical, controls using an enzyme-linked immunosorbent assay. Akt levels were compared to biomarkers known to be associated with epidermal growth factor receptor (EGFR) and c-Met (hepatocyte growth factor (HGF) receptor) pathways and severity levels of 19 autism-related symptoms. We found phosphorylated Akt levels significantly lower in autistic children and low Akt levels correlated with high EGFR and HGF and low gamma-aminobutyric acid, but not other biomarkers. Low Akt levels also correlated significantly with increased severity of receptive language, conversational language, hypotonia, rocking and pacing, and stimming, These results suggest a relationship between decreased phosphorylated Akt and selected symptom severity in autistic children and support the suggestion that the AKT pathways may be associated with the etiology of autism.

Decreased expression of hepatocyte growth factor in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

2016-10-01

Pleuroperitoneal folds (PPFs) are essential for normal diaphragmatic development, representing the only source of the diaphragm's muscle connective tissue. Hepatocyte growth factor (Hgf), which is secreted in PPFs, plays a crucial role in the formation of the muscular diaphragmatic components by regulating the migration of myogenic progenitor cells into the primordial diaphragm. Hgf is also a known downstream target of Gata4 and it has been demonstrated that the expression of Hgf was significantly downregulated in PPF cells of Gata4 knockouts with congenital diaphragmatic hernia (CDH). Furthermore, mutations in PPF-derived cells have been shown to result in CDH. We hypothesized that Hgf expression is decreased in developing diaphragms of fetal rats with nitrofen-induced CDH. Timed-pregnant rats were exposed to either nitrofen or vehicle on gestational day 9 (D9). Fetuses were harvested on selected time-points D13, D15 and D18. Dissected diaphragms (n = 72) were divided into control and nitrofen-exposed specimens (n = 12 per time-point and experimental group, respectively). Diaphragmatic gene expression of Hgf was analyzed by qRT-PCR. Immunofluorescence double staining for Hgf and the mesenchymal marker Gata4 or muscular progenitor marker Myogenin was performed to evaluate protein expression and localization in fetal diaphragms. Relative mRNA expression of Hgf was significantly downregulated in PPFs of nitrofen-exposed fetuses on D13 (3.08 ± 1.46 vs. 5.24 ± 1.93; p < 0.05), developing diaphragms of nitrofen-exposed fetuses on D15 (2.01 ± 0.79 vs. 4.10 ± 1.50; p < 0.05) and fully muscularized diaphragms of nitrofen-exposed fetuses on D18 (1.60 ± 0.78 vs. 3.21 ± 1.89; p < 0.05) compared to controls. Confocal laser scanning microscopy revealed markedly diminished diaphragmatic immunofluorescence of Hgf in nitrofen-exposed fetuses on D13, D15 and D18 compared to controls, which was associated with disruptions in muscle connective tissue

Transforming growth factor (TGF. beta. ) decreases the proliferation of human bone marrow fibroblasts by inhibiting the platelet-derived growth factor (PDGF) binding

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

Bryckaert, M.C.; Tobelem, G.; Lindroth, M.

1988-12-01

Human bone marrow fibroblasts were cultivated and characterized by immunofluorescent staining and electron microscopy. Their interactions with PDGF and TGF{beta} were studied. While a positive intracellular antifibronectin staining was observed, the cultured cells were not labeled with specific antibodies toward factor VIII von Willebrand factor (F VIII/vWF), desmin, and macrophage antigen. The binding of pure human PDGF to the cultured bone marrow fibroblasts was investigated. Addition of an excess of unlabeled PDGF decreased the binding to 75 and 80%, which means that the nonspecific binding represented 20-25% of total binding, whereas epidermal growth factor (EGF) had no effect. Two classesmore » of sites were detected by Scatchard analysis. The stimulation of DNA synthesis of PDGF was quantified by ({sup 3}H)thymidine incorporation. The results suggested that PDGF and TGF{beta} could modulate the growth of bone marrow fibroblasts.« less

Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis.

PubMed

Vilaplana, Cristina; Marzo, Elena; Tapia, Gustavo; Diaz, Jorge; Garcia, Vanesa; Cardona, Pere-Joan

2013-07-15

C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

Empirical evidence for acceleration-dependent amplification factors

USGS Publications Warehouse

Borcherdt, R.D.

2002-01-01

Site-specific amplification factors, Fa and Fv, used in current U.S. building codes decrease with increasing base acceleration level as implied by the Loma Prieta earthquake at 0.1g and extrapolated using numerical models and laboratory results. The Northridge earthquake recordings of 17 January 1994 and subsequent geotechnical data permit empirical estimates of amplification at base acceleration levels up to 0.5g. Distance measures and normalization procedures used to infer amplification ratios from soil-rock pairs in predetermined azimuth-distance bins significantly influence the dependence of amplification estimates on base acceleration. Factors inferred using a hypocentral distance norm do not show a statistically significant dependence on base acceleration. Factors inferred using norms implied by the attenuation functions of Abrahamson and Silva show a statistically significant decrease with increasing base acceleration. The decrease is statistically more significant for stiff clay and sandy soil (site class D) sites than for stiffer sites underlain by gravely soils and soft rock (site class C). The decrease in amplification with increasing base acceleration is more pronounced for the short-period amplification factor, Fa, than for the midperiod factor, Fv.

Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet.

PubMed

Blomquist, Caroline; Chorell, Elin; Ryberg, Mats; Mellberg, Caroline; Worrsjö, Evelina; Makoveichuk, Elena; Larsson, Christel; Lindahl, Bernt; Olivecrona, Gunilla; Olsson, Tommy

2017-10-26

We studied effects of diet-induced postmenopausal weight loss on gene expression and activity of proteins involved in lipogenesis and lipolysis in adipose tissue. Fifty-eight postmenopausal women with overweight (BMI 32.5 ± 5.5) were randomized to eat an ad libitum Paleolithic-type diet (PD) aiming for a high intake of protein and unsaturated fatty acids or a prudent control diet (CD) for 24 months. Anthropometry, plasma adipokines, gene expression of proteins involved in fat metabolism in subcutaneous adipose tissue (SAT) and lipoprotein lipase (LPL) activity and mass in SAT were measured at baseline and after 6 months. LPL mass and activity were also measured after 24 months. The PD led to improved insulin sensitivity (P < 0.01) and decreased circulating triglycerides (P < 0.001), lipogenesis-related factors, including LPL mRNA (P < 0.05), mass (P < 0.01), and activity (P < 0.001); as well as gene expressions of CD36 (P < 0.05), fatty acid synthase, FAS (P < 0.001) and diglyceride acyltransferase 2, DGAT2 (P < 0.001). The LPL activity (P < 0.05) and gene expression of DGAT2 (P < 0.05) and FAS (P < 0.05) were significantly lowered in the PD group versus the CD group at 6 months and the LPL activity (P < 0.05) remained significantly lowered in the PD group compared to the CD group at 24 months. Compared to the CD, the PD led to a more pronounced reduction of lipogenesis-promoting factors in SAT among postmenopausal women with overweight. This could have mediated the favorable metabolic effects of the PD on triglyceride levels and insulin sensitivity.

Fndc5 knockdown induced suppression of mitochondrial integrity and significantly decreased cardiac differentiation of mouse embryonic stem cells.

PubMed

Nazem, Shima; Rabiee, Farzaneh; Ghaedi, Kamran; Babashah, Sadegh; Sadeghizadeh, Majid; Nasr-Esfahani, Mohammad Hossein

2018-06-01

Fibronectin type III domain-containing 5 protein (Fndc5) is a glycosylated protein with elevated expression in high energy demanded tissues as heart, brain, and muscle. It has been shown that upregulation of Fndc5 is regulated by peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α), which is known as a master regulator of mitochondrial function and biogenesis. Also, our group indicated that Fndc5 expression increases gradually during cardiac differentiation of mouse embryonic stem cells (mESCs). In this paper, to clarify the importance of Fndc5 in cardiac differentiation, we south to knock down Fndc5 expression by generation a stably transduced mESC line that derives the expression of a short hairpin RNA (shRNA) against Fndc5 gene following doxycycline (Dox) induction. Knock-down of Fndc5 demonstrated a considerable decrease in expression of cardiac progenitor and cardiomyocyte markers. Considering the fact that mitochondria play a crucial role in cardiac differentiation of ESCs, we investigated the role of Fndc5, as a downstream target of PGC1-α, on mitochondrial indices. Results showed that expression of nuclear encoded mitochondrial genes including PGC1-α, Atp5b, Ndufb5, and SOD2 significantly decreased. Moreover, mitochondrial membrane potential (ΔΨm) and relative ATP content of cardiomyocytes decreased markedly with relative ROS level increase. Together, our results suggest that Fndc5 attenuates process of cardiac differentiation of mESCs which is associated with modulation of mitochondrial function and gene expression. © 2017 Wiley Periodicals, Inc.

Decreased performance of live attenuated, oral rotavirus vaccines in low-income settings: causes and contributing factors.

PubMed

Velasquez, Daniel E; Parashar, Umesh; Jiang, Baoming

2018-02-01

Numerous studies have shown that the oral rotavirus vaccines are less effective in infants born in low income countries compared to those born in developed countries. Identifying the specific factors in developing countries that decrease and/or compromise the protection that rotavirus vaccines offer, could lead to a path for designing new strategies for the vaccines' improvement. Areas covered: We accessed PubMed to identify rotavirus vaccine performance studies (i.e., efficacy, effectiveness and immunogenicity) and correlated performance with several risk factors. Here, we review the factors that might contribute to the low vaccine efficacy, including passive transfer of maternal rotavirus antibodies, rotavirus seasonality, oral polio vaccine (OPV) administered concurrently, microbiome composition and concomitant enteric pathogens, malnutrition, environmental enteropathy, HIV, and histo blood group antigens. Expert commentary: We highlight two major factors that compromise rotavirus vaccines' efficacy: the passive transfer of rotavirus IgG antibodies to infants and the  co-administration of rotavirus vaccines with OPV. We also identify other potential risk factors that require further research because the data about their interference with the efficacy of rotavirus vaccines are inconclusive and at times conflicting.

Determination of significant factors controlling compatibility of asphalt with synthetic polymers : final report.

DOT National Transportation Integrated Search

1995-06-01

The primary objective of this work is to evaluate several significant factors controlling compatibility between asphalt and synthetic polymers. Employing nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), differential scanning calor...

Human mesenchymal stromal cells decrease mortality after intestinal ischemia and reperfusion injury.

PubMed

Markel, Troy A; Crafts, Trevor D; Jensen, Amanda R; Hunsberger, Erin Bailey; Yoder, Mervin C

2015-11-01

Cellular therapy is a novel treatment option for intestinal ischemia. Bone marrow-derived mesenchymal stromal cells (BMSCs) have previously been shown to abate the damage caused by intestinal ischemia/reperfusion (I/R) injury. We therefore hypothesized that (1) human BMSCs (hBMSCs) would produce more beneficial growth factors and lower levels of proinflammatory mediators compared to differentiated cells, (2) direct application of hBMSCs to ischemic intestine would decrease mortality after injury, and (3) decreased mortality would be associated with an altered intestinal and hepatic inflammatory response. Adult hBMSCs and keratinocytes were cultured on polystyrene flasks. For in vitro experiments, cells were exposed to tumor necrosis factor, lipopolysaccharides, or 2% oxygen for 24 h. Supernatants were then analyzed for growth factors and chemokines by multiplex assay. For in vivo experiments, 8- to 12-wk-old male C57Bl6J mice were anesthetized and underwent a midline laparotomy. Experimental groups were exposed to temporary superior mesenteric artery occlusion for 60 min. Immediately after ischemia, 2 × 10(6) hBMSCs or keratinocytes in phosphate-buffered saline were placed into the peritoneal cavity. Animals were then closed and allowed to recover for 6 h (molecular/histologic analysis) or 7 d (survival analysis). After 6-h reperfusion, animals were euthanized. Intestines and livers were harvested and analyzed for inflammatory chemokines, growth factors, and histologic changes. hBMSCs expressed higher levels of human interleukin (IL) 6, IL-8, vascular endothelial growth factor (VEGF), and epidermal growth factor and lower levels of IL-1, IL-3, IL-7, and granulocyte-monocyte colony-stimulating factor after stimulation. In vivo, I/R resulted in significant mortality (70% mortality), whereas application of hBMSCs after ischemia decreased mortality to 10% in a dose-dependent fashion (P = 0.004). Keratinocyte therapy offered no improvements in mortality

Sucroferric oxyhydroxide decreases serum phosphorus level and fibroblast growth factor 23 and improves renal anemia in hemodialysis patients.

PubMed

Shima, Hisato; Miya, Keiko; Okada, Kazuyoshi; Minakuchi, Jun; Kawashima, Shu

2018-06-08

Sucroferric oxyhydroxide, a novel iron-based phosphate-binder, has been shown to have beneficial effects in lowering serum phosphorus levels and improving renal anemia in clinical studies. Although an effect of this agent on fibroblast growth factor 23 (FGF23) has been reported in an animal study, there is little clinical data supporting this finding. This study aimed to evaluate the effect on chronic kidney disease-mineral and bone disorder, FGF23, renal anemia, iron-related parameters, adverse events of sucroferric oxyhydroxide in hemodialysis patients. Hemodialysis patients, receiving existing hyperphosphatemia drugs with insufficient benefit, were administered sucroferric oxyhydroxide with/without calcium carbonate for 16 weeks. Serum phosphorus level declined rapidly in Week 8 (p < 0.0001) and this decrease persisted until Week 16 (p < 0.0001). FGF23 decreased (p = 0.0412, Week 16), and hemoglobin increased (p < 0.0001, Week 16). Cumulative dose of erythropoiesis-stimulating agents (p = 0.0122, Week 16), and intravenous iron (p = 0.0233, Week 12) decreased. All adverse reactions were mild, and diarrhea was the most frequently observed adverse reaction (16.7%). Therefore, hyperphosphatemia treatment with sucroferric oxyhydroxide may safely improve serum phosphorus level, renal anemia, FGF23, and other factors that affect the prognosis of hemodialysis patients.

Decreased prothrombotic effects of pegylated recombinant human megakaryocyte growth and development factor in thrombocytopenic state in a rat thrombosis model.

PubMed

Nishiyama, U; Kuwaki, T; Akahori, H; Kato, T; Ikeda, Y; Miyazaki, H

2005-02-01

Previous in vitro studies demonstrated that thrombopoietin (TPO) acts on platelets to activate a variety of intracellular signaling pathways and to enhance platelet sensitivity to multiple agonists. Little is known, however, about whether TPO exerts prothrombotic effects in vivo. The aim of this study was to examine the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a pegylated N-terminal domain of human TPO, in a rat model of venous thrombosis. A microthrombus was photochemically induced on the vessel wall of a mesenteric venule, but the vessel was not occluded by it. A single intravenous injection of PEG-rHuMGDF (3 microg kg(-1)) after the thrombus generation into normal rats enhanced the thrombus size, resulting in transient thrombotic occlusion in the majority of rats. Stimulatory effects on thrombus growth were also observed following administration of glycosylated recombinant human full-length TPO (6 microg kg(-1)). In rats rendered thrombocytopenic by total body irradiation, however, PEG-rHuMGDF, even at 300 microg kg(-1), did not induce a significant increase in thrombus size or thrombotic occlusion. Platelets from thrombocytopenic rats had decreased surface levels of c-Mpl and decreased sensitivity to PEG-rHuMGDF in an in vitro aggregation response. Thus, decreased prothrombotic effects of PEG-rHuMGDF in thrombocytopenic rats might be the result not only of low platelet counts but also of decreased platelet reactivity to PEG-rHuMGDF. These results indicate that PEG-rHuMGDF has little effect on venous thrombus formation in thrombocytopenic states associated with high endogenous TPO levels.

Clinical and biological significance of hepatoma-derived growth factor in Ewing's sarcoma.

PubMed

Yang, Yang; Li, Hui; Zhang, Fenfen; Shi, Huijuan; Zhen, Tiantian; Dai, Sujuan; Kang, Lili; Liang, Yingjie; Wang, Jin; Han, Anjia

2013-11-01

We sought to investigate the clinicopathological significance and biological function of hepatoma-derived growth factor (HDGF) in Ewing's sarcoma. Our results showed that HDGF expression is up-regulated in Ewing's sarcoma. Nuclear HDGF expression is significantly associated with tumour volume (p < 0.001), metastases at diagnosis (p < 0.001), low overall survival rate (p < 0.001) and low disease-free survival rate (p < 0.001). HDGF knock-down results in significant reduction of Ewing's sarcoma cell growth, proliferation and enhances tumourigenesis, both in vitro and in vivo. Meanwhile, HDGF knock-down causes cell cycle arrest and enhanced sensitization to serum starvation-induced apoptosis. Furthermore, recombinant HDGF promotes proliferation and colony formation of Ewing's sarcoma cells. Ninety-eight candidate HDGF downstream genes were identified in Ewing's sarcoma cells using cDNA microarray analysis. In addition, we found that HDGF knock-down inhibited FLI1 expression in Ewing's sarcoma cells at the mRNA and protein levels. Our findings suggest that HDGF exhibits oncogenic properties and may be a novel prognostic factor in Ewing's sarcoma. Targeting HDGF might be a potential therapeutic strategy for Ewing's sarcoma. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Risk factors of significant pain syndrome 90 days after minor thoracic injury: trajectory analysis.

PubMed

Daoust, Raoul; Emond, Marcel; Bergeron, Eric; LeSage, Natalie; Camden, Stéphanie; Guimont, Chantal; Vanier, Laurent; Chauny, Jean-Marc

2013-11-01

The objective was to identify the risk factors of clinically significant pain at 90 days in patients with minor thoracic injury (MTI) discharged from the emergency department (ED). A prospective, multicenter, cohort study was conducted in four Canadian EDs from November 2006 to November 2010. All consecutive patients aged 16 years or older with MTI were eligible at discharge from EDs. They underwent standardized clinical and radiologic evaluations at 1 and 2 weeks, followed by standardized telephone interviews at 30 and 90 days. A pain trajectory model characterized groups of patients with different pain evolutions and ascertained specific risk factors in each group through multivariate analysis. In this cohort of 1,132 patients, 734 were eligible for study inclusion. The authors identified a pain trajectory that characterized 18.2% of the study population experiencing clinically significant pain (>3 of 10) at 90 days after a MTI. Multivariate modeling found two or more rib fractures, smoking, and initial oxygen saturation below 95% to be predictors of this group of patients. To the authors' knowledge, this is the first prospective study of trajectory modeling to detect risk factors associated with significant pain at 90 days after MTI. These factors may help in planning specific treatment strategies and should be validated in another prospective cohort. © 2013 by the Society for Academic Emergency Medicine.

A mild transient decrease of peripheral red blood cell counts induced by a suprapharmacological dose of pegylated human megakaryocyte growth and development factor in rats.

PubMed

Harada, K; Ide, Y; Tazunoki, Y; Imai, A; Yanagida, M; Kikuchi, Y; Imai, A; Ishii, H; Kawahara, J; Izumi, H; Kusaka, M; Tokiwa, T

1999-07-01

Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in

Plasma FGF21 concentrations, adipose fibroblast growth factor receptor-1 and β-klotho expression decrease with fasting in northern elephant seals.

PubMed

Suzuki, Miwa; Lee, Andrew Y; Vázquez-Medina, José Pablo; Viscarra, Jose A; Crocker, Daniel E; Ortiz, Rudy M

2015-05-15

Fibroblast growth factor (FGF)-21 is secreted from the liver, pancreas, and adipose in response to prolonged fasting/starvation to facilitate lipid and glucose metabolism. Northern elephant seals naturally fast for several months, maintaining a relatively elevated metabolic rate to satisfy their energetic requirements. Thus, to better understand the impact of prolonged food deprivation on FGF21-associated changes, we analyzed the expression of FGF21, FGF receptor-1 (FGFR1), β-klotho (KLB; a co-activator of FGFR) in adipose, and plasma FGF21, glucose and 3-hydroxybutyrate in fasted elephant seal pups. Expression of FGFR1 and KLB mRNA decreased 98% and 43%, respectively, with fasting duration. While the 80% decrease in mean adipose FGF21 mRNA expression with fasting did not reach statistical significance, it paralleled the 39% decrease in plasma FGF21 concentrations suggesting that FGF21 is suppressed with fasting in elephant seals. Data demonstrate an atypical response of FGF21 to prolonged fasting in a mammal suggesting that FGF21-mediated mechanisms have evolved differentially in elephant seals. Furthermore, the typical fasting-induced, FGF21-mediated actions such as the inhibition of lipolysis in adipose may not be required in elephant seals as part of a naturally adapted mechanism to support their unique metabolic demands during prolonged fasting. Copyright © 2015 Elsevier Inc. All rights reserved.

Plasma FGF21 Concentrations, Adipose Fibroblast Growth Factor Receptor-1 and β-Klotho Expression Decrease with Fasting in Northern Elephant Seals

PubMed Central

Suzuki, Miwa; Lee, Andrew; Vázquez-Medina, Jose Pablo; Viscarra, Jose A.; Crocker, Daniel E.; Ortiz, Rudy M.

2015-01-01

Fibroblast growth factor (FGF)-21 is secreted from the liver, pancreas, and adipose in response to prolonged fasting/starvation to facilitate lipid and glucose metabolism. Northern elephant seals naturally fast for several months, maintaining a relatively elevated metabolic rate to satisfy their energetic requirements. Thus, to better understand the impact of prolonged food deprivation on FGF21-associated changes, we analyzed the expression of FGF21, FGF receptor-1 (FGFR1), β-klotho (KLB; a co-activator of FGFR) in adipose, and plasma FGF21, glucose and 3-hydroxybutyrate in fasted elephant seal pups. Expression of FGFR1 and KLB mRNA decreased 98% and 43%, respectively, with fasting duration. While the 80% decrease in mean adipose FGF21 mRNA expression with fasting did not reach statistical significance, it paralleled the 39% decrease in plasma FGF21 concentrations suggesting that FGF21 is suppressed with fasting in elephant seals. Data demonstrate an atypical response of FGF21 to prolonged fasting in a mammal suggesting that FGF21-mediated mechanisms have evolved differentially in elephant seals. Furthermore, the typical fasting-induced, FGF21-mediated actions such as the inhibition of lipolysis in adipose may not be required in elephant seals as part of a naturally adapted mechanism to support their unique metabolic demands during prolonged fasting. PMID:25857751

A Low Glycemic Index and Glycemic Load Diet Decreases Insulin-like Growth Factor-1 among Adults with Moderate and Severe Acne: A Short-Duration, 2-Week Randomized Controlled Trial.

PubMed

Burris, Jennifer; Shikany, James M; Rietkerk, William; Woolf, Kathleen

2018-04-21

A high glycemic index (GI) and glycemic load (GL) diet may stimulate acne proliferative pathways by influencing biochemical factors associated with acne. However, few randomized controlled trials have examined this relationship, and this process is not completely understood. This study examined changes in biochemical factors associated with acne among adults with moderate to severe acne after following a low GI and GL diet or usual eating plan for 2 weeks. This study utilized a parallel randomized controlled design to compare the effect of a low GI and GL diet to usual diet on biochemical factors associated with acne (glucose, insulin, insulin-like growth factor [IGF]-1, and insulin-like growth factor binding protein [IGFBP]-3) and insulin resistance after 2 weeks. Sixty-six participants were randomly allocated to the low GI and GL diet (n=34) or usual eating plan (n=32) and included in the analyses. The primary outcomes were biochemical factors of acne and insulin resistance with dietary intake as a secondary outcome. Independent sample t tests assessed changes in biochemical factors associated with acne, dietary intake, and body composition pre- and postintervention, comparing the two dietary interventions. IGF-1 concentrations decreased significantly among participants randomized to a low GI and GL diet between pre- and postintervention time points (preintervention=267.3±85.6 mg/mL, postintervention=244.5±78.7 ng/mL) (P=0.049). There were no differences in changes in glucose, insulin, or IGFBP-3 concentrations or insulin resistance between treatment groups after 2 weeks. Carbohydrate (P=0.019), available carbohydrate (P<0.001), percent energy from carbohydrate (P<0.001), GI (P<0.001), and GL (P<0.001) decreased significantly among participants following a low GI/GL diet between the pre- and postintervention time points. There were no differences in changes in body composition comparing groups. In this study, a low GI and GL diet decreased IGF-1 concentrations

Inflammation factors in hepatoblastoma and their clinical significance as diagnostic and prognostic biomarkers.

PubMed

Guo, Fei; Ru, Qin; Zhang, Junjie; He, Shen; Yu, Jiekai; Zheng, Shu; Wang, Jiaxiang

2017-09-01

The aims of this study were to identify inflammation factors in hepatoblastoma tissue that correlated with different clinical characteristics, and to explore the probability as predictive biomarkers for diagnosis and prognosis. SELDI-TOF-MS was performed to screen protein peaks that were significantly highly expressed in tumor tissue compared with adjacent liver tissue. After removing proteins larger than 30kDa, the targeted peaks were separated by solid phase extraction and tricine-SDS-PAGE. Protein fragments produced by in-gel digestion were identified by LC-MS/MS. Immunohistochemical assays further confirmed these results. Overall survival curves were graphed by Kaplan-Meier method and multivariate analysis was performed by Cox proportional hazards regression model. Three protein peaks (m/z 12,138, m/z 13,462, and m/z 15,120) that were significantly upregulated in the tumor tissue were identified as macrophage migration inhibitory factor (MIF), chemokine (C-X-C motif) ligand 7 (CXCL7), and interleukin 25 (IL-25). These factors were closely related to clinical stage, lymph node metastasis, vascular invasion and serum AFP level. High expression of each inflammatory marker indicated poor prognosis. Multivariate analysis suggested that MIF, CXCL7, and IL-25 were prognostic factors independent of patient sex, age and tumor histological type. MIF, CXCL7, and IL-25 might be considered as effective inflammation factors for diagnosis and prognosis of hepatoblastoma and as potential novel treatment targets through inhibition of inflammatory function. Prognosis study LEVEL OF EVIDENCE: Level I. Copyright © 2017 Elsevier Inc. All rights reserved.

The significance of organizational factors for the incidence of bullying.

PubMed

Agervold, Mogens

2009-06-01

It is frequently assumed that a poor psychosocial working environment will create conditions that encourage bullying. However, few studies have examined this assumption while comparing work environment ratings of bullied and non-bullied employees who work in the same organization and/or department. The objective of this study was to examine the relationship between organizational factors and the incidence of acts of bullying based on two different approaches: the first by comparing bullied with no-bullied, the second by comparing departments with widespread bullying with departments with little bullying. The study was a part of a general survey study of the work environment and employee well-being in 12 different local social security offices. A total of 898 persons participated in the study (a response rate of 88%). First, the results showed a clear relationship between bullying and fear of organizational change; secondly, weak, but significant, correlations between bullying and other organizational factors; thirdly, the subsequent analyses compared departments in which bullying were most widespread with the rest of the departments. The results supported the hypothesis that departments that suffer from much bullying also have a poorer psychosocial work environment, results that support the assumption that organizational factors such as changes in one's position, pressure of work, performance demands, autocratic management and role conflict and lack of role clarity, as well as a poor social climate can contribute to the emergence of higher incidences of bullying.

Dapagliflozin significantly reduced liver fat accumulation associated with a decrease in abdominal subcutaneous fat in patients with inadequately controlled type 2 diabetes mellitus.

PubMed

Kurinami, Noboru; Sugiyama, Seigo; Yoshida, Akira; Hieshima, Kunio; Miyamoto, Fumio; Kajiwara, Keizo; Jinnouch, Katsunori; Jinnouchi, Tomio; Jinnouchi, Hideaki

2018-05-31

We examined dapagliflozin-induced changes in liver fat accumulation. We prospectively recruited Japanese patients with inadequately controlled type 2 diabetes mellitus (T2DM) [hemoglobin A1c (HbA1c) >7.0%]. Dapagliflozin (5 mg/day) or non-sodium glucose cotransporter 2 inhibitors (SGLT2i) was added to the patients' treatment regimen for 6 months. Changes in liver fat accumulation were assessed by the liver-to-spleen (L/S) attenuation ratio using abdominal computed tomography (CT). This study enrolled 55 Japanese T2DM patients. The L/S ratio significantly increased in the dapagliflozin group compared with the non-SGLT2i group. Abdominal subcutaneous fat area (SFA), visceral fat area, total fat area assessed by abdominal CT, aspartate aminotransferase, alanine aminotransferase (ALT), and γ-glutamyl transpeptidase decreased significantly only in the dapagliflozin group. Changes in the L/S ratio showed a significant negative relationship with changes in abdominal SFA, ALT, and non-esterified fatty acid. In sub-group analyses of non-insulin users, hepatic insulin extraction was assessed by the plasma C-peptide-to-insulin ratio, which was significantly increased in the dapagliflozin group but not in the non-SGLT2i group. In patients with inadequately controlled T2DM, additional dapagliflozin-treatment significantly reduced the liver fat accumulation associated with a decrease in abdominal SFA. Copyright © 2018 Elsevier B.V. All rights reserved.

Short Hairpin Ribonucleic Acid Constructs Targeting Insulin-like Growth Factor Binding Protein-3 Reversed Decreased Testosterone Concentrations in Diabetic Rats

PubMed Central

Zhou, Zhang-Yan; Fei-Li; Cheng, Shao-Ping; Huang, Hui; Peng, Bi-Wen; Wang, Jing; Liu, Chang-Mao; Xing, Cheng; Sun, Ya-Ling; Bsoul, Najeeb; Pan, Hui; Yi, Cun-Jian; Liu, Rong-Hua; Zhong, Guang-Jun

2015-01-01

Background The aim of this study was to determine if shRNA constructs targeting insulin-like growth factor binding protein-3 can rehabilitate decreased serum testosterone concentrations in streptozotocin-induced diabetic rats. Material/Methods After 12 weeks of intracavernous administration of IGFBP-3 shRNA, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 at mRNA and protein levels was detected by quantitative real-time PCR analysis and Western blot, respectively. The concentrations of serum testosterone and cavernous cyclic guanosine monophosphate were detected by enzyme-linked immunosorbent assay. Results After 12 weeks of intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic control group (p<0.01). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. Both serum testosterone and cavernous cyclic guanosine monophosphate concentrations were significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic control group (p<0.01). Conclusions These results suggest that IGFBP-3 shRNA may rehabilitate erectile function via increases of concentrations of serum testosterone and cavernous cyclic guanosine monophosphate in streptozotocin-induced diabetic rats. PMID:25582342

Ecological Factors Affecting Access to General Education Content and Contexts for Students with Significant Disabilities

ERIC Educational Resources Information Center

Ruppar, Andrea L.; Allcock, Heather; Gonsier-Gerdin, Jean

2017-01-01

In this review, we applied Bronfenbrenner's ecological systems theory to examine factors that support or restrict access to the general curriculum for students with significant disabilities. We organize the literature in relationship to factors within the micro-, meso-, macro-, exo-, and chronosystems that influence decisions about access to the…

Expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in brain tissue of diabetic rats with ischemia reperfusion.

PubMed

Liang, Yu-Zhi; Zeng, Zhi-Lei; Hua, Lin-Lin; Li, Jin-Feng; Wang, Yun-Liang; Bi, Xi-Zhuang

2016-06-01

To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. A total of 60 male Wistar rats were randomly divided into the normal group, sham group, diabetic cerebral infarction group and single cerebral infarction group according to the random number table, with 15 rats in each group. The high sucrose diet and intraperitoneal injection of streptozotocin were performed for the modeling of diabetic rats, while the thread-occlusion method was employed to build the model of cerebral ischemia reperfusion. The immunohistochemical staining was performed to detect the expression of angiostatin, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the brain tissue. The expression of angiostatin after the reperfusion in the brain tissue of rats in the single cerebral infarction group and diabetic cerebral infarction group was increased 6 h after the reperfusion, reached to the peak on 1 d and then decreased gradually. The expression of angiostatin in the diabetic cerebral infarction group 6 h, 1 d, 3 d and 7 d after the reperfusion was significantly higher than that in the single cerebral infarction group (P < 0.05). VEGF began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak at 6 h and then decreased gradually. The expression of VEGF in the diabetic cerebral infarction group at each time point after the reperfusion was significantly lower than that in the single cerebral infarction group (P < 0.05). MMP-9 began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak on 1 d and then decreased gradually. The expression of MMP-9 in the diabetic cerebral infarction group at each time point after the reperfusion was significantly

Causes of decreased activity of daily life in elderly patients who need daily living care.

PubMed

Yoshino, Hiroshi; Sakurai, Takashi; Hasegawa, Kazuo; Yokono, Koichi

2011-07-01

The causes of decreased activity of daily life (ADL) in elderly patients include cerebrovascular diseases, bone fracture by falls, and dementia. The present study was conducted among elderly patients with decreased ADL who were hospitalized in nursing wards in order to investigate the causes of becoming early bedridden and to determine precautionary measures against decreased ADL. The study subjects were 224 elderly patients with decreased ADL (mean age: 83.3 ± 8.0 years) and 49 outpatients without decreased ADL (mean age: 76.8 ± 5.3 years). Current age, age at the start of ADL decrease, medical history and history of smoking were investigated. In the groups with decreased ADL, current age and the age of becoming bedridden in non-diabetic versus diabetic groups were 84.7 ± 7.9 versus 80.3 ± 7.5 and 82.7 ± 8.3 versus 77.6 ± 8.0 years, respectively, both showing significantly lower values in the diabetic group (P < 0.05). Multiple regression analysis revealed that sex difference and diabetes were the factors determining the age of becoming early bedridden. Diabetic patients with smoking habit were significantly younger than diabetic and non-diabetic patients without smoking habit. Sex difference, smoking habit and presence of diabetes mellitus are independent risk factors of becoming early bedridden. Therefore, the major targets of medical care among elderly should be diabetic men with a smoking habit to lower the risks of decreased ADL. © 2011 Japan Geriatrics Society.

Prognostic significance of ligands belonging to tumour necrosis factor superfamily in acute lymphoblastic leukaemia.

PubMed

Bolkun, L; Lemancewicz, D; Jablonska, E; Szumowska, A; Bolkun-Skornicka, U; Moniuszko, M; Dzieciol, J; Kloczko, J

2015-03-01

Altered activities of ligands belonging to tumour necrosis factor (TNF) superfamily, namely B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and apoptosis inducing ligand (TRAIL) were demonstrated in several haematological diseases including acute lymphoblastic leukaemia (ALL). BAFF, APRIL and TRAIL provide crucial survival signals to immature, naive and activated B cells. These ligands are capable of activating a broad spectrum of intracellular signalling cascades that can either induce apoptosis or protect from programmed cell death. BAFF and APRIL, which can directly activate the NF-κB pathway, have been identified as crucial survival factors for ALL cells. Here, we have analyzed serum BAFF, APRIL and TRAIL concentrations in 48 patients with newly diagnosed ALL and 44 healthy volunteers. The levels of APRIL and BAFF were significantly higher in ALL patients as compared to healthy volunteers. In contrast, concentrations of TRAIL were significantly lower in ALL patients. Moreover, following induction, the levels of APRIL, but not BAFF or TRAIL, were significantly lower in a group of patients with complete remission (CR) as compared to non-respondent (NR) ALL patients. Furthermore, we demonstrated statistically significant differences in concentrations of APRIL between CR MRD-negative and CR, MRD-positive ALL patients. Notably detection of higher concentrations of APRIL was associated with shorter leukaemia-free survival and overall survival. Altogether, our data indicate that APRIL can play an important role in the pathogenesis of ALL and the measurement of APRIL levels can improve prognostication in ALL patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tumor Necrosis Factor-induced Decrease of Cochlear Blood Flow Can Be Reversed by Etanercept or JTE-013.

PubMed

Sharaf, Kariem; Ihler, Friedrich; Bertlich, Mattis; Reichel, Christoph A; Berghaus, Alexander; Canis, Martin

2016-08-01

This study aimed to quantify the effects of tumor necrosis factor (TNF) inhibitor Etanercept and sphingosine-1-phosphate receptor 2 antagonist JTE-013 on cochlear blood flow in guinea pigs after TNF-induced decrease. Sudden sensorineural hearing loss is a common cause for disability and reduced quality of life. Good understanding of the pathophysiology and strong evidence-based therapy concepts are still missing. In various inner ear disorders, inflammation and impairment of cochlear blood flow (CBF) have been considered factors in the pathophysiology. A central mediator of inflammation and microcirculation in the cochlea is TNF. S1P acts downstream in one TNF pathway. Cochlea lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. Twenty-eight animals were randomly distributed into four groups of seven each. Exposed vessels were superfused by TNF (5.0 ng/ml) and afterward repeatedly either by Etanercept (1.0 μg/ml), JTE-013 (10 μmol/L), or vehicle (0.9 % NaCl solution or ethanol: phosphate-buffered saline buffer, respectively). After decreasing CBF with TNF (p <0.001, two-way RM ANOVA), both treatments reversed CBF, compared with vehicle (p <0.001, two-way RM ANOVA). The comparison of the vehicle groups showed no difference (p = 0.969, two-way RM ANOVA), while there was also no difference between the treatment groups (p = 0.850, two-way RM ANOVA). Both Etanercept and JTE-013 reverse the decreasing effect of TNF on cochlear blood flow and, therefore, TNF and the S1P-signalling pathway might be targets for treatment of microcirculation-related hearing loss.

Significant factors associated with fatal outcome in emergency open surgery for perforated peptic ulcer.

PubMed

Testini, Mario; Portincasa, Piero; Piccinni, Giuseppe; Lissidini, Germana; Pellegrini, Fabio; Greco, Luigi

2003-10-01

To evaluate the main factors associated with mortality in patients undergoing surgery for perforated peptic ulcer referred to an academic department of general surgery in a large southern Italian city. One hundred and forty-nine consecutive patients (M:F ratio=110:39, mean age 52 yrs, range 16-95) with peptic ulcer disease were investigated for clinical history (including age, sex, previous history of peptic ulcer, associated diseases, delayed abdominal surgery, ulcer site, operation type, shock on admission, postoperative general complications, and intra-abdominal and/or wound infections), serum analyses and radiological findings. The overall mortality rate was 4.0%. Among all factors, an age above 65 years, one or more associated diseases, delayed abdominal surgery, shock on admission, postoperative abdominal complications and/or wound infections, were significantly associated (chi2) with increased mortality in patients undergoing surgery (0.0001Factors such as concomitant diseases, shock on admission, delayed surgery, and postoperative abdominal and wound infections are significantly associated with fatal outcomes and need careful evaluation within the general workup of patients admitted for perforated peptic ulcer.

Significant factors for work attractiveness and how these differ from the current work situation among operating department nurses.

PubMed

Björn, Catrine; Lindberg, Magnus; Rissén, Dag

2016-01-01

The aim was to examine significant factors for work attractiveness and how these differ from the current work situation among operating department nurses. A second objective was to examine the associations between age, gender, length of employment, work engagement, work ability, self-rated health indicators and attractiveness of the current work situation. The attractiveness of work is rarely taken into account in research on nurse retention. To expand this knowledge, it is relevant to examine factors that make work attractive and their associations with related concepts. Correlational, cross-sectional survey using a convenience sample. Questionnaires were answered by 147 nurses in four operating departments in Sweden. Correlation and regression analyses were conducted. The nurses rated the significance of all factors of work attractiveness higher than they rated those factors in their current work situation; salary, organisation and physical work environment had the largest differences. The most significant attractive factors were relationships, leadership and status. A statistically significant positive correlation between work engagement and attractive work was found. In the multiple regression model, the independent variables work engagement and older age significantly predicted work attractiveness. Several factors should be considered in the effort to increase work attractiveness in operating departments and thereby to encourage nurse retention. Positive aspects of work seem to unite work engagement and attractive work, while work ability and self-rated health indicators are other important dimensions in nurse retention. The great discrepancies between the significance of attractive factors and the current work situation in salary, organisation and physical work environment suggest ways in which work attractiveness may be increased. To discover exactly what needs to be improved may require a deeper look into the construct of the examined factors. © 2015 John

Decreased plasma concentrations of brain-derived neurotrophic factor (BDNF) in patients with functional hypothalamic amenorrhea.

PubMed

Podfigurna-Stopa, Agnieszka; Casarosa, Elena; Luisi, Michele; Czyzyk, Adam; Meczekalski, Blazej; Genazzani, Andrea Riccardo

2013-09-01

Functional hypothalamic amenorrhea (FHA) is a non organic, secondary amenorrhea related to gonadotropin-releasing hormone pulsatile secretion impairment. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays an important role in the growth, development, maintenance and function of several neuronal systems. The aim of the study was the evaluation of plasma BDNF concentrations in patients with the diagnosis of FHA. We studied 85 subjects diagnosed with FHA who were compared with 10 healthy, eumenorrheic controls with normal body mass index. Plasma BDNF and serum luteinizing hormone, follicle-stimulating hormone and estradiol (E2) concentrations were measured by immunoenzymatic method (enzyme-linked immunosorbent assay). Significantly lower concentration of plasma BDNF was found in FHA patients (196.31 ± 35.26 pg/ml) in comparison to healthy controls (407.20 ± 25.71 pg/ml; p < 0.0001). In the control group, there was a strong positive correlation between plasma BDNF and serum E2 concentrations (r = 0.92, p = 0.0001) but in FHA group it was not found. Role of BDNF in FHA is not yet fully understood. There could be found studies concerning plasma BDNF concentrations in humans and animals in the literature. However, our study is one of the first projects which describes decreased plasma BDNF concentration in patients with diagnosed FHA. Therefore, further studies on BDNF in FHA should clarify the role of this peptide.

[The clinical significance of the measurement of plasma transferrin as a growth factor. II. The changes in various endocrine status].

PubMed

Matsubara, M; Odagaki, E; Morioka, T; Nakagawa, K

1987-05-20

The clinical significance of the measurement of plasma transferrin (Tf) in patients with hypophysial disorders was reported in our previous papers. In the present study, we determined plasma Tf levels in 55 patients with various endocrine states and considered their clinical significance compared with plasma somatomedin-C (SM-C) levels. Plasma Tf levels decreased significantly in patients with anorexia nervosa (p less than 0.02), hyperthyroidism (p less than 0.05), primary hypothyroidism (p less than 0.05) and Cushing's syndrome (p less than 0.05), while they were elevated significantly in pregnancy (p less than 0.01) or females using estrogens (p less than 0.05). The former two declines were considered a reflection of the malnutritional state of the patients since a significant negative correlation was observed between plasma Tf levels and the percentile deficit from the ideal body weight in patients with anorexia nervosa (p less than 0.01), or between plasma Tf levels and elevated T3 levels which induce hypermetabolism in patients with hyperthyroidism (p less than 0.01). A significant correlation was observed between the SM-C and Tf levels in these subjects (including normal controls and patients with hypophysial disorders) as a whole (r = 0.79, p less than 0.001). These data indicate that plasma Tf is changeable according to the endocrinological and nutritional conditions with good correlation to the SM-C, and it is suggested that Tf also operates as a growth factor in vivo.

Significance of primary factors influencing students' performance at the College of Dentistry, King Saud University, Saudi Arabia.

PubMed

Al-Amri, Mohammad; Al-Madi, Ebtissam; Sadig, Walid Mahmoud; Ahmedani, Muhammad Shoaib; Salameh, Ziad

2012-08-01

To determine the effect of different enabling factors such as curriculum, role of faculty, academic advising and availability of learning resources and supportive services on the performance of students pursuing their Bachelor's degree in dentistry. Data was collected from the male and female students of the College of Dentistry, King Saud University, during the academic year 2008-2009. All undergraduate students (576) constituted the total sample size of the study. The respondents were requested to fill a questionnaire form, which was specially designed in accordance with requirements of the Association for Dental Education in Europe (ADEE). The questionnaire comprised 45 questions addressing all aspects of the relevant factors. The five-point Likert scale was used to evaluate the feedback. All the responses (239) were thoroughly examined and only the completely filled forms (169) were subjected to regression analyses, taking student's CGPA as a dependent factor and a depiction of their performance. The t-tests were also worked out to evaluate variations in the responses of male and female students to each sub-factor. The study showed a significant impact of faculty and learning resources and support services on a student's achievement (alpha = 0.05). Surprisingly, academic advising and the dental curriculum had non-significant effect at 95% level of confidence. However, the critical analyses acknowledged that the non-significant impact was due to poor performance of the two factors. The role of faculty and learning resources as well as of support services had significant effect on students' performance. However, there is an immense need to improve the level of academic advising and revise the curriculum to have a significant impact of these factors on the student's achievements.

Somatostatin analogs regress endometriotic implants in rats by decreasing implant levels of vascular endothelial growth factor and matrix metaloproteinase 9.

PubMed

Sevket, Osman; Sevket, Asli; Molla, Taner; Buyukpınarbasılı, Nur; Uysal, Omer; Yılmaz, Bulent; Dane, Banu; Kelekcı, Sefa

2013-06-01

To examine the effect of somatostatin analogs on surgically induced endometriosis in rat models. Endometrial tissue was implanted onto the abdominal peritoneum of 26 rats that were randomized into 3 groups. The rats in group 1(n = 9) were subcutaneously administered with 0.02 mg/kg/d of octreotide (a short-acting analog)for 28 days . The rats in group 2 (n = 8) were subcutaneously injected with 20 mg/kg of a single dose of a long-acting analogue lanreotide The rats in group 3 were given no medication and served as controls (n = 9). Mean volume and histologic score of implants in groups 1 (P < .01 and P < .05, respectively) and 2 (P < .01and P < .05, respectively) were significantly lower than that in group 3. There were significant reductions in vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) immunoreactivities in group 1 (0.67 ± 0.50 and 1.22 ± 0.44, respectively; both P < .01) and group 2 (0.71 ± 0.48 and 0.86 ± 0.69, respectively; both P < .01) when compared with the control group (1.78 ± 0.83 and 2.11 ± 0.78, respectively). Somatostatin analogs has regressed significantly the size of the endometriotic implants and caused atrophy of these lesions in rats by decreasing explant levels of VEGF and MMP-9.

Hypothalamic-pituitary-adrenal axis hyperactivity is associated with decreased brain-derived neurotrophic factor in female suicide attempters.

PubMed

Ambrus, Livia; Lindqvist, Daniel; Träskman-Bendz, Lil; Westrin, Åsa

2016-11-01

Both decreased levels of brain-derived neurotrophic factor (BDNF) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation may be involved in the pathophysiology of suicidal behaviour, as well as cognitive symptoms of depression. Pre-clinical and clinical studies have shown interactions between HPA-axis activity and BDNF, but this has not been studied in a clinical cohort of suicidal subjects. The purpose of this study was, therefore, to investigate associations between HPA-axis activity and BDNF in suicide attempters. Furthermore, this study examined the relationship between the HPA-axis, BDNF, and cognitive symptoms in suicidal patients. Since previous data indicate gender-related differences in BDNF and the HPA axis, males and females were examined separately. Seventy-five recent suicide attempters (n = 41 females; n = 34 males) were enrolled in the study. The Dexamethasone Suppression Test (DST) was performed and BDNF in plasma were analysed. Patients were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) from which items 'Concentration difficulties' and 'Failing memory' were extracted. Only among females, DST non-suppressors had significantly lower BDNF compared to DST suppressors (p = 0.022), and there was a significant correlation between post-DST serum cortisol at 8 a.m. and BDNF (rs = -0.437, p = 0.003). Concentration difficulties correlated significantly with post-DST cortisol in all patients (rs = 0.256, p = 0.035), in females (rs = 0.396, p = 0.015), and with BDNF in females (rs = -0.372, p = 0.020). The findings suggest an inverse relationship between the HPA-axis and BDNF in female suicide attempters. Moreover, concentration difficulties may be associated with low BDNF and DST non-suppression in female suicide attempters.

Lipopolysaccharide and hypoxia significantly alters interleukin-8 and macrophage chemoattractant protein-1 production by human fibroblasts but not fibrosis related factors.

PubMed

Eleftheriadis, T; Liakopoulos, V; Lawson, B; Antoniadi, G; Stefanidis, I; Galaktidou, G

2011-07-01

Besides extracellular matrix production, fibroblasts are able to produce various cytokines. Their ubiquitous position makes fibroblasts appropriate cells for sensing various noxious stimuli and for attracting immune cells in the affected area. In the present study the effect of lipopolysaccharide (LPS) and cobalt chloride (CoCl(2)) on the above fibroblasts functions were evaluated in primary human skin fibroblasts cultures. Collagen, matrix metalloproteinase-1, tissue inhibitor of metalloproteinases-1, transforming growth factor-β1, interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) were measured in fibroblasts culture supernatants. Fibroblasts proliferation and viability were assessed as well. Hypoxia inducible factor-1α and the phosphorylated p65 portion of NF-κB were assessed in fibroblasts protein extracts. LPS and CoCl(2) had a minor effect on fibrosis related factors in human primary fibroblasts, possibly due to the absence of interplay with other cell types in the used experimental system. On the contrary both LPS and CoCl(2) increased significantly IL-8. LPS also increased considerably MCP-1, but CoCl(2) decreased it. Thus LPS and CoCl(2) induce a sentinel, nevertheless not identical, phenotype in primary human fibroblasts. The last disparity could result in different body response to infectious or hypoxic noxious stimuli.

Vascular endothelial growth factor modified macrophages transdifferentiate into endothelial-like cells and decrease foam cell formation.

PubMed

Yan, Dan; He, Yujuan; Dai, Jun; Yang, Lili; Wang, Xiaoyan; Ruan, Qiurong

2017-06-30

Macrophages are largely involved in the whole process of atherosclerosis from an initiation lesion to an advanced lesion. Endothelial disruption is the initial step and macrophage-derived foam cells are the hallmark of atherosclerosis. Promotion of vascular integrity and inhibition of foam cell formation are two important strategies for preventing atherosclerosis. How can we inhibit even the reverse negative role of macrophages in atherosclerosis? The present study was performed to investigate if overexpressing endogenous human vascular endothelial growth factor (VEGF) could facilitate transdifferentiation of macrophages into endothelial-like cells (ELCs) and inhibit foam cell formation. We demonstrated that VEGF-modified macrophages which stably overexpressed human VEGF (hVEGF 165 ) displayed a high capability to alter their phenotype and function into ELCs in vitro Exogenous VEGF could not replace endogenous VEGF to induce the transdifferentiation of macrophages into ELCs in vitro We further showed that VEGF-modified macrophages significantly decreased cytoplasmic lipid accumulation after treatment with oxidized LDL (ox-LDL). Moreover, down-regulation of CD36 expression in these cells was probably one of the mechanisms of reduction in foam cell formation. Our results provided the in vitro proof of VEGF-modified macrophages as atheroprotective therapeutic cells by both promotion of vascular repair and inhibition of foam cell formation. © 2017 The Author(s).

Human extrahepatic portal vein obstruction correlates with decreased factor VII and protein C transcription but increased hepatocyte proliferation.

PubMed

Chiu, Bill; Melin-Aldana, Hector; Superina, Riccardo A

2007-10-01

A 3-year-old girl developed extrahepatic portal vein obstruction (EHPVO) after a liver transplant. She had sequelae of portal hypertension that required another transplantation. The circumstances allowed for comparison of liver-dependent coagulation factor production between the second donor liver and the explanted liver with EHPVO. Liver samples from the explanted first graft and the second transplant were obtained. Fresh tissue was used to perform reverse transcription-polymerase chain reaction with primers against factors V, VII, as well as VIII, protein C, and paraffin-embedded sections for hepatocyte proliferation using Ki-67 antibody as well as for apoptosis using TUNEL assay. The transcription of factor VII and that of protein C were decreased in the explant as compared with the newly transplanted liver (factor VII, 77% of the donor; protein C, 88% of the donor). The transcription of factor V and that of factor VIII were unchanged. The explant had a greater percentage of proliferating hepatocytes than the new organ (0.85% +/- 0.75% vs 0.11% +/- 0.21%). The percentage of apoptotic cells was similar between the 2 livers (0.09% +/- 0.13% vs 0.09% +/- 0.13%). Idiopathic EHPVO is associated with a reduction in liver-dependent coagulation factor transcription and an increase in hepatocyte proliferation. Portal blood flow deprivation alters hepatic homeostasis and initiates mechanisms that attempt to restore liver-dependent coagulation factors.

Medicaid Coverage for Tobacco Dependence Treatments in Massachusetts and Associated Decreases in Smoking Prevalence

PubMed Central

Land, Thomas; Warner, Donna; Paskowsky, Mark; Cammaerts, Ayesha; Wetherell, LeAnn; Kaufmann, Rachel; Zhang, Lei; Malarcher, Ann; Pechacek, Terry; Keithly, Lois

2010-01-01

Background Approximately 50% of smokers die prematurely from tobacco-related diseases. In July 2006, the Massachusetts health care reform law mandated tobacco cessation coverage for the Massachusetts Medicaid population. The new benefit included behavioral counseling and all medications approved for tobacco cessation treatment by the U.S. Food and Drug Administration (FDA). Between July 1, 2006 and December 31, 2008, a total of 70,140 unique Massachusetts Medicaid subscribers used the newly available benefit, which is approximately 37% of all Massachusetts Medicaid smokers. Given the high utilization rate, the objective of this study is to determine if smoking prevalence decreased significantly after the initiation of tobacco cessation coverage. Methods and Findings Smoking prevalence was evaluated pre- to post-benefit using 1999 through 2008 data from the Massachusetts Behavioral Risk Factor Survey (BRFSS). The crude smoking rate decreased from 38.3% (95% C.I. 33.6%–42.9%) in the pre-benefit period compared to 28.3% (95% C.I.: 24.0%–32.7%) in the post-benefit period, representing a decline of 26 percent. A demographically adjusted smoking rate showed a similar decrease in the post-benefit period. Trend analyses reflected prevalence decreases that accrued over time. Specifically, a joinpoint analysis of smoking prevalence among Massachusetts Medicaid benefit-eligible members (age 18–64) from 1999 through 2008 found a decreasing trend that was coincident with the implementation of the benefit. Finally, a logistic regression that controlled for demographic factors also showed that the trend in smoking decreased significantly from July 1, 2006 to December 31, 2008. Conclusion These findings suggest that a tobacco cessation benefit that includes coverage for medications and behavioral treatments, has few barriers to access, and involves broad promotion can significantly reduce smoking prevalence. PMID:20305787

Study on the clinical significance and related factors of thirst and xerostomia in maintenance hemodialysis patients.

PubMed

Fan, Wei-Feng; Zhang, Qi; Luo, Li-Hong; Niu, Jian-Ying; Gu, Yong

2013-01-01

To analyse the clinical significance and related factors of thirst and xerostomia and to find methods to alleviate thirst and xerostomia in maintenance hemodialysis (MHD) patients. Forty-two MHD patients were included for observational study and eleven patients were enrolled for crossover trial. Thirst was assessed by 100-mm visual analog scales (VAS) and dialysis thirst inventory (DTI). Meanwhile, xerostomia was assessed by VAS and xerostomia inventory (XI). Depression, kidney disease quality of life (KDQOL), salivary flow rates and inter dialytic weight gain (IDWG) were measured. Data were analyzed by ANOVA and correlation coefficient was used to assess the correlations between continuous variables. The results of crossover trial were investigated by two-sample T-tests. Strong positive correlations among DTI, VAS thirst score, XI and VAS xerostomia score were found (P=0.000). Daily IDWG was positively correlated with VAS thirst score (r=0.315, P=0.042) and DTI(r=0.391, P=0.010). UWS (unstimulated whole saliva) was negatively correlated with VAS xerostomia score (r=-0.308, P=0.048). Residual urine output was negatively correlated with DTI (r=-0.402, P=0.008), VAS xerostomia score (r=-0.461, P=0.002) and XI (r=-0.403, P=0.008). In the crossover trial, DTI, XI, IDWG2d, IDWG3d, VAS thirst and xerostomia score were significantly reduced by the use of chewing gum (P=0.000, 0.001, 0.009, 0.017, 0.038, 0.001). The VAS thirst score, DTI and IDWG3d were significantly reduced by receiveing straw (P=0.016, 0.003, 0.049). Thirst and xerostomia might affect the quality of life in MHD patients. Both chewing gum and straw could decrease thirst and IDWG. © 2013 S. Karger AG, Basel.

Significant factors associated with fatal outcome in emergency open surgery for perforated peptic ulcer

PubMed Central

Testini, Mario; Portincasa, Piero; Piccinni, Giuseppe; Lissidini, Germana; Pellegrini, Fabio; Greco, Luigi

2003-01-01

AIM: To evaluate the main factors associated with mortality in patients undergoing surgery for perforated peptic ulcer referred to an academic department of general surgery in a large southern Italian city. METHODS: One hundred and forty-nine consecutive patients (M:F ratio = 110:39, mean age 52 yrs, range 16-95) with peptic ulcer disease were investigated for clinical history (including age, sex, previous history of peptic ulcer, associated diseases, delayed abdominal surgery, ulcer site, operation type, shock on admission, postoperative general complications, and intra-abdominal and/or wound infections), serum analyses and radiological findings. RESULTS: The overall mortality rate was 4.0%. Among all factors, an age above 65 years, one or more associated diseases, delayed abdominal surgery, shock on admission, postoperative abdominal complications and/or wound infections, were significantly associated (χ2) with increased mortality in patients undergoing surgery (0.0001 < P < 0.03). CONCLUSION: Factors such as concomitant diseases, shock on admission, delayed surgery, and postoperative abdominal and wound infections are significantly associated with fatal outcomes and need careful evaluation within the general workup of patients admitted for perforated peptic ulcer. PMID:14562406

High-dose ascorbic acid decreases cholesterolemic factors of an atherogenic diet in guinea pigs.

PubMed

Filis, Konstantinos; Anastassopoulou, Aikaterini; Sigala, Fragiska; Theodorou, Dimitrios; Manouras, Andreas; Leandros, Emanouel; Sigalas, Panagiotis; Hepp, Wolfgang; Bramis, John

2007-03-01

The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

Time-dependent analysis of incidence, risk factors and clinical significance of pneumothorax after percutaneous lung biopsy.

PubMed

Lim, Woo Hyeon; Park, Chang Min; Yoon, Soon Ho; Lim, Hyun-Ju; Hwang, Eui Jin; Lee, Jong Hyuk; Goo, Jin Mo

2018-03-01

To evaluate the time-dependent incidence, risk factors and clinical significance of percutaneous lung biopsy (PLB)-related pneumothorax. From January 2012-November 2015, 3,251 patients underwent 3,354 cone-beam CT-guided PLBs for lung lesions. Cox, logistic and linear regression analyses were performed to identify time-dependent risk factors of PLB-related pneumothorax, risk factors of drainage catheter insertion and those of prolonged catheter placement, respectively. Pneumothorax occurred in 915/3,354 PLBs (27.3 %), with 230/915 (25.1 %) occurring during follow-ups. Risk factors for earlier occurrence of PLB-related pneumothorax include emphysema (HR=1.624), smaller target (HR=0.922), deeper location (HR=1.175) and longer puncture time (HR=1.036), while haemoptysis (HR=0.503) showed a protective effect against earlier development of pneumothorax. Seventy-five cases (8.2 %) underwent chest catheter placement. Mean duration of catheter placement was 3.2±2.0 days. Emphysema (odds ratio [OR]=2.400) and longer puncture time (OR=1.053) were assessed as significant risk factors for catheter insertion, and older age (parameter estimate=1.014) was a predictive factor for prolonged catheter placement. PLB-related pneumothorax occurred in 27.3 %, of which 25.1 % developed during follow-ups. Smaller target size, emphysema, deeply-located lesions were significant risk factors of PLB-related pneumothorax. Emphysema and older age were related to drainage catheter insertion and prolonged catheter placement, respectively. • One-fourth of percutaneous lung biopsy (PLB)-related pneumothorax occurs during follow-up. • Smaller, deeply-located target and emphysema lead to early occurrence of pneumothorax. • Emphysema is related to drainage catheter insertion for PLB-related pneumothorax. • Older age may lead to prolonged catheter placement for PLB-related pneumothorax. • Tailored management can be possible with time-dependent information of PLB-related pneumothorax.

A novel epidemic spreading model with decreasing infection rate based on infection times

NASA Astrophysics Data System (ADS)

Huang, Yunhan; Ding, Li; Feng, Yun

2016-02-01

A new epidemic spreading model where individuals can be infected repeatedly is proposed in this paper. The infection rate decreases according to the times it has been infected before. This phenomenon may be caused by immunity or heightened alertness of individuals. We introduce a new parameter called decay factor to evaluate the decrease of infection rate. Our model bridges the Susceptible-Infected-Susceptible(SIS) model and the Susceptible-Infected-Recovered(SIR) model by this parameter. The proposed model has been studied by Monte-Carlo numerical simulation. It is found that initial infection rate has greater impact on peak value comparing with decay factor. The effect of decay factor on final density and threshold of outbreak is dominant but weakens significantly when considering birth and death rates. Besides, simulation results show that the influence of birth and death rates on final density is non-monotonic in some circumstances.

Thyroid Gland Involvement in Carcinoma Larynx and Hypopharynx-Predictive Factors and Prognostic Significance.

PubMed

Iype, Elizabeth Mathew; Jagad, Vijay; Nochikattil, Santhosh Kumar; Varghese, Bipin T; Sebastian, Paul

2016-02-01

Intraoperative management of thyroid gland in laryngeal and hypopharyngeal cancer is controversial. The objectives of this study were to determine the incidence of thyroid gland invasion in patients undergoing surgery for laryngeal or hypopharyngeal carcinoma, to assess predictive factors and to assess the prognosis in patients with and without thyroid gland invasion. One hundred and thirty-three patients who underwent surgery for carcinoma larynx and hypopharynx from 2006 to 2010 were reviewed retrospectively. Surgical specimens were examined to determine the incidence of thyroid gland invasion and predictive factors were analysed. The recurrence rate and the survival in patients with and without thyroid gland invasion were also analysed. Out of the 133 patients with carcinoma larynx and hypopharynx who underwent surgery, histological thyroid gland invasion was observed in 28/133 (21%) patients. Significant relationship was found between histological thyroid gland invasion and preoperative evidence of thyroid cartilage erosion by CT scan and also when gross thyroid gland involvement observed during surgery. There is significant association between thyroid gland invasion when there is upper oesophageal or subglottic involvement. After analysing the retrospective data from our study, we would like to suggest that thyroid gland need not be removed routinely in all laryngectomies, unless there is advanced disease with thyroid cartilage erosion and gross thyroid gland involvement or disease with significant subglottic or oesophageal involvement.

Lupus nephritis and Raynaud's phenomenon are significant risk factors for vascular thrombosis in SLE patients with positive antiphospholipid antibodies.

PubMed

Choojitarom, Kittiwan; Verasertniyom, Orawan; Totemchokchyakarn, Kitti; Nantiruj, Kanokrat; Sumethkul, Vasant; Janwityanujit, Suchela

2008-03-01

This study is aimed to determine the predictors of nongravid vascular thrombosis in systemic lupus erythematosus (SLE) patients with positive antiphospholipid antibodies (SLE-aPL). A cohort of 67 SLE-aPL patients who had at least one positive test for lupus anticoagulant (LA), anticardiolipin (aCL), or anti-beta2glycoprotein-1(B2) was examined. Main outcome was the presence of vascular thrombosis. Association between thrombosis and risk factors was examined by contingency table. The odds ratio (OR) of significant predictors was determined by logistic regression. Three percent of patients were LA(+), 6% were aCL(+), 31% were B2(+), 3% were aCL(+)LA(+), 35.8% were aCL(+)B2(+), 7.5% were LA(+)B2(+), and 13.4% were positive for all tests. As for clinical manifestations, 79% had lymphopenia, 76% had lupus nephritis (LN), 41.8% had autoimmune hemolytic anemia, 34.3% had thrombocytopenia, 20.9% had abortion, and 19.4% had Raynaud's phenomenon (RP). Thrombosis occurred in 26 patients. The prevalence of thrombosis for SLE-aPL was 38.8%. Thrombosis was observed more frequently in patients with LA(+) (12 of 18) than the others (14 of 49; p = 0.01). Two-by-two table showed that oral contraceptive and LN were significantly associated with increased risk of thrombosis, while lymphopenia and antimalarials were significantly associated with decreased risk of thrombosis. Multivariate analysis confirmed that LN and RP were associated with increased risk of thrombosis (OR = 6.2 and 3.2; p = 0.005 and 0.008), while lymphopenia and antimalarials were associated with decreased risk of thrombosis (OR = 0.86 and 0.18; p = 0.02 and 0.034). LA is the strongest test to determine the risk of thrombosis in SLE-aPL. The presence of LN and RP strongly predicts thrombosis, while lymphopenia and antimalarials are protective. These findings help to identify patients who may benefit from prophylactic therapy.

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.

A decreased metabolic clearance of glucose is involved in the hyperglycemic effect of a serum temperature induced factor (TIF).

PubMed

Masson, C; Bougrine, R; Bois, F; Zaïd, A; Nicolas, J P; Guéant, J L

1995-01-01

We have studied the effects of a hyperglycemic temperature induced factor (TIF) on glucose metabolism, in 3 groups of Wistar rats: 10 rats injected with non-heated serum, 10 rats injected with heated serum and 10 rats injected with semi-purified TIF. Seric levels of insulin and glucagon were not modified in rats injected with heated serum. The injection of heated serum induced hyperglycemia (p < 0.0001), a decrease of lactate (p < 0.001) and pyruvate (p < 0.05) levels, and an increase of acetoacetate level (p < 0.001). The levels of beta hydroxybutyrate and amino acids (alanine and glutamine) were not changed. Glucose turn over rate (12.3 +/- 1.3 g/min/kg) and metabolic clearance of glucose (10.0 +/- 0.8 ml/min/kg) were significantly lower in rats treated with heated serum and purified TIF than in controls (respectively, p < 0.05 and p < 0.001). These data suggested that the hyperglycemic effect of heated serum and isolated TIF could correspond to an impaired metabolic clearance of glucose and to an increased gluconeogenesis.

[Significance of vitamin K (VK) administration in patients under chemotherapy during postoperative fasting period].

PubMed

Ojiro, M; Takenoshita, M; Toshinaga, T; Shimazu, H

1992-01-01

Recently coagulopathy caused by vitamin K (VK) deficiency following antibiotic therapy in malnourished patients has been reported. We studied on the same problem particularly in patients under chemotherapy during postoperative fasting period. For this purpose, prothrombin time (PT), vitamin K-dependent coagulation factors (Factor II (F-II), VII (F-VII) and protein C), PIVKA-II (PK-II) and plasma level of VK in two groups of patients with or without VK administration were measured in esophageal cancer patients. In the group with VK, VK2 were given intravenously everyday. In the group without VK, PT prolonged and F-II decreased from the seventh postoperative day, especially on the 14th day significantly. Although F-VII and protein C decreased on the first day and returned subsequently on the seventh day, no significance was observed between two groups. PK-II increased clearly in the group without VK from the seventh day, whereas no significant changes were observed in the group with VK. The plasma level of VK1 decreased in both groups, but VK2, especially MK-4, was high in the group with VK.

Intrauterine growth restriction decreases nuclear factor-kappa B signaling in fetal pulmonary artery endothelial cells of fetal sheep.

PubMed

Dodson, R Blair; Powers, Kyle N; Gien, Jason; Rozance, Paul J; Seedorf, Gregory J; Astling, David; Jones, Kenneth Lloyd; Crombleholme, Timothy M; Abman, Steven H; Alvira, Cristina M

2018-05-03

Intrauterine growth restriction (IUGR) in premature newborns increases the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted pulmonary angiogenesis and alveolarization. We previously showed that experimental IUGR impairs angiogenesis, however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The nuclear factor-kappa-B (NFκB) pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NFκB-regulated pro-angiogenic targets in fetal PAEC. PAECs were isolated from lungs of control fetal sheep and sheep with experimental IUGR from an established model of chronic placental insufficiency. Microarray analysis identified suppression of NFκB signaling and significant alterations in extracellular matrix (ECM) pathways in IUGR PAEC, including decreases in collagen 4α1 and laminin α4, components of the basement membrane and putative NFκB targets. In comparison with controls: (i) immunostaining of active NFκB complexes; (ii) NFκB-DNA binding; (iii) baseline expression of NFκB subunits, p65 and p50; and (iv) LPS-mediated inducible activation of NFκB signaling were decreased in IUGR PAEC. Although pharmacologic NFκB inhibition did not affect angiogenic function in IUGR PAEC, angiogenic function of control PAEC was reduced to a similar degree as that observed in IUGR PAEC. These data identify reductions in endothelial NFκB signaling as central to the disrupted angiogenesis observed in IUGR, likely by impairing both intrinsic PAEC angiogenic function and NFκB-mediated regulation of ECM components necessary for vascular development. These data further suggest that strategies that preserve endothelial NFκB activation may be useful in lung diseases marked by disrupted angiogenesis such as IUGR.

Decreasing spatial variability in precipitation extremes in southwestern China and the local/large-scale influencing factors

NASA Astrophysics Data System (ADS)

Liu, Meixian; Xu, Xianli; Sun, Alex

2015-07-01

Climate extremes can cause devastating damage to human society and ecosystems. Recent studies have drawn many conclusions about trends in climate extremes, but few have focused on quantitative analysis of their spatial variability and underlying mechanisms. By using the techniques of overlapping moving windows, the Mann-Kendall trend test, correlation, and stepwise regression, this study examined the spatial-temporal variation of precipitation extremes and investigated the potential key factors influencing this variation in southwestern (SW) China, a globally important biodiversity hot spot and climate-sensitive region. Results showed that the changing trends of precipitation extremes were not spatially uniform, but the spatial variability of these precipitation extremes decreased from 1959 to 2012. Further analysis found that atmospheric circulations rather than local factors (land cover, topographic conditions, etc.) were the main cause of such precipitation extremes. This study suggests that droughts or floods may become more homogenously widespread throughout SW China. Hence, region-wide assessments and coordination are needed to help mitigate the economic and ecological impacts.

Transforming growth factor-β decreases side population cells in hepatocellular carcinoma in vitro.

PubMed

Kim, Jong Bin; Lee, Seulki; Kim, Hye Ri; Park, Seo-Young; Lee, Minjong; Yoon, Jung-Hwan; Kim, Yoon Jun

2018-06-01

Hepatocellular carcinoma (HCC) can result from hepatitis B or C infection, fibrosis or cirrhosis. Transforming growth factor-β (TGF-β) is one of the main growth factors associated with fibrosis or cirrhosis progression in the liver, but its role is controversial in hepatocarcinogenesis. In the present study, the effect of TGF-β on the HCC Huh-7 and Huh-Bat cell lines was evaluated. To study the effect of TGF-β, Huh-7 and Huh-Bat cells were treated with TGF-β and a TGF-β receptor inhibitor (SB431542). Cell survival, cell cycle, numbers of side population (SP) cells and expression of the cancer stem cell marker cluster of differentiation (CD)133, epithelial-mesenchymal transition markers (E-cadherin, α-smooth muscle actin and vimentin) and TGF-β-regulated proteins [phospho-c-Jun N-terminal kinase (p-JNK), p-c-Jun and p-smad2] were investigated. TGF-β treatment resulted in decreased cell survival with a targeted effect on SP cells. Expression of CD133 and vimentin was upregulated by treatment with the TGF-β receptor antagonist SB431542, but not with TGF-β. By contrast, TGF-β induced accumulation of cells at G0/G1, and upregulated expression of p-JNK, p-c-Jun and p-smad2. However, these effects were blocked when cells were treated with TGF-β plus SB431542, indicating the specificity of the TGF-β effect. The present results indicated that TGF-β has anticancer effects mediated by survival inhibition of cancer stem cells, which may be developed as a novel therapy for HCC.

Psychosocial factors and pre-abortion psychological health: The significance of stigma.

PubMed

Steinberg, Julia R; Tschann, Jeanne M; Furgerson, Dorothy; Harper, Cynthia C

2016-02-01

Most research in mental health and abortion has examined factors associated with post-abortion psychological health. However, research that follows women from before to after their abortion consistently finds that depressive, anxiety, and stress symptoms are highest just before an abortion compared to any time afterwards. This finding suggests that studies investigating psychosocial factors related to pre-abortion mental health are warranted. The current study uses data from 353 women seeking abortions at three community reproductive health clinics to examine predictors of pre-abortion psychological health. Drawing from three perspectives in the abortion and mental health literature, common risks, stress and coping, and sociocultural context, we conducted multivariable analyses to examine the contribution of important factors on depressive, anxiety, and stress symptoms just before an abortion, including sociodemographics, abortion characteristics, childhood adversities, recent adversities with an intimate partner, relationship context, future pregnancy desires, and perceived abortion stigma. Childhood and partner adversities, including reproductive coercion, were associated with negative mental health symptoms, as was perceived abortion stigma. Before perceived abortion stigma was entered into the model, 18.6%, 20.7%, and 16.8% of the variance in depressive, anxiety, and stress symptoms respectively, was explained. Perceived abortion stigma explained an additional 13.2%, 9.7%, and 10.7% of the variance in depressive, anxiety, and stress symptoms pre-abortion. This study, one of the first to focus on pre-abortion mental health as an outcome, suggests that addressing stigma among women seeking abortions may significantly lower their psychological distress. Copyright © 2015 Elsevier Ltd. All rights reserved.

Psychosocial factors and pre-abortion psychological health: The significance of stigma

PubMed Central

Steinberg, Julia R.; Tschann, Jeanne M.; Furgerson, Dorothy; Harper, Cynthia C.

2016-01-01

Rationale Most research in mental health and abortion has examined factors associated with post-abortion psychological health. However, research that follows women from before to after their abortion consistently finds that depressive, anxiety, and stress symptoms are highest just before an abortion compared to any time afterwards. Objective This finding suggests that studies investigating psychosocial factors related to pre-abortion mental health are warranted. Methods The current study uses data from 353 women seeking abortions at three community reproductive health clinics to examine predictors of pre-abortion psychological health. Drawing from three perspectives in the abortion and mental health literature, common risks, stress and coping, and sociocultural context, we conducted multivariable analyses to examine the contribution of important factors on depressive, anxiety, and stress symptoms just before an abortion, including sociodemographics, abortion characteristics, childhood adversities, recent adversities with an intimate partner, relationship context, future pregnancy desires, and perceived abortion stigma. Results Childhood and partner adversities, including reproductive coercion, were associated with negative mental health symptoms, as was perceived abortion stigma. Before perceived abortion stigma was entered into the model, 18.6 %, 20.7 %, and 16.8% of the variance in depressive, anxiety, and stress symptoms respectively, was explained. Perceived abortion stigma explained an additional 13.2 %, 9.7 %, and 10.7 % of the variance in depressive, anxiety, and stress symptoms pre-abortion. Conclusion This study, one of the first to focus on pre-abortion mental health as an outcome, suggests that addressing stigma among women seeking abortions may significantly lower their psychological distress. PMID:26735332

[Role and clinical significance of coagulation and inflammatory factors in moderate and severe ovarian endometriosis].

PubMed

Lin, Q; Ding, S J; Zhu, T H; Li, T T; Huang, X F; Zhang, X M

2018-03-25

Objective: To determine the levels of coagulation and inflammatory factors in women with moderate and severe ovarian endometriosis so as to investigate the possible role of coagulation and inflammatory factors in the pathogenesis, diagnosis and treatment of this disease. Methods: From June 2015 and June 2017, clinical data of 366 patients with pathologically diagnosed moderate and severe ovarian endometriosis (case group) and 244 patients with pathologically diagnosed benign ovarian cysts (control group) in Women's Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The levels of coagulation indicators, inflammatory factors and serum tumor markers were measured. Then, the values of these indicators in diagnosis of endometriosis were analyzed. Results: (1) The levels of plasma prothrombin time (PT) and thrombin time (TT) in patients with ovarian endometriosis [median: 12.8 s (range: 12.4-13.2 s) and 15.5 s (range: 15.1-15.9 s), respectively] were significantly shorter than those with benign ovarian cysts [median: 13.0 s (range: 12.5-13.4 s) and 15.7 s (range: 15.3-16.1 s), respectively; all P <0.01]. The levels of plasma fibrinogen (FIB) and D-dimer [D-D; median: 3.1 g/L (range: 2.8-3.5 g/L) and 0.9 mg/L (range: 0.6-2.1 mg/L) , respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.8 g/L (range: 2.6-3.2 g/L) and 0.6 mg/L (range: 0.4-1.2 mg/L), respectively; P =0.000]. Moreover, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio [PLR; median: 2.3 (range: 1.8-3.1) and 144 (range: 113-179), respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.1 (range: 1.6-2.8) and 128 (range: 104-165), respectively; P <0.01]. Furthermore, in patients with ovarian endometriosis, the levels of PT were significantly shorter in stage Ⅳ endometriosis than that in stage Ⅲ endometriosis ( P <0

Examining Factors That Decrease Attrition among Special Educators

ERIC Educational Resources Information Center

Hampton, Jessica Daneen

2013-01-01

Recruiting and retaining special educators has been a major concern for the department of education, school administration, and parents across the United States. Attrition, defined as the exit of teachers from their positions, has been a contributing factor to the shortage of teachers. The theoretical foundation for this study was based on the…

Insulin-Like growth factor-II (IGF-II) prevents proinflammatory cytokine-induced apoptosis and significantly improves islet survival after transplantation.

PubMed

Hughes, Amy; Mohanasundaram, Daisy; Kireta, Svjetlana; Jessup, Claire F; Drogemuller, Chris J; Coates, P Toby H

2013-03-15

The early loss of functional islet mass (50-70%) due to apoptosis after clinical transplantation contributes to islet allograft failure. Insulin-like growth factor (IGF)-II is an antiapoptotic protein that is highly expressed in β-cells during development but rapidly decreases in postnatal life. We used an adenoviral (Ad) vector to overexpress IGF-II in isolated rat islets and investigated its antiapoptotic action against exogenous cytokines interleukin-1β- and interferon-γ-induced islet cell death in vitro. Using an immunocompromised marginal mass islet transplant model, the ability of Ad-IGF-II-transduced rat islets to restore euglycemia in nonobese diabetic/severe combined immunodeficient diabetic recipients was assessed. Ad-IGF-II transduction did not affect islet viability or function. Ad-IGF-II cytokine-treated islets exhibited decreased cell death (40% ± 2.8%) versus Ad-GFP and untransduced control islets (63.2% ± 2.5% and 53.6% ± 2.3%, respectively). Ad-IGF-II overexpression during cytokine treatment resulted in a marked reduction in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive apoptotic cells (8.3% ± 1.4%) versus Ad-GFP control (41% ± 4.2%) and untransduced control islets (46.5% ± 6.2%). Western blot analysis confirmed that IGF-II inhibits apoptosis via activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. Transplantation of IGF-II overexpressing islets under the kidney capsule of diabetic mice restored euglycemia in 77.8% of recipients compared with 18.2% and 47.5% of Ad-GFP and untransduced control islet recipients, respectively (P<0.05, log-rank [Mantel-Cox] test). Antiapoptotic IGF-II decreases apoptosis in vitro and significantly improved islet transplant outcomes in vivo. Antiapoptotic gene transfer is a potentially powerful tool to improve islet survival after transplantation.

The relationship between BIM deletion polymorphism and clinical significance of epidermal growth factor receptor-mutated non-small cell lung cancer patients with epidermal growth factor receptor-tyrosine kinase inhibitor therapy: a meta-analysis.

PubMed

Zou, Qian; Zhan, Ping; Lv, Tangfeng; Song, Yong

2015-12-01

BIM deletion polymorphism is a germline that might lead to little or no BH3 expression, which affects epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) related apoptosis. Recent studies show that BIM deletion polymorphism might be a critical factor leading to the resistance of EGFR-TKIs in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients. Thus, a meta-analysis was conducted by combing seven original eligible studies including 778 NSCLC patients to investigate a steady and reliable conclusion. Our study indicated that BIM deletion polymorphism was significantly associated with the poor objective response rate (ORR) of EGFR-TKIs in EGFR-mutated NSCLC patients [odds ratios (OR) =0.55, 95% confidence interval (CI), 0.33-0.92]. And disease control rate (DCR) in EGFR-mutate NSCLC patients treated with EGFR-TKIs was significantly decreased in patients with BIM deletion polymorphism (OR=0.55, 95% CI, 0.27-1.12). Moreover, the progression-free survival (PFS) of patients with BIM deletion polymorphism is shorter. These findings suggested that BIM deletion polymorphism might be a genetic cause of intrinsic resistance to TKI therapy and it could be emerged as an independent predictor to identify patients who would benefit from TKI targeted therapy in EGFR-mutated NSCLC.

Vector-based RNA interference against vascular endothelial growth factor-A significantly limits vascularization and growth of prostate cancer in vivo.

PubMed

Wannenes, Francesca; Ciafré, Silvia Anna; Niola, Francesco; Frajese, Gaetano; Farace, Maria Giulia

2005-12-01

RNA interference technology is emerging as a very potent tool to obtain a cellular knockdown of a desired gene. In this work we used vector-based RNA interference to inhibit vascular endothelial growth factor (VEGF) expression in prostate cancer in vitro and in vivo. We demonstrated that transduction with a plasmid carrying a small interfering RNA targeting all isoforms of VEGF, dramatically impairs the expression of this growth factor in the human prostate cancer cell line PC3. As a consequence, PC3 cells loose their ability to induce one of the fundamental steps of angiogenesis, namely the formation of a tube-like network in vitro. Most importantly, our "therapeutic" vector is able to impair tumor growth rate and vascularization in vivo. We show that a single injection of naked plasmid in developing neoplastic mass significantly decreases microvessel density in an androgen-refractory prostate xenograft and is able to sustain a long-term slowing down of tumor growth. In conclusion, our results confirm the basic role of VEGF in the angiogenic development of prostate carcinoma, and suggest that the use of our vector-based RNA interference approach to inhibit angiogenesis could be an effective tool in view of future gene therapy applications for prostate cancer.

Significance of blood group and social factors in carcinoma cervix in a semi-urban population in India.

PubMed

Kai, Lee Jun; Raju, Kalyani; Malligere Lingaiah, Harendra Kumar; Mariyappa, Narayanaswamy

2013-01-01

To assess the significance of social factors as risk factors for carcinoma cervix and to determine the significance of blood group to prevalence of carcinoma cervix in a semi-urban population of Kolar, Karnataka, India. One hundred cases of carcinoma cervix were included in the study, along with 200 females of the same ages considered as controls. Case details were collected from the hospital record section regarding social factors and blood groups and the data were analyzed by descriptive statistical methods. Blood group B showed the highest number of cases (55 cases) followed by blood group O (29 cases) in carcinoma cervix which was statistically significant (p<0.001). Age of marriage between 11 to 20 years showed highest number of carcinoma cervix cases (77 cases) and this also was statistically significant (p<0.001). Patients with rural background were 75 (p=0.112, odds ratio: 1.54), parity of more than or equal to two constituted 96 cases (p=0.006, odds ratio: 4.07) and Hindu patients were 95 in number (p=0.220, odds ratio: 1.89). Blood group B and age of marriage between 11 and 20 years were significantly associated with carcinoma cervix in our population. Region of residence, parity and religion presented with a altered risk for carcinoma cervix.

Xenon decreases cell migration and secretion of a pro-angiogenesis factor in breast adenocarcinoma cells: comparison with sevoflurane.

PubMed

Ash, S A; Valchev, G I; Looney, M; Ni Mhathuna, A; Crowley, P D; Gallagher, H C; Buggy, D J

2014-07-01

While volatile agents have been implicated in metastasis-enhancing effects on cancer cells, the effects of xenon are unknown. We investigated xenon- and sevoflurane-mediated effects on migration and expression of angiogenesis biomarkers in human breast adenocarcinoma cells. MDA-MB-231 and MCF-7 cells were exposed to xenon 70% with O2 25%, CO2 5%; control gas containing O2 25%, CO2 5%, N2 70%; or sevoflurane 2.5 vol% administered in O2 60%, N2 37%, or control gas. Cell viability was determined by the MTT assay. Migration at 24 h was determined using the Oris™ Cell Migration Assay. Secretion of angiogenesis factors was measured using a membrane-based immunoassay array. Xenon reduced MDA-MB-231 migration to 59 (13%) after 1-h exposure (P=0.02), 64 (10%) after 3 h (P=0.01), and 71 (9%) after 5 h (P=0.04) compared with control gas, without affecting viability. Similarly, MCF-7 migration was significantly reduced at all timepoints [to 58 (12%) at 1 h, 65 (12%) at 3 h, and 65% (12%) at 5 h]. Sevoflurane did not affect migration when delivered in control gas. Glycine, an N-methyl-d-aspartate receptor co-agonist, antagonized the effects of xenon on migration. Expression of the pro-angiogenesis factor regulated on activation, normal T cell expressed and secreted (RANTES) was reduced in conditioned medium from xenon-exposed MDA-MB-231 cells compared with cells exposed to either control gas or sevoflurane [mean dot density 2.0 (0.2) compared with 3.0 (0.1) and 3.1 (0.3), respectively (P=0.02)]. Xenon, but not sevoflurane, inhibited migration in both oestrogen receptor positive and negative breast adenocarcinoma cells. Furthermore, xenon decreased release of the pro-angiogenic factor RANTES from MDA-MB-231 cells. © The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bromelain Treatment Decreases Secretion of Pro-Inflammatory Cytokines and Chemokines by Colon Biopsies In Vitro

PubMed Central

Onken, Jane E.; Greer, Paula K.; Calingaert, Brian; Hale, Laura P.

2008-01-01

Oral bromelain has been anecdotally reported to decrease inflammation in ulcerative colitis (UC). Proteolytically active bromelain is known to decrease expression of mRNAs encoding pro-inflammatory cytokines by human leukocytes in vitro. To assess the effect of bromelain on mucosal secretion of cytokines in inflammatory bowel disease (IBD), endoscopic colon biopsies from patients with UC, Crohn’s disease (CD), and non-IBD controls were treated in vitro with bromelain or media, then cultured. Secretion of pro-inflammatory cytokines and chemokines was measured. Significant increases in granulocyte colony stimulating factor (G-CSF), interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) were detected in the media from actively inflamed areas in UC and CD as compared with non-inflamed IBD tissue and non-IBD controls. In vitro bromelain treatment decreased secretion of G-CSF, granulocyte-macrophage colony stimulating factor (GM-CSF), IFN-γ, CCL4/macrophage inhibitory protein (MIP)-1β, and TNF by inflamed tissue in IBD. Bromelain may be a novel therapy for IBD. PMID:18160345

Sulfated Low Molecular Weight Lignins, Allosteric Inhibitors of Coagulation Proteinases via the Heparin Binding Site, Significantly Alter the Active Site of Thrombin and Factor Xa Compared to Heparin

PubMed Central

Henry, Brian L.; Desai, Umesh R.

2014-01-01

Sulfated low molecular weight lignins (LMWLs) have been found to bind in the heparin binding sites of coagulation proteinases. LMWLs represent a library of diverse non-carbohydrate, aromatic molecules which are structures different from heparin, but still potently inhibit thrombin and factor Xa. To better understand their mechanism of action, we studied the effects of three sulfated LMWLs (CDSO3, FDSO3, and SDSO3) on the active sites of thrombin and factor Xa. LMWLs were found to uniformly inhibit the catalytic activity of thrombin and factor Xa, regardless of the substrate used. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of each chromogenic substrate decreases significantly in the presence of sulfated LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. These studies indicate that LMWLs inhibit thrombin and factor Xa through allosteric disruption of the catalytic apparatus, specifically through the catalytic step. As opposed to heparin, LMWLs significantly alter the binding of the active site fluorescent ligand p-aminobenzamidine. LMWLs also had a greater effect on the molecular orientation of fluorescein-labeled His 57 than heparin. The molecular geometry surrounding the most important catalytic amino acid, Ser 195, was significantly altered by the binding of LMWLs while heparin had no measurable effect on Ser 195. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold. PMID:25242245

Sulfated low molecular weight lignins, allosteric inhibitors of coagulation proteinases via the heparin binding site, significantly alter the active site of thrombin and factor xa compared to heparin.

PubMed

Henry, Brian L; Desai, Umesh R

2014-11-01

Sulfated low molecular weight lignins (LMWLs) have been found to bind in the heparin binding sites of coagulation proteinases. LMWLs represent a library of diverse non-carbohydrate, aromatic molecules which are structures different from heparin, but still potently inhibit thrombin and factor Xa. To better understand their mechanism of action, we studied the effects of three sulfated LMWLs (CDSO3, FDSO3, and SDSO3) on the active sites of thrombin and factor Xa. LMWLs were found to uniformly inhibit the catalytic activity of thrombin and factor Xa, regardless of the substrate used. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of each chromogenic substrate decreases significantly in the presence of sulfated LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. These studies indicate that LMWLs inhibit thrombin and factor Xa through allosteric disruption of the catalytic apparatus, specifically through the catalytic step. As opposed to heparin, LMWLs significantly alter the binding of the active site fluorescent ligand p-aminobenzamidine. LMWLs also had a greater effect on the molecular orientation of fluorescein-labeled His 57 than heparin. The molecular geometry surrounding the most important catalytic amino acid, Ser 195, was significantly altered by the binding of LMWLs while heparin had no measurable effect on Ser 195. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold. Copyright © 2014 Elsevier Ltd. All rights reserved.

Increased calcium deposits and decreased Ca2+ -ATPase in erythrocytes of ascitic broiler chickens.

PubMed

Li, Kai; Zhao, Lihong; Geng, Guangrui; Ma, Liqin; Dong, Shishan; Xu, Tong; Wang, Jianlin; Wang, Huiyu; Tian, Yong; Qiao, Jian

2011-06-01

The decrease of erythrocyte deformability may be one of the predisposing factors for pulmonary hypertension and ascites in broiler chickens. In mammals, the cytoplasmic calcium is a major regulator of erythrocyte deformability. In this study, the erythrocyte deformability was measured, and the precise locations of Ca2+ and Ca2+ -ATPase in the erythrocytes were investigated in chickens with ascites syndrome induced by low ambient temperature. The results showed that ascitic broilers had higher filtration index of erythrocyte compared with control groups, indicating a decrease in erythrocyte deformability in ascitic broilers. The more calcium deposits were observed in the erythrocytes of ascitic broilers compared with those of the age-matched control birds. The Ca2+ -ATPase reactive grains were significantly decreased on the erythrocyte membranes of ascitic broilers. Our data suggest that accumulation of intracellular calcium and inhibition of Ca2+ -ATPase might be important factors for the reduced deformability of the erythrocytes of ascitic broilers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Race Disparities and Decreasing Birth Weight: Are All Babies Getting Smaller?

PubMed Central

Catov, Janet M.; Lee, MinJae; Roberts, James M.; Xu, Jia; Simhan, Hyagriv N.

2016-01-01

The mean infant birth weight in the United States increased for decades, but it might now be decreasing. Given race disparities in fetal growth, we explored race-specific trends in birth weight at Magee-Womens Hospital, Pittsburgh, Pennsylvania, from 1997 to 2011. Among singleton births delivered at 37–41 weeks (n = 70,607), we evaluated the proportions who were small for gestational age and large for gestational age and changes in mean birth weights over time. Results were stratified by maternal race/ethnicity. Since 1997, the number of infants born small for their gestational ages increased (8.7%–9.9%), whereas the number born large for their gestational ages decreased (8.9%–7.7%). After adjustment for gestational week at birth, maternal characteristics, and pregnancy conditions, birth weight decreased by 2.20 g per year (P < 0.0001). Decreases were greater for spontaneous births. Reductions were significantly greater in infants born to African-American women than in those born to white women (−3.78 vs. −1.88 per year; P for interaction = 0.010). Quantile regression models indicated that birth weight decreased across the entire distribution, but reductions among infants born to African-American women were limited to those in the upper quartile after accounting for maternal factors. Limiting the analysis to low-risk women eliminated birth weight reductions. Birth weight has decreased in recent years, and reductions were greater in infants born to African-American women. These trends might be explained by accumulation of risk factors such as hypertension and prepregnancy obesity that disproportionately affect African-American women. Our results raise the possibility of worsening race disparities in fetal growth. PMID:26667251

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.

Factoring local sequence composition in motif significance analysis.

PubMed

Ng, Patrick; Keich, Uri

2008-01-01

We recently introduced a biologically realistic and reliable significance analysis of the output of a popular class of motif finders. In this paper we further improve our significance analysis by incorporating local base composition information. Relying on realistic biological data simulation, as well as on FDR analysis applied to real data, we show that our method is significantly better than the increasingly popular practice of using the normal approximation to estimate the significance of a finder's output. Finally we turn to leveraging our reliable significance analysis to improve the actual motif finding task. Specifically, endowing a variant of the Gibbs Sampler with our improved significance analysis we demonstrate that de novo finders can perform better than has been perceived. Significantly, our new variant outperforms all the finders reviewed in a recently published comprehensive analysis of the Harbison genome-wide binding location data. Interestingly, many of these finders incorporate additional information such as nucleosome positioning and the significance of binding data.

Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

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

Rades, Dirk; Kuhn, Hildegard; Schultze, Juergen

2008-03-15

Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age ({<=}68 vs. {>=}69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage ({<=}II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: {<=}50 vs. >50 Gy), and hemoglobin levels before (<12 vs. {>=}12 g/dL)more » and during (majority of levels: <12 vs. {>=}12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels {>=}12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels {>=}12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

NASA Technical Reports Server (NTRS)

Ferrando, A. A.; Lane, H. W.; Stuart, C. A.; Davis-Street, J.; Wolfe, R. R.

1996-01-01

We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P < 0.03) during the 2nd wk of bed rest. Leg and whole body lean mass decreased after bed rest (P < 0.05). Serum cortisol, insulin, insulin-like growth factor I, and testosterone values did not change. Arteriovenous model calculations based on the infusion of L-[ring-13C6]-phenylalanine in five subjects revealed a 50% decrease in muscle protein synthesis (PS; P < 0.03). Fractional PS by tracer incorporation into muscle protein also decreased by 46% (P < 0.05). The decrease in PS was related to a corresponding decrease in the sum of intracellular amino acid appearance from protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P < 0.01). Neither model-derived nor whole body values for protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

Factors controlling reservoir quality in tertiary sandstones and their significance to geopressured geothermal production

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

Loucks, R.G.; Richmann, D.L.; Milliken, K.L.

1981-01-01

Variable intensity of diagenesis is the factor primarily responsible for contrasting regional reservoir quality of Tertiary sandstones from the upper and lower Texas coast. Detailed comparison of Frio sandstone from the Chocolate Bayou/Danbury Dome area, Brazoria County, and Vicksburg sandstones from the McAllen Ranch Field area, Hidalgo County, reveals that extent of diagenetic modification is most strongly influenced by (1) detrital mineralogy and (2) regional geothermal gradients. The regional reservoir quality of Frio sandstones from Brazoria County is far better than that characterizing Vicksburg sandstones from Hidalgo County, especially at depths suitable for geopressured geothermal energy production. However, in predictingmore » reservoir quality on a site-specific basis, locally variable factors such as relative proportions for porosity types, pore geometry as related to permeability, and local depositional environment must also be considered. Even in an area of regionally favorable reservoir quality, such local factors can significantly affect reservoir quality and, hence, the geothermal production potential of a specific sandstone unit.« less

Neutrophil elastase contributes to the development of ischemia/reperfusion-induced liver injury by decreasing the production of insulin-like growth factor-I in rats.

PubMed

Kawai, Miho; Harada, Naoaki; Takeyama, Hiromitsu; Okajima, Kenji

2010-06-01

Neutrophil elastase (NE) decreases the endothelial production of prostacyclin (PGI(2)) through the inhibition of endothelial nitric oxide synthase (NOS) activation and thereby contributes to the development of ischemia/reperfusion (I/R)-induced liver injury. We previously demonstrated that calcitonin gene-related peptide (CGRP) released from sensory neurons increases the insulin-like growth factor- I (IGF-I) production and thereby reduces I/R-induced liver injury. Because PGI(2) is capable of stimulating sensory neurons, we hypothesized that NE contributes to the development of I/R-induced liver injury by decreasing IGF-I production. In the present study, we examined this hypothesis in rats subjected to hepatic I/R. Ischemia/reperfusion-induced decreases of hepatic tissue levels of CGRP and IGF-I were prevented significantly by NE inhibitors, sivelestat, and L-658, 758, and these effects of NE inhibitors were reversed completely by the nonselective cyclooxygenase inhibitor indomethacin (IM) and the nonselective NOS inhibitor L-NAME but not by the selective inducible NOS inhibitor 1400W. I/R-induced increases of hepatic tissue levels of caspase-3, myeloperoxidase and the number of apoptotic cells were inhibited by NE inhibitors, and these effects of NE inhibitors were reversed by IM and L-NAME but not by 1400W. Administration of iloprost, a stable PGI(2) analog, produced effects similar to those induced by NE inhibitors. Taken together, these observations strongly suggest that NE may play a critical role in the development of I/R-induced liver injury by decreasing the IGF-I production through the inhibition of sensory neuron stimulation, which may lead to an increase of neutrophil accumulation and hepatic apoptosis through activation of caspase-3 in rats.

Significance of perioperative infection in survival of patients with ovarian cancer.

PubMed

Matsuo, Koji; Prather, Christina P; Ahn, Edward H; Eno, Michele L; Tierney, Katherine E; Yessaian, Annie A; Im, Dwight D; Rosenshein, Neil B; Roman, Lynda D

2012-02-01

Perioperative infectious diseases comprise some of the most common causes of surgical mortality in women with ovarian cancer. This study was aimed to evaluate the significance of perioperative infections in survival of patients with ovarian cancer. Patients who underwent primary cytoreductive surgery were included in the analysis (n = 276). The enumeration and speciation of pathogens, antimicrobial agents used, and sensitivity assay results were culled from medical records and correlated to clinicopathologic demographics and survival outcomes. Perioperative infection was determined as a positive microbiology result obtained within a 6-week postoperative period. The incidence of perioperative infection was 15.9% (common sites: urinary tract, 57.3%, and surgical wound, 21.4%). Commonly isolated pathogens were Enterococcus species (22.4%) and Escherichia coli (19.4%) in urinary tract infection, and Bacteroides fragilis, E. coli, and Klebsiella pneumoniae (all, 16%) in surgical wound infection. Imipenem represents one of the least resistant antimicrobial agents commonly seen in urinary tract and surgical wound infections in our institution. Perioperative infection was associated with diabetes, serous histology, lymph node metastasis, bowel resection, decreased bicarbonate, and elevated serum urea nitrogen in multivariate analysis. Perioperative infections were associated with increased surgical mortality, delay in chemotherapy treatment, decreased chemotherapy response, shorter progression-free survival (median time, 8.4 vs 17.6 months; P < 0.001), and decreased overall survival (29.0 vs 51.8 months; P = 0.011). Multivariate analysis showed that perioperative infections other than urinary tract infection remained a significant risk factor for decreased survival (progression-free survival, P = 0.02; and overall survival, P = 0.019). Perioperative infectious disease comprises an independent risk factor for survival of patients with ovarian cancer.

Expression of T-box transcription factors 2, 4 and 5 is decreased in the branching airway mesenchyme of nitrofen-induced hypoplastic lungs.

PubMed

Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

2017-02-01

Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major therapeutic challenge in newborns with congenital diaphragmatic hernia (CDH). T-box transcription factors (Tbx) have been identified as key components of the gene network that regulates fetal lung development. Tbx2, Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung, regulating the process of lung branching morphogenesis. Furthermore, lungs of Tbx2-, Tbx4- and Tbx5-deficient mice are hypoplastic and exhibit decreased lung branching, similar to PH in human CDH. We hypothesized that the expression of Tbx2, Tbx4 and Tbx5 is decreased in the branching airway mesenchyme of hypoplastic rat lungs with nitrofen-induced CDH. Time-mated rats received either nitrofen or vehicle on gestational day 9 (D9). Fetuses were killed on D15, D18 and D21, and dissected lungs were divided into control and nitrofen-exposed specimens. Pulmonary gene expression of Tbx2, Tbx4 and Tbx5 was investigated by quantitative real-time polymerase chain reaction. Immunofluorescence double staining for Tbx2, Tbx4 and Tbx5 was combined with the mesenchymal marker Fgf10 to assess protein expression and localization in branching airway tissue. Relative mRNA levels of Tbx2, Tbx4 and Tbx5 were significantly reduced in lungs of nitrofen-exposed fetuses on D15, D18 and D21 compared to controls. Confocal laser scanning microscopy showed markedly diminished immunofluorescence of Tbx2, Tbx4 and Tbx5 in mesenchymal cells surrounding branching airways of nitrofen-exposed fetuses on D15, D18 and D21 compared to controls. Decreased expression of Tbx2, Tbx4 and Tbx5 in the pulmonary mesenchyme during fetal lung development may lead to a decrease or arrest of airway branching, thus contributing to PH in the nitrofen-induced CDH model.

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.

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.

Treated domestic sewage irrigation significantly decreased the CH4, N2O and NH3 emissions from paddy fields with straw incorporation

NASA Astrophysics Data System (ADS)

Xu, Shanshan; Hou, Pengfu; Xue, Lihong; Wang, Shaohua; Yang, Linzhang

2017-11-01

Straw incorporation and domestic sewage irrigation have been recommended as an environmentally friendly agricultural practice and are widely used not only in China but also in other countries. The individual effects on yield and environmental impacts have been studied extensively, but the comprehensive effect when straw returning and domestic sewage irrigation are combined together has seldom been reported. This study was conducted to examine the effects of straw returning and domestic sewage irrigation on rice yields, greenhouse gas emissions (GHGs) and ammonia (NH3) volatilization from paddy fields from 2015 to 2016. The results showed that the rice yield was not affected by the irrigation water sources and straw returning under the same total N input, which was similar in both years. Due to the rich N in the domestic sewage, domestic sewage irrigation could reduce approximately 45.2% of chemical nitrogen fertilizer input without yield loss. Compared to straw removal treatments, straw returning significantly increased the CH4 emissions by approximately 7-9-fold under domestic sewage irrigation and 13-14-fold under tap water irrigation. Straw returning also increased the N2O emissions under the two irrigation water types. In addition, the seasonal NH3 volatilization loss was significantly increased by 88.8% and 61.2% under straw returning compared to straw removal in 2015 and 2016, respectively. However, domestic sewage irrigation could decrease CH4 emissions by 24.5-26.6%, N2O emissions by 37.0-39.0% and seasonal NH3 volatilization loss by 27.2-28.3% under straw returning compared to tap water irrigation treatments. Global warming potentials (GWP) and greenhouse gas intensities (GHGI) were significantly increased with straw returning compared with those of straw removal, while they were decreased by domestic sewage irrigation under straw returning compared to tap water irrigation. Significant interactions between straw returning and domestic sewage irrigation on

Prime Time Sister Circles: evaluating a gender-specific, culturally relevant health intervention to decrease major risk factors in mid-life African-American women.

PubMed Central

Gaston, Marilyn Hughes; Porter, Gayle K.; Thomas, Veronica G.

2007-01-01

PURPOSE: To evaluate the effectiveness of Prime Time Sister Circles (PTSC), a curriculum-based, culture- and gender-specific health intervention, in assisting mid-life African-American women to decrease the major risk factors of physical inactivity, poor nutrition and stress. METHODS: One-hundred-thirty-four African-American women were involved in 11 sites across the country in PTSC and comparison groups. PTSC uses a cognitive behavioral modality based on three theoretical approaches to reduce risk factors and promote positive health changes. Pretest and posttest (10 weeks, and six and 12 months) data were collected on various indicators. RESULTS: t test analyses demonstrated a statistically significant increase in the women's involvement in physical activity at 10 weeks, and six and 12 months. A significant 10-week difference was found in the women's diet, with them reporting eating more nutritious foods, t(77) = 3.32, p < 0.001. The women also indicated from pretest to 10 weeks, and six and 12 months that they changed what they ate to prevent disease (40.4%, 62.8%, 97.5% and 100%, respectively). A majority of the women at 10 weeks (62.7%) and 12 months (65.9%) reported utilizing stress management strategies. There was also a 60% increase in yearly mammograms and a 54% increase in blood pressures checks. Finally, 83.7% of the women at 12 months felt that the positive changes could be maintained over their lifetime. CONCLUSIONS: This study demonstrates the effectiveness of PTSC in modifying health-related knowledge, attitudes and certain high-risk behaviors in mid-life African-American women. PMID:17444433

Expression and clinical significance of connective tissue growth factor in thyroid carcinomas.

PubMed

Wang, Guimin; Zhang, Wei; Meng, Wei; Liu, Jia; Wang, Peisong; Lin, Shan; Xu, Liyan; Li, Enmin; Chen, Guang

2013-08-01

To examine expression of the connective tissue growth factor (CTGF) gene in human thyroid cancer and establish whether a correlation exists between the presence of CTGF protein and clinicopathological parameters of the disease. CTGF protein expression was investigated retrospectively by immunohistochemical analysis of CTGF protein levels in thyroid tumour tissue. Associations between immunohistochemical score and several clinicopathological parameters were examined. In total, 131 thyroid tissue specimens were included. High levels of CTGF protein were observed in papillary thyroid carcinoma tissue; benign thyroid tumour tissue scored negatively for CTGF protein. In papillary thyroid carcinoma, there was a significant relationship between high CTGF protein levels and Union for International Cancer Control disease stage III-IV, and presence of lymph node metastasis. In papillary thyroid carcinomas, CTGF protein levels were not significantly associated with sex or age. These findings suggest that the CTGF protein level is increased in papillary thyroid carcinoma cells compared with benign thyroid tumours. CTGF expression might play a role in the development of malignant tumours in the thyroid.

Significance, definition, classification and risk factors of chronic kidney disease in South Africa.

PubMed

Meyers, A M

2015-03-01

Renal dysfunction or chronic kidney disease (CKD) is found in 10% of the global population and is classified into five stages according to the estimated glomerular filtration rate (eGFR). No matter where a patient lives, estimation of the GFR is mandatory for decision-making and obtained by the simple measurement of a serum creatinine level. The objective of diagnosing CKD lies in its future prevention, early detection and proper treatment, which will prevent or delay functional deterioration. Primary hypertension (PH) occurs in 25% of South Africa (SA)s black population and is the putative cause of stage 5 CKD in 40 - 60% of these patients. Moreover, in this group, stage 5 CKD occurs at a relatively young age (35 - 45 years) compared with other population groups in whom stage 5 CKD resulting from PH usually occurs between 60 and 70 years of age. In the cohort study, PH has been found in 12 - 16% of black school learners (mean age 17 years) compared with 1.8 - 2% of other ethnic groups (mixed race, Asian, white). End-stage renal failure (ESRF) is the fifth most common cause of death in SA, excluding post-traumatic cases. In addition, undiagnosed or poorly controlled PH is a potent risk factor for other cardiovascular disease (CVD), e.g. congestive cardiac failure, myocardial infarction, stroke. Significant protein is also associated with CVD and protein >1 g/d is a significant risk factor for ESRF.

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.

Examining significant factors in micro and small enterprises performance: case study in Amhara region, Ethiopia

NASA Astrophysics Data System (ADS)

Cherkos, Tomas; Zegeye, Muluken; Tilahun, Shimelis; Avvari, Muralidhar

2017-07-01

Furniture manufacturing micro and small enterprises are confronted with several factors that affect their performance. Some enterprises fail to sustain, some others remain for long period of time without transforming, and most are producing similar and non-standard products. The main aim of this manuscript is on improving the performance and contribution of MSEs by analyzing impact of significant internal and external factors. Data was collected via a questionnaire, group discussion with experts and interviewing process. Randomly selected eight representative main cities of Amhara region with 120 furniture manufacturing enterprises are considered. Data analysis and presentation was made using SPSS tools (correlation, proximity, and T test) and impact-effort analysis matrix tool. The correlation analysis shows that politico-legal with infrastructure, leadership with entrepreneurship skills and finance and credit with marketing factors are those factors, which result in high correlation with Pearson correlation values of r = 0.988, 0.983, and 0.939, respectively. The study investigates that the most critical factors faced by MSEs are work premises, access to finance, infrastructure, entrepreneurship and business managerial problems. The impact of these factors is found to be high and is confirmed by the 50% drop-out rate in 2014/2015. Furthermore, more than 25% work time losses due to power interruption daily and around 65% work premises problems challenged MSEs. Further, an impact-effort matrix was developed to help the MSEs to prioritize the affecting factors.

Examining significant factors in micro and small enterprises performance: case study in Amhara region, Ethiopia

NASA Astrophysics Data System (ADS)

Cherkos, Tomas; Zegeye, Muluken; Tilahun, Shimelis; Avvari, Muralidhar

2018-07-01

Furniture manufacturing micro and small enterprises are confronted with several factors that affect their performance. Some enterprises fail to sustain, some others remain for long period of time without transforming, and most are producing similar and non-standard products. The main aim of this manuscript is on improving the performance and contribution of MSEs by analyzing impact of significant internal and external factors. Data was collected via a questionnaire, group discussion with experts and interviewing process. Randomly selected eight representative main cities of Amhara region with 120 furniture manufacturing enterprises are considered. Data analysis and presentation was made using SPSS tools (correlation, proximity, and T test) and impact-effort analysis matrix tool. The correlation analysis shows that politico-legal with infrastructure, leadership with entrepreneurship skills and finance and credit with marketing factors are those factors, which result in high correlation with Pearson correlation values of r = 0.988, 0.983, and 0.939, respectively. The study investigates that the most critical factors faced by MSEs are work premises, access to finance, infrastructure, entrepreneurship and business managerial problems. The impact of these factors is found to be high and is confirmed by the 50% drop-out rate in 2014/2015. Furthermore, more than 25% work time losses due to power interruption daily and around 65% work premises problems challenged MSEs. Further, an impact-effort matrix was developed to help the MSEs to prioritize the affecting factors.

Chronic unpredictable stress decreases expression of brain-derived neurotrophic factor (BDNF) in mouse ovaries: relationship to oocytes developmental potential.

PubMed

Wu, Li-Min; Hu, Mei-Hong; Tong, Xian-Hong; Han, Hui; Shen, Ni; Jin, Ren-Tao; Wang, Wei; Zhou, Gui-Xiang; He, Guo-Ping; Liu, Yu-Sheng

2012-01-01

Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary. Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA) axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated. Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn't affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment. BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress.

Chronic Unpredictable Stress Decreases Expression of Brain-Derived Neurotrophic Factor (BDNF) in Mouse Ovaries: Relationship to Oocytes Developmental Potential

PubMed Central

Tong, Xian-Hong; Han, Hui; Shen, Ni; Jin, Ren-Tao; Wang, Wei; Zhou, Gui-Xiang; He, Guo-Ping; Liu, Yu-Sheng

2012-01-01

Background Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary. Methods Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA) axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated. Results Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn’t affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment. Conclusion BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress. PMID:23284991

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.

[Relationship between factor v Leiden mutation and Chinese Budd-Chiari syndrome and its clinical significance].

PubMed

Feng, B; Xu, K; Jiang, H

2000-05-01

To investigate the relationship between factor v Leiden (FvL) mutation and Chinese sporadic Budd-Chiari syndrome (BCS), familial BCS, and to explore the significance of FvL mutation in the etiology of BCS. Twenty-five patients with sporadic BCS, 6 patients with familial BCS (from A and B families), 39 both A and B family members, and 31 healthy persons were detected for FvL mutation with PCR. Meantime, two family members were explored for the related etiology of BCS. Factor V Leiden mutation was detected in 4 of 6 patients with familial BCS and in 2 family members. AIII(7,11,15) and BII(10), AII(2) and BIII(5) were found FvL mutation, and mutation was heterzygous. FvL mutation in the two degrees was compatible with Mendel hereditery law. The frequency of FvL mutation in 31 BCS and 31 healthy persons showed no statistical significance: but the frequency of FvL mutation between the familial BCS and healthy persons showed statistical significance. Ten persons in A family had varicose vein of the low extremeties, which was compatible with autosomal dominant inheritance. FvL mutation is related to Chinese familial BCS, but is not related to Chinese sporadic BCS. FvL mutation may be a underlying pathogenicity of familial BCS. Varicose vein of the low extremeties may be one of the pathogenicity of familial BCS.

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.

Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia.

PubMed

Kang, Cheol-In; Song, Jae-Hoon; Chung, Doo Ryeon; Peck, Kyong Ran; Ko, Kwan Soo; Yeom, Joon-Sup; Ki, Hyun Kyun; Son, Jun Seong; Lee, Seung Soon; Kim, Yeon-Sook; Jung, Sook-In; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kwon, Ki Tae; Lee, Hyuck; Moon, Chisook

2011-01-01

The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB). From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis. Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P < 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35-4.74), after adjustment for other variables predicting poor prognosis. Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB. Copyright © 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Among Metabolic Factors, Significance of Fasting and Postprandial Increases in Acyl and Desacyl Ghrelin and the Acyl/Desacyl Ratio in Obstructive Sleep Apnea before and after Treatment.

PubMed

Chihara, Yuichi; Akamizu, Takashi; Azuma, Masanori; Murase, Kimihiko; Harada, Yuka; Tanizawa, Kiminobu; Handa, Tomohiro; Oga, Toru; Mishima, Michiaki; Chin, Kazuo

2015-08-15

There are reports suggesting that obstructive sleep apnea (OSA) may itself cause weight gain. However, recent reports showed increases in body mass index (BMI) following continuous positive airway pressure (CPAP) treatments. When considering weight changes, changes in humoral factors that have significant effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin, and glucose and their interactions, examples of which are AG/DAG and AG/insulin, are important. The aim of this study was to test the hypothesis that some appetite-related factors had a specific profile before and after CPAP treatment. Metabolic parameters were measured cross-sectionally while fasting and 30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea-hypopnea index < 15, n = 15) and moderate-to-severe OSA (apnea-hypopnea index ≥ 15, n = 39) participants in a single institute. There were no differences in age, sex, BMI, or visceral fat accumulation between the two groups. Twenty-one patients with moderate-to-severe OSA who received CPAP treatment also prospectively underwent the same testing following 3 months of CPAP treatment. Although fasting and postprandial glucose, insulin, and leptin levels did not differ between no or mild OSA and moderate-to-severe OSA participants, AG and DAG, including AG/DAG and AG/insulin, under fasting and postprandial conditions were significantly increased in the moderate-to-severe OSA patients (p < 0.01). After 3 months of CPAP treatment in 21 of the moderate-to-severe OSA participants, AG/DAG did not change significantly, but other ghrelin-related parameters including AG/insulin significantly decreased compared with values before treatment but remained higher than in no or mild OSA. Among several important metabolic factors, ghrelin-related factors had the strongest associations with moderate-to-severe OSA. These results indicate that continuous changes in ghrelin secretion in OSA patients existed at least within 3 months of

Prognostic significance of hyperfibrinogenemia in patients with esophageal squamous cell carcinoma.

PubMed

Suzuki, Takashi; Shimada, Hideaki; Nanami, Tatsuki; Oshima, Yoko; Yajima, Satoshi; Washizawa, Naohiro; Kaneko, Hironori

2017-06-01

Preoperative hyperfibrinogenemia is associated with inflammatory mediators and a poor prognosis in several types of cancer. However, there is no published information on the monitoring of patients with preoperative hyperfibrinogenemia after surgery. The aim of the study reported here was to assess the clinicopathological and prognostic significance of plasma fibrinogen levels in patients with esophageal squamous cell carcinoma before and after surgical treatment. Plasma fibrinogen levels were analyzed before surgical treatment (endoscopic submucosal dissection and surgery) in 82 patients with esophageal squamous cell carcinoma. The clinicopathological significance of plasma fibrinogen levels and the relationship of plasma fibrinogen levels with several biomarkers were evaluated. The cutoff value for hyperfibrinogenemia was 321 mg/dl. Univariate and multivariate analysis using the Cox proportional hazards model were performed to evaluate the prognostic significance of plasma fibrinogen levels. The changing patterns of plasma fibrinogen were monitored after surgical treatment to evaluate prognostic impact. Hyperfibrinogenemia was significantly associated with advanced pathological stage of cancer and high C-reactive protein levels. Plasma fibrinogen levels significantly decreased after surgical treatment in recurrence-free patients but did not decrease in patients with recurrence. The multivariate analysis indicated that preoperative hyperfibrinogenemia was an independent prognostic factor for poor survival (hazard ratio 1.005, 95% confidence interval 1.000-1.010; P = 0.039). Preoperative hyperfibrinogenemia was associated with inflammatory mediators, tumor progression, and poor survival in patients with esophageal squamous cell carcinoma. The absence of a decrease in plasma fibrinogen levels after surgical treatment may indicate the possibility of tumor recurrence.

Emodin alleviates severe acute pancreatitis-associated acute lung injury by decreasing pre-B-cell colony-enhancing factor expression and promoting polymorphonuclear neutrophil apoptosis.

PubMed

Cui, Hongzhang; Li, Shu; Xu, Caiming; Zhang, Jingwen; Sun, Zhongwei; Chen, Hailong

2017-10-01

The present study aimed to evaluate the protective effects of emodin on severe acute pancreatitis (SAP)‑associated acute lung injury (ALI), and investigated the possible mechanism involved. SAP was induced in Sprague‑Dawley rats by retrograde infusion of 5% sodium taurocholate (1 ml/kg), after which, rats were divided into various groups and were administered emodin, FK866 [a competitive inhibitor of pre‑B‑cell colony‑enhancing factor (PBEF)] or dexamethasone (DEX). DEX was used as a positive control. Subsequently, PBEF expression was detected in polymorphonuclear neutrophils (PMNs) isolated from rat peripheral blood by reverse transcription‑quantitative polymerase chain reaction and western blotting. In addition, histological alterations, apoptosis in lung/pancreatic tissues, apoptosis of peripheral blood PMNs and alterations in the expression of apoptosis‑associated proteins were examined by hematoxylin and eosin staining, terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay, Annexin V/propidium iodide (PI) assay and western blotting, respectively. Serum amylase activity and wet/dry (W/D) weight ratios were also measured. An in vitro study was also conducted, in which PMNs were obtained from normal Sprague‑Dawley rats and were incubated with emodin, FK866 or DEX in the presence of lipopolysaccharide (LPS). Apoptosis of PMNs and the expression levels of apoptosis‑associated proteins were examined in cultured PMNs in vitro by Annexin V/PI assay and western blotting, respectively. The results demonstrated that emodin, FK866 and DEX significantly downregulated PBEF expression in peripheral blood PMNs. In addition, emodin, FK866 and DEX reduced serum amylase activity, decreased lung and pancreas W/D weight ratios, alleviated lung and pancreatic injuries, and promoted PMN apoptosis by regulating the expression of apoptosis‑associated proteins: Fas, Fas ligand, B‑cell lymphoma (Bcl)‑2‑associated X protein, cleaved

Downregulation of aquaporin 9 decreases catabolic factor expression through nuclear factor‑κB signaling ins chondrocytes.

PubMed

Takeuchi, Kazuhiro; Hayashi, Shinya; Matumoto, Tomoyuki; Hashimoto, Shingo; Takayama, Koji; Chinzei, Nobuaki; Kihara, Shinsuke; Haneda, Masahiko; Kirizuki, Shinsuke; Kuroda, Yuichi; Tsubosaka, Masanori; Nishida, Kotaro; Kuroda, Ryosuke

2018-06-13

Aquaporins (AQPs) are small integral membrane proteins that are essential for water transport across membranes. AQP9, one of the 13 mammalian AQPs (including AQP0 to 12), has been reported to be highly expressed in hydrarthrosis and synovitis patients. Given that several studies have identified signal transduction as an additional function of AQPs, it is hypothesized that AQP9 may modulate inflammatory signal transduction in chondrocytes. Therefore, the present study used a model of interleukin (IL)‑1β‑induced inflammation to determine the mechanisms associated with AQP9 functions in chondrocytes. Osteoarthritis (OA) and normal cartilage samples were subjected to immunohistological analysis. In addition, matrix metalloproteinase (MMP)3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS‑5) mRNA and protein analysis was conducted in normal human articular chondrocytes from the knee (NHAC‑Kn) stimulated with IL‑1β by reverse transcription‑polymerase chain reaction (RT‑qPCR) and western blotting, respectively. AQP9 knockdown was also performed by transfection of AQP9‑specific small interfering RNA using Lipofectamine. AQP1, 3, 7, 9 and 11 mRNA expression levels were detected in OA human chondrocytes and in IL‑1β‑treated normal human chondrocytes. The levels of AQP9, MMP‑3, MMP‑13 and ADAMTS‑5 mRNA were increased by treatment with 10 ng/ml IL‑1β in a time‑dependent manner, while knockdown of AQP9 expression significantly decreased the mRNA levels of the MMP3, MMP13 and ADAMTS‑5 genes, as well as the phosphorylation of IκB kinase (IKK). Treatment with a specific IKK inhibitor also significantly decreased the expression levels of MMP‑3, MMP‑13 and ADAMTS‑5 in response to IL‑1β stimulation. Furthermore, immunohistochemical analysis demonstrated that AQP9 and inflammatory markers were highly expressed in OA cartilage. In addition, the downregulation of AQP9 in cultured chondrocytes decreased the

Epidermal growth factor administration decreases liver glycogen and causes mild hyperglycaemia in mice.

PubMed

Grau, M; Tebar, F; Ramírez, I; Soley, M

1996-04-01

Several laboratories report different effects of epidermal growth factor (EGF) on glycogen metabolism in hepatocytes. The discrepancies may be attributed to differences in the experimental conditions. It is therefore important to establish the actual effect of EGF in vivo. Because large physiological variations of EGF concentration in plasma occur in mice, we used this species to address this question. In freshly isolated mouse hepatocytes, EGF increased glycogen degradation in a dose-dependent manner. The maximal effect (36% increase over basal glycogenolysis) was smaller than maximal effects of classical glycogenolytic hormones like adrenaline or glucagon (more than 150% increase over basal). This is in keeping with the smaller effect of EGF on phosphorylase a activity. In contrast with these hormones, EGF did not inhibit glycolysis. Thus these effects of EGF in mouse hepatocytes are similar to those recently described by us in rat hepatocytes [Quintana, Grau, Moreno, Soler, Ramirez and Soley (1995) Biochem J 308, 889-894]. When administered to whole animals, EGF increased phosphorylase a activity, decreased the glycogen content in the liver and caused mild hyperglycaemia. Taking together the results obtained for isolated cells and for whole animals, we suggest that the glucosyl residues released from glycogen are used mostly by the liver rather than released to the circulation. This would be different from the action of the classical glycogenolytic hormones, adrenaline and glucagon.

Risk factors for persistent fatigue with significant school absence in children and adolescents.

PubMed

Bakker, Robert J; van de Putte, Elise M; Kuis, Wietse; Sinnema, Gerben

2009-07-01

To assess children and adolescents with severe fatigue who are referred to pediatricians and to examine whether factors can be identified at their first visit that predict worse outcomes at 1 year. Ninety-one patients, aged 8 to 18 years completed questionnaires about sleep, somatic symptoms, physical activity, and fatigue. They were reassessed 12 months later. Measurements at baseline and outcome were analyzed by using univariable logistic regression with persistent, severe fatigue (yes/no) and persistent school absence (yes/no) as dependent variables and baseline scores as independent variables. After 12 months, 50.6% of the children and adolescents showed improvement; 29.1% had persistent fatigue, and 20.3% had persistent fatigue with significant school absence. Factors associated with the poorest outcome were sleep problems (odds ratio [OR]: 1.4 [95% confidence interval (CI): 1.1-1.8]), initial fatigue score (OR: 1.1 [95% CI: 1.0-1.2]), somatic complaints such as hot and cold spells (OR: 1.9 [95% CI: 1.2-3.0]), blurred vision (OR: 2.1 [95% CI: 1.1-4.0]), pain in arms and legs (OR: 2.0 [95% CI: 1.0-3.2]), back pain (OR: 1.8 [95% CI: 1.0-3.2]), constipation (OR: 1.7 [95% CI: 1.0-2.7]), and memory deficits (OR: 1.8 [95% CI: 1.0-3.2]). Resolved fatigue was associated with male gender (OR: 5.0 [95% CI: 1.6-15.5]) and a physically active lifestyle (OR: 1.3 [95% CI: 1.1-1.5]). Assessment of predictive factors at the first visit enables the pediatrician to identify those patients with severe fatigue who are at risk of a poor outcome. Female gender, poor sleep quality, physically inactive lifestyle, and specific somatic complaints were important predictive factors.

Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool.

PubMed

Auerbach, Raymond K; Chen, Bin; Butte, Atul J

2013-08-01

Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. abutte@stanford.edu Supplementary material is available at Bioinformatics online.

Bardoxolone Methyl Decreases Megalin and Activates Nrf2 in the Kidney

PubMed Central

Chertow, Glenn M.; Hebbar, Sudarshan; Vaziri, Nosratola D.; Ward, Keith W.; Meyer, Colin J.

2012-01-01

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2–related factor 2 (Nrf2)–mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl–induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl–induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets. PMID:22859857

Bardoxolone methyl decreases megalin and activates nrf2 in the kidney.

PubMed

Reisman, Scott A; Chertow, Glenn M; Hebbar, Sudarshan; Vaziri, Nosratola D; Ward, Keith W; Meyer, Colin J

2012-10-01

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl-induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl-induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets.

Among Metabolic Factors, Significance of Fasting and Postprandial Increases in Acyl and Desacyl Ghrelin and the Acyl/Desacyl Ratio in Obstructive Sleep Apnea before and after Treatment

PubMed Central

Chihara, Yuichi; Akamizu, Takashi; Azuma, Masanori; Murase, Kimihiko; Harada, Yuka; Tanizawa, Kiminobu; Handa, Tomohiro; Oga, Toru; Mishima, Michiaki; Chin, Kazuo

2015-01-01

Study Objectives: There are reports suggesting that obstructive sleep apnea (OSA) may itself cause weight gain. However, recent reports showed increases in body mass index (BMI) following continuous positive airway pressure (CPAP) treatments. When considering weight changes, changes in humoral factors that have significant effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin, and glucose and their interactions, examples of which are AG/DAG and AG/insulin, are important. The aim of this study was to test the hypothesis that some appetite-related factors had a specific profile before and after CPAP treatment. Methods: Metabolic parameters were measured cross-sectionally while fasting and 30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea-hypopnea index < 15, n = 15) and moderate-to-severe OSA (apnea-hypopnea index ≥ 15, n = 39) participants in a single institute. There were no differences in age, sex, BMI, or visceral fat accumulation between the two groups. Twenty-one patients with moderate-to-severe OSA who received CPAP treatment also prospectively underwent the same testing following 3 months of CPAP treatment. Results: Although fasting and postprandial glucose, insulin, and leptin levels did not differ between no or mild OSA and moderate-to-severe OSA participants, AG and DAG, including AG/DAG and AG/insulin, under fasting and postprandial conditions were significantly increased in the moderate-to-severe OSA patients (p < 0.01). After 3 months of CPAP treatment in 21 of the moderate-to-severe OSA participants, AG/DAG did not change significantly, but other ghrelin-related parameters including AG/insulin significantly decreased compared with values before treatment but remained higher than in no or mild OSA. Conclusions: Among several important metabolic factors, ghrelin-related factors had the strongest associations with moderate-to-severe OSA. These results indicate that continuous changes in ghrelin secretion in

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.

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.

Reverse shoulder arthroplasty leads to significant biomechanical changes in the remaining rotator cuff.

PubMed

Herrmann, Sebastian; König, Christian; Heller, Markus; Perka, Carsten; Greiner, Stefan

2011-08-16

After reverse shoulder arthroplasty (RSA) external and internal rotation will often remain restricted. A postoperative alteration of the biomechanics in the remaining cuff is discussed as a contributing factor to these functional deficits. In this study, muscle moment arms as well as origin-to-insertion distance (OID) were calculated using three-dimensional models of the shoulder derived from CT scans of seven cadaveric specimens. Moment arms for humeral rotation are significantly smaller for the cranial segments of SSC and all segments of TMIN in abduction angles of 30 degrees and above (p ≤ 0.05). Abduction moment arms were significantly decreased for all segments (p ≤ 0.002). OID was significantly smaller for all muscles at the 15 degree position (p ≤ 0.005), apart from the cranial SSC segment. Reduced rotational moment arms in conjunction with the decrease of OID may be a possible explanation for the clinically observed impaired external and internal rotation.

48 CFR 315.304 - Evaluation factors and significant subfactors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 508 Product Assessment Template—see Section 508 policy on Office of Disability Web site for the... factor development. (b) Before conducting negotiations or making an award, the Contracting Officer shall...

Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD).

PubMed

Notarnicola, Maria; Caruso, Maria Gabriella; Tutino, Valeria; Bonfiglio, Caterina; Cozzolongo, Raffaele; Giannuzzi, Vito; De Nunzio, Valentina; De Leonardis, Giampiero; Abbrescia, Daniela I; Franco, Isabella; Intini, Vincenza; Mirizzi, Antonella; Osella, Alberto R

2017-08-23

The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage. This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD. Diagnosis of liver steatosis was performed by using vibration-controlled elastography implemented on FibroScan. Fatty acids, extracted from phospholipids of erythrocyte membranes, were quantified by gas chromatography method. The subjects with severe NAFLD showed a significant decrease of the ratio of stearic acid to oleic acid (saturation index, SI) compared to controls, 1.281 ± 0.31 vs 1.5 ± 0.29, respectively. Low levels of SI in red blood cell membranes, inversely associated with degree of liver damage, suggest that an impairment of circulating cell membrane structure can reflect modifications that take place in the liver. Subjects with severe NAFLDalso showed higher levels of elongase 5 enzymatic activity, evaluated as vaccenic acid to palmitoleic acid ratio. Starting from these evidences, our findings show the importance of lipidomic approach in the diagnosis and the staging of NAFLD.

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.

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.

[The expression and significance of receptor activator of nuclear factor kappaB ligand and osteoprotegerin in periapical cyst and periapical granuloma].

PubMed

Zhang, Meihua; Yu, Yunzhi; Miao, Yu

2012-08-01

To investigate the expression of receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) in periapical cyst and periapical granuloma by comparison with the expression in the normal periodontal tissue as control, and to identify their functional mechanism in the bone destruction of periapical cyst and granuloma. 20 periapical cyst tissues (cyst group), 20 periapical granuloma tissues (granuloma group), and 20 normal periodontal tissues (control group) were collected respectively. Immunohistochemical technology was performed to detect the expression of RANKL and OPG in above three groups. In cyst group, granuloma group and control group, the expression of RANKL were 75.00 +/- 7.54, 68.40 +/- 6.74 and 29.40 +/- 2.46, respectively. The expression of OPG were 38.10 +/- 7.09, 47.65 +/- 13.85 and 58.60 +/- 5.88, respectively. The differences among the three groups were statistically significant (P<0.05). RANKL and OPG in cysts group were negatively correlated (r=-0.56, P=0.01) and were not correlated with granuloma and control group (P>0.05). RANKL and OPG play roles in the bone absorption of periapical disease. In periapical disease, abnormal expression of RANKL and OPG are detected, RANKL significantly increase, OPG decrease, bone absorption accelerate and osteolytic lesion are observed. In periapical cyst, the bone absorption is more active compared with periapical granuloma.

Factors of Significant Impact on Proficiency Levels of Adult ESL Learners within Post-Secondary Education in Puerto Rico

ERIC Educational Resources Information Center

Perez, Ramon

2011-01-01

This qualitative case study seeks to identify factors that have a significant impact on the second language proficiency levels of adult English as a Second Language (ESL) learners at a four-year university in Puerto Rico. Current data indicate that a significant percentage of adult ESL learners encounter major difficulties within the process of…

Expression of transcription factor Pokemon in non-small cell lung cancer and its clinical significance.

PubMed

Zhao, Zhi-hong; Wang, Sheng-fa; Yu, Liang; Wang, Ju; Chang, Hao; Yan, Wei-li; Fu, Kai; Zhang, Jian

2008-03-05

Transcription factor Pokemon, a central regulation gene of the important tumor suppressor ARF gene, exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in NSCLC and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis. Fifty-five cases of NSCLC were involved in this study. The expression of Pokemon in the tumor tissue, the corresponding tumor adjacent tissue and the surrounding tissue was detected via reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, with the aim of investigating the correlation between the expression of Pokemon in tumor tissue of NSCLC and its clinical pathological characteristics. Moreover, a prognostic analysis was carried out based upon the immunohistochemical (IHC) detection of the expression of Pokemon gene in archival tumor specimens (5 years ago) of 62 cases of NSCLC. Statistical significance of the expression of Pokemon mRNA and protein was determined in the tumor tissue, the tumor adjacent tissue and the surrounding tissue (P<0.05). The expression of Pokemon was determined not to be associated with the patients' sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (P<0.05). Furthermore, it was shown that the survival rate of patients with negative Pokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an independent factor affecting prognosis (P=0.034). Pokemon was over-expressed in NSCLC tissue and the expression of Pokemon might be of clinical significance in non-small cell lung cancer prognostic evaluation.

Predictive factors for long-term survival in patients with clinically significant portal hypertension following resection of hepatocellular carcinoma.

PubMed

Choi, Gi H; Park, Jun Y; Hwang, Ho K; Kim, Dong H; Kang, Chang M; Choi, Jin S; Park, Young N; Kim, Do Y; Ahn, Sang H; Han, Kwang-Hyub; Chon, Chae Y; Lee, Woo J

2011-04-01

Hepatic resection for hepatocellular carcinoma (HCC) is not currently recommended for patients with clinically significant portal hypertension (PHT); however, recent studies have shown similar post-operative outcomes between patients with and without clinically significant PHT. To clarify the post-operative prognostic relevance of clinically significant PHT in Child-Pugh A cirrhotic patients. A total of 100 Child-Pugh A cirrhotic patients who underwent curative resection of HCC were eligible for this analysis. Patients were divided into two groups: PHT group (n=47) and non-PHT group (n=53). Clinicopathological variables showed no significant differences except for prothrombine time. Liver-related complications were significantly higher in the PHT group (P=0.015), and the 5-year overall survival rate was significantly higher in the non-PHT group (78.7 vs. 37.9%, P<0.001). The proportion of patients who died because of complications of cirrhosis was significantly higher in the PHT group (P=0.001). Multivariate analysis indicated that the presence of clinically significant PHT was the most powerful adverse prognostic factor for overall survival. Multivariate analysis of the 47 patients with clinically significant PHT indicated that gross vascular invasion and non-single nodular type were poor prognostic factors. The 5-year survival rate of patients with single nodular type and without gross vascular invasion (n=17) was 78.4%. In Child-Pugh A cirrhotic patients, the presence of clinically significant PHT was significantly associated with post-operative hepatic decompensation and poor prognosis after resection of HCC. However, in patients with clinically significant PHT, those with single nodular tumours lacking gross vascular invasion may be good surgical candidates. © 2011 John Wiley & Sons A/S.

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

48 CFR 215.304 - Evaluation factors and significant subfactors.

Code of Federal Regulations, 2014 CFR

2014-10-01

... of any information technology, whether acquired as a service or as a supply, consider the need for an evaluation factor regarding supply chain risk (see subpart 239.73). [71 FR 3414, Jan. 23, 2006, as amended at...

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.

Risk factors associated with Cryptosporidium parvum infection in dairy cattle in southeastern New York State.

PubMed

Mohammed, H O; Wade, S E; Schaaf, S

1999-06-01

An observational analytical epidemiologic study was carried out to identify factors associated with the risk of infection with Cryptosporidium parvum in dairy herds in southeastern New York state. A random sample of 2943 cattle on 109 farms was selected from the target population. Fecal samples were collected from animals in three different age groups and examined for the presence of C. parvum using a quantitative centrifugation concentration flotation method. Data on intrinsic, preweaning, postweaning, maternity, and general management factors were collected and evaluated for their association with the risk of infection with C. parvum. Indices for each of these categories of management were developed from factors significantly associated with the risk of infection with C. parvum. Significant factors were identified using the logistic regression statistical technique. A final analysis, including the indices, age, and season, was performed to identify factors significantly associated with the risk of infection with C. parvum while simultaneously controlling for the effect of other factors. The farm effect was evaluated using a mixed effect model. Preweaning factors found to be significantly associated with a decreased risk of infection were: use of ventilation in calf rearing areas, daily addition of bedding, feeding of milk replacer, daily disposal and cleaning of bedding, and use of antibiotics. Postweaning factors such as moving of the animals after weaning, cleaning of soiled bedding, and use of antibiotics and ionophores as preventive measures were significantly associated with the decreased risk of an infection with C. parvum. Consideration of maternity management factors showed that winter housing of cows individually within 2 months of calving, use of fresh colostrum to feed calves, and having a concrete floor in the calving area were significantly associated with decreased risk of C. parvum infection. The total number of dairy cattle, total number of other

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.

Gemfibrozil Concentrations are Significantly Decreased in the Presence of Lopinavir/ritonavir

PubMed Central

Busse, Kristin H.; Hadigan, Colleen; Chairez, Cheryl; Alfaro, Raul M.; Formentini, Elizabeth; Kovacs, Joseph A.; Penzak, Scott R.

2009-01-01

Objective: To determine the influence of a two-week course of lopinavir-ritonavir on the pharmacokinetics of the triglyceride-lowering agent, gemfibrozil. Methods: The study was conducted as an open label, single-sequence pharmacokinetic study in healthy human volunteers. Gemfibrozil pharmacokinetic parameter values were compared using a students t test after a single 600 mg dose was administered to healthy volunteers before, and after two weeks of lopinavir-ritonavir (400/100 mg) twice daily. Results: Fifteen healthy volunteers (8 males) completed the study. All study drugs were generally well-tolerated and no subjects withdrew participation. The geometric mean ratio (GMR, 90% CI) for gemfibrozil area under the plasma concentration-time curve (AUC0-∞) after 14 days of lopinavir-ritonavir compared to baseline was 0.59 (0.52, 0.67) (P < 0.001). All 15 study subjects experienced a reduction in gemfibrozil AUC0-∞ after lopinavir-ritonavir (range: −6% to −74%). The GMRs for gemfibrozil apparent oral clearance (Cl/F) and maximum concentration (Cmax) were 1.69 (1.41, 1.97) and 0.67 (0.49, 0.86) after 14 days of lopinavir-ritonavir versus baseline, respectively (P < 0.0001 and 0.01, respectively). Gemfibrozil elimination half-life did not change after lopinavir-ritonavir administration (P = 0.60). Conclusion: Lopinavir/ritonavir significantly reduced the systemic exposure of gemfibrozil by reducing gemfibrozil absorption. Clinicians treating HIV-infected patients with hypertriglyceridemia should be aware of this drug interaction. PMID:19648824

Gemfibrozil concentrations are significantly decreased in the presence of lopinavir-ritonavir.

PubMed

Busse, Kristin H; Hadigan, Colleen; Chairez, Cheryl; Alfaro, Raul M; Formentini, Elizabeth; Kovacs, Joseph A; Penzak, Scott R

2009-10-01

The objective of this study was to determine the influence of a 2-week course of lopinavir-ritonavir on the pharmacokinetics of the triglyceride-lowering agent, gemfibrozil. The study was conducted as an open label, single-sequence pharmacokinetic study in healthy human volunteers. Gemfibrozil pharmacokinetic parameter values were compared using a Student t test after a single 600-mg dose was administered to healthy volunteers before and after 2 weeks of lopinavir-ritonavir (400/100 mg) twice daily. Fifteen healthy volunteers (eight males) completed the study. All study drugs were generally well tolerated and no subjects withdrew participation. The geometric mean ratio (90% confidence interval) for gemfibrozil area under the plasma concentration-time curve after 14 days of lopinavir-ritonavir compared with baseline was 0.59 (0.52, 0.67) (P < 0.001). All 15 study subjects experienced a reduction in gemfibrozil area under the plasma concentration-time curve after lopinavir-ritonavir (range, -6% to -74%). The geometric mean ratios for gemfibrozil apparent oral clearance and maximum concentration were 1.69 (1.41, 1.97) and 0.67 (0.49, 0.86) after 14 days of lopinavir-ritonavir versus baseline, respectively (P < 0.0001 and 0.01, respectively). Gemfibrozil elimination half-life did not change after lopinavir-ritonavir administration (P = 0.60). Lopinavir-ritonavir significantly reduced the systemic exposure of gemfibrozil by reducing gemfibrozil absorption. Clinicians treating HIV-infected patients with hypertriglyceridemia should be aware of this drug interaction.

Review of Significant Incidents and Close Calls in Human Spaceflight from a Human Factors Perspective

NASA Technical Reports Server (NTRS)

Silva-Martinez, Jackelynne; Ellenberger, Richard; Dory, Jonathan

2017-01-01

This project aims to identify poor human factors design decisions that led to error-prone systems, or did not facilitate the flight crew making the right choices; and to verify that NASA is effectively preventing similar incidents from occurring again. This analysis was performed by reviewing significant incidents and close calls in human spaceflight identified by the NASA Johnson Space Center Safety and Mission Assurance Flight Safety Office. The review of incidents shows whether the identified human errors were due to the operational phase (flight crew and ground control) or if they initiated at the design phase (includes manufacturing and test). This classification was performed with the aid of the NASA Human Systems Integration domains. This in-depth analysis resulted in a tool that helps with the human factors classification of significant incidents and close calls in human spaceflight, which can be used to identify human errors at the operational level, and how they were or should be minimized. Current governing documents on human systems integration for both government and commercial crew were reviewed to see if current requirements, processes, training, and standard operating procedures protect the crew and ground control against these issues occurring in the future. Based on the findings, recommendations to target those areas are provided.

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.

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.

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

Lifestyle factors are significantly associated with the locomotive syndrome: a cross-sectional study.

PubMed

Akahane, Manabu; Yoshihara, Shingo; Maeyashiki, Akie; Tanaka, Yasuhito; Imamura, Tomoaki

2017-10-18

The Japanese Orthopedic Association first proposed the concept of "locomotive syndrome" in 2007. It refers to circumstances in which elderly people need nursing care services or are at high risk of requiring such services within a short time. Recently, the public health burden of providing nursing care for elderly individuals has increased. Therefore, locomotive syndrome, and the means of preventing it, are a major public health focus in Japan. The purpose of this study was to investigate the relationships of lifestyle factors, such as smoking, alcohol consumption, sleep duration, and dental health, with locomotive syndrome. We conducted a cross-sectional study using an internet panel survey. The participants comprised 747 individuals aged 30-90 years. Factors related to demographics (age, sex), general health (number of teeth, presence of periodontal disease), and lifestyle (smoking, alcohol consumption, sleep duration) were assessed. We also used the 25-question Geriatric Locomotive Function Scale to determine whether each participant had locomotive syndrome. Multivariate analysis was conducted using logistic regression to investigate the independent relationships between locomotive syndrome and lifestyle factors after adjusting for sex and age. A greater proportion of women (17.7%) than men (11.2%) had locomotive syndrome (p < 0.05). Participants aged ≥65 years showed significantly higher percentages (men: 21.4%, women: 75.7%) of locomotive syndrome compared with those aged <65 years (p < 0.05). Logistic regression analysis revealed that older age (≥ 65 years), sex, current smoking status, number of existing teeth, and presence of periodontal disease were associated with locomotive syndrome, whereas sleep duration was not. The frequency of alcohol consumption, except for daily drinking, was also associated with locomotive syndrome. Our study indicates that lifestyle factors, such as smoking and number of existing teeth, may partly affect the

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.

Proton Pump Inhibitors Decrease Soluble fms-Like Tyrosine Kinase-1 and Soluble Endoglin Secretion, Decrease Hypertension, and Rescue Endothelial Dysfunction.

PubMed

Onda, Kenji; Tong, Stephen; Beard, Sally; Binder, Natalie; Muto, Masanaga; Senadheera, Sevvandi N; Parry, Laura; Dilworth, Mark; Renshall, Lewis; Brownfoot, Fiona; Hastie, Roxanne; Tuohey, Laura; Palmer, Kirsten; Hirano, Toshihiko; Ikawa, Masahito; Kaitu'u-Lino, Tu'uhevaha; Hannan, Natalie J

2017-03-01

Preeclampsia is a severe complication of pregnancy. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, and multiorgan injury. Oxidative stress and vascular inflammation exacerbate the endothelial injury. A drug that can block these pathophysiological steps would be an attractive treatment option. Proton pump inhibitors (PPIs) are safe in pregnancy where they are prescribed for gastric reflux. We performed functional studies on primary human tissues and animal models to examine the effects of PPIs on sFlt-1 and soluble endoglin secretion, vessel dilatation, blood pressure, and endothelial dysfunction. PPIs decreased sFlt-1 and soluble endoglin secretion from trophoblast, placental explants from preeclamptic pregnancies, and endothelial cells. They also mitigated tumor necrosis factor-α-induced endothelial dysfunction: PPIs blocked endothelial vascular cell adhesion molecule-1 expression, leukocyte adhesion to endothelium, and disruption of endothelial tube formation. PPIs decreased endothelin-1 secretion and enhanced endothelial cell migration. Interestingly, the PPI esomeprazole vasodilated maternal blood vessels from normal pregnancies and cases of preterm preeclampsia, but its vasodilatory effects were lost when the vessels were denuded of their endothelium. Esomeprazole decreased blood pressure in a transgenic mouse model where human sFlt-1 was overexpressed in placenta. PPIs upregulated endogenous antioxidant defenses and decreased cytokine secretion from placental tissue and endothelial cells. We have found that PPIs decrease sFlt-1 and soluble endoglin secretion and endothelial dysfunction, dilate blood vessels, decrease blood pressure, and have antioxidant and anti-inflammatory properties. They have therapeutic potential for preeclampsia and other diseases where endothelial dysfunction is involved. © 2017 American Heart Association

Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.

PubMed

Kikuchi, Ryoko; Kikuchi, Yoshihiro; Tsuda, Hitoshi; Maekawa, Hitoshi; Kozaki, Ken-Ichi; Imoto, Issei; Tamai, Seiichi; Shiotani, Akihiro; Iwaya, Keiichi; Sakamoto, Masaru; Sekiya, Takao; Matsubara, Osamu

2014-07-01

Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

PERSONAL AND ENVIRONMENTAL RISK FACTORS SIGNIFICANTLY ASSOCIATED WITH ELEVATED BLOOD LEAD LEVELS IN RURAL THAI CHILDREN.

PubMed

Swaddiwudhipong, Witaya; Kavinum, Suporn; Papwijitsil, Ratchadaporn; Tontiwattanasap, Worawit; Khunyotying, Wanlee; Umpan, Jiraporn; BoonthuM, Ratchaneekorn; Kaewnate, Yingyot; Boonmee, Sasis; Thongchub, Winai; Rodsung, Thassanee

2014-11-01

A community-based study was conducted to determine personal risk factors and environmental sources of lead exposure for elevated blood lead levels (≥ 10 µg/dl, EBLLs) among rural children living at the Thailand-Myanmar border in Tak Province, northwestern Thailand. Six hundred ninety-five children aged 1-14 years old were screened for BLLs. Environmental specimens for lead measurements included samples of water from the streams, taps, and household containers, house floor dust, and foods. Possible lead release from the cooking ware was determined using the leaching method with acetic acid. The overall prevalence of EBLLs was 47.1% and the geometric mean level of blood lead was 9.16 µg/dl. Personal risk factors significantly associated with EBLLs included being male, younger age, anemia, and low weight-for-age. Significant environmental risk factors were exposure to a lead-acid battery of solar energy system and use of a non-certified metal cooking pot. Some families whose children had high BLLs reported production of lead bullets from the used batteries at home. About one-third of the house dust samples taken near batteries contained lead content above the recommended value, compared with none of those taken from other areas and from the houses with no batteries. The metal pots were safe for cooking rice but might be unsafe for acidic food preparation. Both nutritional intervention and lead exposure prevention programs are essential to reduce EBLLs in this population.

Metabolic syndrome is a significant and independent risk factor for increased arterial stiffness in Japanese subjects.

PubMed

Satoh, Hiroki; Kishi, Reiko; Tsutsui, Hiroyuki

2009-12-01

Metabolic syndrome (MetS) has been recognized as a risk factor for cardiovascular disease; however, the impact of MetS on arterial stiffness has not been fully established in the general Japanese population. We analyzed the relationship between MetS and the severity of arterial stiffness using brachial-ankle pulse wave velocity (baPWV) in 2744 male and 358 female subjects aged 38-62 years, adjusted for conventional risk factors and C-reactive protein. The prevalence rates of MetS identified by Japanese criteria were 22.7% (n=624) and 7.8% (n=28) in male and female subjects, respectively. The subjects with MetS had significantly greater mean values of baPWV than those without MetS among both male and female subjects (1444+/-209 vs. 1294+/-165 cm/s in male subjects, P<0.001; 1379+/-151 vs. 1220+/-171 cm/s in female subjects, P<0.001). After adjustment for atherosclerotic variables such as age, smoking habits, total cholesterol and C-reactive protein, the odds ratio (OR) of MetS for increased baPWV was 3.65 in male subjects (95% confidence interval (CI): 2.99-4.47, P<0.001) and 8.02 in female subjects (95% CI: 3.18-20.25 P<0.001). In conclusion, MetS was identified as a significant and independent risk factor for increased arterial stiffness in both the male and female general population in Japan.

Independent from muscle power and balance performance, a creatinine clearance below 65 ml/min is a significant and independent risk factor for falls and fall-related fractures in elderly men and women diagnosed with osteoporosis.

PubMed

Dukas, L; Schacht, E; Runge, M

2010-07-01

We assessed in a cross-sectional study in elderly men and women with osteoporosis, the association between the creatinine clearance (CrCl) and the performance in different balance and muscle power and function tests and found that a decreasing creatinine clearance was significantly associated with lower balance and muscle power. To determine if a creatinine clearance of <65 ml/min is significantly associated with decreasing muscle power and balance and an increased risk for falls and fractures. We assessed in a cross-sectional-study in 1781 German osteoporotic patients, the association between the CrCl, the physical performance, and the number of falls and fractures. Controlling for age, gender, BMI, and osteoporosis treatment (fracture analysis only), a decreasing CrCl was associated with lower physical performance in the timed-up-and-go test (corr -0.2337, P < 0.0001), chair-rising test (corr -0.1706, P < 0.001), and tandem-stand test (corr 0.2193, P < 0.0001), and a CrCl of <65 ml/min was associated with a significantly higher risk for falls (47.7% vs. 36.2%, P = 0.0008) and fall-related fractures (33.1% vs. 22.9%, P = 0.0003) compared with a CrCl of >or=65 ml/min. In this study, we found a significant gender-independent correlation between decreasing CrCl and lower performance in balance and muscle power tests. Reduced muscle power and balance may therefore be involved in the low creatinine clearance associated increased risk for falls and fall-related fractures. Furthermore, we found that a CrCl <65 ml/min., independent from the performance in muscle power, muscle function, and balance tests, is a significant risk factor for falls and fractures.

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.

Laser-assisted delivery of vitamin C, vitamin E, and ferulic acid formula serum decreases fractional laser postoperative recovery by increased beta fibroblast growth factor expression.

PubMed

Waibel, Jill S; Mi, Qing-Sheng; Ozog, David; Qu, Le; Zhou, Li; Rudnick, Ashley; Al-Niaimi, Firas; Woodward, Julie; Campos, Valerie; Mordon, Serge

2016-03-01

Laser-assisted drug delivery is an emerging technology to achieve greater penetration by existing topical medications to reach desired targets in the tissue. The objective of this research was to study whether laser-assisted delivery of Vitamin C, E, and Ferulic immediately postoperatively of fractional ablative laser could improve wound healing. Secondary objectives were to evaluate the potential molecular markers involved in this wound-healing process. A double blinded, prospective, single center, randomized split face trial of Vitamin C, E, and Ferulic topical formula #740019 to decrease postoperative recovery time in fractional ablative laser resurfacing for photo damage. Fifteen healthy men and women of ages 30-55 years were treated with the Vitamin C, E, and Ferulic acid serum to one side of face and vehicle to the other side of face, within 2 minutes immediately after fractional ablative CO2 laser surgery and daily during the healing process. Patients were evaluated daily on days 1-7 using photographs, patient questionnaires, and molecular evaluation. Clinically, postoperative Vitamin C, E, and Ferulic delivery resulted in decreased edema versus vehicle on postoperative day 7 and decreased erythema versus vehicle on postoperative days 3 and 5. Molecularly, the expression of basic fibroblast growth factor (bFGF) was significantly increased at day 5 on the lesion treated with Vitamin C, E, and Ferulic acid serum compared to vehicle control on the other side. This is first study to show that Vitamin C, E, and Ferulic acid correlate with more rapid wound healing post-fractional ablative laser. Elevated bFGF could be involved in the Vitamin C, E, and Ferulic acid-induced rapid wound healing. © 2015 Wiley Periodicals, Inc.

Retinopathy of prematurity: a review of risk factors and their clinical significance.

PubMed

Kim, Sang Jin; Port, Alexander D; Swan, Ryan; Campbell, J Peter; Chan, R V Paul; Chiang, Michael F

2018-04-19

Retinopathy of prematurity (ROP) is a retinal vasoproliferative disease that affects premature infants. Despite improvements in neonatal care and management guidelines, ROP remains a leading cause of childhood blindness worldwide. Current screening guidelines are primarily based on two risk factors: birth weight and gestational age; however, many investigators have suggested other risk factors, including maternal factors, prenatal and perinatal factors, demographics, medical interventions, comorbidities of prematurity, nutrition, and genetic factors. We review the existing literature addressing various possible ROP risk factors. Although there have been contradictory reports, and the risk may vary between different populations, understanding ROP risk factors is essential to develop predictive models, to gain insights into pathophysiology of retinal vascular diseases and diseases of prematurity, and to determine future directions in management of and research in ROP. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Postoperative Decrease in Platelet Counts Is Associated with Delayed Liver Function Recovery and Complications after Partial Hepatectomy.

PubMed

Takahashi, Kazuhiro; Kurokawa, Tomohiro; Oshiro, Yukio; Fukunaga, Kiyoshi; Sakashita, Shingo; Ohkohchi, Nobuhiro

2016-05-01

Peripheral platelet counts decrease after partial hepatectomy; however, the implications of this phenomenon are unclear. We assessed if the observed decrease in platelet counts was associated with postoperative liver function and morbidity (complications grade ≤ II according to the Clavien-Dindo classification). We enrolled 216 consecutive patients who underwent partial hepatectomy for primary liver cancers, metastatic liver cancers, benign tumors, and donor hepatectomy. We classified patients as either low or high platelet percentage (postoperative platelet count/preoperative platelet count) using the optimal cutoff value calculated by a receiver operating characteristic (ROC) curve analysis, and analyzed risk factors for delayed liver functional recovery and morbidity after hepatectomy. Delayed liver function recovery and morbidity were significantly correlated with the lowest value of platelet percentage based on ROC analysis. Using a cutoff value of 60% acquired by ROC analysis, univariate and multivariate analysis determined that postoperative lowest platelet percentage ≤ 60% was identified as an independent risk factor of delayed liver function recovery (odds ratio (OR) 6.85; P < 0.01) and morbidity (OR, 4.90; P < 0.01). Furthermore, patients with the lowest platelet percentage ≤ 60% had decreased postoperative prothrombin time ratio and serum albumin level and increased serum bilirubin level when compared with patients with platelet percentage ≥ 61%. A greater than 40% decrease in platelet count after partial hepatectomy was an independent risk factor for delayed liver function recovery and postoperative morbidity. In conclusion, the decrease in platelet counts is an early marker to predict the liver function recovery and complications after hepatectomy.

OsDREB2A, a Rice Transcription Factor, Significantly Affects Salt Tolerance in Transgenic Soybean

PubMed Central

Ma, Qi-bin; Yang, Cun-yi; Mu, Ying-hui; Suo, Hai-cui; Luo, Lai-hui; Nian, Hai

2013-01-01

The dehydration responsive element binding (DREB) transcription factors play an important role in regulating stress-related genes. OsDREB2A, a member of the DREBP subfamily of AP2/ERF transcription factors in rice (Oryza sativa), is involved in the abiotic stress response. OsDREB2A expression is induced by drought, low-temperature and salt stresses. Here, we report the ability of OsDREB2A to regulate high-salt response in transgenic soybean. Overexpressing OsDREB2A in soybeans enhanced salt tolerance by accumulating osmolytes, such as soluble sugars and free proline, and improving the expression levels of some stress-responsive transcription factors and key genes. The phenotypic characterization of transgenic soybean were significantly better than those of wild-type (WT). Electrophoresis mobility shift assay (EMSA) revealed that the OsDREB2A can bind to the DRE core element in vitro. These results indicate that OsDREB2A may participate in abiotic stress by directly binding with DRE element to regulate the expression of downstream genes. Overexpression of OsDREB2A in soybean might be used to improve tolerance to salt stress. PMID:24376625

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.

Predictors of decreased physical activity level over time among adults: a longitudinal study.

PubMed

Dai, Sulan; Wang, Feng; Morrison, Howard

2014-08-01

Leisure-time physical activity (LTPA) plays a key role in chronic disease prevention and health promotion. The impact of life-changing events on LTPA among adults is unknown. To examine the association between life-changing events and decreased LTPA levels. Eight cycles of Canadian National Population Health Survey data were used for this study. A total of 12,901 respondents aged ≥18 years in 1994-1995 completed biannual follow-ups until 2008-2009. The association between life-changing events and decreased LTPA in any 2-year period was assessed with adjustment of potential confounding factors. Data were analyzed in 2012. From 1994-1995 to 2008-2009, nine of ten people changed their LTPA levels. Within each 2-year period, individuals were more likely to decrease their LTPA levels if they married within the 2-year period (men); became or remained overweight/obese (women); remained a regular smoker (men); became or remained unhealthy (men and women); developed or continued to have body pain (women); and acquired social support or remained without support (men). Most people change their LTPA levels or patterns, which are significantly influenced by life-changing events. An improved understanding of factors that influence LTPA may help better target those at high risk. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Functional Significance of VEGFR-2 on Ovarian Cancer Cells

PubMed Central

Spannuth, Whitney A.; Nick, Alpa M.; Jennings, Nicholas B.; Armaiz-Pena, Guillermo N.; Mangala, Lingegowda S.; Danes, Christopher G.; Lin, Yvonne G.; Merritt, William M.; Thaker, Premal H.; Kamat, Aparna A.; Han, Liz Y.; Tonra, James R.; Coleman, Robert L.; Ellis, Lee M.; Sood, Anil K.

2009-01-01

Vascular endothelial growth factor receptor (VEGFR) has recently been discovered on ovarian cancer cells, but its functional significance is unknown and is the focus of the current study. By protein analysis, A2780-par and HeyA8 ovarian cancer cell lines expressed VEGFR-1 and HeyA8 and SKOV3ip1 expressed VEGFR-2. By in situ hybridization (ISH), 85% of human ovarian cancer specimens showed moderate to high VEGFR-2 expression while only 15% showed moderate to high VEGFR-1 expression. By immunofluorescence, little or no VEGFR-2 was detected in normal ovarian surface epithelial cells, whereas expression was detected in 75% of invasive ovarian cancer specimens. To differentiate between the effects of tumor versus host expression of VEGFR, nude mice were injected with SKOV3ip1 cells and treated with either human VEGFR-2 specific antibody (1121B), murine VEGFR-2 specific antibody (DC101), or the combination. Treatment with 1121B reduced SKOV3ip1 cell migration by 68% (p < 0.01) and invasion by 72% (p < 0.01), but exposure to VEGFR-1 antibody had no effect. Treatment with 1121B effectively blocked VEGF-induced phosphorylation of p130Cas. In vivo, treatment with either DC101 or 1121B significantly reduced tumor growth alone and in combination in the SKOV3ip1 and A2774 models. Decreased tumor burden after treatment with DC101 or 1121B correlated with increased tumor cell apoptosis, decreased proliferative index, and decreased microvessel density. These effects were significantly greater in the combination group (p<0.001). We show functionally active VEGFR-2 is present on most ovarian cancer cells. The observed anti-tumor activity of VEGF-targeted therapies may be mediated by both anti-angiogenic and direct anti-tumor effects. PMID:19058181

The effect of a novel movement strategy in decreasing ACL risk factors in female adolescent soccer players

PubMed Central

Celebrini, Richard G.; Eng, Janice J.; Miller, William C.; Ekegren, Christina L.; Johnston, James D.; MacIntyre, Donna L.

2015-01-01

There is a need to investigate the effect of specific movement strategies in reducing biomechanical risk factors for ACL injury in young female athletes. The purpose of this study was 1) to determine the feasibility of implementing a novel movement strategy (Core-PAC) into a team warm-up prior to soccer training based on subject compliance and integration of the Core-PAC into the warm-up and 2) to determine whether the Core-PAC would improve peak knee flexion angles and peak abduction moments at the knee during a side-cut (SC) and an unanticipated side-cut (USC) prior to kicking a soccer ball, and a side-hop (SH) task after immediate instruction and after a four-week training program. A convenience sample of ten 14–16 year old female soccer players were instructed in the Core-PAC immediately after baseline testing and during a training program consisting of a 20-minute warm-up, two-times per week. The Core-PAC was understood and accepted by the subjects and incorporated into their warm-up activities with good compliance. After the immediate instruction, there were significant increases in peak knee flexion angles of a mean 6.4° during the SC (p = 0.001), 3.5° during the USC (p = 0.007), and 5.8° during the SH (p < 0.001) tasks. Peak knee abduction moments decreased by a mean of 0.25 Nm/kg during the SC (p < 0.03), 0.17 Nm/kg during the USC (p = 0.05), and 0.27 Nm/kg during the SH (p = 0.04) tasks. After the 4-week training program, some individuals showed improvement. The results of this study suggest that the Core-PAC may be one method of modifying high-risk movements for ACL injury such as side-cutting and single-leg landing. PMID:22210470

Alternative pathway regulation by factor H modulates Streptococcus pneumoniae induced proinflammatory cytokine responses by decreasing C5a receptor crosstalk.

PubMed

van der Maten, Erika; de Bont, Cynthia M; de Groot, Ronald; de Jonge, Marien I; Langereis, Jeroen D; van der Flier, Michiel

2016-12-01

Bacterial pathogens not only stimulate innate immune receptors, but also activate the complement system. Crosstalk between complement C5a receptor (C5aR) and other innate immune receptors is known to enhance the proinflammatory cytokine response. An important determinant of the magnitude of complement activation is the activity of the alternative pathway, which serves as an amplification mechanism for complement activation. Both alternative pathway activity as well as plasma levels of factor H, a key inhibitor of the alternative pathway, show large variation within the human population. Here, we studied the effect of factor H-mediated regulation of the alternative pathway on bacterial-induced proinflammatory cytokine responses. We used the human pathogen Streptococcus pneumoniae as a model stimulus to induce proinflammatory cytokine responses in human peripheral blood mononuclear cells. Serum containing active complement enhanced pneumococcal induced proinflammatory cytokine production through C5a release and C5aR crosstalk. We found that inhibition of the alternative pathway by factor H, with a concentration equivalent to a high physiological level, strongly reduced C5a levels and decreased proinflammatory cytokine production in human peripheral blood mononuclear cells. This suggests that variation in alternative pathway activity due to variation in factor H plasma levels affects individual cytokine responses during infection. Copyright © 2016 Elsevier Ltd. 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.

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

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.

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.

Prognostic significance of epidermal growth factor receptor (EGFR) over expression in urothelial carcinoma of urinary bladder.

PubMed

Hashmi, Atif Ali; Hussain, Zubaida Fida; Irfan, Muhammad; Khan, Erum Yousuf; Faridi, Naveen; Naqvi, Hanna; Khan, Amir; Edhi, Muhammad Muzzammil

2018-06-07

Epidermal growth factor receptor (EGFR) has been shown to have abnormal expression in many human cancers and is considered as a marker of poor prognosis. Frequency of over expression in bladder cancer has not been studied in our population; therefore we aimed to evaluate the frequency and prognostic significance of EGFR immunohistochemical expression in locoregional population. We performed EGFR immunohistochemistry on 126 cases of bladder cancer and association of EGFR expression with tumor grade, lamina propria invasion, deep muscle invasion and recurrence of disease was evaluated. High EGFR expression was noted in 26.2% (33 cases), 15.1% (19 cases) and 58.7% (74 cases) revealed low and no EGFR expression respectively. Significant association of EGFR expression was noted with tumor grade, lamina propria invasion, deep muscle invasion and recurrence status while no significant association was seen with age, gender and overall survival. Kaplan- Meier curves revealed significant association of EGFR expression with recurrence while no significant association was seen with overall survival. Significant association of EGFR overexpression with tumor grade, muscularis propria invasion and recurrence signifies its prognostic value; therefore EGFR can be used as a prognostic biomarker in Urothelial bladder carcinoma.

A qualitative examination of factors related to the decrease in physical activity behavior in adolescent girls during the transition from primary to secondary school.

PubMed

Knowles, Ann-Marie; Niven, Ailsa; Fawkner, Samantha

2011-11-01

Quantitative research has suggested that the decline in physical activity levels for adolescent girls is most marked during the transition from primary school to secondary school yet understanding the contributing factors for this decline may be advanced through qualitative research methods to gain an individual perspective of the girls' school transition experience. This study explored factors related to the decrease in physical activity behavior in 14 adolescent girls (mean age = 13.6 ± 0.3 years) during the transition between primary and secondary school through the use of narrative interviews and interpretative phenomenological analysis. The findings suggested that a change in the environment was central to understanding the decline in physical activity levels since primary school. During secondary school, a positive environment can be created by ensuring a choice of activities in Physical Education lessons; allowing a girls-only environment, to reduce the focus on competence and competition, and recognizing the importance of social support. These could enhance self-perceptions, reduce self-presentational concerns, increase enjoyment, and subsequently reduce the decrease in physical activity behavior during this key transitional period.

Increases and decreases in drug use attributed to housing status among street-involved youth in a Canadian setting.

PubMed

Cheng, Tessa; Wood, Evan; Nguyen, Paul; Kerr, Thomas; DeBeck, Kora

2014-04-10

Among a cohort of drug-using street-involved youth, we sought to identify the prevalence of reporting increases and decreases in illicit drug use due to their current housing status and to identify factors associated with reporting these changes. This longitudinal study was based on data collected between June 2008 and May 2012 from a prospective cohort of street-involved youth aged 14-26 in Vancouver, Canada. At semi-annual study follow-up visits, youth were asked if their drug use was affected by their housing status. Using generalized estimating equations, we identified factors associated with perceived increases and decreases in drug use attributed to housing status. Among our sample of 536 participants at baseline, 164 (31%) youth reported increasing their drug use due to their housing situation and 71 (13%) reported decreasing their drug use. In multivariate analysis, factors that were positively associated with perceived increases in drug use attributed to housing status included the following: being homeless, engaging in sex work and drug dealing. Regular employment was negatively associated with increasing drug use due to housing status. Among those who reported decreasing their drug use, only homelessness was significant in bivariate analysis. Perceived changes in drug use due to housing status were relatively common in this setting and were associated with being homeless and, among those who increased their drug use, engaging in risky income generation activities. These findings suggest that structural factors, particularly housing and economic opportunities, may be crucial interventions for reducing or limiting drug use among street-involved youth.

Increases and decreases in drug use attributed to housing status among street-involved youth in a Canadian setting

PubMed Central

2014-01-01

Background Among a cohort of drug-using street-involved youth, we sought to identify the prevalence of reporting increases and decreases in illicit drug use due to their current housing status and to identify factors associated with reporting these changes. Findings This longitudinal study was based on data collected between June 2008 and May 2012 from a prospective cohort of street-involved youth aged 14–26 in Vancouver, Canada. At semi-annual study follow-up visits, youth were asked if their drug use was affected by their housing status. Using generalized estimating equations, we identified factors associated with perceived increases and decreases in drug use attributed to housing status. Among our sample of 536 participants at baseline, 164 (31%) youth reported increasing their drug use due to their housing situation and 71 (13%) reported decreasing their drug use. In multivariate analysis, factors that were positively associated with perceived increases in drug use attributed to housing status included the following: being homeless, engaging in sex work and drug dealing. Regular employment was negatively associated with increasing drug use due to housing status. Among those who reported decreasing their drug use, only homelessness was significant in bivariate analysis. Conclusion Perceived changes in drug use due to housing status were relatively common in this setting and were associated with being homeless and, among those who increased their drug use, engaging in risky income generation activities. These findings suggest that structural factors, particularly housing and economic opportunities, may be crucial interventions for reducing or limiting drug use among street-involved youth. PMID:24721725

Prenatal dexamethasone exposure in rats results in long-term epigenetic histone modifications and tumour necrosis factor-α production decrease.

PubMed

Yu, Hong-Ren; Kuo, Ho-Chang; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Yu-Chieh; Chang, Kow-Aung; Tain, You-Lin; Huang, Li-Tung

2014-12-01

Glucocorticoid (GC) is often given when preterm delivery is expected. This treatment is successful in stimulating the development of the fetal lung. However, reports and related research regarding the prolonged effects of prenatal GC on the development of immunity are very limited. Some data, derived from infants whose mothers were given immunosuppressants during pregnancy for the treatment of autoimmune disorders, suggest that prenatal exposure to GC may have only a limited effect on the development of the immune system. What is unknown is whether the immune modulation effects of prenatal GC might appear at a later childhood stage and beyond. Here we evaluated the immune programming influenced by prenatal GC. Pregnant Sprague-Dawley rats received dexamethasone (DEX; 0.1 mg/kg/day) or saline at gestational days 14-20. Male offspring were killed at day 7 or day 120 after birth. Spleens were collected for immune study. Of the inflammation mediators, matrix metalloproteinase-9, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor mRNAs decreased in the prenatal DEX group at an early stage after birth. Upon concanavalin A stimulation, prenatal DEX treatment reduced TNF-α production, but not interferon-γ production, by splenocytes at day 120 after birth compared with the vehicle group. Decreased levels of active chromatin signs (acetylation of histone H3 lysines, H3K4me1/3, and H3K36me3) in TNF-α promoter were compatible with the expressions of TNF-α. Our results suggest that prenatal DEX has a profound and lasting impact on the developing immune system even to the adult stage. Epigenetic histone modifications regulate TNF-α expression following prenatal DEX in rats. © 2014 John Wiley & Sons Ltd.

Obesity-related cardiovascular risk factors: intervention recommendations to decrease adolescent obesity

NASA Technical Reports Server (NTRS)

Calderon, Kristine S.; Yucha, Carolyn B.; Schaffer, Susan D.

2005-01-01

The incidence of adolescent obesity is increasing dramatically in the United States with associated risks of hypertension, adverse lipid profiles, and Type II diabetes. Unless reversed, this trend predicts an epidemic of adult cardiovascular disease. Interventions at home, at school, and in the community are required to empower teens to increase physical activity and to modify eating habits. This article describes assessment for obesity-related health problems as well as scientific guidelines and research-based intervention strategies to decrease obesity in adolescents.

Poling-assisted bleaching of soda-lime float glasses containing silver nanoparticles with a decreasing filling factor across the depth

NASA Astrophysics Data System (ADS)

Deparis, Olivier; Kazansky, Peter G.; Podlipensky, Alexander; Abdolvand, Amin; Seifert, Gerhard; Graener, Heinrich

2006-08-01

The recently discovered poling-assisted bleaching of glass with embedded silver nanoparticles has renewed the interest in thermal poling as a simple, reliable, and low-cost technique for controlling locally the surface-plasmon-resonant optical properties of metal-doped nanocomposite glasses. In the present study, the emphasis is put on the influence of the volume filling factor of metallic clusters on poling-assisted bleaching. Soda-lime silicate glass samples containing spherical silver nanoparticles with a decreasing filling factor across the depth were subject to thermal poling experiments with various poling temperatures, voltages, and times. Optical extinction spectra were measured from ultraviolet to near-infrared ranges and the surface-plasmon-resonant extinction due to silver nanoparticles (around 410nm) was modeled by the Maxwell Garnett [Philos. Trans. R. Soc. London, Ser. A 203, 385 (1904); 205, 237 (1906)] effective medium theory which was adapted in order to take into account the filling factor depth profile. A method was proposed for the retrieval of the filling factor depth profile from optical extinction spectra recorded in fresh and chemically etched samples. A stretched exponential depth profile turned out to be necessary in order to model samples having a high filling factor near the surface. Based on the fact that the electric-field-assisted dissolution of embedded metallic nanoparticles proceeded progressively from the top surface, a bleaching front was defined that moved forward in depth as time elapsed. The position of the bleaching front was determined after each poling experiment by fitting the measured extinction spectrum to the theoretical one. In samples with higher peak value and steeper gradient of the filling factor, the bleaching front reached more rapidly a steady-state depth as poling time increased. Also it increased less strongly with increasing poling voltage. These results were in agreement with the physics of the dissolution

Influence of nuclear power unit on decreasing emissions of greenhouse gases

NASA Astrophysics Data System (ADS)

Stanek, Wojciech; Szargut, Jan; Kolenda, Zygmunt; Czarnowska, Lucyna

2015-03-01

The paper presents a comparison of selected power technologies from the point of view of emissions of greenhouse gases. Such evaluation is most often based only on analysis of direct emissions from combustion. However, the direct analysis does not show full picture of the problem as significant emissions of GHG appear also in the process of mining and transportation of fuel. It is demonstrated in the paper that comparison of power technologies from the GHG point of view has to be done using the cumulative calculus covering the whole cycle of fuel mining, processing, transportation and end-use. From this point of view coal technologies are in comparable level as gas technologies while nuclear power units are characterised with lowest GHG emissions. Mentioned technologies are compared from the point of view of GHG emissions in full cycle. Specific GHG cumulative emission factors per unit of generated electricity are determined. These factors have been applied to simulation of the influence of introduction of nuclear power units on decrease of GHG emissions in domestic scale. Within the presented simulations the prognosis of domestic power sector development according to the Polish energy policy till 2030 has been taken into account. The profitability of introduction of nuclear power units from the point of view of decreasing GHG emissions has been proved.

Empagliflozin decreases remnant-like particle cholesterol in type 2 diabetes patients with insulin resistance.

PubMed

Hattori, Sachiko

2017-11-28

Remnant lipoproteins are thought to be atherogenic. Remnant-like particle cholesterol (RLP-C), which reflects the levels of various kinds of remnant lipoproteins in the blood, has a significant correlation with insulin resistance. In the present study, we measured the effect of empagliflozin (EMPA) on the levels of RLP-C, and investigated whether EMPA-mediated change in RLP-C is associated with a change in insulin resistance in type 2 diabetes patients who have insulin resistance. Patients were allocated to receive a placebo (n = 51) or EMPA (n = 58) as an add-on treatment. Fasting blood samples were collected before and 12 weeks after this intervention. EMPA significantly decreased glycated hemoglobin, bodyweight, systolic blood pressure, plasma triglycerides, liver transaminases and estimated glomerular filtration rate, and increased high-density lipoprotein cholesterol. Furthermore, EMPA decreased RLP-C and homeostatic model assessment of insulin resistance. In the placebo group, there were no significant changes in these factors except for slight increases in liver transaminases. Multiple regression analysis showed that the change in homeostatic model assessment of insulin resistance (P = 0.0102) and the change in alanine aminotransferase (P = 0.0301) were significantly associated with the change in RLP-C in the EMPA group. The change in RLP-C significantly correlated with the change in homeostatic model assessment of insulin resistance (Pearson correlation coefficient 0.503, 95% confidence interval 0.199-0.719; P = 0.00241). EMPA decreases RLP-C levels, which is closely associated with amelioration of insulin sensitivity in diabetes patients who have insulin resistance. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

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.

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.

Effects of leukemia inhibitory factor and basic fibroblast growth factor on free radicals and endogenous stem cell proliferation in a mouse model of cerebral infarction.

PubMed

Huang, Weihui; Li, Yadan; Lin, Yufeng; Ye, Xue; Zang, Dawei

2012-07-05

The present study established a mouse model of cerebral infarction by middle cerebral artery occlusion, and monitored the effect of 25 μg/kg leukemia inhibitory factor and (or) basic fibroblast growth factor administration 2 hours after model establishment. Results showed that following administration, the number of endogenous neural stem cells in the infarct area significantly increased, malondialdehyde content in brain tissue homogenates significantly decreased, nitric oxide content, glutathione peroxidase and superoxide dismutase activity significantly elevated, and mouse motor function significantly improved as confirmed by the rotarod and bar grab tests. In particular, the effect of leukemia inhibitory factor in combination with basic fibroblast growth factor was the most significant. Results indicate that leukemia inhibitory factor and basic fibroblast growth factor can improve the microenvironment after cerebral infarction by altering free radical levels, improving the quantity of endogenous neural stem cells, and promoting neurological function of mice with cerebral infarction.

The male contraceptive regimen of testosterone and levonorgestrel significantly increases lean mass in healthy young men in 4 weeks, but attenuates a decrease in fat mass induced by testosterone alone.

PubMed

Herbst, Karen L; Anawalt, Bradley D; Amory, John K; Matsumoto, Alvin M; Bremner, William J

2003-03-01

In hypogonadal men, testosterone (T) in replacement dosages is known to increase fat-free mass (lean mass) and decrease fat mass. In young eugonadal men, similar dosages of T increase lean mass, but much higher dosages of T are required to decrease total body fat mass. Current T-based male hormonal contraceptive regimens include a second agent, such as a progestin, to maximize inhibition of pituitary gonadotropins and improve efficacy. To study the effect of such combinations on body composition, we randomized healthy, young, eugonadal men into four combinations of exogenous T and the progestin, levonorgestrel (LNG): 1) 100 mg T enanthate, im, weekly plus 125 micro g LNG, orally, daily (T+LNG); 2) T plus placebo LNG (T alone); 3) placebo T plus LNG (LNG alone); and 4) placebo T plus placebo LNG (placebo). We then analyzed body composition by dual energy x-ray absorptiometry after 4 and 8 wk of treatment. T+LNG significantly increased total lean mass after 4 and 8 wk of treatment (3.5 +/- 0.9% and 4.2 +/- 1.2%, respectively; P < 0.05) and truncal lean mass after 4 and 8 wk of treatment (4.7 +/- 0.9% and 5.0 +/- 0.9%, respectively; P < 0.05) compared with baseline and placebo. T alone also increased total and truncal lean mass significantly compared with placebo after 4 wk of treatment, but not compared with baseline (3.3 +/- 1.4% and 3.2 +/- 2.3%, respectively; P < 0.05 vs. placebo), suggesting an additive effect of T and LNG to increase lean mass. Fat mass significantly decreased in the abdomen in men administered T alone compared with LNG alone (-4.9 +/- 2.8%; P < 0.05). Fat mass significantly increased in the abdomen with LNG alone (4.1 +/- 1.0%; P < 0.05) compared with baseline and was unchanged with the combination of T+LNG, suggesting that LNG attenuates the decrease in fat mass seen with T alone. There was no change in weight or body mass index in any group during the study. This study shows that in young eugonadal men 1) T alone rapidly increases lean mass

The Significance of the Psychosocial Factors Influence in Pathogenesis of Cardiovascular Disease

PubMed Central

Masic, Izet; Alajbegovic, Jasmin

2013-01-01

Background: Cardiovascular diseases (CVD) are the leading cause of death in the world today. Risk factors are those factors that influence the development of CVD. Risk factors can be divided into materialistic (genetic predisposition, smoking, alcohol) and non-materialistic (psychosocial factors). Our goal is to note the role of the health system, to emphasize the importance of psychosocial factors in the pathogenesis of CVD, explain the relationship between psychosocial factors and other risk factors, stress the importance of prevention through the provision of management of the cardiovascular system (CVS) diseases. Methods: A descriptive analysis was performed on scientific studies in several published articles in journals on CVS: Public Health Reviews, CVD, European Heart Journal, Materia Socio Medica and other indexed journals that publish articles on CVS. Results and Conclusions: The importance and role of the health system in the early detection, diagnosis, therapy and CVS disease prevention is presented through three thematic areas: (a) The incidence and prevalence of CVS diseases; (b) treatment of CVS diseases and (c) promotion of health in patients with CVS disease and those the risk of their occurrence. Health promotion is the most important aspect of the health system monitoring. Health promotion is adequately implemented ifthe management ofCVD is proper. The main objectives of CVD management are: Preventing or delaying the occurrence of CVD, reducing the number and severity of worsening and complications of CVD. Management Includes: Individual and family, the health system and the community. Materialistic and non-materialistic risk factors together contribute to the development of CVD. PMID:24404370

The significance of the psychosocial factors influence in pathogenesis of cardiovascular disease.

PubMed

Masic, Izet; Alajbegovic, Jasmin

2013-11-01

Cardiovascular diseases (CVD) are the leading cause of death in the world today. Risk factors are those factors that influence the development of CVD. Risk factors can be divided into materialistic (genetic predisposition, smoking, alcohol) and non-materialistic (psychosocial factors). Our goal is to note the role of the health system, to emphasize the importance of psychosocial factors in the pathogenesis of CVD, explain the relationship between psychosocial factors and other risk factors, stress the importance of prevention through the provision of management of the cardiovascular system (CVS) diseases. A DESCRIPTIVE ANALYSIS WAS PERFORMED ON SCIENTIFIC STUDIES IN SEVERAL PUBLISHED ARTICLES IN JOURNALS ON CVS: Public Health Reviews, CVD, European Heart Journal, Materia Socio Medica and other indexed journals that publish articles on CVS. THE IMPORTANCE AND ROLE OF THE HEALTH SYSTEM IN THE EARLY DETECTION, DIAGNOSIS, THERAPY AND CVS DISEASE PREVENTION IS PRESENTED THROUGH THREE THEMATIC AREAS: (a) The incidence and prevalence of CVS diseases; (b) treatment of CVS diseases and (c) promotion of health in patients with CVS disease and those the risk of their occurrence. Health promotion is the most important aspect of the health system monitoring. Health promotion is adequately implemented ifthe management ofCVD is proper. The main objectives of CVD management are: Preventing or delaying the occurrence of CVD, reducing the number and severity of worsening and complications of CVD. Management Includes: Individual and family, the health system and the community. Materialistic and non-materialistic risk factors together contribute to the development of CVD.

A Study of the Significant Factors That Affect the Job Placement Rates of Students Who Have Completed a HERO Program.

ERIC Educational Resources Information Center

Instructional Development and Evaluation Associates, Inc., Berkeley, MI.

A three-year study examined the significant factors that affect the job placement rates of students completing a Home Economics Related Occupations (HERO) program. Other purposes of the study were to develop and pilot test a model that could be used to determine factors related to student placement in a variety of vocational education programs and…

Binding of Complement Factor H (FH) Decreases Protective Anti-FH Binding Protein Antibody Responses of Infant Rhesus Macaques Immunized With a Meningococcal Serogroup B Vaccine

PubMed Central

Granoff, Dan M.; Costa, Isabella; Konar, Monica; Giuntini, Serena; Van Rompay, Koen K. A.; Beernink, Peter T.

2015-01-01

Background. The meningococcal vaccine antigen, factor H (FH)–binding protein (FHbp), binds human complement FH. In human FH transgenic mice, binding decreased protective antibody responses. Methods. To investigate the effect of primate FH binding, we immunized rhesus macaques with a 4-component serogroup B vaccine (4CMenB). Serum FH in 6 animals bound strongly to FHbp (FHbp-FHhigh) and, in 6 animals, bound weakly to FHbp (FHbp-FHlow). Results. There were no significant differences between the respective serum bactericidal responses of the 2 groups against meningococcal strains susceptible to antibody to the NadA or PorA vaccine antigens. In contrast, anti-FHbp bactericidal titers were 2-fold lower in FHbp-FHhigh macaques against a strain with an exact FHbp match to the vaccine (P = .08) and were ≥4-fold lower against 4 mutants with other FHbp sequence variants (P ≤ .005, compared with FHbp-FHlow macaques). Unexpectedly, postimmunization sera from all 12 macaques enhanced FH binding to meningococci. In contrast, serum anti-FHbp antibodies elicited by 4CMenB in mice whose mouse FH did not bind to the vaccine antigen inhibited FH binding. Conclusions. Binding of FH to FHbp decreases protective anti-FHbp antibody responses of macaques to 4CMenB. Even low levels of FH binding skew the antibody repertoire to FHbp epitopes outside of the FH-binding site, which enhance FH binding. PMID:25676468

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.

Significance of the interleukin-1 receptor antagonist/interleukin-1 beta ratio as a prognostic factor in patients with pulmonary sarcoidosis.

PubMed

Mikuniya, T; Nagai, S; Takeuchi, M; Mio, T; Hoshino, Y; Miki, H; Shigematsu, M; Hamada, K; Izumi, T

2000-01-01

Various factors such as serum angiotensin-converting enzyme (sACE) activity, bronchoalveolar lavage (BAL) fluid lymphocyte percent, CD4/CD8 ratio, and shadows on chest radiograph have been identified as indexes of disease activity in patients with sarcoidosis. However, it remains to be confirmed whether these factors can predict clinical outcomes. To examine whether the interleukin-1 receptor antagonist (IL-1ra)/IL-1 beta ratio can predict the clinical course, we prospectively followed the clinical courses of 30 patients with pulmonary sarcoidosis 4 years after measurement of immunoreactive amounts of IL-1ra or IL-1 beta in the culture supernatants obtained from BAL fluid macrophages. Immunoreactive amounts of IL-1ra or IL-1 beta were measured using ELISA. Changes in pulmonary function, sACE activity, and shadows on chest radiographs during observation periods were evaluated as markers of changes in disease activity. We found that the patients whose shadows on chest radiographs showed improvement had a higher molar IL-1ra/IL-1 beta ratio than the patients whose shadows persistently remained 4 years after BAL examination (p < 0.05). The molar ratio was found to be positively correlated with improvement of percent vital capacity (p < 0.05) and negatively correlated with the ratio of sACE activity at the time of the last observation to sACE activity at the time of BAL (sACE(LAST)/sACE(BAL), p < 0.01). The sACE(LAST)/sACE(BAL) ratio was significantly lower in patients whose shadows on chest radiographs decreased than in those whose shadows remained unchanged (p < 0.005). The IL-1ra/IL-1 beta ratio in the BAL fluid macrophage culture supernatants in patients with pulmonary sarcoidosis could be a useful marker in predicting the persistence of granulomatous lesions (chronicity). Copyright 2000 S. Karger AG, Basel

Receptor for macrophage colony-stimulating factor transduces a signal decreasing erythroid potential in the multipotent hematopoietic EML cell line.

PubMed

Pawlak, G; Grasset, M F; Arnaud, S; Blanchet, J P; Mouchiroud, G

2000-10-01

To test the hypothesis that hematopoietic growth factors may influence lineage choice in pluripotent progenitor cells, we investigated the effects of macrophage colony-stimulating factor (M-CSF) on erythroid and myeloid potentials of multipotent EML cells ectopically expressing M-CSF receptor (M-CSFR). EML cells are stem cell factor (SCF)-dependent murine cells that give rise spontaneously to pre-B cells, burst-forming unit erythroid (BFU-E), and colony-forming unit granulocyte macrophage (CFU-GM). We determined BFU-E and CFU-GM frequencies among EML cells transduced with murine M-CSFR, human M-CSFR, or chimeric receptors, and cultivated in the presence of SCF, M-CSF, or both growth factors. Effects of specific inhibitors of signaling molecules were investigated. EML cells transduced with murine M-CSFR proliferated in response to M-CSF but also exhibited a sharp and rapid decrease in BFU-E frequency associated with an increase in CFU-GM frequency. In contrast, EML cells expressing human M-CSFR proliferated in response to M-CSF without any changes in erythroid or myeloid potential. Using chimeric receptors between human and murine M-CSFR, we showed that the effects of M-CSF on EML cell differentiation potential are mediated by a large region in the intracellular domain of murine M-CSFR. Furthermore, phospholipase C (PLC) inhibitor U73122 interfered with the negative effects of ligand-activated murine M-CSFR on EML cell erythroid potential. We propose that signaling pathways activated by tyrosine kinase receptors may regulate erythroid potential and commitment decisions in multipotent progenitor cells and that PLC may play a key role in this process.

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.

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.

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.

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.

Effect of posture on the diurnal variation in clinically significant diabetic macular edema.

PubMed

Polito, Antonio; Polini, Giovanni; Chiodini, Raffaella Gortana; Isola, Miriam; Soldano, Franca; Bandello, Francesco

2007-07-01

To investigate the role of posture and other systemic factors in the diurnal variation of clinically significant diabetic macular edema (CSDME). Ten eyes of 10 diabetic subjects with CSDME underwent four OCT foveal thickness measurements with StratusOCT at 9 AM and 12, 3, and 6 PM consecutively on two different days, with the subject in an upright position on one and in a recumbent position on the other. For the "recumbent-position" measurements, the patients were admitted the night before and remained in bed during the entire day of testing. Clinical laboratory results at baseline included HbA1c, urinary albumin, and serum creatinine. Refraction and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity were also measured before each OCT measurement was taken. Variations in blood pressure, body temperature, plasma glucose, renin, aldosterone, and cortisol levels were measured and then correlated with macular thickness. Foveal thickening decreased in all cases over the course of the day. The decrease, however, was significantly greater for the upright-position measurements (relative mean +/- SD decrease of 20.6% +/- 6.5% in the upright position and 6.2% +/- 4.6% in the recumbent position). Visual acuity improved by at least 1 ETDRS line in three eyes in the upright position as opposed to only one eye in the recumbent position. There seemed to be no association between any of the systemic factors studied and foveal thickening, with the exception of cortisol. The results support the hypothesis that posture and hydrostatic pressure play a major role in determining time-related shifts in CSDME and suggest that the forces of Starling's law can in part, account for CSDME formation.

Langmuir wave damping decreases slowly

NASA Astrophysics Data System (ADS)

Rose, Harvey

2006-10-01

The onset of stimulated Raman scatter in a single laser speckle occurs (D. S. Montgomery et al., Phys. Plasmas, 9, 2311 (2002)) at lower laser intensity, I, than predicted by linear theory based on classical Landau damping, νL, of the SRS daughter Langmuir wave. Does this imply that SRS onset in a speckled laser beam, propagating through long scale length plasma, is also at odds with linear theory? It has been shown (Harvey A. Rose and D. F. DuBois, Phys. Rev. Lett. 72, 2883 (1994)) that linear convective gain in speckles with large fluctuations of I about the average, , leads to onset at a value of , Ic, small compared to that for onset in a uniform beam. While nonlinear electron trapping effects may occur in very intense speckles, whether or not these effects are sufficient to lower the onset value of below Ic depends on how strongly electrons must be trapped before there is significant reduction in νL. As the amplitude of an SRS daughter Langmuir wave increases, its νL decreases by the factor ν/φb, due to the competition between electron trapping, with electron bounce frequency, φb, and escape of these trapped electrons by advection out of a speckle's side, at rate ν. This result (Harvey A. Rose and David A. Russell, Phys. Plasmas, 8, 4784 (2001)) is valid for ν/φb 1. In this talk I present a nonlinear, transit time damping, calculation of νL and find that reduction by a factor of two does not occur until φb/ν 5. This slow turn on of trapping effects suggests that the linear calculation of Ic is NIF relevant.