Atlanto-occipital dislocation--part 2: The clinical use of (occipital) condyle-C1 interval, comparison with other diagnostic methods, and the manifestation, management, and outcome of atlanto-occipital dislocation in children.

PubMed

Pang, Dachling; Nemzek, William R; Zovickian, John

2007-11-01

The diagnosis of atlanto-occipital dislocation (AOD) remains problematic as a result of a lack of reliable radiodiagnostic criteria. In Part 1 of the AOD series, we showed that the normal occiput-C1 joint in children has an extremely narrow joint gap (condyle-C1 interval [CCI]) with great left-right symmetry. In Part 2, we used a CCI of 4 mm or greater measured on reformatted computed tomographic (CT) scans as the indicator for AOD and tested the diagnostic sensitivity and specificity of CCI against published criteria. The clinical manifestation, neuroimaging findings, management, and outcome of our series of patients with AOD are also reported. For diagnostic sensitivity, we applied the CCI criterion on 16 patients who fulfilled one or more accepted radiodiagnostic criteria of AOD and who showed clinical and imaging hallmarks of the syndrome. All 16 patients had plain cervical spine x-rays, head CT scans, axial cervical spine CT scans with reconstruction, and magnetic resonance imaging scans. The diagnostic yield and false-negative rate of CCI were compared with those of four published "standard" tests, namely Wholey's dens-basion interval, Powers' ratio, Harris' basion-axis interval, and Sun's interspinous ratio. The diagnostic value of "nonstandard" indicators such as cervicomedullary deficits, tectorial membrane and other ligamentous damage, perimedullary subarachnoid hemorrhage, and extra-axial blood at C1-C2 were also assessed. For diagnostic specificity, we applied CCI and the "standard" and "nonstandard" tests on 10 patients from five classes of non-AOD upper cervical injuries. The false-positive diagnostic rates for AOD of all respective tests were documented. The CCI criterion was positive in all 16 patients with AOD with a diagnostic sensitivity of 100%. Fourteen patients had bilateral AOD with disruption and widening of both OC1 joints. Two patients had unilateral AOD with only one joint wider than 4 mm. The abnormal CCI varied from 5 to 34 mm. Eight patients showed blatant left-right joint asymmetry in either CCI or anatomic conformation. The diagnostic sensitivities for the "standard" tests are as follows: Wholey's, 50%; Powers', 37.5%; Harris', 31%; and Sun's, 25%, with false-negative rates of 50, 62.5, 69, and 75%, respectively. The sensitivities for the "nonstandard" indicators are: tectorial membrane damage, 71%; perimedullary blood, 63%; and C1-C2 extra-axial blood, 75%, with false-negative rates of 29, 37, and 25%, respectively. Fifteen patients with AOD had occiput-cervical fusion. There were one early and two delayed deaths (19% mortality); two patients (12%) had complete or severe residual high quadriplegia, but 11 children (69%) enjoyed excellent neurological recovery. CCI was normal in all 10 patients with non-AOD upper cervical injuries with a diagnostic specificity of 100%. The false-positive rates for the four "standard" tests were: Sun's, 60%; Harris', 50%; Wholey's, 30%; and Powers', 10%; for the "nonstandard" indicator, the rates were: cervicomedullary deficits, 70%; tectorial membrane damage, 40%; C1-C2 extra-axial blood, 40%; and perimedullary blood, 30%. The CCI criterion has the highest diagnostic sensitivity and specificity for AOD among all other radiodiagnostic criteria and indicators. CCI is easily computed from reconstructed CT scans, has almost no logistical or technical distortions, can capture occiput-C1 joint dislocation in all three planes, and is unaffected by congenital anomalies or maturation changes of adjacent structures. Because CCI is the only test that directly measures the integrity of the actual joint injured in AOD and a widened CCI cannot be concealed by postinjury changes in the head and neck relationship, it surpasses others that use changeable landmarks.

Glucose administration after traumatic brain injury exerts some benefits and no adverse effects on behavioral and histological outcomes.

PubMed

Shijo, Katsunori; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

2015-07-21

The impact of hyperglycemia after traumatic brain injury (TBI), and even the administration of glucose-containing solutions to head injured patients, remains controversial. In the current study adult male Sprague-Dawley rats were tested on behavioral tasks and then underwent surgery to induce sham injury or unilateral controlled cortical impact (CCI) injury followed by injections (i.p.) with either a 50% glucose solution (Glc; 2g/kg) or an equivalent volume of either 0.9% or 8% saline (Sal) at 0, 1, 3 and 6h post-injury. The type of saline treatment did not significantly affect any outcome measures, so these data were combined. Rats with CCI had significant deficits in beam-walking traversal time and rating scores (p's < 0.001 versus sham) that recovered over test sessions from 1 to 13 days post-injury (p's < 0.001), but these beam-walking deficits were not affected by Glc versus Sal treatments. Persistent post-CCI deficits in forelimb contraflexion scores and forelimb tactile placing ability were also not differentially affected by Glc or Sal treatments. However, deficits in latency to retract the right hind limb after limb extension were significantly attenuated in the CCI-Glc group (p < 0.05 versus CCI-Sal). Both CCI groups were significantly impaired in a plus maze test of spatial working memory on days 4, 9 and 14 post-surgery (p < 0.001 versus sham), and there was no effect of Glc versus Sal on this cognitive outcome measure. At 15 days post-surgery the loss of cortical tissue volume (p < 0.001 versus sham) was significantly less in the CCI-Glc group (30.0%; p < 0.05) compared to the CCI-Sal group (35.7%). Counts of surviving hippocampal hilar neurons revealed a significant (~40%) loss ipsilateral to CCI (p < 0.001 versus sham), but neuronal loss in the hippocampus was not different in the CCI-Sal and CCI-Glc groups. Taken together, these results indicate that an early elevation of blood glucose may improve some neurological outcomes and, importantly, the induction of hyperglycemia after isolated TBI did not adversely affect any sensorimotor, cognitive or histological outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of intermedin on dorsal root ganglia in the transmission of neuropathic pain in chronic constriction injury rats.

PubMed

Xiong, Wei; Qiu, Shu-yi; Xu, Ling-yun; Zhang, Chun-ping; Yi, Yun; Wu, Qin; Huang, Li-ping; Liu, Shuang-mei; Wu, Bing; Peng, Li-chao; Song, Miao-miao; Gao, Yun; Liang, Shang-dong

2015-07-01

Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. The P2X3 receptor plays a crucial role in facilitating pain transmission. Intermedin (IMD), which is also known as adrenomedullin 2 (AMD2) is a newly discovered hormone that is a member of the calcitonin/calcitonin gene-related peptide family. The present research investigates the effects of IMD on pain transmission in neuropathic pain states as mediated by P2X3 receptors in dorsal root ganglia (DRG). Chronic constriction injury (CCI) rats were used as the neuropathic pain model. Adult male Sprague-Dawley rats were randomly assigned to five groups as follows: blank control group (Control), sham operation group (Sham), CCI rats treated with saline group (CCI+NS), CCI rats treated with IMD1-53 group (CCI+IMD1-53 ), and CCI rats treated with IMD inhibitor IMD14-47 group (CCI+IMD14-47 ). The mechanical withdrawal threshold (MWT) was tested by the von Frey method, and the thermal withdrawal latency (TWL) was tested via automatic thermal stimulus instruments. Changes in the expression of P2X3 receptors and IMD in CCI rat L4/L5 DRG were detected using immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blotting. After treatment with intrathecal injection (i.t.), mechanical and thermal hyperalgesia in the CCI+IMD1-53 group was maintained, but MWT and TWL in the CCI+IMD14-47 groups increased. The expression levels of P2X3 receptors and IMD in L4/L5 DRG in the CCI+NS and CCI+IMD1-53 groups were significantly increased compared with those in the Control group or the Sham group. After application of IMD14-47 in CCI rats, there was a decrease in the expression levels of P2X3 receptors and IMD in L4/L5 DRG. The phosphorylation of p38 and ERK1/2 in L4/L5 DRG in the CCI+NS group and the CCI+IMD1-53 group was stronger than that in the Control group or the Sham group; however, the phosphorylation of p38 and ERK1/2 in the CCI+IMD14-47 group was much lower than that in the CCI+NS group or the CCI+IMD1-53 group. Our findings indicate that IMD might increase the sensitization effects of IMD on P2X3 receptors to alleviate chronic neuropathic pain injury. The IMD agonist IMD1-53 might enhance nociceptive responses mediated by P2X3 receptors in neuropathic pain, and the IMD inhibitor IMD14-47 could inhibit the sensitization of the P2X3 receptor in chronic neuropathic pain injury. © 2015 Wiley Publishing Asia Pty Ltd.

Effect of dexmedetomidine and cold stress in a rat model of neuropathic pain: Role of interleukin-6 and tumor necrosis factor-α.

PubMed

Farghaly, Hanan Sayed M; Mahmoud, Ahmed Mostafa; Abdel-Sater, Khaled A

2016-04-05

Dexmedetomidine (Dex) is a novel Alpha 2-adrenoceptor agonist. It decreases sympathetic tone and attenuates the stress responses to anesthesia and surgery. People exposed to cold suffer unpleasant thermal pain, which is experienced as stress and causes the release of noradrenaline from the sympathetic terminals. The present study investigated the effects of cold stress and dexmedetomidine on chronic constriction injury (CCI) model of the sciatic nerve in rats. Sixty four male Wistar rats were divided into seven groups of eight rats each: repeated cold stress (RCS) group, sham RCS group, CCI group, sham CCI group, Dex-treated group received a single dose of Dex (5 μg/kg), CCI+Dex group, CCI+RCS group. Interleukin-6 (IL-6) and tumor necrosis factor- alpha (TNF-α) levels in the serum were measured by enzyme-linked immunosorbent assay. The mean body weight of CCI, RCS, CCI+RCS, CCI+Dex and RCS+Dex groups decreased significantly compared with pre-values. Dexmedetomidine and CCI caused significant changes of the systolic, diastolic and mean blood pressure. Both RCS and CCI groups showed significant decreased of reaction time in the hot plate test. The RCS and CCI groups demonstrated a significant mechanical hyperalgesia, while pain threshold was increased in the RCS+Dex group. A significant decrease of serum IL-6 and TNF-α was demonstrated in CCI+RCS and CCI+Dex groups. The therapeutic effectiveness of dexmedetomidine in neuropathic pain may be through inhibition of proinflammatory cytokines, primarily IL-6 and TNF-α. Moreover, cold stress may result in increased resistance to neuropathic pain. Copyright © 2016 Elsevier B.V. All rights reserved.

Artificial Leaks in Container Closure Integrity Testing: Nonlinear Finite Element Simulation of Aperture Size Originated by a Copper Wire Sandwiched between the Stopper and the Glass Vial.

PubMed

Nieto, Alejandra; Roehl, Holger; Brown, Helen; Adler, Michael; Chalus, Pascal; Mahler, Hanns-Christian

2016-01-01

Container closure integrity (CCI) testing is required by different regulatory authorities in order to provide assurance of tightness of the container closure system against possible contamination, for example, by microorganisms. Microbial ingress CCI testing is performed by incubation of the container closure system with microorganisms under specified testing conditions. Physical CCI uses surrogate endpoints, such as coloration by dye solution ingress or gas flow (helium leakage testing). In order to correlate microbial CCI and physical CCI test methods and to evaluate the methods' capability to detect a given leak, artificial leaks are being introduced into the container closure system in a variety of different ways. In our study, artificial leaks were generated using inserted copper wires between the glass vial opening and rubber stopper. However, the insertion of copper wires introduces leaks of unknown size and shape. With nonlinear finite element simulations, the aperture size between the rubber stopper and the glass vial was calculated, depending on wire diameter and capping force. The dependency of the aperture size on the copper wire diameter was quadratic. With the data obtained, we were able to calculate the leak size and model leak shape. Our results suggest that the size as well as the shape of the artificial leaks should be taken into account when evaluating critical leak sizes, as flow rate does not, independently, correlate to hole size. Capping force also affected leak size. An increase in the capping force from 30 to 70 N resulted in a reduction of the aperture (leak size) by approximately 50% for all wire diameters. From 30 to 50 N, the reduction was approximately 33%. Container closure integrity (CCI) testing is required by different regulatory authorities in order to provide assurance of tightness of the container closure system against contamination, for example, by microorganisms. Microbial ingress CCI testing is performed by incubation of the container closure system with microorganisms under specified testing conditions. Physical CCI uses surrogate endpoints, such as coloration by dye solution ingress or gas flow. In order to correlate microbial ingress CCI and physical CCI test methods and to evaluate the methods' capability to detect a given leak, artificially created defects (artificial leaks) are being introduced into the container closure system in a variety of different ways. In our study, artificial leaks were generated using inserted copper wires between the glass vial opening and rubber stopper. Up to date, the insertion of copper wires introduced leaks of unknown size and shape. With nonlinear finite element simulations, the effective aperture size between the rubber stopper and the glass vial was calculated, depending on wire diameter and capping force, and the leak shape was modelled. Our results suggest that the size as well as the shape of the artificial leaks should be taken into account when evaluating critical leak sizes, as flow rate does not, independently, correlate to the hole size. © PDA, Inc. 2016.

Effects of intrathecal injection of rapamycin on pain threshold and spinal cord glial activation in rats with neuropathic pain.

PubMed

Lv, Jing; Li, Zhenci; She, Shouzhang; Xu, Lixin; Ying, Yanlu

2015-08-01

To evaluate the effects of intrathecal injection of rapamycin on pain threshold and spinal cord glial activation in rats with neuropathic pain. Healthy 30 male Sprague Dawley (SD) rats were randomly divided into six groups (n = 5 in each group): (1) control group without any treatments; (2) chronic constriction injury (CCI) group; (3) Early-rapamycin group with intrathecal injection of rapamycin 4 hours after CCI days; (4) Early-vehicle group with intrathecal injection of DMSO; (5) Late-rapamycin group with intrathecal injection of rapamycin 7 days after CCI; (6) Late-vehicle group with intrathecal injection of DMSO 7 days after CCI. Rapamycin or DMSO was injected for 3 consecutive days. Mechanical and thermal threshold were tested before and after the CCI operation. Lumbar segment of spinal cords was tested for glial fibrillary acidic protein (GFAP) by immunohistochemistry on 14th day after operation. Mechanical and thermal hyperalgesia emerged on fourth day were maintained till fourteenth day after operation. After intrathecal injection of rapamycin 4 hours or 7 days after CCI, mechanical and thermal threshold significantly increased compared to injection of DMSO. The area of GFAP positive and the mean density of GFAP positive area in the dorsal horn of the ipsilateral side greatly increased in rapamycin-treated groups. Intrathecal injection of rapamycin may attenuate CCI-induced hyperalgesia and inhibit the activation of astrocyte.

Preparation of water-soluble glycoconjugated poly(acrylamide) for NMR analyses of carbohydrate-carbohydrate interactions

NASA Astrophysics Data System (ADS)

Xuan, Trinh Anh; Trung, Phan Nghia; Dinh, Bui Long; Yamaguchi, Takumi; Kato, Koichi

2014-05-01

Oligosaccharide chains of glycoconjugates are important biopolymers not only as carriers of information in cell-cell interactions but also as markers of cellular differentiation, aging, and malignant alteration. Molecular interactions where carbohydrates are involved are usually considered as weak interactions, so the study and evaluation of these interactions is still in its infancy. The evidences and studies of carbohydrate-carbohydrate interactions (CCI) will be confirming the importance of this mechanism for specific cell adhesion and communication. Their development will go hand in hand with the development of new and more sensitive techniques to study weak interactions. Recently, synthetic glycopolymers with functions similar to those of such natural carbohydrates and with specific pendant saccharide moieties were used as a solution for enhancement CCI when forming polyvalent interactions. Carbohydrates are ubiquitous components of cell wall membranes and occur as glycolipids, glycoproteins, proteoglycans, and capsular polysaccharides. As such they can participate in forefront intramolecular and intracellular events. Apart from their recognized roles in the physicochemical properties of glycolipids and glycoproteins. In this study, we designed trisaccharide monomers for free radical polymerization. Subsequently, the trisaccharide unit for chemical conjugation was synthesized from galactosamine in good yield. For further NMR analyses of CCI, glycopolymers composed of these sugar derivatives will be provided.

Preventive and curative effects of radon inhalation on chronic constriction injury-induced neuropathic pain in mice.

PubMed

Yamato, K; Kataoka, T; Nishiyama, Y; Taguchi, T; Yamaoka, K

2013-04-01

Radon therapy is clinically useful for the treatment of pain-related diseases. However, there have been no studies regarding the effects of radon inhalation on neuropathic pain. In this study, we aimed to determine whether radon inhalation actually induced a remission of neuropathic pain and improved the quality of life. First, we investigated the antinociceptive effects of radon inhalation in the chronic constriction injury (CCI) model of neuropathic pain. We evaluated pain behaviour in mice before and after CCI surgery, using von Frey test. Pretreated mice received CCI surgery immediately after 24-h inhalation of radon at background (BG) concentration (c. 19 Bq/m(3) ), or at a concentration of 1000 or 2000 Bq/m(3) , and post-treated mice inhaled similar levels of radon 2 days after CCI surgery. CCI surgery induced mechanical allodynia and hyperalgesia on a plantar surface of mice, as assessed using von Frey test, and 2000 Bq/m(3) radon inhalation alleviated hyperalgesic conditions 22-37% compared to BG level concentration. Concurrently, CCI surgery increased norepinephrine (NE), tumour necrosis factor-alpha (TNF-α) and nitric oxide (NO) concentrations in plasma, and leukocyte migration in paws. Furthermore, CCI-induced neuropathy reduced superoxide dismutase (SOD) activity. Treatment with radon inhalation, specifically at a concentration of 2000 Bq/m(3) , produced antinociceptive effects, i.e., lowered plasma TNF-α, NE and NO levels and restored SOD activity, as well as pain-related behaviour. This study showed that inhalation of 2000 Bq/m(3) radon prevented and alleviated CCI-induced neuropathic pain in mice. © 2012 European Federation of International Association for the Study of Pain Chapters.

[Color vision impairment in workers exposed to mercury vapor].

PubMed

Jedrejko, Marta; Skoczyńska, Anna

2011-01-01

Acquired reversible dyschromatopsia has been associated with occupational exposure to mercury vapor. Early-detected impairments in color discrimination precede adverse permanent effects of mercury, so they may help to monitor the health of the exposed workers. The aim of this study was to evaluate the color discrimination ability in this group of workers, using Lanthony D-15d test. Employed in a chloralkali plant, 27 male workers exposed to mercury vapor and 27 healthy white-collar workers (control group) were qualified for the study. To assess color discrimination, the Lanthony 15-Hue desaturated test (Lanthony D-15) was used. In order to investigate quantitative and qualitative results, the Lanthony D-15d scoring software was performed. Urinary mercury was determined using flameless atomic absorption spectrometry. In the workers exposed to mercury vapor, urine mercury concentration was 117.4 +/- 62.6 microg/g creatinine on average compared with 0.279 +/- 0.224 mg/g creatinine in the control group (p < 0.0001). In 18 exposed persons (66.7%), the results of the Lanthony D-15d test showed qualitative changes, which are borderline corresponding to the early stage of developing dyschromatopsia type III. The quantitative analysis of the test findings indicated a significantly higher value of the Color Confusion Index (CCI) in the right eye in the exposed group compared to the control group (p = 0.01), with no significant difference in the CCI in the left eye. In the exposed group, the CCI in the right eye was significantly higher than the CCI in the left eye (p = 0.0005). There was neither correlation between CCI and the level of urinary mercury, nor between CCI and duration of exposure. The results showed that the Lanthony D-15d test is useful in the detection of early toxic effects in the eyesight of the workers exposed to mercury vapor. The observed color vision impairments are borderline corresponding to the early stage of developing dyschromatopsia type III.

Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats.

PubMed

Caspani, Ombretta; Reitz, Marie-Céline; Ceci, Angelo; Kremer, Andreas; Treede, Rolf-Detlef

2014-09-01

Depression and anxiety are common comorbidities of neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. In this study, we investigated the effects of tramadol on nociceptive reflex, depression-associated and anxiety-related behaviors in a NP model in rats. We used chronic constriction injury (CCI) of the sciatic nerve as an animal model of neuropathic pain. We performed electronic von Frey tests (evF) to measure mechanical sensitivity, elevated plus maze tests (EPM) to record anxiety-related behaviors and forced swimming tests (FST) to evaluate depression-associated behaviors. In the evF, CCI rats showed a decrease of 82% of the paw withdrawal threshold (PWT) compared to sham (P<0.001). Tramadol increased the PWT by 336% in CCI rats (P<0.001) and by 16% in sham (P<0.05). On the EPM, CCI rats spent 45% less time than sham on the open arms of the maze (P<0.05). Tramadol increased the time spent on the open arms of CCI rats by 67% (P<0.05) and had no significant effect on sham. During the FST, CCI rats showed 28% longer immobility than sham (P<0.01). Tramadol reduced the immobility time in CCI rats by 22% (P<0.001), while having no effect on sham. Tramadol reversed the changes in mechanical sensitivity as well as anxiety-related and depression-associated behaviors that are caused by injury of the sciatic nerve with only minor effects in the absence of injury. These data suggest that tramadol relieves chronic pain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP. Copyright © 2014 Elsevier Inc. All rights reserved.

Homogeneity testing of the global ESA CCI multi-satellite soil moisture climate data record

NASA Astrophysics Data System (ADS)

Preimesberger, Wolfgang; Su, Chun-Hsu; Gruber, Alexander; Dorigo, Wouter

2017-04-01

ESA's Climate Change Initiative (CCI) creates a global, long-term data record by merging multiple available earth observation products with the goal to provide a product for climate studies, trend analysis, and risk assessments. The blending of soil moisture (SM) time series derived from different active and passive remote sensing instruments with varying sensor characteristics, such as microwave frequency, signal polarization or radiometric accuracy, could potentially lead to inhomogeneities in the merged long-term data series, undercutting the usefulness of the product. To detect the spatio-temporal extent of contiguous periods without inhomogeneities as well as subsequently minimizing their negative impact on the data records, different relative homogeneity tests (namely Fligner-Killeen test of homogeneity of variances and Wilcoxon rank-sums test) are implemented and tested on the combined active-passive ESA CCI SM data set. Inhomogeneities are detected by comparing the data against reference data from in-situ data from ISMN, and model-based estimates from GLDAS-Noah and MERRA-Land. Inhomogeneity testing is performed over the ESA CCI SM data time frame of 38 years (from 1978 to 2015), on a global quarter-degree grid and with regard to six alterations in the combination of observation systems used in the data blending process. This study describes and explains observed variations in the spatial and temporal patterns of inhomogeneities in the combined products. Besides we proposes methodologies for measuring and reducing the impact of inhomogeneities on trends derived from the ESA CCI SM data set, and suggest the use of inhomogeneity-corrected data for future trend studies. This study is supported by the European Union's FP7 EartH2Observe "Global Earth Observation for Integrated Water Resource Assessment" project (grant agreement number 331 603608).

Minocycline Effects on IL-6 Concentration in Macrophage and Microglial Cells in a Rat Model of Neuropathic Pain.

PubMed

Moini-Zanjani, Taraneh; Ostad, Seyed-Nasser; Labibi, Farzaneh; Ameli, Haleh; Mosaffa, Nariman; Sabetkasaei, Masoumeh

2016-11-01

Evidence indicates that neuropathic pain pathogenesis is not confined to changes in the activity of neuronal systems but involves interactions between neurons, inflammatory immune and immune-like glial cells. Substances released from immune cells during inflammation play an important role in development and maintenance of neuropathic pain. It has been found that minocycline suppresses the development of neuropathic pain. Here, we evaluated the analgesic effect of minocycline in a chronic constriction injury (CCI) model of neuropathic pain in rat and assessed IL-6 concentration from cultured macrophage and microglia cells. Male Wistar rat (n=6, 150-200 g) were divided into three different groups: 1) CCI+vehicle, 2) sham+vehicle, and 3) CCI+drug. Minocycline (10, 20, and 40 mg/kg) was injected one hour before surgery and continued daily to day 14 post ligation. Von Frey filaments and acetone, as pain behavioral tests, were used for mechanical allodynia and cold allodynia, respectively. Experiments were performed on day 0 (before surgery) and days 1, 3, 5, 7, 10, and 14 post -injury. At day 14, rats were killed and monocyte-derived macrophage from right ventricle and microglia from lumbar part of the spinal cord were isolated and cultured in RPMI and Leibovitz's media, respectively. IL-6 concentration was evaluated in cell culture supernatant after 24 h. Minocycline (10, 20, and 40 mg/kg) attenuated pain behavior, and a decrease in IL-6 concentration was observed in immune cells compared to CCI vehicle-treated animals. Minocycline reduced pain behavior and decreased IL-6 concentration in macrophage and microglial cells.

Geometry and Material Constraint Effects on Creep Crack Growth Behavior in Welded Joints

NASA Astrophysics Data System (ADS)

Li, Y.; Wang, G. Z.; Xuan, F. Z.; Tu, S. T.

2017-02-01

In this work, the geometry and material constraint effects on creep crack growth (CCG) and behavior in welded joints were investigated. The CCG paths and rates of two kinds of specimen geometry (C(T) and M(T)) with initial cracks located at soft HAZ (heat-affected zone with lower creep strength) and different material mismatches were simulated. The effect of constraint on creep crack initiation (CCI) time was discussed. The results show that there exists interaction between geometry and material constraints in terms of their effects on CCG rate and CCI time of welded joints. Under the condition of low geometry constraint, the effect of material constraint on CCG rate and CCI time becomes more obvious. Higher material constraint can promote CCG due to the formation of higher stress triaxiality around crack tip. Higher geometry constraint can increase CCG rate and reduce CCI time of welded joints. Both geometry and material constraints should be considered in creep life assessment and design for high-temperature welded components.

Hyperbaric oxygen attenuates neuropathic pain and reverses inflammatory signaling likely via the Kindlin-1/Wnt-10a signaling pathway in the chronic pain injury model in rats.

PubMed

Zhao, Baisong; Pan, Yongying; Xu, Haiping; Song, Xingrong

2017-12-01

Hyperbaric oxygen (HBO) therapy is proven to attenuate neuropathic pain in rodents. The goal of the present study was to determine the potential involvement of the Kindlin-1/Wnt-10a signaling pathway during astrocyte activation and inflammation in a rodent model of neuropathic pain. Rats were assigned into sham operation, chronic constriction injury (CCI), and CCI + HBO treatment groups. Neuropathic pain developed in rats following CCI of the sciatic nerve. Rats in the CCI + HBO group received HBO treatment for five consecutive days beginning on postoperative day 1. The mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) tests were performed to determine mechanical and heat hypersensitivity of animals, respectively. Kindlin-1, Wnt-10a and β-catenin protein expression was examined by immunohistochemistry and Western blot analysis. Expression of tumor necrosis factor (TNF)-α was also determined by ELISA. Our findings demonstrated that HBO treatment significantly suppressed mechanical and thermal hypersensitivity in the CCI neuropathic pain model in rats. HBO therapy significantly reversed the up-regulation of Kindlin-1 in dorsal root ganglia (DRG), spinal cord, and hippocampus of CCI rats. CCI-induced astrocyte activation and increased levels of TNF-α were efficiently reversed by HBO (P < 0.05 vs. CCI). HBO also reversed Wnt-10a up-regulation induced by CCI in the DRG, spinal cord, and hippocampus (P < 0.05 vs. CCI). Our findings demonstrate that HBO attenuated CCI-induced rat neuropathic pain and inflammatory responses, possibly through regulation of the Kindlin-1/Wnt-10a signaling pathway.

Depression-like behavior and mechanical allodynia are reduced by bis selenide treatment in mice with chronic constriction injury: a comparison with fluoxetine, amitriptyline, and bupropion.

PubMed

Jesse, Cristiano R; Wilhelm, Ethel A; Nogueira, Cristina W

2010-12-01

Neuropathic pain is associated with significant co-morbidities, including depression, which impact considerably on the overall patient experience. Pain co-morbidity symptoms are rarely assessed in animal models of neuropathic pain. Neuropathic pain is characterized by hyperexcitability within nociceptive pathways and remains difficult to treat with standard analgesics. The present study determined the effect of bis selenide and conventional antidepressants (fluoxetine, amitriptyline, and bupropion) on neuropathic pain using mechanical allodynic and on depressive-like behavior. Male mice were subjected to chronic constriction injury (CCI) or sham surgery and were assessed on day 14 after operation. Mice received oral treatment with bis selenide (1-5 mg/kg), fluoxetine, amitriptyline, or bupropion (10-30 mg/kg). The response frequency to mechanical allodynia in mice was measured with von Frey hairs. Mice were evaluated in the forced swimming test (FST) test for depression-like behavior. The CCI procedure produced mechanical allodynia and increased depressive-like behavior in the FST. All of the drugs produced antiallodynic effects in CCI mice and produced antidepressant effects in control mice without altering locomotor activity. In CCI animals, however, only the amitriptyline and bis selenide treatments significantly reduced immobility in the FST. These data demonstrate an important dissociation between the antiallodynic and antidepressant effects in mice when tested in a model of neuropathic pain. Depressive behavior in CCI mice was reversed by bis selenide and amitriptyline but not by the conventional antidepressants fluoxetine and buproprion. Bis selenide was more potent than the other drugs tested for antidepressant-like and antiallodynic effects in mice.

Dexamethasone Attenuates the Enhanced Rewarding Effects of Cocaine Following Experimental Traumatic Brain Injury.

PubMed

Merkel, Steven F; Andrews, Allison M; Lutton, Evan M; Razmpour, Roshanak; Cannella, Lee Anne; Ramirez, Servio H

2017-07-01

Clinical studies have identified traumatic brain injury (TBI) as a risk factor for the development of cocaine dependence. This claim is supported by our recent preclinical studies showing enhancement of the rewarding effects of cocaine in mice sustaining moderate controlled cortical impact (CCI) injury during adolescence. Here we test the efficacy of dexamethasone, an anti-inflammatory corticosteroid, to attenuate augmentation of the behavioral response to cocaine observed in CCI-TBI animals using the conditioned place preference (CPP) assay. These studies were performed in order to determine whether proinflammatory activity in the nucleus accumbens (NAc), a key brain nucleus in the reward pathway, mediates enhanced cocaine-induced CPP in adolescent animals sustaining moderate CCI-TBI. Our data reveal robust glial activation in the NAc following CCI-TBI and a significant increase in the cocaine-induced CPP of untreated CCI-TBI mice. Furthermore, our results show that dexamethasone treatment following CCI-TBI can attenuate the cocaine place preference of injured animals without producing aversion in the CPP assay. Our studies also found that dexamethasone treatment significantly reduced the expression of select immune response genes including Monocyte chemoattractant protein-1 (MCP-1/CCL2) and intercellular adhesion molecule-1 ( ICAM-1), returning their expression to control levels, which prompted an investigation of peripheral blood monocytes in dexamethasone-treated animals. Experimental findings showed that no craniectomy/dexamethasone mice had a significant increase, while CCI-TBI/dexamethasone animals had a significant decrease in the percentage of circulating nonclassical patrolling monocytes. These results suggest that a portion of these monocytes may migrate to the brain in response to CCI-TBI, potentially sparing the development of chronic neuroinflammation in regions associated with the reward circuitry such as the NAc. Overall, our findings indicate that anti-inflammatory agents, such as dexamethasone, may be effective in normalizing the rewarding effects of cocaine following CCI-TBI.

Hyperbaric oxygen can induce neuroplasticity and improve cognitive functions of patients suffering from anoxic brain damage

PubMed Central

Hadanny, A.; Golan, H.; Fishlev, G.; Bechor, Y.; Volkov, O.; Suzin, G.; Ben-Jacob, E.; Efrati, S.

2015-01-01

Abstract Purpose: Cognitive impairment may occur in 42–50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury. The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest. Methods: Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging. Results: The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5–7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging. Conclusions: Although further research is needed, the results demonstrate the beneficial effects of HBO2 on CCI in patients after cardiac arrest, even months to years after the acute event. PMID:26409406

Education, Information Technology and Cognitive Science.

ERIC Educational Resources Information Center

Scaife, M.

1989-01-01

Discusses information technology and its effects on developmental psychology and children's education. Topics discussed include a theory of child-computer interaction (CCI); programing; communication and computers, including electronic mail; cognitive science; artificial intelligence; modeling the user-system interaction; and the future of…

Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury.

PubMed

Fukushima, Masamichi; Lee, Stefan M; Moro, Nobuhiro; Hovda, David A; Sutton, Richard L

2009-07-01

This study determined the effects of intraperitoneal sodium pyruvate (SP) treatment on the levels of circulating fuels and on cerebral microdialysis levels of glucose (MD(glc)), lactate (MD(lac)), and pyruvate (MD(pyr)), and the effects of SP treatment on neuropathology after left cortical contusion injury (CCI) in rats. SP injection (1000 mg/kg) 5 min after sham injury (Sham-SP) or CCI (CCI-SP) significantly increased arterial pyruvate (p < 0.005) and lactate (p < 0.001) compared to that of saline-treated rats with CCI (CCI-Sal). Serum glucose also increased significantly in CCI-SP compared to that in CCI-Sal rats (p < 0.05), but not in Sham-SP rats. MD(pyr) was not altered after CCI-Sal, whereas MD(lac) levels within the cerebral cortex significantly increased bilaterally (p < 0.05) and those for MD(glc) decreased bilaterally (p < 0.05). MD(pyr) levels increased significantly in both Sham-SP and CCI-SP rats (p < 0.05 vs. CCI-Sal) and were higher in left/injured cortex of the CCI-SP group (p < 0.05 vs. sham-SP). In CCI-SP rats the contralateral MD(lac) decreased below CCI-Sal levels (p < 0.05) and the ipsilateral MD(glc) levels exceeded those of CCI-Sal rats (p < 0.05). Rats with a single low (500 mg/kg) or high dose (1000 mg/kg) SP treatment had fewer damaged cortical cells 6 h post-CCI than did saline-treated rats (p < 0.05), but three hourly injections of SP (1000 mg/kg) were needed to significantly reduce contusion volume 2 weeks after CCI. Thus, a single intraperitoneal SP treatment increases circulating levels of three potential brain fuels, attenuates a CCI-induced reduction in extracellular glucose while increasing extracellular levels of pyruvate, but not lactate, and can attenuate cortical cell damage occurring within 6 h of injury. Enduring (2 week) neuronal protection was achieved only with multiple SP treatments within the first 2 h post-CCI, perhaps reflecting the need for additional fuel throughout the acute period of increased metabolic demands induced by CCI.

Metabolic and Histologic Effects of Sodium Pyruvate Treatment in the Rat after Cortical Contusion Injury

PubMed Central

Fukushima, Masamichi; Lee, Stefan M.; Moro, Nobuhiro; Hovda, David A.

2009-01-01

Abstract This study determined the effects of intraperitoneal sodium pyruvate (SP) treatment on the levels of circulating fuels and on cerebral microdialysis levels of glucose (MDglc), lactate (MDlac), and pyruvate (MDpyr), and the effects of SP treatment on neuropathology after left cortical contusion injury (CCI) in rats. SP injection (1000 mg/kg) 5 min after sham injury (Sham-SP) or CCI (CCI-SP) significantly increased arterial pyruvate (p < 0.005) and lactate (p < 0.001) compared to that of saline-treated rats with CCI (CCI-Sal). Serum glucose also increased significantly in CCI-SP compared to that in CCI-Sal rats (p < 0.05), but not in Sham-SP rats. MDpyr was not altered after CCI-Sal, whereas MDlac levels within the cerebral cortex significantly increased bilaterally (p < 0.05) and those for MDglc decreased bilaterally (p < 0.05). MDpyr levels increased significantly in both Sham-SP and CCI-SP rats (p < 0.05 vs. CCI-Sal) and were higher in left/injured cortex of the CCI-SP group (p < 0.05 vs. sham-SP). In CCI-SP rats the contralateral MDlac decreased below CCI-Sal levels (p < 0.05) and the ipsilateral MDglc levels exceeded those of CCI-Sal rats (p < 0.05). Rats with a single low (500 mg/kg) or high dose (1000 mg/kg) SP treatment had fewer damaged cortical cells 6 h post-CCI than did saline-treated rats (p < 0.05), but three hourly injections of SP (1000 mg/kg) were needed to significantly reduce contusion volume 2 weeks after CCI. Thus, a single intraperitoneal SP treatment increases circulating levels of three potential brain fuels, attenuates a CCI-induced reduction in extracellular glucose while increasing extracellular levels of pyruvate, but not lactate, and can attenuate cortical cell damage occurring within 6 h of injury. Enduring (2 week) neuronal protection was achieved only with multiple SP treatments within the first 2 h post-CCI, perhaps reflecting the need for additional fuel throughout the acute period of increased metabolic demands induced by CCI. PMID:19594384

The Controlled Cortical Impact Model: Applications, Considerations for Researchers, and Future Directions

PubMed Central

Osier, Nicole D.; Dixon, C. Edward

2016-01-01

Controlled cortical impact (CCI) is a mechanical model of traumatic brain injury (TBI) that was developed nearly 30 years ago with the goal of creating a testing platform to determine the biomechanical properties of brain tissue exposed to direct mechanical deformation. Initially used to model TBIs produced by automotive crashes, the CCI model rapidly transformed into a standardized technique to study TBI mechanisms and evaluate therapies. CCI is most commonly produced using a device that rapidly accelerates a rod to impact the surgically exposed cortical dural surface. The tip of the rod can be varied in size and geometry to accommodate scalability to difference species. Typically, the rod is actuated by a pneumatic piston or electromagnetic actuator. With some limits, CCI devices can control the velocity, depth, duration, and site of impact. The CCI model produces morphologic and cerebrovascular injury responses that resemble certain aspects of human TBI. Commonly observed are graded histologic and axonal derangements, disruption of the blood–brain barrier, subdural and intra-parenchymal hematoma, edema, inflammation, and alterations in cerebral blood flow. The CCI model also produces neurobehavioral and cognitive impairments similar to those observed clinically. In contrast to other TBI models, the CCI device induces a significantly pronounced cortical contusion, but is limited in the extent to which it models the diffuse effects of TBI; a related limitation is that not all clinical TBI cases are characterized by a contusion. Another perceived limitation is that a non-clinically relevant craniotomy is performed. Biomechanically, this is irrelevant at the tissue level. However, craniotomies are not atraumatic and the effects of surgery should be controlled by including surgical sham control groups. CCI devices have also been successfully used to impact closed skulls to study mild and repetitive TBI. Future directions for CCI research surround continued refinements to the model through technical improvements in the devices (e.g., minimizing mechanical sources of variation). Like all TBI models, publications should report key injury parameters as outlined in the NIH common data elements (CDEs) for pre-clinical TBI. PMID:27582726

The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model.

PubMed

Farghaly, Hanan Sm; Abd-Ellatief, Rasha B; Moftah, Marie Z; Mostafa, Mostafa G; Khedr, Eman M; Kotb, Hassan I

2014-01-01

Interactions between the sympathetic and somatic nervous system play an essential role in the pathophysiologic mechanisms of neuropathic pain. The α2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Multidrug therapy is potentially valuable to decrease side effects. The aim of the present study was to investigate the possible antinociceptive effect of dexmedetomidine, an α2-adrenoceptor agonist, and its combination with front-line treatment of neuropathic pain, i.e., amitriptyline or tramadol, in a chronic constriction injury (CCI) model of the sciatic nerve in rats. Controlled animal study. Following unilateral ligation of the left sciatic nerve, the effect of intraperitoneal (i.p.) dexmedetomidine (5 ug/kg), tramadol (5 mg/kg), and amitriptyline (30 mg/kg) on mechanical allodynia (measured by electrical von Frey apparatus) and hyperalgesia (measured by Randall and Selitto test) was studied. The sham-operated rats and un-operated hind paw (right paw) press normally on the floor reproduced by a weighted pain score of 0. Behavioral and mechanical tests confirmed the development of neuropathic pain after CCI. All individual drugs and dexmedetomidine combination with either tramadol or amitriptyline were effective in reducing mechanical allodynia and hyperalgesia. Dexmedetomidine, amitriptyline, tramadol, amitriptyline+dexmedetomidine, and tramadol+dexmedetomidine combination did not produce any sedation/motor impairment (P > 0.05). Although the combination of these drugs improved the CCI model of neuropathic pain in this study, an additional interpretation of the underlying mechanism(s) will be needed to confirm these findings. The combination of these drugs appears to be more effective in increasing the pain threshold after peripheral nerve injury, when compared with the administration of either of amitriptyline or tramadol alone and should be considered as a possible alternative to decrease side effects of individual drug therapy.

SM2RAIN-CCI: a new global long-term rainfall data set derived from ESA CCI soil moisture

NASA Astrophysics Data System (ADS)

Ciabatta, Luca; Massari, Christian; Brocca, Luca; Gruber, Alexander; Reimer, Christoph; Hahn, Sebastian; Paulik, Christoph; Dorigo, Wouter; Kidd, Richard; Wagner, Wolfgang

2018-02-01

Accurate and long-term rainfall estimates are the main inputs for several applications, from crop modeling to climate analysis. In this study, we present a new rainfall data set (SM2RAIN-CCI) obtained from the inversion of the satellite soil moisture (SM) observations derived from the ESA Climate Change Initiative (CCI) via SM2RAIN (Brocca et al., 2014). Daily rainfall estimates are generated for an 18-year long period (1998-2015), with a spatial sampling of 0.25° on a global scale, and are based on the integration of the ACTIVE and the PASSIVE ESA CCI SM data sets.The quality of the SM2RAIN-CCI rainfall data set is evaluated by comparing it with two state-of-the-art rainfall satellite products, i.e. the Tropical Measurement Mission Multi-satellite Precipitation Analysis 3B42 real-time product (TMPA 3B42RT) and the Climate Prediction Center Morphing Technique (CMORPH), and one modeled data set (ERA-Interim). A quality check is carried out on a global scale at 1° of spatial sampling and 5 days of temporal sampling by comparing these products with the gauge-based Global Precipitation Climatology Centre Full Data Daily (GPCC-FDD) product. SM2RAIN-CCI shows relatively good results in terms of correlation coefficient (median value > 0.56), root mean square difference (RMSD, median value < 10.34 mm over 5 days) and bias (median value < -14.44 %) during the evaluation period. The validation has been carried out at original resolution (0.25°) over Europe, Australia and five other areas worldwide to test the capabilities of the data set to correctly identify rainfall events under different climate and precipitation regimes.The SM2RAIN-CCI rainfall data set is freely available at https://doi.org/10.5281/zenodo.846259.

STAT3 inhibitor WP1066 as a novel therapeutic agent for bCCI neuropathic pain rats.

PubMed

Xue, Zhao-Jing; Shen, Le; Wang, Zhi-Yao; Hui, Shang-Yi; Huang, Yu-Guang; Ma, Chao

2014-10-02

Activation of signal transducer and activator of transcription-3 (STAT3) is suggested to be critically involved in the development of chronic pain, but the complex regulation of STAT3-dependent pathway and the functional significance of inhibiting this pathway during the development of neuropathic pain remain elusive. To evaluate the contribution of the JAK2/STAT3 pathway to neuropathic pain and the potentiality of this pathway as a novel therapeutic target, we examined the effects of the STAT3 inhibitor WP1066 by intrathecal administration in a rat model of bilateral chronic constriction injury (bCCI). The pain behavior tests were performed before the surgery and on postoperative day 3, 7, 14 and 21. L4-L6 dorsal spinal cord were harvested at each time point. Both RT-PCR and Western blot were performed to evaluate the activation of JAK2/STAT3 pathway. To observe the influence of WP1066 on neuropathic pain and its molecular mechanism, WP1066 (10 μl, 10 mmol/L in DMSO) or the same capacity of DMSO as the control were applied through the intrathecal tube on the day before bCCI surgery, and on the postoperative day 3 and 5. Behavioral tests were performed to observe the therapeutic effect on mechanical, thermal and cold hyperalgesia. L4-L6 dorsal spinal cord was harvested on postoperative day fourteen, followed by RT-PCR and Western blot evaluation of the JAK2/STAT3 pathway activation. The mechanical, thermal and cold hyperalgesia of the bCCI rats were significantly decreased when compared with the Sham or the Naïve group at each postoperative time point (P<0.05). JAK2 mRNA and STAT3 mRNA were significantly increased in the bCCI rats, accompanied by SOCS3 mRNA with a similar tendency. Western blot analysis showed that JAK2 and phosphorylated STAT3 increased significantly since 3 days after bCCI. JAK2 peaked on postoperative day 14 while phosphorylated STAT3 peaked on postoperative day 7 and gradually decreased thereafter and SOCS3׳s peak level on postoperative day 3. When WP1066 were administered intrathecally, the pain behaviors of the bCCI rats were significantly improved (P<0.05). WP1066 also inhibited the mRNA level of JAK2, STAT3 and SOCS3 in bCCI rats significantly, together with the protein level of JAK2, phosphorylated STAT3 and SOCS3 on postoperative day 14 as well. Our results found that the JAK2/STAT3 pathway in the spinal cord dorsal horn was significantly activated in the bCCI neuropathic pain rats. WP1066, which inhibited the STAT3 pathway specifically, could partially alleviate the pain behavior of the bCCI rats. So it may serve as a novel therapeutic strategy against neuropathic pain. Copyright © 2014 Elsevier B.V. All rights reserved.

Relative to typical antipsychotic drugs, aripiprazole is a safer alternative for alleviating behavioral disturbances after experimental brain trauma

PubMed Central

Phelps, Thomas I.; Bondi, Corina O.; Mattiola, Vincent V.; Kline, Anthony E.

2016-01-01

Background Antipsychotic drugs (APDs) are used to manage traumatic brain injury (TBI)-induced behavioral disturbances, such as agitation and aggression. However, APDs exhibiting D2 receptor antagonism impede cognitive recovery after experimental TBI. Hence, empirical evaluation of APDs with different mechanistic actions is warranted. Aripiprazole (ARIP) is a D2 and 5-HT1A receptor agonist; pharmacotherapies with these properties enhance cognition after TBI. Objective To test the hypothesis that ARIP would increase behavioral performance and decrease histopathology after TBI. Methods Adult male rats were subjected to either a controlled cortical impact (CCI) or sham injury and then randomly assigned to ARIP (0.1 or 1.0 mg/kg) or VEH (1.0 mL/kg, saline vehicle) groups. Treatments began 24 hr after surgery and were administered once daily for 19 days. Motor (beam-balance/beam-walk) and cognitive (Morris water maze) performance was assessed on post-operative days 1-5 and 14-19, respectively, followed by quantification of hippocampal CA1/3 neuron survival and cortical lesion volume. Results Beam-balance was significantly improved in the CCI + ARIP (1.0 mg/kg) group vs. CCI + ARIP (0.1 mg/kg) and CCI + VEH [p<0.05]. Spatial learning and memory retention were significantly improved in the CCI + ARIP (0.1 mg/kg) group vs. the CCI + ARIP (1.0 mg/kg) and CCI + VEH groups [p<0.05]. Both doses of ARIP reduced lesion size and CA3 cell loss vs. VEH [p<0.05]. Importantly, neither dose of ARIP impeded functional recovery as previously reported with other APDs. Conclusion These findings support the hypothesis and endorse ARIP as a safer APD for alleviating behavioral disturbances after TBI. PMID:27225976

Pregnancy suppresses neuropathic pain induced by chronic constriction injury in rats through the inhibition of TNF-α

PubMed Central

Onodera, Yoshiko; Kanao-Kanda, Megumi; Kanda, Hirotsugu; Sasakawa, Tomoki; Iwasaki, Hiroshi; Kunisawa, Takayuki

2017-01-01

Purpose Pregnancy-induced analgesia develops during late pregnancy, but it is unclear whether this analgesia is effective against neuropathic pain. The detailed molecular mechanisms underlying pregnancy-induced analgesia have not been investigated. We examined the antinociceptive effect of pregnancy-induced analgesia in a neuropathic pain model and the expression of tumor necrosis factor (TNF)-α, glial fibrillary acidic protein (GFAP), Iba-1, and c-Fos in the spinal dorsal horn just before parturition. Materials and methods Female Sprague Dawley rats (200–250 g) were randomly assigned to one of four groups (pregnant + chronic constriction injury [CCI]; pregnant + sham injury; not pregnant + CCI; and not pregnant + sham injury). Separate groups were used for the behavioral and tissue analyses. CCI of the left sciatic nerve was surgically induced 3 days after confirming pregnancy in the pregnancy group or on day 3 in the not pregnant group. The spinal cord was extracted 18 days after CCI. TNF-α, GFAP, Iba-1, and c-Fos expression levels in the spinal dorsal horn were measured by Western blot analysis. Mechanical threshold was tested using von Frey filaments. Results The lowered mechanical threshold induced by CCI was significantly attenuated within 1 day before parturition and decreased after delivery. TNF-α expression in CCI rats was decreased within 1 day before parturition. Further, GFAP, Iba-1, and c-Fos expression in the spinal dorsal horn was reduced in the pregnant rats. Serum TNF-α in all groups was below measurable limits. Conclusion Our findings indicate that pregnancy-induced analgesia suppresses neuropathic pain through reducing spinal levels of TNF-α, GFAP, Iba-1, and c-Fos in a rat model of CCI. PMID:28331359

Could CCI or FBCI Fully Eliminate the Impact of Curve Flexibility When Evaluating the Surgery Outcome for Thoracic Curve Idiopathic Scoliosis Patient? A Retrospective Study

PubMed Central

Ni, Haijian; Zhu, Xiaodong; Li, Ming

2015-01-01

Purpose To clarify if CCI or FBCI could fully eliminate the influence of curve flexibility on the coronal correction rate. Methods We reviewed medical record of all thoracic curve AIS cases undergoing posterior spinal fusion with all pedicle screw systems from June 2011 to July 2013. Radiographical data was collected and calculated. Student t test, Pearson correlation analysis and linear regression analysis were used to analyze the data. Results 60 were included in this study. The mean age was 14.7y (10-18y) with 10 males (17%) and 50 females (83%). The average Risser sign was 2.7. The mean thoracic Cobb angle before operation was 51.9°. The mean bending Cobb angle was 27.6° and the mean fulcrum bending Cobb angle was 17.4°. The mean Cobb angle at 2 week after surgery was 16.3°. The Pearson correlation coefficient r between CCI and BFR was -0.856(P<0.001), and between FBCI and FFR was -0.728 (P<0.001). A modified FBCI (M-FBCI) = (CR-0.513)/BFR or a modified CCI (M-CCI) = (CR-0.279)/FFR was generated by curve estimation has no significant correlation with FFR (r=-0.08, p=0.950) or with BFR (r=0.123, p=0.349). Conclusions Fulcrum-bending radiographs may better predict the outcome of AIS coronal correction than bending radiographs in thoracic curveAIS patients. Neither CCI nor FBCI can fully eliminate the impact of curve flexibility on the outcome of correction. A modified CCI or FBCI can better evaluating the corrective effects of different surgical techniques or instruments. PMID:25984945

Could CCI or FBCI Fully Eliminate the Impact of Curve Flexibility When Evaluating the Surgery Outcome for Thoracic Curve Idiopathic Scoliosis Patient? A Retrospective Study.

PubMed

Yang, Changwei; Sun, Xiaofei; Li, Chao; Ni, Haijian; Zhu, Xiaodong; Yang, Shichang; Li, Ming

2015-01-01

To clarify if CCI or FBCI could fully eliminate the influence of curve flexibility on the coronal correction rate. We reviewed medical record of all thoracic curve AIS cases undergoing posterior spinal fusion with all pedicle screw systems from June 2011 to July 2013. Radiographical data was collected and calculated. Student t test, Pearson correlation analysis and linear regression analysis were used to analyze the data. 60 were included in this study. The mean age was 14.7 y (10-18 y) with 10 males (17%) and 50 females (83%). The average Risser sign was 2.7. The mean thoracic Cobb angle before operation was 51.9°. The mean bending Cobb angle was 27.6° and the mean fulcrum bending Cobb angle was 17.4°. The mean Cobb angle at 2 week after surgery was 16.3°. The Pearson correlation coefficient r between CCI and BFR was -0.856(P<0.001), and between FBCI and FFR was -0.728 (P<0.001). A modified FBCI (M-FBCI) = (CR-0.513)/BFR or a modified CCI (M-CCI) = (CR-0.279)/FFR was generated by curve estimation has no significant correlation with FFR (r=-0.08, p=0.950) or with BFR (r=0.123, p=0.349). Fulcrum-bending radiographs may better predict the outcome of AIS coronal correction than bending radiographs in thoracic curveAIS patients. Neither CCI nor FBCI can fully eliminate the impact of curve flexibility on the outcome of correction. A modified CCI or FBCI can better evaluating the corrective effects of different surgical techniques or instruments.

Sleep deprivation aggravates median nerve injury-induced neuropathic pain and enhances microglial activation by suppressing melatonin secretion.

PubMed

Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

2014-09-01

Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. © 2014 Associated Professional Sleep Societies, LLC.

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

Zhang, Li; DeRider, Michele; McCornack, Milissa A.

Chemokines (chemotactic cytokines) comprise a large family of proteins that recruit and activate leukocytes, giving chemokines a major role in both the immune response and inflammation-related diseases. The poxvirus-encoded viral CC chemokine inhibitor (vCCI) binds to many CC chemokines with high affinity, acting as a potent inhibitor of chemokine action. We have used heteronuclear multidimensional NMR to determine the first structure of an orthopoxvirus vCCI in complex with a human CC chemokine MIP-1β. vCCI binds to the chemokine with 1:1 stoichiometry, using residues from its β-sheet II to interact with the a surface of MIP-1β that includes the N-terminus, themore » following residues in the so-called N-loop20’s region, and the 40’s loop. This structure reveals a general strategy of vCCI for selective chemokine binding, as vCCI appears to interact most stronglyinteracts most directly with residues that are conserved among a subset of CC chemokines, but are not conservednot among the other chemokine subfamilies. This structure reveals a general strategy of vCCI for selective chemokine binding. Chemokines play critical roles in the immune system, causing chemotaxis of a variety of cells to sites of infection and inflammation, as well as mediating cell homing and immune system development 1(Baggiolini 2001). To date, about 50 chemokines have been identified, and these small proteins (7-14 kDa) are believed to function by binding with endothelial or matrix glycosaminoglycans to form a concentration gradient that is then sensed by high affinity, 7-transmembrane domain G-protein coupled chemokine receptors on the surface of immune cells surface. The chemokine system is critical for host defense in healthy individuals, butand can also lead to diseases including asthma, arthritis, and atherosclerosis in the case of malfunction, often due to inappropriate inflammation and subsequent tissue damage 2(Gerard and Rollins 2001). There are four subfamilies of chemokines, CC, CXC, C, and CX3C, named for the position of conserved N-terminal cysteine residues. Members of the same subfamily often have overlapping receptor binding and cell activation ability while different subfamilies tend to functionwork on different cell subsets1{Baggiolini, 2001 #472} (REF). For example, CC chemokines mostly interact with monocytes, macrophages, T cells and eosinophils, while CXC chemokines mainly interact with neutrophils. Structures of chemokines from different subfamilies have been solved by NMR and X-ray crystallography (XXX Include Fernandez and Lolis review) 3-9{Clore, 1990 #91;Skelton, 1995 #97;Handel, 1996 #93;Crump, 1997 #92;Crump, 1998 #248;Meunier, 1997 #96;Fernandez, 2002 #496}(Clore 1990; Skelton 1995; Handel and Domaille 1996; Crump, Gong et al. 1997; Meunier 1997; Crump, Rajarathnam et al. 1998)(Clore 1990; Skelton 1995; Handel and Domaille 1996; Crump et al. 1997; Meunier 1997; Crump et al. 1998).« less

Pennsylvania's Medical Home Initiative: Reductions in Healthcare Utilization and Cost Among Medicaid Patients with Medicaland Psychiatric Comorbidities.

PubMed

Rhodes, Karin V; Basseyn, Simon; Gallop, Robert; Noll, Elizabeth; Rothbard, Aileen; Crits-Christoph, Paul

2016-11-01

The Chronic Care Initiative (CCI) was a large state-wide patient-centered medical home (PCMH) initiative in Pennsylvania in place from 2008-2011. Determine whether the CCI impacted the utilization and costs for Medicaid patients with chronic medical conditions and comorbid psychiatric or substance use disorders. Analysis of Medicaid claims using difference-in-difference regression analyses to compare changes in utilization and costs for patients treated at CCI practices to propensity score-matched patients treated at comparison non-CCI practices. Ninety-six CCI practices in Pennsylvania and 60 non-CCI practices during the same time period. A total of 11,105 comorbid Medicaid patients treated in CCI practices and an equal number of propensity-matched comparison patients treated in non-CCI practices. Changes in total per-patient costs from 1 year prior to 1 year following an index episode period. Secondary outcomes included utilization and costs for emergency department (ED), inpatient, and outpatient services. The CCI group experienced an average adjusted total cost savings of $4145.28 per patient per year (P = 0.023) for the CCI relative to the non-CCI group. This was largely driven by a $3521.15 savings (P = 0.046) in inpatient medical costs, in addition to relative savings in outpatient psychiatric ($21.54, P < 0.001) and substance abuse service costs ($16.42, P = 0.013), compared to the non-CCI group. The CCI group, related to the non-CCI group, had decreases in expected mean counts of ED visits (for those who had any) and psychiatric hospitalizations of 15.6 (95 % CI: -21, -9) and 40.7 (95 % CI: -57, -18) percentage points respectively. We do not measure quality of care and cannot make conclusions about the overall cost-effectiveness or long-term effects of the CCI. The CCI was associated with substantial cost savings, attributable primarily to reduced inpatient costs, among a high-risk group of Medicaid patients, who may disproportionally benefit from care management in patient-centered medical homes.

Toward a More Sensitive Endpoint for Assessing Postoperative Complications in Patients with Inflammatory Bowel Disease: a Comparison Between Comprehensive Complication Index (CCI) and Clavien-Dindo Classification (CDC).

PubMed

Zhu, Feng; Feng, Dengyu; Zhang, Tenghui; Gu, Lili; Zhu, Weiming; Guo, Zhen; Li, Yi; Gong, Jianfeng; Li, Ning; Li, Jieshou

2018-05-15

The comprehensive complication index (CCI) is a novel approach to evaluate complications. However, application of the CCI in inflammatory bowel disease (IBD) population is scarce and the difference between the CCI and the Clavien-Dindo classification (CDC) remains unknown. The aim of this study was to compare the CCI to the conventional CDC by applying the CCI among the IBD patients. The data of 426 IBD patients who underwent surgery between September 1, 2015 and August 31, 2017 were collected. Univariate and multivariate analyses were conducted to identify risk factors for postoperative complications. The efficacy of CCI and CDC was compared using correlation analysis and logistic regression. Cumulative sum control (CUSUM) models were applied to monitor the CCI continuously. Totally, 297 complications occurred in 144 (33.8%) patients. The rate of severe complications (CDC grade ≥ III) was 12.9% and the mean CCI was 9.8 ± 15.5. Preoperative glucocorticoids usage and previous abdominal surgery were related to higher CCI value (p = 0.002, p = 0.006, respectively) but not related to higher incidence of severe complications (CDC grade ≥ III) (p = 0.117, p = 0.177, respectively). In patients with multiple complications, the CCI demonstrated a stronger correlation with hospital stay (ρ = 0.604, p < 0.001) than CDC (ρ = 0.508, p < 0.001). Higher CCI value (p < 0.001, OR 1.161, 95% CI 1.093-1.234) and the CDC grade (p < 0.001, OR 3.811, 95% CI 2.283-6.362) were risk factors for prolonged LOS. In the CUSUM-CCI model of IBD surgery, a gradual decrease was observed over time. The CCI and the CDC are both risk factors for prolonged postoperative LOS after surgery for IBD patients. The CCI is more strongly correlated with postoperative LOS than is the conventional CDC. The CUSUM-CCI model is effective in monitoring surgical quality.

Contralateral peripheral neurotization for a hemiplegic hindlimb after central neurological injury.

PubMed

Zheng, Mou-Xiong; Hua, Xu-Yun; Jiang, Su; Qiu, Yan-Qun; Shen, Yun-Dong; Xu, Wen-Dong

2018-01-01

OBJECTIVE Contralateral peripheral neurotization surgery has been successfully applied to rescue motor function of the hemiplegic upper extremity in patients with central neurological injury (CNI). It may contribute to strengthened neural pathways between the contralesional cortex and paretic limbs. However, the effect of this surgery in the lower extremities remains unknown. In the present study the authors explored the effectiveness and safety of contralateral peripheral neurotization in treating a hemiplegic lower extremity following CNI in adult rats. METHODS Controlled cortical impact (CCI) was performed on the hindlimb motor cortex of 36 adult Sprague-Dawley rats to create severe unilateral traumatic brain injury models. These CCI rats were randomly divided into 3 groups. At 1 month post-CCI, the experimental group (Group 1, 12 rats) underwent contralateral L-6 to L-6 transfer, 1 control group (Group 2, 12 rats) underwent bilateral L-6 nerve transection, and another control group (Group 3, 12 rats) underwent an L-6 laminectomy without injuring the L-6 nerves. Bilateral L-6 nerve transection rats without CCI (Group 4, 12 rats) and naïve rats (Group 5, 12 rats) were used as 2 additional control groups. Beam and ladder rung walking tests and CatWalk gait analysis were performed in each rat at baseline and at 0.5, 1, 2, 4, 6, 8, and 10 months to detect the skilled walking functions and gait parameters of both hindlimbs. Histological and electromyography studies were used at the final followup to verify establishment of the traumatic brain injury model and regeneration of the L6-L6 neural pathway. RESULTS In behavioral tests, comparable motor injury in the paretic hindlimbs was observed after CCI in Groups 1-3. Group 1 started to show significantly lower slip and error rates in the beam and ladder rung walking tests than Groups 2 and 3 at 6 months post-CCI (p < 0.05). In the CatWalk analysis, Group 1 also showed a higher mean intensity and swing speed after 8 months post-CCI and a longer stride length after 6 months post-CCI than Groups 2 and 3 (p < 0.05). Transection of L-6 resulted in transient skilled walking impairment in the intact hindlimbs in Groups 1 and 2 (compared with Group 3) and in the bilateral hindlimbs in Group 4 (compared with Group 5). All recovered to baseline level within 2 months. Histological study of the rat brains verified comparable injured volumes among Groups 1-3 at final examinations, and electromyography and toluidine blue staining indicated successful regeneration of the L6-L6 neural pathways in Group 1. CONCLUSIONS Contralateral L-6 neurotization could be a promising and safe surgical approach for improving motor recovery of the hemiplegic hindlimb after unilateral CNI in adult rats. Further investigations are needed before extrapolating the present conclusions to humans.

Selective Vasopressin-1a receptor antagonist prevents brain edema, reduces astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic brain injury

PubMed Central

Marmarou, Christina R.; Liang, Xiuyin; Abidi, Naqeeb H.; Parveen, Shanaz; Taya, Keisuke; Henderson, Scott C.; Young, Harold F.; Filippidis, Aristotelis S.; Baumgarten, Clive M.

2014-01-01

A secondary and often lethal consequence of traumatic brain injury is cellular edema that we posit is due to astrocytic swelling caused by transmembrane water fluxes augmented by vasopressin-regulated aquaporin-4 (AQP4). We therefore tested whether vasopressin 1a receptor (V1aR) inhibition would suppress astrocyte AQP4, reduce astrocytic edema, and thereby diminish TBI-induced edematous changes. V1aR inhibition by SR49059 significantly reduced brain edema after cortical contusion injury (CCI) in rat 5 h post-injury. Injured-hemisphere brain water content (n=6 animals/group) and astrocytic area (n=3/group) were significantly higher in CCI-vehicle (80.5±0.3%; 18.0±1.4 µm2) versus sham groups (78.3±0.1%; 9.5±0.9 µm2), and SR49059 blunted CCI-induced increases in brain edema (79.0±0.2%; 9.4±0.8 µm2). CCI significantly up-regulated GFAP, V1aR and AQP4 protein levels and SR49059 suppressed injury induced up regulation (n=6/group). In CCI-vehicle, sham and CCI-SR49059 groups, GFAP was 1.58±0.04, 0.47±0.02, and 0.81±0.03, respectively; V1aR was 1.00±0.06, 0.45±0.05, and 0.46±0.09; and AQP4 was 2.03± 0.34, 0.49±0.04, and 0.92±0.22. Confocal immunohistochemistry gave analogous results. In CCI-vehicle, sham and CCI-SR49059 groups, fluorescence intensity of GFAP was 349±38, 56±5, and 244±30, respectively, V1aR was 601±71, 117.8±14, and 390±76, and AQP4 was 818±117, 158±5, and 458±55 (n=3/group). The results support that edema was predominantly cellular following CCI and documented that V1aR inhibition with SR49059 suppressed injury-induced up regulation of GFAP, V1A and AQP4, blunting edematous changes. Our findings suggest V1aR inhibitors may be potential therapeutic tools to prevent cellular swelling and provide treatment for post-traumatic brain edema. PMID:24933327

Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice.

PubMed

Ma, Elise L; Smith, Allen D; Desai, Neemesh; Cheung, Lumei; Hanscom, Marie; Stoica, Bogdan A; Loane, David J; Shea-Donohue, Terez; Faden, Alan I

2017-11-01

Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury. Moderate-level TBI was induced in C57BL/6mice by controlled cortical impact (CCI). Mucosal barrier function was assessed by transepithelial resistance, fluorescent-labelled dextran flux, and quantification of tight junction proteins. Enteric glial cell number and activation were measured by Sox10 expression and GFAP reactivity, respectively. Separate groups of mice were challenged with Cr infection during the chronic phase of TBI, and host immune response, barrier integrity, enteric glial cell reactivity, and progression of brain injury and inflammation were assessed. Chronic CCI induced changes in colon morphology, including increased mucosal depth and smooth muscle thickening. At day 28 post-CCI, increased paracellular permeability and decreased claudin-1 mRNA and protein expression were observed in the absence of inflammation in the colon. Colonic glial cell GFAP and Sox10 expression were significantly increased 28days after brain injury. Clearance of Cr and upregulation of Th1/Th17 cytokines in the colon were unaffected by CCI; however, colonic paracellular flux and enteric glial cell GFAP expression were significantly increased. Importantly, Cr infection in chronically-injured mice worsened the brain lesion injury and increased astrocyte- and microglial-mediated inflammation. These experimental studies demonstrate chronic and bidirectional brain-gut interactions after TBI, which may negatively impact late outcomes after brain injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Adolescent Traumatic Brain Injury Induces Chronic Mesolimbic Neuroinflammation with Concurrent Enhancement in the Rewarding Effects of Cocaine in Mice during Adulthood.

PubMed

Merkel, Steven F; Razmpour, Roshanak; Lutton, Evan M; Tallarida, Christopher S; Heldt, Nathan A; Cannella, Lee Anne; Persidsky, Yuri; Rawls, Scott M; Ramirez, Servio H

2017-01-01

Clinical psychiatric disorders of depression, anxiety, and substance abuse are most prevalent after traumatic brain injury (TBI). Pre-clinical research has focused on depression and anxiety post-injury; however, virtually no data exist examining whether the preference for illicit drugs is affected by traumatic injury in the developing adolescent brain. Using the controlled cortical impact (CCI) model of TBI and the conditioned place preference (CPP) assay, we tested the underlying hypothesis that brain injury during adolescence exacerbates the rewarding properties of cocaine in adulthood possibly through an active inflammatory status in the mesolimbic pathway. Six-week old, C57BL/6 mice sustained a single CCI-TBI to the right somatosensory cortex. CPP experiments with cocaine began 2 weeks post-TBI. Animals receiving cocaine displayed significant place preference shifts compared to saline controls. Further, within the cocaine-experienced cohort, moderate CCI-TBI during adolescence significantly increased the preference shift in adulthood when compared to naïve controls. Additionally, persistent neuroinflammatory responses were observed in the cortex, nucleus accumbens (NAc), and ventral tegmental area post-CCI-TBI. Significant increases in both astrocytic, glial fibrillary acidic protein, and microglial, ionization basic acid 1, markers were observed in the NAc at the end of CPP testing. Moreover, analysis using focused array gene expression panels identified the upregulation of numerous inflammatory genes in moderate CCI-TBI animals, compared to naïve controls, both in the cortex and NAc at 2 weeks post-TBI, before onset of cocaine administration. These results suggest that sustaining moderate TBI during adolescence may augment the rewarding effects of psychostimulants in adulthood, possibly by induction of chronic mesolimbic neuroinflammation.

Polyphenols from Cymbopogon citratus leaves as topical anti-inflammatory agents.

PubMed

Costa, Gustavo; Ferreira, João Pinto; Vitorino, Carla; Pina, Maria Eugénia; Sousa, João José; Figueiredo, Isabel Vitória; Batista, Maria Teresa

2016-02-03

A variety of plant polyphenols have been reported to have anti-inflammatory, frequently associated with erythema, edema, hyperplasia, skin photoaging and photocarcinogenesis. Cymbopogon citratus (DC). Stapf (Poaceae) is a worldwide known medicinal plant, used in traditional medicine in inflammation-related conditions. In this work, the anti-inflammatory potential of C. citratus infusion (CcI) and its polyphenols as topical agents was evaluated in vivo. The plant extract was prepared and its fractioning led two polyphenol-rich fractions: flavonoids fraction (CcF) and tannins fraction (CcT). An oil/water emulsion was developed with each active (CcI, CcF+CcT and diclofenac), pH and texture having been evaluated. Release tests were further performed using static Franz diffusion cells and all collected samples were monitored by HPLC-PDA. In vivo topical anti-inflammatory activity evaluation was performed by the carrageenan-induced rat paw edema model. The texture analysis revealed statistically significant differences for all tested parameters to CcF+CcT, supporting its topical application. Release experiments lead to the detection of the phenolic compounds from each sample in the receptor medium and the six major flavonoids were quantified, by HPLC-PDA: carlinoside, isoorientin, cynaroside, luteolin 7-O-neohesperidoside, kurilesin A and cassiaoccidentalin B. The CcF+CcT formulation prompted to the higher release rate for all these flavonoids. CcI4%, CcI1% and CcF+CcT exhibited an edema reduction of 43.18, 29.55 and 59.09%, respectively. Our findings highlight that CcI, containing luteolin 7-O-neohesperidoside, cassiaoccidentalin B, carlinoside, cynaroside and tannins have a potential anti-inflammatory topical activity, suggesting their promising application in the treatment of skin inflammatory pathologies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of antioxidant, OPC-14117, on secondary cellular damage and behavioral deficits following cortical contusion in the rat.

PubMed

Aoyama, Naoki; Katayama, Yoichi; Kawamata, Tatsuro; Maeda, Takeshi; Mori, Tatsuro; Yamamoto, Takamitsu; Kikuchi, Tetsuro; Uwahodo, Yasuhumi

2002-05-03

In the present study, we examined the effects of OPC-14117, a superoxide radical scavenger, on the secondary cellular damage and cognitive dysfunction occurring in a rat model of cerebral contusion induced by a controlled cortical impact (CCI). Histological examinations revealed that the contusion necrosis volume reached 13.6+/-5.3 mm(3) in non-treated animals and declined to 1.9+/-0.6 mm(3) in OPC-14117-treated animals (P<0.01). The cell number of the CA3 region was 120.0+/-12.4 cells/mm in the normal controls, 73.6+/-9.9 cells/mm in the non-treated animals, and 111.2+/-10.2 cells/mm in the OPC-14117-treated animals, indicating that CCI-induced selective neuronal cell death in the CA3 region was attenuated by the OPC-14117 administration (P<0.01). The tissue osmolality, as determined with a vapor pressure osmometer, was 314.5+/-15.4 mmol/kg in the normal brain and increased to 426.0+/-20.1 mmol/kg at 12 h following CCI. The increase in tissue osmolality was significantly attenuated by OPC-14117 administration (P<0.01). The OPC-14117 administration also attenuated the CCI-induced cognitive deficits. The OPC-14117-treated animals showed a tendency to improve on the Morris water maze performance test. The impairment of the habituation of exploratory activity elicited by CCI was significantly attenuated by OPC-14117 administration (P<0.05). In conclusion, OPC-14117 may have a potential for decreasing secondary cellular damage due to traumatic brain injury since it is as efficacious as any other compound tested in this model.

Sleep Deprivation Aggravates Median Nerve Injury-Induced Neuropathic Pain and Enhances Microglial Activation by Suppressing Melatonin Secretion

PubMed Central

Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

2014-01-01

Study Objectives: Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Design: Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Participants: Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Measurements: Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. Results: In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Conclusions: Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. Citation: Huang CT, Chiang RP, Chen CL, Tsai YJ. Sleep deprivation aggravates median nerve injury-induced neuropathic pain and enhances microglial activation by suppressing melatonin secretion. SLEEP 2014;37(9):1513-1523. PMID:25142572

Mechanical Conflict System: A Novel Operant Method for the Assessment of Nociceptive Behavior

PubMed Central

Harte, Steven E.; Meyers, Jessica B.; Donahue, Renee R.; Taylor, Bradley K.; Morrow, Thomas J.

2016-01-01

A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor) in rats with neuropathic pain induced by constriction nerve injury (CCI) and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg), morphine (2.5 and 5 mg/kg), and the tachykinin NK1 receptor antagonist, RP 67580 (1 and 10 mg/kg). Results indicate that escape latency increased as a function of probe height in both naive and CCI rats. Pregabalin (10 and 30 mg/kg) and morphine (5 mg/kg), but not RP 67580, decreased latency to escape in CCI rats suggesting an antinociceptive effect. In contrast, morphine (10 mg/kg) but not pregabalin (30 mg/kg) increased escape latency in naive rats suggesting a possible anxiolytic action of morphine in response to light-induced fear. No order effects following multiple test sessions were observed. We conclude that the MCS is a valid method to assess behavioral signs of affective pain in rodents. PMID:26915030

Reference intervals and discrimination values of the Lanthony desaturated D-15 panel test in young to middle-aged Japanese army officials: the Okubo Color Study Report 1.

PubMed

Shoji, T; Sakurai, Y; Chihara, E; Nishikawa, S; Omae, K

2009-06-01

To better understand the reference values and adequate discrimination values of colour vision function with described quantitative systems for the Lanthony desaturated D-15 panel (D-15DS). A total of 1042 Japanese male officials were interviewed and underwent testing using Ishihara pseudoisochromatic plates, standard pseudoisochromatic plates part 2, and the D-15DS. The Farnsworth-Munsell (F-M) 100-hue test and the criteria of Verriest et al were used as definitive tests. Outcomes of the D-15DS were calculated using Bowman's Colour Confusion Index (CCI). The study design included two criteria. In criterion A, subjects with current or past ocular disease and a best-corrected visual acuity less than 0.7 on a decimal visual acuity chart were excluded. In criterion B, among subjects who satisfied criterion A, those who had a congenital colour sense anomaly were excluded. Overall, the 90th percentile (95th percentile) CCI values for criteria A and B in the worse eye were 1.70 (1.95) and 1.59 (1.73), respectively. In subjects satisfying criterion B, the area under the receiver operating characteristic curve was 0.951 (95% confidence interval, 0.931-0.971). The CCI discrimination values of 1.52 or 1.63 showed 90.3% sensitivity and 90% specificity, or 71.5% sensitivity and 95% specificity, respectively, for discriminating acquired colour vision impairment (ACVI). We provided the 90th and 95th percentiles in a young to middle-aged healthy population. The CCI is in good agreement with the diagnosis of ACVI. Our results could be helpful for using D-15DS for screening purposes.

Face-to-face comparison of the predictive validity of two models of neuropathic pain in the rat: analgesic activity of pregabalin, tramadol and duloxetine.

PubMed

Le Cudennec, Camille; Castagné, Vincent

2014-07-15

We compared the preclinical analgesic activity of three marketed drugs with different pharmacological properties, pregabalin, tramadol and duloxetine, described as effective against neuropathic pain in the clinic. These drugs were tested against evoked pain in two different neuropathic models in the rat, the Bennett (CCI) and the Chung (SNL) models. The selected endpoints were tactile allodynia, tactile hyperalgesia, heat hyperalgesia and cold allodynia. Although all three drugs displayed analgesic activity, the effects observed varied according to the behavioral evaluation. Pregabalin showed clear analgesic effects against cold allodynia and tactile hyperalgesia in both the CCI and Chung models. Tramadol was active against all four endpoints in the Chung model with similar effects in the CCI model, apart from tactile allodynia. Duloxetine inhibited tactile allodynia and heat hyperalgesia in both neuropathic pain models. It also displayed efficacy against tactile hyperalgesia in the CCI model and against cold allodynia in the Chung model. These data confirm that the CCI and the Chung models of neuropathic pain do not detect the activity of analgesics with the same sensitivity. Furthermore, the mode of stimulation (tactile or thermal) and the type of endpoint (allodynia or hyperalgesia) can further influence the observed efficacy of gold standards as well as novel compounds developed for treating neuropathic pain symptoms. Copyright © 2014. Published by Elsevier B.V.

Analyzing Conceptual Gains in Introductory Calculus with Interactively-Engaged Teaching Styles

ERIC Educational Resources Information Center

Thomas, Matthew

2013-01-01

This dissertation examines the relationship between an instructional style called Interactive-Engagement (IE) and gains on a measure of conceptual knowledge called the Calculus Concept Inventory (CCI). The data comes from two semesters of introductory calculus courses (Fall 2010 and Spring 2011), consisting of a total of 482 students from the…

Cloud property datasets retrieved from AVHRR, MODIS, AATSR and MERIS in the framework of the Cloud_cci project

NASA Astrophysics Data System (ADS)

Stengel, Martin; Stapelberg, Stefan; Sus, Oliver; Schlundt, Cornelia; Poulsen, Caroline; Thomas, Gareth; Christensen, Matthew; Carbajal Henken, Cintia; Preusker, Rene; Fischer, Jürgen; Devasthale, Abhay; Willén, Ulrika; Karlsson, Karl-Göran; McGarragh, Gregory R.; Proud, Simon; Povey, Adam C.; Grainger, Roy G.; Fokke Meirink, Jan; Feofilov, Artem; Bennartz, Ralf; Bojanowski, Jedrzej S.; Hollmann, Rainer

2017-11-01

New cloud property datasets based on measurements from the passive imaging satellite sensors AVHRR, MODIS, ATSR2, AATSR and MERIS are presented. Two retrieval systems were developed that include components for cloud detection and cloud typing followed by cloud property retrievals based on the optimal estimation (OE) technique. The OE-based retrievals are applied to simultaneously retrieve cloud-top pressure, cloud particle effective radius and cloud optical thickness using measurements at visible, near-infrared and thermal infrared wavelengths, which ensures spectral consistency. The retrieved cloud properties are further processed to derive cloud-top height, cloud-top temperature, cloud liquid water path, cloud ice water path and spectral cloud albedo. The Cloud_cci products are pixel-based retrievals, daily composites of those on a global equal-angle latitude-longitude grid, and monthly cloud properties such as averages, standard deviations and histograms, also on a global grid. All products include rigorous propagation of the retrieval and sampling uncertainties. Grouping the orbital properties of the sensor families, six datasets have been defined, which are named AVHRR-AM, AVHRR-PM, MODIS-Terra, MODIS-Aqua, ATSR2-AATSR and MERIS+AATSR, each comprising a specific subset of all available sensors. The individual characteristics of the datasets are presented together with a summary of the retrieval systems and measurement records on which the dataset generation were based. Example validation results are given, based on comparisons to well-established reference observations, which demonstrate the good quality of the data. In particular the ensured spectral consistency and the rigorous uncertainty propagation through all processing levels can be considered as new features of the Cloud_cci datasets compared to existing datasets. In addition, the consistency among the individual datasets allows for a potential combination of them as well as facilitates studies on the impact of temporal sampling and spatial resolution on cloud climatologies.

For each dataset a digital object identifier has been issued:

Cloud_cci AVHRR-AM: https://doi.org/10.5676/DWD/ESA_Cloud_cci/AVHRR-AM/V002

Cloud_cci AVHRR-PM: https://doi.org/10.5676/DWD/ESA_Cloud_cci/AVHRR-PM/V002

Cloud_cci MODIS-Terra: https://doi.org/10.5676/DWD/ESA_Cloud_cci/MODIS-Terra/V002

Cloud_cci MODIS-Aqua: https://doi.org/10.5676/DWD/ESA_Cloud_cci/MODIS-Aqua/V002

Cloud_cci ATSR2-AATSR: https://doi.org/10.5676/DWD/ESA_Cloud_cci/ATSR2-AATSR/V002

Cloud_cci MERIS+AATSR: https://doi.org/10.5676/DWD/ESA_Cloud_cci/MERIS+AATSR/V002

Mobile technology intervention to improve care coordination between HIV and substance use treatment providers: development, training, and evaluation protocol.

PubMed

Claborn, Kasey; Becker, Sara; Ramsey, Susan; Rich, Josiah; Friedmann, Peter D

2017-03-14

People living with HIV (PLWH) with a substance use disorder (SUD) tend to receive inadequate medical care in part because of a siloed healthcare system in which HIV and substance use services are delivered separately. Ideal treatment requires an interdisciplinary, team-based coordinated care approach, but many structural and systemic barriers impede the integration of HIV and SUD services. The current protocol describes the development and preliminary evaluation of a care coordination intervention (CCI), consisting of a tablet-based mobile platform for HIV and SUD treatment providers, an interagency communication protocol, and a training protocol. We hypothesize that HIV and SUD treatment providers will find the CCI to be acceptable, and that after receipt of the CCI, providers will: exhibit higher retention in dual care among patients, report increased frequency and quality of communication, and report increased rates of relational coordination. A three phase approach is used to refine and evaluate the CCI. Phase 1 consists of in-depth qualitative interviews with 8 key stakeholders as well as clinical audits of participating HIV and SUD treatment agencies. Phase 2 contains functionality testing of the mobile platform with frontline HIV and SUD treatment providers, followed by refinement of the CCI. Phase 3 consists of a pre-, post-test trial with 30 SUD and 30 HIV treatment providers. Data will be collected at the provider, organization, and patient levels. Providers will complete assessments at baseline, immediately post-training, and at 1-, 3-, and 6-months post-training. Organizational data will be collected at baseline, 1-, 3-, and 6-months post training, while patient data will be collected at baseline and 6-months post training. This study will develop and evaluate a CCI consisting of a tablet-based mobile platform for treatment providers, an interagency communication protocol, and a training protocol as a means of improving the integration of care for PLWH who have a SUD. Results have the potential to advance the field by bridging gaps in a fragmented healthcare system, and improving treatment efficiency, work flow, and communication among interdisciplinary providers from different treatment settings. NCT02906215.

Systemic administration of vitamins C and E attenuates nociception induced by chronic constriction injury of the sciatic nerve in rats.

PubMed

Riffel, Ana Paula K; de Souza, Jéssica A; Santos, Maria do Carmo Q; Horst, Andréa; Scheid, Taína; Kolberg, Carolina; Belló-Klein, Adriane; Partata, Wania A

2016-03-01

Antioxidants have been tested to treat neuropathic pain, and α-Tocopherol (vitamin E--vit. E) and ascorbic acid (vitamin C--vit. C) are potent antioxidants. We assessed the effect of intraperitoneal administration of vit. C (30 mg/kg/day) and vit. E (15 mg/kg/day), given alone or in combination, on the mechanical and thermal thresholds and the sciatic functional index (SFI) in rats with chronic constriction injury (CCI) of the sciatic nerve. We also determined the lipid hydroperoxides and total antioxidant capacity (TAC) in the injured sciatic nerve. Further, we assessed the effects of oral administration of vit. C+vit. E (vit. C+E) and of a combination of vit. C+E and gabapentin (100mg/kg/day, i.p.) on the mechanical and thermal thresholds of CCI rats. The vitamins, whether administered orally or i.p., attenuated the reductions in the mechanical and thermal thresholds induced by CCI. The antinociceptive effect was greater with a combination of vit. C+E than with each vitamin given alone. The SFI was also improved in vitamin-treated CCI rats. Co-administration of vit. C+E and gabapentin induced a greater antinociceptive effect than gabapentin alone. No significant change occurred in TAC and lipid hydroperoxide levels, but TAC increased (45%) while lipid hydroperoxides decreased (38%) in the sciatic nerve from vit. C+E-treated CCI rats. Thus, treatment with a combination of vit. C+E was more effective to treat CCI-induced neuropathic pain than vitamins alone, and the antinociceptive effect was greater with co-administration of vit. C+E and gabapentin than with gabapentin alone. Copyright © 2016 Elsevier Inc. All rights reserved.

Combining glial cell line-derived neurotrophic factor gene delivery (AdGDNF) with L-arginine decreases contusion size but not behavioral deficits after traumatic brain injury.

PubMed

Degeorge, M L; Marlowe, D; Werner, E; Soderstrom, K E; Stock, M; Mueller, A; Bohn, M C; Kozlowski, D A

2011-07-27

Our laboratory has previously demonstrated that viral administration of glial cell line-derived neurotrophic factor (AdGDNF), one week prior to a controlled cortical impact (CCI) over the forelimb sensorimotor cortex of the rat (FL-SMC) is neuroprotective, but does not significantly enhance recovery of sensorimotor function. One possible explanation for this discrepancy is that although protected, neurons may not have been functional due to enduring metabolic deficiencies. Additionally, metabolic events following TBI may interfere with expression of therapeutic proteins administered to the injured brain via gene therapy. The current study focused on enhancing the metabolic function of the brain by increasing cerebral blood flow (CBF) with l-arginine in conjunction with administration of AdGDNF immediately following CCI. An adenoviral vector harboring human GDNF was injected unilaterally into FL-SMC of the rat immediately following a unilateral CCI over the FL-SMC. Within 30min of the CCI and AdGDNF injections, some animals were injected with l-arginine (i.v.). Tests of forelimb function and asymmetry were administered for 4weeks post-injury. Animals were sacrificed and contusion size and GDNF protein expression measured. This study demonstrated that rats treated with AdGDNF and l-arginine post-CCI had a significantly smaller contusion than injured rats who did not receive any treatment, or injured rats treated with either AdGDNF or l-arginine alone. Nevertheless, no amelioration of behavioral deficits was seen. These findings suggest that AdGDNF alone following a CCI was not therapeutic and although combining it with l-arginine decreased contusion size, it did not enhance behavioral recovery. Copyright © 2011 Elsevier B.V. All rights reserved.

Lipopolysaccharide-mediated inflammatory priming potentiates painful post-traumatic trigeminal neuropathy.

PubMed

Boucher, Yves; Moreau, Nathan; Mauborgne, Annie; Dieb, Wisam

2018-06-18

We explored the molecular and behavioral effects of a perineural Lipopolysaccharide (LPS)-mediated inflammatory priming on the development and maintenance of painful post-traumatic trigeminal neuropathy (PPTTN) following infra-orbital nerve chronic constriction injury (CCI-IoN) in rats. Rats were pretreated with repetitive perineural injections in the vicinity of the IoN of either LPS or vehicle (Vhcl) before being submitted to CCI-IoN. Orofacial pain-like behaviors (response to Von Frey Filament testing and spontaneous isolated face grooming) were measured during the period of LPS injections (three weeks) and following CCI-IoN surgery (two weeks). Local LPS administration induced an early pain-like behavior (i.e. an increase in spontaneous pain [SP] or mechanical static allodynia [MSA]) in both conditions, and following CCI-IoN, MSA and SP developed earlier and more severely in LPS-pretreated rats than in the control group. Ipsilateral increases of key neuropathic pain mRNA markers in the IoN parenchyma, trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) were observed in CCI-IoN injured animals as compared to controls. Although no significant molecular differences could be observed within the IoN parenchyma between LPS and Vhcl-pretreated animals, a significant increase of key inflammatory cytokine Interleukin 1 beta (IL - 1β) could be found in the TG of LPS-pretreated CCI-injured animals versus controls. Finally, a higher increase of inducible nitric oxide synthase (iNOS) in ipsilateral Sp5C of LPS-pretreated animals was observed as compared to Sp5C of Vhcl-pretreated animals. These results suggest a key role of inflammatory priming in the development and maintenance of PPTTN implicating IL-1β/iNOS-dependent central sensitization mechanisms. Copyright © 2018. Published by Elsevier Inc.

Deficits in novelty exploration after controlled cortical impact.

PubMed

Wagner, Amy K; Postal, Brett A; Darrah, Shaun D; Chen, Xiangbai; Khan, Amina S

2007-08-01

Experimental models of traumatic brain injury (TBI) have been utilized to characterize the behavioral derangements associated with brain trauma. Several studies exist characterizing motor function in the controlled cortical impact (CCI) injury model of TBI, but less research has focused on how CCI affects exploratory behavior. The goal of this study was to characterize deficits in three novelty exploration tasks after the CCI. Under anesthesia, 37 adult male Sprague Dawley rats received CCI (2.7 mm and 2.9 mm; 4 m/sec) over the right parietal cortex or sham surgery. For days 1-6 post-surgery, the beam balance and beam walking tasks were used to assess motor deficits. The Open Field, Y-Maze, and Free Choice Novelty (FCN) tasks were used to measure exploratory deficits from days 7-14 post-surgery. Injured rats displayed a significant, but transient, deficit on each motor task (p < 0.0001). Open Field results showed that injured rats had lower activity levels than shams (p < 0.0001), displayed less habituation to the task, and had more anxiety related behaviors (thigmotaxis) across days (p < 0.0001). Y-maze results suggest that injured rats spent less time in the novel arm versus the familiar arms when compared to shams (p < 0.0001). For FCN, injured rats were less active (p < 0.05) and spent less time and had fewer interactions with objects in the novel environment compared to shams (p < 0.05). These results suggest that several ethological factors contribute to exploratory deficits after CCI and can be effectively characterized with the behavioral tasks described. Future work will utilize these tasks to evaluate the neural substrates underlying exploratory deficits after TBI.

Ice_Sheets_CCI: Essential Climate Variables for the Greenland Ice Sheet

NASA Astrophysics Data System (ADS)

Forsberg, R.; Sørensen, L. S.; Khan, A.; Aas, C.; Evansberget, D.; Adalsteinsdottir, G.; Mottram, R.; Andersen, S. B.; Ahlstrøm, A.; Dall, J.; Kusk, A.; Merryman, J.; Hvidberg, C.; Khvorostovsky, K.; Nagler, T.; Rott, H.; Scharrer, M.; Shepard, A.; Ticconi, F.; Engdahl, M.

2012-04-01

As part of the ESA Climate Change Initiative (www.esa-cci.org) a long-term project "ice_sheets_cci" started January 1, 2012, in addition to the existing 11 projects already generating Essential Climate Variables (ECV) for the Global Climate Observing System (GCOS). The "ice_sheets_cci" goal is to generate a consistent, long-term and timely set of key climate parameters for the Greenland ice sheet, to maximize the impact of European satellite data on climate research, from missions such as ERS, Envisat and the future Sentinel satellites. The climate parameters to be provided, at first in a research context, and in the longer perspective by a routine production system, would be grids of Greenland ice sheet elevation changes from radar altimetry, ice velocity from repeat-pass SAR data, as well as time series of marine-terminating glacier calving front locations and grounding lines for floating-front glaciers. The ice_sheets_cci project will involve a broad interaction of the relevant cryosphere and climate communities, first through user consultations and specifications, and later in 2012 optional participation in "best" algorithm selection activities, where prototype climate parameter variables for selected regions and time frames will be produced and validated using an objective set of criteria ("Round-Robin intercomparison"). This comparative algorithm selection activity will be completely open, and we invite all interested scientific groups with relevant experience to participate. The results of the "Round Robin" exercise will form the algorithmic basis for the future ECV production system. First prototype results will be generated and validated by early 2014. The poster will show the planned outline of the project and some early prototype results.

Change Is Here: ADEA CCI 2.0-A Learning Community for the Advancement of Dental Education.

PubMed

Palatta, Anthony M; Kassebaum, Denise K; Gadbury-Amyot, Cynthia C; Karimbux, Nadeem Y; Licari, Frank W; Nadershahi, Nader A; Walji, Muhammad F; Stewart, Jeffery C B; Valachovic, Richard W

2017-06-01

On May 12, 2005, the inaugural meeting of the American Dental Education Association Commission on Change and Innovation in Dental Education (ADEA CCI) was convened. Comprised of thought leaders representative of dental education and practice, the ADEA CCI published groundbreaking white papers that effectively helped bring dental education across the threshold of the 21st century. Twelve years later, a new ADEA CCI has been convened-ADEA CCI 2.0. The ADEA CCI 2.0 is a broad-ranging, strategically interconnected, flexible, and multifarious community of stakeholders situated within and across all facets of oral health education and practice. Whereas the first iteration of the ADEA CCI made the case for change regarding revisions of the dental curriculum and learning environment, the ADEA CCI 2.0 will focus on external domains that are having a global impact on the content and delivery of health care and health professions education and, ultimately, how health care benefits people. The principal work of the ADEA CCI 2.0 will be to create educational and implementation resources and opportunities for dental educators to contemplate, investigate, and ultimately define the future needs of their academic dental institutions in this constantly changing world.

Selective vasopressin-1a receptor antagonist prevents brain edema, reduces astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic brain injury.

PubMed

Marmarou, Christina R; Liang, Xiuyin; Abidi, Naqeeb H; Parveen, Shanaz; Taya, Keisuke; Henderson, Scott C; Young, Harold F; Filippidis, Aristotelis S; Baumgarten, Clive M

2014-09-18

A secondary and often lethal consequence of traumatic brain injury is cellular edema that we posit is due to astrocytic swelling caused by transmembrane water fluxes augmented by vasopressin-regulated aquaporin-4 (AQP4). We therefore tested whether vasopressin 1a receptor (V1aR) inhibition would suppress astrocyte AQP4, reduce astrocytic edema, and thereby diminish TBI-induced edematous changes. V1aR inhibition by SR49059 significantly reduced brain edema after cortical contusion injury (CCI) in rat 5h post-injury. Injured-hemisphere brain water content (n=6 animals/group) and astrocytic area (n=3/group) were significantly higher in CCI-vehicle (80.5±0.3%; 18.0±1.4 µm(2)) versus sham groups (78.3±0.1%; 9.5±0.9 µm(2)), and SR49059 blunted CCI-induced increases in brain edema (79.0±0.2%; 9.4±0.8µm(2)). CCI significantly up-regulated GFAP, V1aR and AQP4 protein levels and SR49059 suppressed injury induced up regulation (n=6/group). In CCI-vehicle, sham and CCI-SR49059 groups, GFAP was 1.58±0.04, 0.47±0.02, and 0.81±0.03, respectively; V1aR was 1.00±0.06, 0.45±0.05, and 0.46±0.09; and AQP4 was 2.03±0.34, 0.49±0.04, and 0.92±0.22. Confocal immunohistochemistry gave analogous results. In CCI-vehicle, sham and CCI-SR49059 groups, fluorescence intensity of GFAP was 349±38, 56±5, and 244±30, respectively, V1aR was 601±71, 117.8±14, and 390±76, and AQP4 was 818±117, 158±5, and 458±55 (n=3/group). The results support that edema was predominantly cellular following CCI and documented that V1aR inhibition with SR49059 suppressed injury-induced up regulation of GFAP, V1A and AQP4, blunting edematous changes. Our findings suggest V1aR inhibitors may be potential therapeutic tools to prevent cellular swelling and provide treatment for post-traumatic brain edema. Copyright © 2014 Elsevier B.V. All rights reserved.

Anaemia worsens early functional outcome after traumatic brain injury: a preliminary study.

PubMed

Litofsky, N Scott; Miller, Douglas C; Chen, Zhenzhou; Simonyi, Agnes; Klakotskaia, Diana; Giritharan, Andrew; Feng, Qi; McConnell, Diane; Cui, Jiankun; Gu, Zezong

2018-01-01

To determine early effects on outcome from traumatic brain injury (TBI) induced by controlled cortical impact (CCI) associated with anaemia in mice. Outcome from TBI with concomitant anaemia would be worse than TBI without anaemia. CCI was induced with electromagnetic impaction in four groups of C57BL/6J mice: sham, sham+anaemia; TBI; and TBI+anaemia. Anaemia was created by withdrawal of 30% of calculated intravascular blood volume and saline replacement of equal volume. Functional outcome was assessed by beam-walking test and open field test (after pre-injury training) on post-injury days 3 and 7. After functional assessment, brains removed from sacrificed animals were pathological reviewed with haematoxylin and eosin, cresyl violet, Luxol Fast Blue, and IBA-1 immunostains. Beam-walking was similar between animals with TBI and TBI+anaemia (p = 0.9). In open field test, animals with TBI+anaemia walked less distance than TBI alone or sham animals on days 3 (p < 0.001) and 7 (p < 0.05), indicating less exploratory and locomotion behaviours. No specific pathologic differences could be identified. Anaemia associated with TBI from CCI is associated with worse outcome as measured by less distance travelled in the open field test at three days than if anaemia is not present.

Nociceptive Neuropeptide Increases and Periorbital Allodynia in a Model of Traumatic Brain Injury

PubMed Central

Elliott, Melanie B.; Oshinsky, Michael L.; Amenta, Peter S.; Awe, Olatilewa O.; Jallo, Jack I.

2014-01-01

Objective This study tests the hypothesis that injury to the somatosensory cortex is associated with periorbital allodynia and increases in nociceptive neuropeptides in the brainstem in a mouse model of controlled cortical impact (CCI) injury. Methods Male C57BL/6 mice received either CCI or craniotomy-only followed by weekly periorbital von Frey (mechanical) sensory testing for up to 28 days post-injury. Mice receiving an incision only and naïve mice were included as control groups. Changes in calcitonin gene-related peptide (CGRP) and substance P (SP) within the brainstem were determined using enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Activation of ionized calcium-binding adaptor molecule-1–labeled macrophages/microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes were evaluated using immunohistochemistry because of their potential involvement in nociceptor sensitization. Results Incision-only control mice showed no changes from baseline periorbital von Frey mechanical thresholds. CCI significantly reduced mean periorbital von Frey thresholds (periorbital allodynia) compared with baseline and craniotomy-only at each endpoint, analysis of variance P < .0001. Craniotomy significantly reduced periorbital threshold at 14 days but not 7, 21, or 28 days compared with baseline threshold, P < .01. CCI significantly increased SP immunoreactivity in the brainstem at 7 and 14 days but not 28 days compared with craniotomy-only and controls, P < .001. CGRP levels in brainstem tissues were significantly increased in CCI groups compared with controls (incision-only and naïve mice) or craniotomy-only mice at each endpoint examined, P < .0001. There was a significant correlation between CGRP and periorbital allodynia (P < .0001, r = −0.65) but not for SP (r = 0.20). CCI significantly increased the number of macrophage/microglia in the injured cortex at each endpoint up to 28 days, although cell numbers declined over weeks post-injury, P < .001. GFAP+ immunoreactivity was significantly increased at 7 but not 14 or 28 days after CCI, P < .001. Craniotomy resulted in transient periorbital allodynia accompanied by transient increases in SP, CGRP, and GFAP immunoreactivity compared with control mice. There was no increase in the number of macrophage/microglia cells compared with controls after craniotomy. Conclusion Injury to the somatosensory cortex results in persistent periorbital allodynia and increases in brainstem nociceptive neuropeptides. Findings suggest that persistent allodynia and increased neuropeptides are maintained by mechanisms other than activation of macrophage/microglia or astrocyte in the injured somatosensory cortex. PMID:22568499

Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury.

PubMed

Robinson, Shenandoah; Winer, Jesse L; Berkner, Justin; Chan, Lindsay A S; Denson, Jesse L; Maxwell, Jessie R; Yang, Yirong; Sillerud, Laurel O; Tasker, Robert C; Meehan, William P; Mannix, Rebekah; Jantzie, Lauren L

2016-06-01

OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes. METHODS With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U/kg/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1-4, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13-28) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction. RESULTS Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst-like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for αII-spectrin (αII-SDPs; p < 0.001), potassium chloride cotransporter 2 (KCC2-DPs; p = 0.037), and glial fibrillary acidic protein (GFAP-DPs; p = 0.002), as well as serum GFAP (serum GFAP-DPs; p = 0.001). In injured rats multiplex electrochemiluminescence analyses on PID3 revealed elevated serum tumor necrosis factor alpha (TNFα p = 0.01) and chemokine (CXC) ligand 1 (CXCL1). Chronically, that is, in PID13-16 CCI-veh rats, as compared with sham rats, gait deficits were demonstrated (p = 0.033) but then were reversed (p = 0.022) with EPO treatment. Diffusion tensor MRI of the ipsilateral and contralateral cortex and white matter in PID16-23 CCI-veh rats showed widespread injury and significant abnormalities of functional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD); MD, AD, and RD improved after EPO treatment. Chronically, P13-P28 CCI-veh rats also had elevated serum CXCL1 levels, which normalized in CCI-EPO rats. CONCLUSIONS Efficient translation of emerging neuro-reparative interventions dictates the use of age-appropriate preclinical models with human clinical trial-compatible biomarkers. In the present study, the authors showed that CCI produced chronic gait deficits in P12 rats that resolved with EPO treatment and that chronic imaging and serum biomarkers correlated with this improvement.

Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV.

PubMed

Saussele, Susanne; Krauss, Marie-Paloma; Hehlmann, Rüdiger; Lauseker, Michael; Proetel, Ulrike; Kalmanti, Lida; Hanfstein, Benjamin; Fabarius, Alice; Kraemer, Doris; Berdel, Wolfgang E; Bentz, Martin; Staib, Peter; de Wit, Maike; Wernli, Martin; Zettl, Florian; Hebart, Holger F; Hahn, Markus; Heymanns, Jochen; Schmidt-Wolf, Ingo; Schmitz, Norbert; Eckart, Michael J; Gassmann, Winfried; Bartholomäus, Andrea; Pezzutto, Antonio; Leibundgut, Elisabeth Oppliger; Heim, Dominik; Krause, Stefan W; Burchert, Andreas; Hofmann, Wolf-Karsten; Hasford, Joerg; Hochhaus, Andreas; Pfirrmann, Markus; Müller, Martin C

2015-07-02

We studied the influence of comorbidities on remission rate and overall survival (OS) in patients with chronic myeloid leukemia (CML). Participants of the CML Study IV, a randomized 5-arm trial designed to optimize imatinib therapy, were analyzed for comorbidities at diagnosis using the Charlson Comorbidity Index (CCI); 511 indexed comorbidities were reported in 1519 CML patients. Age was an additional risk factor in 863 patients. Resulting CCI scores were as follows: CCI 2, n = 589; CCI 3 or 4, n = 599; CCI 5 or 6, n = 229; and CCI ≥ 7, n = 102. No differences in cumulative incidences of accelerated phase, blast crisis, or remission rates were observed between patients in the different CCI groups. Higher CCI was significantly associated with lower OS probabilities. The 8-year OS probabilities were 93.6%, 89.4%, 77.6%, and 46.4% for patients with CCI 2, 3 to 4, 5 to 6, and ≥7, respectively. In multivariate analysis, CCI was the most powerful predictor of OS, which was still valid after removal of its age-related components. Comorbidities have no impact on treatment success but do have a negative effect on OS, indicating that survival of patients with CML is determined more by comorbidities than by CML itself. OS may therefore be inappropriate as an outcome measure for specific CML treatments. The trial was registered at www.clinicaltrials.gov as #NCT00055874. © 2015 by The American Society of Hematology.

Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML Study IV

PubMed Central

Krauß, Marie-Paloma; Hehlmann, Rüdiger; Lauseker, Michael; Proetel, Ulrike; Kalmanti, Lida; Hanfstein, Benjamin; Fabarius, Alice; Kraemer, Doris; Berdel, Wolfgang E.; Bentz, Martin; Staib, Peter; de Wit, Maike; Wernli, Martin; Zettl, Florian; Hebart, Holger F.; Hahn, Markus; Heymanns, Jochen; Schmidt-Wolf, Ingo; Schmitz, Norbert; Eckart, Michael J.; Gassmann, Winfried; Bartholomäus, Andrea; Pezzutto, Antonio; Leibundgut, Elisabeth Oppliger; Heim, Dominik; Krause, Stefan W.; Burchert, Andreas; Hofmann, Wolf-Karsten; Hasford, Joerg; Hochhaus, Andreas; Pfirrmann, Markus; Müller, Martin C.

2015-01-01

We studied the influence of comorbidities on remission rate and overall survival (OS) in patients with chronic myeloid leukemia (CML). Participants of the CML Study IV, a randomized 5-arm trial designed to optimize imatinib therapy, were analyzed for comorbidities at diagnosis using the Charlson Comorbidity Index (CCI); 511 indexed comorbidities were reported in 1519 CML patients. Age was an additional risk factor in 863 patients. Resulting CCI scores were as follows: CCI 2, n = 589; CCI 3 or 4, n = 599; CCI 5 or 6, n = 229; and CCI ≥ 7, n = 102. No differences in cumulative incidences of accelerated phase, blast crisis, or remission rates were observed between patients in the different CCI groups. Higher CCI was significantly associated with lower OS probabilities. The 8-year OS probabilities were 93.6%, 89.4%, 77.6%, and 46.4% for patients with CCI 2, 3 to 4, 5 to 6, and ≥7, respectively. In multivariate analysis, CCI was the most powerful predictor of OS, which was still valid after removal of its age-related components. Comorbidities have no impact on treatment success but do have a negative effect on OS, indicating that survival of patients with CML is determined more by comorbidities than by CML itself. OS may therefore be inappropriate as an outcome measure for specific CML treatments. The trial was registered at www.clinicaltrials.gov as #NCT00055874. PMID:25918346

Could an endoneurial endothelial crosstalk between Wnt/β-catenin and Sonic Hedgehog pathways underlie the early disruption of the infra-orbital blood-nerve barrier following chronic constriction injury?

PubMed

Moreau, Nathan; Mauborgne, Annie; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette B; Villanueva, Luis; Pohl, Michel; Boucher, Yves

2017-01-01

Blood–nerve barrier disruption is pivotal in the development of neuroinflammation, peripheral sensitization, and neuropathic pain after peripheral nerve injury. Activation of toll-like receptor 4 and inactivation of Sonic Hedgehog signaling pathways within the endoneurial endothelial cells are key events, resulting in the infiltration of harmful molecules and immunocytes within the nerve parenchyma. However, we showed in a previous study that preemptive inactivation of toll-like receptor 4 signaling or sustained activation of Sonic Hedgehog signaling did not prevent the local alterations observed following peripheral nerve injury, suggesting the implication of another signaling pathway. Using a classical neuropathic pain model, the infraorbital nerve chronic constriction injury (IoN-CCI), we investigated the role of the Wnt/β-catenin pathway in chronic constriction injury-mediated blood–nerve barrier disruption and in its interactions with the toll-like receptor 4 and Sonic Hedgehog pathways. In the IoN-CCI model versus control, mRNA expression levels and/or immunochemical detection of major Wnt/Sonic Hedgehog pathway (Frizzled-7, vascular endothelial-cadherin, Patched-1 and Gli-1) and/or tight junction proteins (Claudin-1, Claudin-5, and Occludin) readouts were assessed. Vascular permeability was assessed by sodium fluorescein extravasation. IoN-CCI induced early alterations in the vascular endothelial-cadherin/β-catenin/Frizzled-7 complex, shown to participate in local blood–nerve barrier disruption via a β-catenin-dependent tight junction protein downregulation. Wnt pathway also mediated a crosstalk between toll-like receptor 4 and Sonic Hedgehog signaling within endoneurial endothelial cells. Nevertheless, preemptive inhibition of Wnt/β-catenin signaling before IoN-CCI could not prevent the downregulation of key Sonic Hedgehog pathway readouts or the disruption of the infraorbital blood–nerve barrier, suggesting that Sonic Hedgehog pathway inhibition observed following IoN-CCI is an independent event responsible for blood–nerve barrier disruption. A crosstalk between Wnt/β-catenin- and Sonic Hedgehog-mediated signaling pathways within endoneurial endothelial cells could mediate the chronic disruption of the blood–nerve barrier following IoN-CCI, resulting in increased irreversible endoneurial vascular permeability and neuropathic pain development.

Quantifying nonhomogeneous colors in agricultural materials part I: method development.

PubMed

Balaban, M O

2008-11-01

Measuring the color of food and agricultural materials using machine vision (MV) has advantages not available by other measurement methods such as subjective tests or use of color meters. The perception of consumers may be affected by the nonuniformity of colors. For relatively uniform colors, average color values similar to those given by color meters can be obtained by MV. For nonuniform colors, various image analysis methods (color blocks, contours, and "color change index"[CCI]) can be applied to images obtained by MV. The degree of nonuniformity can be quantified, depending on the level of detail desired. In this article, the development of the CCI concept is presented. For images with a wide range of hue values, the color blocks method quantifies well the nonhomogeneity of colors. For images with a narrow hue range, the CCI method is a better indicator of color nonhomogeneity.

Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury.

PubMed

Geddes, Rastafa I; Hayashi, Kentaro; Bongers, Quinn; Wehber, Marlyse; Anderson, Icelle M; Jansen, Alex D; Nier, Chase; Fares, Emily; Farquhar, Gabrielle; Kapoor, Amita; Ziegler, Toni E; VadakkadathMeethal, Sivan; Bird, Ian M; Atwood, Craig S

2017-01-01

Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA) are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T) biosynthesis, which is known to diminish traumatic brain injury (TBI)-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5-6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17)) or Sham injury (craniectomy alone; n = 12) and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16) or saline (n = 13) every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4) by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068), T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p < 0.05), 11-deoxycorticosterone (11-DOC) by 37.5% (from 289.3 ± 42.0 ng/mL to 180.7 ± 3.3 ng/mL), and corticosterone by 50.8% (from 195.1 ± 22.4 ng/mL to 95.9 ± 2.2 ng/mL), by post-surgery day 1. CCI injury induced similar declines in P4, T, 11-DOC and corticosterone (58.9%, 74.6%, 39.4% and 24.6%, respectively) by post-surgery day 1. These results suggest that both Sham surgery and CCI injury induce hypogonadism and hypoadrenalism in adult male rats. CLA treatment did not reverse hypogonadism in Sham (P4: 2.5 ± 1.0 ng/mL; T: 0.9 ± 0.2 ng/mL) or CCI-injured (P4: 2.2 ± 0.9 ng/mL; T: 1.0 ± 0.2 ng/mL, p > 0.05) animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL) and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL) animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s) compared to saline treated Sham animals (8.8 ± 1.7 s). In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s) compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05). These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1) does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse craniectomy- and craniectomy + CCI-induced hypoadrenalism, 2) is detrimental to medium- and long-term spatial learning and memory in craniectomized uninjured rats, 3) limits cognitive recovery following a moderate-severe CCI injury, and 4) does not alter body weight.

Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury

PubMed Central

Geddes, Rastafa I.; Hayashi, Kentaro; Bongers, Quinn; Wehber, Marlyse; Anderson, Icelle M.; Jansen, Alex D.; Nier, Chase; Fares, Emily; Farquhar, Gabrielle; Kapoor, Amita; Ziegler, Toni E.; VadakkadathMeethal, Sivan; Bird, Ian M.

2017-01-01

Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA) are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T) biosynthesis, which is known to diminish traumatic brain injury (TBI)-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5–6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17)) or Sham injury (craniectomy alone; n = 12) and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16) or saline (n = 13) every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4) by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068), T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p < 0.05), 11-deoxycorticosterone (11-DOC) by 37.5% (from 289.3 ± 42.0 ng/mL to 180.7 ± 3.3 ng/mL), and corticosterone by 50.8% (from 195.1 ± 22.4 ng/mL to 95.9 ± 2.2 ng/mL), by post-surgery day 1. CCI injury induced similar declines in P4, T, 11-DOC and corticosterone (58.9%, 74.6%, 39.4% and 24.6%, respectively) by post-surgery day 1. These results suggest that both Sham surgery and CCI injury induce hypogonadism and hypoadrenalism in adult male rats. CLA treatment did not reverse hypogonadism in Sham (P4: 2.5 ± 1.0 ng/mL; T: 0.9 ± 0.2 ng/mL) or CCI-injured (P4: 2.2 ± 0.9 ng/mL; T: 1.0 ± 0.2 ng/mL, p > 0.05) animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL) and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL) animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s) compared to saline treated Sham animals (8.8 ± 1.7 s). In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s) compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05). These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1) does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse craniectomy- and craniectomy + CCI-induced hypoadrenalism, 2) is detrimental to medium- and long-term spatial learning and memory in craniectomized uninjured rats, 3) limits cognitive recovery following a moderate-severe CCI injury, and 4) does not alter body weight. PMID:28125600

Sealing behavior of Container Closure Systems under Frozen Storage Conditions: Nonlinear Finite Element Simulation of Serum Rubber Stoppers.

PubMed

Nieto, Alejandra; Roehl, Holger

2018-03-15

There has been a growing interest in recent years in the assessment of suitable vial/stopper combinations for storage and shipment of frozen drug products. Considering that the glass transition temperature (Tg) of butyl rubber stoppers used in Container Closure Systems (CCS) is between -55°C to -65°C, a storage or shipment temperature of a frozen product below the Tg of the rubber stopper, may require special attention, since below the Tg the rubber becomes more plastic-like and loses its elastic (sealing) characteristics. Thus they risk maintaining Container Closure Integrity (CCI). Given that the rubber regains its elastic properties and reseals after rewarming to ambient temperature, leaks during frozen temperature storage and transportation are transient and the CCI methods used at room temperature conditions are unable to confirm CCI in the frozen state. Hence, several experimental methods have been developed in recent years in order to evaluate CCI at low temperatures. Finite Element (FE) simulations were applied in order to investigate the sealing behaviour of rubber stoppers for the drug product CCS under frozen storage conditions. FE analysis can help reducing the experimental design space and thus number of measurements needed, as they can be used as an ad-on to experimental testing. Several scenarios have been simulated including the effect of thermal history, rubber type, storage time, worst case CCS geometric tolerances and capping pressure. The results of these calculations have been validated with experimental data derived from laboratory experiments (CCI at low temperatures), and a concept for tightness has been developed. It has been concluded that FE simulations have the potential to become a powerful predictive tool towards a better understanding of the influence of cold storage on the rubber sealing properties (and hence on CCI) when dealing with frozen drug products. Copyright © 2018, Parenteral Drug Association.

Continuous nicotinamide administration improves behavioral recovery and reduces lesion size following bilateral frontal controlled cortical impact injury.

PubMed

Vonder Haar, Cole; Anderson, Gail D; Hoane, Michael R

2011-10-31

Previous research has demonstrated considerable preclinical efficacy of nicotinamide (NAM; vitamin B(3)) in animal models of TBI with systemic dosing at 50 and 500 mg/kg yielding improvements on sensory, motor, cognitive and histological measures. The current study aimed to utilize a more specific dosing paradigm in a clinically relevant delivery mechanism: continuously secreting subcutaneous pumps. A bilateral frontal controlled cortical impact (CCI) or sham surgery was performed and rats were treated with NAM (150 mg/kg day) or saline (1 ml/kg) pumps 30 min after CCI, continuing until seven days post-CCI. Rats were given a loading dose of NAM (50mg/kg) or saline (1 ml/kg) following pump implant. Rats received behavioral testing (bilateral tactile adhesive removal, locomotor placing task and Morris water maze) starting on day two post-CCI and were sacrificed at 31 days post-CCI and brains were stained to examine lesion size. NAM-treated rats had reductions in sensory, motor and cognitive behavioral deficits compared to vehicle-treated rats. Specifically, NAM-treated rats significantly improved on the bilateral tactile adhesive removal task, locomotor placing task and the reference memory paradigm of the Morris water maze. Lesion size was also significantly reduced in the NAM-treated group. The results from this study indicate that at the current dose, NAM produces beneficial effects on recovery from a bilateral frontal brain injury and that it may be a relevant compound to be explored in human studies. Copyright © 2011 Elsevier B.V. All rights reserved.

Seebeck Coefficient of Thermocouples from Nickel-Coated Carbon Fibers: Theory and Experiment.

PubMed

Hardianto, Hardianto; De Mey, Gilbert; Ciesielska-Wrόbel, Izabela; Hertleer, Carla; Van Langenhove, Lieva

2018-05-30

Thermocouples made of etched and non-etched nickel-coated carbon yarn (NiCCY) were investigated. Theoretic Seebeck coefficients were compared to experimental results from measurements of generated electric voltage by these thermocouples. The etching process for making thermocouples was performed by immersion of NiCCY in the solution containing a mixture of hydrochloric acid (HCl) (37% of concentration), and hydrogen peroxide (H₂O₂) in three different concentrations-3%, 6%, and 10%. Thirty minutes of etching to remove Ni from NiCCY was followed by washing and drying. Next, the ability to generate electrical voltage by the thermocouples (being a junction of the etched and the non-etched NiCCY) was measured in different ranges of temperatures, both a cold junction (291.15⁻293.15 K) and a hot junction (293.15⁻325.15 K). A formula predicting the Seebeck coefficient of this thermocouple was elaborated, taking into consideration resistance values of the tested samples. It was proven that there is a good agreement between the theoretical and experimental data, especially for the yarns etched with 6% and 10% peroxide (both were mixed with HCl). The electrical resistance of non-fully etched nickel remaining on the carbon fiber surface ( R 1 ) can have a significant effect on the thermocouples' characteristics.

Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats.

PubMed

Thiagarajan, Venkata R K; Shanmugam, Palanichamy; Krishnan, Uma M; Muthuraman, Arunachalam

2014-08-29

The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats.

PubMed

Thiagarajan, Venkata R K; Shanmugam, Palanichamy; Krishnan, Uma M; Muthuraman, Arunachalam

2014-09-01

The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

Progesterone Treatment Shows Benefit in a Pediatric Model of Moderate to Severe Bilateral Brain Injury

PubMed Central

Geddes, Rastafa I.; Sribnick, Eric A.; Sayeed, Iqbal; Stein, Donald G.

2014-01-01

Purpose Controlled cortical impact (CCI) models in adult and aged Sprague-Dawley (SD) rats have been used extensively to study medial prefrontal cortex (mPFC) injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI) in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury. Methods Twenty-eight-day old (PND 28) male Sprague Dawley rats received sham (n = 24) or CCI (n = 47) injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight) or vehicle injections on post-injury days (PID) 1–7, subjected to behavioral testing from PID 9–27, and analyzed for lesion size at PID 28. Results The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats. Conclusion Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits. PMID:24489882

Forecasting Construction Cost Index based on visibility graph: A network approach

NASA Astrophysics Data System (ADS)

Zhang, Rong; Ashuri, Baabak; Shyr, Yu; Deng, Yong

2018-03-01

Engineering News-Record (ENR), a professional magazine in the field of global construction engineering, publishes Construction Cost Index (CCI) every month. Cost estimators and contractors assess projects, arrange budgets and prepare bids by forecasting CCI. However, fluctuations and uncertainties of CCI cause irrational estimations now and then. This paper aims at achieving more accurate predictions of CCI based on a network approach in which time series is firstly converted into a visibility graph and future values are forecasted relied on link prediction. According to the experimental results, the proposed method shows satisfactory performance since the error measures are acceptable. Compared with other methods, the proposed method is easier to implement and is able to forecast CCI with less errors. It is convinced that the proposed method is efficient to provide considerably accurate CCI predictions, which will make contributions to the construction engineering by assisting individuals and organizations in reducing costs and making project schedules.

Comparison of a treatment strategy combining CCI-779 plus DTIC versus DTIC monotreatment in human melanoma in SCID mice.

PubMed

Thallinger, Christiane; Werzowa, Johannes; Poeppl, Wolfgang; Kovar, Florian M; Pratscher, Barbara; Valent, Peter; Quehenberger, Peter; Joukhadar, Christian

2007-10-01

This study compares the antineoplastic potential of a novel treatment strategy combining cell cycle inhibitor-779 (CCI-779) plus dacarbazine (DTIC) versus DTIC monotreatment, the current chemotherapeutic mainstay in combating metastatic melanoma. A controlled four-group parallel study design comprising 24-40 mice per tumor cell line was used in a severe combined immunodeficiency (SCID)-mouse xenotransplantation model. SCID mice were injected with 518A2, Mel-JUSO, or 607B human melanoma cells. After they developed tumors, mice received daily CCI-779 or solvent over 14 days. From treatment day 4-8 mice were additionally injected with DTIC or saline. Treatment with CCI-779 plus DTIC was superior to single agent DTIC in two out of three cell lines (P<0.05). The tumor weight reduction was 44+/-17 and 61+/-6% compared with DTIC monotreatment in Mel-JUSO and 607B melanomas, respectively (P<0.05). In contrast, in 518A2 xenotransplants, CCI-779 plus DTIC treatment was as effective as DTIC monotreatment. CCI-779 monotherapy exerted no statistically significant antitumor effect. Collectively, these data indicate that CCI-779 has the potential to increase the chemotherapeutic efficacy, as the combination of CCI-779 plus DTIC proved to be more efficacious compared to DTIC monotherapy in two out of three melanoma cell lines in vivo.

Hemorrhagic shock shifts the serum cytokine profile from pro- to anti-inflammatory after experimental traumatic brain injury in mice.

PubMed

Shein, Steven L; Shellington, David K; Exo, Jennifer L; Jackson, Travis C; Wisniewski, Stephen R; Jackson, Edwin K; Vagni, Vincent A; Bayır, Hülya; Clark, Robert S B; Dixon, C Edward; Janesko-Feldman, Keri L; Kochanek, Patrick M

2014-08-15

Secondary insults, such as hemorrhagic shock (HS), worsen outcome from traumatic brain injury (TBI). Both TBI and HS modulate levels of inflammatory mediators. We evaluated the addition of HS on the inflammatory response to TBI. Adult male C57BL6J mice were randomized into five groups (n=4 [naïve] or 8/group): naïve; sham; TBI (through mild-to-moderate controlled cortical impact [CCI] at 5 m/sec, 1-mm depth), HS; and CCI+HS. All non-naïve mice underwent identical monitoring and anesthesia. HS and CCI+HS underwent a 35-min period of pressure-controlled hemorrhage (target mean arterial pressure, 25-27 mm Hg) and a 90-min resuscitation with lactated Ringer's injection and autologous blood transfusion. Mice were sacrificed at 2 or 24 h after injury. Levels of 13 cytokines, six chemokines, and three growth factors were measured in serum and in five brain tissue regions. Serum levels of several proinflammatory mediators (eotaxin, interferon-inducible protein 10 [IP-10], keratinocyte chemoattractant [KC], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1alpha [MIP-1α], interleukin [IL]-5, IL-6, tumor necrosis factor alpha, and granulocyte colony-stimulating factor [G-CSF]) were increased after CCI alone. Serum levels of fewer proinflammatory mediators (IL-5, IL-6, regulated upon activation, normal T-cell expressed, and secreted, and G-CSF) were increased after CCI+HS. Serum level of anti-inflammatory IL-10 was significantly increased after CCI+HS versus CCI alone. Brain tissue levels of eotaxin, IP-10, KC, MCP-1, MIP-1α, IL-6, and G-CSF were increased after both CCI and CCI+HS. There were no significant differences between levels after CCI alone and CCI+HS in any mediator. Addition of HS to experimental TBI led to a shift toward an anti-inflammatory serum profile--specifically, a marked increase in IL-10 levels. The brain cytokine and chemokine profile after TBI was minimally affected by the addition of HS.

The impact of comorbidity on overall survival in elderly nasopharyngeal carcinoma patients: a National Cancer Data Base analysis.

PubMed

Huang, Ying; Chen, Wei; Haque, Waqar; Verma, Vivek; Xing, Yan; Teh, Bin S; Brian Butler, Edward

2018-04-01

The number of elderly patients with cancer is increasing. Medical comorbidities are more common in this population. Little is known regarding the prognostic relevance of comorbidities in elderly patients with nasopharyngeal carcinoma (NPC). Using the National Cancer Data Base (NCDB), we queried patients age >65 years diagnosed with NPC and treated with definitive radiation between 2004 and 2012 to examine the association between comorbidity and survival outcomes. Comorbidity was assessed with the Charlson Comorbidity Index (CCI). The influence of comorbidity on overall survival (OS) was evaluated. Cox proportional hazards model was used to study the impact of comorbidity on OS. A total of 1137 patients met the specified criteria. Median follow-up was 61.2 months. Five-year OS was 50.4%. Comorbidities were present in 22.4% of patients, with 17.6% of patients having a CCI score of 1% and 4.8% having a CCI score of ≥2. Patients with a CCI score of 0 had significantly higher 5-year OS than patients with a CCI score of 1 or ≥2 (53.1% vs. 42.2% vs. 32.9%, P < 0.001). In multivariate analysis, CCI was a statistically significant independent prognostic factor for the risk of death of all causes for patients with a CCI score of 1 (hazard ratio [HR]: 1.242; 95% confidence interval [CI]: 1.002-1.539) or CCI score of ≥2 (HR: 1.625; 95% CI: 1.157-2.283) when compared to patients with a CCI score of 0. Comorbidity as measured by CCI is a strong independent prognostic factor for OS in elderly patients with NPC and lends support to the inclusion of comorbidity assessment due to its prognostic value when treating elderly patients with NPC. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

[Curcumin down-regulates CX3CR1 expression in spinal cord dorsal horn and DRG in neuropathic pain rats].

PubMed

Zheng, Jinwei; Zheng, Changjian; Cao, Hong; Li, Jun; Lian, Qingquan

2011-09-01

To investigate the effects of curcumin on the behavior of chronic constrictive injury (CCI) rats and the CX3CR1 expression in spinal cord dorsal horn and dorsal root ganglia (DRG). Seventy-two male SD rats were randomly divided into 4 groups: 1) Sham operation group (Sham); 2) Chronic constrictive injury group (CCI); 3) Curcumin treated group (Cur), administrated with curcumin 100 mg x kg(-1) x d(-1) ip for 14 days after CCI; 4) Solvent contrast group (SC), administrated with an equal volume of solvent for 14 days after CCI. Paw thermal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) were measured on 2 pre-operative and 1, 3, 5, 7, 10, 14 post-operative days respectively. The lumbar segments L4-5 of the spinal cord and the L4, L5 DRG were removed at 3, 7, 14 days after surgery. The expression of CX3CR1 was determined by immunohistochemical staining. Compared with Sham group, PTWL and PMWT in CCI group were significantly lower on each post-operative day (P<0.01), which reached a nadir on the 3rd day after CCI (PTWL was 6.5 +/- 1.1, PMWT was 22.6 +/- 5.1), and the expression of CX3CR1 were markedly increased in spinal cord dorsal horn and DRG. In Cur group, PTWL were higher than in CCI group on 7, 10, 14 post-operative day (P<0.05), and PMWT were higher than those in CCI group on 10 and 14 post-operative day (P<0.05). The administration of curcumin could significantly attenuate the activation of CX3CR1 induced by CCI. The study suggests that curcumin ameliorates the CCI-induced neuropathic pain, probably by attenuating the expression of CX3CR1 in spinal cord dorsal horn and dorsal root ganglia.

Evaluation of Container Closure System Integrity for Storage of Frozen Drug Products: Impact of Capping Force and Transportation.

PubMed

Nieto, Alejandra; Roehl, Holger; Adler, Michael; Mohl, Silke

2018-05-31

Frozen-state storage and cold-chain transport are key operations in the development and commercialization of biopharmaceuticals. Nowadays, a few marketed drug products are stored (and/or) shipped under frozen conditions to ensure sufficient stability, particularly for live viral vaccines. When these products are stored in glass vials with stoppers, the elastomer of the stopper needs to be flexible enough to seal the vial at the target's lowest temperature to ensure container closure integrity and hence both sterility and safety of the drug product. The container closure integrity assessment in the frozen state (e.g., -20°C, -80°C) should include: Container Closure Integrity (CCI) of the Container Closure System (CCS) itself, impact of processing, e.g. capping process on CCI and impact of shipment and movement on CCI in the frozen state. The objective of this work was an evaluation of the impact of processing and shipment on CCI of a CCS in the frozen state. The impact on other quality attributes was not investigated. In this light, the ThermCCI method was applied to evaluate the impact of shipping stress and variable capping force on CCI of frozen vials and to evaluate the temperature limits of rubber stoppers. In conclusion, retaining CCI during cold storage is mostly a function of vial-stopper combination and temperatures below -40°C may pose a risk to the CCI of a frozen drug product. Variable capping force may have an influence on the CCI of a frozen drug product if not appropriately assessed. Regarding the impact of shipment on the CCI of glass vials, no indication was given either at room temperature, -20°C or -75°C when compared to static storage at such temperatures. Copyright © 2018, Parenteral Drug Association.

Acute Response of the Hippocampal Transcriptome Following Mild Traumatic Brain Injury After Controlled Cortical Impact in the Rat.

PubMed

Samal, Babru B; Waites, Cameron K; Almeida-Suhett, Camila; Li, Zheng; Marini, Ann M; Samal, Nihar R; Elkahloun, Abdel; Braga, Maria F M; Eiden, Lee E

2015-10-01

We have previously demonstrated that mild controlled cortical impact (mCCI) injury to rat cortex causes indirect, concussive injury to underlying hippocampus and other brain regions, providing a reproducible model for mild traumatic brain injury (mTBI) and its neurochemical, synaptic, and behavioral sequelae. Here, we extend a preliminary gene expression study of the hippocampus-specific events occurring after mCCI and identify 193 transcripts significantly upregulated, and 21 transcripts significantly downregulated, 24 h after mCCI. Fifty-three percent of genes altered by mCCI within 24 h of injury are predicted to be expressed only in the non-neuronal/glial cellular compartment, with only 13% predicted to be expressed only in neurons. The set of upregulated genes following mCCI was interrogated using Ingenuity Pathway Analysis (IPA) augmented with manual curation of the literature (190 transcripts accepted for analysis), revealing a core group of 15 first messengers, mostly inflammatory cytokines, predicted to account for >99% of the transcript upregulation occurring 24 h after mCCI. Convergent analysis of predicted transcription factors (TFs) regulating the mCCI target genes, carried out in IPA relative to the entire Affymetrix-curated transcriptome, revealed a high concordance with TFs regulated by the cohort of 15 cytokines/cytokine-like messengers independently accounting for upregulation of the mCCI transcript cohort. TFs predicted to regulate transcription of the 193-gene mCCI cohort also displayed a high degree of overlap with TFs predicted to regulate glia-, rather than neuron-specific genes in cortical tissue. We conclude that mCCI predominantly affects transcription of non-neuronal genes within the first 24 h after insult. This finding suggests that early non-neuronal events trigger later permanent neuronal changes after mTBI, and that early intervention after mTBI could potentially affect the neurochemical cascade leading to later reported synaptic and behavioral dysfunction.

Co-administration of MK-801 and morphine attenuates neuropathic pain in rat.

PubMed

Hamidi, Gholam Ali; Manaheji, Homa; Janahmadi, Mahyar; Noorbakhsh, Sayed Mohammad; Salami, Mahmoud

2006-07-30

Partial peripheral nerve injury often leads to chronic pain states, including allodynia and hyperalgesia. The purpose of this study was to investigate the involvement of the N-methyl-D-aspartate and opioid receptors in the behavioural responses following chronic constriction nerve injury (CCI). The animals were injected a combination of MK-801 (0.3 mg/kg, 20 min before, and 6 h after the operation) and morphine (8 mg/kg, 30 min prior to the operation) and were tested for allodynia and hyperalgesia reactions at 0, 3, 7, 14, 21 and 28 days after CCI. Compound action potentials were also recorded from the injured nerve 2 weeks post-operation to indicate nerve injury state electrophysiologically. Our results indicate that the CCI model importantly influences the behavioural responses to both the thermal and mechanical stimulations. Also, the pre-emptive co-administration of MK-801 and morphine has suppressive effects on the cold allodynia but a slight alleviation on the mechano-allodynia and heat hyperalgesia.

[Analgesic effect of ferulic acid on CCI mice: behavior and neurobiological analysis].

PubMed

Lv, Wei-Hong; Zhang, Lu; Wu, Shu-Juan; Chen, Sai-Zhen; Zhu, Xin-Bo; Pan, Jian-Chun

2013-11-01

To study the analgesic effect of chronic administration with ferulic acid, and preliminarily discuss its mechanism. Thermal hyperalgesia and mechanical allodynia tests were conducted to observe the analgesic effect of chronic administration with ferulic acid on CCI mice. The neurochemical detection method was applied to observe the effect chronic administration with ferulic acid on monoamine neurotransmitter and monoamine oxidase activity. Compared with the normal group, CCI mice showed notable reduction in heat sensation and nociceptive threshold in and mechanical allodynia. Ferulic acid (10, 20, 40 and 80 mg x kg(-1), po) could significantly reverse the situations. In an in-depth study, we found that the reason for these results was that ferulic acid was dose-dependent in increasing 5-HT and NE levels in hippocampus, frontal cortex and amygdale and could inhibit MAO-A activity in mouse brains. These results showed that ferulic acid has the analgesic effect. Its mechanism may be related to the inhibition of monoamine oxidase activity and the increase in monoamine neurotransmitter in mouse brains.

Administration of raloxifene reduces sensorimotor and working memory deficits following traumatic brain injury.

PubMed

Kokiko, Olga N; Murashov, Alexander K; Hoane, Michael R

2006-06-30

Hormonal differences between males and females have surfaced as a crucial component in the search for effective treatments after experimental models of traumatic brain injury (TBI). Recent findings have shown that selective estrogen receptor modulators (SERMs) may have therapeutic benefit. The present study examined the effects of raloxifene, a SERM, on functional recovery after bilateral cortical contusion injury (bCCI) or sham procedure. Male rats received injections of raloxifene (3.0mg/kg, i.p.) or vehicle (1.0 ml/kg, i.p.) 15 min, 24, 48, 72, and 96 h after bCCI or sham procedure. Rats were tested on both sensorimotor (bilateral tactile removal and locomotor placing tests) and cognitive tests (reference and working memory in the Morris water maze). Raloxifene-treated animals showed a significant reduction in the initial magnitude of the deficit and facilitated the rate of recovery for the bilateral tactile removal test, compared to vehicle-treated animals. The raloxifene-treated animals also showed a significant improvement in the acquisition of working memory compared to vehicle-treated animals. However, raloxifene did not significantly improve the acquisition of reference memory or locomotor placing ability. Raloxifene treatment also did not result in a significant reduction in the size of the lesion cavity. Thus, the task-dependent improvements seen following raloxifene treatment do not appear to be the result of cortical neuroprotection. However, these results suggest that raloxifene improves functional outcome following bCCI and may present an interesting avenue for future research.

Prenatal and Early Childhood Exposure to Tetrachloroethylene and Adult Vision

PubMed Central

Getz, Kelly D.; Janulewicz, Patricia A.; Rowe, Susannah; Weinberg, Janice M.; Winter, Michael R.; Martin, Brett R.; Vieira, Veronica M.; White, Roberta F.

2012-01-01

Background: Tetrachloroethylene (PCE; or perchloroethylene) has been implicated in visual impairments among adults with occupational and environmental exposures as well as children born to women with occupational exposure during pregnancy. Objectives: Using a population-based retrospective cohort study, we examined the association between prenatal and early childhood exposure to PCE-contaminated drinking water on Cape Cod, Massachusetts, and deficits in adult color vision and contrast sensitivity. Methods: We estimated the amount of PCE that was delivered to the family residence from participants’ gestation through 5 years of age. We administered to this now adult study population vision tests to assess acuity, contrast sensitivity, and color discrimination. Results: Participants exposed to higher PCE levels exhibited lower contrast sensitivity at intermediate and high spatial frequencies compared with unexposed participants, although the differences were generally not statistically significant. Exposed participants also exhibited poorer color discrimination than unexposed participants. The difference in mean color confusion indices (CCI) was statistically significant for the Farnsworth test but not Lanthony’s D-15d test [Farnsworth CCI mean difference = 0.05, 95% confidence interval (CI): 0.003, 0.10; Lanthony CCI mean difference = 0.07, 95% CI: –0.02, 0.15]. Conclusions: Prenatal and early childhood exposure to PCE-contaminated drinking water may be associated with long-term subclinical visual dysfunction in adulthood, particularly with respect to color discrimination. Further investigation of this association in similarly exposed populations is necessary. PMID:22784657

Biochemical Study of Anti-Inflammatory Proteins vCCI and vMIP-II

DTIC Science & Technology

2014-07-17

protein ), where we showed that vCCI is able to bind so many different chemokines due to its general negatively charged surface , allowing it to bind...sample of these competition curves. Our conclusion from the data in Table 1 and Figure 1 is that the negatively charged surface of vCCI allows it to...Similar to our mutagenesis results, the overall data indicate that vCCI uses a negatively charged surface to bind positive charges on the chemokine

Morphologic features and surgically induced astigmatism of femtosecond laser versus manual clear corneal incisions.

PubMed

Zhu, Sha; Qu, Naibin; Wang, Wei; Zhu, Yanan; Shentu, Xingchao; Chen, Peiqing; Xu, Wen; Yao, Ke

2017-11-01

To compare the morphologic features and surgically induced astigmatism (SIA) between laser and manual clear corneal incisions (CCIs) after femtosecond laser-assisted cataract surgery. Eye Center, 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China. Prospective case series. Patients had femtosecond laser-assisted cataract surgery with a CCI created with the laser or manually after random allocation. The corrected distance visual acuity, corneal topography, and anterior segment optical coherence tomography were assessed at the 1-day, 1-week, 1-month, and 3-month follow-ups. The laser CCI group comprised 45 eyes and the manual CCI group, 48 eyes. The SIA was significantly lower in the manual CCI group than the laser CCI group at all visits (P < .05). At the 1-day and 1-week follow-ups, the mean CCI thickness was significantly smaller in the manual CCI group (P < .05). In the laser CCI group, the perpendicular linear distance between the external wound opening and the corneal vertex central line was statistically shorter than in the manual CCI group (P < .05). At 3 months, the SIA was correlated with the perpendicular linear distance with a Pearson correlation coefficient of -0.341 (P = .001). Femtosecond laser-created CCIs for cataract surgery caused more SIA than manually created CCIs, which could have resulted from inaccurate or uncertain corneal incision positioning of the femtosecond machine. Manual creation of CCIs is recommended in femtosecond laser-assisted cataract surgery until the locating system for the femtosecond laser incision is updated. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Neuropsychiatric Symptom Modeling in Male and Female C57BL/6J Mice after Experimental Traumatic Brain Injury

PubMed Central

Tucker, Laura B.; Burke, John F.; Fu, Amanda H.

2017-01-01

Abstract Psychiatric symptoms such as anxiety and depression are frequent and persistent complaints following traumatic brain injury (TBI). Modeling these symptoms in animal models of TBI affords the opportunity to determine mechanisms underlying behavioral pathologies and to test potential therapeutic agents. However, testing these symptoms in animal models of TBI has yielded inconsistent results. The goal of the current study was to employ a battery of tests to measure multiple anxiety- and depressive-like symptoms following TBI in C57BL/6J mice, and to determine if male and female mice are differentially affected by the injury. Following controlled cortical impact (CCI) at a parietal location, neither male nor female mice showed depressive-like symptoms as measured by the Porsolt forced-swim test and sucrose preference test. Conclusions regarding anxiety-like behaviors were dependent upon the assay employed; CCI-induced thigmotaxis in the open field suggested an anxiogenic effect of the injury; however, results from the elevated zero maze, light-dark box, and marble-burying tests indicated that CCI reduced anxiety-like behaviors. Fewer anxiety-like behaviors were also associated with the female sex. Increased levels of activity were also measured in female mice and injured mice in these tests, and conclusions regarding anxiety should be taken with caution when experimental manipulations induce changes in baseline activity. These results underscore the irreconcilability of results from studies attempting to model TBI-induced neuropsychiatric symptoms. Changes in injury models or better attempts to replicate the clinical syndrome may improve the translational applicability of rodent models of TBI-induced anxiety and depression. PMID:27149139

Cyberdyn supercomputer - a tool for imaging geodinamic processes

NASA Astrophysics Data System (ADS)

Pomeran, Mihai; Manea, Vlad; Besutiu, Lucian; Zlagnean, Luminita

2014-05-01

More and more physical processes developed within the deep interior of our planet, but with significant impact on the Earth's shape and structure, become subject to numerical modelling by using high performance computing facilities. Nowadays, worldwide an increasing number of research centers decide to make use of such powerful and fast computers for simulating complex phenomena involving fluid dynamics and get deeper insight to intricate problems of Earth's evolution. With the CYBERDYN cybernetic infrastructure (CCI), the Solid Earth Dynamics Department in the Institute of Geodynamics of the Romanian Academy boldly steps into the 21st century by entering the research area of computational geodynamics. The project that made possible this advancement, has been jointly supported by EU and Romanian Government through the Structural and Cohesion Funds. It lasted for about three years, ending October 2013. CCI is basically a modern high performance Beowulf-type supercomputer (HPCC), combined with a high performance visualization cluster (HPVC) and a GeoWall. The infrastructure is mainly structured around 1344 cores and 3 TB of RAM. The high speed interconnect is provided by a Qlogic InfiniBand switch, able to transfer up to 40 Gbps. The CCI storage component is a 40 TB Panasas NAS. The operating system is Linux (CentOS). For control and maintenance, the Bright Cluster Manager package is used. The SGE job scheduler manages the job queues. CCI has been designed for a theoretical peak performance up to 11.2 TFlops. Speed tests showed that a high resolution numerical model (256 × 256 × 128 FEM elements) could be resolved with a mean computational speed of 1 time step at 30 seconds, by employing only a fraction of the computing power (20%). After passing the mandatory tests, the CCI has been involved in numerical modelling of various scenarios related to the East Carpathians tectonic and geodynamic evolution, including the Neogene magmatic activity, and the intriguing intermediate-depth seismicity within the so-called Vrancea zone. The CFD code for numerical modelling is CitcomS, a widely employed open source package specifically developed for earth sciences. Several preliminary 3D geodynamic models for simulating an assumed subduction or the effect of a mantle plume will be presented and discussed.

Interleukin-1 receptor 1 deletion in focal and diffuse experimental traumatic brain injury in mice.

PubMed

Chung, Joon Yong; Krapp, Nicolas; Wu, Limin; Lule, Sevda; McAllister, Lauren; Edmiston Iii, William; Martin, Samantha; Levy, Emily; Songtachalert, Tanya; Sherwood, John; Buckley, Erin; Sanders, Bharat; Izzy, Saef; Hickman, Suzanne; Guo, Shuzhen; Lok, Josephine; El Khoury, Joseph; Lo, Eng; Kaplan, David; Whalen, Michael

2018-05-17

Important differences in the biology of focal and diffuse traumatic brain injury (TBI) subtypes may result in unique pathophysiological responses to shared molecular mechanisms. Interleukin-1 (IL-1) signaling has been tested as a potential therapeutic target in preclinical models of cerebral contusion and diffuse TBI, and in a phase II clinical trial, but no published studies have examined IL-1 signaling in an impact/acceleration closed head injury (CHI) model. We hypothesized that genetic deletion of IL-1 receptor-1 (IL-1R1 KO) would be beneficial in focal (contusion) and CHI in mice. Wild type and IL-1R1 KO mice were subjected to controlled cortical impact (CCI), or to CHI. CCI produced brain leukocyte infiltration, HMGB1 translocation and release, edema, cell death, and cognitive deficits. CHI induced peak rotational acceleration of 9.7 x 105 + 8.1 x 104 rad/s2, delayed time to righting reflex, and robust Morris water maze deficits without deficits in tests of anxiety, locomotion, sensorimotor function, or depression. CHI produced no discernable acute plasmalemma damage or cell death, blood-brain barrier permeability to IgG, or brain edema and only a modest increase in brain leukocyte infiltration at 72 h. In both models, mature (17 kDa) interleukin-1 beta (IL-1β) was induced by 24 h in CD31+ endothelial cells isolated from injured brain but was not induced in CD11b+ cells in either model. High mobility group box protein-1 was released from injured brain cells in CCI but not CHI. Surprisingly, cognitive outcome in mice with global deletion of IL-1R1 was improved in CHI, but worse after CCI without affecting lesion size, edema, or infiltration of CD11b+/CD45+ leukocytes in CCI. IL-1R1 may induce unique biological responses, beneficial or detrimental to cognitive outcome, after TBI depending on the pathoanatomical subtype. Brain endothelium is a hitherto unrecognized source of mature IL-1β in both models.

Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats

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

Liu, Hao; Rose, Marie E.; Department of Neurology, University of Pittsburgh School of Medicine, PA

Rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been shown to confer neuroprotective effects in stroke and spinal cord injury, but its role in the traumatic brain injury (TBI) is still controversial. Using a controlled cortical impact model in rats, the current study was designed to determine the effects of rosiglitazone treatment (6 mg/kg at 5 min, 6 h and 24 h post injury) upon inflammation and histological outcome at 21 d after TBI. In addition, the effects of rosiglitazone upon inflammatory cytokine transcription, vestibulomotor behavior and spatial memory function were determined at earlier time points (24 h, 1–5 d, 14–20 d post injury, respectively). Compared withmore » the vehicle-treated group, rosiglitazone treatment suppressed production of TNFα at 24 h after TBI, attenuated activation of microglia/macrophages and increased survival of CA3 neurons but had no effect on lesion volume at 21 d after TBI. Rosiglitazone-treated animals had improved performance on beam balance testing, but there was no difference in spatial memory function as determined by Morris water maze. In summary, this study indicates that rosiglitazone treatment in the first 24 h after TBI has limited anti-inflammatory and neuroprotective effects in rat traumatic injury. Further study using an alternative dosage paradigm and more sensitive behavioral testing may be warranted. - Highlights: • Effects of rosiglitazone after CCI were evaluated using a rat TBI model. • Rosiglitazone suppressed production of TNFα at 24 h after CCI. • Rosiglitazone inhibited microglial activation at 21 d after CCI. • Rosiglitazone increased survival of CA3 neurons at 21 d after CCI. • Rosiglitazone-treated animals had improved performance in beam balance testing.« less

Comorbidity Assessment Using Charlson Comorbidity Index and Simplified Comorbidity Score and Its Association With Clinical Outcomes During First-Line Chemotherapy for Lung Cancer.

PubMed

Singh, Navneet; Singh, Potsangbam Sarat; Aggarwal, Ashutosh N; Behera, Digambar

2016-05-01

Limited data is available on comorbidity assessment in patients with lung cancer. The present prospective study assessed the prevalence and association of the Charlson comorbidity index (CCI) and simplified comorbidity score (SCS) with clinical outcomes in patients with newly diagnosed lung cancer undergoing chemotherapy. All patients received histology-guided platinum doublets. The outcomes assessed were overall survival (OS), radiologic responses using Response Evaluation Criteria in Solid Tumors and toxicity using the Common Toxicity Criteria, version 3.0. The groups analyzed were SCS ≤ 9 (n = 173) and > 9 (n = 65) and CCI = 0 (n = 88), 1 (n = 97), and ≥ 2 (n = 53). Correlations of the CCI and SCS were assessed using Spearman's (rho) method. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for the factors affecting OS using Cox proportional hazard (CPH) modeling. Most patients had advanced disease (stage IIIB in 33.6%, stage IV in 42.4%). The median SCS was 7 (interquartile range, 7-11), and the median CCI was 1 (interquartile range, 0-1). The correlation between the CCI and SCS was moderate (rho = 0.474; P < .001). Age correlated weakly with both SCS (rho = 0.293; P < .001) and CCI (rho = 0.205; P < .001). The SCS > 9 group (vs. SCS ≤ 9) had a significantly older mean age, patients aged ≥ 70 years, men, smokers, and squamous cell histologic type. The mean age in the CCI groups was 55.2 years for a CCI of 0, 59.6 years for a CCI of 1, and 60.3 years for a CCI of 2, with a statistically significant difference (P = .002). The radiologic responses and toxicity profiles were similar between the SCS and CCI groups. The median OS was 287 days (95% CI, 232-342 days) and did not differ between the SCS and CCI groups. On multivariate CPH analyses, worse OS was independently associated with stage IV disease (adjusted HR, 2.0; 95% CI, 1.4-2.7) and poor performance status (Eastern Cooperative Oncology Group score ≥ 2; adjusted HR, 1.8; 95% CI, 1.1-2.8) but not with comorbidity, histologic type, or age. The SCS and CCI scores correlated moderately with each other and weakly with age. The presence of comorbidities did not adversely influence clinical outcomes in this Indian cohort of lung cancer patients undergoing first-line chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Glibenclamide Produces Region-Dependent Effects on Cerebral Edema in a Combined Injury Model of Traumatic Brain Injury and Hemorrhagic Shock in Mice.

PubMed

Jha, Ruchira M; Molyneaux, Bradley J; Jackson, Travis C; Wallisch, Jessica S; Park, Seo-Young; Poloyac, Samuel; Vagni, Vincent A; Janesko-Feldman, Keri L; Hoshitsuki, Keito; Minnigh, M Beth; Kochanek, Patrick M

2018-06-06

Cerebral edema is critical to morbidity/mortality in traumatic brain injury (TBI) and is worsened by hypotension. Glibenclamide may reduce cerebral edema by inhibiting sulfonylurea receptor-1 (Sur1); its effect on diffuse cerebral edema exacerbated by hypotension/resuscitation is unknown. We aimed to determine if glibenclamide improves pericontusional and/or diffuse edema in controlled cortical impact (CCI) (5m/sec, 1 mm depth) plus hemorrhagic shock (HS) (35 min), and compare its effects in CCI alone. C57BL/6 mice were divided into five groups (n = 10/group): naïve, CCI+vehicle, CCI+glibenclamide, CCI+HS+vehicle, and CCI+HS+glibenclamide. Intravenous glibenclamide (10 min post-injury) was followed by a subcutaneous infusion for 24 h. Brain edema in injured and contralateral hemispheres was subsequently quantified (wet-dry weight). This protocol brain water (BW) = 80.4% vehicle vs. 78.3% naïve, p < 0.01) but was not reduced by glibenclamide (I%BW = 80.4%). Ipsilateral edema also developed in CCI alone (I%BW = 80.2% vehicle vs. 78.3% naïve, p < 0.01); again unaffected by glibenclamide (I%BW = 80.5%). Contralateral (C) %BW in CCI+HS was increased in vehicle (78.6%) versus naive (78.3%, p = 0.02) but unchanged in CCI (78.3%). At 24 h, glibenclamide treatment in CCI+HS eliminated contralateral cerebral edema (C%BW = 78.3%) with no difference versus naïve. By 72 h, contralateral cerebral edema had resolved (C%BW = 78.5 ± 0.09% vehicle vs. 78.3 ± 0.05% naïve). Glibenclamide decreased 24 h contralateral cerebral edema in CCI+HS. This beneficial effect merits additional exploration in the important setting of TBI with polytrauma, shock, and resuscitation. Contralateral edema did not develop in CCI alone. Surprisingly, 24 h of glibenclamide treatment failed to decrease ipsilateral edema in either model. Interspecies dosing differences versus prior studies may play an important role in these findings. Mechanisms underlying brain edema may differ regionally, with pericontusional/osmolar swelling refractory to glibenclamide but diffuse edema (via Sur1) from combined injury and/or resuscitation responsive to this therapy. TBI phenotype may mandate precision medicine approaches to treat brain edema.

Diagnosis and Monitoring of Chronic Myeloid Leukemia: Chiang Mai University Experience.

PubMed

Tantiworawit, Adisak; Kongjarern, Supanat; Rattarittamrong, Ekarat; Lekawanvijit, Suree; Bumroongkit, Kanokkan; Boonma, Nonglak; Rattanathammethee, Thanawat; Hantrakool, Sasinee; Chai-Adisaksopha, Chatree; Norasetthada, Lalita

2016-01-01

A diagnosis of chronic myeloid leukemia (CML) is made on discovery of the presence of a Philadelphia (Ph) chromosome. The success of the treatment of this form of leukemia with tyrosine kinase inhibitor (TKI) is monitored by reduction of the Ph chromosome. To compare the role of conventional cytogenetic (CC) methods with a real time quantitative polymerase chain reaction (RQ-PCR) and fluorescence in situ hybridization (FISH) for diagnosis and treatment monitoring of CML patients. The secondary outcome was to analyze the treatment responses to TKI in CML patients. This was a retrospective study of CML patients who attended the Hematology clinic at Chiang Mai University Hospital from 2005-2010. Medical records were reviewed for demographic data, risk score, treatment response and the results of CC methods, FISH and RQ-PCR. One hundred and twenty three cases were included in the study, 57.7% of whom were male with a mean age of 46.9 years. Most of the patients registered as intermediate to high risk on the Sokal score. At diagnosis, 121 patients were tested using the CC method and 118 (95.9%) were identified as positive. Five patients failed to be diagnosed by CC methods but were positive for BCR-ABL1 using the FISH method. Imatinib was the first-line treatment used in 120 patients (97.6%). In most patients (108 out of 122, 88.5%), a complete cytogenetic response (CCyR) was achieved after TKI therapy and in 86 patients (70.5%) CCyR was achieved long term by the CC method. Five out of the 35 analyzed patients in which CCyR was achieved by the CC method had a positive FISH result. Out of the 76 patients in which CCyR was achieved, RQ-PCR classified patients to only CCyR in 17 patients (22.4%) with a deeper major molecular response (MMR) in 4 patients (5.3%) and complete molecular response (CMR) in 55 patients (72.4%). In the case of initial therapy, CCyR was achieved in 95 patients (79.1%) who received imatinib and in both patients who received dasatinib (100%). For the second line treatment, nilotinib were used in 30 patients and in 19 of them (63.3%) CCyR was achieved. In half of the 6 patients (50%) who received dasatinib as second line or third line treatment CCyR was also achieved. CML patients had a good response to TKI treatment. FISH could be useful for diagnosis in cases where CC analysis failed to detect the Ph chromosome. RQ-PCR was helpful in detecting any residual disease and determining the depth of the treatment response at levels greater than the CC methods.

Motor cortex stimulation does not lead to functional recovery after experimental cortical injury in rats.

PubMed

Schönfeld, Lisa-Maria; Jahanshahi, Ali; Lemmens, Evi; Bauwens, Matthias; Hescham, Sarah-Anna; Schipper, Sandra; Lagiere, Melanie; Hendrix, Sven; Temel, Yasin

2017-01-01

Motor impairments are among the major complications that develop after cortical damage caused by either stroke or traumatic brain injury. Motor cortex stimulation (MCS) can improve motor functions in animal models of stroke by inducing neuroplasticity. In the current study, the therapeutic effect of chronic MCS was assessed in a rat model of severe cortical damage. A controlled cortical impact (CCI) was applied to the forelimb area of the motor cortex followed by implantation of a flat electrode covering the lesioned area. Forelimb function was assessed using the Montoya staircase test and the cylinder test before and after a period of chronic MCS. Furthermore, the effect of MCS on tissue metabolism and lesion size was measured using [18F]-fluorodesoxyglucose (FDG) μPET scanning. CCI caused a considerable lesion at the level of the motor cortex and dorsal striatum together with a long-lasting behavioral phenotype of forelimb impairment. However, MCS applied to the CCI lesion did not lead to any improvement in limb functioning when compared to non-stimulated control rats. Also, MCS neither changed lesion size nor distribution of FDG. The use of MCS as a standalone treatment did not improve motor impairments in a rat model of severe cortical damage using our specific treatment modalities.

Downregulations of TRPM8 expression and membrane trafficking in dorsal root ganglion mediate the attenuation of cold hyperalgesia in CCI rats induced by GFRα3 knockdown.

PubMed

Su, Lin; Shu, Ruichen; Song, Chengcheng; Yu, Yonghao; Wang, Guolin; Li, Yazhuo; Liu, Changxiao

2017-10-01

Cold hyperalgesia is an intractable sensory abnormality commonly seen in peripheral neuropathies. Although glial cell line-derived neurotrophic factor family receptor alpha3 (GFRα3) is required for the formation of pathological cold pain has been revealed, potential transduction mechanism is poorly elucidated. We have previously demonstrated the contribution of enhanced activity of transient receptor potential melastatin 8 (TRPM8) to cold hyperalgesia in neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve. Recently, the enhancement of TRPM8 activity is attributed to the increased TRPM8 plasma membrane trafficking. In addition, TRPM8 can be sensitized by the activation of GFRα3, leading to increased cold responses in vivo. The aim of this study was to investigate whether GFRα3 could influence cold hyperalgesia of CCI rats via modulating TRPM8 expression and plasma membrane trafficking in dorsal root ganglion (DRG). Mechanical allodynia, cold and heat hyperalgesia were measured on 1day before CCI and the 1st, 4th, 7th, 10th and 14th day after CCI. TRPM8 total expression and membrane trafficking as well as GFRα3 expression in DRG were detected by immunofluorescence and western blot. Furthermore, GFRα3 small interfering RNA (siRNA) was intrathecally administrated to reduce GFRα3 expression in DRG, and the effects of GFRα3 knockdown on CCI-induced behavioral sensitization as well as TRPM8 total expression and membrane trafficking in both mRNA and protein levels were investigated, and the change in coexpression of TRPM8 with GFRα3 was also evaluated. Then, the effect of GFRα3 activation with artemin on pain behavior of CCI rats pretreated with the selective TRPM8 antagonist RQ-00203078 was observed. Here we found that TRPM8 total expression and plasma membrane trafficking as well as GFRα3 expression in DRG were initially increased on the 4th day after CCI, and maintained at the peak level from the 10th to the 14th day, which entirely conformed with the induction and maintenance of behavioral-reflex facilitation following CCI. The coexpression of TRPM8 with GFRα3, which was mainly located in peptidergic C-fibers DRG neurons, was also increased after CCI. Downregulation of GFRα3 protein in DRG attenuated CCI-induced cold hyperalgesia without affecting mechanical allodynia and heat hyperalgesia, and reduced the upregulations of TRPM8 total expression and plasma membrane trafficking as well as coexpression of TRPM8 with GFRα3 induced by CCI. Additionally, the inhibition of TRPM8 abolished the influence of GFRα3 activation on cold hyperalgesia after CCI. Our results demonstrate that GFRα3 knockdown specially inhibits cold hyperalgesia following CCI via decreasing the expression level and plasma membrane trafficking of TRPM8 in DRG. GFRα3 and its downstream mediator, TRPM8, represent a new analgesia axis which can be further exploited in sensitized cold reflex under the condition of chronic pain. Copyright © 2017 Elsevier Inc. All rights reserved.

Mass extraction container closure integrity physical testing method development for parenteral container closure systems.

PubMed

Yoon, Seung-Yil; Sagi, Hemi; Goldhammer, Craig; Li, Lei

2012-01-01

Container closure integrity (CCI) is a critical factor to ensure that product sterility is maintained over its entire shelf life. Assuring the CCI during container closure (C/C) system qualification, routine manufacturing and stability is important. FDA guidance also encourages industry to develop a CCI physical testing method in lieu of sterility testing in a stability program. A mass extraction system has been developed to check CCI for a variety of container closure systems such as vials, syringes, and cartridges. Various types of defects (e.g., glass micropipette, laser drill, wire) were created and used to demonstrate a detection limit. Leakage, detected as mass flow in this study, changes as a function of defect length and diameter. Therefore, the morphology of defects has been examined in detail with fluid theories. This study demonstrated that a mass extraction system was able to distinguish between intact samples and samples with 2 μm defects reliably when the defect was exposed to air, water, placebo, or drug product (3 mg/mL concentration) solution. Also, it has been verified that the method was robust, and capable of determining the acceptance limit using 3σ for syringes and 6σ for vials. Sterile products must maintain their sterility over their entire shelf life. Container closure systems such as those found in syringes and vials provide a seal between rubber and glass containers. This seal must be ensured to maintain product sterility. A mass extraction system has been developed to check container closure integrity for a variety of container closure systems such as vials, syringes, and cartridges. In order to demonstrate the method's capability, various types of defects (e.g., glass micropipette, laser drill, wire) were created in syringes and vials and were tested. This study demonstrated that a mass extraction system was able to distinguish between intact samples and samples with 2 μm defects reliably when the defect was exposed to air, water, placebo, or drug product (3 mg/mL concentration) solution. Also, it was verified that the method showed consistent results, and was able to determine the acceptance limit using 3σ for syringes and 6σ for vials.

A 2D threshold of the condylar-C1 interval to maximize identification of patients at high risk for atlantooccipital dislocation using computed tomography.

PubMed

Ravindra, Vijay M; Riva-Cambrin, Jay; Horn, Kevin P; Ginos, Jason; Brockmeyer, Russell; Guan, Jian; Rampton, John; Brockmeyer, Douglas L

2017-04-01

OBJECTIVE Measurement of the occipital condyle-C1 interval (CCI) is important in the evaluation of atlantooccipital dislocation (AOD) in pediatric trauma patients. The authors studied a large cohort of children with and without AOD to identify a 2D measurement threshold that maximizes the diagnostic yield of the CCI on cervical spine CT scans obtained in trauma patients. METHODS This retrospective, single-center study included all children who underwent CT of the cervical spine at Primary Children's Hospital from January 1, 2011, through December 31, 2014, for trauma evaluation. Bilateral CCI measurements in the coronal (3 measurements per side) and sagittal (4 measurements per side) planes were recorded. Using an iterative method, the authors determined optimal cutoffs for the maximal CCI in each plane in relation to AOD. The primary outcome was AOD requiring occipitocervical fusion. RESULTS A total of 597 pediatric patients underwent cervical spine CT for trauma evaluation: 578 patients without AOD and 19 patients with AOD requiring occipitocervical fusion. The authors found a statistically significant correlation between CCI and age (p < 0.001), with younger patients having higher CCIs. Using a 2D threshold requiring a sagittal CCI ≥ 2.5 mm and a coronal CCI ≥ 3.5 mm predicted AOD with a sensitivity of 95%, a specificity of 73%, positive predictive value of 10.3%, and negative predictive value of 99%. The accuracy of this 2D threshold was 84%. CONCLUSIONS In the present study population, age-dependent differences in the CCI were found on CT scans of the cervical spine in a large cohort of patients with and without AOD. A 2D CCI threshold as a screening method maximizes identification of patients at high risk for AOD while minimizing unnecessary imaging studies in children being evaluated for trauma.

Collaborating with Communities and Higher Education to Address the Health-care Needs of Individuals with Disabilities in Ecuador.

PubMed

Cech, Donna J; Alvarado, Zully J

2017-01-01

Individuals with disabilities experience inequities in access to health care, education, employment, and social inclusion. Causes for Change International (CCI), a non-governmental Organization (NGO), using a community-based rehabilitation approach has worked for 20 years to build self-sufficiency, improve health-care services, and education for women, children, and persons with disabilities in Ecuador. CCI initially addressed health; advocacy for individuals with disabilities; and promoted educational opportunities for children with disabilities, starting in one rural community. CCI's outreach has expanded through Ecuador's coastal provinces, Andean provinces, and Galapagos Islands. CCI also focused on local health-care workforce development, developing employment skills for individuals with disabilities and social inclusion for this population. CCI collaborated with local organizations, government, and universities to provide resources, managed by local leadership. Key program elements of the CCI approach include (1) develop trust between CCI, local communities, local agencies, and government; (2) empower local groups to assume leadership and sustain programs; (3) support communities and groups invested in developing self-sufficiency; and (4) strengthen collaborations and partnerships between local and international organizations, universities, and government agencies. Key lessons learned by CCI are to be supportive of cultural differences; understand that limited financial and material resources may limit the program development; recognize that it is difficult not to foster dependent relationships with communities and appreciate the importance of working with and within the host country's governmental systems. CCI is expanding its service base to other regions of Ecuador and is focusing on development of the Ecuadorian health-care workforce and social inclusion opportunities for individuals with disability. The efforts of a small NGO have helped build community self-sufficiency in meeting the health care and rehabilitation needs of all Ecuadorian citizens and a greater awareness of the abilities and potential contributions of individuals with disabilities.

Effects of XIST/miR-137 axis on neuropathic pain by targeting TNFAIP1 in a rat model.

PubMed

Zhao, Ying; Li, Sen; Xia, Nin; Shi, Yan; Zhao, Chang-Ming

2018-05-01

Non-coding RNAs have been reported to participate in the pathophysiology of neuropathic pain. The objective of our study was to investigate the biological role of XIST in neuropathic pain development. In our study, we identify and validate that lncRNA XIST was markedly increased and miR-137 was significantly decreased in chronic constriction injury (CCI) rats. XIST silencing alleviated pain behaviors including both mechanical and thermal hyperalgesia in the CCI rats. XIST was predicted to interact with miR-137 by bioinformatics technology and dual-luciferase reporter assays confirmed the correlation between XIST and miR-137. miR-137 was negatively modulated by XIST and upregulation of miR-137 greatly reduced neuropathic pain development in CCI rats. Moreover, we observed that tumor necrosis factor alpha-induced protein 1 (TNFAIP1) was enhanced in CCI rats and 3'-untranslated region (UTR) of TNFAIP1 was exhibited to be a target of miR-137 by bioinformatics prediction. TNFAIP1 can act as a crucial inflammation regulator by activating NF-kB activity. Overexpression of miR-137 significantly suppressed TNFAIP1 both in vitro and in vivo. Furthermore, upregulation of XIST reversed the inhibitory role of miR-137 in neuropathic pain development by inhibiting TNFAIP1. In conclusion, our current study indicates that XIST can positively regulate neuropathic pain in rats through regulating the expression of miR-137 and TNFAIP1. Our results imply that XIST/miR-137/TNFAIP1 axis may serve as a novel therapeutic target in neuropathic pain. © 2017 Wiley Periodicals, Inc.

Trigeminal Pain Molecules, Allodynia, and Photosensitivity Are Pharmacologically and Genetically Modulated in a Model of Traumatic Brain Injury

PubMed Central

Daiutolo, Brittany V.; Tyburski, Ashley; Clark, Shannon W.

2016-01-01

Abstract The pain-signaling molecules, nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP), are implicated in the pathophysiology of post-traumatic headache (PTH) as they are for migraine. This study assessed the changes of inducible NOS (iNOS) and its cellular source in the trigeminal pain circuit, as well as the relationship between iNOS and CGRP after controlled cortical impact (CCI) injury in mice. The effects of a CGRP antagonist (MK8825) and sumatriptan on iNOS messenger RNA (mRNA) and protein were compared to vehicle at 2 weeks postinjury. Changes in CGRP levels in the trigeminal nucleus caudalis (TNC) in iNOS knockouts with CCI were compared to wild-type (WT) mice at 3 days and 2 weeks post injury. Trigeminal allodynia and photosensitivity were measured. MK8825 and sumatriptan increased allodynic thresholds in CCI groups compared to vehicle (p < 0.01), whereas iNOS knockouts were not different from WT. Photosensitivity was attenuated in MK8825 mice and iNOS knockouts compared to WT (p < 0.05). MK8825 and sumatriptan reduced levels of iNOS mRNA and iNOS immunoreactivity in the TNC and ganglia (p < 0.01). Differences in iNOS cellular localization were found between the trigeminal ganglia and TNC. Although the knockout of iNOS attenuated CGRP at 3 days (p < 0.05), it did not reduce CGRP at 2 weeks. CGRP immunoreactivity was found in the meningeal layers post-CCI, while negligible in controls. Findings support the importance of interactions between CGRP and iNOS in mediating allodynia, as well as the individual roles in photosensitivity. Mitigating prolonged increases in CGRP may be a promising intervention for treating acute PTH. PMID:26472135

Mediators of a Coping and Communication-Enhancing Intervention and a Supportive Counseling Intervention among Women Diagnosed with Gynecological Cancers

ERIC Educational Resources Information Center

Manne, Sharon L.; Winkel, Gary; Rubin, Stephen; Edelson, Mitchell; Rosenblum, Norman; Bergman, Cynthia; Hernandez, Enrique; Carlson, John; Rocereto, Thomas

2008-01-01

The authors evaluated mechanisms of change for a coping and communication-enhancing intervention (CCI) and supportive counseling (SC). They proposed that the effects of CCI on depressive symptoms would be mediated by psychological processes targeted by CCI, namely increases in the following: positive reappraisal, acceptance, planful problem…

Impairment of color vision in aircraft maintenance workers.

PubMed

Guest, Maya; D'Este, Catherine; Attia, John; Boggess, May; Brown, Anthony; Tavener, Meredith; Gibson, Richard; Gardner, Ian; Harrex, Warren; Ross, James

2011-10-01

The purpose of the study was to examine possible persisting effects to color vision in a group from the Royal Australian Air Force who had exposure to formulations containing neurotoxins during F-111 fuel tank maintenance, relative to two contemporaneous comparison groups. Color vision was tested in 512 exposed personnel, 458 technical-trade comparisons, and 330 non-technical comparisons using the Ishihara test plates and the Lanthony D-15 Desaturated Color disk arrangement test. Participants were excluded if they failed the Ishihara test as this indicates congenital color blindness. From the Lanthony results, the type of color deficient vision (CDV) was diagnosed, and additionally, the Bowman's color confusion index (CCI) was calculated. Regression models were used to examine whether there was an association between color vision deficiencies and F-111 fuel tank maintenance, adjusting for possible confounders. The CCI ranged from 1 to 2.8 (median 1.2, quartiles 1.1, 1.4) in the 2,600 eyes tested. Forty five percent of all participants had blue-yellow CDV in at least one eye. Deficiencies of this nature are caused by environmental exposures. Logistic regression demonstrated statistically significant differences in CCI category in the exposed group versus technical group (odds ratio 1.7: 95% CI 1.3-2.0) and a blue-yellow confusion in the exposed group versus technical group (odds ratio 1.4: 95% CI 1.1-1.7). No differences were observed between the exposed group and the non-technical group. The results indicate reduced color discrimination among the exposed subjects compared to one of two control groups. The findings may be due to previous exposure to solvents among the air force personnel.

Changes in shape and astigmatism of total, anterior, and posterior cornea after long versus short clear corneal incision cataract surgery.

PubMed

Hayashi, Ken; Yoshida, Motoaki; Hirata, Akira; Yoshimura, Koichi

2018-01-01

To compare changes in the shape and astigmatism of the total, anterior, and posterior cornea between eyes with long-length clear corneal incisions (CCIs) and eyes with short-length CCIs in cataract surgery. Hayashi Eye Hospital, Fukuoka, Japan. Prospective case series. Both eyes of patients having phacoemulsification with temporal CCIs were randomized to have a long-length (≥1.75 mm) or short-length (<1.75 mm) CCI. Corneal astigmatic changes were decomposed to vertical/horizontal (Jackson cross-cylinder, axes at 180 degrees and 90 degrees [J0]) and oblique changes (Jackson cross-cylinder, axes at 45 degrees and 135 degrees [J45]) using power vector analysis. Corneal shape changes were assessed using the average of the difference map on videokeratography 2 days and 2, 4, and 8 weeks postoperatively. The mean J0 and J45 values of the total cornea in the 120 eyes evaluated were significantly greater in the long CCI group than in the short CCI group at all follow-ups (P ≤ .0290). The videokeratography showed a wedge-shaped flattening in the total and anterior cornea and a steepening in the posterior cornea around the CCI 2 days postoperatively in both groups. This wound-related flattening of the total and anterior cornea rapidly reduced but persisted until 8 weeks, whereas the steepening of the posterior cornea disappeared within 4 weeks. These changes extended closer to the central cornea in the long CCI group than in the short CCI group. Corneal astigmatic changes were significantly greater after long CCI than after short CCI. The wound-related shape changes occurred immediately postoperatively but rapidly diminished. Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Wound stability and surgically induced corneal astigmatism after transconjunctival single-plane sclerocorneal incision cataract surgery.

PubMed

Hayashi, Ken; Ogawa, Soichiro; Yoshida, Motoaki; Yoshimura, Koichi

2017-01-01

To compare intraocular pressure (IOP) immediately after cataract surgery, and surgically induced corneal astigmatism (SIA) and corneal shape changes between eyes with transconjunctival single-plane sclerocorneal incisions (TSSIs) and eyes with clear corneal incisions (CCIs). Bilateral eyes of 64 patients undergoing phacoemulsification were randomized to undergo 2.4-mm temporal TSSI or CCI. IOP was measured preoperatively, and in the immediate postoperative periods. SIA was determined using vector analysis, and corneal shape changes and irregular astigmatism were evaluated using a videokeratography preoperatively, and in the early postoperative periods. Wound hydration was performed in 23 eyes (35.9 %) of the TSSI group and in 60 (93.8 %) of the CCI group (P < 0.0001). Mean IOP was significantly higher in the TSSI group than in the CCI group at 30, 60, and 120 min postoperatively (P ≤ 0.0179). SIA tended to be smaller in the TSSI group than the CCI group, but the difference was not significant. The higher order irregular astigmatism was smaller in the TSSI group than in the CCI group at 2 days (P = 0.0312). The videokeratography revealed a wound-related flattening postoperatively in both groups; this change disappeared within 4 weeks in the TSSI group, whereas it persisted until 12 weeks in the CCI group. IOP was significantly higher immediately after TSSI than after CCI and required less wound hydration, suggesting better stability with TSSI. Higher order irregular astigmatism and wound-related corneal flattening were smaller after TSSI than after CCI in the early periods, suggesting that fewer corneal shape changes with TSSI.

Treatment with ascorbic acid and α-tocopherol modulates oxidative-stress markers in the spinal cord of rats with neuropathic pain

PubMed Central

Riffel, A.P.K.; Santos, M.C.Q.; de Souza, J.A.; Scheid, T.; Horst, A.; Kolberg, C.; Belló-Klein, A.; Partata, W.A.

2018-01-01

Vitamin E (vit. E) and vitamin C (vit. C) are antioxidants that inhibit nociception. The effect of these vitamins on oxidative-stress markers in the spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve is unknown. This study investigated the effect of intraperitoneal administration of vit. E (15 mg·kg-1·day-1) and vit. C (30 mg·kg-1·day-1), given alone or in combination, on spinal cord oxidative-stress markers in CCI rats. Adult male Wistar rats weighing 200–250 g were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received injections of vitamins or vehicle (saline containing 1% Tween 80) for 3 or 10 days (n=6/each group). The vitamins prevented the reduction in total thiol content and the increase in superoxide-anion generation that were found in vehicle-treated CCI rats. While nitric-oxide metabolites increased in vehicle-treated CCI rats 3 days after surgery, these metabolites did not show significant changes in vitamin-treated CCI rats. In all rats, total antioxidant capacity and hydrogen-peroxide levels did not change significantly. Lipid hydroperoxides increased 25% only in vehicle-treated CCI rats. These changes may contribute to vit. C- and vit. E-induced antinociception, because scavenging reactive oxygen species seems to help normalize the spinal cord oxidative status altered by pain. PMID:29513797

Implications of gallbladder cholesterolosis and cholesterol polyps?

PubMed

Dairi, Saif; Demeusy, Andrew; Sill, Anne M; Patel, Shirali T; Kowdley, Gopal C; Cunningham, Steven C

2016-02-01

The clinical significance of cholesterolosis has not been well established but there are some provocative, if not robust, studies of the role it may play in the pathophysiology of pancreatitis and biliary dyskinesia, as well as hypercholesterolemia. Our aim was to take advantage of a very large cholecystectomy (CCY) database to support or refute these potentially important reported associations. A retrospective review of 6868 patients who underwent CCY from 2001-2013 was performed. Comparisons were made using the student t-test for continuous and chi-square analysis for categorical, variables. Among patients for whom the CCY was the primary operation, 1053 (18%) had cholesterolosis and 4596 did not. Compared to those without cholesterolosis, those with cholesterolosis were no more likely to have elevated cholesterol levels (P = 0.64) nor low gallbladder ejection fraction (P = 0.2). To evaluate cholesterolosis as a cause of pancreatitis, all patients with gallstones were eliminated, leaving 639 patients. Among these, not only was cholesterolosis not associated with more pancreatitis, but rather there was not a single patient with or without cholesterolosis who had pancreatitis. Despite prior reports of associations between cholesterolosis and elevated serum cholesterol, depressed ejection fraction, and increased risk of pancreatitis, careful analysis of this current, larger data set does not support these associations. Any patient with stones or sludge, or with biliary dyskinesia, and appropriate symptoms, should be considered for CCY, with or without suspected cholesterolosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of comorbidity on survival by tumour location: Breast, colorectal and lung cancer (2000-2014).

PubMed

Parés-Badell, Oleguer; Banqué, Marta; Macià, Francesc; Castells, Xavier; Sala, Maria

2017-08-01

To assess the impact of comorbidity, measured by the Charlson Comorbidity Index (CCI), on survival in breast, colorectal and lung cancer. We identified 3455 breast cancer, 3336 colorectal cancer and 2654 lung cancer patients through the Hospital del Mar cancer registry. The prevalence of comorbidities according to the CCI was calculated. Kaplan-Meier curves and the log-rank test were used to compare survival curves for each cancer location. Cox regression was used to calculate survival hazard ratios and 1-, 3- and 5-year mortality rate ratios adjusted by age, sex, CCI, place of first consultation, stage, treatment and period of diagnosis. The overall unadjusted 5-year follow-up survival proportion was 82.6% for breast cancer, 55.7% for colorectal cancer, and 16.3% for lung cancer. Overall survival was associated with CCI≥3 in breast cancer (HR: 2.33 95%CI: 1.76-3.08), colorectal cancer (HR: 1.39; 95%CI: 1.13-1.70) and lung cancer (HR: 1.22; 95%CI: 1.06-1.40). In breast cancer, the higher the CCI, the higher the adjusted mortality rate ratio and differences were greater in 5-year than in 1-year follow-up survival. Comorbidity is a significant predictor of overall survival in cancer patients; however, it has a stronger impact on survival in breast cancer than in colorectal and lung cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevention of symptomatic vasospasm by continuous cisternal irrigation with mock-CSF containing ascorbic acid and Mg(2+).

PubMed

Satoh, Akira; Sugiyama, Tatsuya; Ooigawa, Hidetoshi; Nakajima, Hiroyuki; Ogura, Takeshi; Neki, Hiroaki; Morikawa, Eiharu

2010-01-01

Symptomatic vasospasm (SVS) is still a major cause of poor outcome in cases undergoing early surgical intervention for ruptured intracranial aneurysm. Among the numbers of therapeutic trials to prevent and ameliorate neurological deterioration due to SVS, removal or quenching of oxy-hemoglobin (OxyHb) from subarachnoid colts and administration of Mg(2+) (Mg) have especially been expected to be effective. In this report the authors investigated the effect of continuous cisternal irrigation (CCI) with mock CSF containing ascorbic acid (ASA) and Mg, performed after early surgery for ruptured aneurysm. Sixty-three cases which had received CCI were retrospectively compared with 40 control cases as to the incidence of SVS and outcome. Incidence of SVS was significantly less frequent (P < 0.05) in the CCI group (11%) than in the control group (25%). Severe and definitive SVS requiring additional specific treatment occurred only in 3.2% of the CCI group, while 22.5% in the control (P < 0.01). Overall outcome at discharge was significantly better in the CCI group than in the control (P < 0.01). Postoperative CCI with ASA and Mg was definitively effective in preventing SVS and in lessening severity of SVS if it occurs.

Subjective Cognitive Complaints and Objective Cognitive Impairment in Parkinson's Disease.

PubMed

Hong, Jin Yong; Lee, Yoonju; Sunwoo, Mun Kyung; Sohn, Young H; Lee, Phil Hyu

2018-01-01

Subjective cognitive complaints (SCCs) are very common in patients with Parkinson's disease (PD). However, the relationship between SCCs and objective cognitive impairment is still unclear. This study aimed to determine whether SCCs are correlated with objective cognitive performance in patients with PD. Totals of 148 cognitively normal patients, 71 patients with mild cognitive impairment (MCI), and 31 demented patients were recruited consecutively from a movement-disorders clinic. Their SCCs and cognitive performances were evaluated using the Cognitive Complaints Interview (CCI) and a comprehensive neuropsychological battery. The CCI score increased with age, duration of PD, and depression score, and was inversely correlated with cognitive performance. The association between CCI score and performance remained significant after adjustment for the depression score, age, and duration of PD. The CCI score could be used to discriminate patients with dementia from cognitively normal and MCI patients [area under the receiver operating characteristics curve (AUC) of 0.80], but not patients with MCI or dementia from cognitively normal patients (AUC of 0.67). SCCs as measured by the CCI are strongly correlated with objective cognitive performance in patients with PD. The CCI can also be used to screen for dementia in patients with PD. Copyright © 2018 Korean Neurological Association.

Early low-anticoagulant desulfated heparin after traumatic brain injury: Reduced brain edema and leukocyte mobilization is associated with improved watermaze learning ability weeks after injury.

PubMed

Nagata, Katsuhiro; Suto, Yujin; Cognetti, John; Browne, Kevin D; Kumasaka, Kenichiro; Johnson, Victoria E; Kaplan, Lewis; Marks, Joshua; Smith, Douglas H; Pascual, Jose L

2018-05-01

Unfractionated heparin administered immediately after traumatic brain injury (TBI) reduces brain leukocyte (LEU) accumulation, and enhances early cognitive recovery, but may increase bleeding after injury. It is unknown how non-anticoagulant heparins, such as 2,3-O desulfated heparin (ODSH), impact post-TBI cerebral inflammation and long-term recovery. We hypothesized that ODSH after TBI reduces LEU-mediated brain inflammation and improves long-term neurologic recovery. CD1 male mice (n = 66) underwent either TBI (controlled cortical impact [CCI]) or sham craniotomy. 2,3-O desulfated heparin (25 mg/kg [25ODSH] or 50 mg/kg [50ODSH]) or saline was administered for 48 hours after TBI in 46 animals. At 48 hours, intravital microscopy visualized rolling LEUs and fluorescent albumin leakage in the pial circulation, and the Garcia Neurologic Test assessed neurologic function. Brain edema (wet/dry ratio) was evaluated post mortem. In a separate group of animals (n = 20), learning/memory ability (% time swimming in the Probe platform quadrant) was assessed by the Morris Water Maze 17 days after TBI. Analysis of variance with Bonferroni correction determined significance (p < 0.05). Compared with CCI (LEU rolling: 32.3 ± 13.7 LEUs/100 μm per minute, cerebrovascular albumin leakage: 57.4 ± 5.6%), both ODSH doses reduced post-TBI pial LEU rolling (25ODSH: 18.5 ± 9.2 LEUs/100 μm per minute, p = 0.036; 50ODSH: 7.8 ± 3.9 LEUs/100 μm per minute, p < 0.001) and cerebrovascular albumin leakage (25ODSH: 37.9 ± 11.7%, p = 0.001, 50ODSH: 32.3 ± 8.7%, p < 0.001). 50ODSH also reduced injured cerebral hemisphere edema (77.7 ± 0.4%) vs. CCI (78.7 ± 0.4 %, p = 0.003). Compared with CCI, both ODSH doses improved Garcia Neurologic Test at 48 hours. Learning/memory ability (% time swimming in target quadrant) was lowest in CCI (5.9 ± 6.4%) and significantly improved in the 25ODSH group (27.5 ± 8.2%, p = 0.025). 2,3-O desulfated heparin after TBI reduces cerebral LEU recruitment, microvascular permeability and edema. 2,3-O desulfated heparin may also improve acute neurologic recovery leading to improved learning/memory ability weeks after injury.

A bacosides containing Bacopa monnieri extract alleviates allodynia and hyperalgesia in the chronic constriction injury model of neuropathic pain in rats.

PubMed

Shahid, Muhammad; Subhan, Fazal; Ahmad, Nisar; Ullah, Ihsan

2017-06-05

The current therapy of neuropathic pain is inadequate and is limited by the extent of pain relief and the occurrence of dose dependant side effects. Insufficient control of pain with conventional medications prompts the use of complementary and alternative medicine therapies by patients with neuropathic pain. This study therefore investigated a standardized methanolic extract of Bacopa monnieri, a widely reputed nootropic plant, for prospective antinociceptive effect in the chronic constriction injury (CCI) model of neuropathic pain. Placement of four loose ligatures around the sciatic nerve produced partial denervation of the hindpaw in rats. Bacopa monnieri (40 and 80 mg/kg, p.o) and the positive control, gabapentin (75 mg/kg, i.p), were administered daily after CCI or sham surgery and the behavioral paradigms of static- and dynamic-allodynia (paw withdrawal threshold to von Frey filament stimulation [PWT] and paw withdrawal latency to light-brushing [PWL]), cold-allodynia (paw withdrawal duration [PWD] to acetone), heat- (PWL to heat-stimulus) and punctate-hyperalgesia (PWD to pin-prick) were assessed on days 3, 7, 14 and 21. CCI consistently generated static- (days 3-21), dynamic- (days 14-21) and cold-allodynia (days 3-21) plus heat- and mechano-hyperalgesia (days 3-21). The tested doses of Bacopa monnieri significantly attenuated the CCI-induced allodynia and hyperalgesia, exemplified by increased PWT (days 7-21), PWL to light brushing (days 14-21) and heat (days 7-21) as well as decreased PWD to pin prick and cold stimuli (days 3-21). The extract also counterbalanced the CCI-induced aberrations in the nociceptive behaviors by increasing the pain threshold to that of pre-surgery baseline. Gabapentin also afforded analogous beneficial behavioral profile but of higher magnitude. Our findings suggest that Bacopa monnieri can be used as adjuvant therapy for neuropathic pain conditions afflicted with allodynia and hyperalgesia.

HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model.

PubMed

Yang, Lijun; Wang, Feng; Yang, Liang; Yuan, Yunchao; Chen, Yan; Zhang, Gengshen; Fan, Zhenzeng

2018-01-01

Traumatic brain injury (TBI) is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB), subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1) has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. TBI was induced by controlled cortical impact (CCI) in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan's blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI. © 2018 The Author(s). Published by S. Karger AG, Basel.

Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury.

PubMed

Schober, Michelle E; Requena, Daniela F; Abdullah, Osama M; Casper, T Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R

2016-02-15

Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI.

Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury

PubMed Central

Requena, Daniela F.; Abdullah, Osama M.; Casper, T. Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R.

2016-01-01

Abstract Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI. PMID:26247583

Novel epigallocatechin-3-gallate (EGCG) derivative as a new therapeutic strategy for reducing neuropathic pain after chronic constriction nerve injury in mice.

PubMed

Xifró, Xavier; Vidal-Sancho, Laura; Boadas-Vaello, Pere; Turrado, Carlos; Alberch, Jordi; Puig, Teresa; Verdú, Enrique

2015-01-01

Neuropathic pain is common in peripheral nerve injury and often fails to respond to ordinary medication. Here, we investigated whether the two novel epigallocatechin-3-gallate (EGCG) polyphenolic derivatives, compound 23 and 30, reduce the neuropathic pain in mice chronic constriction nerve injury (CCI). First, we performed a dose-response study to evaluate nociceptive sensation after administration of EGCG and its derivatives 23 and 30, using the Hargreaves test at 7 and 21 days after injury (dpi). We daily administered EGCG, 23 and 30 (10 to 100 mg/Kg; i.p.) during the first week post-CCI. None of the doses of compound 23 caused significant pain diminution, whereas 50mg/kg was optimal for both EGCG and 30 to delay the latency of paw withdrawal. With 50 mg/Kg, we showed that EGCC prevented the thermal hyperalgesia from 7 to 21 dpi and compound 30 from 14 to 56 dpi. To evaluate the molecular mechanisms underpinning why EGCG and compound 30 differentially prevented the thermal hyperalgesia, we studied several biochemical parameters in the dorsal horn of the spinal cord at 14 and 56 dpi. We showed that the effect observed with EGCG and compound 30 was related to the inhibition of fatty acid synthase (FASN), a known target of these polyphenolic compounds. Additionally, we observed that EGCG and compound 30 reduced the expression of CCI-mediated inflammatory proteins and the nuclear localization of nuclear factor-kappa B at 14 dpi, but not at 56 dpi. We also strongly detected a decrease of synaptic plasma membrane levels of N-methyl-D-asparte receptor 2B in CCI-mice treated with compound 30 at 56 dpi. Altogether, compound 30 reduced the chronic thermal hyperalgesia induced by CCI better than the natural compound EGCG. Thus, our findings provide a rationale for the preclinical development of compound 30 as an agent to treat neuropathic pain.

Pulsed magnetic field enhances therapeutic efficiency of mesenchymal stem cells in chronic neuropathic pain model.

PubMed

Mert, Tufan; Kurt, Akif Hakan; Altun, İdiris; Celik, Ahmet; Baran, Furkan; Gunay, Ismail

2017-05-01

Cell-based or magnetic field therapies as alternative approaches to pain management have been tested in several experimental pain models. The aim of this study therefore was to investigate the actions of the cell-based therapy (adipose tissue derived mesenchymal stem cells; ADMSC) or pulsed magnetic field (PMF) therapy and magneto-cell therapy (combination of ADMSC and PMF) in chronic constriction nerve injury model (CCI). The actions of individual ADMSC (route dependent [systemic or local], time-dependent [a day or a week after surgery]), or PMF and their combination (magneto-cell) therapies on hyperalgesia and allodynia were investigated by using thermal plantar test and a dynamic plantar aesthesiometer, respectively. In addition, various cytokine levels (IL-1β, IL-6, and IL-10) of rat sciatic nerve after CCI were analyzed. Following the CCI, both latency and threshold significantly decreased. ADMSC or PMF significantly increased latencies and thresholds. The combination of ADMSC with PMF even more significantly increased latency and threshold when compared with ADMSC alone. However, ADMSC-induced decrease in pro-inflammatory or increase in anti-inflammatory cytokines levels were partially prevented by PMF treatments. Present findings may suggest that both cell-based and magnetic therapies can effectively attenuate chronic neuropathic pain symptoms. Combined magneto-cell therapy may also efficiently reverse neuropathic signs. Bioelectromagnetics. 38:255-264, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Report of CCI Early Childhood Think Tank on Governance

ERIC Educational Resources Information Center

Child Care, Inc., 2008

2008-01-01

Child Care, Inc. (CCI) invited a group of early childhood experts to help reflect on what CCI had learned from other states about governance and to apply that knowledge to New York City. The goal was to foster more systemic thinking about how to move toward a more coherent early care and education system in New York City that would better meet the…

A New CCI ECV Release (v2.0) to Accurately Measure the Sea Level Change from space (1993-2015)

NASA Astrophysics Data System (ADS)

Legeais, Jean-Francois; Benveniste, Jérôme

2017-04-01

Accurate monitoring of the sea level is required to better understand its variability and changes. Sea level is one of the Essential Climate Variables (ECV) selected in the frame of the ESA Climate Change Initiative (CCI) program. It aims at providing a long-term homogeneous and accurate sea level record. The needs and feedback of the climate research community have been collected so that the development of the products is adapted to the users. A first version of the sea level ECV product has been generated during phase I of the project (2011-2013). Within phase II (2014-2016), the 15 partner consortium has prepared the production of a new reprocessed homogeneous and accurate altimeter sea level record which is now available (see http://www.esa-sealevel-cci.org/products ). New level 2 altimeter standards developed and tested within the project as well as external contributions have been identified, processed and evaluated by comparison with a reference for different altimeter missions (TOPEX/Poseidon, Jason-1 & 2, ERS-1 & 2, Envisat, GFO, SARAL/AltiKa and CryoSat-2). The main evolutions are associated with the wet troposphere correction (based on the GPD+ algorithm including inter calibration with respect to external sensors) but also to the orbit solutions (POE-E and GFZ15), the ERA-Interim based atmospheric corrections and the FES2014 ocean tide model. A new pole tide solution is used and anomalies are referenced to the MSS DTU15. The presentation will focus on the main achievements of the ESA CCI Sea Level project and on the description of the new SL_cci ECV release covering 1993-2015. The major steps required to produce the reprocessed 23 year climate time series will be described. The impacts of the selected level 2 altimeter standards on the SL_cci ECV have been assessed on different spatial scales (global, regional, mesoscale) and temporal scales (long-term, inter-annual, periodic signals). A significant improvement is observed compared to the current v1.1, with the main impacts observed on the long-term evolution on decadal time scale, on global and regional scales, and for mesoscale signals. The results from product validation, carried out by several groups of the ocean and climate modeling community will be also presented.

Specific Stimuli Induce Specific Adaptations: Sensorimotor Training vs. Reactive Balance Training

PubMed Central

Freyler, Kathrin; Krause, Anne; Gollhofer, Albert; Ritzmann, Ramona

2016-01-01

Typically, balance training has been used as an intervention paradigm either as static or as reactive balance training. Possible differences in functional outcomes between the two modalities have not been profoundly studied. The objective of the study was to investigate the specificity of neuromuscular adaptations in response to two balance intervention modalities within test and intervention paradigms containing characteristics of both profiles: classical sensorimotor training (SMT) referring to a static ledger pivoting around the ankle joint vs. reactive balance training (RBT) using externally applied perturbations to deteriorate body equilibrium. Thirty-eight subjects were assigned to either SMT or RBT. Before and after four weeks of intervention training, postural sway and electromyographic activities of shank and thigh muscles were recorded and co-contraction indices (CCI) were calculated. We argue that specificity of training interventions could be transferred into corresponding test settings containing properties of SMT and RBT, respectively. The results revealed that i) postural sway was reduced in both intervention groups in all test paradigms; magnitude of changes and effect sizes differed dependent on the paradigm: when training and paradigm coincided most, effects were augmented (P<0.05). ii) These specificities were accompanied by segmental modulations in the amount of CCI, with a greater reduction within the CCI of thigh muscles after RBT compared to the shank muscles after SMT (P<0.05). The results clearly indicate the relationship between test and intervention specificity in balance performance. Hence, specific training modalities of postural control cause multi-segmental and context-specific adaptations, depending upon the characteristics of the trained postural strategy. In relation to fall prevention, perturbation training could serve as an extension to SMT to include the proximal segment, and thus the control of structures near to the body’s centre of mass, into training. PMID:27911944

Closed form expressions for ABER and capacity over EGK fading channel in presence of CCI

NASA Astrophysics Data System (ADS)

Singh, S. Pratap; Kumar, Sanjay

2017-03-01

Goal of next generation wireless communication system is to achieve very high data rate. Femto-cell is one of the possibilities to achieve the above target. However, co-channel interference (CCI) is the important concern in femto-cell. This paper presents closed form expressions for average bit error rate (ABER) and capacity for different adaptive schemes under extended generalised-K (EGK) fading channel in the presence of CCI. A novel conditional unified expression (CUE) is derived, which results different conditional error probability and normalised average capacity. Using CUE, a generic expression for ABER is obtained. In addition, closed form expressions for ABER for different modulation schemes under EGK fading channel in presence of CCI are also derived. Further, it is shown that generic ABER expression results into ABER of different modulation schemes. Besides, the closed form expressions of capacity for different adaptive schemes under EGK in presence of CCI are derived. Finally, analytical and simulated results are obtained with excellent agreement.

Overview of different scoring systems in Fournier’s Gangrene and assessment of prognostic factors

PubMed Central

Doluoğlu, Ömer Gökhan; Karagöz, Mehmet Ali; Kılınç, Muhammet Fatih; Karakan, Tolga; Yücetürk, Cem Nedim; Sarıcı, Haşmet; Özgür, Berat Cem; Eroğlu, Muzaffer

2016-01-01

Objective In this study we aimed to evaluate prognostic factors for the survival of patients with Fournier’s gangrene (FG), and overview different validated scoring systems for outcome prediction. Material and methods We retrospectively analyzed the data of 39 patients treated for FG in our clinic. Data were collected on medical history, symptoms, physical examination findings, vital signs, laboratory parameters at admission and at the end of treatment, timing and extent of surgical debridement, and the antibiotic treatment used. The Fournier’s Gangrene Severity Index (FGSI) and Charlson Comorbidity Index (CCI) were used to predict outcome. The data were analyzed in relation with the survival of the patients. Mann-Whitney U test, chi -square test, Wilcoxon signed rank test, and Cox regression analysis were used for the statistical analysis. Results Of 39 patients analyzed, 8 (20.5%) died and 31 (79.5%) survived. The median FGSI score on admission was 2 (0–9) for the survivors and 6 (2–14) for the non-survivors (p=0.004). The median CCI scores of the survivors and non-survivors were 2 (0–10) and 6.5 (5–11), respectively (p=0.001). Except for urea, albumin and hematocrit levels, no significant differences were found between survivors and non-survivors for other laboratory parameters on admission. Lower albumin levels and advanced age were found to be associated with mortality. Conclusion High blood urea, low albumin, and low hematocrit levels were associated with poor prognosis. High CCI and FGSI scores could be associated with a poor prognosis in patients with FG. PMID:27635295

Therapeutic Time Window for Edaravone Treatment of Traumatic Brain Injury in Mice

PubMed Central

Miyamoto, Kazuyuki; Ohtaki, Hirokazu; Dohi, Kenji; Tsumuraya, Tomomi; Song, Dandan; Kiriyama, Keisuke; Satoh, Kazue; Shimizu, Ai; Aruga, Tohru; Shioda, Seiji

2013-01-01

Traumatic brain injury (TBI) is a major cause of death and disability in young people. No effective therapy is available to ameliorate its damaging effects. Our aim was to investigate the optimal therapeutic time window of edaravone, a free radical scavenger which is currently used in Japan. We also determined the temporal profile of reactive oxygen species (ROS) production, oxidative stress, and neuronal death. Male C57Bl/6 mice were subjected to a controlled cortical impact (CCI). Edaravone (3.0 mg/kg), or vehicle, was administered intravenously at 0, 3, or 6 hours following CCI. The production of superoxide radicals (O2 ∙−) as a marker of ROS, of nitrotyrosine (NT) as an indicator of oxidative stress, and neuronal death were measured for 24 hours following CCI. Superoxide radical production was clearly evident 3 hours after CCI, with oxidative stress and neuronal cell death becoming apparent after 6 hours. Edaravone administration after CCI resulted in a significant reduction in the injury volume and oxidative stress, particularly at the 3-hour time point. Moreover, the greatest decrease in O2 ∙− levels was observed when edaravone was administered 3 hours following CCI. These findings suggest that edaravone could prove clinically useful to ameliorate the devastating effects of TBI. PMID:23710445

Antarctic and Greenland ice sheet mass balance products from satellite gravimetry

NASA Astrophysics Data System (ADS)

Horwath, Martin; Groh, Andreas; Horvath, Alexander; Forsberg, René; Meister, Rakia; Barletta, Valentina R.; Shepherd, Andrew

2017-04-01

Because of their important role in the Earth's climate system, ESA's Climate Change Initiative (CCI) has identified both the Antarctic Ice Sheet (AIS) and the Greenland Ice Sheet (GIS) as Essential Climate Variables (ECV). Since respondents of a user survey indicated that the ice sheet mass balance is one of the most important ECV data products needed to better understand climate change, the AIS_cci and the GIS_cci project provide Gravimetric Mass Balance (GMB) products based on satellite gravimetry data. The GMB products are derived from GRACE (Gravity Recovery and Climate Experiment) monthly solutions of release ITSG-Grace2016 produced at TU Graz. GMB basin products (i.e. time series of monthly mass changes for the entire ice sheets and selected drainage basins) and GMB gridded products (e.g. mass balance estimates with a formal resolution of about 50km, covering the entire ice sheets) are generated for the period from 2002 until present. The first GMB product was released in mid 2016. Here we present an extended and updated version of the ESA CCI GMB products, which are freely available through data portals hosted by the projects (https://data1.geo.tu-dresden.de/ais_gmb, http://products.esa-icesheets-cci.org/products/downloadlist/GMB). Since the initial product release, the applied processing strategies have been improved in order to further reduce GRACE errors and to enhance the separation of signals super-imposed to the ice mass changes. While a regional integration approach is used by the AIS_cci project, the GMB products of the GIS_cci project are derived using a point mass inversion. The differences between both approaches are investigated through the example of the GIS, where an alternative GMB product was generated using the regional integration approach implemented by the AIS_cci. Finally, we present the latest mass balance estimates for both ice sheets as well as their corresponding contributions to global sea level rise.

Collaborating with Communities and Higher Education to Address the Health-care Needs of Individuals with Disabilities in Ecuador

PubMed Central

Cech, Donna J.; Alvarado, Zully J.

2017-01-01

Individuals with disabilities experience inequities in access to health care, education, employment, and social inclusion. Causes for Change International (CCI), a non-governmental Organization (NGO), using a community-based rehabilitation approach has worked for 20 years to build self-sufficiency, improve health-care services, and education for women, children, and persons with disabilities in Ecuador. CCI initially addressed health; advocacy for individuals with disabilities; and promoted educational opportunities for children with disabilities, starting in one rural community. CCI’s outreach has expanded through Ecuador’s coastal provinces, Andean provinces, and Galapagos Islands. CCI also focused on local health-care workforce development, developing employment skills for individuals with disabilities and social inclusion for this population. CCI collaborated with local organizations, government, and universities to provide resources, managed by local leadership. Key program elements of the CCI approach include (1) develop trust between CCI, local communities, local agencies, and government; (2) empower local groups to assume leadership and sustain programs; (3) support communities and groups invested in developing self-sufficiency; and (4) strengthen collaborations and partnerships between local and international organizations, universities, and government agencies. Key lessons learned by CCI are to be supportive of cultural differences; understand that limited financial and material resources may limit the program development; recognize that it is difficult not to foster dependent relationships with communities and appreciate the importance of working with and within the host country’s governmental systems. CCI is expanding its service base to other regions of Ecuador and is focusing on development of the Ecuadorian health-care workforce and social inclusion opportunities for individuals with disability. The efforts of a small NGO have helped build community self-sufficiency in meeting the health care and rehabilitation needs of all Ecuadorian citizens and a greater awareness of the abilities and potential contributions of individuals with disabilities. PMID:28484696

KSC-2013-3092

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068344 - NASA astronaut Randy Bresnik gets into position in The Boeing Company's CST-100 spacecraft for a fit check evaluation at the company's Houston Product Support Center. Bresnik's fit check will help evaluate a crew's maneuverability in the spacecraft and test communications. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3088

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068317 - NASA astronaut Serena Aunon exits The Boeing Company's CST-100 spacecraft following a fit check evaluation at the company's Houston Product Support Center. Aunon's fit check will help evaluate a crew's maneuverability in the spacecraft and test communications. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3080

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068269 - NASA astronaut Serena Aunon prepares to enter The Boeing Company's CST-100 spacecraft for a fit check evaluation at the company's Houston Product Support Center. Aunon's fit check will help evaluate a crew's maneuverability in the spacecraft and test communications. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3091

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068333 - NASA astronaut Randy Bresnik prepares to enter The Boeing Company's CST-100 spacecraft for a fit check evaluation at the company's Houston Product Support Center. Bresnik's fit check will help evaluate a crew's maneuverability in the spacecraft and test communications. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3078

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068260 - NASA astronaut Serena Aunon suits up for a fit check evaluation of The Boeing Company's CST-100 spacecraft at the company's Houston Product Support Center. Aunon's fit check will help evaluate a crew's maneuverability in the spacecraft and test communications. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

The Controlled Cortical Impact Model of Experimental Brain Trauma: Overview, Research Applications, and Protocol

PubMed Central

Osier, Nicole; Dixon, C. Edward

2017-01-01

Controlled cortical impact (CCI) is a commonly used and highly regarded model of brain trauma that uses a pneumatically or electromagnetically controlled piston to induce reproducible and well-controlled injury. The CCI model was originally used in ferrets and it has since been scaled for use in many other species. This chapter will describe the historical development of the CCI model, compare and contrast the pneumatic and electromagnetic models, and summarize key short- and long-term consequences of TBI that have been gleaned using this model. In accordance with the recent efforts to promote high-quality evidence through the reporting of common data elements (CDEs), relevant study details—that should be reported in CCI studies—will be noted. PMID:27604719

The Controlled Cortical Impact Model of Experimental Brain Trauma: Overview, Research Applications, and Protocol.

PubMed

Osier, Nicole; Dixon, C Edward

2016-01-01

Controlled cortical impact (CCI) is a commonly used and highly regarded model of brain trauma that uses a pneumatically or electromagnetically controlled piston to induce reproducible and well-controlled injury. The CCI model was originally used in ferrets and it has since been scaled for use in many other species. This chapter will describe the historical development of the CCI model, compare and contrast the pneumatic and electromagnetic models, and summarize key short- and long-term consequences of TBI that have been gleaned using this model. In accordance with the recent efforts to promote high-quality evidence through the reporting of common data elements (CDEs), relevant study details-that should be reported in CCI studies-will be noted.

Rapid screening for perceived cognitive impairment in major depressive disorder.

PubMed

Iverson, Grant L; Lam, Raymond W

2013-05-01

Subjectively experienced cognitive impairment is common in patients with mood disorders. The British Columbia Cognitive Complaints Inventory (BC-CCI) is a 6-item scale that measures perceived cognitive problems. The purpose of this study is to examine the reliability of the scale in healthy volunteers and depressed patients and to evaluate the sensitivity of the measure to perceived cognitive problems in depression. Participants were 62 physician-diagnosed inpatients or outpatients with depression, who had independently confirmed diagnoses on the Structured Clinical Interview for DSM-IV, and a large sample of healthy community volunteers (n=112). The internal consistency reliability of the BC-CCI was α=.86 for patients with depression and α=.82 for healthy controls. Principal components analyses revealed a one-factor solution accounting for 54% of the total variability in the control sample and a 2-factor solution (cognitive impairment and difficulty with expressive language) accounting for 76% of the variance in the depression sample. The total score difference between the groups was very large (Cohen's d=2.2). The BC-CCI has high internal consistency in both depressed patients and community controls, despite its small number of items. The test is sensitive to cognitive complaints in patients with depression.

Metabolic fate of glucose in rats with traumatic brain injury and pyruvate or glucose treatments: A NMR spectroscopy study.

PubMed

Shijo, Katsunori; Sutton, Richard L; Ghavim, Sima S; Harris, Neil G; Bartnik-Olson, Brenda L

2017-01-01

Administration of sodium pyruvate (SP; 9.08 μmol/kg, i.p.), ethyl pyruvate (EP; 0.34 μmol/kg, i.p.) or glucose (GLC; 11.1 μmol/kg, i.p.) to rats after unilateral controlled cortical impact (CCI) injury has been reported to reduce neuronal loss and improve cerebral metabolism. In the present study these doses of each fuel or 8% saline (SAL; 5.47 nmoles/kg) were administered immediately and at 1, 3, 6 and 23 h post-CCI. At 24 h all CCI groups and non-treated Sham injury controls were infused with [1,2 13 C] glucose for 68 min 13 C nuclear magnetic resonance (NMR) spectra were obtained from cortex + hippocampus tissues from left (injured) and right (contralateral) hemispheres. All three fuels increased lactate labeling to a similar degree in the injured hemisphere. The amount of lactate labeled via the pentose phosphate and pyruvate recycling (PPP + PR) pathway increased in CCI-SAL and was not improved by SP, EP, and GLC treatments. Oxidative metabolism, as assessed by glutamate labeling, was reduced in CCI-SAL animals. The greatest improvement in oxidative metabolism was observed in animals treated with SP and fewer improvements after EP or GLC treatments. Compared to SAL, all three fuels restored glutamate and glutamine labeling via pyruvate carboxylase (PC), suggesting improved astrocyte metabolism following fuel treatment. Only SP treatments restored the amount of [4 13 C] glutamate labeled by the PPP + PR pathway to sham levels. Milder injury effects in the contralateral hemisphere appear normalized by either SP or EP treatments, as increases in the total pool of 13 C lactate and labeling of lactate in glycolysis, or decreases in the ratio of PC/PDH labeling of glutamine, were found only for CCI-SAL and CCI-GLC groups compared to Sham. The doses of SP, EP and GLC examined in this study all enhanced lactate labeling and restored astrocyte-specific PC activity but differentially affected neuronal metabolism after CCI injury. The restoration of astrocyte metabolism by all three fuel treatments may partially underlie their abilities to improve cerebral glucose utilization and to reduce neuronal loss following CCI injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metabolic fate of glucose in rats with traumatic brain injury and pyruvate or glucose treatments: A NMR spectroscopy study

PubMed Central

Shijo, Katsunori; Sutton, Richard L.; Ghavim, Sima S.; Harris, Neil G.; Bartnik-Olson, Brenda L.

2016-01-01

Administration of sodium pyruvate (SP; 9.08 μmol/kg, i.p.), ethyl pyruvate (EP; 0.34 μmol/kg, i.p.) or glucose (GLC; 11.1 μmol/kg, i.p.) to rats after unilateral controlled cortical impact (CCI) injury has been reported to reduce neuronal loss and improve cerebral metabolism. In the present study these doses of each fuel or 8% saline (SAL; 5.47 nmoles/kg) were administered immediately and at 1, 3, 6 and 23 h post-CCI. At 24 h all CCI groups and non-treated Sham injury controls were infused with [1,2 13C] glucose for 68 min 13C nuclear magnetic resonance (NMR) spectra were obtained from cortex + hippocampus tissues from left (injured) and right (contralateral) hemispheres. All three fuels increased lactate labeling to a similar degree in the injured hemisphere. The amount of lactate labeled via the pentose phosphate and pyruvate recycling (PPP + PR) pathway increased in CCI-SAL and was not improved by SP, EP, and GLC treatments. Oxidative metabolism, as assessed by glutamate labeling, was reduced in CCI-SAL animals. The greatest improvement in oxidative metabolism was observed in animals treated with SP and fewer improvements after EP or GLC treatments. Compared to SAL, all three fuels restored glutamate and glutamine labeling via pyruvate carboxylase (PC), suggesting improved astrocyte metabolism following fuel treatment. Only SP treatments restored the amount of [4 13C] glutamate labeled by the PPP + PR pathway to sham levels. Milder injury effects in the contralateral hemisphere appear normalized by either SP or EP treatments, as increases in the total pool of 13C lactate and labeling of lactate in glycolysis, or decreases in the ratio of PC/PDH labeling of glutamine, were found only for CCI-SAL and CCI-GLC groups compared to Sham. The doses of SP, EP and GLC examined in this study all enhanced lactate labeling and restored astrocyte-specific PC activity but differentially affected neuronal metabolism after CCI injury. The restoration of astrocyte metabolism by all three fuel treatments may partially underlie their abilities to improve cerebral glucose utilization and to reduce neuronal loss following CCI injury. PMID:27919624

Subjective Global Assessment-Dialysis Malnutrition Score and cardiovascular risk in hemodialysis patients: an observational cohort study.

PubMed

Spatola, Leonardo; Finazzi, Silvia; Calvetta, Albania; Reggiani, Francesco; Morenghi, Emanuela; Santostasi, Silvia; Angelini, Claudio; Badalamenti, Salvatore; Mugnai, Giacomo

2018-06-23

Malnutrition is an important risk factor for cardiovascular mortality in hemodialysis (HD) patients. However, current malnutrition biomarkers seem unable to accurately estimate the role of malnutrition in predicting cardiovascular risk. Our aim was to investigate the role of the Subjective Global Assessment-Dialysis Malnutrition Score (SGA-DMS) compared to two well-recognized comorbidity scores-Charlson Comorbidity Index (CCI) and modified CCI (excluding age-factor) (mCCI)-in predicting cardiovascular events in HD patients. In 86 maintenance HD patients followed from June 2015 to June 2017, we analyzed biohumoral data and clinical scores as risk factors for cardiovascular events (acute heart failure, acute coronary syndrome and stroke). Their impact on outcome was investigated by linear regression, Cox regression models and ROC analysis. Cardiovascular events occurred in 26/86 (30%) patients during the 2-year follow-up. Linear regression showed only age and dialysis vintage to be positively related to SGA-DMS: B 0.21 (95% CI 0.01; 0.30) p 0.05, and B 0.24 (0.09; 0.34) p 0.02, respectively, while serum albumin, normalized protein catabolic rate (nPCR) and dialysis dose (Kt/V) were negatively related to SGA-DMS: B - 1.29 (- 3.29; - 0.81) p 0.02; B - 0.08 (- 1.52; - 0.35) p 0.04 and B - 2.63 (- 5.25; - 0.22) p 0.03, respectively. At Cox regression analysis, SGA-DMS was not a risk predictor for cardiovascular events: HR 1.09 (0.9; 1.22), while both CCI and mCCI were significant predictors: HR 1.43 (1.13; 1.87) and HR 1.57 (1.20; 2.06) also in Cox adjusted models. ROC analysis reported similar AUCs for CCI and mCCI: 0.72 (0.60; 0.89) p 0.00 and 0.70 (0.58; 0.82) p 0.00, respectively, compared to SGA-DMS 0.56 (0.49; 0.72) p 0.14. SGA-DMS is not a superior and significant prognostic tool compared to CCI and mCCI in assessing cardiovascular risk in HD patients, even it allows to appraise both malnutrition and comorbidity status.

Silencing of FKBP51 alleviates the mechanical pain threshold, inhibits DRG inflammatory factors and pain mediators through the NF-kappaB signaling pathway.

PubMed

Yu, Hong-Mei; Wang, Qi; Sun, Wen-Bo

2017-09-05

Neuropathic pain is chronic pain caused by lesions or diseases of the somatosensory system, currently available analgesics provide only temporal relief. The precise role of FK506 binding protein 51 (FKBP51) in neuropathic pain induced by chronic constriction injury (CCI) is not clear. The purpose of the present study was to investigate the effects and possible mechanisms of FKBP51 in neuropathic pain in the rat model of CCI. Our results showed that FKBP51 was obviously upregulated in a time-dependent manner in the dorsal root ganglion (DRG) of CCI rats. Additionally, silencing of FKBP51 remarkably attenuated mechanical allodynia and thermal hyperalgesia as reflected by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in CCI rats. Moreover, knockdown of FKBP51 reduced the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in the DRG of CCI rats. Furthermore, we revealed that inhibition of FKBP51 greatly suppressed the activation of the NF-kappaB (NF-κB) signaling in the DRG of CCI rats. Interestingly, similar to the FKBP51 siRNA (si-FKBP51), ammonium pyrrolidinedithiocarbamate (PDTC, an inhibitor of NF-κB) also alleviated neuropathic pain and neuro-inflammation, indicating that knockdown of FKBP51 alleviated neuropathic pain development of CCI rats by inhibiting the activation of NF-κB signaling pathway. Taken together, our findings indicate that FKBP51 may serve as a novel therapeutic target for neuropathic pain. Copyright © 2017. Published by Elsevier B.V.

Emergency radiology: straightening of the cervical spine in MDCT after trauma—a sign of injury or normal variant?

PubMed Central

Deak, Zsuszsanna; Krtakovska, Aina; Ruschi, Francesco; Kammer, Nora; Wirth, Stefan; Reiser, Maximilian; Geyer, Lucas

2016-01-01

Objective: To evaluate whether straightening of the cervical spine (C-spine) alignment after trauma can be considered a significant multidetector CT (MDCT) finding. Methods: 160 consecutive patients after C-spine trauma admitted to a Level 1 trauma centre received MDCT according to Canadian Cervical Spine Rule and National Emergency X-Radiography Utilization Study indication rule; subgroups with and without cervical collar immobilization (CCI +/−) were compared with a control group (n = 20) of non-traumatized patients. Two independent readers evaluated retrospectively the alignment, determined the absolute rotational angle of the posterior surface of C2 and C7 (ARA C2–7) and grouped the results for lordosis (<−13°), straight (−13 to +6°) and kyphosis (>+6°). Results: In the two CCI−/CCI+ study groups, the straight or kyphotic alignment significantly (p = 0.001) predominated over lordosis. The number of patients with straight C-spine alignment was higher in the CCI+ group (CCI+ 69% vs CCI− 49%, p = 0.05). A comparison of the CCI+ group vs the CCI− group revealed a slightly smaller number of kyphotic (10% vs 18%, p = 0.34) and lordotic (21% vs 33%, p = 0.33) alignments. Statistically, however, the differences were of no significance. The control group revealed no significant differences. Conclusion: Straightening of the C-spine alone is not a definitive sign of injury but is a biomechanical variation due to CCI and neck positioning during MDCT or active patient control. Advances in knowledge: Straightening of the C-spine alignment in MDCT alone is not a definitive sign of injury. Straightening of the C-spine alignment is related to neck positioning and active patient control. CCI has a straightening effect on the cervical alignment. PMID:26764283

Tissue mortality by Caribbean ciliate infection and white band disease in three reef-building coral species

PubMed Central

Bastidas, Carolina; Croquer, Aldo

2016-01-01

Caribbean ciliate infection (CCI) and white band disease (WBD) are diseases that affect a multitude of coral hosts and are associated with rapid rates of tissue losses, thus contributing to declining coral cover in Caribbean reefs. In this study we compared tissue mortality rates associated to CCI in three species of corals with different growth forms: Orbicella faveolata (massive-boulder), O. annularis (massive-columnar) and Acropora cervicornis (branching). We also compared mortality rates in colonies of A. cervicornis bearing WBD and CCI. The study was conducted at two locations in Los Roques Archipelago National Park between April 2012 and March 2013. In A. cervicornis, the rate of tissue loss was similar between WBD (0.8 ± 1 mm/day, mean ± SD) and CCI (0.7 ± 0.9 mm/day). However, mortality rate by CCI in A. cervicornis was faster than in the massive species O. faveolata (0.5 ± 0.6 mm/day) and O. annularis (0.3 ± 0.3 mm/day). Tissue regeneration was at least fifteen times slower than the mortality rates for both diseases regardless of coral species. This is the first study providing coral tissue mortality and regeneration rates associated to CCI in colonies with massive morphologies, and it highlights the risks of further cover losses of the three most important reef-building species in the Caribbean. PMID:27547525

Anti-nociceptive and anti-inflammatory actions of sulforaphane in chronic constriction injury-induced neuropathic pain mice.

PubMed

Wang, Cheng; Wang, Congpin

2017-02-01

Neuropathic pain is still considered as incurable disease as current therapies are not ideal in terms of efficacy and tolerability. It is imperative to search for novel drugs to obtain better treatments. Sulforaphane (SFN), a derivative of glucoraphanin present in cruciferous vegetables, exhibits therapeutic effects on inflammation-related diseases. Since inflammation plays an important role in regulating chronic pain, in the present study, we investigated anti-nociceptive effects of SFN and its underlying mechanisms in a neuropathic pain mouse model, sciatic nerve chronic constriction injury (CCI). SFN (0.1-100 mg/kg) was injected intraperitoneally for 7 days when pain behaviors, including mechanical allodynia and thermal hyperalgesia, reached to the maximum in CCI mice. We observed that SFN dose-dependently attenuated CCI-induced pain behavioral hypersensitivity, accompanied by reduction in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and upregulation of an anti-inflammatory cytokine (IL-10). Moreover, SFN counteracted CCI enhancement of COX2 and iNOS in injured nerves, two key enzymes implicated in inflammation and neuropathic pain. Furthermore, pretreatment of naloxone, an antagonist of opioid receptors, significantly blocked SFN attenuation of behavioral hypersensitivity without affecting SFN modulation of inflammatory cytokines in CCI mice. Interestingly, CCI-induced increase in µ-opioid receptors in injured sciatic nerves was further increased by SFN treatment. Taken together, SFN has both anti-nociceptive and anti-inflammatory actions.

Electroacupuncture Reduces the Effects of Acute Noxious Stimulation on the Electrical Activity of Pain-Related Neurons in the Hippocampus of Control and Neuropathic Pain Rats

PubMed Central

Wang, Jun-Ying; Chen, Renbo; Feng, Xiu-Mei; Yan, Yaxia; Lippe, Irmgard Th.

2016-01-01

To study the effects of acupuncture analgesia on the hippocampus, we observed the effects of electroacupuncture (EA) and mitogen-activated protein kinase (MEK) inhibitor on pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal area CA1 of sham or chronic constrictive injury (CCI) rats. The animals were randomly divided into a control, a CCI, and a U0126 (MEK1/2 inhibitor) group. In all experiments, we briefly (10-second duration) stimulated the sciatic nerve electrically and recorded the firing rates of PENs and PINs. The results showed that in both sham and CCI rats brief sciatic nerve stimulation significantly increased the electrical activity of PENs and markedly decreased the electrical activity of PINs. These effects were significantly greater in CCI rats compared to sham rats. EA treatment reduced the effects of the noxious stimulus on PENs and PINs in both sham and CCI rats. The effects of EA treatment could be inhibited by U0126 in sham-operated rats. The results suggest that EA reduces effects of acute sciatic nerve stimulation on PENs and PINs in the CA1 region of the hippocampus of both sham and CCI rats and that the ERK (extracellular regulated kinase) signaling pathway is involved in the modulation of EA analgesia. PMID:27833763

"Product on Stopper" in a Lyophilized Drug Product: Cosmetic Defect or a Product Quality Concern?

PubMed

Mehta, Shyam B; Roy, Shouvik; Yang, Han-Chang Cathy

2018-06-01

During manufacturing of a lyophilized drug product, operator errors in product handling during loading of product filled vials onto the lyophilizer can lead to a seemingly cosmetic defect which can impact certain critical quality attributes of finished product. In this study, filling of a formulated monoclonal antibody in vials was performed using a peristaltic pump filling unit, and subsequently, the product was lyophilized. After lyophilization, upon visual inspection, around 40% of vials had cosmetic defect with residual product around stopper of the vial and were categorized as "product on stopper" vials, whereas remaining 60% vials with no cosmetic defect were called "acceptable vials." Both groups of vials from 1 single batch were tested for critical quality attributes including protein concentration (ultraviolet absorbance at 280), residual moisture (Karl Fischer), sterility (membrane filtration), and container closure integrity (CCI) (blue dye ingress). Analysis of protein quality attributes such as aggregation, protein concentration, residual moisture showed no significant difference between vials with "product on stopper" and "acceptable vials." However, CCI of the "product on stopper" vials was compromised due to the presence of product around stopper of the vial. The results from this case study demonstrate the following 2 important findings: (1) that a seemingly cosmetic defect may impact product quality, compromising the integrity of the product and (2) that CCI test method can be used as an orthogonal method to sterility testing to evaluate sterility assurance of the product. The corrective action proposed to mitigate this defect is use of a larger sized vial that can potentially minimize this defect that arises because of product handling errors. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Reconciling the aerosol-liquid water path relationship in the ECHAM6-HAM GCM and the Aerosol_cci/Cloud_cci (A)ATSR dataset by minimizing the effect of aerosol swelling

NASA Astrophysics Data System (ADS)

Neubauer, D.; Christensen, M.; Lohmann, U.; Poulsen, C. A.

2016-12-01

Studies using present day variability to assess statistical relationships between aerosol and cloud properties find different strengths of these relationships between satellite data and general circulation model (GCM) data. This discrepancy can be explained by structural uncertainties due to differences in the analysis/observational scale and the process scale or spurious relationships between aerosol and cloud properties. Such spurious relationships are the growth of aerosol particles in the humid environment surrounding clouds, misclassification of partly cloudy satellite pixels as cloud free pixels, brightening of aerosol particles by sunlight reflected at cloud edges, or effects of clouds on aerosol like processing of aerosol particles in clouds by nucleation or impact scavenging and subsequent growth by heterogeneous chemistry and release by cloud droplet evaporation or wet scavenging of aerosol particles. To minimize the effects of spatial aggregation and spurious relationships we apply a new nearest neighbour approach to high resolution (A)ATSR datasets from the Aerosol_cci and Cloud_cci projects of the Climate Change Initiative (CCI) programme of ESA. For the ECHAM6-HAM GCM we quantify the impact of using dry aerosol (without aerosol water) in the analysis to mimic the effect of the nearest neighbour approach. The aerosol-liquid water path relationship in ECHAM6-HAM is systematically stronger than in (A)ATSR data and cannot be explained by an overestimation of autoconversion when using diagnostic precipitation but rather by aerosol swelling in regions where humidity is high and clouds are present. When aerosol water is removed from the analysis in ECHAM6-HAM the strength of the aerosol-liquid water path relationship agrees much better with the ones of (A)ATSR or MODIS. We further find that while the observed relationships of different satellite sensors ((A)ATSR vs. MODIS) are not always consistent for tested environmental conditions the relationships in ECHAM6-HAM are missing a strong dependence on environmental conditions which is critical for bridging the gap between satellite and model estimates of aerosol indirect forcing.

KSC-2013-3076

NASA Image and Video Library

2013-07-22

HOUSTON - NASA astronaut Serena Aunon puts on her orange launch-and-entry suit for a fit check evaluation of The Boeing Company's CST-100 spacecraft at the company's Houston Product Support Center. Aunon's fit check will help evaluate a crew's maneuverability in the spacecraft and test communications. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3090

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068329 - NASA astronaut Randy Bresnik is interviewed by the media before he enters The Boeing Company's CST-100 spacecraft for a fit check evaluation at the company's Houston Product Support Center. Bresnik's fit check will help evaluate a crew's maneuverability in the spacecraft and test communications. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3079

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068264 - NASA astronaut Serena Aunon's boots are covered before she enters The Boeing Company's CST-100 spacecraft for a fit check evaluation at the company's Houston Product Support Center. Aunon's fit check will help evaluate a crew's maneuverability in the spacecraft and test communications. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

Charlson Comorbidity Index, inappropriate medication use and cognitive impairment : Bermuda Triangle.

PubMed

Silay, Kamile; Yalcin, Ahmet; Akinci, Sema; Gursoy, Fatma Gul; Sener Dede, Didem

2017-11-01

The aim is to evaluate the association between the Charlson Comorbidity Index (CCI), polypharmacy, inappropriate medication use and cognitive impairment in long-term care facility patients. A cross-sectional study including 105 long-term care facility residents was performed. The Charlson Comorbidity Index (CCI) was used. Inappropriate drug use (IDU) was defined according to the STOPP (Screening Tool of Older People's Prescriptions) criteria. Univariate analysis to identify variables associated with patient outcome related with cognitive impairment was investigated with χ 2 , Pearson correlation, Fisher exact, and Mann-Whitney U test where appropriate. For the multivariate analysis, the possible factors identified with univariate analysis were further entered into logistic regression analysis. A significant difference was found between gender, CCI and cognitive impairment (p = 0.038, p = 0.01). While every one point increment in the CCI increases the risk of cognitive impairment 3.1 fold (95% CI = 1.8-5.4, p < 0.001), hypertension increases the risk 12 fold (95% CI = 2.5-67.8, p = 0.002). While the correlation between Mini-Mental Status Examination (MMSE) score and polypharmacy is significant (p = 0.015), the correlation between MMSE and IDU was insignificant (p = 0.739). The association of urogenital system drugs and dementia was significant (p = 0.044). Comorbidities, especially hypertension and old age, are risk factors for cognitive impairment. Polypharmacy correlates with MMSE and is considered a risk factor for cognitive impairment. Inappropriate medication use is high among long-term care facility residents. More studies on large cohorts are needed regarding optimal drug prescription and detection of specific drugs that may have an impact on cognitive performance.

Attenuating effect of Acorus calamus extract in chronic constriction injury induced neuropathic pain in rats: an evidence of anti-oxidative, anti-inflammatory, neuroprotective and calcium inhibitory effects

PubMed Central

2011-01-01

Background Acorus calamus (family: Araceae), is an indigenous plant, traditionally it is used as an ingredient of various cocktail preparations and for the management of severe inflammatory disorders in Indian system of medicine. Present study investigated the attenuating role of Acorus calamus plant extract in chronic constriction injury (CCI) of sciatic nerve induced peripheral neuropathy in rats. Methods Hot plate, plantar, Randall Selitto, Von Frey Hair, pin prick, acetone drop, photoactometer and rota-rod tests were performed to assess degree of thermal, radiant, mechanical, chemical sensation, spontaneous motor activity and motor co-ordination changes respectively, at different time intervals i.e., day 0, 1, 3, 6, 9, 12, 15, 18 and 21. Tissue myeloperoxidase, superoxide anion and total calcium levels were determined after 21st day to assess biochemical alterations. Histopathological evaluations were also performed. Hydroalcoholic extract of Acorus calamus (HAE-AC, 100 and 200 mg/kg, p.o.) and pregabalin (10 mg/kg, p.o.) were administered from the day of surgery for 14 days. Results CCI of sciatic nerve significantly induced thermal, radiant, mechanical hyperalgesia and thermal, chemical, tactile allodynia, along with increase in the levels of superoxide anion, total calcium and myeloperoxidase activity. Moreover significant histological changes were also observed. HAE-AC attenuated CCI induced development of painful behavioural, biochemical and histological changes in a dose dependent manner similar to that of pregabalin serving as positive control. Conclusions Acorus calamus prevented CCI induced neuropathy which may be attributed to its multiple actions including anti-oxidative, anti-inflammatory, neuroprotective and calcium inhibitory actions. PMID:21426568

A PROSPECTIVE STUDY OF PHOBIC ANXIETY, RISK OF OVARIAN CANCER, AND SURVIVAL AMONG PATIENTS

PubMed Central

Poole, Elizabeth M.; Kubzansky, Laura D.; Sood, Anil K.; Okereke, Olivia I.; Tworoger, Shelley S.

2016-01-01

Purpose In ovarian cancer patients and mouse models, psychosocial stress is associated with higher circulating markers of angiogenesis and cell migration, impaired immune response, and increasing tumor burden and aggressiveness. In the Nurses’ Health Studies (NHS/NHSII), we assessed whether phobic anxiety, a marker of chronic distress, was associated with risk of incident ovarian cancer as well as survival among ovarian cancer patients. Methods We used Cox proportional hazards regression to model the relative risks (RR) and 95% confidence intervals (CI) of ovarian cancer incidence and survival by categories of the Crown-Crisp phobic anxiety index (CCI). Results We identified 779 cases of ovarian cancer during 2,497,892 person-years of follow-up. For baseline CCI (NHS: 1988; NHSII: 1993), we observed a statistically non-significant increased risk of epithelial ovarian cancer (RR for CCI ≥4 vs. 0 or 1: 1.14; 95% CI: 0.96–1.36). However, when we updated CCI (NHS: 2004; NHSII: 2005), the associations were attenuated. Pre-diagnosis CCI was not associated with ovarian cancer survival (RR: for ≥4 vs. 0 or 1: 1.00; 95% CI: 0.77–1.31); results were similar for post-diagnosis CCI. Conclusions Distress, as measured by phobic anxiety symptoms, was not associated with ovarian cancer risk, although we cannot rule out a modest association. Future research should explore the role of phobic anxiety and other forms of psychological distress and ovarian cancer risk and survival. PMID:27023470

Effect of artemisinin on neuropathic pain mediated by P2X4 receptor in dorsal root ganglia.

PubMed

Ying, Mofeng; Liu, Hui; Zhang, Tengling; Jiang, Chenxu; Gong, Yingxin; Wu, Bing; Zou, Lifang; Yi, Zhihua; Rao, Shenqiang; Li, Guilin; Zhang, Chunping; Jia, Tianyu; Zhao, Shanhong; Yuan, Huilong; Shi, Liran; Li, Lin; Liang, Shangdong; Liu, Shuangmei

2017-09-01

Neuropathic pain is a type of chronic pain caused by nervous system damage and dysfunction. The pathogenesis of chronic pain is complicated, and there are no effective therapies for neuropathic pain. Studies show that the P2X 4 receptor expressed in the satellite glial cells (SGCs) of dorsal root ganglia (DRG) is related to neuropathic pain. Artemisinin is a monomeric component extracted from traditional Chinese medicine and has a variety of important pharmacological effects and potential applications. This study observed the effect of artemisinin on neuropathic pain and delineated its possible mechanism. The chronic constriction injury (CCI) rat model was used in this study. The results demonstrated that artemisinin relieved pain behaviors in the CCI rats, inhibited the expression of P2X 4 receptor in the DRG, and decreased the ATP-activated currents in HEK293 cells transfected with P2X 4 plasmid. Dual-labeling immunofluorescence showed that the coexpression of P2X 4 receptor and glial fibrillary acidic protein (GFAP) in the DRG of CCI rats was increased compared to control rats. After CCI rats were treated with artemisinin, the coexpression of P2X 4 receptor and GFAP in the DRG was significantly decreased compared to the CCI group. This finding suggested that artemisinin could inhibit the nociceptive transmission mediated by P2X 4 receptor in the DRG SGCs and thus relieve pain behaviors in the CCI rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

A cross-assessment of CCI-ECVs and RCSM simulations over the Mediterranean area

NASA Astrophysics Data System (ADS)

D'Errico, Miriam; Planton, Serge; Nabat, Pierre

2017-04-01

A first objective of this study, conducted in the framework of the Climate Modelling Users Group (CMUG), one of the projects of the European Space Agency Climate Change Initiative (ESA CCI) program, is a cross-assessment of simulations of a Med-CORDEX regional climate system model (CNRM-RCSM5) and a sub-set of atmosphere, marine and surface interrelated Satellite-Derived Essential Climate Variables (CCI-ECVs) (i.e. sea surface temperature, sea level, aerosols and soil moisture content) over the Mediterranean area. The consistency between the model and the CCI-ECVs is evaluated through the analysis of a climate specific event that can be observed with the CCI-ECVs, in atmospheric reanalysis and reproduced in the RCSM simulations. In this presentation we focus on the July 2006 heat wave that affected the western part of the Mediterranean continental and marine area. The application of a spectral nudging method using ERA-Interim reanalysis in our simulation allows to reproduce this event with a proper chronology. As a result we show that the consistency between the simulated model aerosol optical depth and the ECV products (being produced by the ESA Aerosol CCI project consortium) depends on the choice of the algorithm used to infer the variable from the satellite observations. In particular the heat wave main characteristics become consistent between the model and the satellite-derived observations for sea surface temperature, soil moisture and sea level. The link between the atmospheric circulation and the aerosols distribution is also investigated.

A prospective study of phobic anxiety, risk of ovarian cancer, and survival among patients.

PubMed

Poole, Elizabeth M; Kubzansky, Laura D; Sood, Anil K; Okereke, Olivia I; Tworoger, Shelley S

2016-05-01

In ovarian cancer patients and mouse models, psychosocial stress is associated with higher circulating markers of angiogenesis and cell migration, impaired immune response, and increasing tumor burden and aggressiveness. In the Nurses' Health Studies (NHS/NHSII), we assessed whether phobic anxiety, a marker of chronic distress, was associated with risk of incident ovarian cancer as well as survival among ovarian cancer patients. We used Cox proportional hazards regression to model the relative risks (RRs) and 95 % confidence intervals (CI) of ovarian cancer incidence and survival by categories of the Crown-Crisp phobic anxiety index (CCI). We identified 779 cases of ovarian cancer during 2,497,892 person-years of follow-up. For baseline CCI (NHS: 1988; NHSII: 1993), we observed a statistically nonsignificant increased risk of epithelial ovarian cancer (RR for CCI ≥ 4 vs. 0 or 1: 1.14; 95 % CI 0.96-1.36). However, when we updated CCI (NHS: 2004; NHSII: 2005), the associations were attenuated. Pre-diagnosis CCI was not associated with ovarian cancer survival (RR for ≥4 vs. 0 or 1: 1.00; 95 % CI 0.77-1.31); results were similar for post-diagnosis CCI. Distress, as measured by phobic anxiety symptoms, was not associated with ovarian cancer risk, although we cannot rule out a modest association. Future research should explore the role of phobic anxiety and other forms of psychological distress and ovarian cancer risk and survival.

Decreased voltage-gated potassium currents in rat dorsal root ganglion neurons after chronic constriction injury.

PubMed

Xiao, Yun; Wu, Yang; Zhao, Bo; Xia, Zhongyuan

2016-01-20

Voltage-gated potassium channels (KV) regulate pain transmission by controlling neuronal excitability. Changes in KV expression patterns may thus contribute toward hyperalgesia following nerve injury. The aim of this study was to characterize KV current density in dorsal root ganglion (DRG) neurons following chronic constriction injury (CCI) of the right sciatic nerve, a robust model of post-traumatic neuropathic pain. The study examined changes in small-diameter potassium ion currents (<30 µm) in neurons in the L4-L6 DRG following CCI by whole-cell patch-clamping and the association with post-CCI mechanical and thermal nociceptive thresholds. Compared with the control group, 7 days after CCI, the mechanical force and temperature required to elicit ipsilateral foot withdrawal decreased significantly, indicating tactile allodynia and thermal hyperalgesia. Post-CCI neurons had a significantly lower rheobase current and depolarized resting membrane potential than controls, suggesting KV current downregulation. Some ipsilateral DRG neurons also had spontaneous action potentials and repetitive firing. There was a 55% reduction in the total KV current density caused by a 55% decrease in the sustained delayed rectifier potassium ion current (IK) density and a 17% decrease in the transient A-type potassium ion current (IA) density. These results indicated that changes in DRG neuron IK and IA current density and concomitant afferent hyperexcitability may contribute toward neuropathic pain following injury. The rat CCI model may prove valuable for examining pathogenic mechanisms and potential therapies, such as KV channel modulators.

Models of care for orphaned and separated children and upholding children's rights: cross-sectional evidence from western Kenya.

PubMed

Embleton, Lonnie; Ayuku, David; Kamanda, Allan; Atwoli, Lukoye; Ayaya, Samuel; Vreeman, Rachel; Nyandiko, Winstone; Gisore, Peter; Koech, Julius; Braitstein, Paula

2014-04-01

Sub-Saharan Africa is home to approximately 55 million orphaned children. The growing orphan crisis has overwhelmed many communities and has weakened the ability of extended families to meet traditional care-taking expectations. Other models of care and support have emerged in sub-Saharan Africa to address the growing orphan crisis, yet there is a lack of information on these models available in the literature. We applied a human rights framework using the United Nations Convention on the Rights of the Child to understand what extent children's basic human rights were being upheld in institutional vs. community- or family-based care settings in Uasin Gishu County, Kenya. The Orphaned and Separated Children's Assessments Related to their Health and Well-Being Project is a 5-year cohort of orphaned children and adolescents aged ≤18 year. This descriptive analysis was restricted to baseline data. Chi-Square test was used to test for associations between categorical /dichotomous variables. Fisher's exact test was also used if some cells had expected value of less than 5. Included in this analysis are data from 300 households, 19 Charitable Children's Institutions (CCIs) and 7 community-based organizations. In total, 2871 children were enrolled and had baseline assessments done: 1390 in CCI's and 1481 living in households in the community. We identified and described four broad models of care for orphaned and separated children, including: institutional care (sub-classified as 'Pure CCI' for those only providing residential care, 'CCI-Plus' for those providing both residential care and community-based supports to orphaned children , and 'CCI-Shelter' which are rescue, detention, or other short-term residential support), family-based care, community-based care and self-care. Children in institutional care (95%) were significantly (p < 0.0001) more likely to have their basic material needs met in comparison to those in family-based care (17%) and institutions were better able to provide an adequate standard of living. Each model of care we identified has strengths and weaknesses. The orphan crisis in sub-Saharan Africa requires a diversity of care environments in order to meet the needs of children and uphold their rights. Family-based care plays an essential role; however, households require increased support to adequately care for children.

Attenuation of the Infiltration of Angiotensin II Expressing CD3+ T-Cells and the Modulation of Nerve Growth Factor in Lumbar Dorsal Root Ganglia – A Possible Mechanism Underpinning Analgesia Produced by EMA300, An Angiotensin II Type 2 (AT2) Receptor Antagonist

PubMed Central

Khan, Nemat; Muralidharan, Arjun; Smith, Maree T.

2017-01-01

Recent preclinical and proof-of-concept clinical studies have shown promising analgesic efficacy of selective small molecule angiotensin II type 2 (AT2) receptor antagonists in the alleviation of peripheral neuropathic pain. However, their cellular and molecular mechanism of action requires further investigation. To address this issue, groups of adult male Sprague–Dawley rats with fully developed unilateral hindpaw hypersensitivity, following chronic constriction injury (CCI) of the sciatic nerve, received a single intraperitoneal bolus dose of the small molecule AT2 receptor antagonist, EMA300 (10 mg kg-1), or vehicle. At the time of peak EMA300-mediated analgesia (∼1 h post-dosing), groups of CCI-rats administered either EMA300 or vehicle were euthanized. A separate group of rats that underwent sham surgery were also included. The lumbar (L4–L6) dorsal root ganglia (DRGs) were obtained from all experimental cohorts and processed for immunohistochemistry and western blot studies. In vehicle treated CCI-rats, there was a significant increase in the expression levels of angiotensin II (Ang II), but not the AT2 receptor, in the ipsilateral lumbar DRGs. The elevated levels of Ang II in the ipsilateral lumbar DRGs of CCI-rats were at least in part contributed by CD3+ T-cells, satellite glial cells (SGCs) and subsets of neurons. Our findings suggest that the analgesic effect of EMA300 in CCI-rats involves multimodal actions that appear to be mediated at least in part by a significant reduction in the otherwise increased expression levels of Ang II as well as the number of Ang II-expressing CD3+ T-cells in the ipsilateral lumbar DRGs of CCI-rats. Additionally, the acute anti-allodynic effects of EMA300 in CCI-rats were accompanied by rescue of the otherwise decreased expression of mature nerve growth factor (NGF) in the ipsilateral lumbar DRGs of CCI-rats. In contrast, the increased expression levels of TrkA and glial fibrillary acidic protein in the ipsilateral lumbar DRGs of vehicle-treated CCI-rats were not attenuated by a single bolus dose of EMA300. Consistent with our previous findings, there was also a significant decrease in the augmented levels of the downstream mediators of Ang II/AT2 receptor signaling, i.e., phosphorylated-p38 mitogen-activated protein kinase (MAPK) and phosphorylated-p44/p42 MAPK, in the ipsilateral lumbar DRGs. PMID:29200998

The Association between Charlson Comorbidity Index and the Medical Care Cost of Cancer: A Retrospective Study.

PubMed

Yoon, Seok-Jun; Kim, Eun-Jung; Seo, Hyun-Ju; Oh, In-Hwan

2015-01-01

This study compared comorbidity-related medical care cost associated with different types of cancer, by examining breast (N = 287), colon (N = 272), stomach (N = 614), and lung (N = 391) cancer patients undergoing surgery. Using medical benefits claims data, we calculated Charlson Comorbidity Index (CCI) and total medical cost. The effect of comorbidity on the medical care cost was investigated using multiple regression and logistic regression models and controlling for demographic characteristics and cancer stage. The treatment costs incurred by stomach and colon cancer patients were 1.05- and 1.01-fold higher, respectively, in patients with higher CCI determined. For breast cancer, the highest costs were seen in those with chronic obstructive pulmonary disease (COPD), but the increase in cost reduced as CCI increased. Colon cancer patients with diabetes mellitus and a CCI = 1 score had the highest medical costs. The lowest medical costs were incurred by lung cancer patients with COPD and a CCI = 2 score. The comorbidities had a major impact on the use of medical resources, with chronic comorbidities incurring the highest medical costs. The results indicate that comorbidities affect cancer outcomes and that they must be considered strategies mitigating cancer's economic and social impact.

Trajectories of Health and Behavioral Health Services Use among Community Corrections–Involved Rural Adults

PubMed Central

Mowbray, Orion; McBeath, Bowen; Bank, Lew; Newell, Summer

2016-01-01

This article seeks to establish time-based trajectories of health and behavioral health services utilization for community corrections–involved (CCI) adults and to examine demographic and clinical correlates associated with these trajectories. To accomplish this aim, the authors applied a latent class growth analysis (LCGA) to services use data from a sample of rural CCI adults who reported their medical, mental health, and substance use treatment utilization behavior every 60 days for 1.5 years. LCGA established 1.5-year trajectories and demographic correlates of health services among rural CCI adults. For medical services, three classes emerged (stable-low users, 13%; stable-intermediate users, 40%; and stable-high users, 47%). For mental health and substance use services, three classes emerged (stable-low, 69% and 61%, respectively; low-baseline-increase, 10% and 12%, respectively; high-baseline decline, 21% and 28%, respectively). Employment, gender, medication usage, and depression severity predicted membership across all services. Results underscore the importance of social workers and other community services providers aligning health services access with the needs of the CCI population, and highlight CCI adults as being at risk of underservice in critical prevention and intervention domains. PMID:27257353

Color discrimination impairment in workers exposed to mercury vapor.

PubMed

Urban, Pavel; Gobba, Fabriziomaria; Nerudová, Jana; Lukás, Edgar; Cábelková, Zdena; Cikrt, Miroslav

2003-08-01

To study color discrimination impairment in workers exposed to elemental mercury (Hg) vapor. Twenty-four male workers from a chloralkali plant exposed to Hg vapor, aged 42+/-9.8 years, duration of exposure 14.7+/-9.7 years, were examined. The 8h TWA air-borne Hg concentration in workplace was 59 microg/m(3); mean Hg urinary excretion (HgU) was 20.5+/-19.3 microg/g creatinine; mean Hg urinary excretion after the administration of a chelating agent, sodium 2,3-dimercapto-1-propane-sulfonate (DMPS), was 751.9+/-648 microg/48h. Twenty-four age- and gender-matched control subjects were compared. Visual acuity, alcohol intake, smoking habits, and history of diseases or drugs potentially influencing color vision were registered. The Lanthony 15-Hue desaturated test (L-D15-d) was used to assess color vision. The results were expressed quantitatively as Bowman's Color Confusion Index (CCI), and qualitatively according to Verriest's classification of acquired dyschromatopsias. The CCI was significantly higher in the exposed group than in the control (mean CCI 1.15 versus 1.04; P=0.04). The proportion of subjects with errorless performance on the Lanthony test was significantly lower in the Hg exposed group compared to referents (52% versus 73%; P=0.035). The exposed group showed higher frequency of type III dyschromatopsias (blue-yellow confusion axis) in comparison with the control group (12.5% versus 8.3%), however, the difference did not reach statistical significance. Multiple regression did not show any significant relationship between the CCI, and age, alcohol consumption, or measures of exposure. In agreement with previous studies by Cavalleri et al. [Toxicol. Lett. 77 (1995) 351; Environ. Res. Sec. A 77 (1998) 173], the results of this study support the hypothesis that exposure to mercury vapor can induce sub-clinical color vision impairment. This effect was observed at an exposure level below the current biological limit for occupational exposure to mercury. This raises doubts on the actual protection afforded by this limit concerning the effect of mercury on color vision.

Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

PubMed

Zweckberger, K; Hackenberg, K; Jung, C S; Hertle, D N; Kiening, K L; Unterberg, A W; Sakowitz, O W

2014-07-11

Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); p<0.05; n=14). Contusion sizes increased continuously within 72h following CCI injury, but glibenclamide-treated animals had significantly smaller volumes at any time-points, like 172.53±38.74mm(3) (glibenclamide) vs. 299.20±64.02mm(3) (control) (p<0.01; n=10; 24h) or 211.10±41.03mm(3) (glibenclamide) vs. 309.76±19.45mm(3) (control) (p<0.05; n=10; 72h), respectively. An effect on acute parameters, however, could not be detected, most likely because of the up-regulation of the channel within 3-6h after injury. Furthermore, there was no significant effect on motor function assessed by the beam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

The Rapalogue, CCI-779, improves salivary gland function following radiation.

PubMed

Morgan-Bathke, Maria; Harris, Zoey I; Arnett, Deborah G; Klein, Rob R; Burd, Randy; Ann, David K; Limesand, Kirsten H

2014-01-01

The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5f/f; Aqp5-Cre, Atg5+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side effects in head and neck cancer patients who have completed anti-tumor therapy.

[Effect of M8046 on expression of COX-2/PGE2 in spinal cord and DRG in rats with neuropathic pain].

PubMed

Ou, Guo-Kun; Wang, Rui-Xian; Li, Jia-Jia; Cao, Hong; Lian, Qing-Quan; Li, Jun

2013-03-01

To investigate the effects of glucocorticoid receptor antagonist-M8046 on the behavior and the cyclooxygenase-2/prostaglandin E2( COX-2/PGE2) expression in spinal cord dorsal horn and dorsal root ganglia (DRG) in chronic constrictive injury (CCI) rats. One hundred and forty-four male SD rats were randomly divided into 4 groups, 36 rats in each group: Sham operation group (Sham), chronic constrictive group (CCI), M8046 treated group (M8046) and solvent controlled group (Sc). M8046 3 mg/(kg x d) intraperitoneal injection was given after operation in group M8046. Paw thennal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured on 2 pre-operative and 1, 3, 7, 10, 14 post-operative days. The spinal cord and L15 DRG of the operated side was removed at 3, 7, 14 days after surgery. The change of COX-2 and PGE2 expression was determined by immunohistochemical staining and ELISA separately. PTWL and PMWT in CCI group were significantly lower than those in Sham group on every post-operative day (P < 0.05). PTWL and PMWT in M8046 group were significantly higher than those in CCI group on 7, 10, 14 post-operative day (P < 0.05). In spinal dorsal horn, the level of COX-2 and PGE2 expression in CCI group was significantly higher than that in Sham group (P < 0.05). M8046 could significantly attenuate the activation of COX-2 and PGE2 induced by CCI (P < 0.05). The expression of COX-2 and PGE2 in DRG was similar to that in spinal dorsal horn. The effects of M8046 ameliorate the CCI-induced neuropathic pain may be related to attenuate the expression of COX-2 and PGE2 in spinal cord and DRG.

ESA fire_cci product assessment

NASA Astrophysics Data System (ADS)

Heil, Angelika; Yue, Chao; Mouillot, Florent; Storm, Thomas; Chuvieco, Emilio; Ramo Sanchez, Ruben; Kaiser, Johannes W.

2017-04-01

Vegetation fires are a major disturbance in the Earth System. Fires change the biophysical properties and dynamics of ecosystems and alter terrestrial carbon pools. By altering the atmosphere's composition, fire emissions exert a significant climate forcing. To realistically model past and future changes of the Earth System, fire disturbances must be taken into account. Related modelling efforts require consistent global burned area observations covering at least 10 to 20 years. Guided by the specific requirements of a wide range of end users, the ESA fire_cci project has computed a new global burned area dataset. It applies a newly developed spectral change detection algorithm upon the ENVISAT-MERIS archive. The algorithm relies on MODIS active fire information as "seed". It comprises a pixel burned area product (spatial resolution of 333 m) with date detection information and a biweekly grid product at 0.25 degree spatial resolution. We compare fire_cci burned area with other global burned area products (MCD64 Collection 6, MCD45, GFED4, GFED4s and GEOLAND) and a set of active fires data (hotspots from MODIS, TRMM, AATSR and fire radiative power from GFAS). The analysis of patterns of agreement and disagreement between fire_cci and other products provides a better understanding of product characteristics and uncertainties. The intercomparison of the 2005-2011 fire_cci time series shows a close agreement with GFED4 data in terms of global burned area and the general spatial and temporal patterns. Pronounced differences, however, emerge for specific regions or fire events. Burned area mapped by fire_cci tends to be notably higher in regions where small agricultural fires predominate. The improved detection of small agricultural fires by fire_cci can be related to the increased spatial resolution of the MERIS sensor (333 m compared to 500 in MODIS). This is illustrated in detail using the example of the extreme 2006 spring fires in Eastern Europe.

Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain.

PubMed

Shibuta, Kazuo; Suzuki, Ikuko; Shinoda, Masamichi; Tsuboi, Yoshiyuki; Honda, Kuniya; Shimizu, Noriyoshi; Sessle, Barry J; Iwata, Koichi

2012-04-27

The aim of this study was to evaluate spatial organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1), and to clarify the involvement in mechanisms underlying orofacial secondary hyperalgesia following infraorbital nerve injury. We found that the head-withdrawal threshold to non-noxious mechanical stimulation of the maxillary whisker pad skin was significantly reduced in chronic constriction injury of the infraorbital nerve (ION-CCI) rats from day 1 to day 14 after ION-CCI. On day 3 after ION-CCI, mechanical allodynia was obvious in the orofacial skin areas innervated by the 1st and 3rd branches of the trigeminal nerve as well as the 2nd branch area. Hyperactive microglial cells in Vc and C1 were observed on days 3 and 7 after ION-CCI. On day 3 after ION-CCI, a large number of phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) cells were observed in Vc and C1. Many hyperactive microglial cells were also distributed over a wide area of Vc and C1 innervated by the trigeminal nerve. The intraperitoneal administration of minocycline significantly reduced the activation of microglial cells and the number of pERK-IR cells in Vc and C1, and also significantly attenuated the development of mechanical allodynia. Furthermore, enhanced background activity and mechanical evoked responses of Vc wide dynamic range neurons in ION-CCI rats were significantly reversed following minocycline administration. These findings suggest that activation of microglial cells over a wide area of Vc and C1 is involved in the enhancement of Vc and C1 neuronal excitability in the early period after ION-CCI, resulting in the neuropathic pain in orofacial areas innervated by the injured as well as uninjured nerves. Copyright © 2012 Elsevier B.V. All rights reserved.

Differences in carbachol dose, pain condition, and sex following lateral hypothalamic stimulation.

PubMed

Holden, J E; Wang, E; Moes, J R; Wagner, M; Maduko, A; Jeong, Y

2014-06-13

Lateral hypothalamic (LH) stimulation produces antinociception in female rats in acute, nociceptive pain. Whether this effect occurs in neuropathic pain or whether male-female sex differences exist is unknown. We examined the effect of LH stimulation in male and female rats using conditions of nociceptive and neuropathic pain. Neuropathic groups received chronic constriction injury (CCI) to induce thermal hyperalgesia, a sign of neuropathic pain. Nociceptive rats were naive for CCI, but received the same thermal stimulus following LH stimulation. To demonstrate that CCI ligation produced thermal hyperalgesia, males and females received either ligation or sham surgery for control. Both males and females demonstrated significant thermal hyperalgesia following CCI ligation (p<0.05), but male sham surgery rats also showed a significant left-right difference not present in female sham rats. In the second experiment, rats randomly assigned to CCI or nociceptive groups were given one of three doses of the cholinergic agonist carbachol (125, 250, or 500 nmol) or normal saline for control, microinjected into the left LH. Paw withdrawal from a thermal stimulus (paw withdrawal latency; PWL) was measured every 5 min for 45 min. Linear mixed models analysis showed that males and females in both pain conditions demonstrated significant antinociception, with the 500-nmol dose producing the greatest effect across groups compared with controls for the left paw (p<0.05). Female CCI rats showed equivalent responses to the three doses, while male CCI rats showed more variability for dose. However, nociceptive females responded only to the 500-nmol dose, while nociceptive males responded to all doses (p<0.05). For right PWL, only nociceptive males showed a significant carbachol dose response. These findings are suggestive that LH stimulation produces antinociception in male and female rats in both nociceptive and neuropathic pain, but dose response differences exist based on sex and pain condition. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Greenhouse gas observations from space: The GHG-CCI project of ESA's Climate Change Initiative

NASA Astrophysics Data System (ADS)

Buchwitz, Michael; Noël, Stefan; Bergamaschi, Peter; Boesch, Hartmut; Bovensmann, Heinrich; Notholt, Justus; Schneising, Oliver; Hasekamp, Otto; Reuter, Maximilian; Parker, Robert; Dils, Bart; Chevallier, Frederic; Zehner, Claus; Burrows, John

2012-07-01

The GHG-CCI project (http://www.esa-ghg-cci.org) is one of several projects of ESA's Climate Change Initiative (CCI), which will deliver various Essential Climate Variables (ECVs). The goal of GHG-CCI is to deliver global satellite-derived data sets of the two most important anthropogenic greenhouse gases (GHGs) carbon dioxide (CO2) and methane (CH4) suitable to obtain information on regional CO2 and CH4 surface sources and sinks as needed for better climate prediction. The GHG-CCI core ECV data products are column-averaged mole fractions of CO2 and CH4, XCO2 and XCH4, retrieved from SCIAMACHY on ENVISAT and TANSO on GOSAT. Other satellite instruments will be used to provide constraints in upper layers such as IASI, MIPAS, and ACE-FTS. Which of the advanced algorithms, which are under development, will be the best for a given data product still needs to be determined. For each of the 4 GHG-CCI core data products - XCO2 and XCH4 from SCIAMACHY and GOSAT - several algorithms are being further developed and the corresponding data products are inter-compared to identify which data product is the most appropriate. This includes comparisons with corresponding data products generated elsewhere, most notably with the operational data products of GOSAT generated at NIES and the NASA/ACOS GOSAT XCO2 product. This activity, the so-called "Round Robin exercise", will be performed in the first two years of this project. At the end of the 2 year Round Robin phase (end of August 2012) a decision will be made which of the algorithms performs best. The selected algorithms will be used to generate the first version of the ECV GHG. In the last six months of this 3 year project the resulting data products will be validated and made available to all interested users. In the presentation and overview about this project will be given focussing on the latest results.

Greenhouse Gas CCI Project (GHG-CCI): Overview and current status

NASA Astrophysics Data System (ADS)

Buchwitz, M.; Burrows, J. P.; Reuter, M.; Schneising, O.; Noel, S.; Bovensmann, H.; Notholt, J.; Boesch, H.; Parker, R.; Hasekamp, O. P.; Guerlet, S.; Aben, I.; Lichtenberg, G.; Crevoisier, C. D.; Chedin, A.; Stiller, G. P.; Laeng, A.; Butz, A.; Blumenstock, T.; Orphal, J.; Sussmann, R.; De Maziere, M. M.; Dils, B.; Brunner, D.; Popp, C. T.; Buchmann, B.; Chevallier, F.; Bergamaschi, P. M.; Frankenberg, C.; Zehner, C.

2011-12-01

The GHG-CCI project is one of several projects of ESA's Climate Change Initiative (CCI), which will deliver various Essential Climate Variables (ECVs). The goal of GHG-CCI is to deliver global satellite-derived data sets of the two most important anthropogenic greenhouse gases (GHGs) carbon dioxide (CO2) and methane (CH4) suitable to obtain information on regional CO2 and CH4 surface sources and sinks as needed for better climate prediction. The GHG-CCI core ECV data products are column-averaged mole fractions of CO2 and CH4, i.e., XCO2 and XCH4, retrieved from SCIAMACHY on ENVISAT and TANSO on GOSAT. Other satellite instruments will be used to provide constraints in upper layers such as IASI, MIPAS, and ACE-FTS. Which of the advanced algorithms, which are under development, will be the best for a given data product still needs to be determined. For each of the 4 GHG-CCI core data products - XCO2 and XCH4 from SCIAMACHY and GOSAT - several algorithms will be further developed and the corresponding data products will be inter-compared to identify which data product is the most appropriate. This includes comparisons with corresponding data products generated elsewhere, most notably with the operational data products of GOSAT generated at NIES and the NASA/ACOS GOSAT XCO2 product. This activity, the so-called "Round Robin exercise", will be performed in the first two years of this project. At the end of the 2 year Round Robin phase a decision will be made which of the algorithms performs best. The selected algorithms will be used to generate the first version of the ECV GHG. In the last six months of this 3 year project the resulting data products will be validated and made available to all interested users. In the presentation and overview about this project will be given. Focus will be on a discussion and intercomparison of the various data products focusing on CO2.

The GHG-CCI Project to Deliver the Essential Climate Variable Greenhouse Gases: Current status

NASA Astrophysics Data System (ADS)

Buchwitz, M.; Boesch, H.; Reuter, M.

2012-04-01

The GHG-CCI project (http://www.esa-ghg-cci.org) is one of several projects of ESA's Climate Change Initiative (CCI), which will deliver various Essential Climate Variables (ECVs). The goal of GHG-CCI is to deliver global satellite-derived data sets of the two most important anthropogenic greenhouse gases (GHGs) carbon dioxide (CO2) and methane (CH4) suitable to obtain information on regional CO2 and CH4 surface sources and sinks as needed for better climate prediction. The GHG-CCI core ECV data products are column-averaged mole fractions of CO2 and CH4, XCO2 and XCH4, retrieved from SCIAMACHY on ENVISAT and TANSO on GOSAT. Other satellite instruments will be used to provide constraints in upper layers such as IASI, MIPAS, and ACE-FTS. Which of the advanced algorithms, which are under development, will be the best for a given data product still needs to be determined. For each of the 4 GHG-CCI core data products - XCO2 and XCH4 from SCIAMACHY and GOSAT - several algorithms are bing further developed and the corresponding data products are inter-compared to identify which data product is the most appropriate. This includes comparisons with corresponding data products generated elsewhere, most notably with the operational data products of GOSAT generated at NIES and the NASA/ACOS GOSAT XCO2 product. This activity, the so-called "Round Robin exercise", will be performed in the first two years of this project. At the end of the 2 year Round Robin phase (end of August 2012) a decision will be made which of the algorithms performs best. The selected algorithms will be used to generate the first version of the ECV GHG. In the last six months of this 3 year project the resulting data products will be validated and made available to all interested users. In the presentation and overview about this project will be given focussing on the latest results.

Population-Level Incidence and Predictors of Surgically Induced Diabetes and Exocrine Insufficiency after Partial Pancreatic Resection.

PubMed

Elliott, Irmina A; Epelboym, Irene; Winner, Megan; Allendorf, John D; Haigh, Philip I

2017-01-01

Endocrine and exocrine insufficiency after partial pancreatectomy affect quality of life, cardiovascular health, and nutritional status. However, their incidence and predictors are unknown. To identify the incidence and predictors of new-onset diabetes and exocrine insufficiency after partial pancreatectomy. We retrospectively reviewed 1165 cases of partial pancreatectomy, performed from 1998 to 2010, from a large population-based database. Incidence of new onset diabetes and exocrine insufficiency RESULTS: Of 1165 patients undergoing partial pancreatectomy, 41.8% had preexisting diabetes. In the remaining 678 patients, at a median 3.6 months, diabetes developed in 274 (40.4%) and pancreatic insufficiency developed in 235 (34.7%) patients. Independent predictors of new-onset diabetes were higher Charlson Comorbidity Index (CCI; hazard ratio [HR] = 1.62 for CCI of 1, p = 0.02; HR = 1.95 for CCI ≥ 2, p < 0.01) and pancreatitis (HR = 1.51, p = 0.03). There was no difference in diabetes after Whipple procedure vs distal pancreatic resections, or malignant vs benign pathologic findings. Independent predictors of exocrine insufficiency were female sex (HR = 1.32, p = 0.002) and higher CCI (HR = 1.85 for CCI of 1, p < 0.01; HR = 2.05 for CCI ≥ 2, p < 0.01). Distal resection and Asian race predicted decreased exocrine insufficiency (HR = 0.35, p < 0.01; HR = 0.54, p < 0.01, respectively). In a large population-based database, the rates of postpancreatectomy endocrine and exocrine insufficiency were 40% and 35%, respectively. These data are critical for informing patients' and physicians' expectations.

Comorbidity Burden of Dementia: A Hospital-Based Retrospective Study from 2003 to 2012 in Seven Cities in China.

PubMed

Wang, Qing-Hua; Wang, Xin; Bu, Xian-Le; Lian, Yan; Xiang, Yang; Luo, Hong-Bo; Zou, Hai-Qiang; Pu, Jie; Zhou, Zhong-He; Cui, Xiao-Ping; Wang, Qing-Song; Shi, Xiang-Qun; Han, Wei; Wu, Qiang; Chen, Hui-Sheng; Lin, Hang; Gao, Chang-Yue; Zhang, Li-Li; Xu, Zhi-Qiang; Zhang, Meng; Zhou, Hua-Dong; Wang, Yan-Jiang

2017-12-01

Dementia is increasing dramatically and imposes a huge burden on society. To date, there is a lack of data on the health status of patients with dementia in China. In an attempt to investigate the comorbidity burden of dementia patients in China at the national level, we enrolled 2,938 patients with Alzheimer's disease (AD), vascular dementia (VaD), or other types of dementia, who were admitted to tertiary hospitals in seven regions of China from January 2003 to December 2012. The Charlson Comorbidity Index (CCI) was used to evaluate the comorbidity burden of the patients with dementia. Among these patients, 53.4% had AD, 26.3% had VaD, and 20.3% had other types of dementia. The CCI was 3.0 ± 1.9 for all patients, 3.4 ± 1.8 for those with VaD, and 3.0 ± 2.1 for those with AD. The CCI increased with age in all patients, and the length of hospital stay and daily expenses rose with age and CCI. Males had a higher CCI and a longer stay than females. Moreover, patients admitted in the last 5 years of the study had a higher CCI than those admitted in the first 5 years. We found that the comorbidity burden of patients with dementia is heavy. These findings provide a better understanding of the overall health status of dementia patients, and help to increase the awareness of clinicians and policy-makers to improve medical care for patients.

Innate Immunity in the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome and Its Implications for Therapy

PubMed Central

Horiguchi, Hiroyuki; Loftus, Tyler J.; Hawkins, Russell B.; Raymond, Steven L.; Stortz, Julie A.; Hollen, McKenzie K.; Weiss, Brett P.; Miller, Elizabeth S.; Bihorac, Azra; Larson, Shawn D.; Mohr, Alicia M.; Brakenridge, Scott C.; Tsujimoto, Hironori; Ueno, Hideki; Moore, Frederick A.; Moldawer, Lyle L.; Efron, Philip A.

2018-01-01

Clinical and technological advances promoting early hemorrhage control and physiologic resuscitation as well as early diagnosis and optimal treatment of sepsis have significantly decreased in-hospital mortality for many critically ill patient populations. However, a substantial proportion of severe trauma and sepsis survivors will develop protracted organ dysfunction termed chronic critical illness (CCI), defined as ≥14 days requiring intensive care unit (ICU) resources with ongoing organ dysfunction. A subset of CCI patients will develop the persistent inflammation, immunosuppression, and catabolism syndrome (PICS), and these individuals are predisposed to a poor quality of life and indolent death. We propose that CCI and PICS after trauma or sepsis are the result of an inappropriate bone marrow response characterized by the generation of dysfunctional myeloid populations at the expense of lympho- and erythropoiesis. This review describes similarities among CCI/PICS phenotypes in sepsis, cancer, and aging and reviews the role of aberrant myelopoiesis in the pathophysiology of CCI and PICS. In addition, we characterize pathogen recognition, the interface between innate and adaptive immune systems, and therapeutic approaches including immune modulators, gut microbiota support, and nutritional and exercise therapy. Finally, we discuss the future of diagnostic and prognostic approaches guided by machine and deep-learning models trained and validated on big data to identify patients for whom these approaches will yield the greatest benefits. A deeper understanding of the pathophysiology of CCI and PICS and continued investigation into novel therapies harbor the potential to improve the current dismal long-term outcomes for critically ill post-injury and post-infection patients. PMID:29670613

Preemptive application of QX-314 attenuates trigeminal neuropathic mechanical allodynia in rats.

PubMed

Yoon, Jeong-Ho; Son, Jo-Young; Kim, Min-Ji; Kang, Song-Hee; Ju, Jin-Sook; Bae, Yong-Chul; Ahn, Dong-Kuk

2018-05-01

The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.

ASA grade and Charlson Comorbidity Index of spinal surgery patients: correlation with complications and societal costs.

PubMed

Whitmore, Robert G; Stephen, James H; Vernick, Coleen; Campbell, Peter G; Yadla, Sanjay; Ghobrial, George M; Maltenfort, Mitchell G; Ratliff, John K

2014-01-01

The Charlson Comorbidity Index (CCI) and the American Society of Anesthesiologists (ASA) Physical Status Classification System (ASA grade) are useful for predicting morbidity and mortality for a variety of disease processes. To evaluate CCI and ASA grade as predictors of complications after spinal surgery and examine the correlation between these comorbidity indices and the cost of care. Prospective observational study. All patients undergoing any spine surgery at a single academic tertiary center over a 6-month period. Direct health-care costs estimated from diagnosis related group and Current Procedural Terminology (CPT) codes. Demographic data, including all patient comorbidities, procedural data, and all complications, occurring within 30 days of the index procedure were prospectively recorded. Charlson Comorbidity Index was calculated from International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and ASA grades determined from the operative record. Diagnosis related group and CPT codes were captured for each patient. Direct costs were estimated from a societal perspective using Medicare rates of reimbursement. A multivariable analysis was performed to assess the association of the CCI and ASA grade to the rate of complication and direct health-care costs. Two hundred twenty-six cases were analyzed. The average CCI score for the patient cohort was 0.92, and the average ASA grade was 2.65. The CCI and ASA grade were significantly correlated, with Spearman ρ of 0.458 (p<.001). Both CCI and ASA grade were associated with increasing body mass index (p<.01) and increasing patient age (p<.0001). Increasing CCI was associated with an increasing likelihood of occurrence of any complication (p=.0093) and of minor complications (p=.0032). Increasing ASA grade was significantly associated with an increasing likelihood of occurrence of a major complication (p=.0035). Increasing ASA grade showed a significant association with increasing direct costs (p=.0062). American Society of Anesthesiologists and CCI scores are useful comorbidity indices for the spine patient population, although neither was completely predictive of complication occurrence. A spine-specific comorbidity index, based on ICD-9-CM coding that could be easily captured from patient records, and which is predictive of patient likelihood of complications and mortality, would be beneficial in patient counseling and choice of operative intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

Predictors of posttraumatic stress and quality of life in family members of chronically critically ill patients after intensive care.

PubMed

Wintermann, Gloria-Beatrice; Weidner, Kerstin; Strauß, Bernhard; Rosendahl, Jenny; Petrowski, Katja

2016-12-01

Prolonged mechanical ventilation for acute medical conditions increases the risk of chronic critical illness (CCI). Close family members are confronted with the life-threatening condition of the CCI patients and are prone to develop posttraumatic stress disorder affecting their health-related quality of life (HRQL). Main aim of the present study was to investigate patient- and family-related risk factors for posttraumatic stress and decreased HRQL in family members of CCI patients. In a cross-sectional design nested within a prospective longitudinal cohort study, posttraumatic stress symptoms and quality of life were assessed in family members of CCI patients (n = 83, aged between 18 and 72 years) up to 6 months after transfer from ICU at acute care hospital to post-acute rehabilitation. Patients admitted a large rehabilitation hospital for ventilator weaning. The Posttraumatic Stress Scale-10 and the Euro-Quality of life-5D-3L were applied in both patients and their family members via telephone interview. A significant proportion of CCI patients and their family members (14.5 and 15.7 %, respectively) showed clinically relevant scores of posttraumatic stress. Both CCI patients and family members reported poorer HRQL than a normative sample. Factors independently associated with posttraumatic stress in family members were the time following ICU discharge (β = .256, 95 % confidence interval .053-.470) and the patients' diagnosis of PTSD (β = .264, 95 % confidence interval .045-.453). Perceived satisfaction with the relationship turned out to be a protective factor for posttraumatic stress in family members of CCI patients (β = -.231, 95 % confidence interval -.423 to -.015). Regarding HRQL in family members, patients' acute posttraumatic stress at ICU (β = -.290, 95 % confidence interval -.360 to -.088) and their own posttraumatic stress 3 to 6 months post-transfer (β = -.622, 95 % confidence interval -.640 to -.358) turned out to be significant predictors. Posttraumatic stress and HRQL should be routinely assessed in family members of CCI patients at regular intervals starting early at ICU. Preventive family-centered interventions are needed to improve posttraumatic stress and HRQL in both patients and their family members.

KSC-2013-3081

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068284 - John Elbon, vice president for Space Exploration for The Boeing Company, addresses the media before the unveiling of a CST-100 mock-up at the company's Houston Product Support Center. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3089

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068324 - Kathy Lueders, NASA deputy manager for the Commercial Crew Program, is interviewed by the media during the unveiling of a CST-100 mock-up at the company's Houston Product Support Center. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3083

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068290 - Kathy Lueders, NASA deputy manager for the Commercial Crew Program, addresses the media before the unveiling of a CST-100 mock-up at the company's Houston Product Support Center. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3084

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068296 - John Mulholland, vice president and program manager, Commercial Crew, for The Boeing Company, addresses the media before the unveiling of a CST-100 mock-up at the company's Houston Product Support Center. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3082

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068287 - John Elbon, vice president for Space Exploration for The Boeing Company, addresses the media before the unveiling of a CST-100 mock-up at the company's Houston Product Support Center. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3077

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068259 - NASA astronaut Serena Aunon prepares for a fit check evaluation of The Boeing Company's CST-100 spacecraft at the company's Houston Product Support Center. Assisting her is Andrea Gilkey, a human factors engineer with The Boeing Company. Aunon's fit check will help evaluate a crew's maneuverability in the spacecraft and test communications. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats.

PubMed

Lu, Lijuan; Pan, Cailong; Chen, Lu; Hu, Liang; Wang, Chaoyu; Han, Yuan; Yang, Yanjing; Cheng, Zhixiang; Liu, Wen-Tao

2017-04-01

Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical allodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C γ, N-methyl-D-aspartate receptor, and extracellular signal-regulated kinase in a chronic constriction injury (CCI) model in rat sciatic nerve. Meanwhile, ozone significantly suppressed CCI-induced activation of spinal microglia. More importantly, the anti-nociceptive effect of ozone depended on the activation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), which was proved by the fact that the phosphorylated AMPK level increased during the ozone therapy and AMPK antagonist abolished the effect of ozone in vivo and in vitro. In addition, direct injection of AMPK agonist could replicate the anti-nociceptive effect of ozone in CCI rats. In conclusion, our observations indicate that peri-sciatic nerve injection of ozone activates AMPK to attenuate CCI-induced neuropathic pain. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

Role of sodium ferulate in the nociceptive sensory facilitation of neuropathic pain injury mediated by P2X(3) receptor.

PubMed

Zhang, Aixia; Xu, Changshui; Liang, Shangdong; Gao, Yun; Li, Guilin; Wei, Jie; Wan, Fang; Liu, Shuangmei; Lin, Jiari

2008-12-01

Neuropathic pain usually is persistent and no effective treatment. ATP plays an important role in the initiation of pain. P2X(3) receptors are localized in the dorsal root ganglion (DRG) neurons and activated by extracellular ATP. Sodium ferulate (SF) is an active principle from Chinese herbal medicine and has anti-inflammatory activities. This study observed the effects of SF on the nociceptive facilitation of the primary sensory afferent after chronic constriction injury (CCI) mediated by P2X(3) receptor. In this study, the content of ATP in DRG neurons was measured by high-performance liquid chromatography (HPLC). P2X(3) agonist-activated currents in DRG neurons was recorded by the whole-cell patch-clamp skill. The expression of P2X(3) mRNA in DRG neurons was analyzed by in situ hybridization. The ATP content of DRG was increased after CCI. In CCI rats treated with SF, the content of ATP in DRG neurons was reduced. SF decreased the increment of P2X(3) agonist-activated currents and P2X(3) mRNA expression in DRG neurons during CCI. SF may inhibit the initiation of pain and primary afferent sensitization mediated by P2X(3) receptor during CCI.

Mortality risk from comorbidities independent of triple-negative breast cancer status: NCI-SEER-based cohort analysis.

PubMed

Swede, Helen; Sarwar, Amna; Magge, Anil; Braithwaite, Dejana; Cook, Linda S; Gregorio, David I; Jones, Beth A; R Hoag, Jessica; Gonsalves, Lou; L Salner, Andrew; Zarfos, Kristen; Andemariam, Biree; Stevens, Richard G; G Dugan, Alicia; Pensa, Mellisa; A Brockmeyer, Jessica

2016-05-01

A comparatively high prevalence of comorbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients. We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors. Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74-3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90-11.02). A lower and nonsignificant effect was observed for whites with a CCI of ≥3 (Adj. HR 1.90, 95 % CI 0.68-5.29). comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk.

A Craniomaxillofacial Surgical Assistance Workstation for Enhanced Single-Stage Reconstruction Using Patient-Specific Implants.

PubMed

Murphy, Ryan J; Liacouras, Peter C; Grant, Gerald T; Wolfe, Kevin C; Armand, Mehran; Gordon, Chad R

2016-11-01

Craniomaxillofacial reconstruction with patient-specific, customized craniofacial implants (CCIs) is ideal for skeletal defects involving areas of aesthetic concern-the non-weight-bearing facial skeleton, temporal skull, and/or frontal-forehead region. Results to date are superior to a variety of "off-the-shelf" materials, but require a protocol computed tomography scan and preexisting defect for computer-assisted design/computer-assisted manufacturing of the CCI. The authors developed a craniomaxillofacial surgical assistance workstation to address these challenges and intraoperatively guide CCI modification for an unknown defect size/shape. First, the surgeon designed an oversized CCI based on his/her surgical plan. Intraoperatively, the surgeon resected the bone and digitized the resection using a navigation pointer. Next, a projector displayed the limits of the craniofacial bone defect onto the prefabricated, oversized CCI for the size modification process; the surgeon followed the projected trace to modify the implant. A cadaveric study compared the standard technique (n = 1) to the experimental technique (n = 5) using surgical time and implant fit. The technology reduced the time and effort needed to resize the oversized CCI by an order of magnitude as compared with the standard manual resizing process. Implant fit was consistently better for the computer-assisted case compared with the control by at least 30%, requiring only 5.17 minutes in the computer-assisted cases compared with 35 minutes for the control. This approach demonstrated improvement in surgical time and accuracy of CCI-based craniomaxillofacial reconstruction compared with previously reported methods. The craniomaxillofacial surgical assistance workstation will provide craniofacial surgeons a computer-assisted technology for effective and efficient single-stage reconstruction when exact craniofacial bone defect sizes are unknown.

CCI-007, a novel small molecule with cytotoxic activity against infant leukemia with MLL rearrangements

PubMed Central

Middlemiss, Shiloh M.C.; Wen, Victoria W.; Clifton, Molly; Kwek, Alan; Liu, Bing; Mayoh, Chelsea; Bongers, Angelika; Karsa, Mawar; Pan, Sukey; Cruikshank, Sarah; Scandlyn, Marissa; Hoang, Wendi; Imamura, Toshihiko; Kees, Ursula R.; Gudkov, Andrei V.; Chernova, Olga B.

2016-01-01

There is an urgent need for the development of less toxic, more selective and targeted therapies for infants with leukemia characterized by translocation of the mixed lineage leukemia (MLL) gene. In this study, we performed a cell-based small molecule library screen on an infant MLL-rearranged (MLL-r) cell line, PER-485, in order to identify selective inhibitors for MLL-r leukemia. After screening initial hits for a cytotoxic effect against a panel of 30 cell lines including MLL-r and MLL wild-type (MLL-wt) leukemia, solid tumours and control cells, small molecule CCI-007 was identified as a compound that selectively and significantly decreased the viability of a subset of MLL-r and related leukemia cell lines with CALM-AF10 and SET-NUP214 translocation. CCI-007 induced a rapid caspase-dependent apoptosis with mitochondrial depolarization within twenty-four hours of treatment. CCI-007 altered the characteristic MLL-r gene expression signature in sensitive cells with downregulation of the expression of HOXA9, MEIS1, CMYC and BCL2, important drivers in MLL-r leukemia, within a few hours of treatment. MLL-r leukemia cells that were resistant to the compound were characterised by significantly higher baseline gene expression levels of MEIS1 and BCL2 in comparison to CCI-007 sensitive MLL-r leukemia cells. In conclusion, we have identified CCI-007 as a novel small molecule that displays rapid toxicity towards a subset of MLL-r, CALM-AF10 and SET-NUP214 leukemia cell lines. Our findings suggest an important new avenue in the development of targeted therapies for these deadly diseases and indicate that different therapeutic strategies might be needed for different subtypes of MLL-r leukemia. PMID:27317766

Erythropoietin Improved Cognitive Function and Decreased Hippocampal Caspase Activity in Rat Pups after Traumatic Brain Injury

PubMed Central

Requena, Daniela F.; Block, Benjamin; Davis, Lizeth J.; Rodesch, Christopher; Casper, T. Charles; Juul, Sandra E.; Kesner, Raymond P.; Lane, Robert H.

2014-01-01

Abstract Traumatic brain injury (TBI) is a leading cause of acquired neurologic disability in children. Erythropoietin (EPO), an anti-apoptotic cytokine, improved cognitive outcome in adult rats after TBI. To our knowledge, EPO has not been studied in a developmental TBI model. Hypothesis: We hypothesized that EPO would improve cognitive outcome and increase neuron fraction in the hippocampus in 17-day-old (P17) rat pups after controlled cortical impact (CCI). Methods: EPO or vehicle was given at 1, 24, and 48 h after CCI and at post injury day (PID) 7. Cognitive outcome at PID14 was assessed using Novel Object Recognition (NOR). Hippocampal EPO levels, caspase activity, and mRNA levels of the apoptosis factors Bcl2, Bax, Bcl-xL, and Bad were measured during the first 14 days after injury. Neuron fraction and caspase activation in CA1, CA3, and DG were studied at PID2. Results: EPO normalized recognition memory after CCI. EPO blunted the increased hippocampal caspase activity induced by CCI at PID1, but not at PID2. EPO increased neuron fraction in CA3 at PID2. Brain levels of exogenous EPO appeared low relative to endogenous. Timing of EPO administration was associated with temporal changes in hippocampal mRNA levels of EPO and pro-apoptotic factors. Conclusion/Speculation: EPO improved recognition memory, increased regional hippocampal neuron fraction, and decreased caspase activity in P17 rats after CCI. We speculate that EPO improved cognitive outcome in rat pups after CCI as a result of improved neuronal survival via inhibition of caspase-dependent apoptosis early after injury. PMID:23972011

Comorbidity, Use of Common Medications, and Risk of Early Death in Patients with Localized or Locally Advanced Prostate Cancer

PubMed Central

Nieder, Carsten; Dalhaug, Astrid; Pawinski, Adam; Aandahl, Gro; Norum, Jan

2011-01-01

In this paper, we analyze predictive factors for early death from comorbidity (defined as death within 3 years from diagnosis and unrelated to prostate cancer) in patients with localized or locally advanced prostate cancer. Such information may guide individually tailored treatment or observation strategies, and help to avoid overtreatment. We retrospectively analyzed baseline parameters including information on comorbidity and medication use among 177 patients (median age at diagnosis 70 years). Actuarial survival analyses were performed. During the first 3 years, two patients (1.1%) died from progressive prostate cancer after they had developed distant metastases. The risk of dying from other causes (3.4%) was numerically higher, although not to a statistically significant degree. Six patients who died from other causes had age-adjusted Charlson comorbidity index (CCI) scores ≥5 (CCI is a sum score where each comorbid condition is assigned with a score depending on the risk of dying associated with this condition). The main comorbidity was cardiovascular disease. The two statistically significant predictive factors were medication use and age-adjusted CCI score ≥5 (univariate analysis). However, medication use was not an independent factor as all patients with age-adjusted CCI score ≥5 also used at least one class of medication. Median survival was 30 months in patients with age-adjusted CCI score ≥5. Prediction of non-prostate cancer death may be important to prevent overtreatment in patients who are more threatened by comorbidity. Our data suggest that simple parameters such as use of medications vs. none, or presence of serious cardiac disease vs. none, are not sufficient, and that age-adjusted CCI scores outperform the other factors included in our analysis. PMID:21666987

μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain

PubMed Central

Chen, Wenling; McRoberts, James A.; Marvizón, Juan Carlos G.

2014-01-01

Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI produced inconsistent NK1R internalization, suggesting that transmission of nociceptive signals by the injured nerve was variably impaired after CCI. This idea was supported by the fact that CCI produced only small changes in the ability of exogenous substance P to induce NK1R internalization or in the release of substance P evoked centrally from site of nerve injury. In subsequent experiments, NK1R internalization was induced in spinal cord slices by stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of the inhibition of substance P release by the μ-opioid receptor agonist [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO) in CCI rats but not in sham-operated rats. In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund’s adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms. PMID:24583035

μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain.

PubMed

Chen, W; McRoberts, J A; Marvizón, J C G

2014-05-16

Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI produced inconsistent NK1R internalization, suggesting that transmission of nociceptive signals by the injured nerve was variably impaired after CCI. This idea was supported by the fact that CCI produced only small changes in the ability of exogenous substance P to induce NK1R internalization or in the release of substance P evoked centrally from site of nerve injury. In subsequent experiments, NK1R internalization was induced in spinal cord slices by stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of the inhibition of substance P release by the μ-opioid receptor agonist [D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO) in CCI rats but not in sham-operated rats. In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund's adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms. Published by Elsevier Ltd.

Assessing the fitness-for-purpose of satellite multi-mission ocean color climate data records: A protocol applied to OC-CCI chlorophyll-a data.

PubMed

Mélin, F; Vantrepotte, V; Chuprin, A; Grant, M; Jackson, T; Sathyendranath, S

2017-12-15

In this work, trend estimates are used as indicators to compare the multi-annual variability of different satellite chlorophyll- a (Chl a ) data and to assess the fitness-for-purpose of multi-mission Chl a products as climate data records (CDR). Under the assumption that single-mission products are free from spurious temporal artifacts and can be used as benchmark time series, multi-mission CDRs should reproduce the main trend patterns observed by single-mission series when computed over their respective periods. This study introduces and applies quantitative metrics to compare trend distributions from different data records. First, contingency matrices compare the trend diagnostics associated with two satellite products when expressed in binary categories such as existence, significance and signs of trends. Contingency matrices can be further summarized by metrics such as Cohen's κ index that rates the overall agreement between the two distributions of diagnostics. A more quantitative measure of the discrepancies between trends is provided by the distributions of differences between trend slopes. Thirdly, maps of the level of significance P of a t -test quantifying the degree to which two trend estimates differ provide a statistical, spatially-resolved, evaluation. The proposed methodology is applied to the multi-mission Ocean Colour-Climate Change Initiative (OC-CCI) Chl a data. The agreement between trend distributions associated with OC-CCI data and single-mission products usually appears as good as when single-mission products are compared. As the period of analysis is extended beyond 2012 to 2015, the level of agreement tends to be degraded, which might be at least partly due to the aging of the MODIS sensor on-board Aqua. On the other hand, the trends displayed by the OC-CCI series over the short period 2012-2015 are very consistent with those observed with VIIRS. These results overall suggest that the OC-CCI Chl a data can be used for multi-annual time series analysis (including trend detection), but with some caution required if recent years are included, particularly in the central tropical Pacific. The study also recalls the challenges associated with creating a multi-mission ocean color data record suitable for climate research.

A New CCI ECV Release (v2.0) to Accurately Measure the Sea Level Change (1993-2015)

NASA Astrophysics Data System (ADS)

Legeais, J.; Cazenave, A. A.; Ablain, M.; Gilles, G.; Johannessen, J. A.; Scharffenberg, M. G.; Timms, G.; Andersen, O. B.; Cipollini, P.; Roca, M.; Rudenko, S.; Fernandes, J.; Balmaseda, M.; Quartly, G.; Fenoglio Marc, L.; Meyssignac, B.; Benveniste, J.; Ambrozio, A.; Restano, M.

2016-12-01

Accurate monitoring of the sea level is required to better understand its variability and changes. Sea level is one of the Essential Climate Variables (ECV) selected in the frame of the ESA Climate Change Initiative (CCI) program. It aims at providing a long-term homogeneous and accurate sea level record. The needs and feedback of the climate research community have been collected and a first version of the sea level ECV product has been generated with the best algorithms and altimeter standards. This record (1993-2014) has been validated by the climate research community. Within phase II (2014-2016), the 15 partner consortium has prepared the production of a new reprocessed homogeneous and accurate altimeter sea level record which will be distributed in Autumn 2016. New level 2 altimeter standards developed and tested within the project as well as external contributions have been identified, processed and evaluated by comparison with a reference for different altimeter missions (TOPEX/Poseidon, Jason-1 & 2, ERS-1 & 2, Envisat and GFO). The main evolutions are associated with the wet troposphere correction (based on the GPD+ algorithm including inter calibration with respect to external sensors) but also to the orbit solutions (POE-E and GFZ15), the ERA-Interim based atmospheric corrections and the FES2014 ocean tide model. A new pole tide solution is used and anomalies are referenced to the MSS DTU15. The presentation will focus on the main achievements of the ESA CCI Sea Level project and on the description of the new SL_cci ECV release covering 1993-2015. The major steps required to produce the reprocessed 23 year climate time series will be described. The impacts of the selected level 2 altimeter standards on the SL_cci ECV have been assessed on different spatial scales (global, regional, mesoscale) and temporal scales (long-term, inter-annual, periodic). A significant improvement is expected compared to the current v1.1, with the main impacts observed on the long-term evolution on decadal time scale, on global and regional scales, and for mesoscale signals. The results from product validation, carried out by several groups of the ocean and climate modeling community will be also presented.

Role of APOE Isoforms in the Pathogenesis of TBI induced Alzheimer’s Disease

DTIC Science & Technology

2016-10-01

deletion, APOE targeted replacement, complex breeding, CCI model optimization, mRNA library generation, high throughput massive parallel sequencing...demonstrate that the lack of Abca1 increases amyloid plaques and decreased APOE protein levels in AD-model mice. In this proposal we will test the hypothesis...injury, inflammatory reaction, transcriptome, high throughput massive parallel sequencing, mRNA-seq., behavioral testing, memory impairment, recovery 3

Effects of removal of dietary polyunsaturated fatty acids on plasma extravasation and mechanical allodynia in a trigeminal neuropathic pain model

PubMed Central

Martin, Yasmina B; Avendaño, Carlos

2009-01-01

Background Neuropathic pain (NP) is partially mediated by neuroinflammatory mechanisms, and also modulates local neurogenic inflammation. Dietary lipids, in particular the total amount and relative proportions of polyunsaturated fatty acids (PUFAs) of the ω-3 and ω-6 families, have been reported to modify the threshold for thermal and mechanical allodynia in the partial sciatic nerve ligation model of NP in rats. The effects of dietary lipids on other popular NP models, such as the chronic constriction injury (CCI), have not yet been examined. It is also unknown whether dietary PUFAs exert any effect on the capsaicin (CAP)-induced neurogenic inflammation under control or NP conditions. In this study we investigated these interrelated phenomena in the trigeminal territory, which has been much less explored, and for which not all data derived from limb nerves can be directly applied. Results We studied the effects of a CCI of the infraorbital nerve (IoN) on the development of mechanical allodynia and CAP-induced plasma extravasation in rats fed either a regular diet (RD), or a modified diet (MD) with much lower total content and ω-3:ω-6 ratio of PUFAs. In rats kept on MD, mechanical allodynia following CCI-IoN was more pronounced and developed earlier. Extravasation was substantially increased in naive rats fed MD, and displayed differential diet-depending changes one and four weeks after CCI-IoN. When compared with basal levels (in naive and/or sham cases), the net effect of CCI-IoN on ipsilateral extravasation was a reduction in the MD group, but an increase in the RD group, effectively neutralizing the original intergroup differences. Conclusion In summary, PUFA intake reduces CAP-induced neurogenic plasma extravasation in the trigeminal territory, and their removal significantly alters the mechanical allodynia and the plasma extravasation that result from a unilateral CCI-IoN. It is likely that this "protective" effect of dietary lipids is temporary. Also, the presence of contralateral effects of CCI-IoN precludes using the contralateral side as control. PMID:19243598

ESA Fire CCI product assessment

NASA Astrophysics Data System (ADS)

Heil, Angelika; Yue, Chao; Mouillot, Florent; Storm, Thomas; Chuvieco, Emilio; Kaiser, Johannes

2016-04-01

Vegetation fires are a major disturbance in the Earth System. Fires change the biophysical properties and dynamics of ecosystems and alter terrestrial carbon pools. By altering the atmosphere's composition, fire emissions exert a significant climate forcing. To realistically model past and future changes of the Earth System, fire disturbances must be taken into account. Related modelling efforts require consistent global burned area observations covering at least 10 to 20 years. Guided by the specific requirements of a wide range of end users, the ESA fire_cci project is currently computing a new global burned area dataset. It applies a newly developed spectral change detection algorithm upon the full ENVISAT-MERIS archive (2002 to 2012). The algorithm relies on MODIS active fire information as "seed". A first, formally validated version has been released for the period 2006 to 2008. It comprises a pixel burned area product (spatial resolution of 333 m) with date detection information and a biweekly grid product at 0.5 degree spatial resolution. We compare fire_cci burned area with other global burned area products (MCD64, GFED4(s), GEOLAND) and a set of active fires data (hotspots from MODIS, TRMM, AATSR and fire radiative power from GFAS). Output from the ongoing processing of the full MERIS timeseries will be incorporated into the study, as far as available. The analysis of patterns of agreement and disagreement between fire_cci and other products provides a better understanding of product characteristics and uncertainties. The intercomparison of the 2006-2008 fire_cci time series shows a close agreement with GFED4 data in terms of global burned area and the general spatial and temporal patterns. Pronounced differences, however, emerge for specific regions or fire events. Burned area mapped by fire_cci tends to be notably higher in regions where small agricultural fires predominate. The improved detection of small agricultural fires by fire_cci can be related to the increased spatial resolution of the MERIS sensor (333 m compared to 500 in MODIS). This is illustrated in detail using the example of the extreme 2006 spring fires in Eastern Europe.

Mild Concussion, but Not Moderate Traumatic Brain Injury, Is Associated with Long-Term Depression-Like Phenotype in Mice

PubMed Central

Hamer, Mary; Semple, Bridgette D.; Noble-Haeusslein, Linda J.; Baghchechi, Mohsen; Hiroto, Alex; Hartman, Richard E.; Obenaus, André

2016-01-01

Mild traumatic brain injuries can lead to long-lasting cognitive and motor deficits, increasing the risk of future behavioral, neurological, and affective disorders. Our study focused on long-term behavioral deficits after repeated injury in which mice received either a single mild CHI (mCHI), a repeated mild CHI (rmCHI) consisting of one impact to each hemisphere separated by 3 days, or a moderate controlled cortical impact injury (CCI). Shams received only anesthesia. Behavioral tests were administered at 1, 3, 5, 7, and 90 days post-injury (dpi). CCI animals showed significant motor and sensory deficits in the early (1–7 dpi) and long-term (90 dpi) stages of testing. Interestingly, sensory and subtle motor deficits in rmCHI animals were found at 90 dpi. Most importantly, depression-like behaviors and social passiveness were observed in rmCHI animals at 90 dpi. These data suggest that mild concussive injuries lead to motor and sensory deficits and affective disorders that are not observed after moderate TBI. PMID:26796696

Chronic sciatic neuropathy in rat reduces voluntary wheel running activity with concurrent chronic mechanical allodynia

PubMed Central

Whitehead, RA; Lam, NL; Sun, MS; Sanchez, JJ; Noor, S; Vanderwall, AG; Petersen, TR; Martin, HB

2016-01-01

BACKGROUND Animal models of peripheral neuropathy produced by a number of manipulations are assessed for the presence of pathological pain states such as allodynia. While stimulus-induced behavioral assays are frequently used and important to examine allodynia (i.e. sensitivity to light mechanical touch; von Frey fiber test) other measures of behavior that reflect overall function are not only complementary to stimulus-induced responsive measures, but are also critical to gain a complete understanding of the effects of the pain model on quality of life, a clinically relevant aspect of pain on general function. Voluntary wheel running activity in rodent models of inflammatory and muscle pain is emerging as a reliable index of general function that extends beyond stimulus-induced behavioral assays. Clinically, reports of increased pain intensity occur at night, a period typically characterized with reduced activity during the diurnal cycle. We therefore examined in rats whether alterations in wheel running activity were more robust during the inactive phase compared to the active phase of their diurnal cycle in a widely used rodent model of chronic peripheral neuropathic pain, the sciatic nerve chronic constriction injury (CCI) model. METHODS In adult male Sprague Dawley rats, baseline (BL) hindpaw threshold responses to light mechanical touch were assessed using the von Frey test prior to measuring BL activity levels using freely accessible running wheels (1 hr/day for 7 sequential days) to quantify distance traveled. Running wheel activity BL values are expressed as total distance traveled (m). The overall experimental design was: following BL measures, rats underwent either sham or CCI surgery followed by repeated behavioral re-assessment of hindpaw thresholds and wheel running activity levels for up to 18 days after surgery. Specifically, separate groups of rats were assessed for wheel running activity levels (1 hr total/trial) during the onset (within first 2 hrs) of either the (1) inactive (n=8/gp) or (2) active (n = 8/gp) phase of the diurnal cycle. An additional group of CCI-treated rats (n = 8/gp) were exposed to a locked running wheel to control for the potential effects of wheel running exercise on allodynia. The 1-hr running wheel trial period was further examined at discrete 20-min intervals to identify possible pattern differences in activity during the first, middle and last portion of the 1-hr trial. The effect of neuropathy on activity levels were assessed by measuring the change from their respective BLs to distance traveled in the running wheels. RESULTS While wheel running distances between groups were not different at BL from rats examined during either the inactive phase of the diurnal cycle or active phase of the diurnal cycle, sciatic nerve CCI reduced running wheel activity levels compared to sham-operated controls during the inactive phase. Additionally, compared to sham controls, bilateral low threshold mechanical allodynia was observed at all time-points after surgical induction of neuropathy in rats with free-wheel and locked-wheel access. Allodynia in CCI compared to shams was replicated in rats whose running wheel activity was examined during the active phase of the diurnal cycle. Conversely, no significant reduction in wheel running activity was observed in CCI-treated rats compared to sham controls at any timepoint when activity levels were examined during the active diurnal phase. Lastly, running wheel activity patterns within the 1 hr trial period during the inactive phase of the diurnal cycle were relatively consistent throughout each 20 min phase. CONCLUSIONS Compared to non-neuropathic sham controls, a profound and stable reduction of running wheel activity was observed in CCI rats during the inactive phase of the diurnal cycle. A concurrent robust allodynia persisted in all rats regardless of when wheel running activity was examined or whether they ran on wheels, suggesting that acute wheel running activity does not alter chronic low intensity mechanical allodynia as measured using the von Frey fiber test. Overall, these data support that acute wheel running exercise with limited repeated exposures does not itself alter allodynia and offers a behavioral assay complementary to stimulus-induced measures of neuropathic pain. PMID:27782944

Electroconvulsive stimulation (ECS) increases the expression of neuropeptide Y (NPY) in rat brains in a model of neuropathic pain: a quantitative real-time polymerase chain reaction (RT-PCR) study.

PubMed

Okabe, Tadashi; Sato, Chiyo; Matsumoto, Keisuke; Ozawa, Hitoshi; Sakamoto, Atsuhiro

2009-11-01

Electroconvulsive shock therapy (ECT) has been widely used as an effective and established treatment for refractory depression and schizophrenia. Some reports have shown that ECT is also effective for treating refractory neuropathic pain. In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from day 2 after surgery. An electroconvulsive shock (ECS) was administered to rodents once daily for 6 days on days 7-12 after CCI operation using a pulse generator. Thermal and mechanical stimulation tests were performed to assess pain thresholds. Real-time polymerase chain reaction was used to measure the gene expression levels for 5HT(1A)R, 5HT(2A)R, neuropeptide Y (NPY), and GABAA(alpha1)R in the brain. After ECS, the latency to withdrawal from thermal stimulation was significantly increased; however, pain withdrawal thresholds in response to mechanical stimulation were not significantly changed. Expression ratios of NPY were significantly greater after ECS. Symptoms of neuropathic pain improved and expression of NPY in the brain was increased in CCI model rats after ECS, suggesting that changes in the expression of NPY in the brain may be related to the mechanism of action of ECT in treating neuropathic pain.

Duloxetine and 8-OH-DPAT, but not fluoxetine, reduce depression-like behaviour in an animal model of chronic neuropathic pain.

PubMed

Hu, Bing; Doods, Henri; Treede, Rolf-Detlef; Ceci, Angelo

2016-04-21

The current study assessed whether antidepressant and/or antinociceptive drugs, duloxetine, fluoxetine as well as (±)-8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), are able to reverse depression-like behaviour in animals with chronic neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve in rats was selected as neuropathic pain model. Mechanical hypersensitivity and depression-like behaviour were evaluated 4 weeks after surgery by "electronic algometer" and forced swimming test (FST), which measured the time of immobility, and active behaviours climbing and swimming. The selective noradrenergic and serotonergic uptake blocker duloxetine (20mg/kg) and the selective 5-HT1A agonist 8-OH-DPAT (0.5mg/kg) significantly reversed both mechanical hypersensitivity and depression-like behaviour in CCI animals. Duloxetine significantly reversed depression-like behaviour in CCI rats by increasing the time of climbing and swimming, while 8-OH-DPAT attenuated depression-like behaviour mainly by increasing the time of swimming. However, the selective serotonergic uptake blocker fluoxetine (20mg/kg) failed to attenuate mechanical hypersensitivity and depression-like behaviour, possibly due to confounding pro-nociceptive actions at 5-HT3 receptors. These data suggest to target noradrenergic and 5-HT1A receptors for treatment of chronic pain and its comorbidity depression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ovine model of neuropathic pain for assessing mechanisms of spinal cord stimulation therapy via dorsal horn recordings, von Frey filaments, and gait analysis

PubMed Central

Reddy, Chandan G; Miller, John W; Abode-Iyamah, Kingsley O; Safayi, Sina; Wilson, Saul; Dalm, Brian D; Fredericks, Douglas C; Gillies, George T; Howard, Matthew A; Brennan, Timothy J

2018-01-01

Background It is becoming increasingly important to understand the mechanisms of spinal cord stimulation (SCS) in alleviating neuropathic pain as novel stimulation paradigms arise. Purpose Additionally, the small anatomic scale of current SCS animal models is a barrier to more translational research. Methods Using chronic constriction injury (CCI) of the common peroneal nerve (CPN) in sheep (ovine), we have created a chronic model of neuropathic pain that avoids motor deficits present in prior large animal models. This large animal model has allowed us to implant clinical grade SCS hardware, which enables both acute and chronic testing using von Frey filament thresholds and gait analysis. Furthermore, the larger anatomic scale of the sheep allows for simultaneous single-unit recordings from the dorsal horn and SCS with minimal electrical artifact. Results Detectable tactile hypersensitivity occurred 21 days after nerve injury, with preliminary indications that chronic SCS may reverse it in the painful limb. Gait analysis revealed no hoof drop in the CCI model. Single neurons were identified and discriminated in the dorsal horn, and their activity was modulated via SCS. Unlike previous large animal models that employed a complete transection of the nerve, no motor deficit was observed in the sheep with CCI. Conclusion To our knowledge, this is the first reported large animal model of chronic neuropathic pain which facilitates the study of both acute and chronic SCS using complementary behavioral and electrophysiologic measures. As demonstrated by our successful establishment of these techniques, an ovine model of neuropathic pain is suitable for testing the mechanisms of SCS. PMID:29942150

Rapid antifungal susceptibility testing by matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis.

PubMed

Vella, Antonietta; De Carolis, Elena; Vaccaro, Luisa; Posteraro, Patrizia; Perlin, David S; Kostrzewa, Markus; Posteraro, Brunella; Sanguinetti, Maurizio

2013-09-01

The widespread use of antifungal agents, which is likely to expand with their enhanced availability, has promoted the emergence of drug-resistant strains. Antifungal susceptibility testing (AFST) is now an essential procedure for guiding appropriate antifungal therapy. Recently, we developed a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based method that enables the detection of fungal isolates with reduced echinocandin susceptibility, relying on the proteome changes that are detectable after a 15-h exposure of fungal cells to serial drug concentrations. Here, we describe a simplified version of this approach that facilitates discrimination of the susceptible and resistant isolates of Candida albicans after a 3-h incubation in the presence of "breakpoint" level drug concentrations of the echinocandin caspofungin (CSF). Spectra at concentrations of 0 (null), 0.03 (intermediate), and 32 (maximal) μg/ml of CSF were used to create individual composite correlation index (CCI) matrices for 65 C. albicans isolates, including 13 fks1 mutants. Isolates are then classified as susceptible or resistant to CSF if the CCI values of spectra at 0.03 and 32 μg/ml are higher or lower, respectively, than the CCI values of spectra at 0.03 and 0 μg/ml. In this way, the drug resistance of C. albicans isolates to echinocandin antifungals can be quickly assessed. Furthermore, the isolate categorizations determined using MALDI-TOF MS-based AFST (ms-AFST) were consistent with the wild-type and mutant FKS1 genotypes and the AFST reference methodology. The ms-AFST approach may provide a rapid and reliable means of detecting emerging antifungal resistance and accelerating the initiation of appropriate antifungal treatment.

The protective effect of hydrogen sulfide (H2S) on traumatic brain injury (TBI) induced memory deficits in rats.

PubMed

Karimi, Seyed Asaad; Hosseinmardi, Narges; Janahmadi, Mahyar; Sayyah, Mohammad; Hajisoltani, Razieh

2017-09-01

Traumatic brain injury (TBI), as an expanding public health epidemic, is a common cause of death among youth. TBI is associated with cognitive deficits and memory impairment. Hydrogen sulfide (H 2 S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the central nervous system. In the present study the potential neuroprotective role of sodium hydrosulfide (NaHS), an H 2 S donor on TBI induced memory deficit in a rat model of controlled cortical impact (CCI) injury was investigated. CCI model was used to induce TBI. Male rats were randomly assigned into the following groups: control, sham, sham treated with NaHS, TBI, and TBI treated with NaHS (3 and 5mg/kg). NaHS was injected intraperitoneally 5min before TBI induction. Learning and memory were assessed using Morris water maze (MWM) on days 8-12 following injury. CCI resulted in MWM deficits. Injured animals showed a slower rate of acquisition with respect to the sham-operated animals [F (1, 24)=13.97, P<0.01, two-way ANOVA]. NaHS improved spatial memory impairment of injured rats. Treatment with NaHS (5 mg/kg) decreased the escape latency [F (1, 24)=7.559, P<0.05, two-way ANOVA] and traveled distance [F (1, 12)=6.398, P<0.05, Two way ANOVA)]. In probe test, injured animals spent less time in target zone (P<0.05, unpaired t-test) and NaHS did not have any effect on this parameter (p>0.05, one way ANOVA). These findings suggest that NaHS has a neuroprotective effect on TBI-induced memory impairment in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

KSC-2013-3086

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068304 - Chris Ferguson, director of Crew and Mission Operations for The Boeing Company and former NASA astronaut, is interviewed by the media during the unveiling of a CST-100 mock-up at the company's Houston Product Support Center. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3087

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068310 - Chris Ferguson, director of Crew and Mission Operations for The Boeing Company and former NASA astronaut, discusses the fit check evaluation of the CST-100 mock-up with the media during its unveiling at the company's Houston Product Support Center. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3074

NASA Image and Video Library

2013-07-22

HOUSTON - NASA astronaut Serena Aunon and Andrea Gilkey, a human factors engineer with The Boeing Company, tag up before Aunon puts on her orange launch-and-entry suit for a fit check evaluation of the CST-100 spacecraft at the company's Houston Product Support Center. Aunon's fit check will help evaluate a crew's maneuverability in the spacecraft and test communications. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations, including the International Space Station. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3085

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068300 - Chris Ferguson, director of Crew and Mission Operations for The Boeing Company and former NASA astronaut, addresses the media before the unveiling of a CST-100 mock-up at the company's Houston Product Support Center. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations. The evaluation is part of the ongoing work supporting Boeing's funded Space Act Agreement with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative. CCiCap is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

Effects of curcumin on pain threshold and on the expression of nuclear factor κ B and CX3C receptor 1 after sciatic nerve chronic constrictive injury in rats.

PubMed

Cao, Hong; Zheng, Jin-Wei; Li, Jia-Jia; Meng, Bo; Li, Jun; Ge, Ren-Shan

2014-11-01

To investigate the effects of curcumin on pain threshold and the expressions of nuclear factor κ B (NF-κ B) and CX3C chemokine receptor 1 (CX3CR1) in spinal cord and dorsal root ganglion (DRG) of the rats with sciatic nerve chronic constrictive injury. One hundred and twenty male Sprague Dawley rats, weighing 220-250 g, were randomly divided into 4 groups. Sham surgery (sham) group: the sciatic nerves of rats were only made apart but not ligated; chronic constrictive injury (CCI) group: the sciatic nerves of rats were only ligated without any drug treatment; curcumin treated injury (Cur) model group: the rats were administrated with curcumin 100 mg/(kg·d) by intraperitoneal injection for 14 days after CCI; solvent control (SC) group: the rats were administrated with the solvent at the same dose for 14 days after CCI. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of rats were respectively measured on pre-operative day 2 and postoperative day 1, 3, 5, 7, 10 and 14. The lumbar segment L4-5 of the spinal cord and the L4, L5 DRG was removed at post-operative day 3, 7 and 14. The change of nuclear factor κ B (NF-κ B) p65 expression was detected by Western blotting while the expression of CX3CR1 was determined by immunohistochemical staining. Compared with the sham group, the TWL and MWT of rats in the CCI group were significantly decreased on each post-operative day (P<0.01), which reached a nadir on the 3rd day after CCI, and the expressions of NF-κ B p65 and CX3CR1 were markedly increased in spinal cord dorsal horn and DRG. In the Cur group, the TWL of rats were significantly increased than those in the CCI group on post-operative day 7, 10 and 14 (P<0.05) and MWT increased than those in the CCI group on post-operative day 10 and 14 (P<0.05). In addition, the administration of curcumin significantly decreased the positive expressions of NF-κ B p65 and CX3CR1 in spinal cord and DRG (P<0.05). Our study suggests that curcumin could ameliorate the CCI-induced neuropathic pain, probably through inhibiting CX3CR1 expression by the activation of NF-κ B p65 in spinal cord and DRG.

In-situ databases and comparison of ESA Ocean Colour Climate Change Initiative (OC-CCI) products with precursor data, towards an integrated approach for ocean colour validation and climate studies

NASA Astrophysics Data System (ADS)

Brotas, Vanda; Valente, André; Couto, André B.; Grant, Mike; Chuprin, Andrei; Jackson, Thomas; Groom, Steve; Sathyendranath, Shubha

2014-05-01

Ocean colour (OC) is an Oceanic Essential Climate Variable, which is used by climate modellers and researchers. The European Space Agency (ESA) Climate Change Initiative project, is the ESA response for the need of climate-quality satellite data, with the goal of providing stable, long-term, satellite-based ECV data products. The ESA Ocean Colour CCI focuses on the production of Ocean Colour ECV uses remote sensing reflectances to derive inherent optical properties and chlorophyll a concentration from ESA's MERIS (2002-2012) and NASA's SeaWiFS (1997 - 2010) and MODIS (2002-2012) sensor archives. This work presents an integrated approach by setting up a global database of in situ measurements and by inter-comparing OC-CCI products with pre-cursor datasets. The availability of in situ databases is fundamental for the validation of satellite derived ocean colour products. A global distribution in situ database was assembled, from several pre-existing datasets, with data spanning between 1997 and 2012. It includes in-situ measurements of remote sensing reflectances, concentration of chlorophyll-a, inherent optical properties and diffuse attenuation coefficient. The database is composed from observations of the following datasets: NOMAD, SeaBASS, MERMAID, AERONET-OC, BOUSSOLE and HOTS. The result was a merged dataset tuned for the validation of satellite-derived ocean colour products. This was an attempt to gather, homogenize and merge, a large high-quality bio-optical marine in situ data, as using all datasets in a single validation exercise increases the number of matchups and enhances the representativeness of different marine regimes. An inter-comparison analysis between OC-CCI chlorophyll-a product and satellite pre-cursor datasets was done with single missions and merged single mission products. Single mission datasets considered were SeaWiFS, MODIS-Aqua and MERIS; merged mission datasets were obtained from the GlobColour (GC) as well as the Making Earth Science Data Records for Use in Research Environments (MEaSUREs). OC-CCI product was found to be most similar to SeaWiFS record, and generally, the OC-CCI record was most similar to records derived from single mission than merged mission initiatives. Results suggest that CCI product is a more consistent dataset than other available merged mission initiatives. In conclusion, climate related science, requires long term data records to provide robust results, OC-CCI product proves to be a worthy data record for climate research, as it combines multi-sensor OC observations to provide a >15-year global error-characterized record.

Kollidon VA64, a membrane-resealing agent, reduces histopathology and improves functional outcome after controlled cortical impact in mice.

PubMed

Mbye, Lamin H; Keles, Eyup; Tao, Luyang; Zhang, Jimmy; Chung, Joonyong; Larvie, Mykol; Koppula, Rajani; Lo, Eng H; Whalen, Michael J

2012-03-01

Loss of plasma membrane integrity is a feature of acute cellular injury/death in vitro and in vivo. Plasmalemma-resealing agents are protective in acute central nervous system injury models, but their ability to reseal cell membranes in vivo has not been reported. Using a mouse controlled cortical impact (CCI) model, we found that propidium iodide-positive (PI+) cells pulse labeled at 6, 24, or 48 hours maintained a degenerative phenotype and disappeared from the injured brain by 7 days, suggesting that plasmalemma permeability is a biomarker of fatal cellular injury after CCI. Intravenous or intracerebroventricular administration of Kollidon VA64, poloxamer P188, or polyethylene glycol 8000 resealed injured cell membranes in vivo (P<0.05 versus vehicle or poloxamer P407). Kollidon VA64 (1 mmol/L, 500 μL) administered intravenously to mice 1  hour after CCI significantly reduced acute cellular degeneration, chronic brain tissue damage, brain edema, blood-brain barrier damage, and postinjury motor deficits (all P<0.05 versus vehicle). However, VA64 did not rescue pulse-labeled PI+ cells from eventual demise. We conclude that PI permeability within 48 hours of CCI is a biomarker of eventual cell death/loss. Kollidon VA64 reduces secondary damage after CCI by mechanisms other than or in addition to resealing permeable cells.

Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats

PubMed Central

Wen, Hui-Zhong; Gao, Shi-Hao; Zhao, Yan-Dong; He, Wen-Juan; Tian, Xue-Long; Ruan, Huai-Zhen

2017-01-01

Background: Transcranial direct current stimulation (tDCS) is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters. Objective: This study aims to assess the effects of tDCS of primary motor cortex (M1) on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia. Methods: Using the chronic neuropathic pain models of chronic constriction injury (CCI), we measured pain thresholds before and after anodal-tDCS (A-tDCS) using different parameter conditions, including stimulation intensity, stimulation time, intervention time and electrode located (ipsilateral or contralateral M1 of the ligated paw on male/female CCI models). Results: Following the application of A-tDCS over M1, we observed that the antinociceptive effects were depended on different parameters. First, we found that repetitive A-tDCS had a longer analgesic effect than single stimulus, and both ipsilateral-tDCS (ip-tDCS) and contralateral-tDCS (con-tDCS) produce a long-lasting analgesic effect on neuropathic pain. Second, the antinociceptive effects were intensity-dependent and time-dependent, high intensities worked better than low intensities and long stimulus durations worked better than short stimulus durations. Third, timing of the intervention after injury affected the stimulation outcome, early use of tDCS was an effective method to prevent the development of pain, and more frequent intervention induced more analgesia in CCI rats, finally, similar antinociceptive effects of con- and ip-tDCS were observed in both sexes of CCI rats. Conclusion: Optimized protocols of tDCS for treating antinociceptive effects were developed. These findings should be taken into consideration when using tDCS to produce analgesic effects in clinical applications. PMID:28659772

Development and Validation of the Career Competencies Indicator (CCI)

ERIC Educational Resources Information Center

Francis-Smythe, Jan; Haase, Sandra; Thomas, Erica; Steele, Catherine

2013-01-01

This article describes the development and validation of the Career Competencies Indicator (CCI); a 43-item measure to assess career competencies (CCs). Following an extensive literature review, a comprehensive item generation process involving consultation with subject matter experts, a pilot study and a factor analytic study on a large sample…

An Empirical Assessment of the Communication Components Inventory

ERIC Educational Resources Information Center

Keaton, Shaughan A.; Bodie, Graham D.

2012-01-01

This article attempts to demonstrate the psychometric properties and evidence of validity for a measure recently proposed in this journal, the Communication Components Inventory (CCI). Across two studies, a total of 903 undergraduate students completed one of the two response formats--dichotomous and scaled--of the CCI and the Multiple…

Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system

PubMed Central

Zhao, Xin; Wang, Chuang; Cui, Wu-Geng; Ma, Qing; Zhou, Wen-Hua

2015-01-01

Fisetin, a natural flavonoid, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential antinociceptive efficacies of fisetin against neuropathic pain and explore mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely ligating the sciatic nerves, and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but not mechanical allodynia) in CCI mice, concomitant with escalated levels of spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The antihyperalgesic action of fisetin was abolished by chemical depletion of spinal serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7 receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia. These findings confirm that chronic fisetin treatment exerts antinociceptive effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic system (coupled with 5-HT7) being critically involved. Of special benefit, fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety (evaluated in forced swim test, novelty suppressed feeding test and light-dark test) evoked by neuropathic pain. PMID:25761874

Single Crystal Epitaxy and Characterization of Beta-SiC.

DTIC Science & Technology

1982-07-01

and CH4 (35, 40), SiC] 4 and C3H8 (40-43), SiCl4 and C6H6 (37), SiCl4 and C7H8 (37, 44), and SiC]4 and CCI 4 (45-47). In all cases, the carrier gas...crystal layer on top of the as-formed 8-SiC substrate. Their problem may arise from the use of the gas combination of SiCl4 and CCI 4, because still...falling between those for the CH4- and the C2H4-c-ritaining systems. (4) The SiCl4 /CCI4/H2 System The species considered to be in the gaseous phase of

Systems Biology Approaches for Discovering Biomarkers for Traumatic Brain Injury

DTIC Science & Technology

2013-07-01

injury (FPI), in which injury is produced by the impact of a pendulum onto a fluid reservoir, or controlled cortical impact (CCI), in which a rigid...algorithm, and the MSigDB Web site in Table 3 allows users to run GSEA on up- loaded data. One drawback to GSEA and the hypergeometric test is that

Prognostic indices of perioperative outcome following transperitoneal laparoscopic adrenalectomy.

PubMed

Kiziloz, Halil; Meraney, Anoop; Dorin, Ryan; Nip, Jonathan; Kesler, Stuart; Shichman, Steven

2014-08-01

We sought to identify preoperative patient and tumor characteristics that may be useful prognostic indicators of postsurgical outcome in patients undergoing laparoscopic adrenalectomy (LA). Data from 92 patients who underwent 93 transabdominal LA procedures between 2006-2012 were retrieved. Patients were stratified based on estimated blood loss (EBL), length of stay (LOS), and perioperative complications. Interdependencies between surgical outcome and patient demographics, tumor characteristics, comorbidities, and Charlson Comorbidity Index (CCI) were statistically analyzed. The predictive capacity of each index was assessed using receiver operating characteristic curves. Neither age, gender, tumor laterality, body mass index, American Society of Anesthesiologists (ASA) score, nor CCI predicted the occurrence of perioperative complications. EBL was significantly associated with increased age, tumor size, ASA score, and CCI, whereas prolonged LOS was associated with higher ASA score. Tumor size was related, although not significantly, to LOS and perioperative complications. Tumors ≥7.5 cm in diameter were significantly associated with worse perioperative outcomes. LA for adrenal lesions demonstrated reasonable complication rates and perioperative outcomes. Tumor size, CCI, and ASA score are predictive of increased EBL and LOS.

17 years of aerosol and clouds from the ATSR Series of Instruments

NASA Astrophysics Data System (ADS)

Poulsen, C. A.

2015-12-01

Aerosols play a significant role in Earth's climate by scattering and absorbing incoming sunlight and affecting the formation and radiative properties of clouds. The extent to which aerosols affect cloud remains one of the largest sources of uncertainty amongst all influences on climate change. Now, a new comprehensive datasets has been developed under the ESA Climate Change Initiative (CCI) programme to quantify how changes in aerosol levels affect these clouds. The unique dataset is constructed from the Optimal Retrieval of Aerosol and Cloud (ORAC) algorithm used in (A)ATSR (Along Track Scanning Radiometer) retrievals of aerosols generated in the Aerosol CCI and the CC4CL ( Community Code for CLimate) for cloud retrieval in the Cloud CCI. The ATSR instrument is a dual viewing instrument with on board visible and infra red calibration systems making it an ideal instrument to study trends of Aerosol and Clouds and their interactions. The data set begins in 1995 and ends in 2012. A new instrument in the series SLSTR(Sea and Land Surface Temperature Radiometer) will be launch in 2015. The Aerosol and Clouds are retreived using similar algorithms to maximise the consistency of the results These state-of-the-art retrievals have been merged together to quantify the susceptibility of cloud properties to changes in aerosol concentration. Aerosol-cloud susceptibilities are calculated from several thousand samples in each 1x1 degree globally gridded region. Two-D histograms of the aerosol and cloud properties are also included to facilitate seamless comparisons between other satellite and modelling data sets. The analysis of these two long term records will be discussed individually and the initial comparisons between these new joint products and models will be presented.

Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury

PubMed Central

Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G.; Hovda, David A.; Sutton, Richard L.

2013-01-01

Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients’ remains under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6 h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. PMID:23994447

Long non-coding RNA CCAT1 modulates neuropathic pain progression through sponging miR-155.

PubMed

Dou, Lidong; Lin, Hongqi; Wang, Kaiwei; Zhu, Guosong; Zou, Xuli; Chang, Enqiang; Zhu, Yongfeng

2017-10-27

Neuropathic pain is caused by dysfunction or primary injury of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) play important roles in the development of neuropathic pain. However, the effects of lncRNA colon cancer associated transcript-1 (CCAT1) in neuropathic pain have not been reported. The model of bilateral sciatic nerve chronic constriction injuries (bCCI) is regarded as long-lasting mechanical hypersensitivity and cold allodynia, which is the representative symptom in the human subjects suffering from the neuropathic pain. In this study, we found that CCAT1 expression was decreased in the spinal dorsal horn, dorsal root ganglion (DRG), hippocampus, and anterior cingulate cortex (ACC) of rats with bCCI. The rats of bCCI presented the cold allodynia after the 14 th day of postoperation. We furtherly showed that lncRNA CCAT1 decreased miR-155 expression and enhanced Serum and glucocorticoid regulated protein kinase 3 (SGK3) expression in the NGF-differentiated PC12 cell. We found that miR-155 expression was increased in the spinal dorsal horn, DRG, hippocampus, and ACC of rats with bCCI injuries. However, SGK3 expression was downregulated in the spinal dorsal horn, DRG, hippocampus, and ACC of rats with bCCI injuries. Moreover, lncRNA CCAT1 overexpression could alleviate the pain thresholds and inhibited expression of SGK3 could rescue this effect. In conclusion, these results suggested the crucial roles of CCAT1 and SGK3 in the neuropathic pain.

Long non-coding RNA CCAT1 modulates neuropathic pain progression through sponging miR-155

PubMed Central

Dou, Lidong; Lin, Hongqi; Wang, Kaiwei; Zhu, Guosong; Zou, Xuli; Chang, Enqiang; Zhu, Yongfeng

2017-01-01

Neuropathic pain is caused by dysfunction or primary injury of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) play important roles in the development of neuropathic pain. However, the effects of lncRNA colon cancer associated transcript-1 (CCAT1) in neuropathic pain have not been reported. The model of bilateral sciatic nerve chronic constriction injuries (bCCI) is regarded as long-lasting mechanical hypersensitivity and cold allodynia, which is the representative symptom in the human subjects suffering from the neuropathic pain. In this study, we found that CCAT1 expression was decreased in the spinal dorsal horn, dorsal root ganglion (DRG), hippocampus, and anterior cingulate cortex (ACC) of rats with bCCI. The rats of bCCI presented the cold allodynia after the 14th day of postoperation. We furtherly showed that lncRNA CCAT1 decreased miR-155 expression and enhanced Serum and glucocorticoid regulated protein kinase 3 (SGK3) expression in the NGF-differentiated PC12 cell. We found that miR-155 expression was increased in the spinal dorsal horn, DRG, hippocampus, and ACC of rats with bCCI injuries. However, SGK3 expression was downregulated in the spinal dorsal horn, DRG, hippocampus, and ACC of rats with bCCI injuries. Moreover, lncRNA CCAT1 overexpression could alleviate the pain thresholds and inhibited expression of SGK3 could rescue this effect. In conclusion, these results suggested the crucial roles of CCAT1 and SGK3 in the neuropathic pain. PMID:29163801

Mortality Risk from Co-Morbidities independent of Triple-Negative Breast Cancer Status: NCI SEER-based Cohort Analysis

PubMed Central

Swede, Helen; Sarwar, Amna; Magge, Anil; Braithwaite, Dejana; Cook, Linda S.; Gregorio, David I.; Jones, Beth A; Hoag, Jessica; Gonsalves, Lou; Salner, Andrew; Zarfos, Kristen; Andemariam, Biree; Stevens, Richard G; Dugan, Alicia; Pensa, Mellisa; Brockmeyer, Jessica

2017-01-01

Purpose A comparatively high prevalence of co-morbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at three-fold the rate in AA/B compared to white breast cancer patients. Methods We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-07. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox Survival Analyses estimated hazard ratios (HR) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors. Results Among patients with SEER-Local Stage, TNBC increased the risk of death (HR=2.18, 95% CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR=1.50, 95% CI 0.74-3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR=1.49, 95% CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER-Regional Stage but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR=5.65, 95% CI 2.90-11.02). A lower and non-significant effect was observed for whites with a CCI of ≥3 (Adj. HR=1.90, 95% CI 0.68-5.29). Conclusions Co-morbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk. PMID:27000206

Suppression of MyD88-dependent signaling alleviates neuropathic pain induced by peripheral nerve injury in the rat.

PubMed

Liu, Fan; Wang, Zhiyao; Qiu, Yue; Wei, Min; Li, Chunyan; Xie, Yikuan; Shen, Le; Huang, Yuguang; Ma, Chao

2017-03-31

MyD88 is the adaptor protein of MyD88-dependent signaling pathway of TLRs and IL-1 receptor and regulates innate immune response. However, it was not clear whether and how MyD88 and related signaling pathways in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) are involved in neuropathic pain. Chronic constriction injury (CCI) was used to induce neuropathic pain in the rat. The expression of MyD88, TRIF, IBA1, and GFAP was detected with immunofluorescent staining and Western blot. The expression of interleukin-1 beta (IL-1β), high mobility group box 1 (HMGB1), NF-κB-p65, phosphorylated NF-κB-p65, ERK, phosphorylated ERK, and tumor necrosis factor-alpha (TNF-α) was detected with Western blot. Pain-related behavioral effects of MyD88 homodimerization inhibitory peptide (MIP) were accessed up to 3 weeks after intrathecal administration. Peripheral nerve injury significantly increased the protein level of MyD88 in the DRG and SDH, but had no effect on TRIF. MyD88 was found partly distributed in the nociceptive neurons in the DRGs and the astrocytes and microglia in the SDH. HMGB1 and IL-1β were also found upregulated in nociceptive pathways of CCI rats. Intrathecal application of MIP significantly alleviated mechanical and thermal hyperalgesia in the CCI rats and also reversed CCI-induced upregulation of MyD88 in both DRG and SDH. Further investigation revealed that suppression of MyD88 protein reduced the release of TNF-α and glial activation in the SDH in the CCI rats. MyD88-dependent TIR pathway in the DRG and SDH may play a role in CCI-induced neuropathic pain. MyD88 might serve as a potential therapeutic target for neuropathic pain.

Impact of a disease management program upon caregivers of chronically critically ill patients.

PubMed

Douglas, Sara L; Daly, Barbara J; Kelley, Carol Genet; O'Toole, Elizabeth; Montenegro, Hugo

2005-12-01

Few studies have examined the effects of caregiving on the caregivers of chronically critically ill (CCI) patients, and no one has examined the impact of a disease management program (DMP) on physical and psychological outcomes for the caregivers of CCI patients. The purposes of this study of caregivers of CCI patients were as follows: (1) to describe the characteristics of CCI patients and caregivers and to examine the frequency of depression, subjective burden, and physical health; (2) to examine factors related to depression after hospital discharge; and (3) to examine the effects of a DMP on the physical health, depression, and burden of caregivers 2 months post-hospital discharge. Prospective experimental design. Caregivers of 290 patients who had received > 3 days of mechanical ventilation while in the ICU of a university medical center. Sociodemographics, caregiver burden, physical health status, and depression were measured using established tools. Interviews of caregivers were conducted at hospital discharge and 2 months later. Seventy-three percent of patients survived, completed the study period, and required caregiving 2 months later. Caregivers of patients residing in an institution reported higher depression (p = 0.0001), higher burden (ie, disrupted schedule, p = 0.0001; lack of family support, p = 0.036), and greater health problem scores (p = 0.0001) than did caregivers of patients residing at home. The DMP did not have a statistically significant impact on any of the outcome variables. However, by 2 months, 54% of caregivers in the experimental group had no depression or mild depression compared with 34.5% of the control group. Two months after hospital discharge, approximately 25% of caregivers were classified as depressed with 16.7% of the depressed group classified as moderately or severely depressed. The caregivers of CCI patients are at risk for post-hospital discharge depression, and the caregivers of institutionalized CCI patients are at highest risk of long-term negative effects from caregiving.

The inhibition of nitric oxide-activated poly(ADP-ribose) synthetase attenuates transsynaptic alteration of spinal cord dorsal horn neurons and neuropathic pain in the rat.

PubMed

Mao, J; Price, D D; Zhu, J; Lu, J; Mayer, D J

1997-09-01

Transsynaptic alteration of spinal cord dorsal horn neurons characterized by hyperchromatosis of cytoplasm and nucleoplasm (so-called 'dark' neurons) occurs in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the common sciatic nerve. The incidence of dark neurons in CCI rats has been proposed to be mediated by glutamate-induced neurotoxicity. In the present study, we examined whether the inhibition of the nitric oxide (NO)-activated poly(ADP-ribose) synthetase (PARS), a nuclear enzyme critical to glutamate-induced neurotoxicity, would both reduce the incidence of dark neurons and attenuate behavioral manifestations of neuropathic pain in CCI rats. Dark neurons were observed bilaterally (with ipsilateral predominance) within the spinal cord dorsal horn, particularly in laminae I-II, of rats 8 days after unilateral sciatic nerve ligation as compared to sham operated rats. The number of dark neurons in the dorsal horn was dose-dependently reduced in CCI rats receiving once daily intrathecal (i.t.) treatment with the PARS inhibitor benzamide (200 or 400 nmol, but not 100 nmol benzamide or saline) for 7 days. Consistent with the histological improvement, thermal hyperalgesia, mechanical hyperalgesia, and low threshold mechano-allodynia also were reliably reduced in CCI rats treated with either 200 or 400 nmol benzamide. Neither dark neurons nor neuropathic pain behaviors were reliably affected by i.t. administration of either 800 nmol novobiocin (a mono(ADP-ribose) synthetase) or 800 nmol benzoic acid (the backbone structure of benzamide), indicating a selective effect of benzamide. Intrathecal treatment with an NO synthase inhibitor NG-nitro-L-arginine methyl ester (40 nmol, but not its inactive D-isomer) utilizing the same benzamide treatment regimen resulted in similar reductions of both dark neurons and neuropathic pain behaviors in CCI rats. These results provide, for the first time, in vivo evidence indicating that benzamide is neuroprotective and that the PARS-mediated transsynaptic alteration of spinal cord dorsal horn neurons contributes to behavioral manifestations of neuropathic pain in CCI rats. These observations may have general implications beyond treatment of neuropathic pain in that PARS-mediated neuronal alterations may play a significant role in glutamate-mediated neurotoxicity under many other circumstances.

An improved and homogeneous altimeter sea level record from the ESA Climate Change Initiative

NASA Astrophysics Data System (ADS)

Legeais, Jean-François; Ablain, Michaël; Zawadzki, Lionel; Zuo, Hao; Johannessen, Johnny A.; Scharffenberg, Martin G.; Fenoglio-Marc, Luciana; Joana Fernandes, M.; Baltazar Andersen, Ole; Rudenko, Sergei; Cipollini, Paolo; Quartly, Graham D.; Passaro, Marcello; Cazenave, Anny; Benveniste, Jérôme

2018-02-01

Sea level is a very sensitive index of climate change since it integrates the impacts of ocean warming and ice mass loss from glaciers and the ice sheets. Sea level has been listed as an essential climate variable (ECV) by the Global Climate Observing System (GCOS). During the past 25 years, the sea level ECV has been measured from space by different altimetry missions that have provided global and regional observations of sea level variations. As part of the Climate Change Initiative (CCI) program of the European Space Agency (ESA) (established in 2010), the Sea Level project (SL_cci) aimed to provide an accurate and homogeneous long-term satellite-based sea level record. At the end of the first phase of the project (2010-2013), an initial version (v1.1) of the sea level ECV was made available to users (Ablain et al., 2015). During the second phase of the project (2014-2017), improved altimeter standards were selected to produce new sea level products (called SL_cci v2.0) based on nine altimeter missions for the period 1993-2015 (https://doi.org/10.5270/esa-sea_level_cci-1993_2015-v_2.0-201612; Legeais and the ESA SL_cci team, 2016c). Corresponding orbit solutions, geophysical corrections and altimeter standards used in this v2.0 dataset are described in detail in Quartly et al. (2017). The present paper focuses on the description of the SL_cci v2.0 ECV and associated uncertainty and discusses how it has been validated. Various approaches have been used for the quality assessment such as internal validation, comparisons with sea level records from other groups and with in situ measurements, sea level budget closure analyses and comparisons with model outputs. Compared with the previous version of the sea level ECV, we show that use of improved geophysical corrections, careful bias reduction between missions and inclusion of new altimeter missions lead to improved sea level products with reduced uncertainties on different spatial and temporal scales. However, there is still room for improvement since the uncertainties remain larger than the GCOS requirements (GCOS, 2011). Perspectives on subsequent evolution are also discussed.

Intracellular delivery and antitumor effects of pH-sensitive liposomes based on zwitterionic oligopeptide lipids.

PubMed

Mo, Ran; Sun, Qiong; Li, Nan; Zhang, Can

2013-04-01

pH-sensitive liposomes (HHG2C(18)-L and PEGHG2C(18)-L) based on zwitterionic oligopeptide lipids as anticancer drug carriers were developed and evaluated for effective intracellular delivery and enhanced antitumor activity. The amino acid-based lipids, 1,5-dioctadecyl-l-glutamyl 2-histidyl-hexahydrobenzoic acid (HHG2C(18)) and 1,5-distearyl N-(N-α-(4-mPEG2000) butanedione)-histidyl-l-glutamate (PEGHG2C(18)), were synthesized, which have the multistage pH-response to tumor microenvironmental pH (pH(e), pH 6.0-7.0) and endosomal/lysosomal pH (pH(i), pH 4.0-6.0) successively. HHG2C(18)-L contains HHG2C(18), while PEGHG2C(18)-L includes HHG2C(18) and PEGHG2C(18). Both of them displayed the capability of charge conversion to the surrounding pH. The zeta potentials of HHG2C(18)-L and PEGHG2C(18)-L were negative at pH 7.4, whereas positive at pH 6.5 and more positive at lower pH. Coumarin 6-loaded HHG2C(18)-L (C6/HHG2C(18)-L) and PEGHG2C(18)-L (C6/PEGHG2C(18)-L) showed higher tumor cellular uptake due to electrostatic absorptive endocytosis at pH(e) (pH 6.5), produced proton sponge effect for endo-lysosomal escape, and accumulated to the mitochondria based on stronger positive charge by the hydrolysis of a pH-sensitive linker at pH(i) (pH 5.5 and pH 4.5). Furthermore, temsirolimus (CCI-779)-loaded HHG2C(18)-L (CCI-779/HHG2C(18)-L) and PEGHG2C(18)-L (CCI-779/PEGHG2C(18)-L) had significantly higher antiproliferative and apoptosis inducing effects toward the human renal carcinoma (A498) cells at pH 6.5 relative to that at pH 7.4. The half maximal inhibitory concentration (IC50) of CCI-779/HHG2C(18)-L and CCI-779/PEGHG2C(18)-L were about 3 μg/mL and 5 μg/mL at pH 6.5, 1.67-fold and 1.60-fold improved relative to that at pH 7.4, respectively. The total apoptotic ratio of CCI-779/HHG2C(18)-L and CCI-779/PEGHG2C(18)-L increased from 9.90% and 7.78% at pH 7.4 to 19.53% and 12.10% at pH 6.5, respectively. In vivo, CCI-779/PEGHG2C(18)-L after intravenous administration presented remarkably higher bioavailability and blood persistence compared with unPEGylated CCI-779/HHG2C(18)-L, and had the strongest antitumor efficacy against xenograft renal cancer (Renca) tumor models. Accordingly, the results provide the feasibility of using pH-sensitive zwitterionic oligopeptide lipids to extend the applications of liposomes to efficient anticancer drug delivery in cancer therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gross and net land cover changes in the main plant functional types derived from the annual ESA CCI land cover maps (1992-2015)

NASA Astrophysics Data System (ADS)

Li, Wei; MacBean, Natasha; Ciais, Philippe; Defourny, Pierre; Lamarche, Céline; Bontemps, Sophie; Houghton, Richard A.; Peng, Shushi

2018-01-01

Land-use and land-cover change (LULCC) impacts local energy and water balance and contributes on global scale to a net carbon emission to the atmosphere. The newly released annual ESA CCI (climate change initiative) land cover maps provide continuous land cover changes at 300 m resolution from 1992 to 2015, and can be used in land surface models (LSMs) to simulate LULCC effects on carbon stocks and on surface energy budgets. Here we investigate the absolute areas and gross and net changes in different plant functional types (PFTs) derived from ESA CCI products. The results are compared with other datasets. Global areas of forest, cropland and grassland PFTs from ESA are 30.4, 19.3 and 35.7 million km2 in the year 2000. The global forest area is lower than that from LUH2v2h (Hurtt et al., 2011), Hansen et al. (2013) or Houghton and Nassikas (2017) while cropland area is higher than LUH2v2h (Hurtt et al., 2011), in which cropland area is from HYDE 3.2 (Klein Goldewijk et al., 2016). Gross forest loss and gain during 1992-2015 are 1.5 and 0.9 million km2 respectively, resulting in a net forest loss of 0.6 million km2, mainly occurring in South and Central America. The magnitudes of gross changes in forest, cropland and grassland PFTs in the ESA CCI are smaller than those in other datasets. The magnitude of global net cropland gain for the whole period is consistent with HYDE 3.2 (Klein Goldewijk et al., 2016), but most of the increases happened before 2004 in ESA and after 2007 in HYDE 3.2. Brazil, Bolivia and Indonesia are the countries with the largest net forest loss from 1992 to 2015, and the decreased areas are generally consistent with those from Hansen et al. (2013) based on Landsat 30 m resolution images. Despite discrepancies compared to other datasets, and uncertainties in converting into PFTs, the new ESA CCI products provide the first detailed long-term time series of land-cover change and can be implemented in LSMs to characterize recent carbon dynamics, and in climate models to simulate land-cover change feedbacks on climate. The annual ESA CCI land cover products can be downloaded from http://maps.elie.ucl.ac.be/CCI/viewer/download.php (Land Cover Maps - v2.0.7; see details in Sect. 5). The PFT map translation protocol and an example in 2000 can be downloaded from https://doi.org/10.5281/zenodo.834229. The annual ESA CCI PFT maps from 1992 to 2015 at 0.5° × 0.5° resolution can also be downloaded from https://doi.org/10.5281/zenodo.1048163.

Lessons learned and way forward from 6 years of Aerosol_cci

NASA Astrophysics Data System (ADS)

Popp, Thomas; de Leeuw, Gerrit; Pinnock, Simon

2017-04-01

Within the ESA Climate Change Initiative (CCI) Aerosol_cci (2010 - 2017) conducts intensive work to improve and qualify algorithms for the retrieval of aerosol information from European sensors. Meanwhile, several validated (multi-) decadal time series of different aerosol parameters from complementary sensors are available: Aerosol Optical Depth (AOD), stratospheric extinction profiles, a qualitative Absorbing Aerosol Index (AAI), fine mode AOD, mineral dust AOD; absorption information and aerosol layer height are in an evaluation phase and the multi-pixel GRASP algorithm for the POLDER instrument is used for selected regions. Validation (vs. AERONET, MAN) and inter-comparison to other satellite datasets (MODIS, MISR, SeaWIFS) proved the high quality of the available datasets comparable to other satellite retrievals and revealed needs for algorithm improvement (for example for higher AOD values) which were taken into account in an iterative evolution cycle. The datasets contain pixel level uncertainty estimates which were also validated and improved in the reprocessing. The use of an ensemble method was tested, where several algorithms are applied to the same sensor. The presentation will summarize and discuss the lessons learned from the 6 years of intensive collaboration and highlight major achievements (significantly improved AOD quality, fine mode AOD, dust AOD, pixel level uncertainties, ensemble approach); also limitations and remaining deficits shall be discussed. An outlook will discuss the way forward for the continuous algorithm improvement and re-processing together with opportunities for time series extension with successor instruments of the Sentinel family and the complementarity of the different satellite aerosol products.

Effect of agmatine on acute and mononeuropathic pain.

PubMed

Aricioglu, Feyza; Korcegez, Eylem; Bozkurt, Ayhan; Ozyalcin, Suleyman

2003-12-01

Agmatine is a polycationic amine synthesized from L-arginine by arginine decarboxylase in brain and several tissues. It binds to N-methyl-D-aspartate (NMDA) subtype of glutamatergic, alpha(2)-adrenergic and imidazoline (I) receptors. The present study was designed to investigate effect of agmatine on acute and mononeuropathic pain after chronic constriction injury (CCI). CCI was created by four loose ligations around the right sciatic nerve. The analgesic threshold in rats was evaluated by using thermal hyperalgesia/allodynia (THA) at 4 degrees C. The evaluations were made preoperatively, on postoperative day 15, and after drug administration. Agmatine (10, 20, 40, 80, and 100 mg/kg) was administered intraperitoneally for 5 days beginning on postoperative day 15. Agmatine significantly reduced the hyperalgesia in all doses applied. When agmatine was injected intraperitoneally (10, 20, 40, 80, and 100 mg/kg), it increased the nociceptive threshold in the tail-immersion test in a dose-dependent manner, but it had no effect in the hot-plate test. This effect of agmatine in the tail-immersion test was blocked by both yohimbine (1 mg/kg) and idazoxan (0.5 mg/kg). When agmatine was administered intracerebroventricularly (25-200 microg/10 microL), it increased the nociceptive threshold in the hot-plate but not in the tail-immersion test. We conclude that agmatine, an endogenous substance derived from arginine, can modulate both acute and chronic pain.

Bridging College and Careers: Using Dual Enrollment to Enhance Career and Technical Education Pathways. An NCPR Working Paper

ERIC Educational Resources Information Center

Rodriguez, Olga; Hughes, Katherine L.; Belfield, Clive

2012-01-01

The Concurrent Courses Initiative (CCI), funded by The James Irvine Foundation from 2008 until 2011, comprised eight secondary/postsecondary partnerships across California that offered dual enrollment programs with supplemental student supports. The goal of the CCI was to expand access to supportive, career-focused dual enrollment for students…

Correlation between Charge Contrast Imaging and the Distribution of Some Trace Level Impurities in Gibbsite

NASA Astrophysics Data System (ADS)

Baroni, Travis C.; Griffin, Brendan J.; Browne, James R.; Lincoln, Frank J.

2000-01-01

Charge contrast images (CCI) of synthetic gibbsite obtained on an environmental scanning electron microscope gives information on the crystallization process. Furthermore, X-ray mapping of the same grains shows that impurities are localized during the initial stages of growth and that the resulting composition images have features similar to these observed in CCI. This suggests a possible correlation between impurity distributions and the emission detected during CCI. X-ray line profiles, simulating the spatial distribution of impurities derived from the Monte Carlo program CASINO, have been compared with experimental line profiles and give an estimate of the localization. The model suggests that a main impurity, Ca, is depleted from the solution within approximately 3 4 [mu]m of growth.

Numerical study of the current-convective instability driven by asymmetry of detachment in inner and outer divertors

NASA Astrophysics Data System (ADS)

Stepanenko, A. A.; Krasheninnikov, S. I.

2018-01-01

One of the possible mechanisms responsible for strong radiation fluctuations observed in recent experiments with detached plasmas at ASDEX Upgrade [Potzel et al., Nucl. Fusion 54, 013001 (2014)] can be related to the onset of the current-convective instability (CCI) driven by strong asymmetry of detachment in the inner and outer divertors of the tokamak [S. Krasheninnikov and A. Smolyakov, Phys. Plasmas 23, 092505 (2016)]. In this study, we present the physical model, used to simulate the CCI, and the first numerical results of modeling of the CCI dynamics in ASDEX Upgrade-like conditions. The simulation results provide frequency spectra of turbulent divertor plasma oscillations showing reasonably good agreement with the available experimental data.

Impairments of colour vision induced by organic solvents: a meta-analysis study.

PubMed

Paramei, Galina V; Meyer-Baron, Monika; Seeber, Andreas

2004-09-01

The impairment of colour discrimination induced by occupational exposure to toluene, styrene and mixtures of organic solvents is reviewed and analysed using a meta-analytical approach. Thirty-nine studies were surveyed covering a wide range of exposure conditions. Those studies using the Lanthony Panel D-15 desaturated test (D-15d) were further considered. From these for 15 samples data on colour discrimination ability (Colour Confusion Index, CCI) and exposure levels were provided, required for the meta-analysis. In accordance with previously reported higher CCI values for the exposed groups, the computations yielded positive effect sizes for 13 of the 15 samples, indicating that in the great majority of the studies the exposed groups showed inferior colour discrimination. However, the meta-analysis showed great variation in effect sizes across the studies. Possible reasons for inconsistency among the reported findings are discussed. These pertain to exposure-related parameters, as well as to confounders such as conditions of test administration and characteristics of subject samples. Those factors vary considerably among the studies and might have greatly contributed to divergence in measured colour vision capacity, thereby obscuring consistent effects of organic solvents on colour discrimination.

Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

PubMed

Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

2013-10-16

Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

Fecal bulk, energy intake, and serum cholesterol: regression response of serum cholesterol to apparent digestibility of dry matter and suboptimal energy intake in rats on fiber-fat diet.

PubMed

Normani, M Z; Hussain, S S; Lim, J K; Albrink, M J; Gunnells, C K; Davis, G K

1981-10-01

Two experiments were conducted in the rat to determine the relationships of serum cholesterol (SC, mg/dl), apparent digestibility of dry matter (DDM, %), and digested energy intake (DE, kcal/day) at suboptimal level of energy. The energies in diet and feces were determined by calorimetry. DE as percentage of the National Research Council requirement (DE%) was suboptimal (70 to 85%). The experiments had four to five isofibrous diets, and no fiber diets, supplemented with 0.2% crystalline cholesterol (CChol). Animals in experiment 1 were fed varying amounts of feed with 18% coconut oil in the diets where as these in experiment 2 were given fixed amounts of feed with either 6 or 18% oil. The following regressions (p less than 0.001) for SC were found: experiment 1: -1157.7 -5.97 DDM +105.5 CCI -1.48 CCI2 (r2 0.35), where CCI = CChol, mg/day; -1888.4 -2.66 DE +120.97 CCI -1.62 CCI2 (r2 0.37). Experiment 2: 762.99 -6.15 DDM -0.8 fat cal % -0.87DE% (r2 0.31), where fat cal % = fat calories % of DE. Data indicate that at suboptimal energy intake, SC was inversely related to (1) DDM, (2) fat cal, and (3) total energy intake. Liver cholesterol lowering effect of the dietary fiber was also observed. The above findings help to elucidate various conflicting reports related to diet and blood cholesterol.

Sustained alterations of hypothalamic tanycytes during posttraumatic hypopituitarism in male mice.

PubMed

Osterstock, Guillaume; El Yandouzi, Taoufik; Romanò, Nicola; Carmignac, Danielle; Langlet, Fanny; Coutry, Nathalie; Guillou, Anne; Schaeffer, Marie; Chauvet, Norbert; Vanacker, Charlotte; Galibert, Evelyne; Dehouck, Bénédicte; Robinson, Iain C A F; Prévot, Vincent; Mollard, Patrice; Plesnila, Nikolaus; Méry, Pierre-François

2014-05-01

Traumatic brain injury is a leading cause of hypopituitarism, which compromises patients' recovery, quality of life, and life span. To date, there are no means other than standardized animal studies to provide insights into the mechanisms of posttraumatic hypopituitarism. We have found that GH levels were impaired after inducing a controlled cortical impact (CCI) in mice. Furthermore, GHRH stimulation enhanced GH to lower level in injured than in control or sham mice. Because many characteristics were unchanged in the pituitary glands of CCI mice, we looked for changes at the hypothalamic level. Hypertrophied astrocytes were seen both within the arcuate nucleus and the median eminence, two pivotal structures of the GH axis, spatially remote to the injury site. In the arcuate nucleus, GHRH neurons were unaltered. In the median eminence, injured mice exhibited unexpected alterations. First, the distributions of claudin-1 and zonula occludens-1 between tanycytes were disorganized, suggesting tight junction disruptions. Second, endogenous IgG was increased in the vicinity of the third ventricle, suggesting abnormal barrier properties after CCI. Third, intracerebroventricular injection of a fluorescent-dextran derivative highly stained the hypothalamic parenchyma only after CCI, demonstrating an increased permeability of the third ventricle edges. This alteration of the third ventricle might jeopardize the communication between the hypothalamus and the pituitary gland. In conclusion, the phenotype of CCI mice had similarities to the posttraumatic hypopituitarism seen in humans with intact pituitary gland and pituitary stalk. It is the first report of a pathological status in which tanycyte dysfunctions appear as a major acquired syndrome.

Released polysaccharides (RPS) from Cyanothece sp. CCY 0110 as biosorbent for heavy metals bioremediation: interactions between metals and RPS binding sites.

PubMed

Mota, Rita; Rossi, Federico; Andrenelli, Luisa; Pereira, Sara Bernardes; De Philippis, Roberto; Tamagnini, Paula

2016-09-01

Bioremediation of heavy metals using microorganisms can be advantageous compared to conventional physicochemical methods due to the use of renewable resources and efficiencies of removal particularly cations at low concentrations. In this context, cyanobacteria/cyanobacterial extracellular polymeric substances (EPS) emerge as a valid alternative due to the anionic nature and particular composition of these polymers. In this work, various culture fractions of the unicellular cyanobacterium Cyanothece sp. CCY 0110 were employed in bioremoval assays using three of the most common heavy metal pollutants in water bodies-copper, cadmium, and lead-separately or in combined systems. Our study showed that the released polysaccharides (RPS) were the most efficient fraction, removing the metal(s) by biosorption. Therefore, this polymer was subsequently used to evaluate the interactions between the metals/RPS binding sites using SEM-EDX, ICP-OES, and FTIR. Acid and basic pretreatments applied to the polymer further improve the process efficiency, and the exposure to an alkaline solution seems to alter the RPS conformation. The differences observed in the specific metal bioremoval seem to be mainly due to the RPS organic functional groups available, mainly carboxyl and hydroxyl, than to an ion exchange mechanism. Considering that Cyanothece is a highly efficient RPS-producer and that RPS can be easily separated from the culture, immobilized or confined, this polymer can be advantageous for the establishment/improvement of heavy metal removal systems.

Igniting the Fire within Marginalized Youth: The Role of Critical Civic Inquiry in Fostering Ethnic Identity and Civic Self-Efficacy

ERIC Educational Resources Information Center

Hipolito-Delgado, Carlos P.; Zion, Shelley

2017-01-01

Critical Civic Inquiry (CCI) is a transformative student voice initiative that engages students in critical conversations about educational equity and inquiry-based learning to increase student voice and promote civic action. A quasi-experimental study was conducted to assess if participation in CCI increased the psychological empowerment (as…

The Competitive, Crowd sourced Investment (CCI) Initiative

DTIC Science & Technology

2016-03-01

any other organization of the Department of Defense. * * * Within the private sector, investment capital flows to the businesses that can best...The Competitive, Crowdsourced Investment (CCI) Initiative Col. Scott T. Wallace, USAF This article proposes an initiative for consideration by the...generate returns for investors. A result of this incentive structure is a business culture that relentlessly turns capital into future returns.Within the

Evidence for a Role of Connexin 43 in Trigeminal Pain Using RNA Interference In Vivo

PubMed Central

Ohara, Peter T.; Vit, Jean-Philippe; Bhargava, Aditi; Jasmin, Luc

2008-01-01

The importance of glial cells in the generation and maintenance of neuropathic pain is becoming widely accepted. We examined the role of glial-specific gap junctions in nociception in the rat trigeminal ganglion in nerve-injured and -uninjured states. The connexin 43 (Cx43) gap-junction subunit was found to be confined to the satellite glial cells (SGCs) that tightly envelop primary sensory neurons in the trigeminal ganglion and we therefore used Cx43 RNA interference (RNAi) to alter gap-junction function in SGCs. Using behavioral evaluation, together with immunocytochemical and Western blot monitoring, we show that Cx43 increased in the trigeminal ganglion in rats with a chronic constriction injury (CCI) of the infraorbital nerve. Reducing Cx43 expression using RNAi in CCI rats reduced painlike behavior, whereas in non-CCI rats, reducing Cx43 expression increased painlike behavior. The degree of painlike behavior in CCI rats and intact, Cx43-silenced rats was similar. Our results support previous suggestions that increases in glial gap junctions after nerve injury increases nociceptive behavior but paradoxically the reduction of gap junctions in normal ganglia also increases nociceptive behavior, possibly a reflection of the multiple functions performed by glia. PMID:18715894

Coumarinocoumarin-Based Two-Photon Fluorescent Cysteine Biosensor for Targeting Lysosome.

PubMed

Chen, Chunyang; Zhou, Liuqing; Liu, Wei; Liu, Weisheng

2018-05-15

Coumarinocoumarin, one of the coumarin derivatives, is easy to synthesize and has rich modification sites. The large conjugate plane of coumarinocoumarin gives it a more excellent optical property than conventional coumarin, for example, the two-photon fluorescence property. So, the coumarinocoumarin-based probe (CCy) has been designed and synthesized, which is the first lysosomal targeting fluorescent biosensor for cysteine. This probe was prepared by a three-step procedure as a latent fluorescence probe to achieve high sensitivity and fluorescence turn-on response toward cysteine (Cys) over homocysteine (Hcy), glutathione (GSH), and other various natural amino acids under physiological conditions. Upon addition of Cys to the solution of CCy, remarkable enhancement on 520 nm of fluorescence spectra can be monitored. This probe was then successfully used for fluorescence imaging of Cys in mice organ tissues and HeLa cells, and quantitative determination has been achieved within a certain range, which proved the permeability of CCy. The concentration of Cys in animal serum was measured and the viability exceeded 80%, indicating that CCy can be a biocompatible and rapid probe for Cys in vivo. Simultaneously, its ability to detect Cys in lysosome has been validated by its lysosomal targeting.

E3 Ubiquitin Ligase c-cbl Inhibits Microglia Activation After Chronic Constriction Injury.

PubMed

Xue, Pengfei; Liu, Xiaojuan; Shen, Yiming; Ju, Yuanyuan; Lu, Xiongsong; Zhang, Jinlong; Xu, Guanhua; Sun, Yuyu; Chen, Jiajia; Gu, Haiyan; Cui, Zhiming; Bao, Guofeng

2018-06-22

E3 ubiquitin ligase c-Caritas B cell lymphoma (c-cbl) is associated with negative regulation of receptor tyrosine kinases, signal transduction of antigens and cytokine receptors, and immune response. However, the expression and function of c-cbl in the regulation of neuropathic pain after chronic constriction injury (CCI) are unknown. In rat CCI model, c-cbl inhibited the activation of spinal cord microglia and the release of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), which alleviated mechanical and heat pain through down-regulating extracellular signal-regulated kinase (ERK) pathway. Additionally, exogenous TNF-α inhibited c-cbl protein level vice versa. In the primary microglia transfected with c-cbl siRNA, when treated with TNF-α or TNF-α inhibitor, the corresponding secretion of IL-1β and IL-6 did not change. In summary, CCI down-regulated c-cbl expression and induced the activation of microglia, then activated microglia released inflammatory factors via ERK signaling to cause pain. Our data might supply a novel molecular target for the therapy of CCI-induced neuropathic pain.

3D nonlinear numerical simulation of the current-convective instability in detached diverter plasma

NASA Astrophysics Data System (ADS)

Stepanenko, Alexander; Krasheninnikov, Sergei

2017-10-01

One of the possible mechanisms responsible for strong radiation fluctuations observed in the recent experiments with detached plasmas at ASDEX Upgrade [Potzel et al., Nuclear Fusion, 2014] can be related to the onset of the current-convective instability (CCI) driven by strong asymmetry of detachment in the inner and outer tokamak divertors [Krasheninnikov and Smolyakov, PoP, 2016]. In this study we present the first results of 3D nonlinear numerical simulations of the CCI in divertor plasma for the conditions relevant to the AUG experiment. The general physical model used to simulate the CCI, qualitative estimates for the instability characteristic growth rate and transverse wavelengths derived for plasma, which is spatially inhomogeneous both across and along the magnetic field lines, are presented. The simulation results, demonstrating nonlinear dynamics of the CCI, provide the frequency spectra of turbulent divertor plasma fluctuations showing good agreement with the available experimental data. This material is based upon the work supported by the U.S. Department of Energy under Award No. DE-FG02-04ER54739 at UCSD and by the Russian Ministry of Education and Science Grant No. 14.Y26.31.0008 at MEPhI.

The importance of cutaneous feedback on neural activation during maximal voluntary contraction.

PubMed

Cruz-Montecinos, Carlos; Maas, Huub; Pellegrin-Friedmann, Carla; Tapia, Claudio

2017-12-01

The purpose of this study was to investigate the importance of cutaneous feedback on neural activation during maximal voluntary contraction (MVC) of the ankle plantar flexors. The effects of cutaneous plantar anaesthesia were assessed in 15 subjects and compared to 15 controls, using a one-day pre/post-repeated measures design. Cutaneous plantar anaesthesia was induced by lidocaine injection at the centre of forefoot, lateral midfoot, and heel. Each subject performed isometric MVCs of the ankle plantar flexors. During each isometric ramp contraction, the following variables were assessed: maximal isometric torque; surface electromyography (EMG) activity of the medial gastrocnemius (MG) and tibialis anterior (TA) muscles; and co-contraction index (CCI) between the MG and TA. For ankle torque, two-way ANOVA showed no significant interaction between the pre/post-measurements × group (p = 0.166). However, MG activity presented significant interactions between the pre/post-measurements × group (p = 0.014). Post hoc comparisons indicated a decrease of MG activity in the experimental group, from 85.9 ± 11.9 to 62.7 ± 30.8% (p = 0.016). Additionally, the post-anaesthesia MG activity of the experimental group differed statistically with pre- and post-MG activity of the control group (p = 0.027 and p = 0.008, respectively). For TA activity and CCI, two-way ANOVA detected no significant interactions between the pre/post-measurements × group (p = 0.605 and p = 0.332, respectively). Our results indicate that during MVC, cutaneous feedback modulates neural activity to MG muscle, without changing the extent of MG-TA co-contraction.

Chronic constriction injury-induced microRNA-146a-5p alleviates neuropathic pain through suppression of IRAK1/TRAF6 signaling pathway.

PubMed

Wang, Zhiyao; Liu, Fan; Wei, Min; Qiu, Yue; Ma, Chao; Shen, Le; Huang, Yuguang

2018-06-09

microRNA-146a-5p (miRNA-146a-5p) is a key molecule in the negative regulation pathway of TLRs and IL-1 receptor (TIR) signaling. Our recent study demonstrated that MyD88-dependent signaling pathway of TIR in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) plays a role in peripheral nerve injury-induced neuropathic pain. However, it was not clear whether and how miRNA-146a-5p regulates the TIR pathway of DRG and SDH in the development of neuropathic pain. The sciatic nerve chronic constriction injury (CCI) model of rat was used to induce chronic neuropathic pain. The levels and cellular distribution of miRNA-146a-5p were detected with quantitative real-time PCR (qPCR) and fluorescent in situ hybridization (FISH). The RNA level, protein level, and cellular distribution of IRAK1 and TRAF6 that is targeted by miRNA-146a-5p were detected with qPCR, western blot, and immunofluorescent. The pain-related behavioral effect of miRNA-146a-5p was accessed after intrathecal administration. Mechanical stimuli and radiant heat were used to evaluate mechanical allodynia and thermal hyperalgesia. We found that the level of miRNA-146a-5p significantly increased in L4-L6 DRGs and SDH after CCI surgery; meanwhile, the protein level of IRAK1 and TRAF6 in DRGs was significantly increased after CCI. Intrathecal injection of miR146a-5p agomir or miRNA-146a-5p antagomir regulates miRNA-146a-5p level of L4-L6 DRGs and SDH. We found that intrathecal injection of miR146a-5p agomir can alleviate mechanical and thermal hyperalgesia in CCI rats and reverse the upregulation of IRAK1 and TRAF6 of L4-L6 DRGs and SDH induced by CCI. We furthermore found that intrathecal injection of miRNA-146a-5p antagomir can exacerbate the mechanical and thermal pain-related behavior of CCI rats and meanwhile increase IRAK1 and TRAF6 of L4-L6 DRGs and SDH expression even further. miRNA-146a-5p of DRG and SDH can modulate the development of CCI-induced neuropathic pain through inhibition of IRAK1 and TRAF6 in the TIR signaling pathway. Hence, miRNA-146a-5p may serve as a potential therapeutic target for neuropathic pain.

[Transcription of protein arginine N-methyltransferase genes in mouse dorsal root ganglia following peripheral nerve injury].

PubMed

Xu, Hua-Li; Xu, Shi-Yuan; Mo, Kai

2017-12-20

To investigate the changes in the transcription of protein arginine methylation enzyme family genes in the dorsal root ganglia (DRG) following peripheral nerve injury in mice. C57BL6 mouse models of neuropathic pain induced by peripheral nerve injury were established by bilateral L4 spinal nerve ligation (SNL). At 7 days after SNL or sham operation, the DRG tissue was collected for transcriptional analysis of 9 protein arginine methylation enzyme genes (Prmt1?3, Carm1, and Prmt5?9) using RNA?Seq to identify the differentially expressed genes in the injured DRGs. We also established mouse models of lateral L4 SNL and models of chronic constriction injury (CCI) of the sciatic nerve and tested the paw withdrawal frequency (PWF) in response to mechanical stimulation and paw withdrawal latency (PWL) in response to thermal stimulation on 0, 3, 7 and 14 days after SNL or CCI; the expressions of the differentially expressed genes in the injured DRGs were verified in the two models using RT?qPCR. Among the 9 protein arginine methylation enzyme family genes that were tissue?specifically expressed in the DRG, Prmt2 and Prmt3 showed the highest and Prmt6 showed the lowest basal expression. Compared with the sham?operated mice group, the mice receiving SNL exhibited upregulated Carm1 gene transcription (by 1.7 folds) but downregulated Prmt5, Prmt8 and Prmt9 transcription in the injured DRG (Prmt8 gene showed the most significant down?regulation by 16.3 folds). In mouse models of SNL and CCI, Carm1 gene expression increased progressively with time while Prmt8 transcription was obviously lowered on days 3, 7 and 14 after the injury; the transcription levels of Prmt1, Prmt5 and Prmt9 presented with no significant changes following the injuries. Both SNL and CCI induced mechanical allodynia and thermal hypersensitivities in the mice shown by increased PWF and decreased PWL on days 3, 7 and 14 after the injuries. Periphery nerve injury induces Carm1 upregulation and Prmt8 downregulation in the injured DRG in mice, which sheds light on new targets for treatment of neuropathic pain.

Is governance, gross domestic product, inequality, population size or country surface area associated with coverage and equity of health interventions? Ecological analyses of cross-sectional surveys from 80 countries.

PubMed

Wehrmeister, Fernando C; da Silva, Inácio Crochemore M; Barros, Aluisio J D; Victora, Cesar G

2017-01-01

To assess associations between national characteristics, including governance indicators, with a proxy for universal health coverage in reproductive, maternal, newborn and child health (RMNCH). Ecological analysis based on data from national standardised cross-sectional surveys. Low-income and middle-income countries with a Demographic and Health Survey or a Multiple Indicator Cluster Survey since 2005. 1 246 710 mothers and 2 129 212 children from 80 national surveys. Gross domestic product (GDP), country surface area, population, Gini index and six governance indicators (control of corruption, political stability and absence of violence, government effectiveness, regulatory quality, rule of law, and voice and accountability). Levels and inequality in the composite coverage index (CCI), a weighted average of eight RMNCH interventions. Relative and absolute inequalities were measured through the concentration index (CIX) and slope index of inequality (SII) for CCI, respectively. The average values of CCI (70.5% (SD=13.3)), CIX (5.3 (SD=5.1)) and mean slope index (19.8 (SD=14.7)) were calculated. In the unadjusted analysis, all governance variables and GDP were positively associated with the CCI and negatively with inequalities. Country surface showed inverse associations with both inequality indices. After adjustment, among the governance indicators, only political stability and absence of violence was directly related to CCI (β=6.3; 95% CI 3.6 to 9.1; p<0.001) and inversely associated with relative (CIX; β=-1.4; 95% CI -2.4 to -0.4; p=0.007) and absolute (SII; β=-5.3; 95% CI -8.9 to -1.7; p=0.005) inequalities. The strongest associations with governance indicators were found in the poorest wealth quintile. Similar patterns were observed for GDP. Country surface area was inversely related to inequalities on CCI. Levels and equity in RMNCH interventions are positively associated with political stability and absence of violence, and with GDP, and inversely associated with country surface area.

Prevalence and Impact of Co-morbidity Burden as Defined by the Charlson Co-morbidity Index on 30-Day and 1- and 5-Year Outcomes After Coronary Stent Implantation (from the Nobori-2 Study).

PubMed

Mamas, Mamas A; Fath-Ordoubadi, Farzin; Danzi, Gian B; Spaepen, Erik; Kwok, Chun Shing; Buchan, Iain; Peek, Niels; de Belder, Mark A; Ludman, Peter F; Paunovic, Dragica; Urban, Philip

2015-08-01

Co-morbidities have typically been considered as prevalent cardiovascular risk factors and cardiovascular diseases rather than systematic measures of general co-morbidity burden in patients who underwent percutaneous coronary intervention (PCI). Charlson co-morbidity index (CCI) is a measure of co-morbidity burden providing a means of quantifying the prognostic impact of 22 co-morbid conditions on the basis of their number and prognostic impact. The study evaluated the impact of the CCI on cardiac mortality and major adverse cardiovascular events (MACE) after PCI through analysis of the Nobori-2 study. The prognostic impact of CCI was studied in 3,067 patients who underwent PCI in 4,479 lesions across 125 centers worldwide on 30-day and 1- and 5-year cardiac mortality and MACE. Data were adjusted for potential confounders using stepwise logistic regression; 2,280 of 3,067 patients (74.4%) had ≥1 co-morbid conditions. CCI (per unit increase) was independently associated with an increase in both cardiac death (odds ratio [OR] 1.47 95% confidence interval [CI] 1.20 to 1.80, p = 0.0002) and MACE (OR 1.29 95% CI 1.14 to 1.47, p ≤0.0011) at 30 days, with similar observations recorded at 1 and 5 years. CCI score ≥2 was independently associated with increased 30-day cardiac death (OR 4.25, 95% CI 1.24 to 14.56, p = 0.02) at 1 month, and this increased risk was also observed at 1 and 5 years. In conclusion, co-morbid burden, as measured using CCI, is an independent predictor of adverse outcomes in the short, medium, and long term. Co-morbidity should be considered in the decision-making process when counseling patients regarding the periprocedural risks associated with PCI, in conjunction with traditional risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Is governance, gross domestic product, inequality, population size or country surface area associated with coverage and equity of health interventions? Ecological analyses of cross-sectional surveys from 80 countries

PubMed Central

Wehrmeister, Fernando C; da Silva, Inácio Crochemore M; Barros, Aluisio J D; Victora, Cesar G

2017-01-01

Objective To assess associations between national characteristics, including governance indicators, with a proxy for universal health coverage in reproductive, maternal, newborn and child health (RMNCH). Design Ecological analysis based on data from national standardised cross-sectional surveys. Setting Low-income and middle-income countries with a Demographic and Health Survey or a Multiple Indicator Cluster Survey since 2005. Participants 1 246 710 mothers and 2 129 212 children from 80 national surveys. Exposures of interest Gross domestic product (GDP), country surface area, population, Gini index and six governance indicators (control of corruption, political stability and absence of violence, government effectiveness, regulatory quality, rule of law, and voice and accountability). Main outcomes Levels and inequality in the composite coverage index (CCI), a weighted average of eight RMNCH interventions. Relative and absolute inequalities were measured through the concentration index (CIX) and slope index of inequality (SII) for CCI, respectively. Results The average values of CCI (70.5% (SD=13.3)), CIX (5.3 (SD=5.1)) and mean slope index (19.8 (SD=14.7)) were calculated. In the unadjusted analysis, all governance variables and GDP were positively associated with the CCI and negatively with inequalities. Country surface showed inverse associations with both inequality indices. After adjustment, among the governance indicators, only political stability and absence of violence was directly related to CCI (β=6.3; 95% CI 3.6 to 9.1; p<0.001) and inversely associated with relative (CIX; β=−1.4; 95% CI −2.4 to −0.4; p=0.007) and absolute (SII; β=−5.3; 95% CI –8.9 to −1.7; p=0.005) inequalities. The strongest associations with governance indicators were found in the poorest wealth quintile. Similar patterns were observed for GDP. Country surface area was inversely related to inequalities on CCI. Conclusions Levels and equity in RMNCH interventions are positively associated with political stability and absence of violence, and with GDP, and inversely associated with country surface area. PMID:29225951

Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial.

PubMed

Brümmendorf, Tim H; Cortes, Jorge E; de Souza, Cármino Antonio; Guilhot, Francois; Duvillié, Ladan; Pavlov, Dmitri; Gogat, Karïn; Countouriotis, Athena M; Gambacorti-Passerini, Carlo

2015-01-01

Bosutinib is an oral, dual SRC/ABL1 tyrosine kinase inhibitor for resistant/intolerant chronic myeloid leukaemia (CML). We assessed the efficacy and safety of bosutinib 500 mg/d (n = 250) versus imatinib 400 mg/d (n = 252) after >24 months from accrual completion in newly diagnosed chronic phase (CP)-CML (Bosutinib Efficacy and Safety in Newly Diagnosed CML trial [BELA]). Cumulative complete cytogenetic response (CCyR) rates by 24 months were similar (bosutinib, 79%; imatinib, 80%); cumulative major molecular response (MMR) rates were 59% for bosutinib and 49% for imatinib. Responses were durable; 151/197 vs. 172/204 and 125/153 vs. 117/131 responders remained on treatment and maintained CCyR and MMR, respectively. Since the 12-month primary analysis, no new accelerated-/blast-phase transformations occurred with bosutinib; four occurred with imatinib. Early response (BCR-ABL1/ABL1 ≤ 10%, 3 months) was associated with better CCyR and MMR rates by 12 and 24 months (both arms). Gastrointestinal events and liver function test elevations were more common, and neutropenia, musculoskeletal events and oedema were less common with bosutinib. Discontinuations due to adverse events were more common with bosutinib versus imatinib (most commonly alanine aminotransferase elevation: 4% vs. <1%); most occurred within the first 12 months. Cardiovascular adverse events were similar in both arms. Bosutinib continues to demonstrate good efficacy and manageable tolerability in newly diagnosed CP-CML patients. © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Blue light differentially represses mesophyll conductance in high vs low latitude genotypes of Populus trichocarpa Torr. & Gray.

PubMed

Momayyezi, Mina; Guy, Robert D

2017-06-01

To explore what role chloroplast positioning might have in relation to latitudinal variation in mesophyll conductance (g m ) of Populus trichocarpa Torr. & Gray (black cottonwood), we examined photosynthetic response to different blue light treatments in six representative genotypes (three northern and three southern). The proportion of blue (B) to red light was varied from 0:100, 10:90, 20:80, 40:60, and 60:40 while keeping the total photosynthetic photon flux density constant. Mesophyll conductance was estimated by monitoring chlorophyll fluorescence in combination with gas exchange. Compared to the control (10% B), g m was significantly lower with increasing blue light. Consistent with a change in chloroplast positioning, there was a simultaneous but reversible decrease in chlorophyll content index (CCI), as measured by foliar greenness, while the extracted, actual chlorophyll content (ACC) remained unchanged. Blue-light-induced decreases in g m and CCI were greater in northern genotypes than in southern genotypes, both absolutely and proportionally, consistent with their inherently higher photosynthetic rate. Treatment of leaves with cytochalasin D, an inhibitor of actin-based chloroplast motility, reduced both CCI and ACC but had no effect on the CCI/ACC ratio and fully blocked any effect of blue light on CCI. Cytochalasin D reduced g m by ∼56% under 10% B, but did not block the effect of 60% B on g m , which was reduced a further 20%. These results suggest that the effect of high blue light on g m is at least partially independent of chloroplast repositioning. High blue light reduced carbonic anhydrase activity by 20% (P<0.05), consistent with a possible reduction in protein-mediated facilitation of CO 2 diffusion. Copyright © 2017 Elsevier GmbH. All rights reserved.

Conservative Management of Staghorn Calculi: When Is It Safe?

PubMed

Morgan, Tara Nikonow; Shahait, Mohammad; Maganty, Avinash; Ost, Michael; Jackman, Stephen; Averch, Timothy; Semins, Michelle Jo

2018-06-01

To describe the clinical characteristics, infectious and kidney function patterns, and overall outcomes in a cohort of patients with staghorn calculi treated conservatively. Staghorn calculi treated nonoperatively between January 2009 and January 2017 were identified. A retrospective analysis was completed. Twenty-nine patients were identified with a median age of 74 years (interquartile range [IQR] 61-81). Mean follow-up was 24 months. Fifty-nine percent (17/29) had complete staghorn calculi with 6/29 (21%) bilateral. Mean body mass index was 29.4 (IQR 24.8-31.7). Of the 29 patients, 14 were treated conservatively due to comorbidities, 12 refused treatments, and 3 were due to aberrant anatomy. The age-adjusted Charlson Comorbidity Index (CCI) score demonstrated 8 patients in our cohort with a CCI of <3, 11 patients with a CCI of 4 or 5, 7 patients with a CCI of 6 or 7, and 3 patients with a CCI of >8. Overall, kidney function remained stable for 19/29 patients (66%) and the glomerular filtration rate decreased by <10% for 4/29 (14%), by 10%-29% for 2/29 (7%), and >30% for 4/29 patients (14%) over the study period. None of the study patients required hemodialysis. No patients in the cohort developed an abscess, nor were any patients on daily prophylactic antibiotics. There was only one related admission for a complication during the study; this was for pyelonephritis. There were two deaths during the study period. One death was an unrelated cardiac death and the other was from urosepsis; this patient had been noncompliant with follow-up. Outcomes for patients treated conservatively were reasonable in this select group. There is a need for future prospective studies to show whether conservative treatment of these patients is safe.

Alteration of the exopolysaccharide production and the transcriptional profile of free-living Frankia strain CcI3 under nitrogen-fixing conditions.

PubMed

Lee, Hae-In; Donati, Andrew J; Hahn, Dittmar; Tisa, Louis S; Chang, Woo-Suk

2013-12-01

We investigated the effect of different nitrogen (N) sources on exopolysaccharide (EPS) production and composition by Frankia strain CcI3, a N2-fixing actinomycete that forms root nodules with Casuarina species. Frankia cells grown in the absence of NH4Cl (i.e., under N2-fixing conditions) produced 1.7-fold more EPS, with lower galactose (45.1 vs. 54.7 mol%) and higher mannose (17.3 vs. 9.7 mol%) contents than those grown in the presence of NH4Cl as a combined N-source. In the absence of the combined N-source, terminally linked and branched residue contents were nearly twice as high with 32.8 vs. 15.1 mol% and 15.1 vs. 8.7 mol%, respectively, than in its presence, while the content of linearly linked residues was lower with 52.1 mol% compared to 76.2 mol%. To find out clues for the altered EPS production at the transcriptional level, we performed whole-gene expression profiling using quantitative reverse transcription PCR and microarray technology. The transcription profiles of Frankia strain CcI3 grown in the absence of NH4Cl revealed up to 2 orders of magnitude higher transcription of nitrogen fixation-related genes compared to those of CcI3 cells grown in the presence of NH4Cl. Unexpectedly, microarray data did not provide evidence for transcriptional regulation as a mechanism for differences in EPS production. These findings indicate effects of nitrogen fixation on the production and composition of EPS in Frankia strain CcI3 and suggest posttranscriptional regulation of enhanced EPS production in the absence of the combined N-source.

The neural mobilization technique modulates the expression of endogenous opioids in the periaqueductal gray and improves muscle strength and mobility in rats with neuropathic pain

PubMed Central

2014-01-01

Background The neural mobilization (NM) technique is a noninvasive method that has been proven to be clinically effective in reducing pain; however, the molecular mechanisms involved remain poorly understood. The aim of this study was to analyze whether NM alters the expression of the mu-opioid receptor (MOR), the delta-opioid receptor (DOR) and the Kappa-opioid receptor (KOR) in the periaqueductal gray (PAG) and improves locomotion and muscle force after chronic constriction injury (CCI) in rats. Methods The CCI was imposed on adult male rats followed by 10 sessions of NM every other day, starting 14 days after the CCI injury. At the end of the sessions, the PAG was analyzed using Western blot assays for opioid receptors. Locomotion was analyzed by the Sciatic functional index (SFI), and muscle force was analyzed by the BIOPAC system. Results An improvement in locomotion was observed in animals treated with NM compared with injured animals. Animals treated with NM showed an increase in maximal tetanic force of the tibialis anterior muscle of 172% (p < 0.001) compared with the CCI group. We also observed a decrease of 53% (p < 0.001) and 23% (p < 0.05) in DOR and KOR levels, respectively, after CCI injury compared to those from naive animals and an increase of 17% (p < 0.05) in KOR expression only after NM treatment compared to naive animals. There were no significant changes in MOR expression in the PAG. Conclusion These data provide evidence that a non-pharmacological NM technique facilitates pain relief by endogenous analgesic modulation. PMID:24884961

MiR-203 involves in neuropathic pain development and represses Rap1a expression in nerve growth factor differentiated neuronal PC12 cells.

PubMed

Li, Haixia; Huang, Yuguang; Ma, Chao; Yu, Xuerong; Zhang, Zhiyong; Shen, Le

2015-01-01

Although microRNAs (miRNAs) have been shown to play a role in numerous biological processes, their function in neuropathic pain is not clear. The rat bilateral sciatic nerve chronic constriction injury (bCCI) is an established model of neuropathic pain, so we examined miRNA expression and function in the spinal dorsal horn in bCCI rats. Microarray and real-time polymerase chain reaction were used to examine the expression of miRNA in nerve system of bCCI rats, and the targets of miRNA were predicted by bioinformatic approaches. The function of specific miRNA was estimated through the methods of gene engineering. This study revealed substantially (∼10-fold) decreased miR-203 expression in the spinal dorsal horns but not the dorsal root ganglions, hippocampus, or anterior cingulate cortexes of bCCI rats. Rap1a protein expression was upregulated in bCCI rat spinal dorsal horns. We further verified that miR-203 directly targeted the 3'-untranslated region of the rap1a gene, thereby decreasing rap1a protein expression in neuron-like cells. Rap1a has diverse neuronal functions and their perturbation is responsible for several mental disorders. For example, Rap1a/MEK/ERK is involved in peripheral sensitization. These data suggest a potential role for miR-203 in regulating neuropathic pain development, and Rap1a is a validated target gene in vitro. Results from our study and others indicate the possibility that Rap1a may be involved in pain. We hope that these results can provide support for future research into miR-203 in gene therapy for neuropathic pain.

Assimilation of the ESA CCI Soil Moisture ACTIVE and PASSIVE Product into the SURFEX Land Surface Model using the Ensemble Transform Kalman Filter

NASA Astrophysics Data System (ADS)

Blyverket, J.; Hamer, P.; Bertino, L.; Lahoz, W. A.

2017-12-01

The European Space Agency Climate Change Initiative for soil moisture (ESA CCI SM) was initiated in 2012 for a period of six years, the objective for this period was to produce the most complete and consistent global soil moisture data record based on both active and passive sensors. The ESA CCI SM products consist of three surface soil moisture datasets: The ACTIVE product and the PASSIVE product were created by fusing scatterometer and radiometer soil moisture data, respectively. The COMBINED product is a blended product based on the former two datasets. In this study we assimilate globally both the ACTIVE and PASSIVE product at a 25 km spatial resolution. The different satellite platforms have different overpass times, an observation is mapped to the hours 00.00, 06.00, 12.00 or 18.00 if it falls within a 3 hour window centred at these times. We use the SURFEX land surface model with the ISBA diffusion scheme for the soil hydrology. For the assimilation routine we apply the Ensemble Transform Kalman Filter (ETKF). The land surface model is driven by perturbed MERRA-2 atmospheric forcing data, which has a temporal resolution of one hour and is mapped to the SURFEX model grid. Bias between the land surface model and the ESA CCI product is removed by cumulative distribution function (CDF) matching. This work is a step towards creating a global root zone soil moisture product from the most comprehensive satellite surface soil moisture product available. As a first step we consider the period from 2010 - 2016. This allows for comparison against other global root zone soil moisture products (SMAP Level 4, which is independent of the ESA CCI SM product).

Methylprednisolone prevents nerve injury-induced hyperalgesia in neprilysin knockout mice.

PubMed

He, Lan; Uçeyler, Nurcan; Krämer, Heidrun H; Colaço, Maria Nandini; Lu, Bao; Birklein, Frank; Sommer, Claudia

2014-03-01

The pathophysiology of the complex regional pain syndrome involves enhanced neurogenic inflammation mediated by neuropeptides. Neutral endopeptidase (neprilysin, NEP) is a key enzyme in neuropeptide catabolism. Our previous work revealed that NEP knock out (ko) mice develop more severe hypersensitivity to thermal and mechanical stimuli after chronic constriction injury (CCI) of the sciatic nerve than wild-type (wt) mice. Because treatment with glucocorticoids is effective in early complex regional pain syndrome, we investigated whether methylprednisolone (MP) reduces pain and sciatic nerve neuropeptide content in NEP ko and wt mice with nerve injury. After CCI, NEP ko mice developed more severe thermal and mechanical hypersensitivity and hind paw edema than wt mice, confirming previous findings. Hypersensitivity was prevented by MP treatment in NEP ko but not in wt mice. MP treatment had no effect on protein levels of calcitonin-gene related peptide, substance P, and bradykinin in sciatic nerves of NEP ko mice. Endothelin-1 (ET-1) levels were higher in naïve and nerve-injured NEP ko than in wt mice, without an effect of MP treatment. Gene expression of the ET-1 receptors ETAR and ETBR was not different between genotypes and was not altered after CCI, but was increased after additional MP treatment. The ETBR agonist IRL-1620 was analgesic in NEP ko mice after CCI, and the ETBR antagonist BQ-788 showed a trend to reduce the analgesic effect of MP. The results provide evidence that MP reduces CCI-induced hyperalgesia in NEP ko mice, and that this may be related to ET-1 via analgesic actions of ETBR. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Chronic Neuropathic Pain in Mice Reduces μ-Opioid Receptor-Mediated G-protein Activity in the Thalamus

PubMed Central

Hoot, Michelle R.; Sim-Selley, Laura J.; Selley, Dana E.; Scoggins, Krista L.; Dewey, William L.

2011-01-01

Neuropathic pain is a debilitating condition that is often difficult to treat using conventional pharmacological interventions and the exact mechanisms involved in the establishment and maintenance of this type of chronic pain have yet to be fully elucidated. The present studies examined the effect of chronic nerve injury on μ-opioid receptors and receptor-mediated G-protein activity within the supraspinal brain regions involved in pain processing of mice. Chronic constriction injury (CCI) reduced paw withdrawal latency, which was maximal at 10 days post-injury. [d-Ala2,(N-Me)Phe4, Gly5-OH] enkephalin (DAMGO)-stimulated [35S]GTPγS binding was then conducted at this time point in membranes prepared from the rostral ACC (rACC), thalamus and periaqueductal grey (PAG) of CCI and sham-operated mice. Results showed reduced DAMGO-stimulated [35S]GTPγS binding in the thalamus and PAG of CCI mice, with no change in the rACC. In thalamus, this reduction was due to decreased maximal stimulation by DAMGO, with no difference in EC50 values. In PAG, however, DAMGO Emax values did not significantly differ between groups, possibly due to the small magnitude of the main effect. [3H]Naloxone binding in membranes of the thalamus showed no significant differences in Bmax values between CCI and sham-operated mice, indicating that the difference in G-protein activation did not result from differences in μ-opioid receptor levels. These results suggest that CCI induced a region-specific adaptation of μ-opioid receptor-mediated G-protein activity, with apparent desensitization of the μ-opioid receptor in the thalamus and PAG and could have implications for treatment of neuropathic pain. PMID:21762883

Ashy Storm-Petrel Oceanodroma homochroa mist-netting and capture rates in the California Channel Islands, 2004–2007

USGS Publications Warehouse

Adams, Josh

2016-01-01

The California Channel Islands (CCI) provide essential nesting habitat for a significant portion of the world’s Ashy Storm-Petrel Oceanodroma homochroa (ASSP) breeding population, but true abundance at this locality is not well known. Land-based nocturnal mistnetting has been conducted sporadically in the CCI since 1976, with variation in techniques and methods. Using a standardized catch-perunit-effort (CPUE) is one of the few methods available to monitor trends in relative abundance, but there currently are no guidelines for a standardized, repeatable approach for the CCI. During 2004–2007, I conducted mist-netting for ASSP at three colony sites within the CCI: Scorpion Rock (SR), Santa Barbara Island (SBI), and Prince Island (PI). During 47 site-nights (22 sessions), I obtained 1 177 unique captures, including 34 recaptures (2.9%) of previously banded individuals. ASSP captured at all three islands showed peak proportions of fully developed incubation patches in July and August. ASSP captured in the CCI had 5%–9% lower body mass than individuals captured off central California during the early 1970s; it is not known whether this difference reflects natural inter-annual variation or differences in body condition. ASSP from SBI had the lowest body condition index (BCI) compared with those from PI and SR, indicating different foraging environments. Overall, 22 netting-sessions at three islands yielded a power of 84% to detect a 30% lesser CPUE; 19 sessions would be required in a future effort to evaluate this level of change. Evaluation of additional factors that affect CPUE and other independent measures of abundance or attendance should be included in future mist-netting efforts.

Altered spinal arachidonic acid turnover after peripheral nerve injury regulates regional glutamate concentration and neuropathic pain behaviors in rats.

PubMed

Sung, Backil; Wang, Shuxing; Zhou, Bei; Lim, Grewo; Yang, Liling; Zeng, Qing; Lim, Jeong-Ae; Wang, Jing Dong; Kang, Jing X; Mao, Jianren

2007-09-01

Spinal glutamate transporters (GT) have been implicated in the mechanisms of neuropathic pain; however, how spinal GT uptake activity is regulated remains unclear. Here we show that alteration of spinal arachidonic acid (AA) turnover after peripheral nerve injury regulated regional GT uptake activity and glutamate homeostasis. Chronic constriction nerve injury (CCI) in rats significantly reduced spinal GT uptake activity ((3)H-glutamate uptake) with an associated increase in extracellular AA and glutamate concentration from spinal microdialysates on postoperative day 8. AACOCF3 (a cytosolic phospholipase A2 inhibitor, 30mug) given intrathecally twice a day for postoperative day 1-7 reversed this CCI-induced spinal AA production, prevented the reduced spinal GT uptake activity and increased extracellular glutamate concentration. Conversely, alteration of spinal AA metabolism by diclofenac (a cyclooxygenase 1/2 inhibitor, 200mug) further reduced spinal GT uptake activity and increased extracellular glutamate concentration in CCI rats. GT uptake activity was also attenuated when AA (10 or 100nM) was directly added into spinal samples of naïve rats in an in vitro(3)H-glutamate uptake assay, indicating a direct inhibitory effect of AA on GT uptake activity. Consistent with these findings, AACOCF3 reduced the development of both thermal hyperalgesia and mechanical allodynia, whereas diclofenac exacerbated thermal hyperalgesia, in CCI rats. Thus, spinal AA turnover may serve as a regulator in CCI-induced changes in regional GT uptake activity, glutamate homeostasis, and neuropathic pain behaviors. These data suggest that regulating spinal AA turnover may be a useful approach to improving the clinical management of neuropathic pain.

Comparison of Comorbidity Collection Methods

PubMed Central

Kallogjeri, Dorina; Gaynor, Sheila M; Piccirillo, Marilyn L; Jean, Raymond A; Spitznagel, Edward L; Piccirillo, Jay F

2014-01-01

Background Multiple valid comorbidity indices exist to quantify the presence and role of comorbidities in cancer patient survival. Our goal was to compare chart-based Adult Comorbidity Evaluation-27 index (ACE-27), and claims-based Charlson Comorbidity Index (CCI) methods of identifying comorbid ailments, and their prognostic ability. Study Design Prospective cohort study of 6138 newly-diagnosed cancer patients at 12 different institutions. Participating registrars were trained to collect comorbidities from the abstracted chart using the ACE-27 method. ACE-27 assessment was compared with comorbidities captured through hospital discharge face-sheets using ICD-coding. The prognostic accomplishments of each comorbidity method was examined using follow-up data assessed at 24 months after data abstraction. Results Distribution of the ACE-27 scores was: “None” for 1453 (24%) of the patients; “Mild” for 2388 (39%); “Moderate” for 1344 (22%) and “Severe” for 950 (15%) of the patients. Deyo’s adaption of the Charlson Comorbidity Index (CCI) identified 4265 (69%) patients with a CCI score of 0, and the remaining 31% had CCI scores of 1 (n=1341, 22%), 2 (n=365, 6%), or 3 or more (n=167, 3%). Of the 4265 patients with a CCI score of 0, 394 (9%) were coded with severe comorbidities based on ACE-27 method. A higher comorbidity score was significantly associated with higher risk of death for both comorbidity indices. The multivariable Cox model including both comorbidity indices had the best performance (Nagelkerke’s R-square=0.37) and the best discrimination (c-index=0.827). Conclusion The number, type, and overall severity of comorbid ailments identified by chart- and claims-based approaches in newly-diagnosed cancer patients were notably different. Both indices were prognostically significant and able to provide unique prognostic information. PMID:24933715

Targeting the Tissue Factor-Factor VIIa Signaling Pathway to Enhance Activity of mTOR Inhibitors in the Treatment of Breast Cancer

DTIC Science & Technology

2009-09-01

Salzberg M, Ostapenko V, Illiger HJ, Behringer D, Bardy -Bouxin N, Boni J , Kong S, Cincotta M, and Moore L. Phase II study of temsirolimus (CCI-779), a ...factor interaction results in a tissue factor cytoplasmic domain- independent activation of protein synthesis, p70, and p90 S6 kinase phosphorylation. J ...The mTOR Pathway in Breast Cancer. J Mammary Gland Biol Neoplasia 2006; 11: 53-61. 23. Guba M, Yezhelyev, Eichhorn ME, Schmid G, Ischenko, Papyan A

Targeting Tissue Factor-Factor VIIa Signaling Pathway to Enhance Activity of mTOR Inhibitors in the Treatment of Breast Cancer

DTIC Science & Technology

2010-03-01

Salzberg M, Ostapenko V, Illiger HJ, Behringer D, Bardy -Bouxin N, Boni J , Kong S, Cincotta M, and Moore L. Phase II study of temsirolimus (CCI-779), a novel...interaction results in a tissue factor cytoplasmic domain- independent activation of protein synthesis, p70, and p90 S6 kinase phosphorylation. J ...mTOR Pathway in Breast Cancer. J Mammary Gland Biol Neoplasia 2006; 11: 53-61. 23. Guba M, Yezhelyev, Eichhorn ME, Schmid G, Ischenko, Papyan A

Transcranial low-level laser therapy enhances learning, memory, and neuroprogenitor cells after traumatic brain injury in mice

NASA Astrophysics Data System (ADS)

Xuan, Weijun; Vatansever, Fatma; Huang, Liyi; Hamblin, Michael R.

2014-10-01

The use of transcranial low-level laser (light) therapy (tLLLT) to treat stroke and traumatic brain injury (TBI) is attracting increasing attention. We previously showed that LLLT using an 810-nm laser 4 h after controlled cortical impact (CCI)-TBI in mice could significantly improve the neurological severity score, decrease lesion volume, and reduce Fluoro-Jade staining for degenerating neurons. We obtained some evidence for neurogenesis in the region of the lesion. We now tested the hypothesis that tLLLT can improve performance on the Morris water maze (MWM, learning, and memory) and increase neurogenesis in the hippocampus and subventricular zone (SVZ) after CCI-TBI in mice. One and (to a greater extent) three daily laser treatments commencing 4-h post-TBI improved neurological performance as measured by wire grip and motion test especially at 3 and 4 weeks post-TBI. Improvements in visible and hidden platform latency and probe tests in MWM were seen at 4 weeks. Caspase-3 expression was lower in the lesion region at 4 days post-TBI. Double-stained BrdU-NeuN (neuroprogenitor cells) was increased in the dentate gyrus and SVZ. Increases in double-cortin (DCX) and TUJ-1 were also seen. Our study results suggest that tLLLT may improve TBI both by reducing cell death in the lesion and by stimulating neurogenesis.

Comorbidities and Quality of Life among Breast Cancer Survivors: A Prospective Study

PubMed Central

Fu, Mei R.; Axelrod, Deborah; Guth, Amber A.; Cleland, Charles M.; Ryan, Caitlin E.; Weaver, Kristen R.; Qiu, Jeanna M.; Kleinman, Robin; Scagliola, Joan; Palamar, Joseph J.; Melkus, Gail D’Eramo

2015-01-01

Many breast cancer survivors have coexistent chronic diseases or comorbidities at the time of their cancer diagnosis. The purpose of the study was to evaluate the association of comorbidities on breast cancer survivors’ quality of life. A prospective design was used to recruit 140 women before cancer surgery, 134 women completed the study. Comorbidities were assessed using self-report and verified by medical record review and the Charlson Comorbidity Index (CCI) before and 12-month after cancer surgery. Quality of life was evaluated using Short-Form Health Survey (SF-36 v2). Descriptive statistics, chi-square tests, t-tests, Fisher’s exact test, and correlations were performed for data analysis. A total of 28 comorbidities were identified. Among the 134 patients, 73.8% had at least one of the comorbidities, 54.7% had 2–4, and only 7.4% had 5–8. Comorbidities did not change at 12 months after surgery. Numbers of comorbidities by patients’ self-report and weighted categorization of comorbidities by CCI had a similar negative correlation with overall quality of life scores as well as domains of general health, physical functioning, bodily pain, and vitality. Comorbidities, specifically hypertension, arthritis, and diabetes, were associated with poorer quality of life in multiple domains among breast cancer survivors. Future research should consider the combined influence of comorbidity and cancer on patients’ quality of life. PMID:26132751

Evaluation of three different data fusion approaches that uses satellite soil moisture from different passive microwave sensors to construct one consistent climate record

NASA Astrophysics Data System (ADS)

van der Schalie, Robin; de Jeu, Richard; Kerr, Yann; Wigneron, Jean-Pierre; Rodríguez-Fernández, Nemesio; Al-Yaari, Amen; Drusch, Matthias; Mecklenburg, Susanne; Dolman, Han

2016-04-01

Datasets that are derived from satellite observations are becoming increasingly important for measuring key parameters of the Earth's climate and are therefore crucial in research on climate change, giving the opportunity to researchers to detect anomalies and long-term trends globally. One of these key parameters is soil moisture (SM), which has a large impact on water, energy and biogeochemical cycles worldwide. A long-term SM data record from active and passive microwave satellite observations was developed as part of ESA's Climate Change Initiative (ESA-CCI-SM, http://www.esa-soilmoisture-cci.org/). Currently the dataset covers a period from 1978 to 2014 and is updated regularly, observations from a several microwave satellites including: ERS-1, ERS-2, METOP-A, Nimbus 7 SMMR, DMSP SSM/I, TRMM TMI, Aqua AMSRE, Coriolis WindSat, and GCOM-W1 AMSR2. In 2009, ESA launched the Soil Moisture and Ocean Salinity (SMOS, Kerr et al., 2010) mission, carrying onboard a unique L-band radiometer, but its SM retrievals are not yet part of this dataset. Due to the different radiometric characteristics of SMOS, integrating SMOS into the ESA-CCI-SM dataset is not straight forward. Therefore several approaches have been tested to fuse soil moisture retrievals from SMOS and AMSRE, which currently forms the basis of the passive microwave part within ESA-CCI-SM project. These approaches are: 1. A Neural Network Fusion approach (Rodríguez-Fernández et al., 2015), 2. A regression approach (Wigneron et al., 2004; Al-Yaari et al., 2015) and 3. A radiative transfer based approach, using the Land Parameter Retrieval Model (Van der Schalie et al., 2016). This study evaluates the three different approaches and tests their skills against multiple datasets, including MERRA-Land, ERA-Interim/Land, the current ESA-CCI-SM v2.2 and in situ measurements from the International Soil Moisture Network and present a recommendation for the potential integration of SMOS soil moisture into the ESA-CCI-SM dataset. This recommendation is based on a series of statistical metrics (i.e. correlation, unbiased root mean square error, bias, spatial correspondence and single to noise ratios (Gruber et al., 2015)) and will provide guidelines for a seamless integration. References Al-Yaari, A., Wigneron, J.P., Kerr, Y., De Jeu, R.A.M., Rodriguez-Fernandez, N., Van der Schalie, R., Al Bitar, A., Mialon, A., Richaume, P., Dolman, A., and Ducharne, A. (2015), "Testing regression equations to derive long-term global soil moisture datasets from passive microwave observations", Remote Sensing of Environment, IN PRESS. Gruber, A., Su, C.-H., Zwieback, S., Crowd, W., Dorigo, W., and Wagner, W. (2015), "Recent advances in (soil moisture) triple collocation analysis", Int. J. Appl. Earth Observ. Geoinf, doi: http://dx.doi.org/10.1016/j.jag.2015.09.002. Kerr, Y.H., Waldteufel, P., Wigneron, J.P., Delwart, S., Cabot, F., Boutin, J., Escorihuela, M.J., Font, J., Reul, N., Gruhier, C., Juglea, S.E., Drinkwater, M.R., Hahne, A., Martin-Neira, M., and Mecklenburg, S. (2010), "The SMOS mission: New tool for monitoring key elements of the global water cycle", Proceedings of the IEEE, vol. 98, no. 5, doi: 10.1109/JPROC.2010.2043043. Rodríguez-Fernández, N.J., Aires, F., Richaume, P., Kerr, Y.H., Prigent, C., Kolassa, J., Cabot, F., Jiménez, C., Mahmoodi, A., and Drusch, M. (2015), "Soil Moisture Retrieval Using Neural Networks: Application to SMOS", IEEE Trans. on Geosc. and Remote Sens., vol. 53, no. 11, doi: 10.1109/TGRS.2015.2430845. Van der Schalie, R., Kerr, Y.H., Wigneron, J.P., Rodriguez-Fernandez, N.J., Al-Yaari, A., and De Jeu, R.A.M. (2015), "Global SMOS Soil Moisture Retrievals from The Land Parameter Retrieval Model", Int. J. Appl. Earth Observ. Geoinf, doi: http://dx.doi.org/10.1016/j.jag.2015.08.005. Wigneron J.-P., Calvet, J.-C., De Rosnay, P., Kerr, Y., Waldteufel, P., Saleh, K., Escorihuela, M.J. and Kruszewski, A. (2004), "Soil Moisture Retrievals from Bi-Angular L-band Passive Microwave Observations", IEEE Trans. Geosc. Remote Sens. Let., vol. 1, no. 4, pp. 277-281.

Using a Simple Knowledge Organization System to facilitate Catalogue and Search for the ESA CCI Open Data Portal

NASA Astrophysics Data System (ADS)

Wilson, Antony; Bennett, Victoria; Donegan, Steve; Juckes, Martin; Kershaw, Philip; Petrie, Ruth; Stephens, Ag; Waterfall, Alison

2016-04-01

The ESA Climate Change Initiative (CCI) is a €75m programme that runs from 2009-2016, with a goal to provide stable, long-term, satellite-based essential climate variable (ECV) data products for climate modellers and researchers. As part of the CCI, ESA have funded the Open Data Portal project to establish a central repository to bring together the data from these multiple sources and make it available in a consistent way, in order to maximise its dissemination amongst the international user community. Search capabilities are a critical component to attaining this goal. To this end, the project is providing dataset-level metadata in the form of ISO 19115 records served via a standard OGC CSW interface. In addition, the Open Data Portal is re-using the search system from the Earth System Grid Federation (ESGF), successfully applied to support CMIP5 (5th Coupled Model Intercomparison Project) and obs4MIPs. This uses a tightly defined controlled vocabulary of metadata terms, the DRS (The Data Reference Syntax) which encompass different aspects of the data. This system hs facilitated the construction of a powerful faceted search interface to enable users to discover data at the individual file level of granularity through ESGF's web portal frontend. The use of a consistent set of model experiments for CMIP5 allowed the definition of a uniform DRS for all model data served from ESGF. For CCI however, there are thirteen ECVs, each of which is derived from multiple sources and different science communities resulting in highly heterogeneous metadata. An analysis has been undertaken of the concepts in use, with the aim to produce a CCI DRS which could be provide a single authoritative source for cataloguing and searching the CCI data for the Open Data Portal. The use of SKOS (Simple Knowledge Organization System) and OWL (Web Ontology Language) to represent the DRS are a natural fit and provide controlled vocabularies as well as a way to represent relationships between similar terms used in different ECVs. An iterative approach has been adopted for the model development working closely with domain experts and drawing on practical experience working with content in the input datasets. Tooling has been developed to enable the definition of vocabulary terms via a simple spreadsheet format which can then be automatically converted into Turtle notation and uploaded to the CCI DRS vocabulary service. With a baseline model established, work is underway to develop an ingestion pipeline to import validated search metadata into the ESGF and OGC CSW search services. In addition to the search terms indexed into the ESGF search system, ISO 19115 records will also be similarly tagged during this process with search terms from the data model. In this way it will be possible to construct a faceted search user interface for the Portal which can yield linked search results for data both at the file and dataset level granularity. It is hoped that this will also provide a rich range of content for third-party organisations wishing to incorporate access to CCI data in their own applications and services.

Operation Brain Trauma Therapy

DTIC Science & Technology

2016-12-01

either clinical trials in TBI if shown to be highly effective across OBTT, or tested in a precision medicine TBI phenotype (such as contusion) based...clinical trial if shown to be potently effective in one of the models in OBTT (i.e., a model that mimicked a specific clinical TBI phenotype). In... effective drug seen thus far in primary screening albeit with benefit highly model dependent, largely restricted to the CCI model. This suggests

The Effects of a Nutrition Media Literacy Intervention on Parents' and Youths' Communication about Food.

PubMed

Austin, Erica Weintraub; Austin, Bruce W; French, Brian F; Cohen, Marilyn A

2018-01-01

Interventions addressing links between media exposure and obesity risk for school-age youth have not explicitly addressed the role of family communication about media. Youths' influence attempts on parents to purchase advertised foods can create conflict and negatively affect parental food choices. This study tested whether a family-based media literacy curriculum improves parents' media management skills and decreases youths' susceptibility to appealing but unrealistic food marketing. A matched-group pretest/posttest field experiment of parent-youth dyads with control group (N = 100 dyads, youth M = 11 years of age) tested the six-session curriculum. Hypotheses were analyzed using a Bayesian structural equation model. The curriculum increased parents' active negative mediation to foster youths' critical thinking about food marketing, b* = 0.35, 95% CCI [0.17, 0.50], increased parent Efficacy for making healthy dietary changes for their families, b* = 0.59, 95% CCI [0.41, 0.75], and fostered family discussion about nutrition labels (total effect = 0.22). Additionally, cumulative influences of Perceived Desirability and Wishful Identification on youths' requests for marketed foods were reduced (total effect = 0.04). Media literacy education can empower parents and improve youths' critical thinking to reduce effects of food marketing on families and improve use of media to obtain nutrition information.

Intranasal insulin treatment of an experimental model of moderate traumatic brain injury.

PubMed

Brabazon, Fiona; Wilson, Colin M; Jaiswal, Shalini; Reed, John; Frey, William H; Byrnes, Kimberly R

2017-09-01

Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.

Physician involvement in disease management as part of the CCM.

PubMed

Wallace, Paul J

2005-01-01

Phase I of the voluntary chronic care improvement (CCI-I) under traditional fee-for-service Medicare initiative seeks to extend the benefits of disease management to an elderly population with comorbid chronic medical conditions. Active, sustained involvement of treating physicians, a historical deficit of disease management programs, is a CCI-I program goal. During the last decade, Kaiser Permanente, an integrated health care delivery system with more than 60 years of experience in managing the care of individuals and populations, has applied the chronic care model (CCM) to develop care management strategies for populations of patients with chronic medical conditions. Physician leadership and involvement have been key to successfully incorporating these practices into care. The scope of physician involvement in leading, developing, and delivering chronic illness care management at Kaiser Permanente is described as a basis for identifying opportunities to involve practicing physicians in the CCI-I.

Physician Involvement in Disease Management as Part of the CCM

PubMed Central

Wallace, Paul J.

2005-01-01

Phase I of the voluntary chronic care improvement (CCI-I) under traditional fee-for-service Medicare initiative seeks to extend the benefits of disease management to an elderly population with comorbid chronic medical conditions. Active, sustained involvement of treating physicians, a historical deficit of disease management programs, is a CCI-I program goal. During the last decade, Kaiser Permanente, an integrated health care delivery system with more than 60 years of experience in managing the care of individuals and populations, has applied the chronic care model (CCM) to develop care management strategies for populations of patients with chronic medical conditions. Physician leadership and involvement have been key to successfully incorporating these practices into care. The scope of physician involvement in leading, developing, and delivering chronic illness care management at Kaiser Permanente is described as a basis for identifying opportunities to involve practicing physicians in the CCI-I. PMID:17288075

[Expressions of neuropathic pain-related proteins in the spinal cord dorsal horn in rats with bilateral chronic constriction injury].

PubMed

Shen, Le; Li, Xu; Wang, Hai-tang; Yu, Xue-rong; Huang, Yu-guang

2013-12-01

To evaluate the pain-related behavioral changes in rats with bilateral chronic constriction injury(bCCI)and identify the expressions of neuropathic pain-related proteins. The bCCI models were established by ligating the sciatic nerves in female Sprague Dawley rats. Both mechanical hyperalgesia and cold hyperalgesia were evaluated through electronic von Frey and acetone method. Liquid chromatography-mass spectrometry/mass spectrometry was applied to characterize the differentially expressed proteins. Both mechanical withdrawal threshold and cold hyperalgesia threshold decreased significantly on the postoperative day 7 and 14, when compared with na ve or sham rats(P <0.05). Twenty five differentially expressed proteins associated with bilateral CCI were discovered, with eighteen of them were upregulated and seven of them downregulated. The bCCT rats have remarkably decreased mechanical and cold hyperalgesia thresholds. Twenty five neuropathic pain-related proteins are found in the spinal cord dorsal horn.

Combination strategy of PARP inhibitor with antioxidant prevent bioenergetic deficits and inflammatory changes in CCI-induced neuropathy.

PubMed

Komirishetty, Prashanth; Areti, Aparna; Gogoi, Ranadeep; Sistla, Ramakrishna; Kumar, Ashutosh

2017-02-01

Neuropathic pain, a debilitating pain condition and the underlying pathogenic mechanisms are complex and interwoven amongst each other and still there is scant information available regarding therapies which promise to treat the condition. Evidence indicate that oxidative/nitrosative stress induced poly (ADP-ribose) polymerase (PARP) overactivation initiate neuroinflammation and bioenergetic crisis culminating into neurodegenerative changes following nerve injury. Hence, we investigated the therapeutic effect of combining an antioxidant, quercetin and a PARP inhibitor, 4-amino 1, 8-naphthalimide (4-ANI) on the hallmark deficits induced by chronic constriction injury (CCI) of sciatic nerve in rats. Quercetin (25 mg/kg, p.o.) and 4-ANI (3 mg/kg, p.o.) were administered either alone or in combination for 14 days to examine sciatic functional index, allodynia and hyperalgesia using walking track analysis, Von Frey, acetone spray and hot plate tests respectively. Malondialdehyde, nitrite and glutathione levels were estimated to detect oxidative/nitrosative stress; mitochondrial membrane potential and cytochrome c oxidase activity to assess mitochondrial function; NAD & ATP levels to examine the bioenergetic status and levels of inflammatory markers were evaluated in ipsilateral sciatic nerve. Quercetin and 4-ANI alone improved the pain behaviour and biochemical alterations but the combination therapy demonstrated an appreciable reversal of CCI-induced changes. Nitrotyrosine and Poly ADP-Ribose (PAR) immunopositivity was decreased and nuclear factor erythroid 2-related factor (Nrf-2) levels were increased significantly in micro-sections of the sciatic nerve and dorsal root ganglion (DRG) of treatment group. These results suggest that simultaneous inhibition of oxidative stress-PARP activation cascade may potentially be useful strategies for management of trauma induced neuropathic pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

The ADOPT-LC score: a novel predictive index of in-hospital mortality of cirrhotic patients following surgical procedures, based on a national survey.

PubMed

Sato, Masaya; Tateishi, Ryosuke; Yasunaga, Hideo; Horiguchi, Hiromasa; Matsui, Hiroki; Yoshida, Haruhiko; Fushimi, Kiyohide; Koike, Kazuhiko

2017-03-01

We aimed to develop a model for predicting in-hospital mortality of cirrhotic patients following major surgical procedures using a large sample of patients derived from a Japanese nationwide administrative database. We enrolled 2197 cirrhotic patients who underwent elective (n = 1973) or emergency (n = 224) surgery. We analyzed the risk factors for postoperative mortality and established a scoring system for predicting postoperative mortality in cirrhotic patients using a split-sample method. In-hospital mortality rates following elective or emergency surgery were 4.7% and 20.5%, respectively. In multivariate analysis, patient age, Child-Pugh (CP) class, Charlson Comorbidity Index (CCI), and duration of anesthesia in elective surgery were significantly associated with in-hospital mortality. In emergency surgery, CP class and duration of anesthesia were significant factors. Based on multivariate analysis in the training set (n = 987), the Adequate Operative Treatment for Liver Cirrhosis (ADOPT-LC) score that used patient age, CP class, CCI, and duration of anesthesia to predict in-hospital mortality following elective surgery was developed. This scoring system was validated in the testing set (n = 986) and produced an area under the curve of 0.881. We also developed iOS/Android apps to calculate ADOPT-LC scores to allow easy access to the current evidence in daily clinical practice. Patient age, CP class, CCI, and duration of anesthesia were identified as important risk factors for predicting postoperative mortality in cirrhotic patients. The ADOPT-LC score effectively predicts in-hospital mortality following elective surgery and may assist decisions regarding surgical procedures in cirrhotic patients based on a quantitative risk assessment. © 2016 The Authors Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.

The thalidomide analgesic effect is associated with differential TNF-α receptor expression in the dorsal horn of the spinal cord as studied in a rat model of neuropathic pain.

PubMed

Andrade, Pablo; Visser-Vandewalle, Veerle; Del Rosario, John S; Daemen, Marc A; Buurman, Wim A; Steinbusch, Harry W; Hoogland, Govert

2012-04-23

The proinflammatory cytokine tumor necrosis factor-α (TNF-α) is well recognized as a key player in nociceptive signaling. Yet, therapeutic capitalization of this knowledge requires a better understanding of how TNF receptors (TNFR) contribute to pain. To address this question, we studied TNFR expression in the chronic sciatic nerve constriction (CCI) model of neuropathic pain. CCI and sham operated rats received two subcutaneous injections (one immediately after surgery, the other on postoperative day 5) containing either saline, GABA-reuptake inhibitor (NO-711), insulin-like growth factor-1 (IGF-1), ZVAD or thalidomide. Mechanical (using von Frey filaments) and thermal hypersensitivity (Hargreaves test) were assessed preoperatively and weekly during the first four postoperative weeks. Spinal cord dorsal horn samples were collected from animals that were sacrificed at 2 weeks and 4 weeks after surgery, and analyzed for TNFR1 and TNFR2 mRNA levels by qPCR and protein levels by Western blot. Compared to saline, all applied drug treatments resulted in a faster recovery from mechanical and thermal hypersensitivity, yet in a potency order of thalidomide>ZVAD=IGF-1>NO-711. CCI resulted in increased TNFR1 and TNFR2 mRNA and protein levels in the ipsilateral dorsal horn. Thalidomide was the only treatment that attenuated these increases. Finally, animals that showed a poor behavioral recovery were characterized by a significantly higher TNFR1/TNFR2 mRNA ratio. These data show that differential expression of TNFR in the dorsal horn is associated with recovery from pain in this model and suggest that the analgesic effects of thalidomide may act via this mechanism. Copyright © 2012 Elsevier B.V. All rights reserved.

Predictors of postoperative decline in estimated glomerular filtration rate in patients undergoing robotic partial nephrectomy.

PubMed

Wiener, Scott; Kiziloz, Halil; Dorin, Ryan P; Finnegan, Kyle; Shichman, Steven S; Meraney, Anoop

2014-07-01

To identify prognostic indicators of estimated glomerular filtration rate (eGFR) following robotic partial nephrectomy (RPN). In a retrospective study of RPN patients, we examined data describing age, gender, eGFR, body mass index (BMI), tumor size (TS), length of stay, and estimated blood loss (EBL). Changes in eGFR (i.e., renal function trajectory [RFT]) and chronic kidney disease (CKD) stage shift were analyzed with mixed model linear and logistic regression analyses, Chi-squared, and t-tests. Changes in eGFR (RFT) were determined in 122 patients at baseline and at 6- and 12-month follow-up visits. Mean age, TS, and Charlson comorbidity index (CCI) were 62±11 years, 3±1.2 cm, and 4.8±1.8, respectively. The pre- and postoperative eGFR was lower in patients >60 years. Preoperative eGFR was unrelated to gender, BMI>30 kg/m(2), histopathology, nuclear grade, and TS. Univariate analyses determined that age, BMI>30, EBL>200 mL, CCI>5, and TS were associated with greater declines in eGFR. Reduced eGFR was also associated with warm ischemia time ≥22 minutes, while age was associated with a ≥1 worsening of British CKD classification. Using multivariate analysis, only age was significantly associated with a decline in eGFR, which was greater in patients with a normal preoperative eGFR. Patient age, BMI>30, EBL>200 mL, CCI>5, and TS were predictors of greater postoperative declines in eGFR. Although a decline in eGFR was proportionally greater in low stage CKD, postoperative changes are associated with advancing age.

Experimental Study of Thoracoabdominal Injuries Suffered from Caudocephalad Impacts Using Pigs

PubMed Central

Guan, Sishu; Liao, Zhikang; Xiang, Hongyi; Zhu, Xiyan; Wang, Zhong; Lai, Xinan

2018-01-01

To know the caudocephalad impact- (CCI-) induced injuries more clearly, 21 adult minipigs, randomly divided into three groups: control group (n = 3), group I (n = 9), and group II (n = 9), were used to perform the CCI experiments on a modified deceleration sled. Configured impact velocity was 0 m/s in the control group, 8 m/s in group I, and 11 m/s in group II. The kinematics and mechanical responses of the subjects were recorded and investigated. The functional change examination and the autopsies were carried out, with which the injuries were evaluated from the Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS). The subjects in group I and group II experienced the caudocephalad loading at the peak pelvic accelerations of 108.92 ± 58.87 g and 139.13 g ± 78.54 g, with the peak abdomen pressures, 41.24 ± 16.89 kPa and 63.61 ± 65.83 kPa, respectively. The injuries of the spleen, lung, heart, and spine were detected frequently among the tested subjects. The maximal AIS (MAIS) of chest injuries was 4 in group I and 5 in group II, while both the MAIS of abdomen injuries in group I and group II were 5. The ISS in group II was 52.71 ± 6.13, significantly higher than in group I, 26.67 ± 5.02 (p < 0.05). The thoracoabdomen CCI injuries and the mechanical response addressed presently may be useful to conduct both the prevention studies against military or civilian injuries. PMID:29861783

[Assessment of Three Risk Adjustment Systems as Predictors of the Consumption of Medicines and Medical Supplies at Polyvalent Hospitalization Units. Spain].

PubMed

Mera Flores, Ana María; Del Busto Bonifaz, Sebastián; Bernal Sobrino, José Luis

2016-09-26

The use of medicines and medical supplies is a significant component of health expenditure, linked to healthcare quality and efficient resource allocation. This study aimed to evaluate three risk adjustment systems predictive power of the consumption of medicines and medical supplies at polyvalent hospitalization units (PHU). This is an observational, retrospective study of the resources utilization in PHU between 2010 and 2013. We fitted linear regression models and evaluated their goodness of fit for three different predictors: Charlson Comorbidity Index (CCI), All Patients DRG (AP-DRG) and All Patients Refined DRG (APR-DRG) relative weights, and each one of them corrected by the length of stay. We analyzed hospitalization episodes included in the Minimum Basic Data Set (MBDS) from Fuenlabrada University Hospital. Data about the use of medicines and medical supplies were obtained from pharmacy and supply chain management information systems. Significant correlation was found between the annual consumption and the predictors considered (r=0,879 for CCI; r=0,622 for AP-DRG and r=0,514 for APR-DRG). The CCI corrected by length of stay was the variable that best fit presented (Ṝ2=0,863). The best predictive ability of CCI indicates that resource utilization depends more of the concurrent presence of additional pathology than the case mix calculated for iso-resource groups.

FCG (FLIPI, Charlson comorbidity index, and histological grade) score is superior to FLIPI in advanced follicular lymphoma.

PubMed

Mihaljevic, Biljana; Jelicic, Jelena; Andjelic, Bosko; Antic, Darko; Markovic, Olivera; Petkovic, Ivan; Jovanovic, Maja Perunicic; Trajkovic, Goran; Bila, Jelena; Djurasinovic, Vladislava; Sretenovic, Aleksandra; Vukovic, Vojin; Smiljanic, Mihailo; Balint, Milena Todorovic

2016-12-01

The Follicular Lymphoma International Prognostic Index (FLIPI) is widely used in the identification of risk groups among follicular lymphoma (FL) patients. The aim of the present study was to evaluate the prognostic value of FLIPI combined with the Charlson comorbidity index (CCI) and histological grade of lymphoma. 224 newly diagnosed FL patients (median age 56 years) treated with immunochemotherapy were retrospectively analysed. Low FLIPI had 21.0 % of patients, intermediate 28.1 % and high 46.9 %. 50.9 % of patients had no comorbidities. Only 7.1 % of patients had a high CCI score (≥2), while 25.9 % of patients were histological grade 3. Parameters that influenced overall survival were evaluated using Cox regression analysis, in which CCI, FLIPI and histological grade (p < 0.05) retained prognostic significance. By combining these parameters, we have developed the FCG score, which incorporates FLIPI, CCI, and histological grade. This score defines three risk categories (low: 41.5 %; intermediate: 37.5 %; high: 13.4 %), associated with significantly different survival (p < 0.0001); this consequently improves discriminative power by 9.1 % compared to FLIPI. FCG score represents a possible new prognostic index, highlighting the role of the patient's clinical state and the histological characteristics of disease, as indicated by comorbidity index and histological grade of lymphoma.

Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.

PubMed

Belousov, Andrei B; Wang, Yongfu; Song, Ji-Hoon; Denisova, Janna V; Berman, Nancy E; Fontes, Joseph D

2012-08-22

In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Calcium Channel α2δ1 Proteins Mediate Trigeminal Neuropathic Pain States Associated with Aberrant Excitatory Synaptogenesis*

PubMed Central

Li, Kang-Wu; Yu, Yanhui Peter; Zhou, Chunyi; Kim, Doo-Sik; Lin, Bin; Sharp, Kelli; Steward, Oswald; Luo, Z. David

2014-01-01

To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel α2δ1 (Cavα2δ1) protein dysregulation in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial hypersensitivity that correlated with Cavα2δ1 up-regulation in trigeminal ganglion neurons and Vc/C2. Blocking Cavα2δ1 with gabapentin, a ligand for the Cavα2δ1 proteins, or Cavα2δ1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of Cavα2δ1 in orofacial pain processing. Importantly, increased Cavα2δ1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis and increased frequency, but not the amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin. Thus, CCI-ION-induced Cavα2δ1 up-regulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter release in Vc/C2. PMID:24459143

Evaluating ESA CCI soil moisture in East Africa.

PubMed

McNally, Amy; Shukla, Shraddhanand; Arsenault, Kristi R; Wang, Shugong; Peters-Lidard, Christa D; Verdin, James P

2016-06-01

To assess growing season conditions where ground based observations are limited or unavailable, food security and agricultural drought monitoring analysts rely on publicly available remotely sensed rainfall and vegetation greenness. There are also remotely sensed soil moisture observations from missions like the European Space Agency (ESA) Soil Moisture and Ocean Salinity (SMOS) and NASA's Soil Moisture Active Passive (SMAP), however these time series are still too short to conduct studies that demonstrate the utility of these data for operational applications, or to provide historical context for extreme wet or dry events. To promote the use of remotely sensed soil moisture in agricultural drought and food security monitoring, we use East Africa as a case study to evaluate the quality of a 30+ year time series of merged active-passive microwave soil moisture from the ESA Climate Change Initiative (CCI-SM). Compared to the Normalized Difference Vegetation index (NDVI) and modeled soil moisture products, we found substantial spatial and temporal gaps in the early part of the CCI-SM record, with adequate data coverage beginning in 1992. From this point forward, growing season CCI-SM anomalies were well correlated (R>0.5) with modeled, seasonal soil moisture, and in some regions, NDVI. We use correlation analysis and qualitative comparisons at seasonal time scales to show that remotely sensed soil moisture can add information to a convergence of evidence framework that traditionally relies on rainfall and NDVI in moderately vegetated regions.

Watchful waiting and active surveillance approach in patients with low risk localized prostatic cancer: an experience of out-patients clinic with 12-year follow-up.

PubMed

Kravchick, Sergey; Peled, Ronit; Cytron, Shmuel

2011-12-01

In this study we evaluated the safety of expectant approach in the patients with low risk prostate cancer in the reality of community based out-patients clinics. 48 men were enrolled into the study. The inclusion criteria were age ranged from 60 to 75 years and the Epstein criteria for low risk prostate cancer. Patients were managed expectantly while curative treatment was offered when indicated. Initial and final Charlson comorbidity index (CCI) and BMI were assessed for all men. Patients' median follow-up was 81.1 ± 29.1 years. During this study 41.7% of the patients chose active forms of treatment. Cancer was found in 20.8% (n-10) of our patients. Two first sessions of re-biopsy diagnosed 92% of T1c upgrading. Six men with CCI ≥2 died from concomitant disease and no one died from PCa. Significant correlation was found between BMI and final CCI ≥2 (p-0.001). Expectant approach can be considered as self alternative to active treatment model in selected group of patients with well differentiated PCa, however 20.8% of these patients are still at risk of having aggressive form of cancer. Expectant approach is particular beneficial for the patients with CCI 1-2 and high BMI.

Role of APOE Isoforms in the Pathogenesis of TBI Induced Alzheimer’s Disease

DTIC Science & Technology

2015-10-01

global deletion, APOE targeted replacement, complex breeding, CCI model optimization, mRNA library generation, high throughput massive parallel ...ATP binding cassette transporter A1 (ABCA1) is a lipid transporter that controls the generation of HDL in plasma and ApoE-containing lipoproteins in... parallel sequencing, mRNA-seq, behavioral testing, mem- ory impairement, recovery. 3 Overall Project Summary During the reported period, we have been able

Effect of Electroacupuncture on Rats with Chronic Constriction Injury-Induced Neuropathic Pain

PubMed Central

Tang, Nou-Ying; Lin, Yi-Wen; Li, Tsai-Chung; Liu, Hsu-Jan

2014-01-01

We adopt the chronic constriction injury (CCI) model to induce neuropathic pain to Spragrue-Dawley (SD) rats by ligating the right sciatic nerve of using four 4-0 chromic gut sutures and subsequently applying 2 and 15 Hz electroacupuncture (EA), respectively, to the right (ipsilateral) Zusanli (St-36) and Shangjuxu (St-37) acupoints. The results of this study are summarized as follows: (1) the differences in withdrawal latencies for the radiant heat test and total lift leg counts for the cold plate test (4°C) of the control (i.e., non-EA) and sham groups were greater than those of the 2 Hz EA (2EA) and 15 Hz EA (15EA) groups; (2) the von Frey test filament gram counts of the control and sham groups were less than those of the 2EA and 15EA groups on the 6th, 7th, 8th, 11th, 12th, and 13th day following ligation; and (3) the 2EA and 15EA groups exhibited reduced cerebral transient receptor potential vanilloid type 4 (TRPV4) expressions, although we did not observe a similar effect for cerebral TRPV1 or spinal TRPV4/TRPV1 expressions. These findings show that 2 and 15 Hz EA can reduce CCI-induced neuropathic pain, which indicates that various spinal segmental and gate effects have a crucial function in pain reduction. The relationship between EA and TRPV4/TRPV1 expression requires further study. PMID:24605047

Increased fall risk is associated with elevated co-contraction about the ankle during static balance challenges in older adults.

PubMed

Nelson-Wong, Erika; Appell, Ryan; McKay, Mike; Nawaz, Hannah; Roth, Joanna; Sigler, Robert; Third, Jacqueline; Walker, Mark

2012-04-01

Falls are a leading contributor to disability in older adults. Increased muscle co-contraction in the lower extremities during static and dynamic balance challenges has been associated with aging, and also with a history of falling. Co-contraction during static balance challenges has not been previously linked with performance on clinical tests designed to ascertain fall risk. The purpose of this study was to investigate the relationship between co-contraction about the ankle during static balance challenges with fall risk on a commonly used dynamic balance assessment, the Four Square Step Test (FSST). Twenty-three volunteers (mean age 73 years) performed a series of five static balance challenges (Romberg eyes open/closed, Sharpened Romberg eyes open/closed, and Single Leg Standing) with continuous electromyography (EMG) of bilateral tibialis anterior and gastrocnemius muscles. Participants then completed the FSST and were categorized as 'at-risk' or 'not-at-risk' to fall based on a cutoff time of 12 s. Co-contraction was quantified with co-contraction index (CCI). CCI during narrow base conditions was positively correlated with time to complete FSST. High CCIs during all static balance challenges with the exception of Romberg stance with eyes closed were predictive of being at-risk to fall based on FSST time, odds ratio 19.3. The authors conclude that co-contraction about the ankle during static balance challenges can be predictive of performance on a dynamic balance test.

Dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of chronic myeloid leukaemia: systematic reviews and economic analyses.

PubMed

Pavey, T; Hoyle, M; Ciani, O; Crathorne, L; Jones-Hughes, T; Cooper, C; Osipenko, L; Venkatachalam, M; Rudin, C; Ukoumunne, O; Garside, R; Anderson, R

2012-01-01

Nilotinib and dasatinib are now being considered as alternative treatments to imatinib as a first-line treatment of chronic myeloid leukaemia (CML). This technology assessment reviews the available evidence for the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of Philadelphia chromosome-positive CML. Databases [including MEDLINE (Ovid), EMBASE, Current Controlled Trials, ClinicalTrials.gov, the US Food and Drug Administration website and the European Medicines Agency website] were searched from search end date of the last technology appraisal report on this topic in October 2002 to September 2011. A systematic review of clinical effectiveness and cost-effectiveness studies; a review of surrogate relationships with survival; a review and critique of manufacturer submissions; and a model-based economic analysis. Two clinical trials (dasatinib vs imatinib and nilotinib vs imatinib) were included in the effectiveness review. Survival was not significantly different for dasatinib or nilotinib compared with imatinib with the 24-month follow-up data available. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were higher for patients receiving dasatinib than for those with imatinib for 12 months' follow-up (CCyR 83% vs 72%, p < 0.001; MMR 46% vs 28%, p < 0.0001). The rates of CCyR and MMR were higher for patients receiving nilotinib than for those receiving imatinib for 12 months' follow-up (CCyR 80% vs 65%, p < 0.001; MMR 44% vs 22%, p < 0.0001). An indirect comparison analysis showed no difference between dasatinib and nilotinib for CCyR or MMR rates for 12 months' follow-up (CCyR, odds ratio 1.09, 95% CI 0.61 to 1.92; MMR, odds ratio 1.28, 95% CI 0.77 to 2.16). There is observational association evidence from imatinib studies supporting the use of CCyR and MMR at 12 months as surrogates for overall all-cause survival and progression-free survival in patients with CML in chronic phase. In the cost-effectiveness modelling scenario, analyses were provided to reflect the extensive structural uncertainty and different approaches to estimating OS. First-line dasatinib is predicted to provide very poor value for money compared with first-line imatinib, with deterministic incremental cost-effectiveness ratios (ICERs) of between £256,000 and £450,000 per quality-adjusted life-year (QALY). Conversely, first-line nilotinib provided favourable ICERs at the willingness-to-pay threshold of £20,000-30,000 per QALY. Immaturity of empirical trial data relative to life expectancy, forcing either reliance on surrogate relationships or cumulative survival/treatment duration assumptions. From the two trials available, dasatinib and nilotinib have a statistically significant advantage compared with imatinib as measured by MMR or CCyR. Taking into account the treatment pathways for patients with CML, i.e. assuming the use of second-line nilotinib, first-line nilotinib appears to be more cost-effective than first-line imatinib. Dasatinib was not cost-effective if decision thresholds of £20,000 per QALY or £30,000 per QALY were used, compared with imatinib and nilotinib. Uncertainty in the cost-effectiveness analysis would be substantially reduced with better and more UK-specific data on the incidence and cost of stem cell transplantation in patients with chronic CML. The Health Technology Assessment Programme of the National Institute for Health Research.

Influence of Clouds On The Surface Radiative Balance For Two Mediterranean Sites

NASA Astrophysics Data System (ADS)

Bortoli, D.; Costa, M. J.; Nardino, M.

Clouds strongly affect the Earth's climate influencing the surface radiative balance by reducing the incident solar radiation and increasing the downward longwave flux. Al- though the quantitative impact of clouds on the surface radiative balance is necessarily associated with great uncertainties due to the complexity and variation of the under- lying parameters, cloud radiative forcing is one of the main regulating factors of the Earth's climate. The present work aims at determining the effect of cloud coverage on the surface radiative balance, in order to contribute for a better understanding of local variations in the Mediterranean climate. Measurements of the cloud cover index (CCI) require the presence of an observer capable of quantifying cloud amounts in the sky in sight above the measurements' site. Since such measurements are not always available the cloud cover index is re- trieved using two different methodologies. On one hand the CCI is computed from the surface radiometer measurements throughout a parameterisation. On the other it is retrieved using a bi-spectral algorithm based on the METEOSAT satellite measure- ments from the visible and infrared spectral regions. Results of the CCI are compared with co-located observations to perform a general check against the available "ground truth". At the same time the CCI values obtained from both methodologies are inter- compared. Results of the CCI and their implications on the surface radiative balance are presented for the two Mediterranean sites selected, one located in Italy and the other in the south of Portugal. The cloud radiative forcing calculations show a cooling effect of the surface in presence of clouds for both sites. Moreover, a seasonal dependence is obtained, with a stronger cooling effect during summer. Acknowledgements: The work was supported by Instituto de Cooperação Científica e Tecnológica Internacional (ICCTI) - Portugal and Consiglio Nazionale delle Ricerche (CNR) - Italy, through the bilateral agreement "Study of cloud and aerosol radiative forcing on the surface radiative balance".

Participation of pro- and anti-nociceptive interleukins in botulinum toxin A-induced analgesia in a rat model of neuropathic pain.

PubMed

Zychowska, Magdalena; Rojewska, Ewelina; Makuch, Wioletta; Luvisetto, Siro; Pavone, Flaminia; Marinelli, Sara; Przewlocka, Barbara; Mika, Joanna

2016-11-15

Botulinum neurotoxin serotype A (BoNT/A) shows antinociceptive properties, and its clinical applications in pain therapy are continuously increasing. BoNT/A specifically cleaves SNAP-25, which results in the formation of a non-functional SNARE complex, thereby potently inhibiting the release of neurotransmitters and neuropeptides, including those involved in nociception. The aim of the present study was to determine the effects of BoNT/A (300pg/paw) on pain-related behavior and the levels of glial markers and interleukins in the spinal cord and dorsal root ganglia (DRG) after chronic constriction injury (CCI) to the sciatic nerve in rats. Glial activity was also examined after repeated intraperitoneal injection of minocycline combined with a single BoNT/A injection. Our results show that a single intraplantar BoNT/A injection did not influence motor function but strongly diminished pain-related behaviors in naïve and CCI-exposed rats. Additionally, microglial inhibition using minocycline enhanced the analgesic effects of BoNT/A. Western blotting results suggested that CCI induces the upregulation of the pronociceptive proteins IL-18, IL-6 and IL-1β in the ipsilateral lumbar spinal cord and DRG, but no changes in the levels of the antinociceptive proteins IL-18BP, IL-1RA and IL-10 were observed. Interestingly, BoNT/A injection suppressed the CCI-induced upregulation of IL-18 and IL-1β in the spinal cord and/or DRG and increased the levels of IL-10 and IL-1RA in the DRG. In summary, our results suggest that BoNT/A significantly attenuates pain-related behavior and microglial activation and restores the neuroimmune balance in a CCI model by decreasing the levels of pronociceptive factors (IL-1β and IL-18) and increasing the levels of antinociceptive factors (IL-10 and IL-1RA) in the spinal cord and DRG. Copyright © 2016 Elsevier B.V. All rights reserved.

Estimating trace gas and aerosol emissions over South America: Relationship between fire radiative energy released and aerosol optical depth observations

NASA Astrophysics Data System (ADS)

Pereira, Gabriel; Freitas, Saulo R.; Moraes, Elisabete Caria; Ferreira, Nelson Jesus; Shimabukuro, Yosio Edemir; Rao, Vadlamudi Brahmananda; Longo, Karla M.

2009-12-01

Contemporary human activities such as tropical deforestation, land clearing for agriculture, pest control and grassland management lead to biomass burning, which in turn leads to land-cover changes. However, biomass burning emissions are not correctly measured and the methods to assess these emissions form a part of current research area. The traditional methods for estimating aerosols and trace gases released into the atmosphere generally use emission factors associated with fuel loading and moisture characteristics and other parameters that are hard to estimate in near real-time applications. In this paper, fire radiative power (FRP) products were extracted from Moderate Resolution Imaging Spectroradiometer (MODIS) and from the Geostationary Operational Environmental Satellites (GOES) fire products and new South America generic biomes FRE-based smoke aerosol emission coefficients were derived and applied in 2002 South America fire season. The inventory estimated by MODIS and GOES FRP measurements were included in Coupled Aerosol-Tracer Transport model coupled to the Brazilian developments on the Regional Atmospheric Modeling System (CATT-BRAMS) and evaluated with ground truth collected in Large Scale Biosphere-Atmosphere Smoke, Aerosols, Clouds, rainfall, and Climate (SMOCC) and Radiation, Cloud, and Climate Interactions (RaCCI). Although the linear regression showed that GOES FRP overestimates MODIS FRP observations, the use of a common external parameter such as MODIS aerosol optical depth product could minimize the difference between sensors. The relationship between the PM 2.5μm (Particulate Matter with diameter less than 2.5 μm) and CO (Carbon Monoxide) model shows a good agreement with SMOCC/RaCCI data in the general pattern of temporal evolution. The results showed high correlations, with values between 0.80 and 0.95 (significant at 0.5 level by student t test), for the CATT-BRAMS simulations with PM 2.5μm and CO.

Sensorimotor control and neuromuscular activity of the shoulder in adolescent competitive swimmers with generalized joint hypermobility.

PubMed

Frydendal, Thomas; Eshøj, Henrik; Liaghat, Behnam; Edouard, Pascal; Søgaard, Karen; Juul-Kristensen, Birgit

2018-05-05

Shoulder pain is highly prevalent in competitive swimmers, and generalized joint hypermobility (GJH) is considered a risk factor. Sensorimotor control deficiencies and altered neuromuscular activation of the shoulder may represent underlying factors. To investigate whether competitive swimmers with GJH including shoulder hypermobility (GJHS) differ in shoulder sensorimotor control and muscle activity from those without GJH and no shoulder hypermobility (NGJH). Competitive swimmers (aged 13-17) were recruited. GJHS or NGJH status was determined using the Beighton score (0-9) and Rotès-Quérol test (positive/negative). Inclusion criteria for GJHS were a Beighton score ≥5 and minimum one hypermobile shoulder, while NGJH was defined as a Beighton score ≤3 and no shoulder hypermobility. Three prone lying, upper-extremity weight-bearing shoulder stabilometric tests were performed on a force platform: Bilateral upper-extremity support eyes open (BL-EO) and eyes closed (BL-EC) and unilateral upper-extremity support eyes open (UL-EO). Surface electromyography (SEMG) was measured from the upper trapezius, lower trapezius, serratus anterior, infraspinatus and pectoralis major muscles. SEMG was normalized using maximal voluntary isometric contractions and presented relative to maximal voluntary SEMG (%MVE). Co-contraction index (CCI) was calculated for the following muscle pairs: upper trapezius-lower trapezius, upper trapezius-serratus anterior, and infraspinatus-pectoralis major. Between-group differences in stabilometric parameters, %MVE, and CCI were analyzed with a mixed effects model. Thirty-eight swimmers were enrolled as GJHS (n = 19) or NGJH (n = 19). There were no group differences in stabilometric parameters or CCI. GJHS displayed significantly decreased (29%) pectoralis major activity during BL-EO compared to NGJH (5.35 ± 1.77%MVE vs. 7.51 ± 1.96%MVE; p = 0.043). Adolescent competitive swimmers with GJHS displayed no shoulder sensorimotor control deficiencies and no generally altered shoulder muscle activity pattern, except for decreased pectoralis major activity in BL-EO. Longitudinal studies are needed to investigate whether decreased pectoralis major activation contributes to the development of shoulder pain in swimmers with GJHS. Copyright © 2018 Elsevier B.V. All rights reserved.

Intrathecal transplantation of neuroblastoma cells decreases heat hyperalgesia and cold allodynia in a rat model of neuropathic pain.

PubMed

De la Calle, J L; Mena, M A; González-Escalada, J R; Paíno, C L

2002-11-30

Intrathecal grafting of cells as biological pumps to deliver monoamines, endorphins, and/or trophic factors, has been shown to be effective in treating chronic pain both in experimental animals and in clinical trials. We have tested whether intrathecal implantation of neuroblastoma cells reduces heat hyperalgesia and cold allodynia in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Behavioral tests and cerebrospinal fluid (CSF) collection were performed before CCI, 1 week later (after which, vehicle or NB69 cells were intrathecally injected) and at 4, 7, and 14 days post-injection. Both CSF sampling and injection of the cells were performed by direct lumbar puncture. Intrathecal grafting of 4 x 10(6) NB69 neuroblastoma cells reduced to basal levels the nociceptive response to heat in nerve-injured hindpaws, while the response of control limbs remained unchanged. Similarly, the allodynic response to cold elicited by acetone evaporation decreased in the animals implanted with NB69 cells. An increase in the concentrations of dopamine and serotonin metabolites of around 150% was observed in the CSF of animals that received grafts of NB69 cells. These data suggest that the monoamines released by NB69 cells in the intrathecal space produce analgesia to neuropathic pain in rats. Copyright 2002 Elsevier Science Inc.

Evaluating ESA CCI Soil Moisture in East Africa

NASA Technical Reports Server (NTRS)

McNally, Amy; Shukla, Shraddhanand; Arsenault, Kristi R.; Wang, Shugong; Peters-Lidard, Christa D.; Verdin, James P.

2016-01-01

To assess growing season conditions where ground based observations are limited or unavailable, food security and agricultural drought monitoring analysts rely on publicly available remotely sensed rainfall and vegetation greenness. There are also remotely sensed soil moisture observations from missions like the European Space Agency (ESA) Soil Moisture and Ocean Salinity (SMOS) and NASAs Soil Moisture Active Passive (SMAP), however these time series are still too short to conduct studies that demonstrate the utility of these data for operational applications, or to provide historical context for extreme wet or dry events. To promote the use of remotely sensed soil moisture in agricultural drought and food security monitoring, we use East Africa as a case study to evaluate the quality of a 30+ year time series of merged active-passive microwave soil moisture from the ESA Climate Change Initiative (CCI-SM). Compared to the Normalized Difference Vegetation index (NDVI) and modeled soil moisture products, we found substantial spatial and temporal gaps in the early part of the CCI-SM record, with adequate data coverage beginning in 1992. From this point forward, growing season CCI-SM anomalies were well correlated (R greater than 0.5) with modeled, seasonal soil moisture, and in some regions, NDVI. We use correlation analysis and qualitative comparisons at seasonal time scales to show that remotely sensed soil moisture can add information to a convergence of evidence framework that traditionally relies on rainfall and NDVI in moderately vegetated regions.

Charlson comorbidity index as a predictor of periodontal disease in elderly participants

PubMed Central

2018-01-01

Purpose This study investigated the validity of the Charlson comorbidity index (CCI) as a predictor of periodontal disease (PD) over a 12-year period. Methods Nationwide representative samples of 149,785 adults aged ≥60 years with PD (International Classification of Disease, 10th revision [ICD-10], K052–K056) were derived from the National Health Insurance Service-Elderly Cohort during 2002–2013. The degree of comorbidity was measured using the CCI (grade 0–6), including 17 diseases weighted on the basis of their association with mortality, and data were analyzed using multivariate Cox proportional-hazards regression in order to investigate the associations of comorbid diseases (CDs) with PD. Results The multivariate Cox regression analysis with adjustment for sociodemographic factors (sex, age, household income, insurance status, residence area, and health status) and CDs (acute myocardial infarction, congestive heart failure, peripheral vascular disease, cerebral vascular accident, dementia, pulmonary disease, connective tissue disorders, peptic ulcer, liver disease, diabetes, diabetes complications, paraplegia, renal disease, cancer, metastatic cancer, severe liver disease, and human immunodeficiency virus [HIV]) showed that the CCI in elderly comorbid participants was significantly and positively correlated with the presence of PD (grade 1: hazard ratio [HR], 1.11; P<0.001; grade ≥2: HR, 1.12, P<0.001). Conclusions We demonstrated that a higher CCI was a significant predictor of greater risk for PD in the South Korean elderly population. PMID:29770238

Molecular Hydrogen in Drinking Water Protects against Neurodegenerative Changes Induced by Traumatic Brain Injury

PubMed Central

Dohi, Kenji; Kraemer, Brian C.; Erickson, Michelle A.; McMillan, Pamela J.; Kovac, Andrej; Flachbartova, Zuzana; Hansen, Kim M.; Shah, Gul N.; Sheibani, Nader; Salameh, Therese; Banks, William A.

2014-01-01

Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1–40 or 1–42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI. PMID:25251220

The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival, cytogenetic and molecular responses in chronic myeloid leukaemia patients.

PubMed

Kurtovic-Kozaric, Amina; Hasic, Azra; Radich, Jerald P; Bijedic, Vildan; Nefic, Hilada; Eminovic, Izet; Kurtovic, Sabira; Colakovic, Ferida; Kozaric, Mirza; Vranic, Semir; Bovan, Nada S

2016-02-01

Cancer patients in developing and low-income countries have limited access to target therapies. For example, tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia patients (CML) is often delayed. In Bosnia, 16% of patients received immediate TKI treatment (<3 months of diagnosis), while 66% of patients received therapy after a median 14-month wait period. To assess the effect of delayed treatment on outcome, three patient groups were studied according to the time they received TKI treatment (0-5 months, 6-12 months and >13 months delay). The primary endpoints were complete cytogenetic (CCyR) and major molecular response (MMR) at 12 months. At 12 months of therapy, CCyR and MMR rates on imatinib decreased significantly: CCyR was achieved in 67% of patients in the immediate imatinib treatment group, 18% of patients in 6-12 months group and 15% of patients in >13 months wait group. MMR rates at 12 months occurred in 10% of patients with immediate treatment, 6% of those in 6-12 months group and 0% of patients in >13 months wait group. However, CCyR and MMR rates in patients on nilotinib were not associated with duration of treatment delay. Our data suggests that the deleterious effect of a prolonged TKI therapy delay may be ameliorated by the more active TKI nilotinib. © 2015 John Wiley & Sons Ltd.

A BEHAVIORAL AND HISTOLOGICAL COMPARISON OF FLUID PERCUSSION INJURY AND CONTROLLED CORTICAL IMPACT INJURY TO THE RAT SENSORIMOTOR CORTEX

PubMed Central

Peterson, Todd C.; Maass, William R.; Anderson, Jordan R.; Anderson, Gail D.; Hoane, Michael R.

2015-01-01

Our primary goal was to evaluate the behavioral and histological outcome of fluid percussion injury (FPI) and cortical contusion injury (CCI) to the sensorimotor cortex (SMC). The SMC has been used to evaluate neuroplasticity following CCI, but has not been extensively examined with FPI. In both the CCI and FPI models, a mechanical force of 4 mm in diameter was applied over the SMC, allowing for a direct comparison to measure the relative rates of histology and recovery of function in these models. Gross behavioral deficits were found on the sensory task (tactile adhesive removal task) and multiple motor assessments (forelimb asymmetry task, forelimb placing task, and rotorod). These sensorimotor deficits occurred in the absence of cognitive deficits in the water maze. The CCI model creates focal damage with a localized injury wheras the FPI model creates a more diffuse injury causing widespread damage. Both behavioral and histological deficits ensued following both models of injury to the SMC. The neuroplastic changes and ease at which damage to this area can be measured behaviorally make this an excellent location to assess traumatic brain injury (TBI) treatments. No injury model can completely mimic the full spectrum of human TBI and any potential treatments should be validated across both focal and diffuse injury models. Both of these injury models to the SMC produce severe and enduring behavioral deficits, which are ideal for evaluating treatment options. PMID:26275924

Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion

PubMed Central

Chen, Gang; Park, Chul-Kyu; Xie, Rou-Gang; Ji, Ru-Rong

2015-01-01

Neuropathic pain remains a pressing clinical problem. Here, we demonstrate that a local, intrathecal (i.t.) injection of bone marrow stromal cells (BMSCs) following lumbar puncture alleviates early- and late-phase neuropathic pain symptoms, such as allodynia and hyperalgesia, for several weeks in murine chronic constriction injury (CCI) and spared nerve injury models. Moreover, i.t. BMSCs reduced CCI-induced spontaneous pain and axonal injury of dorsal root ganglion (DRG) neurons and inhibited CCI-evoked neuroinflammation in DRGs and spinal cord tissues. BMSCs secreted TGF-β1 into the cerebrospinal fluid, and neutralization of TGF-β1, but not IL-10, reversed the analgesic effect of BMSCs. Conversely, i.t. administration of TGF-β1 potently inhibited neuropathic pain. TGF-β1 acted as a powerful neuromodulator and rapidly (within minutes) suppressed CCI-evoked spinal synaptic plasticity and DRG neuronal hyperexcitability via TGF-β receptor 1–mediated noncanonical signaling. Finally, nerve injury upregulated CXCL12 in lumbar L4–L6 DRGs, and this upregulation caused migration of i.t.-injected BMSCs to DRGs through the CXCL12 receptor CXCR4, which was expressed on BMSCs. BMSCs that migrated from the injection site survived at the border of DRGs for more than 2 months. Our findings support a paracrine mechanism by which i.t. BMSCs target CXCL12-producing DRGs to elicit neuroprotection and sustained neuropathic pain relief via TGF-β1 secretion. PMID:26168219

Protective actions of PJ34, a poly(ADP-ribose)polymerase inhibitor, on the blood-brain barrier after traumatic brain injury in mice.

PubMed

Tao, X; Chen, X; Hao, S; Hou, Z; Lu, T; Sun, M; Liu, B

2015-04-16

Poly(ADP-ribose) polymerase (PARP) is activated by oxidative stress and plays an important role in traumatic brain injury (TBI). The objective of this study was to investigate whether PARP activation participated in the blood-brain barrier (BBB) disruption and edema formation in a mouse model of controlled cortical impact (CCI). N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide (PJ34) (10 mg/kg), a selective PARP inhibitor, was administered intraperitoneally at 5 min and 8 h after experimental CCI. After 6 h and 24 h of CCI, the permeability of the cortical BBB was determined after Evans Blue administration. The water content of the brain was also measured. Treatment with PJ34 markedly attenuated the permeability of the BBB and decreased the brain edema at 6 h and 24 h after CCI. Our data showed the up-regulation of nuclear factor-κB in cytosolic fractions and nuclear fractions in the injured cortex, and these changes were reversed by PJ34. Moreover, PJ34 significantly lessened the activities of myeloperoxidase and the levels of matrix metalloproteinase-9, enhanced the levels of occludin, laminin, collagen IV and integrin β1, reduced neurological deficits, decreased the contusion volume, and attenuated the necrotic and apoptotic neuronal cell death. These data suggest the protective effects of PJ34 on BBB integrity and cell death during acute TBI. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Central glucocorticoid receptors regulate the upregulation of spinal cannabinoid-1 receptors after peripheral nerve injury in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Yang, Liling; Mao, Jianren

2007-09-01

Previous studies have shown that peripheral nerve injury upregulated both glucocorticoid receptors (GR) and cannabinoid-1 receptors (CB1R) within the spinal cord dorsal horn in rats. However, the relationship between the expression of spinal GR and CB1R after nerve injury remains unclear. Here, we examined the hypothesis that the upregulation of spinal CB1R induced by chronic constriction nerve injury (CCI) in rats would be regulated by spinal GR. CCI induced the upregulation of spinal CB1R primarily within the ipsilateral spinal cord dorsal horn as revealed by Western blot and immunohistochemistry. The expression of CB1R in CCI rats was substantially attenuated by intrathecal treatment with either the GR antagonist RU38486 or a GR antisense oligonucleotide given twice daily for postoperative day 1-6, whereas the expression of spinal CB1R was enhanced following intrathecal administration of a GR sense oligonucleotide twice daily for postoperative day 1-6. Furthermore, the upregulation of spinal CB1R after nerve injury was prevented in adrenalectomized rats, which was at least partially restored with the intrathecal administration of an exogenous GR agonist dexamethasone, indicating that corticosteroids (endogenous GR agonists) were critical to spinal GR actions. Since the development of neuropathic pain behaviors in CCI rats was attenuated by either RU38486 or a GR antisense oligonucleotide, these results suggest that CB1R is a downstream target for spinal GR actions contributory to the mechanisms of neuropathic pain.

Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury.

PubMed

Dohi, Kenji; Kraemer, Brian C; Erickson, Michelle A; McMillan, Pamela J; Kovac, Andrej; Flachbartova, Zuzana; Hansen, Kim M; Shah, Gul N; Sheibani, Nader; Salameh, Therese; Banks, William A

2014-01-01

Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1-40 or 1-42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.

A new phase in the production of quality-controlled sea level data

NASA Astrophysics Data System (ADS)

Quartly, Graham D.; Legeais, Jean-François; Ablain, Michaël; Zawadzki, Lionel; Joana Fernandes, M.; Rudenko, Sergei; Carrère, Loren; Nilo García, Pablo; Cipollini, Paolo; Andersen, Ole B.; Poisson, Jean-Christophe; Mbajon Njiche, Sabrina; Cazenave, Anny; Benveniste, Jérôme

2017-08-01

Sea level is an essential climate variable (ECV) that has a direct effect on many people through inundations of coastal areas, and it is also a clear indicator of climate changes due to external forcing factors and internal climate variability. Regional patterns of sea level change inform us on ocean circulation variations in response to natural climate modes such as El Niño and the Pacific Decadal Oscillation, and anthropogenic forcing. Comparing numerical climate models to a consistent set of observations enables us to assess the performance of these models and help us to understand and predict these phenomena, and thereby alleviate some of the environmental conditions associated with them. All such studies rely on the existence of long-term consistent high-accuracy datasets of sea level. The Climate Change Initiative (CCI) of the European Space Agency was established in 2010 to provide improved time series of some ECVs, including sea level, with the purpose of providing such data openly to all to enable the widest possible utilisation of such data. Now in its second phase, the Sea Level CCI project (SL_cci) merges data from nine different altimeter missions in a clear, consistent and well-documented manner, selecting the most appropriate satellite orbits and geophysical corrections in order to further reduce the error budget. This paper summarises the corrections required, the provenance of corrections and the evaluation of options that have been adopted for the recently released v2.0 dataset (https://doi.org/10.5270/esa-sea_level_cci-1993_2015-v_2.0-201612). This information enables scientists and other users to clearly understand which corrections have been applied and their effects on the sea level dataset. The overall result of these changes is that the rate of rise of global mean sea level (GMSL) still equates to ˜ 3.2 mm yr-1 during 1992-2015, but there is now greater confidence in this result as the errors associated with several of the corrections have been reduced. Compared with v1.1 of the SL_cci dataset, the new rate of change is 0.2 mm yr-1 less during 1993 to 2001 and 0.2 mm yr-1 higher during 2002 to 2014. Application of new correction models brought a reduction of altimeter crossover variances for most corrections.

Curcumin attenuates mechanical and thermal hyperalgesia in chronic constrictive injury model of neuropathic pain.

PubMed

Di, Yu Xiang; Hong, Cao; Jun, Li; Renshan, Ge; Qinquan, Lian

2014-06-01

The aim of this study was to observe the effect of stress caused by neuropathic pain on serum cortisol concentration and expression of 11β-hydroxysteroid dehydrogenase type I enzyme (11βHSD1) in spinal cord and dorsal root ganglions (DRG) and investigate the role and mechanism of curcumin in the neuropathic pain of stressful rats. Neuropathic pain is a prevalent disease that greatly impairs the patients' quality of life. A lack of the understanding of its etiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of curcumin and its effect on expression of 11β-hydroxysteroid dehydrogenase type I enzyme (11βHSD1) in spinal dorsal horn and DRG in chronic constriction injury (CCI) mode of neuropathic pain of rats. Seventy-two male Sprague-Dawley rats were randomized into four groups with 18 rats in each: sham operation group (Sham), chronic constrictive injury group (CCI), solvent contrast group (SC), and curcumin-treated group (Cur100). Curcumin, 100 mg/kg/day intraperitoneal, was given for 14 days starting from the first day after operation in the Cur100 group. Paw thermal withdrawal latency (PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured 2 days pre-operative, and 1, 3, 5, 7, 10, and 14 days post-operative. The animals were deeply anesthetized and blood was taken from the heart, the lumbar segment (L4, 5) of the spinal cord and DRG were dissected out and homogenized. The change of cortisol was measured by enzyme-linked immunosorbent assay and the change of 11βHSD1 expression was determined by immunochemistry and Western blot. Compared with sham group, PTWL and PMWT significantly decrease after operation in the CCI group; serum cortisol concentration was significantly increased and the expression of 11βHSD1 was significantly increased in the CCI group. Comparing with CCI group, the PMWT and PTWL were increased and the serum cortisol concentration was decreased and the expression of 11βHSD1 was inhibited in Cur100 group. Stress caused by neuropathic pain triggers release of cortisol to the blood and expression of 11βHSD1 would increase at the same time. Curcumin could alleviate thermal and mechanical hyperalgesia induced by CCI and inhibit the serum cortisol concentration and expression of 11βHSD1 in the spinal cord and DRG.

Altered Excitability and Local Connectivity of mPFC-PAG Neurons in a Mouse Model of Neuropathic Pain.

PubMed

Cheriyan, John; Sheets, Patrick L

2018-05-16

The medial prefrontal cortex (mPFC) plays a major role in both sensory and affective aspects of pain. There is extensive evidence that chronic pain produces functional changes within the mPFC. However, our understanding of local circuit changes to defined subpopulations of mPFC neurons in chronic pain models remains unclear. A major subpopulation of mPFC neurons project to the periaqueductal gray (PAG), which is a key midbrain structure involved in endogenous pain suppression and facilitation. Here, we used laser scanning photostimulation of caged glutamate to map cortical circuits of retrogradely labeled cortico-PAG (CP) neurons in layer 5 (L5) of mPFC in brain slices prepared from male mice having undergone chronic constriction injury (CCI) of the sciatic nerve. Whole-cell recordings revealed a significant reduction in excitability for L5 CP neurons contralateral to CCI in the prelimbic (PL), but not infralimbic (IL), region of mPFC. Circuit mapping showed that excitatory inputs to L5 CP neurons in both PL and IL arose primarily from layer 2/3 (L2/3) and were significantly reduced in CCI mice. Glutamate stimulation of L2/3 and L5 elicited inhibitory inputs to CP neurons in both PL and IL, but only L2/3 input was significantly reduced in CP neurons of CCI mice. We also observed significant reduction in excitability and L2/3 inhibitory input to CP neurons ipsilateral to CCI. These results demonstrating region and laminar specific changes to mPFC-PAG neurons suggest that a unilateral CCI bilaterally alters cortical circuits upstream of the endogenous analgesic network, which may contribute to persistence of chronic pain. SIGNIFICANCE STATEMENT Chronic pain is a significant unresolved medical problem that is refractory to traditional analgesics and can negatively affect emotional health. The role of central circuits in mediating the persistent nature of chronic pain remains unclear. Local circuits within the medial prefrontal cortex (mPFC) process ascending pain inputs and can modulate endogenous analgesia via direct projections to the periaqueductal gray (PAG). However, the mechanisms by which chronic pain alters intracortical circuitry of mPFC-PAG neurons are unknown. Here, we report specific changes to local circuits of mPFC-PAG neurons in mice displaying chronic pain behavior after nerve injury. These findings provide evidence for a neural mechanism by which chronic pain disrupts the descending analgesic system via functional changes to cortical circuits. Copyright © 2018 the authors 0270-6474/18/384829-11$15.00/0.

Doctor, where is my iris?

PubMed

Sophocleous, Sophocles

2016-05-05

Phacoemulsification cataract surgery with small clear corneal incision (CCI) is the standard of care for cataract treatment. Self-sealing, clear corneal wounds have been found to be stable and able to withstand high pressures. Nevertheless, there are a few cases published describing patients with previous cataract surgery and manually performed CCI who sustained blunt trauma with associated wound dehiscence, iris disinsertion and expulsion through the wound. The case described here demonstrates an eye that had traumatic aniridia post-blunt trauma, while the intraocular lens and the rest of the ocular structures remained intact. 2016 BMJ Publishing Group Ltd.

A COMBINED EFFECT OF DEXTROMETHORPHAN AND MELATONIN ON NEUROPATHIC PAIN BEHAVIOR IN RATS

PubMed Central

Wang, Shuxing; Zhang, Lin; Lim, Grewo; Sung, Backil; Tian, Yinghong; Chou, Chiu-Wen; Hernstadt, Hayley; Rusanescu, Gabriel; Ma, Yuxin; Mao, Jianren

2009-01-01

Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-D-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain. PMID:19595681

A combined effect of dextromethorphan and melatonin on neuropathic pain behavior in rats.

PubMed

Wang, Shuxing; Zhang, Lin; Lim, Grewo; Sung, Backil; Tian, Yinghong; Chou, Chiu-Wen; Hernstadt, Hayley; Rusanescu, Gabriel; Ma, Yuxin; Mao, Jianren

2009-09-08

Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-d-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain.

Antinociceptive effects of oxymatrine from Sophora flavescens, through regulation of NR2B-containing NMDA receptor-ERK/CREB signaling in a mice model of neuropathic pain.

PubMed

Wang, Haiyan; Li, Yuxiang; Dun, Linglu; Xu, Yaqiong; Jin, Shaojv; Du, Juan; Ma, Lin; Li, Juan; Zhou, Ru; He, Xiaoliang; Sun, Tao; Yu, Jianqiang

2013-08-15

In this study we investigated antinociceptive effects of oxymatrine through regulation of NR2B-containing NMDA receptor-ERK/CREB signaling in a chronic neuropathic pain model induced by chronic constrictive injury (CCI) of the sciatic nerve. The von Frey and plantar tests were performed to assess the degree of mechanical and thermal changes respectively. Immunohistochemistry assay was used to evaluate the expressions of NR2B. Western blotting assay were used to evaluate the expressions of NR2B, tERK, p-ERK, tCREB and p-CREB. The intraperitoneal administration of OMT (160, 80 mg/kg) could prevent the development of mechanical allodynia, thermal hyperalgesia induced by CCI. Intraperitoneal administration of OMT decreased the mean IOD of NR2B in the dorsal horn and expression of NR2B, p-ERK and p-CREB protein. Regulation of NMDA NR2B receptor-ERK/CREB signaling maybe the targets for the antinociceptive effects of OMT on a chronic neuropathic pain model induced by chronic constrictive injury of the sciatic nerve. Copyright © 2013 Elsevier GmbH. All rights reserved.

Applications of Known Quantitative Techniques for Developing Airborne ASW Crew Performance Criteria,

DTIC Science & Technology

1967-07-01

environmental foot tunnel enable’s accurate tests to be conducted under specifications, controlled conditions, MA Ch I N E ( ‘OMI ’l ’F t T ION SERVICES C...ph~- 51 olo gical nioni tur ing equ ip— cc i dt’ a r t e ’t~ cci C ~~ii ’ ri iue ’nt s can hi’ ~‘onc1ui-ted u ndc r V a t t e s t s nie ’ni ; I

Self-reported fatigue following intensive care of chronically critically ill patients: a prospective cohort study.

PubMed

Wintermann, Gloria-Beatrice; Rosendahl, Jenny; Weidner, Kerstin; Strauß, Bernhard; Hinz, Andreas; Petrowski, Katja

2018-01-01

Protracted treatment on intensive care unit (ICU) sets the patients at increased risk for the development of chronic critical illness (CCI). Muscular and cardio-respiratory deconditioning are common long-term sequelae, going along with a state of chronic fatigue. At present, findings regarding the frequency, long-term course, and associated factors of self-reported fatigue following ICU treatment of CCI patients are lacking. CCI patients with the diagnosis of critical illness polyneuropathy/myopathy (CIP/CIM) were assessed at three time points. Four weeks following the discharge from ICU at acute care hospital (t1), eligibility for study participation was asserted. Self-reported fatigue was measured using the Multidimensional Fatigue Inventory (MFI-20) via telephone contact at 3 (t2, n  = 113) and 6 months (t3, n  = 91) following discharge from ICU at acute care hospital. At both 3 and 6 months, nearly every second CCI patient showed clinically relevant fatigue symptoms (t2/t3: n  = 53/ n  = 51, point prevalence rates: 46.9%/45.1%). While total fatigue scores remained stable in the whole sample, female patients showed a decrease from 3 to 6 months. The presence of a coronary heart disease, the perceived fear of dying at acute care ICU, a diagnosis of major depression, and the perceived social support were confirmed as significant correlates of fatigue at 3 months. At 6 months, male gender, the number of medical comorbidities, a diagnosis of major depression, and a prior history of anxiety disorder could be identified. A negative impact of fatigue on the perceived health-related quality of life could be ascertained. Nearly every second CCI patient showed fatigue symptoms up to 6 months post-ICU. Patients at risk should be informed about fatigue, and appropriate treatment options should be offered to them. The present study was registered retrospectively at the German Clinical Trials Register (date of registration: 13th of December 2011; registration number: DRKS00003386). Date of enrolment of the first participant to the present trial: 09th of November 2011.

Accuracy assessment of seven global land cover datasets over China

NASA Astrophysics Data System (ADS)

Yang, Yongke; Xiao, Pengfeng; Feng, Xuezhi; Li, Haixing

2017-03-01

Land cover (LC) is the vital foundation to Earth science. Up to now, several global LC datasets have arisen with efforts of many scientific communities. To provide guidelines for data usage over China, nine LC maps from seven global LC datasets (IGBP DISCover, UMD, GLC, MCD12Q1, GLCNMO, CCI-LC, and GlobeLand30) were evaluated in this study. First, we compared their similarities and discrepancies in both area and spatial patterns, and analysed their inherent relations to data sources and classification schemes and methods. Next, five sets of validation sample units (VSUs) were collected to calculate their accuracy quantitatively. Further, we built a spatial analysis model and depicted their spatial variation in accuracy based on the five sets of VSUs. The results show that, there are evident discrepancies among these LC maps in both area and spatial patterns. For LC maps produced by different institutes, GLC 2000 and CCI-LC 2000 have the highest overall spatial agreement (53.8%). For LC maps produced by same institutes, overall spatial agreement of CCI-LC 2000 and 2010, and MCD12Q1 2001 and 2010 reach up to 99.8% and 73.2%, respectively; while more efforts are still needed if we hope to use these LC maps as time series data for model inputting, since both CCI-LC and MCD12Q1 fail to represent the rapid changing trend of several key LC classes in the early 21st century, in particular urban and built-up, snow and ice, water bodies, and permanent wetlands. With the highest spatial resolution, the overall accuracy of GlobeLand30 2010 is 82.39%. For the other six LC datasets with coarse resolution, CCI-LC 2010/2000 has the highest overall accuracy, and following are MCD12Q1 2010/2001, GLC 2000, GLCNMO 2008, IGBP DISCover, and UMD in turn. Beside that all maps exhibit high accuracy in homogeneous regions; local accuracies in other regions are quite different, particularly in Farming-Pastoral Zone of North China, mountains in Northeast China, and Southeast Hills. Special attention should be paid for data users who are interested in these regions.

Spinal sigma-1 receptor activation increases the production of D-serine in astrocytes which contributes to the development of mechanical allodynia in a mouse model of neuropathic pain.

PubMed

Moon, Ji-Young; Choi, Sheu-Ran; Roh, Dae-Hyun; Yoon, Seo-Yeon; Kwon, Soon-Gu; Choi, Hoon-Seong; Kang, Suk-Yun; Han, Ho-Jae; Kim, Hyun-Woo; Beitz, Alvin J; Oh, Seog-Bae; Lee, Jang-Hern

2015-10-01

We have previously demonstrated that activation of the spinal sigma-1 receptor (Sig-1R) plays an important role in the development of mechanical allodynia (MA) via secondary activation of the N-methyl-d-aspartate (NMDA) receptor. Sig-1Rs have been shown to localize to astrocytes, and blockade of Sig-1Rs inhibits the pathologic activation of astrocytes in neuropathic mice. However, the mechanism by which Sig-1R activation in astrocytes modulates NMDA receptors in neurons is currently unknown. d-serine, synthesized from l-serine by serine racemase (Srr) in astrocytes, is an endogenous co-agonist for the NMDA receptor glycine site and can control NMDA receptor activity. Here, we investigated the role of d-serine in the development of MA induced by spinal Sig-1R activation in chronic constriction injury (CCI) mice. The production of d-serine and Srr expression were both significantly increased in the spinal cord dorsal horn post-CCI surgery. Srr and d-serine were only localized to astrocytes in the superficial dorsal horn, while d-serine was also localized to neurons in the deep dorsal horn. Moreover, we found that Srr exists in astrocytes that express Sig-1Rs. The CCI-induced increase in the levels of d-serine and Srr was attenuated by sustained intrathecal treatment with the Sig-1R antagonist, BD-1047 during the induction phase of neuropathic pain. In behavioral experiments, degradation of endogenous d-serine with DAAO, or selective blockade of Srr by LSOS, effectively reduced the development of MA, but not thermal hyperalgesia in CCI mice. Finally, BD-1047 administration inhibited the development of MA and this inhibition was reversed by intrathecal treatment with exogenous d-serine. These findings demonstrate for the first time that the activation of Sig-1Rs increases the expression of Srr and d-serine in astrocytes. The increased production of d-serine induced by CCI ultimately affects dorsal horn neurons that are involved in the development of MA in neuropathic mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of the Prostaglandin E2 EP1 Receptor in Traumatic Brain Injury

PubMed Central

Glushakov, Alexander V.; Fazal, Jawad A.; Narumiya, Shuh; Doré, Sylvain

2014-01-01

Brain injuries promote upregulation of so-called proinflammatory prostaglandins, notably prostaglandin E2 (PGE2), leading to overactivation of a class of its cognate G-protein-coupled receptors, including EP1, which is considered a promising target for treatment of ischemic stroke. However, the role of the EP1 receptor is complex and depends on the type of brain injury. This study is focused on the investigation of the role of the EP1 receptor in a controlled cortical impact (CCI) model, a preclinical model of traumatic brain injury (TBI). The therapeutic effects of post-treatments with a widely studied EP1 receptor antagonist, SC-51089, were examined in wildtype and EP1 receptor knockout C57BL/6 mice. Neurological deficit scores (NDS) were assessed 24 and 48 h following CCI or sham surgery, and brain immunohistochemical pathology was assessed 48 h after surgery. In wildtype mice, CCI resulted in an obvious cortical lesion and localized hippocampal edema with an associated significant increase in NDS compared to sham-operated animals. Post-treatments with the selective EP1 receptor antagonist SC-51089 or genetic knockout of EP1 receptor had no significant effects on cortical lesions and hippocampal swelling or on the NDS 24 and 48 h after CCI. Immunohistochemistry studies revealed CCI-induced gliosis and microglial activation in selected ipsilateral brain regions that were not affected by SC-51089 or in the EP1 receptor-deleted mice. This study provides further clarification on the respective contribution of the EP1 receptor in TBI and suggests that, under this experimental paradigm, the EP1 receptor would have limited effects in modulating acute neurological and anatomical pathologies following contusive brain trauma. Findings from this protocol, in combination with previous studies demonstrating differential roles of EP1 receptor in ischemic, neurotoxic, and hemorrhagic conditions, provide scientific background and further clarification of potential therapeutic application of prospective prostaglandin G-protein-coupled receptor drugs in the clinic for treatment of TBI and other acute brain injuries. PMID:25426930

The Assessment of Atmospheric Correction Processors for MERIS Based on In-Situ Measurements-Updates in OC-CCI Round Robin

NASA Astrophysics Data System (ADS)

Muller, Dagmar; Krasemann, Hajo; Zuhilke, Marco; Doerffer, Roland; Brockmann, Carsten; Steinmetz, Francois; Valente, Andre; Brotas, Vanda; Grant, kMicheal G.; Sathyendranath, Shubha; Melin, Frederic; Franz, Bryan A.; Mazeran, Constant; Regner, Peter

2016-08-01

The Ocean Colour Climate Change Initiative (OC- CCI) provides a long-term time series of ocean colour data and investigates the detectable climate impact. A reliable and stable atmospheric correction (AC) procedure is the basis for ocean colour products of the necessary high quality.The selection of atmospheric correction processors is repeated regularly based on a round robin exercise, at the latest when a revised production and release of the OC-CCI merged product is scheduled. Most of the AC processors are under constant development and changes are implemented to improve the quality of satellite-derived retrievals of remote sensing reflectances. The changes between versions of the inter-comparison are not restricted to the implementation of AC processors. There are activities to improve the quality flagging for some processors, and the system vicarious calibration for AC algorithms in their sensor specific behaviour are widely studied. Each inter-comparison starts with an updated in-situ database, as more spectra are included in order to broaden the temporal and spatial range of satellite match-ups. While the OC-CCI's focus has laid on case-1 waters in the past, it has expanded to the retrieval of case-2 products now. In light of this goal, new bidirectional correction procedures (normalisation) for the remote sensing spectra have been introduced. As in-situ measurements are not always available at the satellite sensor specific central wave- lengths, a band-shift algorithm has to be applied to the dataset.In order to guarantee an objective selection from a set of four atmospheric correction processors, the common validation strategy of comparisons between in-situ and satellite-derived water leaving reflectance spectra, is aided by a ranking system. In principal, the statistical parameters are transformed into relative scores, which evaluate the relationship of quality dependent on the algorithms under study. The sensitivity of these scores to the selected database has been assessed by a bootstrapping exercise, which allows identification of the uncertainty in the scoring results.A comparison of round robin results for the OC-CCI version 2 and the current version 3 is presented and some major changes are highlighted.

The effect of exercise frequency on neuropathic pain and pain-related cellular reactions in the spinal cord and midbrain in a rat sciatic nerve injury model

PubMed Central

Sumizono, Megumi; Otsuka, Shotaro; Terashi, Takuto; Nakanishi, Kazuki; Ueda, Koki; Takada, Seiya; Kikuchi, Kiyoshi

2018-01-01

Background Exercise regimens are established methods that can relieve neuropathic pain. However, the relationship between frequency and intensity of exercise and multiple cellular responses of exercise-induced alleviation of neuropathic pain is still unclear. We examined the influence of exercise frequency on neuropathic pain and the intracellular responses in a sciatic nerve chronic constriction injury (CCI) model. Materials and methods Rats were assigned to four groups as follows: CCI and high-frequency exercise (HFE group), CCI and low-frequency exercise (LFE group), CCI and no exercise (No-Ex group), and naive animals (control group). Rats ran on a treadmill, at a speed of 20 m/min, for 30 min, for 5 (HFE) or 3 (LFE) days a week, for a total of 5 weeks. The 50% withdrawal threshold was evaluated for mechanical sensitivity. The activation of glial cells (microglia and astrocytes), expression of brain-derived neurotrophic factor (BDNF) and μ-opioid receptor in the spinal dorsal horn and endogenous opioid in the midbrain were examined using immunohistochemistry. Opioid receptor antagonists (naloxone) were administered using intraperitoneal injection. Results The development of neuropathic pain was related to the activation of glial cells, increased BDNF expression, and downregulation of the μ-opioid receptor in the ipsilateral spinal dorsal horn. In the No-Ex group, neuropathic pain showed the highest level of mechanical hypersensitivity at 2 weeks, which improved slightly until 5 weeks after CCI. In both exercise groups, the alleviation of neuropathic pain was accelerated through the regulation of glial activation, BDNF expression, and the endogenous opioid system. The expression of BDNF and endogenous opioid in relation to exercise-induced alleviation of neuropathic pain differed in the HFE and LFE groups. The effects of exercise-induced alleviation of mechanical hypersensitivity were reversed by the administration of naloxone. Conclusion The LFE and HFE program reduced neuropathic pain. Our findings indicated that aerobic exercise-induced alleviated neuropathic pain through the regulation of glial cell activation, expression of BDNF in the ipsilateral spinal dorsal horn, and the endogenous opioid system. PMID:29445295

Comparison of "Nil by Mouth" Versus Early Oral Intake in Three Different Diet Regimens Following Esophagectomy.

PubMed

Eberhard, Kristine Elisabeth; Achiam, Michael Patrick; Rolff, Hans Christian; Belmouhand, Mohamed; Svendsen, Lars Bo; Thorsteinsson, Morten

2017-06-01

The literature on oral intake after esophagectomy and its influence on anastomotic leakage and complications is sparse. This retrospective study included 359 patients undergoing esophagectomy between January 2011 and August 2015. Three oral intake protocols were evaluated: regimen 1, nil by mouth until postoperative day (POD) 7 followed by a normal diet; regimen 2, oral intake of clear fluids from POD 1 followed by a normal diet; regimen 3, nil by mouth until POD 7 followed by a slow increase to a blended diet. The outcome endpoints were: (1) anastomotic leakage, (2) complications [severity and number described using the Dindo-Clavien Classification and Comprehensive Complication Index (CCI)] and (3) length of stay. A multivariate logistic regression model was obtained for CCI and anastomotic leakage using Wald's stepwise selection. CCI was significantly lower in regimen 3 (16 vs. 22 and 26 in regimen 1 and 2, p = 0.027). Additionally, significantly fewer patients in regimen 3 suffered from severe complications of Dindo-Clavien grade IIIb-IV (p = 0.025). The incidence of anastomotic leakage reached its lowest in regimen 3, 2%, compared to 7-9%. Multivariate analyses revealed that high American Society of Anesthesiologist score was a predicting factor for both CCI and anastomotic leakage. The study indicates that nil by mouth until postoperative day 7 followed by a slow increase to a blended diet after esophagectomy results in less severe complications and a tendency of fewer anastomotic leakages. Multiple comorbidities proved to be an important predictive factor of the postoperative course.

Craniofacial reconstruction with poly(methyl methacrylate) customized cranial implants.

PubMed

Huang, Gary J; Zhong, Susan; Susarla, Srinivas M; Swanson, Edward W; Huang, Judy; Gordon, Chad R

2015-01-01

Secondary cranioplasty with customized craniofacial implants (CCIs) are often used to restore cerebral protection and reverse syndromes of the trephined, and for reconstruction of acquired cranial deformities. The 2 most widely used implant materials are polyetheretherketone and poly(methylmethacrylate) (PMMA). Previous series with CCIs report several major complications, including implant infection leading to removal, extended hospital stays, and surgical revisions. With this in mind, we chose to review our large case series of 22 consecutive PMMA CCI cranioplasties treated by a single craniofacial surgeon. A cohort of 20 consecutive patients receiving 22 PMMA implants during a 2-year period was identified and outcomes reviewed. The mechanism of initial insult, time from craniectomy to cranioplasty, anesthesia time, major and minor postoperative complications, radiation history, and length of follow-up were statistically analyzed. There were no complications related to infection, hematoma/seroma, or cerebrospinal fluid leak (0/22, 0%). Two patients experienced major complications related to persistent temporal hollowing (PTH) following standard CCI cranioplasty, which required revision surgery with modified implants (2/22, 9%). One minor complication of self-resolving transient diplopia was noted (1/22, 5%). In this consecutive series, PMMA CCIs were associated with a very low complication rate, suggesting that PMMA may be a preferred material for CCI fabrication. However, with 10% (2/20) of patients experiencing PTH and dissatisfaction related to asymmetry, future research must be directed at modifying CCI shape, to address the overlying soft-tissue deformity. If successful, this may increase patient satisfaction, prevent PTH, and avoid additional costs of revision surgery.

Incision integrity and postoperative outcomes after microcoaxial phacoemulsification performed using 2 incision-dependent systems.

PubMed

Vasavada, Vaishali; Vasavada, Abhay R; Vasavada, Viraj A; Srivastava, Samaresh; Gajjar, Devarshi U; Mehta, Siddharth

2013-04-01

To compare incision integrity and clinical outcomes of 2 microcoaxial phacoemulsification systems. Iladevi Cataract & IOL Research Centre, Ahmedabad, India. Prospective randomized clinical trial. Eyes were randomized to have phacoemulsification using a 1.8 mm clear corneal incision (CCI) system (Group 1, Stellaris system) or a 2.2 mm CCI system (Group 2, Intrepid Infiniti system). Incision enlargement at end of surgery was measured. At the conclusion of surgery, trypan blue was applied over the conjunctival surface, anterior chamber aspirate withdrawn, and ingress into anterior chamber measured. Postoperative observations included evaluation of the CCI using anterior segment optical coherence tomography (AS-OCT), change in central corneal thickness (CCT), and anterior segment inflammation at 1 day, 1 week, and 1 month and endothelial cell loss and surgically induced astigmatism (SIA) at 3 months. Incision enlargement (P<.001) and trypan blue ingress in the anterior chamber (mean 1.7 log units ± 0.6 [SD] versus 3.8 ± 0.6 log units, P<.001) was significantly greater in Group 1 (n = 50) than in Group 2 (n = 50). On AS-OCT, endothelial misalignment and gaping were more frequent in Group 1 at 1 day (P=.001) and 1 week (P=.018). There were no significant differences in SIA, change in CCT, endothelial cell loss, or anterior segment inflammation (P>.05). At the end of surgery, it is not the initial incision size alone but also the distortion of the incision during subsequent stages of surgery that determine the integrity of the CCI. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Merged SAGE II, Ozone_cci and OMPS ozone profiles dataset and evaluation of ozone trends in the stratosphere

NASA Astrophysics Data System (ADS)

Tamminen, J.; Sofieva, V.; Kyrölä, E.; Laine, M.; Degenstein, D. A.; Bourassa, A. E.; Roth, C.; Zawada, D.; Weber, M.; Rozanov, A.; Rahpoe, N.; Stiller, G. P.; Laeng, A.; von Clarmann, T.; Walker, K. A.; Sheese, P.; Hubert, D.; Van Roozendael, M.; Zehner, C.; Damadeo, R. P.; Zawodny, J. M.; Kramarova, N. A.; Bhartia, P. K.

2017-12-01

We present a merged dataset of ozone profiles from several satellite instruments: SAGE II on ERBS, GOMOS, SCIAMACHY and MIPAS on Envisat, OSIRIS on Odin, ACE-FTS on SCISAT, and OMPS on Suomi-NPP. The merged dataset is created in the framework of European Space Agency Climate Change Initiative (Ozone_cci) with the aim of analyzing stratospheric ozone trends. For the merged dataset, we used the latest versions of the original ozone datasets. The datasets from the individual instruments have been extensively validated and inter-compared; only those datasets, which are in good agreement and do not exhibit significant drifts with respect to collocated ground-based observations and with respect to each other, are used for merging. The long-term SAGE-CCI-OMPS dataset is created by computation and merging of deseasonalized anomalies from individual instruments. The merged SAGE-CCI-OMPS dataset consists of deseasonalized anomalies of ozone in 10° latitude bands from 90°S to 90°N and from 10 to 50 km in steps of 1 km covering the period from October 1984 to July 2016. This newly created dataset is used for evaluating ozone trends in the stratosphere through multiple linear regression. Negative ozone trends in the upper stratosphere are observed before 1997 and positive trends are found after 1997. The upper stratospheric trends are statistically significant at mid-latitudes in the upper stratosphere and indicate ozone recovery, as expected from the decrease of stratospheric halogens that started in the middle of the 1990s.

Prioritizing Clinician Wellbeing: The University of Virginia's Compassionate Care Initiative

PubMed Central

Fontaine, Dorrie

2015-01-01

Background: Working in healthcare is increasingly challenging for nurses, physicians, and other health professionals. Ongoing high stress takes a toll on clinicians and interferes with the quality of their patient care. Fostering clinician wellbeing needs to be a priority; if not, the human and financial consequences are significant. Objective: To describe the University of Virginia (UVA) School of Nursing's Compassionate Care Initiative (CCI) as an example of an organizational case study that is engaged in multipronged efforts to cultivate a resilient healthcare workforce committed to high-quality, compassionate, relationship-based care. Methods: This case report describes the development, implementation, and evaluation of the CCI at UVA. Various elements of the program are reviewed, which include harnessing talents and interests of the larger institution in the establishment of Compassionate Care Ambassadors, outreach to the community, innovative student-specific educational activities, and a national media program. Conclusion: The UVA CCI is a successful model of an organizational effort to promote clinician wellbeing and resilience. Aspects from this program can be adapted to other organizations that are committed to addressing this critical issue in US healthcare today. PMID:26421230

Maternal separation as a risk factor for aggravation of neuropathic pain in later life in mice.

PubMed

Mizoguchi, Hiroyuki; Fukumoto, Kazuya; Sakamoto, Gaku; Jin, Shijie; Toyama, Asako; Wang, Tian; Suzumura, Akio; Sato, Jun

2018-06-20

Psychological stresses such as social loss and separation during childhood induce hardship, referred to as emotional pain. These experiences are well-documented risk factors for the development of physical pain in adulthood. However, the underlying neuronal mechanisms of this exacerbation of pain are largely unknown, and consequently there is no effective pharmacotherapy. In this study, we sought to determine whether infant maternal separation (MS) contributes to aggravation of neuropathic pain in adult mice. MS increased anxiety- and depression-like behavioral responses to adult stress. In MS animals, chronic constriction injury (CCI) heightened the sensory dimension of chronic pain relative to that of control mice. However, MS mice treated with fluoxetine for 4 weeks after MS did not exhibit augmentation of allodynia, and their emotional response was attenuated. Microglia were more abundant in the spinal cord in MS/CCI mice than in control/CCI mice. These results suggest that emotional impairment is related to augmentation of neuropathic pain, and that dysfunction of microglial activation contributes to heightened pain sensitivity. Copyright © 2018. Published by Elsevier B.V.

Increased pain and neurogenic inflammation in mice deficient of neutral endopeptidase.

PubMed

Krämer, Heidrun H; He, Lan; Lu, Bao; Birklein, Frank; Sommer, Claudia

2009-08-01

The complex regional pain syndrome (CRPS) is characterized by enhanced neurogenic inflammation, mediated by neuropeptides. Neutral endopeptidase (NEP) is a key enzyme in neuropeptide catabolism. We used NEP knock out (ko) mice to investigate whether NEP deficiency leads to increased pain behavior and signs of neurogenic inflammation after soft tissue trauma with and without nerve injury. After chronic constriction injury (CCI) of the right sciatic nerve, NEP ko mice were more sensitive to heat, to mechanical stimuli, and to cold than wild type mice. Tissue injury without nerve injury produced no differences between genotypes. After CCI, NEP ko mice showed increased hind paw edema but lower skin temperatures than wild type mice. Substance P (SP) and endothelin 1 (ET 1) determined by enzyme immuno assay (EIA) were increased in sciatic nerves from NEP ko mice after CCI. Tissue CGRP content did not differ between the genotypes. The results provide evidence that pain behavior and neurogenic inflammation are enhanced in NEP ko mice after nerve injury. These findings resemble human 'cold' CRPS and suggest that ET 1 plays an important role in the pathogenesis of CRPS with nerve injury.

a Comparative Analysis of Five Cropland Datasets in Africa

NASA Astrophysics Data System (ADS)

Wei, Y.; Lu, M.; Wu, W.

2018-04-01

The food security, particularly in Africa, is a challenge to be resolved. The cropland area and spatial distribution obtained from remote sensing imagery are vital information. In this paper, according to cropland area and spatial location, we compare five global cropland datasets including CCI Land Cover, GlobCover, MODIS Collection 5, GlobeLand30 and Unified Cropland in circa 2010 of Africa in terms of cropland area and spatial location. The accuracy of cropland area calculated from five datasets was analyzed compared with statistic data. Based on validation samples, the accuracies of spatial location for the five cropland products were assessed by error matrix. The results show that GlobeLand30 has the best fitness with the statistics, followed by MODIS Collection 5 and Unified Cropland, GlobCover and CCI Land Cover have the lower accuracies. For the accuracy of spatial location of cropland, GlobeLand30 reaches the highest accuracy, followed by Unified Cropland, MODIS Collection 5 and GlobCover, CCI Land Cover has the lowest accuracy. The spatial location accuracy of five datasets in the Csa with suitable farming condition is generally higher than in the Bsk.

Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain

PubMed Central

Kostich, Walter; Hamman, Brian D.; Li, Yu-Wen; Naidu, Sreenivasulu; Dandapani, Kumaran; Feng, Jianlin; Easton, Amy; Bourin, Clotilde; Baker, Kevin; Allen, Jason; Savelieva, Katerina; Louis, Justin V.; Dokania, Manoj; Elavazhagan, Saravanan; Vattikundala, Pradeep; Sharma, Vivek; Das, Manish Lal; Shankar, Ganesh; Kumar, Anoop; Holenarsipur, Vinay K.; Gulianello, Michael; Molski, Ted; Brown, Jeffrey M.; Lewis, Martin; Huang, Yanling; Lu, Yifeng; Pieschl, Rick; O’Malley, Kevin; Lippy, Jonathan; Nouraldeen, Amr; Lanthorn, Thomas H.; Ye, Guilan; Wilson, Alan; Balakrishnan, Anand; Denton, Rex; Grace, James E.; Lentz, Kimberley A.; Santone, Kenneth S.; Bi, Yingzhi; Main, Alan; Swaffield, Jon; Carson, Ken; Mandlekar, Sandhya; Vikramadithyan, Reeba K.; Nara, Susheel J.; Dzierba, Carolyn; Bronson, Joanne; Macor, John E.; Zaczek, Robert; Westphal, Ryan; Kiss, Laszlo; Bristow, Linda; Conway, Charles M.

2016-01-01

To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy. Using a nonbrain-penetrant AAK1 inhibitor and local administration of an AAK1 inhibitor, the relevant pool of AAK1 for antineuropathic action was found to be in the spinal cord. Consistent with these results, AAK1 inhibitors dose-dependently reduced the increased spontaneous neural activity in the spinal cord caused by CCI and blocked the development of windup induced by repeated electrical stimulation of the paw. The mechanism of AAK1 antinociception was further investigated with inhibitors of α2 adrenergic and opioid receptors. These studies showed that α2 adrenergic receptor inhibitors, but not opioid receptor inhibitors, not only prevented AAK1 inhibitor antineuropathic action in behavioral assays, but also blocked the AAK1 inhibitor–induced reduction in spinal neural activity in the rat CCI model. Hence, AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to α2 adrenergic signaling, a pathway known to be antinociceptive in humans. PMID:27411717

Aerosol Climate Time Series in ESA Aerosol_cci

NASA Astrophysics Data System (ADS)

Popp, Thomas; de Leeuw, Gerrit; Pinnock, Simon

2016-04-01

Within the ESA Climate Change Initiative (CCI) Aerosol_cci (2010 - 2017) conducts intensive work to improve algorithms for the retrieval of aerosol information from European sensors. Meanwhile, full mission time series of 2 GCOS-required aerosol parameters are completely validated and released: Aerosol Optical Depth (AOD) from dual view ATSR-2 / AATSR radiometers (3 algorithms, 1995 - 2012), and stratospheric extinction profiles from star occultation GOMOS spectrometer (2002 - 2012). Additionally, a 35-year multi-sensor time series of the qualitative Absorbing Aerosol Index (AAI) together with sensitivity information and an AAI model simulator is available. Complementary aerosol properties requested by GCOS are in a "round robin" phase, where various algorithms are inter-compared: fine mode AOD, mineral dust AOD (from the thermal IASI spectrometer, but also from ATSR instruments and the POLDER sensor), absorption information and aerosol layer height. As a quasi-reference for validation in few selected regions with sparse ground-based observations the multi-pixel GRASP algorithm for the POLDER instrument is used. Validation of first dataset versions (vs. AERONET, MAN) and inter-comparison to other satellite datasets (MODIS, MISR, SeaWIFS) proved the high quality of the available datasets comparable to other satellite retrievals and revealed needs for algorithm improvement (for example for higher AOD values) which were taken into account for a reprocessing. The datasets contain pixel level uncertainty estimates which were also validated and improved in the reprocessing. For the three ATSR algorithms the use of an ensemble method was tested. The paper will summarize and discuss the status of dataset reprocessing and validation. The focus will be on the ATSR, GOMOS and IASI datasets. Pixel level uncertainties validation will be summarized and discussed including unknown components and their potential usefulness and limitations. Opportunities for time series extension with successor instruments of the Sentinel family will be described and the complementarity of the different satellite aerosol products (e.g. dust vs. total AOD, ensembles from different algorithms for the same sensor) will be discussed.

Physician's first clinical impression of emergency department patients with nonspecific complaints is associated with morbidity and mortality.

PubMed

Beglinger, Bettina; Rohacek, Martin; Ackermann, Selina; Hertwig, Ralph; Karakoumis-Ilsemann, Julia; Boutellier, Susanne; Geigy, Nicolas; Nickel, Christian; Bingisser, Roland

2015-02-01

The association between the physician's first clinical impression of a patient with nonspecific complaints and morbidity and mortality is unknown. The aim was to evaluate the association of the physician's first clinical impression with acute morbidity and mortality. We conducted a prospective observational study with a 30-day follow-up. This study was performed at the emergency departments (EDs) of 1 secondary and 1 tertiary care hospital, from May 2007 to February 2011. The first clinical impression ("looking ill"), expressed on a numerical rating scale from 0 to 100, age, sex, and the Charlson Comorbidity Index (CCI) were evaluated. The association was determined between these variables and acute morbidity and mortality, together with receiver operating characteristics, and validity. Of 217,699 presentations to the ED, a total of 1278 adult nontrauma patients with nonspecific complaints were enrolled by a study team. No patient was lost to follow-up. A total of 84 (6.6%) patients died during follow-up, and 742 (58.0%) patients were classified as suffering from acute morbidity. The variable "looking ill" was significantly associated with mortality and morbidity (per 10 point increase, odds ratio 1.23, 95% confidence interval [CI] 1.12-1.34, P < 0.001, and odds ratio 1.19, 95% CI 1.14-1.24, P < 0.001, respectively). The combination of the variables "looking ill," "age," "male sex," and "CCI" resulted in the best prediction of these outcomes (mortality: area under the curve [AUC] 0.77, 95% CI 0.72-0.82; morbidity: AUC 0.68, 95% CI 0.65-0.71). The physician's first impression, with or without additional variables such as age, male sex, and CCI, was associated with morbidity and mortality. This might help in the decision to perform further diagnostic tests and to hospitalize ED patients.

Coronary calcium visualization using dual energy chest radiography with sliding organ registration

NASA Astrophysics Data System (ADS)

Wen, Di; Nye, Katelyn; Zhou, Bo; Gilkeson, Robert C.; Wilson, David L.

2016-03-01

Coronary artery calcification (CAC) is the lead biomarker for atherosclerotic heart disease. We are developing a new technique to image CAC using ubiquitously ordered, low cost, low radiation dual energy (DE) chest radiography (using the two-shot GE Revolution XRd system). In this paper, we proposed a novel image processing method (CorCalDx) based on sliding organ registration to create a bone-image-like, coronary calcium image (CCI) that significantly reduces motion artifacts and improves CAC conspicuity. Experiments on images of a physical dynamic cardiac phantom showed that CorCalDx reduced 73% of the motion artifact area as compared to standard DE over a range of heart rates up to 90 bpm and varying x-ray radiation exposures. Residual motion artifact in the phantom CCI is greatly suppressed in gray level and area (0.88% of the heart area). In a Functional Measurement Test (FMT) with 20 clinical exams, image quality improvement of CorCalDx against standard DE (measured from -10 to +10) was significantly suggested (p<0.0001) by three radiologists for cardiac motion artifacts (7.2+/-2.1) and cardiac anatomy visibility (6.1+/-3.5). CorCalDx was always chosen best in every image tested. In preliminary assessments of 12 patients with 18 calcifications, 90% of motion artifact regions in standard DE results were removed in CorCalDx results, with 100% sensitivity of calcification detection, showing great potential of CorCalDx to improve CAC detection and grading in DE chest radiography.

Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study.

PubMed

Bhanpuri, Nasir H; Hallberg, Sarah J; Williams, Paul T; McKenzie, Amy L; Ballard, Kevin D; Campbell, Wayne W; McCarter, James P; Phinney, Stephen D; Volek, Jeff S

2018-05-01

Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort. We investigated CVD risk factors in patients with T2D who participated in a 1 year open label, non-randomized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined. A significance level of P < 0.0019 ensured two-tailed significance at the 5% level when Bonferroni adjusted for multiple comparisons. The CCI group consisted of 262 participants (baseline mean (SD): age 54 (8) year, BMI 40.4 (8.8) kg m -2 ). Intention-to-treat analysis (% change) revealed the following at 1-year: total LDL-particles (LDL-P) (- 4.9%, P = 0.02), small LDL-P (- 20.8%, P = 1.2 × 10 -12 ), LDL-P size (+ 1.1%, P = 6.0 × 10 -10 ), ApoB (- 1.6%, P = 0.37), ApoA1 (+ 9.8%, P < 10 -16 ), ApoB/ApoA1 ratio (- 9.5%, P = 1.9 × 10 -7 ), triglyceride/HDL-C ratio (- 29.1%, P < 10 -16 ), large VLDL-P (- 38.9%, P = 4.2 × 10 -15 ), and LDL-C (+ 9.9%, P = 4.9 × 10 -5 ). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P < 1 × 10 -7 ) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased - 11.9% (P = 4.9 × 10 -5 ). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P = 5.3 × 10 -5 ). The UC group of 87 participants [baseline mean (SD): age 52 (10) year, BMI 36.7 (7.2) kg m -2 ] showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hsCRP, and LP-IR score in addition to other biomarkers that were previously reported. The CCI group showed a greater rise in LDL-C. A continuous care treatment including nutritional ketosis in patients with T2D improved most biomarkers of CVD risk after 1 year. The increase in LDL-cholesterol appeared limited to the large LDL subfraction. LDL particle size increased, total LDL-P and ApoB were unchanged, and inflammation and blood pressure decreased. Trial registration Clinicaltrials.gov: NCT02519309. Registered 10 August 2015.

Effect of steepest-meridian clear corneal incision for reducing preexisting corneal astigmatism using a meridian-marking method or surgeon's intuition.

PubMed

Hayashi, Ken; Yoshida, Motoaki; Yoshimura, Koichi

2014-12-01

To compare the effect of steepest-meridian clear corneal incisions (CCIs) for reducing preexisting corneal astigmatism between a meridian-marking method and a surgeon's-intuition method. Hayashi Eye Hospital, Fukuoka, Japan. Randomized controlled trials. Eyes scheduled for phacoemulsification were randomized to 1 of 2 groups: a 2.65 mm steepest-meridian CCI using the meridian-marking method or a 2.65 mm steepest-meridian CCI using the surgeon's intuition. Regular and irregular corneal astigmatism, surgically induced astigmatism (SIA) vector, refractive status, higher-order aberrations (HOAs), uncorrected (UDVA) and corrected (CDVA) distance visual acuities, and physical meridian misalignment of the steepest-meridian CCI measured using anterior segment optical coherence tomography were evaluated preoperatively and 1 month and 3 months postoperatively. The mean meridian misalignment of the steepest-meridian CCIs was significantly smaller in the meridian-marking group (4.4 degrees ± 2.8 [SD]) than in the surgeon's-intuition group (8.6 ± 4.4 degrees) (P ≤.0001). Regular and irregular corneal astigmatism and corneal HOAs did not change significantly postoperatively in either group. No significant difference was found in regular or irregular corneal astigmatism, refractive cylinder, manifest spherical equivalent value, SIA, HOAs, UDVA, or CDVA between the meridian-marking group and the surgeon's-intuition group throughout the follow-up. The physical meridian misalignment of steepest-meridian CCI was significantly smaller with the meridian-marking method than with the surgeon's-intuition method; however, the effect of the difference was not large enough to decrease remaining astigmatism and HOAs or to improve the UDVA. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Datasets related to in-land water for limnology and remote sensing applications: distance-to-land, distance-to-water, water-body identifier and lake-centre co-ordinates.

PubMed

Carrea, Laura; Embury, Owen; Merchant, Christopher J

2015-11-01

Datasets containing information to locate and identify water bodies have been generated from data locating static-water-bodies with resolution of about 300 m (1/360 ∘ ) recently released by the Land Cover Climate Change Initiative (LC CCI) of the European Space Agency. The LC CCI water-bodies dataset has been obtained from multi-temporal metrics based on time series of the backscattered intensity recorded by ASAR on Envisat between 2005 and 2010. The new derived datasets provide coherently: distance to land, distance to water, water-body identifiers and lake-centre locations. The water-body identifier dataset locates the water bodies assigning the identifiers of the Global Lakes and Wetlands Database (GLWD), and lake centres are defined for in-land waters for which GLWD IDs were determined. The new datasets therefore link recent lake/reservoir/wetlands extent to the GLWD, together with a set of coordinates which locates unambiguously the water bodies in the database. Information on distance-to-land for each water cell and the distance-to-water for each land cell has many potential applications in remote sensing, where the applicability of geophysical retrieval algorithms may be affected by the presence of water or land within a satellite field of view (image pixel). During the generation and validation of the datasets some limitations of the GLWD database and of the LC CCI water-bodies mask have been found. Some examples of the inaccuracies/limitations are presented and discussed. Temporal change in water-body extent is common. Future versions of the LC CCI dataset are planned to represent temporal variation, and this will permit these derived datasets to be updated.

Impaired cortical mitochondrial function following TBI precedes behavioral changes

PubMed Central

Watson, William D.; Buonora, John E.; Yarnell, Angela M.; Lucky, Jessica J.; D’Acchille, Michaela I.; McMullen, David C.; Boston, Andrew G.; Kuczmarski, Andrew V.; Kean, William S.; Verma, Ajay; Grunberg, Neil E.; Cole, Jeffrey T.

2014-01-01

Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last for a significant time period post-TBI, they are primary research targets for new therapeutics. To investigate changes in mitochondrial function after a brain injury, both the cortical impact site and ipsilateral hippocampus of adult male rats 7 and 17 days after a controlled cortical impact (CCI) injury were examined. State 3, state 4, and uncoupler-stimulated rates of oxygen consumption, respiratory control ratios (RCRs) were measured and membrane potential quantified, and all were significantly decreased in 7 day post-TBI cortical mitochondria. By contrast, hippocampal mitochondria at 7 days showed only non-significant decreases in rates of oxygen consumption and membrane potential. NADH oxidase activities measured in disrupted mitochondria were normal in both injured cortex and hippocampus at 7 days post-CCI. Respiratory and phosphorylation capacities at 17 days post-CCI were comparable to naïve animals for both cortical and hippocampus mitochondria. However, unlike oxidative phosphorylation, membrane potential of mitochondria in the cortical lining of the impact site did not recover at 17 days, suggesting that while diminished cortical membrane potential at 17 days does not adversely affect mitochondrial capacity to synthesize ATP, it may negatively impact other membrane potential-sensitive mitochondrial functions. Memory status, as assessed by a passive avoidance paradigm, was not significantly impaired until 17 days after injury. These results indicate pronounced disturbances in cortical mitochondrial function 7 days after CCI which precede the behavioral impairment observed at 17 days. PMID:24550822

Analgesic effects elicited by neuroactive mediators injected into the ST 36 acupuncture point on inflammatory and neuropathic pain in mice.

PubMed

Vieira, Jadina Santos; Toreti, Jéssica Aline; Carvalho, Ravena Carolina de; de Araújo, João Eduardo; Silva, Marcelo Lourenço; Silva, Josie Resende Torres

2018-05-31

The present study evaluates whether the injection of serotonin, acetylcholine, glutamate, bradykinin, histamine or substance P into the Zusanli (Stomach 36, ST 36) acupoint can also produce the acupuncture-induced antinociceptive effect on inflammatory or neuropathic pain. In this in vivo experimental study a total of 450 male Swiss mice were used. Mice were injected with saline or complete Freund's adjuvant (CFA) or subjected to sham or chronic constriction injury (CCI) surgery. After the establishment of the inflammatory (4 hours) or the neuropathic pain (3 days) the animals (n=6) received manual acupuncture (MA), sham acupuncture (OUT) or injection of saline, serotonin, acetylcholine, glutamate, bradykinin, histamine or substance P into the ST 36 and were evaluated for up to 24 hours. Mechanical threshold was evaluated and the L4-L6 dorsal root ganglion (DRG) was used for analysis of the transient receptor potential vanilloid type 1 (TRPV1) overexpression. The mice from both the CFA or CCI models and treated with MA had significant increases in the thresholds for more than 24 hours. OUT stimulation did not change the thresholds. In the mice injected with each of the mediators, the thresholds were significantly increased for all times in both the CFA and CCI models. TRPV1 overexpression in CFA and CCI mice was reduced at all times by injection of serotonin, acetylcholine or substance P but not by injection of glutamate, histamine or bradykinin. Our data suggests that the neuroactive mediators released by acupuncture-induced tissue injury may contribute to acupuncture-induced analgesia. Copyright © 2018. Published by Elsevier B.V.

Revised Baux Score and updated Charlson comorbidity index are independently associated with mortality in burns intensive care patients.

PubMed

Heng, Jacob S; Clancy, Olivia; Atkins, Joanne; Leon-Villapalos, Jorge; Williams, Andrew J; Keays, Richard; Hayes, Michelle; Takata, Masao; Jones, Isabel; Vizcaychipi, Marcela P

2015-11-01

The purpose of the current study was to utilise established scoring systems to analyse the association of (i) burn injury severity, (ii) comorbid status and (iii) associated systemic physiological disturbance with inpatient mortality in patients with severe burn injuries admitted to intensive care. Case notes of all patients with acute thermal injuries affecting ≥15% total body surface area (TBSA) admitted to the Burns Intensive Care Unit (BICU) at Chelsea and Westminster Hospital during a 10-year period were retrospectively reviewed. Revised Baux Score, Belgian Outcome in Burn Injury (BOBI) Score, Abbreviated Burn Severity Index (ABSI), APACHE II Score, Sequential Organ Failure Assessment (SOFA) Score and Updated Charlson Comorbidity Index (CCI) were computed for each patient and analysed for association with inpatient mortality. Ninety mechanically ventilated patients (median age 45.7 years, median % TBSA burned 36.5%) were included. 72 patients had full thickness burns and 35 patients had inhalational injuries. Forty-four patients died in hospital while 46 survived to discharge. In a multivariate logistic regression model, only the Revised Baux Score (p<0.001) and updated CCI (p=0.014) were independently associated with mortality. This gave a ROC curve with area under the curve of 0.920. On multivariate cox regression survival analysis, only the Revised Baux Score (p<0.001) and the updated CCI (p=0.004) were independently associated with shorter time to death. Our data suggest that the Revised Baux Score and the updated CCI are independently associated with inpatient mortality in patients admitted to intensive care with burn injuries affecting ≥15% TBSA. This emphasises the importance of comorbidities in the prognosis of patients with severe burn injuries. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

The predictive value of early molecular response in chronic myeloid leukaemia patients treated with imatinib in a single real-world medical centre in a developing country.

PubMed

Bee, Ping Chong; Sekaran, Veera; Ng, Richard Rui Jie; Kweh, Ting Yi; Gan, Gin Gin

2017-03-01

The prognosis of patients with chronic myeloid leukaemia (CML) has improved since the introduction of imatinib. However, patients who do not achieve complete cytogenetic response (CCyR) and major molecular response (MMR) have poorer prognosis. Recent clinical trials have demonstrated that early and deeper cytogenetic and molecular responses predict a better long-term outcome. This study aimed to analyse the relationship between early molecular response and clinical outcome in a real-life setting. This retrospective study included all patients with CML, in chronic or accelerated phase, who were treated with imatinib at University of Malaya Medical Centre, Malaysia. A total of 70 patients were analysed. The median follow-up duration was 74 months, and the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%, respectively. Overall survival (OS) and event-free survival (EFS) at ten years were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had significantly better OS and EFS than those who did not. At six months, patients who had a BCR-ABL level ≤ 10% had significantly better OS and EFS than those who had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at 18 months showed no survival advantage in our patients. Our data showed that imatinib is still useful as first-line therapy. However, vigilant monitoring of patients who have a BCR-ABL level > 10% at six months of treatment should be implemented so that prompt action can be taken to provide the best outcome for these patients. Copyright: © Singapore Medical Association

Protective effects of melatonin and quercetin on experimental lung injury induced by carbon tetrachloride in rats.

PubMed

Taslidere, Elif; Esrefoglu, Mukaddes; Elbe, Hulya; Cetin, Asli; Ates, Burhan

2014-03-01

Exposure to carbon tetrachloride (CCl4), a well-known toxicant, causes tissue damage by inducing oxidative stress via formation of free radicals. The fundamental structure of the organs of rats and humans is similar, so administration of CCl4 to rats is an accepted experimental model to produce oxidative damage to various tissues including pulmonary tissue. In this study, we evaluated the protective capacity of melatonin and quercetin against CCl4-induced oxidative lung damage in rats. Rats were divided into five groups each containing seven rats as follows: Control group, Olive oil group CCl4 group, CCl4+Melatonin, and CCl4+Quercetin group. The tissue samples were processed by routine histological and biochemical procedures. Sections were stained with Hematoxylin-eosin and Masson's trichrome. Histopathologic damage score was calculated. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activities were assayed. The lung sections of control groups showed normal histological characteristics. Fibrosis, interstitial hemorrhage, epithelial desquamation in bronchiole and alveoli, intra-alveolar edema, leukocyte, and macrophage infiltration were observed in lung sections of rats exposed to CCl4 alone. The findings were reduced in the treatments groups. The MDA level in the CCI4 group were significantly higher than in the other groups (p < .001), and the CAT and GSH levels in the CCI4+Mel and CCI4+Quer groups were significantly higher than in the CCI4 group (p < .05). In conclusion, we suggest that agents with antioxidant properties such as melatonin and quercetin may have positive effects in the treatment of pulmonary diseases characterized by especially edema, inflammation, and fibrosis.

Spinal sigma-1 receptors activate NADPH oxidase 2 leading to the induction of pain hypersensitivity in mice and mechanical allodynia in neuropathic rats.

PubMed

Choi, Sheu-Ran; Roh, Dae-Hyun; Yoon, Seo-Yeon; Kang, Suk-Yun; Moon, Ji-Young; Kwon, Soon-Gu; Choi, Hoon-Seong; Han, Ho-Jae; Beitz, Alvin J; Oh, Seog-Bae; Lee, Jang-Hern

2013-08-01

We have recently demonstrated that spinal sigma-1 receptors (Sig-1Rs) mediate pain hypersensitivity in mice and neuropathic pain in rats. In this study, we examine the role of NADPH oxidase 2 (Nox2)-induced reactive oxygen species (ROS) on Sig-1R-induced pain hypersensitivity and the induction of chronic neuropathic pain. Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. Mechanical allodynia and thermal hyperalgesia were evaluated in mice and CCI-rats. Western blotting and dihydroethidium (DHE) staining were performed to assess the changes in Nox2 activation and ROS production in spinal cord, respectively. Direct activation of spinal Sig-1Rs with the Sig-1R agonist, PRE084 induced mechanical allodynia and thermal hyperalgesia, which were dose-dependently attenuated by pretreatment with the ROS scavenger, NAC or the Nox inhibitor, apocynin. PRE084 also induced an increase in Nox2 activation and ROS production, which were attenuated by pretreatment with the Sig-1R antagonist, BD1047 or apocynin. CCI-induced nerve injury produced an increase in Nox2 activation and ROS production in the spinal cord, all of which were attenuated by intrathecal administration with BD1047 during the induction phase of neuropathic pain. Furthermore, administration with BD1047 or apocynin reversed CCI-induced mechanical allodynia during the induction phase, but not the maintenance phase. These findings demonstrate that spinal Sig-1Rs modulate Nox2 activation and ROS production in the spinal cord, and ultimately contribute to the Sig-1R-induced pain hypersensitivity and the peripheral nerve injury-induced induction of chronic neuropathic pain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Towards Portable Large-Scale Image Processing with High-Performance Computing.

PubMed

Huo, Yuankai; Blaber, Justin; Damon, Stephen M; Boyd, Brian D; Bao, Shunxing; Parvathaneni, Prasanna; Noguera, Camilo Bermudez; Chaganti, Shikha; Nath, Vishwesh; Greer, Jasmine M; Lyu, Ilwoo; French, William R; Newton, Allen T; Rogers, Baxter P; Landman, Bennett A

2018-05-03

High-throughput, large-scale medical image computing demands tight integration of high-performance computing (HPC) infrastructure for data storage, job distribution, and image processing. The Vanderbilt University Institute for Imaging Science (VUIIS) Center for Computational Imaging (CCI) has constructed a large-scale image storage and processing infrastructure that is composed of (1) a large-scale image database using the eXtensible Neuroimaging Archive Toolkit (XNAT), (2) a content-aware job scheduling platform using the Distributed Automation for XNAT pipeline automation tool (DAX), and (3) a wide variety of encapsulated image processing pipelines called "spiders." The VUIIS CCI medical image data storage and processing infrastructure have housed and processed nearly half-million medical image volumes with Vanderbilt Advanced Computing Center for Research and Education (ACCRE), which is the HPC facility at the Vanderbilt University. The initial deployment was natively deployed (i.e., direct installations on a bare-metal server) within the ACCRE hardware and software environments, which lead to issues of portability and sustainability. First, it could be laborious to deploy the entire VUIIS CCI medical image data storage and processing infrastructure to another HPC center with varying hardware infrastructure, library availability, and software permission policies. Second, the spiders were not developed in an isolated manner, which has led to software dependency issues during system upgrades or remote software installation. To address such issues, herein, we describe recent innovations using containerization techniques with XNAT/DAX which are used to isolate the VUIIS CCI medical image data storage and processing infrastructure from the underlying hardware and software environments. The newly presented XNAT/DAX solution has the following new features: (1) multi-level portability from system level to the application level, (2) flexible and dynamic software development and expansion, and (3) scalable spider deployment compatible with HPC clusters and local workstations.

KSC-2013-3016

NASA Image and Video Library

2013-05-30

Edwards, Calif. – ED13-161-35 - Sierra Nevada Corporation SNC Space Systems' team members tow the Dream Chaser flight vehicle out to a concrete runway at NASA's Dryden Flight Research Center in California for range and taxi tow tests. The ground testing will validate the performance of the spacecraft's nose skid, brakes, tires and other systems prior to captive-carry and free-flight tests scheduled for later this year. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Ken Ulbrich

KSC-2013-3022

NASA Image and Video Library

2013-05-31

Edwards, Calif. – ED13-164-34 - Sierra Nevada Corporation SNC Space Systems' team members tow the Dream Chaser flight vehicle out to a concrete runway at NASA's Dryden Flight Research Center in California for range and taxi tow tests. The ground testing will validate the performance of the spacecraft's nose skid, brakes, tires and other systems prior to captive-carry and free-flight tests scheduled for later this year. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Ken Ulbrich

KSC-2013-3021

NASA Image and Video Library

2013-05-31

Edwards, Calif. – ED13-164-34 - Sierra Nevada Corporation SNC Space Systems' team members tow the Dream Chaser flight vehicle out to a concrete runway at NASA's Dryden Flight Research Center in California for range and taxi tow tests. The ground testing will validate the performance of the spacecraft's nose skid, brakes, tires and other systems prior to captive-carry and free-flight tests scheduled for later this year. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Ken Ulbrich

KSC-2013-3025

NASA Image and Video Library

2013-06-27

Edwards, Calif. – ED13-0215-072 - Sierra Nevada Corporation SNC Space Systems' team members tow the Dream Chaser flight vehicle along a concrete runway at NASA's Dryden Flight Research Center in California for range and taxi tow tests. The ground testing will validate the performance of the spacecraft's nose skid, brakes, tires and other systems prior to captive-carry and free-flight tests scheduled for later this year. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Ken Ulbrich

KSC-2013-3020

NASA Image and Video Library

2013-05-31

Edwards, Calif. – ED13-164-33 - Sierra Nevada Corporation SNC Space Systems' team members tow the Dream Chaser flight vehicle out to a concrete runway at NASA's Dryden Flight Research Center in California for range and taxi tow tests. The ground testing will validate the performance of the spacecraft's nose skid, brakes, tires and other systems prior to captive-carry and free-flight tests scheduled for later this year. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Ken Ulbrich

KSC-2013-3019

NASA Image and Video Library

2013-05-31

Edwards, Calif. – ED13-164-32 - Sierra Nevada Corporation SNC Space Systems' team members tow the Dream Chaser flight vehicle out to a concrete runway at NASA's Dryden Flight Research Center in California for range and taxi tow tests. The ground testing will validate the performance of the spacecraft's nose skid, brakes, tires and other systems prior to captive-carry and free-flight tests scheduled for later this year. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Ken Ulbrich

Analysis of Survival of Patients with Chronic Myeloid Leukemia Treated with Imatinib in the Last 15 Years in Lebanon.

PubMed

Massoud, Marcel; Sakr, Riwa; Kerbage, Fouad; Makdissi, Joseph; Hawi, Jenny; Rached, Layale; Nasr, Fady; Chahine, Georges

2017-07-01

In the 2000s, the introduction of the tyrosine kinase inhibitor (TKI), imatinib, improved the survival outcomes of patients with chronic myeloid leukemia (CML). In Lebanon, we rapidly adopted this treatment strategy. To the best of our knowledge, this is the first study reporting the survival rates of Lebanese CML patients. We examined the rates of major molecular response (MMR) and complete cytogenetic response (CCyR) and analyzed the overall survival, progression-free survival, and event-free survival of CML patients treated with front-line imatinib in 3 university hospitals in Lebanon. We retrospectively reviewed the medical records of 46 patients diagnosed with CML and treated with front-line imatinib 400 mg/day from 2000 and followed up to 2015. In all patients, initially, 2 diagnostic tests were performed: cytogenetic analysis and qualitative molecular testing of the BCR-ABL transcript. The male-to-female sex ratio was 3:1. The median age at diagnosis was 49 years, and the mean age was 44.52 years. At diagnosis, 46 patients were in the chronic phase. All patients started imatinib 400 mg/day. Of the 46 patients, 35 had a typical karyotype, 8 an atypical karyotype, and 3 hypoploidism. The MMR rate at 18 months was 58.69%. The cumulative CCyR rate at 18 months of therapy with imatinib at the standard dose was 67.39%. The event-free survival rate was 75.86% and 74.14% at 5 and 8 years, respectively. The progression-free survival rate was 77.59% and 75.86% at 5 and 8 years, respectively. The overall survival rate was 98.27% and 98.27% at 5 and 8 years, respectively. Of the 46 patients, 12 developed disease progression and were salvaged by second-generation TKIs. These 12 patients were still alive with a MMR. In our study population, the achievement of a MMR and CCyR and overall survival, progression-free survival, and event-free survival were similar to previous published data. Reaching high survival rates with a first-generation TKI in a country with limited resources is a reasonable treatment approach for CML patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Automated assessment of pain in rats using a voluntarily accessed static weight-bearing test.

PubMed

Kim, Hung Tae; Uchimoto, Kazuhiro; Duellman, Tyler; Yang, Jay

2015-11-01

The weight-bearing test is one method to assess pain in rodent animal models; however, the acceptance of this convenient method is limited by the low throughput data acquisition and necessity of confining the rodents to a small chamber. We developed novel data acquisition hardware and software, data analysis software, and a conditioning protocol for an automated high throughput static weight-bearing assessment of pain. With this device, the rats voluntarily enter the weighing chamber, precluding the necessity to restrain the animals and thereby removing the potential stress-induced confounds as well as operator selection bias during data collection. We name this device the Voluntarily Accessed Static Incapacitance Chamber (VASIC). Control rats subjected to the VASIC device provided hundreds of weight-bearing data points in a single behavioral assay. Chronic constriction injury (CCI) surgery and paw pad injection of complete Freund's adjuvant (CFA) or carrageenan in rats generated hundreds of weight-bearing data during a 30 minute recording session. Rats subjected to CCI, CFA, or carrageenan demonstrated the expected bias in weight distribution favoring the un-operated leg, and the analgesic effect of i.p. morphine was demonstrated. In comparison with existing methods, brief water restriction encouraged the rats to enter the weighing chamber to access water, and an infrared detector confirmed the rat position with feet properly positioned on the footplates, triggering data collection. This allowed hands-off measurement of weight distribution data reducing operator selection bias. The VASIC device should enhance the hands-free parallel collection of unbiased weight-bearing data in a high throughput manner, allowing further testing of this behavioral measure as an effective assessment of pain in rodents. Copyright © 2015. Published by Elsevier Inc.

Automated assessment of pain in rats using a voluntarily accessed static weight-bearing test

PubMed Central

Kim, Hung Tae; Uchimoto, Kazuhiro; Duellman, Tyler; Yang, Jay

2015-01-01

The weight-bearing test is one method to assess pain in rodent animal models; however, the acceptance of this convenient method is limited by the low throughput data acquisition and necessity of confining the rodents to a small chamber. New methods We developed novel data acquisition hardware and software, data analysis software, and a conditioning protocol for an automated high throughput static weight-bearing assessment of pain. With this device, the rats voluntarily enter the weighing chamber, precluding the necessity to restrain the animals and thereby removing the potential stress-induced confounds as well as operator selection bias during data collection. We name this device the Voluntarily Accessed Static Incapacitance Chamber (VASIC). Results Control rats subjected to the VASIC device provided hundreds of weight-bearing data points in a single behavioral assay. Chronic constriction injury (CCI) surgery and paw pad injection of complete Freund's adjuvant (CFA) or carrageenan in rats generated hundreds of weight-bearing data during a 30 minute recording session. Rats subjected to CCI, CFA, or carrageenan demonstrated the expected bias in weight distribution favoring the un-operated leg, and the analgesic effect of i.p. morphine was demonstrated. In comparison with existing methods, brief water restriction encouraged the rats to enter the weighing chamber to access water, and an infrared detector confirmed the rat position with feet properly positioned on the footplates, triggering data collection. This allowed hands-off measurement of weight distribution data reducing operator selection bias. Conclusion The VASIC device should enhance the hands-free parallel collection of unbiased weight-bearing data in a high throughput manner, allowing further testing of this behavioral measure as an effective assessment of pain in rodents. PMID:26143745

In vivo studies of low level laser (light) therapy for traumatic brain injury

NASA Astrophysics Data System (ADS)

Xuan, Weijun; Wu, Qiuhe; Huang, Ying-Ying; Ando, Takahiro; Huang, Liyi; Hamblin, Michael R.

2012-03-01

Low-level laser (or light) therapy (LLLT) is attracting growing interest to treat both stroke and traumatic brain injury (TBI). The fact that near-infrared light can penetrate into the brain allows non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. It is proposed that red and NIR light is absorbed by chromophores in the mitochondria of cells leading to changes in gene transcription and upregulation of proteins involved in cell survival, antioxidant production, collagen synthesis, reduction of chronic inflammation and cell migration and proliferation. We developed a mouse model of controlled cortical impact (CCI) TBI and examined the effect of 0, 1, 3, and 14 daily 810-nm CW laser treatments in the CCI model as measured by neurological severity score and wire grip and motion test. 1 laser Tx gave a significant improvement while 3 laser Tx was even better. Surprisingly 14 laser Tx was no better than no treatment. Histological studies at necropsy suggested that the neurodegeneration was reduced at 14 days and that the cortical lesion was repaired by BrdU+ve neural progenitor (stem) cells at 28 days. Transcranial laser therapy is a promising treatment for acute (and chronic TBI) and the lack of side-effects and paucity of alternative treatments encourages early clinical trials.

Exact outage analysis of the effect of co-channel interference on secured multi-hop relaying networks

NASA Astrophysics Data System (ADS)

Quang Nguyen, Sang; Kong, Hyung Yun

2016-11-01

In this article, the presence of multi-hop relaying, eavesdropper and co-channel interference (CCI) in the same system model is investigated. Specifically, the effect of CCI on a secured multi-hop relaying network is studied, in which the source communicates with the destination via multi-relay-hopping under the presence of an eavesdropper and CCI at each node. The optimal relay at each cluster is selected to help forward the message from the source to the destination. We apply two relay selection approaches to such a system model, i.e. the optimal relay is chosen based on (1) the maximum channel gain from the transmitter to all relays in the desired cluster and (2) the minimum channel gain from the eavesdropper to all relays in each cluster. For the performance evaluation and comparison, we derived the exact closed form of the secrecy outage probability of the two approaches. That analysis is verified by Monte Carlo simulation. Finally, the effects of the number of hops, the transmit power at the source, relays and the external sources, the distance between the external sources and each node in the system, and the location of the eavesdropper are presented and discussed.

Surgical Stabilization of Costoclavicular Injuries - A Combination of Flail Chest Injuries and a Clavicula Fracture.

PubMed

Langenbach, Andreas; Pinther, Melina; Krinner, Sebastian; Grupp, Sina; Ekkernkamp, Axel; Hennig, Friedrich F; Schulz-Drost, Stefan

2017-01-01

Background: Flail chest injuries (FCI) are associated with a high morbidity and mortality rate. As a concomitant clavicle fracture in FCI even worsens the outcome, the question is how can those costoclavicular injuries (CCI) be managed surgically. Methods: 11 patients with CCI were surgically treated by a locked plate osteosynthesis of the Clavicle and the underlying ribs through limited surgical approaches under general anesthesia. Patients were followed up after 2, 6, 12, 26 and 52 weeks. Results: All patients showed severe chest wall deformity due to severely displaced fractures of the ribs and the clavicle. They were suffering from pain and restriction of respiratory movements. The chest wall could be restored to normal shape in all cases with uneventful bone healing and a high patient convenience. Fractures of the clavicle and the second rib were managed through an innovative clavipectoral approach, the others through standard approaches to the anterolateral and the posterolateral chest wall. Two patients complained about numbness around the lateral approach and lasting periscapular pain. Conclusions: Surgical stabilization might be the appropriate therapy in CCI with dislocated fractures since they would cause severe deformity and loss of function of the chest wall and the shoulder. Celsius.

Disruption of the Smad7 gene enhances CCI4-dependent liver damage and fibrogenesis in mice

PubMed Central

Hamzavi, Jafar; Ehnert, Sabrina; Godoy, Patricio; Ciuclan, Loredana; Weng, Honglei; Mertens, Peter R; Heuchel, Rainer; Dooley, Steven

2008-01-01

Transforming growth factor-β (TGF-β) signalling is induced in liver as a consequence of damage and contributes to wound healing with transient activation, whereas it mediates fibrogenesis with long-term up-regulation in chronic disease. Smad-dependent TGF-β effects are blunted by antagonistic Smad7, which is transcriptionally activated as an immediate early response upon initiation of TGF-β signalling in most cell types, thereby providing negative feedback regulation. Smad7 can be induced by other cytokines, e.g. IFN-γ, leading to a crosstalk of these signalling pathways. Here we report on a novel mouse strain, denoted S7ΔE1, with a deletion of exon I from the endogenous smad7 gene. The mice were viable and exhibited normal adult liver architecture. To obtain insight into Smad7-depend-ent protective effects, chronic liver damage was induced in mice by carbon tetrachloride (CCI4) administration. Subsequent treatment, elevated serum liver enzymes indicated enhanced liver damage in mice lacking functional Smad7. CCI4-dependent Smad2 phosphoryla-tion was pronounced in S7ΔE1 mice and accompanied by increased numbers of α-smooth muscle actin positive ‘activated’ HSCs. There was evidence for matrix accumulation, with elevated collagen deposition as assessed morphometrically in Sirius red stained tissue and confirmed with higher levels of hydroxyproline in S7ΔE1 mice. In addition, the number of CD43 positive infiltrating lymphocytes as well as of apoptotic hepatocytes was increased. Studies with primary hepatocytes from S7ΔE1 and wild-type mice indicate that in the absence of functional Smad7 protein, hepatocytes are more sensitive for TGF-β effects resulting in enhanced cell death. Furthermore, S7ΔE1 hepatocytes display increased oxidative stress and cell damage in response to CCI4, as measured by reactive oxygen species production, glutathione depletion, lactate dehydrogenase release and lipid peroxidation. Using an ALK-5 inhibitor all investigated CCI4 effects on hepatocytes were blunted, confirming participation of TGF-β signalling. We conclude that Smad7 mediates a protective effect from adverse TGF-β signalling in damaged liver, re-iterating its negative regulatory loop on signalling. PMID:18266971

Combining stable insect cell lines with baculovirus-mediated expression for multi-HA influenza VLP production.

PubMed

Sequeira, Daniela P; Correia, Ricardo; Carrondo, Manuel J T; Roldão, António; Teixeira, Ana P; Alves, Paula M

2018-05-24

Safer and broadly protective vaccines are needed to cope with the continuous evolution of circulating influenza virus strains and promising approaches based on the expression of multiple hemagglutinins (HA) in a virus-like particle (VLP) have been proposed. However, expression of multiple genes in the same vector can lead to its instability due to tandem repetition of similar sequences. By combining stable with transient expression systems we can rationally distribute the number of genes to be expressed per platform and thus mitigate this risk. In this work, we developed a modular system comprising stable and baculovirus-mediated expression in insect cells for production of multi-HA influenza enveloped VLPs. First, a stable insect High Five cell population expressing two different HA proteins from subtype H3 was established. Infection of this cell population with a baculovirus vector encoding three other HA proteins from H3 subtype proved to be as competitive as traditional co-infection approaches in producing a pentavalent H3 VLP. Aiming at increasing HA expression, the stable insect cell population was infected at increasingly higher cell concentrations (CCI). However, cultures infected at CCI of 3×10 6 cells/mL showed lower HA titers per cell in comparison to standard CCI of 2×10 6 cells/mL, a phenomenon named "cell density effect". To lessen the negative impact of this phenomenon, a tailor-made refeed strategy was designed based on the exhaustion of key nutrients during cell growth. Noteworthy, cultures supplemented and infected at a CCI of 4×10 6 cells/mL showed comparable HA titers per cell to those of CCI of 2×10 6 cells/mL, thus leading to an increase of up to 4-fold in HA titers per mL. Scalability of the modular strategy herein proposed was successfully demonstrated in 2L stirred tank bioreactors with comparable HA protein levels observed between bioreactor and shake flasks cultures. Overall, this work demonstrates the suitability of combining stable with baculovirus-mediated expression in insect cells as an efficient platform for production of multi-HA influenza VLPs, surpassing the drawbacks of traditional co-infection strategies and/or the use of larger, unstable vectors. Copyright © 2017 Elsevier Ltd. All rights reserved.

KSC-2013-3024

NASA Image and Video Library

2013-06-27

Edwards, Calif. – ED13-0215-024 - Sierra Nevada Corporation SNC Space Systems' team members prepare to tow the Dream Chaser flight vehicle along a concrete runway at NASA's Dryden Flight Research Center in California for range and taxi tow tests. The ground testing will validate the performance of the spacecraft's nose skid, brakes, tires and other systems prior to captive-carry and free-flight tests scheduled for later this year. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Ken Ulbrich

KSC-2013-3023

NASA Image and Video Library

2013-06-27

Edwards, Calif. – ED13-0215-016 - Sierra Nevada Corporation SNC Space Systems' team members prepare to tow the Dream Chaser flight vehicle along a concrete runway at NASA's Dryden Flight Research Center in California for range and taxi tow tests. The ground testing will validate the performance of the spacecraft's nose skid, brakes, tires and other systems prior to captive-carry and free-flight tests scheduled for later this year. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Ken Ulbrich

Cloning and sequencing the genes encoding goldfish and carp ependymin.

PubMed

Adams, D S; Shashoua, V E

1994-04-20

Ependymins (EPNs) are brain glycoproteins thought to function in optic nerve regeneration and long-term memory consolidation. To date, epn genes have been characterized in two orders of teleost fish. In this study, polymerase chain reactions (PCR) were used to amplify the complete 1.6-kb epn genes, gf-I and cc-I, from genomic DNA of Cypriniformes, goldfish and carp, respectively. Amplified bands were cloned and sequenced. Each gene consists of six exons and five introns. The exon portion of gf-I encodes a predicted 215-amino-acid (aa) protein previously characterized as GF-I, while cc-I encodes a predicted 215-aa protein 95% homologous to GF-I.

Conservation of the Sinclair Inn Museum, and the Painted Room Annapolis Royal, Nova Scotia, Canada

NASA Astrophysics Data System (ADS)

Shaftel, A.; Ward, J.

2017-08-01

Conservation of the historic 18thC. Sinclair Inn Museum, and of the recently discovered late 18th/early 19thC. unique panoramic wall paintings located in an upstairs room, are co-dependent. This project was carried out with Canadian Conservation Institute (CCI) staff, and Conservator in Private Practice Ann Shaftel. This paper will introduce the Sinclair Inn Museum, outline the CCI murals and building investigations of 2011-15, the mural investigation of 2015-16, which confirmed that the mural extended to all four walls of the function room, now referred to as the Painted Room, and to describe how it has been revealed and conserved to date.

Using the Clear Communication Index to Improve Materials for a Behavioral Intervention.

PubMed

Porter, Kathleen J; Alexander, Ramine; Perzynski, Katelynn M; Kruzliakova, Natalie; Zoellner, Jamie M

2018-02-08

Ensuring that written materials used in behavioral interventions are clear is important to support behavior change. This study used the Clear Communication Index (CCI) to assess the original and revised versions of three types of written participant materials from the SIPsmartER intervention. Materials were revised based on original scoring. Scores for the entire index were significantly higher among revised versions than originals (57% versus 41%, p < 0.001); however, few revised materials (n = 2 of 53) achieved the benchmark of ≥90%. Handouts scored higher than worksheets and slide sets for both versions. The proportion of materials scored as having "a single main message" significantly increased between versions for worksheets (7% to 57%, p = 0.003) and slide sets (33% to 67%, p = 0.004). Across individual items, most significant improvements were in Core, with four-items related to the material having a single main message. Findings demonstrate that SIPsmartER's revised materials improved after CCI-informed edits. They advance the evidence and application of the CCI, suggesting it can be effectively used to support improvement in clarity of different types of written materials used in behavioral interventions. Implications for practical considerations of using the tool and suggestions for modifications for specific types of materials are presented.

Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa.

PubMed

Itonaga, Hidehiro; Tsushima, Hideki; Hata, Tomoko; Matsuo, Emi; Imanishi, Daisuke; Imaizumi, Yoshitaka; Kawaguchi, Yasuhisa; Fukushima, Takuya; Doi, Yuko; Mori, Sayaka; Kamihira, Shimeru; Tomonaga, Masao; Miyazaki, Yasushi

2012-02-01

The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation.

Non-pharmacological treatment affects neuropeptide expression in neuropathic pain model.

PubMed

Santos, Fabio Martinez; Silva, Joyce Teixeira; Rocha, Igor Rafael Correia; Martins, Daniel Oliveira; Chacur, Marucia

2018-05-15

Chronic constriction injury (CCI) of the sciatic nerve elicits changes in neuropeptide expression on the dorsal root ganglia (DRG). The neural mobilization (NM) technique is a noninvasive method that has been proven clinically effective in reducing pain. The aim of this study was to analyze the expression of substance P, transient receptor potential vanilloid 1 (TRPV1) and opioid receptors in the DRG of rats with chronic constriction injury and to compare it to animals that received NM treatment. CCI was performed on adult male rats. Each animal was submitted to 10 sessions of neural mobilization every other day, starting 14 days after the CCI injury. At the end of the sessions, the DRG (L4-L6) were analyzed using Western blot assays for substance P, TRPV1 and opioid receptors (µ-opioid receptor, δ-opioid receptor and κ-opioid receptor). We observed a decreased substance P and TRPV1 expression (48% and 35%, respectively) and an important increase of µ-opioid receptor expression (200%) in the DRG after NM treatment compared to control animals. The data provide evidence that NM promotes substantial changes in neuropeptide expression in the DRG; these results may provide new options for treating neuropathic pain. Copyright © 2018 Elsevier B.V. All rights reserved.

Fiabilité test retest et validité de construit de la version française de L'Échelle fonctionnelle des membres inférieurs (ÉFMI), partie II

PubMed Central

René, Frédéric; Casimiro, Lynn; Tremblay, Manon; Chea, Phanny; Létourneau, Liliane; Silva, Megan; Stockwell, Victoria; Bergeron, Louis-Philippe

2011-01-01

RÉSUMÉ Introduction : Le Lower Extremity Functional Scale a été traduit en français en 2006. La version canadienne-française se nomme l'Échelle fonctionnelle des membres inférieurs (ÉFMI). La validité de construit et la fiabilité test-retest de l'ÉFMI n'ont pas encore été examinées. But : Examiner la fiabilité test-retest, la consistance interne et la validité de construit de l'ÉFMI. Méthodologie : Trente-quatre participants ayant subi une chirurgie ou une blessure à un membre inférieur ont rempli un questionnaire démographique et complété l'ÉFMI lors d'une évaluation initiale alors qu'ils étaient hospitalisés. Ils ont à nouveau complété l'ÉFMI dans un intervalle de 72 heures après la première évaluation. Le coefficient de corrélation intra-classe (CCI) et le coefficient kappa ont été utilisés afin d'examiner la fiabilité de type test-retest de l'ÉFMI. Le coefficient alpha Cronbach a été calculé pour évaluer la consistance interne. L'analyse factorielle a été utilisée pour examiner la validité de construit afin de déterminer le nombre de dimensions et leur signification respective. Résultats : Le CCI s'élève à une valeur de 0,92 [0,88–0,96] (IC: 95%). Le résultat du test α-Cronbach est de 0,95 (0,91–0,99) IC à 95%. L'analyse factorielle révèle que tous les éléments de l'ÉFMI se logent sur une dimension principale. Conclusion : Les résultats montrent que la version canadienne-française de l'ÉFMI est un outil unidimensionnel qui offre une fiabilité test-retest et une consistance interne excellentes. PMID:22379266

Effect of lappaconitine on neuropathic pain mediated by P2X3 receptor in rat dorsal root ganglion.

PubMed

Ou, Shan; Zhao, Yan-Dong; Xiao, Zhi; Wen, Hui-Zhong; Cui, Jian; Ruan, Huai-Zhen

2011-04-01

ATP facilitates initiation and transmission of the neuropathic pain at the dorsal root ganglion (DRG) level via the P2X receptors, especially the subtype P2X(3). Lappaconitine (LA) is an active principle isolated from Chinese herbal medicine and possesses analgesic effect. The aim of this study was to investigate the effect of LA on chronic constriction injury (CCI)-induced neuropathic pain mediated by P2X(3) receptor in the DRG neurons. In the presence of CCI and/or LA, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured and P2X(3) receptor expression in the DRG neurons was evaluated by immunohistochemistry and Western blotting. Following intrathecal administration of P2X(3) receptor oligonucleotide, the effect of LA on pain thresholds was assessed. Furthermore, the effect of LA on the P2X(3) receptor agonists ATP- and α,β-meATP-induced inward currents (I(ATP) and I(α,β-meATP)) in the acutely dissociated rat DRG neurons was investigated by whole cell patch-clamp. The results included: (1) There showed reduction of pain thresholds, enhancement of I(ATP) and I(α,β-meATP) and up-regulation of P2X(3) receptor expression in rat DRG neurons when neuropathic pain occurred. (2) In the presence of LA, the decreased pain thresholds, the up-regulated P2X(3) receptor expression and the enhanced I(ATP) and I(α,β-meATP) were reversible in the CCI rats. (3) The down-regulated P2X(3) receptor expression with pretreatment of P2X(3) receptor antisense oligonucleotide significantly attenuated the analgesic effect of LA. These results indicate that the analgesic effect of LA involves decrease of expression and sensitization of the P2X(3) receptors of the rat DRG neurons following CCI. Copyright © 2011 Elsevier Ltd. All rights reserved.

Educational strategies associated with development of problem-solving, critical thinking, and self-directed learning.

PubMed

Hendricson, William D; Andrieu, Sandra C; Chadwick, D Gregory; Chmar, Jacqueline E; Cole, James R; George, Mary C; Glickman, Gerald N; Glover, Joel F; Goldberg, Jerold S; Haden, N Karl; Meyerowitz, Cyril; Neumann, Laura; Pyle, Marsha; Tedesco, Lisa A; Valachovic, Richard W; Weaver, Richard G; Winder, Ronald L; Young, Stephen K; Kalkwarf, Kenneth L

2006-09-01

This article was developed for the Commission on Change and Innovation in Dental Education (CCI), established by the American Dental Education Association. CCI was created because numerous organizations within organized dentistry and the educational community have initiated studies or proposed modifications to the process of dental education, often working to achieve positive and desirable goals but without coordination or communication. The fundamental mission of CCI is to serve as a focal meeting place where dental educators and administrators, representatives from organized dentistry, the dental licensure community, the Commission on Dental Accreditation, the ADA Council on Dental Education and Licensure, and the Joint Commission on National Dental Examinations can meet and coordinate efforts to improve dental education and the nation's oral health. One of the objectives of the CCI is to provide guidance to dental schools related to curriculum design. In pursuit of that objective, this article summarizes the evidence related to this question: What are educational best practices for helping dental students acquire the capacity to function as an entry-level general dentist or to be a better candidate to begin advanced studies? Three issues are addressed, with special emphasis on the third: 1) What constitutes expertise, and when does an individual become an expert? 2) What are the differences between novice and expert thinking? and 3) What educational best practices can help our students acquire mental capacities associated with expert function, including critical thinking and self-directed learning? The purpose of this review is to provide a benchmark that faculty and academic planners can use to assess the degree to which their curricula include learning experiences associated with development of problem-solving, critical thinking, self-directed learning, and other cognitive skills necessary for dental school graduates to ultimately become expert performers as they develop professionally in the years after graduation.

Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons.

PubMed

Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

2015-01-01

Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top-down pathway. These findings may help researchers and clinicians to better understand the underlying modulation mechanisms of orofacial neuropathic pain and indicate a novel mechanism of ERK inhibitor-induced analgesia.

Hepatoprotective Potential of Chestnut Bee Pollen on Carbon Tetrachloride-Induced Hepatic Damages in Rats

PubMed Central

Yıldız, Oktay; Can, Zehra; Saral, Özlem; Yuluğ, Esin; Öztürk, Ferhat; Aliyazıcıoğlu, Rezzan; Canpolat, Sinan; Kolaylı, Sevgi

2013-01-01

Bee pollen has been used as an apitherapy agent for several centuries to treat burns, wounds, gastrointestinal disorders, and various other diseases. The aim of our study was to investigate the hepatoprotective effects of chestnut bee pollen against carbon tetrachloride (CCI4)-induced liver damage. Total phenolic content, flavonoid, ferric reducing/antioxidant power, and DPPH radical activity measurements were used as antioxidant capacity determinants of the pollen. The study was conducted in rats as seven groups. Two different concentrations of chestnut bee pollens (200 and 400 mg/kg/day) were given orally and one group was administered with silibinin (50 mg/kg/day, i.p.) for seven days to the rats following the CCI4 treatment. The protective effect of the bee pollen was monitored by aspartate transaminase (AST) and alanine transaminase (AST) activities, histopathological imaging, and antioxidant parameters from the blood and liver samples of the rats. The results were compared with the silibinin-treated and untreated groups. We detected that CCI4 treatment induced liver damage and both the bee pollen and silibinin-treated groups reversed the damage; however, silibinin caused significant weight loss and mortality due, severe diarrhea in the rats. The chestnut pollen had showed 28.87 mg GAE/g DW of total phenolic substance, 8.07 mg QUE/g DW of total flavonoid, 92.71 mg Cyn-3-glu/kg DW of total anthocyanins, and 9 mg β-carotene/100 g DW of total carotenoid and substantial amount of antioxidant power according to FRAP and DPPH activity. The results demonstrated that the chestnut bee pollen protects the hepatocytes from the oxidative stress and promotes the healing of the liver damage induced by CCI4 toxicity. Our findings suggest that chestnut bee pollen can be used as a safe alternative to the silibinin in the treatment of liver injuries. PMID:24250716

Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

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

Xu, Ya-Qiong; Jin, Shao-Ju; Luohe Medical College, Luohe 462002, Henan Province

Highlights: • Aloperine has anti-nociceptive effects on neuropathic pain induced CCI. • Aloperine reduces ROS in neuropathic pain mice. • Aloperine down-regulates the expression of NF-κB and its downstream pro-inflammatory cytokines in neuropathic pain mice. - Abstract: Objective: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. Methods: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressuremore » and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot. Results: Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.). Conclusion: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.« less

Sialic Acid-Responsive Polymeric Interface Material: From Molecular Recognition to Macroscopic Property Switching

NASA Astrophysics Data System (ADS)

Xiong, Yuting; Jiang, Ge; Li, Minmin; Qing, Guangyan; Li, Xiuling; Liang, Xinmiao; Sun, Taolei

2017-01-01

Biological systems that utilize multiple weak non-covalent interactions and hierarchical assemblies to achieve various bio-functions bring much inspiration for the design of artificial biomaterials. However, it remains a big challenge to correlate underlying biomolecule interactions with macroscopic level of materials, for example, recognizing such weak interaction, further transforming it into regulating material’s macroscopic property and contributing to some new bio-applications. Here we designed a novel smart polymer based on polyacrylamide (PAM) grafted with lactose units (PAM-g-lactose0.11), and reported carbohydrate-carbohydrate interaction (CCI)-promoted macroscopic properties switching on this smart polymer surface. Detailed investigations indicated that the binding of sialic acid molecules with the grafted lactose units via the CCIs induced conformational transformation of the polymer chains, further resulted in remarkable and reversible switching in surface topography, wettability and stiffness. With these excellent recognition and response capacities towards sialic acid, the PAM-g-lactose0.11 further facilitated good selectivity, strong anti-interference and high adsorption capacity in the capture of sialylated glycopeptides (important biomarkers for cancers). This work provides some enlightenment for the development of biointerface materials with tunable property, as well as high-performance glycopeptide enrichment materials.

Genomic, transcriptomic, and proteomic approaches towards understanding the molecular mechanisms of salt tolerance in Frankia strains isolated from Casuarina trees.

PubMed

Oshone, Rediet; Ngom, Mariama; Chu, Feixia; Mansour, Samira; Sy, Mame Ourèye; Champion, Antony; Tisa, Louis S

2017-08-18

Soil salinization is a worldwide problem that is intensifying because of the effects of climate change. An effective method for the reclamation of salt-affected soils involves initiating plant succession using fast growing, nitrogen fixing actinorhizal trees such as the Casuarina. The salt tolerance of Casuarina is enhanced by the nitrogen-fixing symbiosis that they form with the actinobacterium Frankia. Identification and molecular characterization of salt-tolerant Casuarina species and associated Frankia is imperative for the successful utilization of Casuarina trees in saline soil reclamation efforts. In this study, salt-tolerant and salt-sensitive Casuarina associated Frankia strains were identified and comparative genomics, transcriptome profiling, and proteomics were employed to elucidate the molecular mechanisms of salt and osmotic stress tolerance. Salt-tolerant Frankia strains (CcI6 and Allo2) that could withstand up to 1000 mM NaCl and a salt-sensitive Frankia strain (CcI3) which could withstand only up to 475 mM NaCl were identified. The remaining isolates had intermediate levels of salt tolerance with MIC values ranging from 650 mM to 750 mM. Comparative genomic analysis showed that all of the Frankia isolates from Casuarina belonged to the same species (Frankia casuarinae). Pangenome analysis revealed a high abundance of singletons among all Casuarina isolates. The two salt-tolerant strains contained 153 shared single copy genes (most of which code for hypothetical proteins) that were not found in the salt-sensitive(CcI3) and moderately salt-tolerant (CeD) strains. RNA-seq analysis of one of the two salt-tolerant strains (Frankia sp. strain CcI6) revealed hundreds of genes differentially expressed under salt and/or osmotic stress. Among the 153 genes, 7 and 7 were responsive to salt and osmotic stress, respectively. Proteomic profiling confirmed the transcriptome results and identified 19 and 8 salt and/or osmotic stress-responsive proteins in the salt-tolerant (CcI6) and the salt-sensitive (CcI3) strains, respectively. Genetic differences between salt-tolerant and salt-sensitive Frankia strains isolated from Casuarina were identified. Transcriptome and proteome profiling of a salt-tolerant strain was used to determine molecular differences correlated with differential salt-tolerance and several candidate genes were identified. Mechanisms involving transcriptional and translational regulation, cell envelop remodeling, and previously uncharacterized proteins appear to be important for salt tolerance. Physiological and mutational analyses will further shed light on the molecular mechanism of salt tolerance in Casuarina associated Frankia isolates.

Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury

PubMed Central

Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I.

2015-01-01

Abstract Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3–only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI. PMID:25419789

KSC-2013-2360

NASA Image and Video Library

2013-05-15

EDWARDS, Calif. – ED13-0142-10: The flatbed truck and trailer that transported Sierra Nevada Corporation, or SNC, Space Systems' Dream Chaser engineering test article pauses on the aircraft ramp at NASA's Dryden Flight Research Center on Edwards Air Force Base, Calif., upon arrival at the center. Following removal of the protective plastic wrap and reinstallation of its wings and tail structure, the Dream Chaser will begin ground tests in the next few weeks leading to approach and landing flight tests this summer. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Tom Tschida

Photobiomodulation therapy by NIR laser in persistent pain: an analytical study in the rat.

PubMed

Micheli, Laura; Di Cesare Mannelli, Lorenzo; Lucarini, Elena; Cialdai, Francesca; Vignali, Leonardo; Ghelardini, Carla; Monici, Monica

2017-11-01

Over the past three decades, physicians have used laser sources for the management of different pain conditions obtaining controversial results that call for further investigations. In order to evaluate the pain relieving possibilities of photobiomodulation therapy (PBMT), we tested two near infrared (NIR) laser systems, with different power, against various kinds of persistent hyperalgesia animal models. In rats, articular pain was reproduced by the intra-articular injection of sodium monoiodoacetate (MIA) and complete Freund's adjuvant (CFA), while compressive neuropathy was modelled by the chronic constriction injury of the sciatic nerve (CCI). In MIA and CFA models, (NIR) laser (MLS-Mphi, ASA S.r.l., Vicenza, Italy) application was started 14 days after injury and was performed once a day for a total of 13 applications. In MIA-treated animals, the anti-hyperalgesic effect of laser began 5 min after treatment and vanished after 60 min. The subsequent applications evoked similar effects. In CFA-treated rats, laser efficacy started 5 min after treatment and disappeared after 180 min. In rats that underwent CCI, two treatment protocols with similar fluence but different power output were tested using a new experimental device called Multiwave Locked System laser (MLS-HPP). Treatments began 7 days after injury and were performed during 3 weeks for a total of 10 applications. Both protocols reduced mechanical hyperalgesia and hindlimb weight bearing alterations until 60 min after treatment with a higher efficacy recorded for the animals treated using the higher power output. In conclusion, this study supports laser therapy as a potential treatment for immediate relief of chronic articular or neuropathic pain.

Interacting helical surfaces of the transmembrane segments of subunits a and c' of the yeast V-ATPase defined by disulfide-mediated cross-linking.

PubMed

Kawasaki-Nishi, Shoko; Nishi, Tsuyoshi; Forgac, Michael

2003-10-24

Proton translocation by the vacuolar (H+)-ATPase (or V-ATPase) has been shown by mutagenesis to be dependent upon charged residues present within transmembrane segments of subunit a as well as the three proteolipid subunits (c, c', and c"). Interaction between R735 in TM7 of subunit a and the glutamic acid residue in the middle of TM4 of subunits c and c' or TM2 of subunit c" has been proposed to be essential for proton release to the luminal compartment. In order to determine whether the helical face of TM7 of subunit a containing R735 is capable of interacting with the helical face of TM4 of subunit c' containing the essential glutamic acid residue (Glu-145), cysteine-mediated cross-linking between these subunits in yeast has been performed. Cys-less forms of subunits a and c' as well as forms containing unique cysteine residues were constructed, introduced together into a strain disrupted in both endogenous subunits, and tested for growth at neutral pH, for assembly competence and for cross-linking in the presence of cupric-phenanthroline by SDS-PAGE and Western blot analysis. Four different cysteine mutants of subunit a were each tested pairwise with ten different unique cysteine mutants of subunit c'. Strong cross-linking was observed for the pairs aS728C/c'I142C, aA731C/c'E145C, aA738C/c'F143C, aA738C/c'L147C, and aL739C/c'L147C. Partial cross-linking was observed for an additional 13 of 40 pairs analyzed. When arrayed on a helical wheel diagram, the results suggest that the helical face of TM7 of subunit a containing Arg-735 interacts with the helical face of TM4 of subunit c' centered on Val-146 and bounded by Glu-145 and Leu-147. The results are consistent with a possible rotational flexibility of one or both of these transmembrane segments as well as some flexibility of movement perpendicular to the membrane.

Synchronous cardiocerebral infarction in the era of endovascular therapy: which to treat first?

PubMed

Yeo, Leonard L L; Andersson, Tommy; Yee, Kong Wan; Tan, Benjamin Y Q; Paliwal, Prakash; Gopinathan, Anil; Nadarajah, Mahendran; Ting, Eric; Teoh, Hock L; Cherian, Robin; Lundström, Erik; Tay, Edgar L W; Sharma, Vijay K

2017-07-01

A cardiocerebral ischemic attack (CCI) or a concurrent acute ischemic stroke (AIS) and myocardial infarction (AMI) is a severe event with no clear recommendations for ideal management because of the rarity of the scenario. The narrow time window for treatment and complexity of the treatment decision puts immense pressure on the treating physician. We evaluated this challenging situation at our tertiary center. Using our prospective stroke database out of a total of 555 patients with acute ischemic stroke between 2009 and 2014, we identified five consecutive cases with CCI (incidence 0.009%). Demography, risk factor characteristics, vascular occlusions and treatment approach were recorded. Good functional outcome was defined by the modified Rankin scale (mRS) score of 0-2 points. Out of five patients, AIS was treated with endovascular treatment in three cases, while two were treated with intravenous thrombolysis only. One out of three patients had embolectomy of the brain performed prior to the coronary intervention, while the other two patients underwent coronary intervention first. One patient developed sudden cardiac arrest on day-2 and passed away. CCI is an uncommon and devastating clinical scenario, further research is needed for the ideal management strategy that provides the best outcomes. However, the rarity of the disease does not lend itself to the conduct of a trial easily. We have proposed a considered treatment algorithm based on the current literature and our experience.

Soil moisture downscaling using a simple thermal based proxy

NASA Astrophysics Data System (ADS)

Peng, Jian; Loew, Alexander; Niesel, Jonathan

2016-04-01

Microwave remote sensing has been largely applied to retrieve soil moisture (SM) from active and passive sensors. The obvious advantage of microwave sensor is that SM can be obtained regardless of atmospheric conditions. However, existing global SM products only provide observations at coarse spatial resolutions, which often hamper their applications in regional hydrological studies. Therefore, various downscaling methods have been proposed to enhance the spatial resolution of satellite soil moisture products. The aim of this study is to investigate the validity and robustness of a simple Vegetation Temperature Condition Index (VTCI) downscaling scheme over different climates and regions. Both polar orbiting (MODIS) and geostationary (MSG SEVIRI) satellite data are used to improve the spatial resolution of the European Space Agency's Water Cycle Multi-mission Observation Strategy and Climate Change Initiative (ESA CCI) soil moisture, which is a merged product based on both active and passive microwave observations. The results from direct validation against soil moisture in-situ measurements, spatial pattern comparison, as well as seasonal and land use analyses show that the downscaling method can significantly improve the spatial details of CCI soil moisture while maintain the accuracy of CCI soil moisture. The application of the scheme with different satellite platforms and over different regions further demonstrate the robustness and effectiveness of the proposed method. Therefore, the VTCI downscaling method has the potential to facilitate relevant hydrological applications that require high spatial and temporal resolution soil moisture.

Risk factors for competing noncancer mortality after definitive treatment for advanced-stage head and neck cancer.

PubMed

Kim, Yong Han; Roh, Jong-Lyel; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2018-05-27

Patients with head and neck cancer (HNC) can die of index tumor progression and second tumor or noncancer causes. Here, we investigated the risk factors for competing noncancer mortality (NCM) in a prospective cohort of patients with advanced-stage HNC. A prospective observational study was conducted with 604 patients who underwent definitive treatment for advanced-stage HNC between 2010 and 2015. Main outcomes were NCM and cancer mortality (CM) defined as death from noncancer causes and HNC or second cancers, respectively. Cumulative incidence and cause-specific hazard functions were used to analyze the risk factors of NCM and CM. Age, smoking, Charlson comorbidity index (CCI), performance status, body mass index, rural residence, education and hemoglobin level at diagnosis, and chemotherapy were significantly associated with NCM (all P<0.05). Multivariate analyses showed that age, CCI, and hemoglobin were independent factors of NCM. Age (≥65 years), CCI (≥2), and hemoglobin (<11 g/dL) were related to 4.5-, 3.2-, and 2.7-fold increased adjusted risk of NCM, respectively. Old age, comorbidity, and hemoglobin at diagnosis were independent predictors of NCM. The risk factors could be used to predict noncancer death after definitive treatment for advanced-stage HNC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The transcription factor C/EBPβ in the dorsal root ganglion contributes to peripheral nerve trauma–induced nociceptive hypersensitivity

PubMed Central

Li, Zhisong; Mao, Yuanyuan; Liang, Lingli; Wu, Shaogen; Yuan, Jingjing; Mo, Kai; Cai, Weihua; Mao, Qingxiang; Cao, Jing; Bekker, Alex; Zhang, Wei; Tao, Yuan-Xiang

2017-01-01

Changes in gene transcription in the dorsal root ganglion (DRG) after nerve trauma contribute to the genesis of neuropathic pain. We report that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPβ (CCAAT/enhancer binding protein β) in the DRG. Blocking this increase mitigated the development and maintenance of CCI-induced mechanical, thermal, and cold pain hypersensitivities without affecting basal responses to acute pain and locomotor activity. Conversely, mimicking this increase produced hypersensitivity to mechanical, thermal, or cold pain. In the ipsilateral DRG, C/EBPβ promoted a decrease in the abundance of the voltage-gated potassium channel subunit Kv1.2 and µ opioid receptor (MOR) at the mRNA and protein levels, which would be predicted to increase excitability in the ipsilateral DRG neurons and reduce the efficacy of morphine analgesia. These effects required C/EPBβ-mediated transcriptional activation of Ehmt2 (euchromatic histonelysine N-methyltransferase 2), which encodes G9a, an epigenetic silencer of the genes encoding Kv1.2 and MOR. Blocking the increase in C/EBPβ in the DRG improved morphine analgesia after CCI. These results suggest that C/EBPβ is an endogenous initiator of neuropathic pain and could be a potential target for the prevention and treatment of this disorder. PMID:28698219

Relationship between co-morbidities at diagnosis, survival and ultimate cause of death in patients with chronic lymphocytic leukaemia (CLL): a prospective cohort study.

PubMed

Strati, Paolo; Parikh, Sameer A; Chaffee, Kari G; Kay, Neil E; Call, Timothy G; Achenbach, Sara J; Cerhan, James R; Slager, Susan L; Shanafelt, Tait D

2017-08-01

The ultimate cause of death for most patients with newly diagnosed chronic lymphocytic leukaemia (CLL) and its relationship to co-morbid health conditions is poorly defined. We conducted a prospective cohort study that systematically followed 1143 patients diagnosed with CLL between June 2002 and November 2014. Comorbid health conditions at the time of CLL diagnosis and their relationship to survival and cause of death were evaluated. Collectively, 1061 (93%) patients had at least one co-morbid health condition at the time of CLL diagnosis (median number 3). Despite this, 89% of patients had a low-intermediate Charlson Comorbidity Index score (CCI) at diagnosis. After a median follow-up of 6 years, 225 patients have died. Death was due to CLL progression in 85 (46%) patients, infection in 14 (8%) patients, other cancer in 35 (19%) patients and comorbid health conditions in 50 (27%) patients. Higher CCI score and a greater number of major comorbid health conditions at the time of CLL diagnosis was associated with shorter non-CLL specific survival, but not with shorter CLL-specific survival on multivariate analysis. In conclusion, CLL and CLL-related complications (infections and second cancers) are the overwhelming cause of death in patients with CLL, regardless of CCI score and number of comorbid health conditions at diagnosis. © 2017 John Wiley & Sons Ltd.

Toward an integrated view of ionospheric plasma instabilities: Altitudinal transitions and strong gradient case

NASA Astrophysics Data System (ADS)

Makarevich, Roman A.

2016-04-01

A general dispersion relation is derived that integrates the Farley-Buneman, gradient-drift, and current-convective plasma instabilities (FBI, GDI, and CCI) within the same formalism for an arbitrary altitude, wave propagation vector, and background density gradient. The limiting cases of the FBI/GDI in the E region for nearly field-aligned irregularities, GDI/CCI in the main F region at long wavelengths, and GDI at high altitudes are successfully recovered using analytic analysis. Numerical solutions are found for more general representative cases spanning the entire ionosphere. It is demonstrated that the results are consistent with those obtained using a general FBI/GDI/CCI theory developed previously at and near E region altitudes under most conditions. The most significant differences are obtained for strong gradients (scale lengths of 100 m) at high altitudes such as those that may occur during highly structured soft particle precipitation events. It is shown that the strong gradient case is dominated by inertial effects and, for some scales, surprisingly strong additional damping due to higher-order gradient terms. The growth rate behavior is examined with a particular focus on the range of wave propagations with positive growth (instability cone) and its transitions between altitudinal regions. It is shown that these transitions are largely controlled by the plasma density gradients even when FBI is operational.

Impact of Malnutrition on Physical, Cognitive Function and Mortality among Older Men Living in Veteran Homes by Minimum Data Set: A Prospective Cohort Study in Taiwan.

PubMed

Chen, L-Y; Liu, L-K; Hwang, A-C; Lin, M-H; Peng, L-N; Chen, L-K; Lan, C-F; Chang, P-L

2016-01-01

To evaluate the prevalence of malnutrition and its impact on mortality, functional decline and cognitive impairment among elder residents in long-term care settings. A prospective cohort study. Two veteran homes in Taiwan. A total of 1,248 male residents aged equal or more than 65 years. Charlson's comorbidity index (CCI), Minimum data set (MDS), resident assessment protocols (RAP), Activity of daily living-Hierarchy scale, Cognitive Performance Scale, MDS Social engagement scale. The mean age of participants is 83.1 ± 5.1 years, and the prevalence of malnutrition was 6.1%. Inadequate dietary content (57.9%) and unintentional weight loss (31.6%) account for the majority of malnutrition identified by MDS tool. Higher 18-month mortality rate (25% vs. 14.2%), higher baseline CCI (median 1 vs. 0), and higher baseline sum of RAP triggers (median 8.5 vs. 5) were noted among residents with malnutrition. Furthermore, malnutrition was shown predictive for functional decline (OR: 3.096, 95% CI: 1.715-5.587) and potential cognitive improvement (OR: 2.469, 95% CI: 1.188-5.128) among survivors after adjustment for age, body mass index and CCI. Malnutrition among elder men residing in veteran homes was associated with multimorbidities and higher care complexity, and was predictive for mortality and functional decline.

Cymbopogon citratus industrial waste as a potential source of bioactive compounds.

PubMed

Tavares, Filipa; Costa, Gustavo; Francisco, Vera; Liberal, Joana; Figueirinha, Artur; Lopes, Maria Celeste; Cruz, Maria Teresa; Batista, Maria Teresa

2015-10-01

Cymbopogon citratus (Cc), commonly known as lemongrass, is a very important crop worldwide, being grown in tropical countries. It is widely used in the food, pharmaceutical, cosmetic and perfumery industries for its essential oil. Cc aqueous extracts are also used in traditional medicine. They contain high levels of polyphenols, which are known for their antioxidant and anti-inflammatory properties. Hydrodistillation of lemongrass essential oil produces an aqueous waste (CcHD) which is discarded. Therefore a comparative study between CcHD and Cc infusion (CcI) was performed to characterize its phytochemical profile and to research its antioxidant and anti-inflammatory potential. HPLC-PDA/ESI-MS(n) analysis showed that CcI and CcHD have similar phenolic profiles, with CcHD presenting a higher amount of polyphenols. Additionally, both CcI and CcHD showed antioxidant activity against DPPH (EC50 of 41.72 ± 0.05 and 42.29 ± 0.05 µg mL(-1) respectively) and strong anti-inflammatory properties, by reducing NO production and iNOS expression in macrophages and through their NO-scavenging activity, in a dose-dependent manner. Furthermore, no cytotoxicity was observed. The data of this study encourage considering the aqueous solution from Cc leaf hydrodistillation as a source of bioactive compounds, which may add great industrial value to this crop. © 2014 Society of Chemical Industry.

Up-Regulation of the Biosynthesis and Release of Substance P through Wnt/β-Catenin Signaling Pathway in Rat Dorsal Root Ganglion Cells

PubMed Central

Li, Yu-Sang; Xi, Yang; Li, Xiao-Jun; Leng, Chang-Long; Jia, Mei-Mei; Zhang, Wei Kevin; Tang, He-Bin

2015-01-01

To examine regulatory effects of β-catenin on the biosynthesis and release of substance P, a rat chronic constriction injury (CCI) model and a rat dorsal root ganglion (DRG) cell culture model were used in the present study. The CCI treatment significantly induced the overall expression of β-catenin (158 ± 6% of sham) in the ipsilateral L5 DRGs in comparison with the sham group (109 ± 4% of sham). The CCI-induced aberrant expression of β-catenin was significantly attenuated by oral administration of diclofenac (119 ± 6% of the sham value; 10 mg/kg). Importantly, aberrant nuclear accumulation of β-catenin in cultured DRG cells resulted in up-regulation of the PPT-A mRNA expression and the substance P release. The up-regulation of both the PPT-A mRNA expression and the substance P release by either a GSK-3β inhibitor TWS119 (10 μM) or a Wnt signaling agonist Wnt-3a (100 ng/ml) were significantly abolished by an inhibitor of cyclooxygenase-2 (COX-2; NS-398, 1 μM). Collectively, these data suggest that nociceptive input-activated β-catenin signaling plays an important role in regulating the biosynthesis and release of substance P, which may contribute to the inflammation responses related to chronic pain. PMID:26054011

Up-Regulation of the Biosynthesis and Release of Substance P through Wnt/β-Catenin Signaling Pathway in Rat Dorsal Root Ganglion Cells.

PubMed

Li, Yu-Sang; Xi, Yang; Li, Xiao-Jun; Leng, Chang-Long; Jia, Mei-Mei; Zhang, Wei Kevin; Tang, He-Bin

2015-01-01

To examine regulatory effects of β-catenin on the biosynthesis and release of substance P, a rat chronic constriction injury (CCI) model and a rat dorsal root ganglion (DRG) cell culture model were used in the present study. The CCI treatment significantly induced the overall expression of β-catenin (158 ± 6% of sham) in the ipsilateral L5 DRGs in comparison with the sham group (109 ± 4% of sham). The CCI-induced aberrant expression of β-catenin was significantly attenuated by oral administration of diclofenac (119 ± 6% of the sham value; 10 mg/kg). Importantly, aberrant nuclear accumulation of β-catenin in cultured DRG cells resulted in up-regulation of the PPT-A mRNA expression and the substance P release. The up-regulation of both the PPT-A mRNA expression and the substance P release by either a GSK-3β inhibitor TWS119 (10 μM) or a Wnt signaling agonist Wnt-3a (100 ng/ml) were significantly abolished by an inhibitor of cyclooxygenase-2 (COX-2; NS-398, 1 μM). Collectively, these data suggest that nociceptive input-activated β-catenin signaling plays an important role in regulating the biosynthesis and release of substance P, which may contribute to the inflammation responses related to chronic pain.

Neuroprotective Effects of Platonin, a Therapeutic Immunomodulating Medicine, on Traumatic Brain Injury in Mice after Controlled Cortical Impact.

PubMed

Yen, Ting-Lin; Chang, Chao-Chien; Chung, Chi-Li; Ko, Wen-Chin; Yang, Chih-Hao; Hsieh, Cheng-Ying

2018-04-06

Traumatic brain injury (TBI) is one of the leading causes of mortality worldwide and leads to persistent cognitive, sensory, motor dysfunction, and emotional disorders. TBI-caused primary injury results in structural damage to brain tissues. Following the primary injury, secondary injuries which are accompanied by neuroinflammation, microglial activation, and additional cell death subsequently occur. Platonin, a cyanine photosensitizing dye, has been used to treat trauma, ulcers, and some types of acute inflammation. In the present study, the neuroprotective effects of platonin against TBI were explored in a controlled cortical impact (CCI) injury model in mice. Treatment with platonin (200 µg/kg) significantly reduced the neurological severity score, general locomotor activity, and anxiety-related behavior, and improved the rotarod performance of CCI-injured mice. In addition, platonin reduced lesion volumes, the expression of cleaved caspase-3, and microglial activation in TBI-insulted brains. Platonin also suppressed messenger (m)RNA levels of caspase-3, caspase-1, cyclooxygenase-2, tumor necrosis factor-α, interleukin-6, and interleukin-1β. On the other hand, free radical production after TBI was obviously attenuated in platonin-treated mice. Treatment with platonin exhibited prominent neuroprotective properties against TBI in a CCI mouse model through its anti-inflammatory, anti-apoptotic, and anti-free radical capabilities. This evidence collectively indicates that platonin may be a potential therapeutic medicine for use with TBIs.

Vanderbilt University Institute of Imaging Science Center for Computational Imaging XNAT: A multimodal data archive and processing environment.

PubMed

Harrigan, Robert L; Yvernault, Benjamin C; Boyd, Brian D; Damon, Stephen M; Gibney, Kyla David; Conrad, Benjamin N; Phillips, Nicholas S; Rogers, Baxter P; Gao, Yurui; Landman, Bennett A

2016-01-01

The Vanderbilt University Institute for Imaging Science (VUIIS) Center for Computational Imaging (CCI) has developed a database built on XNAT housing over a quarter of a million scans. The database provides framework for (1) rapid prototyping, (2) large scale batch processing of images and (3) scalable project management. The system uses the web-based interfaces of XNAT and REDCap to allow for graphical interaction. A python middleware layer, the Distributed Automation for XNAT (DAX) package, distributes computation across the Vanderbilt Advanced Computing Center for Research and Education high performance computing center. All software are made available in open source for use in combining portable batch scripting (PBS) grids and XNAT servers. Copyright © 2015 Elsevier Inc. All rights reserved.

Progression to Uncontrolled Severe Asthma: A Novel Risk Equation.

PubMed

Casciano, Julian; Krishnan, Jerry; Small, Mary Buatti; Li, Chenghui; Dotiwala, Zenobia; Martin, Bradley C

2017-01-01

Recently published asthma guidelines by the European Respiratory Society and the American Thoracic Society (ERS-ATS) define severe disease based on medication use and control level. These guidelines also emphasize that asthma severity involves certain biomarker phenotypes, one of them being eosinophilic phenotype. The quantification of the influence of eosinophil level toward predicting disease severity can help decision makers manage therapy better earlier. To develop a risk-scoring algorithm to identify patients at greater risk of developing uncontrolled severe asthma as defined by ERS-ATS guidelines. Data on asthma patients were extracted from the EMRClaims + database from January 2004 to July 2011. Patients with continuous enrollment 12 months before and after the date of the first encounter with a diagnosis of asthma (index date) with at least 1 blood eosinophil test result in the 12 months after the index date, but before the development of uncontrolled severe asthma or the study end date, were included. Uncontrolled severe asthma was defined as the first date on which all criteria of the ERS-ATS definition were first satisfied in the 12 months after the index date. Age (≥ 50 years vs. < 50 years), race, and sex were measured at index, and the Charlson Comorbidity Index (CCI) score (> 0 vs. 0) was measured in the pre-index period. Elevated eosinophil level was defined as a test result with ≥ 400 cells/µL. The study cohort was randomly split 50-50 into derivation and validation samples. Cox proportional hazards regression was used to develop the risk score for uncontrolled severe asthma using the derivation cohort with independent variables of eosinophil level, age, sex, race, and CCI. A bootstrapping procedure was used to generate 1,000 samples from the derivation cohort. Variables significant in ≥ 50% of the samples were retained in the final regression model. A risk score was then calculated based on the coefficient estimates of the final model. C-statistic was used to test the model's discrimination power. The study included 2,405 patients, 147 (6%) of whom developed uncontrolled severe asthma. Higher eosinophil level and CCI score > 0 were significantly and independently associated with an increased risk of uncontrolled severe asthma in the derivation cohort (HR = 1.90, 95% CI = 1.17-3.08 and HR = 2.00, 95% CI = 1.28-3.13, respectively); findings were similar in the validation cohort. Total risk score was categorized as 0, 2, and 4. All models showed good C-statistics (0.79-0.80), indicating favorable model discrimination. There was a significantly greater number of patients with uncontrolled severe asthma in the risk score segments of 2 and 4 compared with 0 (each P < 0.0001). A risk stratification tool using peripheral eosinophil counts and CCI can be used to predict the development of uncontrolled severe asthma. This study was funded by Teva Pharmaceuticals. eMAX Health Systems was a consultant to Teva Pharmaceuticals for this study and received payment from Teva Pharmaceuticals for work on this study. Casciano and Dotiwala are employed by eMAX Health Systems. Krishnan, Li, and Martin received payment from eMAX Health Systems for work on this study. Small was employed by Teva Pharmaceuticals at the time of this study. Study concept and design were contributed primarily by Casciano, Krishnan, Small, and Martin, along with Li and Dotiwala. Dotiwala, Casciano, Small, and Li collected the data, along with Martin and Li and Krishnan. Data interpretation was provided by Martin, Casciano, and Li, with assistance from the other authors. The manuscript was written by Li, Casciano, Dotiwala, and Small, with assistance from the other authors, and revised by Dotiwala, Small, Li, and Martin, with assistance from Krishnan and Casciano.

KSC-2013-2357

NASA Image and Video Library

2013-05-15

EDWARDS, Calif. – ED13-0142-01: With its wings and tail structure removed and shrouded in plastic wrap for ground transport, Sierra Nevada Corporation, or SNC, Space Systems' Dream Chaser engineering test article is hauled across the bed of Rogers Dry Lake at Edwards Air Force Base, Calif., to NASA's Dryden Flight Research Center. The Dream Chaser will begin its approach-and-landing flight test program in collaboration with NASA's Commercial Crew Program this summer. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Tom Tschida

KSC-2013-2358

NASA Image and Video Library

2013-05-15

EDWARDS, Calif. – ED13-0142-03: Shrouded in plastic wrap with its wings and tail structure removed for ground transport, Sierra Nevada Corporation, or SNC, Space Systems' Dream Chaser engineering test article is hauled across the bed of Rogers Dry Lake in front of the control tower at Edwards Air Force Base, Calif., to NASA's Dryden Flight Research Center. The Dream Chaser will begin its flight test program in collaboration with NASA's Commercial Crew Program this summer. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Tom Tschida

The ESA Cloud CCI project: Generation of Multi Sensor consistent Cloud Properties with an Optimal Estimation Based Retrieval Algorithm

NASA Astrophysics Data System (ADS)

Jerg, M.; Stengel, M.; Hollmann, R.; Poulsen, C.

2012-04-01

The ultimate objective of the ESA Climate Change Initiative (CCI) Cloud project is to provide long-term coherent cloud property data sets exploiting and improving on the synergetic capabilities of past, existing, and upcoming European and American satellite missions. The synergetic approach allows not only for improved accuracy and extended temporal and spatial sampling of retrieved cloud properties better than those provided by single instruments alone but potentially also for improved (inter-)calibration and enhanced homogeneity and stability of the derived time series. Such advances are required by the scientific community to facilitate further progress in satellite-based climate monitoring, which leads to a better understanding of climate. Some of the primary objectives of ESA Cloud CCI Cloud are (1) the development of inter-calibrated radiance data sets, so called Fundamental Climate Data Records - for ESA and non ESA instruments through an international collaboration, (2) the development of an optimal estimation based retrieval framework for cloud related essential climate variables like cloud cover, cloud top height and temperature, liquid and ice water path, and (3) the development of two multi-annual global data sets for the mentioned cloud properties including uncertainty estimates. These two data sets are characterized by different combinations of satellite systems: the AVHRR heritage product comprising (A)ATSR, AVHRR and MODIS and the novel (A)ATSR - MERIS product which is based on a synergetic retrieval using both instruments. Both datasets cover the years 2007-2009 in the first project phase. ESA Cloud CCI will also carry out a comprehensive validation of the cloud property products and provide a common data base as in the framework of the Global Energy and Water Cycle Experiment (GEWEX). The presentation will give an overview of the ESA Cloud CCI project and its goals and approaches and then continue with results from the Round Robin algorithm comparison exercise carried out at the beginning of the project which included three algorithms. The purpose of the exercise was to assess and compare existing cloud retrieval algorithms in order to chose one of them as backbone of the retrieval system and also identify areas of potential improvement and general strengths and weaknesses of the algorithm. Furthermore the presentation will elaborate on the optimal estimation algorithm subsequently chosen to derive the heritage product and which is presently further developed and will be employed for the AVHRR heritage product. The algorithm's capabilities to coherently and simultaneously process all radiative input and yield retrieval parameters together with associated uncertainty estimates will be presented together with first results for the heritage product. In the course of the project the algorithm is being developed into a freely and publicly available community retrieval system for interested scientists.

Neuroprotective effect of Da Chuanxiong Formula against cognitive and motor deficits in a rat controlled cortical impact model of traumatic brain injury.

PubMed

Liu, Zhi-Ke; Ng, Chun-Fai; Shiu, Hoi-Ting; Wong, Hing-Lok; Chin, Wai-Ching; Zhang, Jin-Fang; Lam, Ping-Kuen; Poon, Wai-Sang; Lau, Clara Bik-San; Leung, Ping-Chung; Ko, Chun-Hay

2018-05-10

Da Chuanxiong Formula (DCXF) is one of the famous herb pairs that contains dried rhizomes of Ligusticum chuanxiong Hort. and Gastrodia elata Bl. in the mass ratio of 4:1. This classic representative traditional Chinese medicine has been widely used to treat brain diseases like headache and migraine caused by blood stasis and wind pathogen. However, the therapeutic effect of DCXF on traumatic brain injury (TBI) has not been reported yet. The present study was performed to investigate the neuroprotective effects of DCXF and its underlying mechanisms in the controlled cortical impact (CCI)-induced TBI rat model. Male Sprague-Dawley rats were divided into four groups: Sham, TBI control, 1X DCXF (520.6 mg/kg) and 5X DCXF (2603.0 mg/kg). Two treatment groups (1X and 5X DCXF) were intragastrically administered daily for 7 days before CCI-induced TBI and then DCXF treatments were continued post-TBI until the animal behavioral tests, including Morris water maze test, acceleration rotarod motor test and CatWalk quantitative gait analysis test, were done. The brain water content and blood brain barrier (BBB) integrity were measured by wet-dry weight method and Evans blue method, respectively. The number of neuron cells, neural stem cells (NSCs), GFAP positive cells (astrocyte) as well as Iba-1 positive cells (microglia) were determined by histology and immunohistochemistry. Treatment with DCXF significantly improved the learning ability and memory retention in Morris water maze test, and remarkably enhanced motor performances in acceleration rotarod motor test and catwalk quantitative gait analysis test after TBI. Moreover, DCXF treatment was able to reduce BBB permeability, brain edema, microglia and astrocyte activation, improve the proliferation of NSCs and decrease neurons loss in the brain with TBI. The present study demonstrated that DCXF treatment could decrease BBB leakage and brain edema, reduce neuron loss, microglia and astrocyte activation, and increase NSCs proliferation, which may contribute to the cognitive and motor protection of DCXF in the TBI rats. It is the first time to provide potentially underlying mechanisms of the neuroprotective effect of DCXF on TBI-induced brain damage and functional outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

KSC-2013-3299

NASA Image and Video Library

2013-08-02

Edwards, Calif. – ED13-0266-013- Sierra Nevada Corporation, or SNC, team members prepare for 60 mph tow tests of the company's Dream Chaser flight vehicle on taxi and runways at NASA's Dryden Flight Research Center at Edwards Air Force Base in California. Ground testing at 10, 20, 40 and 60 miles per hour is helping the company validate the performance of the spacecraft's braking and landing systems prior to captive-carry and free-flight tests scheduled for later this year. SNC is continuing the development of its Dream Chaser spacecraft under the agency's Commercial Crew Development Round 2, or CCDev2, and Commercial Crew Integrated Capability, or CCiCap, phases, which are intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Ken Ulbrich

Orbiter Crew Compartment Integration-Stowage

NASA Technical Reports Server (NTRS)

Morgan, L. Gary

2007-01-01

This viewgraph presentation describes the Orbiter Crew Compartment Integration (CCI) stowage. The evolution of orbiter crew compartment stowage volume is also described, along with photographs presented of the on-orbit volume stowage capacity.

Phobic anxiety symptom scores and incidence of type 2 diabetes in US men and women

PubMed Central

Farvid, Maryam S; Qi, Lu; Hu, Frank B; Kawachi, Ichiro; Okereke, Olivia I; Kubzansky, Laura; Willett, Walter C

2013-01-01

Context Emotional stress may be a risk factor for type 2 diabetes (T2D), but the relation between phobic anxiety symptom scores and risk of T2D is uncertain. Objective To evaluate prospectively the association between phobic anxiety symptom scores and incident T2D in three cohorts of US men and women. Design, Setting and Patients We followed 30,830 men in the Health Professional’s Follow-Up Study (HPFS) (1988–2008), 69,336 women in the Nurses’ Health Study (NHS) (1988–2008), and 80,120 women in the Nurses’ Health Study II (NHS II) (1993–2011). Phobic anxiety symptom scores, as measured by the Crown-Crisp index (CCI), calculated from 8 questions, was administered at baseline and updated in 2004 for NHS, in 2005 for NHS II, and in 2000 for HPFS. Incident T2D was confirmed by a validated supplementary questionnaire. We used Cox proportional hazards analysis to evaluate associations with incident T2D. Results During 3,110,248 person-years of follow-up, we documented 12,876 incident T2D cases. In multivariable Cox regression models with adjustment for major lifestyle and dietary risk factors, the HRs of T2D across categories of increasing levels of CCI (scores= 2-<3, 3-<4, 4-<6, 6), compared with a score of <2, were increased significantly by 6%, 10%, 11% and 13% (Ptrend =0.0005) for NHS; and by 19%, 11%, 22%, and 29% (Ptrend <0.0001) for NHS II. Each score increment in CCI was associated with 3% higher risk of T2D in NHS (HRs, 1.03, 95%CI:1.02-1.04) and 4% higher risk of T2D in NHS II (HRs, 1.04, 95%CI:1.03-1.05). Further adjustment for self-reported depression and antidepressant use did not change the results. In HPFS, the association between CCI and T2D was not significant after adjusting for lifestyle variables. Conclusion Our results suggest that higher phobic anxiety symptom scores are associated with an increased risk of T2D in women. PMID:24184473

Evaluating a New Homogeneous Total Ozone Climate Data Record from GOME/ERS-2, SCIAMACHY/Envisat, and GOME-2/MetOp-A

NASA Technical Reports Server (NTRS)

Koukouli, M.E.; Lerot, C.; Granville, J.; Goutail, F.; Lambert, J.-C.; Pommereau, J.-P.; Balis, D.; Zyrichidou, I.; Van Roozendael, M.; Coldewey-Egbers, M.;

Assimilation of passive and active CCI soil moisture products into hydrological modelling: an intercomparison study in Europe

NASA Astrophysics Data System (ADS)

Maggioni, V.; Massari, C.; Camici, S.; Brocca, L.; Marchesini, I.

2017-12-01

Soil moisture (SM) is a key variable in rainfall-runoff partitioning since it acts on the main hydrological processes taking part within a catchment. Modeling SM is often a difficult task due to its large variability at different temporal and spatial scales. Ground soil moisture measurements are a valuable tool for improving runoff prediction but are often limited and suffer from spatial representativeness issues. Remotely sensed observations offer a new source of data able to cope the latter issues thus opening new possibilities for improving flood simulations worldwide. Today, several different SM products are available at increased accuracy with respect to the past. Some interesting products are those derived from the Climate Change Initiative (CCI) which offer the most complete and most consistent global SM data record based on active and passive microwave sensors.Thanks to the combination of multiple sensors within an active, a passive and an active+passive products, the CCI SM is expected to provide a significant benefit for the improvement of rainfall-runoff simulations through data assimilation. However, previous studies have shown that the success of the assimilation is not only related to the accuracy of the observations but also to the specific climate and the catchment physical and hydrological characteristics as well as to many necessary choices related to the assimilation technique. These choices along with the type of SM observations (i.e. passive or active) might play an important role for the success or the failure of the assimilation exercise which is not still clear. In this study, based on a large dataset of catchments covering large part of the Europe, we assimilated satellite SM observations from the passive and the active CCI SM products into Modello Idrologico Semiditribuito in Continuo (MISDc, Brocca et al. 2011). Rainfall and temperature data were collected from the European Climate Assessment & Dataset (E-OBS) while discharge data were obtained from the Global Runoff Data Centre (GRDC). Preliminary results show a general improvement of the hydrological simulations for catchments located in the Mediterranean areas specifically for the active product while lower performance is obtained at northern latitudes due to the presence of snow and ice.

On the Comparison of the Global Surface Soil Moisture product and Land Surface Modeling

NASA Astrophysics Data System (ADS)

Delorme, B., Jr.; Ottlé, C.; Peylin, P.; Polcher, J.

2016-12-01

Thanks to its large spatio-temporal coverage, the new ESA CCI multi-instruments dataset offers a good opportunity to assess and improve land surface models parametrization. In this study, the ESA CCI surface soil moisture (SSM) combined product (v2.2) has been compared to the simulated top first layers of the ORCHIDEE LSM (the continental part of the IPSL earth system model), in order to evaluate its potential of improvements with data assimilation techniques. The ambition of the work was to develop a comprehensive comparison methodology by analyzing simultaneously the temporal and spatial structures of both datasets. We analyzed the SSM synoptic, seasonal, and inter-annual variations by decomposing the signals into fast and slow components. ORCHIDEE was shown to adequately reproduce the observed SSM dynamics in terms of temporal correlation. However, these correlation scores are supposed to be strongly influenced by SSM seasonal variability and the quality of the model input forcing. Autocorrelation and spectral analyses brought out disagreements in the temporal inertia of the upper soil moisture reservoirs. By linking our results to land cover maps, we found that ORCHIDEE is more dependent on rainfall events compared to the observations in regions with sparse vegetation cover. These diflerences might be due to a wrong partition of rainfall between soil evaporation, transpiration, runofl and drainage in ORCHIDEE. To refine this analysis, a single value decomposition (SVD) of the co-variability between rainfall provided by WFDEI and soil moisture was pursued over Central Europe and South Africa. It showed that spatio-temporal co-varying patterns between ORCHIDEE and rainfall and the ESA-CCI product and rainfall are in relatively good agreement. However, the leading SVD pattern, which exhibits a strong annual cycle and explains the same portion of covariance for both datasets, explains a much larger fraction of variance for ORCHIDEE than for the ESA-CCI product. These results highlight that the role of other surface variables presenting a strong seasonal variability (like vegetation cover, possibly irrigation) is not accounted for similarly in both the model and the product, and that further work is needed to explore these discrepancies.

Anesthesia for euthanasia influences mRNA expression in healthy mice and after traumatic brain injury.

PubMed

Staib-Lasarzik, Irina; Kriege, Oliver; Timaru-Kast, Ralph; Pieter, Dana; Werner, Christian; Engelhard, Kristin; Thal, Serge C

2014-10-01

Tissue sampling for gene expression analysis is usually performed under general anesthesia. Anesthetics are known to modulate hemodynamics, receptor-mediated signaling cascades, and outcome parameters. The present study determined the influence of anesthetic paradigms typically used for euthanization and tissue sampling on cerebral mRNA expression in mice. Naïve mice and animals with acute traumatic brain injury induced by controlled cortical impact (CCI) were randomized to the following euthanasia protocols (n=10-11/group): no anesthesia (NA), 1 min of 4 vol% isoflurane in room air (ISO), 3 min of a combination of 5 mg/kg midazolam, 0.05 mg/kg fentanyl, and 0.5 mg/kg medetomidine intraperitoneally (COMB), or 3 min of 360 mg/kg chloral hydrate intraperitoneally (CH). mRNA expression of actin-1-related gene (Act1), FBJ murine osteosarcoma viral oncogene homolog B (FosB), tumor necrosis factor alpha (TNFα), heat shock protein beta-1 (HspB1), interleukin (IL)-6, tight junction protein 1 (ZO-1), IL-1ß, cyclophilin A, micro RNA 497 (miR497), and small cajal body-specific RNA 17 were determined by real-time polymerase chain reaction (PCR) in hippocampus samples. In naïve animals, Act1 expression was downregulated in the CH group compared with NA. FosB expression was downregulated in COMB and CH groups compared with NA. CCI reduced Act1 and FosB expression, whereas HspB1 and TNFα expression increased. After CCI, HspB1 expression was significantly higher in ISO, COMB, and CH groups, and TNFα expression was elevated in ISO and COMB groups. MiR497, IL-6, and IL-1ß were upregulated after CCI but not affected by anesthetics. Effects were independent of absolute mRNA copy numbers. The data demonstrate that a few minutes of anesthesia before tissue sampling are sufficient to induce immediate mRNA changes, which seem to predominate in the early-regulated gene cluster. Anesthesia-related effects on gene expression might explain limited reproduciblity of real-time PCR data between studies or research groups and should therefore be considered for quantitative PCR data.

Evaluating the Quality and Readability of Internet Information on Meningiomas.

PubMed

Saeed, Fozia; Anderson, Ian

2017-01-01

The Internet is a highly powerful resource for patients and provides an extensive amount of information on medical conditions. It is therefore important that the information accessible is accurate, up to date, and at an appropriate comprehensive level for the general public. This article aims to evaluate the quality of patient information on meningiomas. The term meningioma was searched using the following search engines: Google, Bing, Yahoo, Ask, and AOL. The top 100 meningioma Web sites were analyzed for readability using the Flesch Reading Ease score and the Flesch-Kincaid grade level. The quality of each Web page was assessed with the DISCERN instrument and the Centers for Disease Control and Prevention (CDC) Clear Communication Index (CCI). The quality of information on the Internet on meningiomas is highly variable. The overall mean Flesch Reading Ease score was 43.1 (standard deviation = 13.3) and the mean Flesch-Kincaid grade of all the Web sites was 11.2 (standard deviation = 2.3). This finding suggests that the information is on average difficult to read. Only one Web site was at the recommended seventh-grade level and the remainder were above this grade. Only one third of the Web pages had Health On the Net Code of Conduct or The Information Standard certification and were found to be significantly of higher quality: DISCERN (P = 0.022) and CDC CCI (P = 0.027). More than 50% of the Web sites had significantly poor or average DISCERN scores and only 2 Web sites fulfilled the CDC CCI criteria. It is recommended that clinicians personally research material for their patients to be able to guide them to reliable and accurate Web sites. It is also encouraged to become Health On the Net Code of Conduct/The Information Standard certified because this may indicate information of high quality. In addition, it is also recommended that authors of existing information assess the quality of their online health information against the CDC CCI criteria. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Phobic anxiety symptom scores and incidence of type 2 diabetes in US men and women.

PubMed

Farvid, Maryam S; Qi, Lu; Hu, Frank B; Kawachi, Ichiro; Okereke, Olivia I; Kubzansky, Laura D; Willett, Walter C

2014-02-01

Emotional stress may be a risk factor for type 2 diabetes (T2D), but the relation between phobic anxiety symptoms and risk of T2D is uncertain. To evaluate prospectively the association between phobic anxiety symptoms and incident T2D in three cohorts of US men and women. We followed 30,791 men in the Health Professional's Follow-Up Study (HPFS) (1988-2008), 68,904 women in the Nurses' Health Study (NHS) (1988-2008), and 79,960 women in the Nurses' Health Study II (NHS II) (1993-2011). Phobic anxiety symptom scores, as measured by the Crown-Crisp index (CCI), calculated from 8 questions, were administered at baseline and updated in 2004 for NHS, in 2005 for NHS II, and in 2000 for HPFS. Incident T2D was confirmed by a validated supplementary questionnaire. We used Cox proportional hazards analysis to evaluate associations with incident T2D. During 3,099,651 person-years of follow-up, we documented 12,831 incident T2D cases. In multivariate Cox proportional-hazards models with adjustment for major lifestyle and dietary risk factors, the hazard ratios (HRs) of T2D across categories of increasing levels of CCI (scores=2 to <3, 3 to <4, 4 to <6, ⩾6), compared with a score of <2, were increased significantly by 6%, 10%, 10% and 13% (Ptrend=0.001) for NHS; and by 19%, 11%, 21%, and 29% (Ptrend<0.0001) for NHS II. Each score increment in CCI was associated with 2% higher risk of T2D in NHS (HRs, 1.02, 95% confidence intervals: 1.01-1.03) and 4% higher risk of T2D in NHS II (HRs, 1.04, 95% confidence intervals: 1.02-1.05). Further adjustment for depression did not change the results. In HPFS, the association between CCI and T2D was not significant after adjusting for lifestyle variables. Our results suggest that higher phobic anxiety symptoms are associated with an increased risk of T2D in women. Copyright © 2013 Elsevier Inc. All rights reserved.

External Validation of Risk Prediction Scores for Invasive Candidiasis in a Medical/Surgical Intensive Care Unit: An Observational Study

PubMed Central

Ahmed, Armin; Baronia, Arvind Kumar; Azim, Afzal; Marak, Rungmei S. K.; Yadav, Reema; Sharma, Preeti; Gurjar, Mohan; Poddar, Banani; Singh, Ratender Kumar

2017-01-01

Background: The aim of this study was to conduct external validation of risk prediction scores for invasive candidiasis. Methods: We conducted a prospective observational study in a 12-bedded adult medical/surgical Intensive Care Unit (ICU) to evaluate Candida score >3, colonization index (CI) >0.5, corrected CI >0.4 (CCI), and Ostrosky's clinical prediction rule (CPR). Patients' characteristics and risk factors for invasive candidiasis were noted. Patients were divided into two groups; invasive candidiasis and no-invasive candidiasis. Results: Of 198 patients, 17 developed invasive candidiasis. Discriminatory power (area under receiver operator curve [AUROC]) for Candida score, CI, CCI, and CPR were 0.66, 0.67, 0.63, and 0.62, respectively. A large number of patients in the no-invasive candidiasis group (114 out of 181) were exposed to antifungal agents during their stay in ICU. Subgroup analysis was carried out after excluding such patients from no-invasive candidiasis group. AUROC of Candida score, CI, CCI, and CPR were 0.7, 0.7, 0.65, and 0.72, respectively, and positive predictive values (PPVs) were in the range of 25%–47%, along with negative predictive values (NPVs) in the range of 84%–96% in the subgroup analysis. Conclusion: Currently available risk prediction scores have good NPV but poor PPV. They are useful for selecting patients who are not likely to benefit from antifungal therapy. PMID:28904481

Sutured clear corneal incision: wound apposition and permeability to bacterial-sized particles.

PubMed

May, William N; Castro-Combs, Juan; Kashiwabuchi, Renata T; Tattiyakul, Woranart; Qureshi-Said, Saima; Hirai, Flavio; Behrens, Ashley

2013-03-01

To determine the effects of single radial or horizontal suture placement in 2-step clear corneal incision (CCI) wound apposition and permeability to particles of India ink. Five fresh human globes were included. Two 25-gauge needles connected to a saline solution bag and to a digital manometer were inserted through the limbus, 120 degrees apart from each other. Four 2-step CCIs (2.75 mm wide and 3 mm length) were constructed in each cornea. Incisions were divided into 3 groups: single radial suture (SRS), single horizontal suture (SHS), and unsutured group. Optical coherence tomography (OCT) was performed before and after suture placement. With a preset 10 mm Hg intraocular pressure (IOP), India ink was applied to the incision site and a standardized sudden IOP fluctuation was induced. OCT and superficial images were recorded before and after suture placement. India ink inflow and internal and external CCI gapping were outlined and measured by planimeter. The area and linear distance of India ink inflow after pressure challenge in all study groups were higher when compared with pre-pressure measurements; however, this increase was significant in the SRS and SHS groups (P < 0.05). Additionally, SRS placement significantly increased inner wound gapping (P = 0.018), and SHS significantly widened outer wound gape (P = 0.02). Well-constructed unsutured 2-step CCI seems to be more efficient at preventing bacterial-sized particles inflow during sudden changes in IOP, and it seems to offer better wound apposition as assessed by OCT.

Effects of chemical structure on the thermodynamic efficiency of radical chain carriers for organic synthesis.

PubMed

Lin, Ching Yeh; Peh, Jessie; Coote, Michelle L

2011-03-18

The chain carrier index (CCI), defined as the ratio of the bond dissociation free energies (BDFE) of corresponding chain carrier halides and hydrides, is proposed as a measure of the thermodynamic efficiency of chain carriers for radical dehalogenation. The larger this value is relative to the corresponding value of the organic substrate, the more thermodynamically efficient the process. The chloride and bromide CCIs were evaluated at the G3(MP2)-RAD(+) level of theory for 120 different R-groups, covering a broad range of carbon-centered and noncarbon-centered species; the effects of solvent and temperature have also been studied. The broad finding from this work is that successful chain carriers generally maximize the strength of their halide (versus hydride bonds) through charge-shift bonding. As a result, the thermodynamic efficiency of a chain carrier tends to increase down the periodic table, and also with the inclusion of stronger electron donating substituents. The CCIs of carbon-centered species fall into a relatively narrow range so that, even when the CCI is maximized through inclusion of lone pair donor OMe or NMe(2) groups, the thermodynamic driving force for dehalogenation of other organic substrates is modest at best, and the process is likely to be kinetically hampered. Among the noncarbon-centered species studied, bismuth- and borane-centered compounds have some of the highest CCI values and, although their kinetics requires further optimization, these classes of compounds would be worth further investigation as tin-free radical reducing agents.

The Effect of Repeated Electroacupuncture Analgesia on Neurotrophic and Cytokine Factors in Neuropathic Pain Rats

PubMed Central

Wang, Junying; Duanmu, Chenlin; Feng, Xiumei; Yan, Yaxia

2016-01-01

Chronic pain is a common disability influencing quality of life. Results of previous studies showed that acupuncture has a cumulative analgesic effect, but the relationship with spinal cytokines neurotrophic factors released by astrocytes remains unknown. The present study was designed to observe the effect of electroacupuncture (EA) treatment on spinal cytokines neurotrophic factors in chronic neuropathic pain rats. The chronic neuropathic pain was established by chronic constrictive injury (CCI). EA treatment was applied at Zusanli (ST36) and Yanglingquan (GB34) (both bilateral) once a day, for 30 min. IL-1β mRNA, TNF-α mRNA, and IL-1 mRNA were detected by quantitative real-time PCR, and the proteins of BDNF, NGF, and NT3/4 were detected by Western blot. The expression levels of cytokines such as IL-1β mRNA, TNF-α mRNA, IL-6 mRNA, and neurotrophic factors such as BDNF, NGF, and NT3/4 in the spinal cord were increased significantly after CCI. The astrocytes released more IL-1β and BDNF after CCI. Repeated EA treatment could suppress the elevated expression of IL-1β mRNA, TNFα mRNA, and BDNF, NGF, and NT3/4 but had no effect on IL-6 mRNA. It is suggested that cytokines and neurotrophic factors which may be closely associated with astrocytes participated in the process of EA relieving chronic pain. PMID:27800006

Nasal inhalation of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in the model of chronic constriction injury to the sciatic nerve of rat.

PubMed

Chen, Feng; Wang, LiQin; Chen, ShuJun; Li, ZhiGao; Chen, ZhouLin; Zhou, XinHua; Zhai, Dong

2014-01-01

The aim of the present study is to explore the impact of butorphanol in combination with ketamine via nasal inhalation (NI) on neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve in a rat model. CCI rats (n = 12) were equally randomized to four groups based on the treatments received as follows: 100 μL of 0.9% normal saline via NI (NS/NI group); 100 μg of butorphanol plus 1 mg of ketamine via NI (B + K/NI group); 100 μg of butorphanol alone via NI (B/NI group); and 100 μg of butorphanol plus 1 mg of ketamine via subcutaneous injection (B + K/SC group). Mechanical pain threshold was measured at 10 min, 30 min, 2 h, 4 h, and 6 h after drug administration. The mechanical pain threshold in the B + K/NI group was improved significantly 4 h after drug administration as compared with that in the B/NI or B + K/SC group (P < 0.05). The onset and intensity of drug action in the B + K/NI group were better than those of the other two groups, but the duration of drug action was not prolonged. NI of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in a rat neuropathic pain model induced by CCI to the sciatic nerve. Copyright © 2014 Elsevier Inc. All rights reserved.

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice

PubMed Central

Madathil, Sindhu K.; Carlson, Shaun W.; Brelsfoard, Jennifer M.; Ye, Ping; D’Ercole, A. Joseph; Saatman, Kathryn E.

2013-01-01

Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI. PMID:23826235

Neuroanatomy of Creativity

PubMed Central

Jung, Rex E.; Segall, Judith M.; Bockholt, H. Jeremy; Flores, Ranee A.; Smith, Shirley M.; Chavez, Robert S.; Haier, Richard J.

2009-01-01

Creativity has long been a construct of interest to philosophers, psychologists and, more recently, neuroscientists. Recent efforts have focused on cognitive processes likely to be important to the manifestation of novelty and usefulness within a given social context. One such cognitive process – divergent thinking – is the process by which one extrapolates many possible answers to an initial stimulus or target data set. We sought to link well established measures of divergent thinking and creative achievement (Creative Achievement Questionnaire – CAQ) to cortical thickness in a cohort of young (23.7 ± 4.2 years), healthy subjects. Three independent judges ranked the creative products of each subject using the consensual assessment technique (Amabile, 1982) from which a “composite creativity index” (CCI) was derived. Structural magnetic resonance imaging was obtained at 1.5 Tesla Siemens scanner. Cortical reconstruction and volumetric segmentation were performed with the FreeSurfer image analysis suite. A region within the lingual gyrus was negatively correlated with CCI; the right posterior cingulate correlated positively with the CCI. For the CAQ, lower left lateral orbitofrontal volume correlated with higher creative achievement; higher cortical thickness was related to higher scores on the CAQ in the right angular gyrus. This is the first study to link cortical thickness measures to psychometric measures of creativity. The distribution of brain regions, associated with both divergent thinking and creative achievement, suggests that cognitive control of information flow among brain areas may be critical to understanding creative cognition. PMID:19722171

Hemoglobin concentration does not impact 3-month outcome following acute ischemic stroke.

PubMed

Sharma, Kartavya; Johnson, Daniel J; Johnson, Brenda; Frank, Steven M; Stevens, Robert D

2018-06-02

There is uncertainty regarding the effect of anemia and red blood cell transfusion on functional outcome following acute ischemic stroke. We studied the relationship of hemoglobin parameters and red cell transfusion with post stroke functional outcome after adjustment for neurological severity and medical comorbidities. Retrospective cohort study of 536 patients discharged with a diagnosis of ischemic stroke from a tertiary care hospital between January 2012 and April 2015. Hemoglobin level at hospital admission, lowest recorded value during hospitalization (nadir), delta hemoglobin (admission minus nadir), red cell transfusion during hospitalization were noted. Charlson Comorbidity Index (CCI) was computed as a summary measure of medical comorbidities. A multivariable logistic regression model was used to determine risk-adjusted odds of unfavorable outcome, defined as a modified Rankin Score of > 2. Anemia was present on hospital admission in 31% of patients. Forty five percent of patients had unfavorable outcome. In the univariable analysis increasing age, admission National Institutes of Health Stroke Scale (NIHSS), CCI, nadir hemoglobin, delta hemoglobin and blood transfusion were associated with unfavorable outcome. In the multivariable model, only increasing age, CCI and NIHSS remained associated with unfavorable outcome. No quadratic association was found on repeating the model to identify a possible U-shaped relationship of hemoglobin with outcome. Our findings contradict prior observational studies and highlight an area of clinical equipoise regarding the optimal management of anemia in patients hospitalized for ischemic stroke. This uncertainty could be addressed with appropriately designed clinical trials.

[Comparison of three methods for measuring multiple morbidity according to the use of health resources in primary healthcare].

PubMed

Sicras-Mainar, Antoni; Velasco-Velasco, Soledad; Navarro-Artieda, Ruth; Blanca Tamayo, Milagrosa; Aguado Jodar, Alba; Ruíz Torrejón, Amador; Prados-Torres, Alexandra; Violan-Fors, Concepción

2012-06-01

To compare three methods of measuring multiple morbidity according to the use of health resources (cost of care) in primary healthcare (PHC). Retrospective study using computerized medical records. Thirteen PHC teams in Catalonia (Spain). Assigned patients requiring care in 2008. The socio-demographic variables were co-morbidity and costs. Methods of comparison were: a) Combined Comorbidity Index (CCI): an index itself was developed from the scores of acute and chronic episodes, b) Charlson Index (ChI), and c) Adjusted Clinical Groups case-mix: resource use bands (RUB). The cost model was constructed by differentiating between fixed (operational) and variable costs. 3 multiple lineal regression models were developed to assess the explanatory power of each measurement of co-morbidity which were compared from the determination coefficient (R(2)), p< .05. The study included 227,235 patients. The mean unit of cost was €654.2. The CCI explained an R(2)=50.4%, the ChI an R(2)=29.2% and BUR an R(2)=39.7% of the variability of the cost. The behaviour of the ICC is acceptable, albeit with low scores (1 to 3 points), showing inconclusive results. The CCI may be a simple method of predicting PHC costs in routine clinical practice. If confirmed, these results will allow improvements in the comparison of the case-mix. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice.

PubMed

Madathil, Sindhu K; Carlson, Shaun W; Brelsfoard, Jennifer M; Ye, Ping; D'Ercole, A Joseph; Saatman, Kathryn E

2013-01-01

Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI.

Adoptive transfer of M2 macrophages reduces neuropathic pain via opioid peptides.

PubMed

Pannell, Maria; Labuz, Dominika; Celik, Melih Ö; Keye, Jacqueline; Batra, Arvind; Siegmund, Britta; Machelska, Halina

2016-10-07

During the inflammation which occurs following nerve damage, macrophages are recruited to the site of injury. Phenotypic diversity is a hallmark of the macrophage lineage and includes pro-inflammatory M1 and anti-inflammatory M2 populations. Our aim in this study was to investigate the ability of polarized M0, M1, and M2 macrophages to secrete opioid peptides and to examine their relative contribution to the modulation of neuropathic pain. Mouse bone marrow-derived cells were cultured as unstimulated M0 macrophages or were stimulated into an M1 phenotype using lipopolysaccharide and interferon-γ or into an M2 phenotype using interleukin-4. The macrophage phenotypes were verified using flow cytometry for surface marker analysis and cytokine bead array for cytokine profile assessment. Opioid peptide levels were measured by radioimmunoassay and enzyme immunoassay. As a model of neuropathic pain, a chronic constriction injury (CCI) of the sciatic nerve was employed. Polarized M0, M1, and M2 macrophages (5 × 10 5 cells) were injected perineurally twice, on days 14 and 15 following CCI or sham surgery. Mechanical and heat sensitivity were measured using the von Frey and Hargreaves tests, respectively. To track the injected macrophages, we also transferred fluorescently stained polarized cells and analyzed the surface marker profile of endogenous and injected cells in the nerves ex vivo. Compared to M0 and M1 cells, M2 macrophages contained and released higher amounts of opioid peptides, including Met-enkephalin, dynorphin A (1-17), and β-endorphin. M2 cells transferred perineurally at the nerve injury site reduced mechanical, but not heat hypersensitivity following the second injection. The analgesic effect was reversed by the perineurally applied opioid receptor antagonist naloxone methiodide. M2 cells did not affect sensitivity following sham surgery. Neither M0 nor M1 cells altered mechanical and heat sensitivity in CCI or sham-operated animals. Tracing the fluorescently labeled M0, M1, and M2 cells ex vivo showed that they remained in the nerve and preserved their phenotype. Perineural transplantation of M2 macrophages resulted in opioid-mediated amelioration of neuropathy-induced mechanical hypersensitivity, while M1 macrophages did not exacerbate pain. Therefore, rather than focusing on macrophage-induced pain generation, promoting opioid-mediated M2 actions may be more relevant for pain control.

Low Earth Orbit satellite traffic simulator

NASA Technical Reports Server (NTRS)

Hoelzel, John

1995-01-01

This paper describes a significant tool for Low Earth Orbit (LEO) capacity analysis, needed to support marketing, economic, and design analysis, known as a Satellite Traffic Simulator (STS). LEO satellites typically use multiple beams to help achieve the desired communication capacity, but the traffic demand in these beams in usually not uniform. Simulations of dynamic, average, and peak expected demand per beam is a very critical part of the marketing, economic, and design analysis necessary to field a viable LEO system. An STS is described in this paper which can simulate voice, data and FAX traffic carried by LEO satellite beams and Earth Station Gateways. It is applicable world-wide for any LEO satellite constellations operating over any regions. For aeronautical applications to LEO satellites. the anticipates aeronautical traffic (Erlangs for each hour of the day to be simulated) is prepared for geographically defined 'area targets' (each major operational region for the respective aircraft), and used as input to the STS. The STS was designed by Constellations Communications Inc. (CCI) and E-Systems for usage in Brazil in accordance with an ESCA/INPE Statement Of Work, and developed by Analytical Graphics Inc. (AGI) to execute on top of its Satellite Tool Kit (STK) commercial software. The STS simulates constellations of LEO satellite orbits, with input of traffic intensity (Erlangs) for each hour of the day generated from area targets (such as Brazilian States). accumulated in custom LEO satellite beams, and then accumulated in Earth Station Gateways. The STS is a very general simulator which can accommodate: many forms of orbital element and Walker Constellation input; simple beams or any user defined custom beams; and any location of Gateways. The paper describes some of these features, including Manual Mode dynamic graphical display of communication links, to illustrate which Gateway links are accessible and which links are not, at each 'step' of the satellite orbit. In the two Performance Modes, either Channel capacity or Grade Of Service (GOS) for objects (Satellite beams, Gateways, and an entire satellite) are computed respectively by standard traffic table capacity lookup and blocking probability equations. GOS can be input, with number of channels calculated, or number of channels can be input, with GOS calculated. Also described are some of the STS Test Procedure approach and results. AGI plans to make the STS features available through their normal commercial STK products. E-Systems is a co-developer, tester, and user of the STS. The Test Procedure for the STS was prepared by E-Systems, as an independent tester for CCI, to support the CCI delivery of the STS to ESCA, for their customer INPE.

Proposal of e-learning strategy to teach Atraumatic Restorative Treatment (ART) to undergraduate and graduate students.

PubMed

Camargo, Lucila Basto; Raggio, Daniela Prócida; Bonacina, Carlos Felipe; Wen, Chao Lung; Mendes, Fausto Medeiros; Bönecker, Marcelo José Strazzeri; Haddad, Ana Estela

2014-07-17

The aim of this study was to evaluate e-learning strategy in teaching Atraumatic Restorative Treatment (ART) to undergraduate and graduate students. The sample comprised 76 participants-38 dental students and 38 pediatric dentistry students-in a specialization course. To evaluate knowledge improvement, participants were subjected to a test performed before and after the course. A single researcher corrected the tests and intraexaminer reproducibility was calculated (CCI = 0.991; 95% IC = 0.975-0.996). All students improved their performances after the e-learning course (Paired t-tests p < 0.001). The means of undergraduate students were 4.7 (initial) and 6.4 (final) and those of graduate students were 6.8 (initial) and 8.2 (final). The comparison of the final evaluation means showed a statistically significant difference (t-tests p < 0.0001). The e-learning strategy has the potential of improving students' knowledge in ART. Mature students perform better in this teaching modality when it is applied exclusively via distance learning.

KSC-2013-3627

NASA Image and Video Library

2013-07-11

HAMPTON, Va. –An engineer monitors high-speed wind tunnel testing of a 10-inch long ceramic model of the Sierra Nevada Corporation, or SNC, Dream Chaser spacecraft at NASA's Langley Research Center in Hampton, Va. The tests measure how much heat the winged vehicle would experience during ascent and re-entry through the atmosphere, including the spacecraft's lower- and upper-body flaps, elevons and a rudder. They're also helping the company obtain necessary data for the material selection and design of the spacecraft's thermal protection system. SNC is continuing the development of its Dream Chaser spacecraft under the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/David Bowman

KSC-2013-3626

NASA Image and Video Library

2013-07-11

HAMPTON, Va. –A 10-inch long ceramic model of the Sierra Nevada Corporation, or SNC, Dream Chaser spacecraft is prepared for high-speed wind tunnel tests at NASA's Langley Research Center in Hampton, Va. The tests measure how much heat the winged vehicle would experience during ascent and re-entry through the atmosphere, including the spacecraft's lower- and upper-body flaps, elevons and a rudder. They're also helping the company obtain necessary data for the material selection and design of the spacecraft's thermal protection system. SNC is continuing the development of its Dream Chaser spacecraft under the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/David Bowman

KSC-2013-3629

NASA Image and Video Library

2013-07-11

HAMPTON, Va. –Engineers monitor high-speed wind tunnel testing of a 10-inch long ceramic model of the Sierra Nevada Corporation, or SNC, Dream Chaser spacecraft at NASA's Langley Research Center in Hampton, Va. The tests measure how much heat the winged vehicle would experience during ascent and re-entry through the atmosphere, including the spacecraft's lower- and upper-body flaps, elevons and a rudder. They're also helping the company obtain necessary data for the material selection and design of the spacecraft's thermal protection system. SNC is continuing the development of its Dream Chaser spacecraft under the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/David Bowman

KSC-2013-3630

NASA Image and Video Library

2013-07-11

HAMPTON, Va. –A 10-inch long ceramic model of the Sierra Nevada Corporation, or SNC, Dream Chaser spacecraft undergoes high-speed wind tunnel tests at NASA's Langley Research Center in Hampton, Va. The tests measure how much heat the winged vehicle would experience during ascent and re-entry through the atmosphere, including the spacecraft's lower- and upper-body flaps, elevons and a rudder. They're also helping the company obtain necessary data for the material selection and design of the spacecraft's thermal protection system. SNC is continuing the development of its Dream Chaser spacecraft under the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/David Bowman

KSC-2013-3628

NASA Image and Video Library

2013-07-11

HAMPTON, Va. –A 10-inch long ceramic model of the Sierra Nevada Corporation, or SNC, Dream Chaser spacecraft is prepared for high-speed wind tunnel tests at NASA's Langley Research Center in Hampton, Va. The tests measure how much heat the winged vehicle would experience during ascent and re-entry through the atmosphere, including the spacecraft's lower- and upper-body flaps, elevons and a rudder. They're also helping the company obtain necessary data for the material selection and design of the spacecraft's thermal protection system. SNC is continuing the development of its Dream Chaser spacecraft under the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/David Bowman

KSC-2013-2361

NASA Image and Video Library

2013-05-15

EDWARDS, Calif. – ED13-0142-11: The truck and trailer that transported the Dream Chaser engineering test article from Sierra Nevada Corporation, or SNC, Space Systems facility in Louisville, Colo., arrives on the aircraft ramp at NASA's Dryden Flight Research Center on Edwards Air Force Base, Calif., early in the morning. Based on NASA's HL-20 lifting body design, the Dream Chaser will begin its approach-and-landing flight test program in collaboration with NASA's Commercial Crew Program this summer. SNC is one of three companies working with NASA's Commercial Crew Program, or CCP, during the agency's Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to lead to the availability of commercial human spaceflight services for government and commercial customers. To learn more about CCP and its industry partners, visit www.nasa.gov/commercialcrew. Image credit: NASA/Tom Tschida

KSC-2013-3069

NASA Image and Video Library

2013-07-22

HOUSTON - The Boeing Company unveils its fully outfitted CST-100 mock-up at the company's Houston Product Support Center in Texas. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is designed being to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations, including the International Space Station. Boeing is one of three aerospace industry partners working with CCP during its Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3068

NASA Image and Video Library

2013-07-22

HOUSTON - The Boeing Company unveils its fully outfitted CST-100 mock-up at the company's Houston Product Support Center in Texas. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations, including the International Space Station. Boeing is one of three aerospace industry partners working with CCP during its Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

Chronic Constriction Injury of the Infraorbital Nerve in the Rat using modified syringe needle

PubMed Central

Kernisant, Melanie; Gear, Robert; Jasmin, Luc; Vit, Jean-Philippe; Ohara, Peter T.

2008-01-01

Here we report a method for performing a chronic constriction injury (CCI) of the infraorbital nerve (ION) in the rat as a component of a chronic pain model. The surgical approach to the ION is described together with the use of a modified dental syringe needle that simplifies placing two chromic gut ligatures around the ION. This method makes the surgical procedure easier, the nerve injury more consistent across animals and reduces secondary damage to the ION and surrounding tissue. Pain behavior testing together with immunostaining for markers of nerve injury in the spinal trigeminal nucleus show the suitability of this procedure as a model of orofacial pain. PMID:18501433

75 FR 10464 - Broadband Technology Opportunities Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-08

... DEPARTMENT OF COMMERCE National Telecommunications and Information Administration [Docket Number 0907141137-0119-08] RIN 0660-ZA28 Broadband Technology Opportunities Program AGENCY: National... Infrastructure (CCI) projects under the Broadband Technology Opportunities Program (BTOP) is extended until 5:00...

A remotely sensed pigment index reveals photosynthetic phenology in evergreen conifers

PubMed Central

Huemmrich, K. Fred; Ensminger, Ingo; Garrity, Steven; Noormets, Asko; Peñuelas, Josep

2016-01-01

In evergreen conifers, where the foliage amount changes little with season, accurate detection of the underlying “photosynthetic phenology” from satellite remote sensing has been difficult, presenting challenges for global models of ecosystem carbon uptake. Here, we report a close correspondence between seasonally changing foliar pigment levels, expressed as chlorophyll/carotenoid ratios, and evergreen photosynthetic activity, leading to a “chlorophyll/carotenoid index” (CCI) that tracks evergreen photosynthesis at multiple spatial scales. When calculated from NASA’s Moderate Resolution Imaging Spectroradiometer satellite sensor, the CCI closely follows the seasonal patterns of daily gross primary productivity of evergreen conifer stands measured by eddy covariance. This discovery provides a way of monitoring evergreen photosynthetic activity from optical remote sensing, and indicates an important regulatory role for carotenoid pigments in evergreen photosynthesis. Improved methods of monitoring photosynthesis from space can improve our understanding of the global carbon budget in a warming world of changing vegetation phenology. PMID:27803333

A remotely sensed pigment index reveals photosynthetic phenology in evergreen conifers.

PubMed

Gamon, John A; Huemmrich, K Fred; Wong, Christopher Y S; Ensminger, Ingo; Garrity, Steven; Hollinger, David Y; Noormets, Asko; Peñuelas, Josep

2016-11-15

In evergreen conifers, where the foliage amount changes little with season, accurate detection of the underlying "photosynthetic phenology" from satellite remote sensing has been difficult, presenting challenges for global models of ecosystem carbon uptake. Here, we report a close correspondence between seasonally changing foliar pigment levels, expressed as chlorophyll/carotenoid ratios, and evergreen photosynthetic activity, leading to a "chlorophyll/carotenoid index" (CCI) that tracks evergreen photosynthesis at multiple spatial scales. When calculated from NASA's Moderate Resolution Imaging Spectroradiometer satellite sensor, the CCI closely follows the seasonal patterns of daily gross primary productivity of evergreen conifer stands measured by eddy covariance. This discovery provides a way of monitoring evergreen photosynthetic activity from optical remote sensing, and indicates an important regulatory role for carotenoid pigments in evergreen photosynthesis. Improved methods of monitoring photosynthesis from space can improve our understanding of the global carbon budget in a warming world of changing vegetation phenology.

Cross-field Current Instability for Substorm Expansions

NASA Technical Reports Server (NTRS)

Lui, Anthony

1997-01-01

The funding provided by the above-referenced NASA grant has enabled us: (1) to investigate the quasi-linear evolution of the IWI [Lui et al., 1993] and that of the generalized MTSI/IWI [Yoon and Lui, 1993], (2) to carry out the linear analysis of the LHDI to elucidate the difference between it and the MTSI/PM instability [Yoon et al., 1994], (3) to conduct some preliminary nonlocal analyses of the MTSI [Lui et al., 1995] and the IWI [Yoon and Lui, 1996] modes, (4) to study low-frequency shear-driven instability and its nonlinear evolution, which might compete with the CCI [Yoon et al., 1996], and (5) to study the evolution of current sheet during late substorm growth phase by means of 2-D Hall-MHD simulation in order to obtain a better understanding of the current sheet equilibrium crucial for CCI theory [Yoon and Lui, 1997].

[Classification of Colombian children with malnutrition according to NCHS reference or WHO standard].

PubMed

Velásquez, Claudia; Bermúdez, Juliana; Echeverri, Claudia; Estrada, Alejandro

2011-12-01

A descriptive study was conducted to evaluate the concordance of National Center for Health Statistics reference (NCHS) used to classify undernourished children from Colombia with the WHO Child Growth Standards. We used data from children aged 6 to 59 months with acute malnutrition (Z <-2) and severe (Z <-3) who were admitted to the "Unidad Vida Infantil" nutrition program in Colombia. Indicators height-for-age, weight for-height were analyzed when they were admitted to the hospital and weight for-height leaving the hospital. A statistical method used to compare means was T-student. Correlation coefficient intraclass (CCI) and Kappa index evaluated the concordance between NCHS and OMS; McNemar method evaluated the changes on the nutritional classification for children according to growth devices used. Of the total number of children classified as normal by NCHS, 10.4% were classified as stunted by WHO. 64% of the children admitted to the hospital presented acute malnutrition according to NCHS, of these 44,8% presented severe emaciation according to OMS, indeed severe emaciation increased of 36,0% to 63,3% using OMS. 5% of children leaving the hospital could need to stay more days if they had been evaluated with OMS. Growth devices shown high concordance in height-for-age (CCI = 0,988; k= 0,866) and weight for-height (CCI = 0,901; k = 0,578). Concluded that OMS growth standards classified more malnourished children and more severe states, in addition more malnourished children could be hospitalized and they could stay more days.

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats

PubMed Central

Combs, Hannah L.; Jones, Theresa A.; Kozlowski, Dorothy A.

2016-01-01

Abstract Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI. PMID:26421759

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats.

PubMed

Combs, Hannah L; Jones, Theresa A; Kozlowski, Dorothy A; Adkins, DeAnna L

2016-04-15

Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI.

Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone

PubMed Central

Hutchinson, Mark R.; Zhang, Yingning; Brown, Kimberley; Coats, Benjamen D.; Shridhar, Mitesh; Sholar, Paige W.; Patel, Sonica J.; Crysdale, Nicole Y.; Harrison, Jacqueline A.; Maier, Steven F.; Rice, Kenner C.; Watkins, Linda R.

2008-01-01

Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 (TLR4) may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury (CCI). Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived from lipopolysaccharide. Additionally, (+)-naltrexone, (+)-naloxone, and (-))-naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by (+)-naloxone and (-))-naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists (+)-naloxone and (-))-naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with (+)-naloxone is of potential clinical relevance. This is because (+)-naloxone is an antagonist that is inactive at the (-))-opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that (+)-opioid antagonists such as (+)-naloxone may be useful clinically to suppress glial activation, yet (-))-opioid agonists suppress pain. PMID:18662331

Demonstration of tumor-selective retention of fluorinated nitroimidazole probes by /sup 19/F magnetic resonance spectroscopy in vivo

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

Maxwell, R.J.; Workman, P.; Griffiths, J.R.

1989-04-01

We have evaluated two fluorinated misonidazole analogues, Ro 07-0741 and CCI-103F, as potential probes for the non-invasive identification of hypoxic tumor cells by /sup 19/F magnetic resonance spectroscopy (MRS) in vivo. The equipment used was a 1.9 T Oxford Research Systems TMR-32 spectrometer, fitted with a 15 mm diameter surface coil. Signal was readily detectable, with similar intensity from EMT6 tumor, liver, and brain at early times (1-2 hr) after i.v. injection in BALB/c mice, indicative of an initial uniform biodistribution of parent probes. At later times (5-10 hr) there was a progressive reduction in signal intensity from brain andmore » liver, but tumor levels remained constant or declined more slowly. This is illustrated by tumor/brain ratios at 6-7 hr of 2.9 (Ro 07-0741) and 4.2 (CCI-103F). In 4/5 mice analyzed at 20-24 hr after Ro 07-0741, and 1/2 following CCI-103F, tumor signal remained detectable. This occurred in the absence of parent probe as measured by HPLC, suggesting the involvement of a product of nitroreductive bioactivation. Studies with KHT and RIF-1 tumors in C3H/He mice showed a similar trend but retention in RIF-1 was less dramatic, and this was consistent with the known hypoxic fractions and comparative in vivo nitroreductase activities. These promising results support the continuing development of /sup 19/F nitroimidazole probes for non-invasive identification of hypoxic cells in vivo.« less

An evaluation of the antinociceptive effects of Phα1β, a neurotoxin from the spider Phoneutria nigriventer, and ω-conotoxin MVIIA, a cone snail Conus magus toxin, in rat model of inflammatory and neuropathic pain.

PubMed

de Souza, Alessandra Hubner; Castro, Célio J; Rigo, Flavia Karine; de Oliveira, Sara Marchesan; Gomez, Renato Santiago; Diniz, Danuza Montijo; Borges, Marcia Helena; Cordeiro, Marta Nascimento; Silva, Marco Aurélio Romano; Ferreira, Juliano; Gomez, Marcus Vinicius

2013-01-01

Voltage-sensitive calcium channels (VSCCs) underlie cell excitability and are involved in the mechanisms that generate and maintain neuropathic and inflammatory pain. We evaluated in rats the effects of two VSCC blockers, ω-conotoxin MVIIA and Phα1β, in models of inflammatory and neuropathic pain induced with complete Freund's adjuvant (CFA) and chronic constrictive injury (CCI), respectively. We also evaluated the effects of the toxins on capsaicin-induced Ca(2+) influx in dorsal root ganglion (DRG) neurons obtained from rats exposed to both models of pain. A single intrathecal injection of Phα1β reversibly inhibits CFA and CCI-induced mechanical hyperalgesia longer than a single injection of ω-conotoxin MVIIA. Phα1β and MVIIA also inhibited capsaicin-induced Ca(2+) influx in DRG neurons. The inhibitory effect of Phα1β on capsaicin-induced calcium transients in DRG neurons was greater in the CFA model of pain, while the inhibitory effect of ω-conotoxin MVIIA was greater in the CCI model. The management of chronic inflammatory and neuropathic pain is still a major challenge for clinicians. Phα1β, a reversible inhibitor of VSCCs with a preference for N-type Ca(2+) channels, has potential as a novel therapeutic agent for inflammatory and neuropathic pain. Clinical studies are necessary to establish the role of Phα1β in the treatment of chronic pain.

Weight bearing evaluation in inflammatory, neuropathic and cancer chronic pain in freely moving rats.

PubMed

Tétreault, Pascal; Dansereau, Marc-André; Doré-Savard, Louis; Beaudet, Nicolas; Sarret, Philippe

2011-09-01

Preclinical pain assessment remains a key step for the development of new and potent painkillers. Significant progress in pain evaluation has been achieved with the development of non-reflexive tools. Seeking efficient and clinically relevant devices for pain-related quality of life assessment, we evaluated a new Dynamic Weight Bearing (DWB) device based on pressure captors in three different preclinical chronic pain models. Inflammatory (CFA), neuropathic (CCI) and bone cancer pain (femoral tumor) models were evaluated in Sprague Dawley rats for mechanical allodynia using dynamic von Frey for pain-related behaviors and DWB for discomfort. We observed similar impairment patterns in all of the models for both von Frey (allodynia) and DWB (weight balance) during the complete observation period, starting at day 3 in CCI- and CFA-affected limbs and at day 14 in bone cancer-afflicted rats, indicating that the DWB could be a useful tool for supporting pain assessment. Interestingly, we demonstrated that the main compensation, when animals experienced pain, was seen in the forepaws, ranging from 46% to 69% of increased load compared to normal. Other pain-related coping behaviors were also measured, such as the time spent on each paw and the contact surface. Our results revealed that CFA, CCI and cancerous rats decreased the use of their ipsilateral hind paws by 30% and showed a 50% reduction in paw surface pressed against the floor. In conclusion, this new device improves methods for preclinical evaluation of discomfort and quality of life proxies and could be helpful in screening putative analgesics. Copyright © 2011 Elsevier Inc. All rights reserved.

Potassium Aspartate Attenuates Brain Injury Induced by Controlled Cortical Impact in Rats Through Increasing Adenosine Triphosphate (ATP) Levels, Na+/K+-ATPase Activity and Reducing Brain Edema.

PubMed

Gu, Yi; Zhang, Jie; Zhao, Yumei; Su, Yujin; Zhang, Yazhuo

2016-12-13

BACKGROUND Potassium aspartate (PA), as an electrolyte supplement, is widely used in clinical practice. In our previous study, we found PA had neuroprotective effects against apoptosis after cerebral ischemia/reperfusion in rats. In this study, we examine whether PA has protective effects on traumatic brain injury (TBI). MATERIAL AND METHODS TBI was induced by controlled cortical impact (CCI) in rats. Vehicle treatment (control) or PA treatment was administered intraperitoneally at 30 minutes after CCI. The modified neurological severity score (mNSS) and cortical lesion volume were examined. Brain edema and blood-brain barrier (BBB) integrity were measured, as well as brain ATP contents, lactic acid levels, and Na+/K+-ATPase activities. RESULTS We found that CCI induced cortical injury in rats. Acute PA treatment at the dose of 62.5 mg/kg and 125 mg/kg significantly improved neurological deficits (p<0.05 and p<0.001, respectively) and decreased the cortical lesion volume (p<0.05 and p<0.001, respectively) compared with vehicle-only treatment. PA treatment at the dose of 125 mg/kg attenuated brain edema and ameliorated BBB integrity. In addition, PA treatment significantly reduced the loss of ATP (p<0.01), reduced lactic acid levels (p<0.001), and increased the activity of Na+/K+-ATPase (p<0.01). CONCLUSIONS Our results indicate PA has neuroprotective effects on TBI through increasing ATP levels, Na+/K+-ATPase activity, and reducing brain edema. It provides experimental evidence for the clinical application of PA.

Effect of Pulsed Radiofrequency on Rat Sciatic Nerve Chronic Constriction Injury: A Preliminary Study

PubMed Central

Li, Duo-Yi; Meng, Lan; Ji, Nan; Luo, Fang

2015-01-01

Background: Pulsed radiofrequency (PRF) application to the dorsal root ganglia can reduce neuropathic pain (NP) in animal models, but the effect of PRF on damaged peripheral nerves has not been examined. We investigated the effect of PRF to the rat sciatic nerve (SN) on pain-related behavior and SN ultrastructure following chronic constriction injury (CCI). Methods: The analgesic effect was measured by hindpaw mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Twenty rats with NP induced by ligating the common SN were then randomly divided into a PRF treatment group and a sham group. The contralateral SN served as a control. The MWT and TWL were determined again 2, 4, 6, 8, 10, 12, and 14 days after the PRF or sham treatment. On day 14, ipsilateral and contralateral common SNs were excised and examined by electron microscopy. Results: Ipsilateral MWT was significantly reduced and TWL significantly shorter compared to the contralateral side 14 days after CCI (both P = 0.000). In the PRF group, MWT was significantly higher and TWL significantly longer 14 days after the PRF treatment compared to before PRF treatment (both P = 0.000), while no such difference was observed in the sham group (P > 0.05). Electron microscopy revealed extensive demyelination and collagen fiber formation in the ipsilateral SN of sham-treated rats but sparse demyelination and some nerve fiber regrowth in the PRF treatment group. Conclusions: Hyperalgesia is relieved, and ultrastructural damage ameliorated after direct PRF treatment to the SN in the CCI rat model of NP. PMID:25673460

Significant Natural Product Biosynthetic Potential of Actinorhizal Symbionts of the Genus Frankia, as Revealed by Comparative Genomic and Proteomic Analyses▿

PubMed Central

Udwary, Daniel W.; Gontang, Erin A.; Jones, Adam C.; Jones, Carla S.; Schultz, Andrew W.; Winter, Jaclyn M.; Yang, Jane Y.; Beauchemin, Nicholas; Capson, Todd L.; Clark, Benjamin R.; Esquenazi, Eduardo; Eustáquio, Alessandra S.; Freel, Kelle; Gerwick, Lena; Gerwick, William H.; Gonzalez, David; Liu, Wei-Ting; Malloy, Karla L.; Maloney, Katherine N.; Nett, Markus; Nunnery, Joshawna K.; Penn, Kevin; Prieto-Davo, Alejandra; Simmons, Thomas L.; Weitz, Sara; Wilson, Micheal C.; Tisa, Louis S.; Dorrestein, Pieter C.; Moore, Bradley S.

2011-01-01

Bacteria of the genus Frankia are mycelium-forming actinomycetes that are found as nitrogen-fixing facultative symbionts of actinorhizal plants. Although soil-dwelling actinomycetes are well-known producers of bioactive compounds, the genus Frankia has largely gone uninvestigated for this potential. Bioinformatic analysis of the genome sequences of Frankia strains ACN14a, CcI3, and EAN1pec revealed an unexpected number of secondary metabolic biosynthesis gene clusters. Our analysis led to the identification of at least 65 biosynthetic gene clusters, the vast majority of which appear to be unique and for which products have not been observed or characterized. More than 25 secondary metabolite structures or structure fragments were predicted, and these are expected to include cyclic peptides, siderophores, pigments, signaling molecules, and specialized lipids. Outside the hopanoid gene locus, no cluster could be convincingly demonstrated to be responsible for the few secondary metabolites previously isolated from other Frankia strains. Few clusters were shared among the three species, demonstrating species-specific biosynthetic diversity. Proteomic analysis of Frankia sp. strains CcI3 and EAN1pec showed that significant and diverse secondary metabolic activity was expressed in laboratory cultures. In addition, several prominent signals in the mass range of peptide natural products were observed in Frankia sp. CcI3 by intact-cell matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS). This work supports the value of bioinformatic investigation in natural products biosynthesis using genomic information and presents a clear roadmap for natural products discovery in the Frankia genus. PMID:21498757

Validation of Carotid Artery Revascularization Coding in Ontario Health Administrative Databases.

PubMed

Hussain, Mohamad A; Mamdani, Muhammad; Saposnik, Gustavo; Tu, Jack V; Turkel-Parrella, David; Spears, Julian; Al-Omran, Mohammed

2016-04-02

The positive predictive value (PPV) of carotid endarterectomy (CEA) and carotid artery stenting (CAS) procedure and post-operative complication coding were assessed in Ontario health administrative databases. Between 1 April 2002 and 31 March 2014, a random sample of 428 patients were identified using Canadian Classification of Health Intervention (CCI) procedure codes and Ontario Health Insurance Plan (OHIP) billing codes from administrative data. A blinded chart review was conducted at two high-volume vascular centers to assess the level of agreement between the administrative records and the corresponding patients' hospital charts. PPV was calculated with 95% confidence intervals (CIs) to estimate the validity of CEA and CAS coding, utilizing hospital charts as the gold standard. Sensitivity of CEA and CAS coding were also assessed by linking two independent databases of 540 CEA-treated patients (Ontario Stroke Registry) and 140 CAS-treated patients (single-center CAS database) to administrative records. PPV for CEA ranged from 99% to 100% and sensitivity ranged from 81.5% to 89.6% using CCI and OHIP codes. A CCI code with a PPV of 87% (95% CI, 78.8-92.9) and sensitivity of 92.9% (95% CI, 87.4-96.1) in identifying CAS was also identified. PPV for post-admission complication diagnosis coding was 71.4% (95% CI, 53.7-85.4) for stroke/transient ischemic attack, and 82.4% (95% CI, 56.6-96.2) for myocardial infarction. Our analysis demonstrated that the codes used in administrative databases accurately identify CEA and CAS-treated patients. Researchers can confidently use administrative data to conduct population-based studies of CEA and CAS.

The relationship between nutritional status of hip fracture operated elderly patients and their functioning, comorbidity and outcome.

PubMed

Koren-Hakim, Tamar; Weiss, Avraham; Hershkovitz, Avital; Otzrateni, Irena; Grosman, Boris; Frishman, Sigal; Salai, Moshe; Beloosesky, Yichayaou

2012-12-01

Malnutrition is common in hip fracture elderly patients. The purpose of this study was to examine the relationship between the Mini Nutrition Assessment Short Form (MNA-SF) and cognitive, functional status, comorbidity and outcome of operated patients. Clinical data, MNA, functioning, cognition were prospectively determined. Retrospectively, the Charlson Comorbidity Index (CCI) and Cumulative Illness Rating Scale for Geriatrics (CIRS-G) were applied. The study consisted of 95 well-nourished (WN), 95 at risk of malnutrition (ARM) and 25 malnourished (MN) patients. More WN patients were independent vs. partially or fully dependent; more WN patients were cognitively normal vs. cognitively impaired (p < 0.001). CIRS-G was higher in MN vs. WN patients and CCI was higher in MN and ARM vs. WN patients (p < 0.001). During a 6 month period, 100 patients were readmitted, with less readmissions in the WN group (p = 0.024). During a 36 month follow-up, 79 patients died. The mortality rate was lower in the WN group (p = 0.01). Stepwise regression analysis found that the only independent variables for mortality were CCI and functioning (p < 0.01). Patients with higher cognitive and functional status were in superior nutritional condition. Poor nutritional status was associated with higher comorbidity indices, mortality and readmissions. However, we found that only comorbidity and low functioning can predict long-term mortality. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Impact of chronic kidney disease on mortality in older adults treated with pacemaker implantation

PubMed Central

Fabbian, Fabio; De Giorgi, Alfredo; Guarino, Matteo; Malagù, Michele; Bertini, Matteo

2017-01-01

Objective To investigate whether chronic kidney disease could negatively impact survival in older adults needing pacemaker implantation after admission for bradyarrhythmias. Methods This retrospective observational study considered 538 older adults consecutively admitted, who had been followed-up for 31 ± 20 months. Subjects with poor short-term prognosis were excluded. Charlson comorbidity index (CCI) and estimated glomerular filtration rate (eGFR) was calculated, along with the independent relationship between all-cause mortality and clinical data. Hazard Ratio (HR) was calculated by Cox regression analysis. Results Mean age of the population was 85 ± 3.7 years, and causes for implantation were atrioventricular block in 51.9% and other bradyarrhythmias in 48.1% of cases. Mean eGFR was 58.3 ± 24 mL/min per 1.73 m2, and mean CCI was 3.65 ± 2.28. Death for all-causes was recorded in 213 subjects. Deceased patients were older, had lower eGFR, higher comorbidity, higher prevalence of myocardial infarction, congestive heart failure, cerebrovascular disease, dementia and chronic pulmonary disease. Age (HR: 1.081, 95% CI: 1.044–1.119; P < 001), CCI (HR: 1.651, 95% CI: 1.286–2.121, P < 001) and eGFR ≤ 45 mL/min per 1.73 m2 (HR: 1.360, 95% CI: 1.024–1.806; P = 0.033) were predictors of death. Conclusions Renal dysfunction, as well as comorbidity, impacts negatively survival of older adults treated with pacemaker implantation because of bradyarrhythmias. PMID:29238360

Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model

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

Fokas, Emmanouil, E-mail: emmanouil.fokas@yahoo.d; Haenze, Joerg; Kamlah, Florentine

2010-08-01

Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas aftermore » IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.« less

Brain Injury-Induced Synaptic Reorganization in Hilar Inhibitory Neurons Is Differentially Suppressed by Rapamycin

PubMed Central

2017-01-01

Abstract Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Reemergence of seizures after cessation of rapamycin treatment suggests, however, an incomplete suppression of epileptogenesis. Hilar inhibitory interneurons regulate dentate granule cell (DGC) activity, and de novo synaptic input from both DGCs and CA3 pyramidal cells after TBI increases their excitability but effects of rapamycin treatment on the injury-induced plasticity of interneurons is only partially described. Using transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed in the somatostatinergic subset of hilar inhibitory interneurons, we tested the effect of daily systemic rapamycin treatment (3 mg/kg) on the excitability of hilar inhibitory interneurons after controlled cortical impact (CCI)-induced focal brain injury. Rapamycin treatment reduced, but did not normalize, the injury-induced increase in excitability of surviving eGFP+ hilar interneurons. The injury-induced increase in response to selective glutamate photostimulation of DGCs was reduced to normal levels after mTOR inhibition, but the postinjury increase in synaptic excitation arising from CA3 pyramidal cell activity was unaffected by rapamycin treatment. The incomplete suppression of synaptic reorganization in inhibitory circuits after brain injury could contribute to hippocampal hyperexcitability and the eventual reemergence of the epileptogenic process upon cessation of mTOR inhibition. Further, the cell-selective effect of mTOR inhibition on synaptic reorganization after CCI suggests possible mechanisms by which rapamycin treatment modifies epileptogenesis in some models but not others. PMID:29085896

Long-term recovery of normal sexual function in testicular cancer survivors.

PubMed

Capogrosso, Paolo; Boeri, Luca; Ferrari, Matteo; Ventimiglia, Eugenio; La Croce, Giovanni; Capitanio, Umberto; Briganti, Alberto; Damiano, Rocco; Montorsi, Francesco; Salonia, Andrea

2016-01-01

Testicular cancer (TC) is the most common solid cancer in men between the third and fourth decade of life. Due to successful treatment approaches, TC survivors (TCSs) have long life expectancy, but with numerous potential long-term sequelae, including sexual dysfunction. We investigated predictors of long-term normal sexual function (SF) recovery in TCSs. Sociodemographic, medical, and psychometric data were analyzed in 143 Caucasian-European TCSs, who underwent orchiectomy at a single institution. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF). Statistical models tested the association between predictors (including age at surgery, body mass index, CCI, and adjuvant therapy: radiotherapy [RT], chemotherapy [CT], CT followed by retroperitoneal lymph node dissection [RPLND] and RPLND alone) and the long-term recovery of normal SF (defined as IIEF-erectile function [EF] ≥26, and sexual desire [SD], intercourse satisfaction [IS] orgasmic function [OF], and overall satisfaction [OS] domain scores in the upper tertiles). At a mean follow-up of 86 months, 35 (25.5%) TCSs had erectile dysfunction (ED), with 16 (11.2%) experiencing severe ED. Median time of EF recovery was 60, 60, and 70 months after CT, RT, and RPLND, respectively. Only adjuvant RT emerged as an independent predictor of nonrecovery of normal EF (HR: 0.55, P= 0.01). Neither adjuvant CT nor CT plus RPLND or RPLND alone significantly impaired the recovery of normal erections. Adjuvant therapy was not associated with impaired recovery of normal sexuality as a whole, considering the IIEF-SD, -OF, -IS, and OS domains.

MiR-19a targets suppressor of cytokine signaling 1 to modulate the progression of neuropathic pain

PubMed Central

Wang, Conghui; Jiang, Qi; Wang, Min; Li, Dong

2015-01-01

Purpose: we aimed to investigate whether miR-19a is associated with neuropathic pain and elucidate the underlying regulatory mechanism. Methods: We established a neuropathic pain model of bilateral chronic constriction injury (bCCI). Then bCCI rats were injected with mo-miR-19a, siR-SOCS1 or blank expression vector through a microinjection syringe via an intrathecal catheter on 3 day before surgery and after surgery. Behavioral tests, such as mechanical allodynia, thermal hyperalgesia and acetone induced cold allodynia, were performed to evaluate the pain threshold. Besides, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of miR-19a and western blotting was carried out to measure the expression of SOCS1. Results: miR-19a expression levels were markedly increased in neuropathic pain models. Moreover, miR-19a significantly attenuated mechanical allodynia and thermal hyperalgesia, and similar results were obtained after knockdown of SOCS1 expression. However, miR-19a markedly increased the times that the rats appeared a sign of cold allodynia, and knockdown of SOCS1 expression had similar effects. Besides, the results of bioinformatics analysis and western blotting analysis were all confirmed that SOCS1 was a direct target of miR-19a in neuropathic pain models. Conclusions: Our finding indicate that SOCS1 is a direct target of miR-19a in neuropathic pain rats and miR-19a may play a critical role in regulating of neuropathic pain via targeting SOCS1. PMID:26617805

MiR-19a targets suppressor of cytokine signaling 1 to modulate the progression of neuropathic pain.

PubMed

Wang, Conghui; Jiang, Qi; Wang, Min; Li, Dong

2015-01-01

We aimed to investigate whether miR-19a is associated with neuropathic pain and elucidate the underlying regulatory mechanism. We established a neuropathic pain model of bilateral chronic constriction injury (bCCI). Then bCCI rats were injected with mo-miR-19a, siR-SOCS1 or blank expression vector through a microinjection syringe via an intrathecal catheter on 3 day before surgery and after surgery. Behavioral tests, such as mechanical allodynia, thermal hyperalgesia and acetone induced cold allodynia, were performed to evaluate the pain threshold. Besides, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of miR-19a and western blotting was carried out to measure the expression of SOCS1. miR-19a expression levels were markedly increased in neuropathic pain models. Moreover, miR-19a significantly attenuated mechanical allodynia and thermal hyperalgesia, and similar results were obtained after knockdown of SOCS1 expression. However, miR-19a markedly increased the times that the rats appeared a sign of cold allodynia, and knockdown of SOCS1 expression had similar effects. Besides, the results of bioinformatics analysis and western blotting analysis were all confirmed that SOCS1 was a direct target of miR-19a in neuropathic pain models. Our finding indicate that SOCS1 is a direct target of miR-19a in neuropathic pain rats and miR-19a may play a critical role in regulating of neuropathic pain via targeting SOCS1.

Brain Injury-Induced Synaptic Reorganization in Hilar Inhibitory Neurons Is Differentially Suppressed by Rapamycin.

PubMed

Butler, Corwin R; Boychuk, Jeffery A; Smith, Bret N

2017-01-01

Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Reemergence of seizures after cessation of rapamycin treatment suggests, however, an incomplete suppression of epileptogenesis. Hilar inhibitory interneurons regulate dentate granule cell (DGC) activity, and de novo synaptic input from both DGCs and CA3 pyramidal cells after TBI increases their excitability but effects of rapamycin treatment on the injury-induced plasticity of interneurons is only partially described. Using transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed in the somatostatinergic subset of hilar inhibitory interneurons, we tested the effect of daily systemic rapamycin treatment (3 mg/kg) on the excitability of hilar inhibitory interneurons after controlled cortical impact (CCI)-induced focal brain injury. Rapamycin treatment reduced, but did not normalize, the injury-induced increase in excitability of surviving eGFP+ hilar interneurons. The injury-induced increase in response to selective glutamate photostimulation of DGCs was reduced to normal levels after mTOR inhibition, but the postinjury increase in synaptic excitation arising from CA3 pyramidal cell activity was unaffected by rapamycin treatment. The incomplete suppression of synaptic reorganization in inhibitory circuits after brain injury could contribute to hippocampal hyperexcitability and the eventual reemergence of the epileptogenic process upon cessation of mTOR inhibition. Further, the cell-selective effect of mTOR inhibition on synaptic reorganization after CCI suggests possible mechanisms by which rapamycin treatment modifies epileptogenesis in some models but not others.

Effects of S 38093, an antagonist/inverse agonist of histamine H3 receptors, in models of neuropathic pain in rats.

PubMed

Chaumette, T; Chapuy, E; Berrocoso, E; Llorca-Torralba, M; Bravo, L; Mico, J A; Chalus, M; Eschalier, A; Ardid, D; Marchand, F; Sors, A

2018-01-01

Histamine H3 receptors are mainly expressed on CNS neurons, particularly along the nociceptive pathways. The potential involvement of these receptors in pain processing has been suggested using H3 receptor inverse agonists. The antinociceptive effect of S 38093, a novel inverse agonist of H3 receptors, has been evaluated in several neuropathic pain models in rat and compared with those of gabapentin and pregabalin. While S 38093 did not change vocalization thresholds to paw pressure in healthy rats, it exhibited a significant antihyperalgesic effect in the Streptozocin-induced diabetic (STZ) neuropathy model after acute and chronic administration and, in the chronic constriction injury (CCI) model only after chronic administration, submitted to the paw-pressure test. Acute S 38093 administration at all doses tested displayed a significant cold antiallodynic effect in a model of acute or repeated administration of oxaliplatin-induced neuropathy submitted to cold tail immersion, cold allodynia being the main side effect of oxaliplatin in patients. The effect of S 38093 increased following chronic administration (i.e. twice a day during 5 days) in the CCI and STZ models except in the oxaliplatin models where its effect was already maximal from the first administration The kinetics and size of effect of S 38093 were similar to gabapentin and/or pregabalin. Finally, the antinociceptive effect of S 38093 could be partially mediated by α2 adrenoreceptors desensitization in the locus coeruleus. These results highlight the interest of S 38093 to relieve neuropathic pain and warrant clinical trials especially in chemotherapeutic agent-induced neuropathic pain. S 38093, a new H3 antagonist/inverse agonist, displays antiallodynic and antihyperalgesic effect in neuropathic pain, especially in oxaliplatin-induced neuropathy after chronic administration. This effect of S 38093 in neuropathic pain could be partly mediated by α2 receptors desensitization in the locus coeruleus. © 2017 European Pain Federation - EFIC®.

The impact of medical insurance coverage and molecular monitoring frequency on outcomes in chronic myeloid leukemia: real-world evidence in China.

PubMed

Sheng, Guangying; Chen, Suning; Zhang, Ri; Miao, Miao; Wu, Depei; Tan, Seng Chuen; Liu, Chao; Xiong, Tengbin

2017-04-01

Imatinib (Glivec) has been covered by critical disease insurance for treatment of chronic myeloid leukemia (CML) in Jiangsu province of China since 2013. Further, free molecular monitoring has been provided to patients at top clinical centers as part of a pilot study that has changed the local treatment pattern and outcomes of patients with CML. This study evaluates the impact of medical insurance coverage and the molecular monitoring frequency on outcomes of patients with CML treated at a central hospital in Jiangsu, China, according to patient-level data. The study investigated 335 CML patients receiving medical treatment in a central hospital between January 1, 2011 and December 31, 2014. Demographic and clinical characteristics were extracted from the patients' clinical records. Univariate and multivariate analyses using the logistic regression model were performed to identify the differences in outcomes of major molecular response (MMR) or complete cytogenetic response (CCyR) between patients who were insured vs uninsured, or between patients with frequency of PCR monitoring ≤2 times vs ≥3 times per year. Both the achievement of MMR (BCR-ABL IS ≤0.1%) (50.4% vs 37.5%) and CCyR (80.7% vs 62.8%) at 12 months have shown significant differences that favored patients with insurance coverage of imatinib, while there was no significant difference in the outcome of BCR-ABL IS ≤1% between insured and non-insured groups (56.0% vs 51.3%) at 6 months. The long-term results at 24 months demonstrated that there was a statistically significant difference in MMR rates between the group with 3 or more PCR monitoring tests per year and the group of patients with 2 or less PCR tests per year (76.9% vs 52.2%). The study findings suggest that CML patients benefit from insurance coverage of imatinib and higher frequency (≥3) of regularly scheduled molecular monitoring PCR in China.

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats

PubMed Central

Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J.; Greig, Nigel H.; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin

2016-01-01

Abstract Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment. PMID:26972789

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats.

PubMed

Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J; Greig, Nigel H; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin; Yang, Liang-Yo; Chiang, Yung-Hsiao

2016-11-15

Mild traumatic brain injury (mTBI) is a major public health issue, representing 75-90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13-15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.

78 FR 40175 - Agency Information Collection Activities; Proposed New Collection; Comments Requested: Police-Led...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-03

... Uniform Crime Reporting. CCI will subcontract with a professional survey research firm to administer the survey. (5) An estimate of the total number of respondents and the amount of time estimated for an...

Anesthesia for Euthanasia Influences mRNA Expression in Healthy Mice and after Traumatic Brain Injury

PubMed Central

Staib-Lasarzik, Irina; Kriege, Oliver; Timaru-Kast, Ralph; Pieter, Dana; Werner, Christian; Engelhard, Kristin

2014-01-01

Abstract Tissue sampling for gene expression analysis is usually performed under general anesthesia. Anesthetics are known to modulate hemodynamics, receptor-mediated signaling cascades, and outcome parameters. The present study determined the influence of anesthetic paradigms typically used for euthanization and tissue sampling on cerebral mRNA expression in mice. Naïve mice and animals with acute traumatic brain injury induced by controlled cortical impact (CCI) were randomized to the following euthanasia protocols (n=10–11/group): no anesthesia (NA), 1 min of 4 vol% isoflurane in room air (ISO), 3 min of a combination of 5 mg/kg midazolam, 0.05 mg/kg fentanyl, and 0.5 mg/kg medetomidine intraperitoneally (COMB), or 3 min of 360 mg/kg chloral hydrate intraperitoneally (CH). mRNA expression of actin-1-related gene (Act1), FBJ murine osteosarcoma viral oncogene homolog B (FosB), tumor necrosis factor alpha (TNFα), heat shock protein beta-1 (HspB1), interleukin (IL)-6, tight junction protein 1 (ZO-1), IL-1ß, cyclophilin A, micro RNA 497 (miR497), and small cajal body-specific RNA 17 were determined by real-time polymerase chain reaction (PCR) in hippocampus samples. In naïve animals, Act1 expression was downregulated in the CH group compared with NA. FosB expression was downregulated in COMB and CH groups compared with NA. CCI reduced Act1 and FosB expression, whereas HspB1 and TNFα expression increased. After CCI, HspB1 expression was significantly higher in ISO, COMB, and CH groups, and TNFα expression was elevated in ISO and COMB groups. MiR497, IL-6, and IL-1ß were upregulated after CCI but not affected by anesthetics. Effects were independent of absolute mRNA copy numbers. The data demonstrate that a few minutes of anesthesia before tissue sampling are sufficient to induce immediate mRNA changes, which seem to predominate in the early-regulated gene cluster. Anesthesia-related effects on gene expression might explain limited reproduciblity of real-time PCR data between studies or research groups and should therefore be considered for quantitative PCR data. PMID:24945082

Climate controls on fire pattern in African and Australian continents

NASA Astrophysics Data System (ADS)

Zubkova, M.; Boschetti, L.; Abatzoglou, J. T.

2017-12-01

Studies have primarily attributed the recent decrease in global fire activity in many savanna and grassland regions as detected by the Global Fire Emission Database (GFEDv4s) to anthropogenic changes such as deforestation and cropland expansion (Andela et al. 2017, van der Werf et al. 2008). These changes have occurred despite increases in fire weather season length (Jolly et al. 2015). Efforts to better resolve retrospective and future changes in fire activity require refining the host of influences on societal and environmental factors on fire activity. In this study, we analyzed how climate variability influences interannual fire activity in Africa and Australia, the two continents most affected by fire and responsible for over half of the global pyrogenic emissions. We expand on the analysis presented in Andela et al. (2017) by using the most recent Collection 6 MODIS MCD64 Burned Area Product and exploring the explanatory power of a broader suite of climate variables that have been previously shown to explain fire variability (Bowman et al. 2017). We examined which climate metrics show a strong interannual relationship with the amount of burned area and fire size accounting for antecedent and in-season atmospheric conditions. Fire characteristics were calculated using the 500m resolution MCD64A1 product (2002-2016); the analysis was conducted at the ecoregion scale, and further stratified by landcover using a broad aggregation (forest, shrublands and grasslands) of the Landcover CCI maps (CCI-LC, 2014); all agricultural areas fires were excluded from the analysis. The results of the analysis improve our knowledge of climate controls on fire dynamics in the most fire-prone places in the world which is critical for statistical fire and vegetation models. Being able to predict the impact of climate on fire activity has a strategic importance in designing future fire management scenarios, help to avoid degradation of biodiversity and ecosystem services and improve our understanding of future ecological problems that we can face due to climate change. Andela et al. 2017. doi: 10.1126/science.aal4108 Bowman et al. 2017. doi:10.1038/s41559-016-0058 CCI-LC. 2014. CCI-LC Product User Guide. UCL-Geomatics, Belgium Lolly et al. 2015. doi:10.1038/ncomms8537 van der Werf et al. 2008. doi:10.1029/2007GB003122

Sialic acid-triggered macroscopic properties switching on a smart polymer surface

NASA Astrophysics Data System (ADS)

Xiong, Yuting; Li, Minmin; Wang, Hongxi; Qing, Guangyan; Sun, Taolei

2018-01-01

Constructing smart surfaces with responsive polymers capable of dynamically and reversibly changing their chemical and physical properties by responding to the recognition of biomolecules remains a challenging task. And, the key to achieving this purpose relies on the design of polymers to precisely interact with the target molecule and successfully transform the interaction signal into tunable macroscopic properties, further achieve special bio-functions. Herein, inspired by carbohydrate-carbohydrate interaction (CCI) in life system, we developed a three-component copolymer poly(NIPAAm-co-PT-co-Glc) bearing a binding unit glucose (Glc) capable of recognizing sialic acid, a type of important molecular targets for cancer diagnosis and therapy, and reported the sialic acid triggered macroscopic properties switching on this smart polymer surface. Detailed mechanism studies indicated that multiple hydrogen bonding interactions between Glc unit and Neu5Ac destroyed the initial hydrogen bond network of the copolymer, leading to a reversible "contraction-to-swelling" conformational transition of the copolymer chains, accompanied with distinct macroscopic property switching (i.e., surface wettability, morphology, stiffness) of the copolymer film. And these features enabled this copolymer to selectively capture sialic acid-containing glycopeptides from complex protein samples. This work provides an inspiration for the design of novel smart polymeric materials with sensitive responsiveness to sialic acid, which would promote the development of sialic acid-specific bio-devices and drug delivery systems.

Continued Development of Python-Based Thomson Data Analysis and Associated Visualization Tool for NSTX-U

NASA Astrophysics Data System (ADS)

Wallace, William; Miller, Jared; Diallo, Ahmed

2015-11-01

MultiPoint Thomson Scattering (MPTS) is an established, accurate method of finding the temperature, density, and pressure of a magnetically confined plasma. Two Nd:YAG (1064 nm) lasers are fired into the plasma with a effective frequency of 60 Hz, and the light is Doppler shifted by Thomson scattering. Polychromators on the NSTX-U midplane collect the scattered photons at various radii/scattering angles, and the avalanche photodiode voltages are saved to an MDSplus tree for later analysis. IDL code is then used to determine plasma temperature, pressure, and density from the captured polychromator measurements via Selden formulas. [1] Previous work [2] converted the single-processor IDL code into Python code, and prepared a new architecture for multiprocessing MPTS in parallel. However, that work was not completed to the generation of output data and curve fits that match with the previous IDL. This project refactored the Python code into a object-oriented architecture, and created a software test suite for the new architecture which allowed identification of the code which generated the difference in output. Another effort currently underway is to display the Thomson data in an intuitive, interactive format. This work was supported in part by the U.S. Department of Energy, Office of Science, Office of Workforce Development for Teachers and Scientists (WDTS) under the Community College Internship (CCI) program.

KSC-2013-3072

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068247 - The Boeing Company unveils its fully outfitted CST-100 mock-up at the company's Houston Product Support Center in Texas. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is designed being to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations, including the International Space Station. Boeing is one of three aerospace industry partners working with CCP during its Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3070

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068244 - The Boeing Company unveils the interior of its fully outfitted CST-100 mock-up at the company's Houston Product Support Center in Texas. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations, including the International Space Station. Boeing is one of three aerospace industry partners working with CCP during its Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

KSC-2013-3071

NASA Image and Video Library

2013-07-22

HOUSTON - JSC2013e068245 - The Boeing Company unveils the interior its fully outfitted CST-100 mock-up at the company's Houston Product Support Center in Texas. This test version is optimized to support five crew members and will allow the company to evaluate crew safety, interfaces, communications, maneuverability and ergonomics. Boeing's CST-100 is being designed to transport crew members or a mix of crew and cargo to low-Earth-orbit destinations, including the International Space Station. Boeing is one of three aerospace industry partners working with CCP during its Commercial Crew Integrated Capability, or CCiCap, initiative, which is intended to make commercial human spaceflight services available for government and commercial customers. To learn more about CCP, visit http://www.nasa.gov/commercialcrew. Photo credit: NASA/Robert Markowitz

Aerosol retrieval experiments in the ESA Aerosol_cci project

NASA Astrophysics Data System (ADS)

Holzer-Popp, T.; de Leeuw, G.; Martynenko, D.; Klüser, L.; Bevan, S.; Davies, W.; Ducos, F.; Deuzé, J. L.; Graigner, R. G.; Heckel, A.; von Hoyningen-Hüne, W.; Kolmonen, P.; Litvinov, P.; North, P.; Poulsen, C. A.; Ramon, D.; Siddans, R.; Sogacheva, L.; Tanre, D.; Thomas, G. E.; Vountas, M.; Descloitres, J.; Griesfeller, J.; Kinne, S.; Schulz, M.; Pinnock, S.

2013-03-01

Within the ESA Climate Change Initiative (CCI) project Aerosol_cci (2010-2013) algorithms for the production of long-term total column aerosol optical depth (AOD) datasets from European Earth Observation sensors are developed. Starting with eight existing pre-cursor algorithms three analysis steps are conducted to improve and qualify the algorithms: (1) a series of experiments applied to one month of global data to understand several major sensitivities to assumptions needed due to the ill-posed nature of the underlying inversion problem, (2) a round robin exercise of "best" versions of each of these algorithms (defined using the step 1 outcome) applied to four months of global data to identify mature algorithms, and (3) a comprehensive validation exercise applied to one complete year of global data produced by the algorithms selected as mature based on the round robin exercise. The algorithms tested included four using AATSR, three using MERIS and one using PARASOL. This paper summarizes the first step. Three experiments were conducted to assess the potential impact of major assumptions in the various aerosol retrieval algorithms. In the first experiment a common set of four aerosol components was used to provide all algorithms with the same assumptions. The second experiment introduced an aerosol property climatology, derived from a combination of model and sun photometer observations, as a priori information in the retrievals on the occurrence of the common aerosol components and their mixing ratios. The third experiment assessed the impact of using a common nadir cloud mask for AATSR and MERIS algorithms in order to characterize the sensitivity to remaining cloud contamination in the retrievals against the baseline dataset versions. The impact of the algorithm changes was assessed for one month (September 2008) of data qualitatively by visible analysis of monthly mean AOD maps and quantitatively by comparing global daily gridded satellite data against daily average AERONET sun photometer observations for the different versions of each algorithm. The analysis allowed an assessment of sensitivities of all algorithms which helped define the best algorithm version for the subsequent round robin exercise; all algorithms (except for MERIS) showed some, in parts significant, improvement. In particular, using common aerosol components and partly also a priori aerosol type climatology is beneficial. On the other hand the use of an AATSR-based common cloud mask meant a clear improvement (though with significant reduction of coverage) for the MERIS standard product, but not for the algorithms using AATSR.

Manage customer-centric innovation--systematically.

PubMed

Selden, Larry; MacMillan, Ian C

2006-04-01

No matter how hard companies try, their approaches to innovation often don't grow the top line in the sustained, profitable way investors expect. For many companies, there's a huge difference between what's in their business plans and the market's expectations for growth (as reflected in firms' share prices, market capitalizations, and P/E ratios). This growth gap springs from the fact that companies are pouring money into their insular R&D labs instead of working to understand what the customer wants and using that understanding to drive innovation. As a result, even companies that spend the most on R&D remain starved for both customer innovation and market-capitalization growth. In this article, the authors spell out a systematic approach to innovation that continuously fuels sustained, profitable growth. They call this approach customer-centric innovation, or CCI. At the heart of CCI is a rigorous customer R&D process that helps companies to continually improve their understanding of who their customers are and what they need. By so doing, they consistently create or improve their customer value proposition. Customer R&D also focuses on better ways of communicating value propositions and delivering the complete experience to real customers. Since so much of the learning about customers and so much of the experimentation with different segmentations, value propositions, and delivery mechanisms involve the people who regularly deal with customers, it is absolutely essential for frontline employees to be at the center of the CCI process. Simply put, customer R&D propels the innovation effort away from headquarters and the traditional R&D lab out to those closest to the customer. Using the example of the luggage manufacturer Tumi, the authors provide a step-by-step approach for achieving true customer-centric innovation.

Effects of platelet concentrate storage time reduction in patients after blood stem cell transplantation.

PubMed

Heuft, H-G; Goudeva, L; Krauter, J; Peest, D; Buchholz, S; Tiede, A

2013-07-01

To evaluate the clinical effect of platelet concentrate (PC) transfusions after PC storage time reduction to 4 days. This was a single-centre cohort study comparing two 3-month periods of time, before and after the reduction of PC storage time from 5 to 4 days. Seventy-seven consecutive patients with PC transfusions were enrolled after blood stem cell transplantation. Corrected platelet count increment (CCI) on the morning after transfusion, time to next platelet transfusion, need for red blood cell (RBC) transfusion and clinical bleeding symptoms were compared. Platelet concentrate storage time was reduced between period 1 (storage for up to 5 days, median storage time 78 h, range 11-136 h) and period 2 (storage for up to 4 days, median storage time 53 h, range 11-112 h). Patients were comparable for age, weight, body surface area, underlying disorder, type of transplantation and transfused platelet dose. The CCI increased from a median of 4 (range 0-20) to 8 (0-68) × 10(9) /l per 10(11) platelets/m(2) (P < 0·0001). Time to next PC transfusion increased from 1·1 to 2·0 days (P < 0·0001). Any bleeding symptom was noted in 20 of 36 patients (56%) vs. 9/41 patients (22%, P < 0·01). Nose bleeds, haematuria and bleeding at more than one site were significantly reduced. Frequency of RBC transfusion within 5 days after PC transfusion was reduced from 74 to 58% (P < 0·0001). Platelet concentrate storage time shortening was associated with highly significant CCI increase, reduced RC needs and lower patient numbers with bleeding events. © 2013 International Society of Blood Transfusion.

High frequency transcutaneous electrical nerve stimulation with diphenidol administration results in an additive antiallodynic effect in rats following chronic constriction injury.

PubMed

Lin, Heng-Teng; Chiu, Chong-Chi; Wang, Jhi-Joung; Hung, Ching-Hsia; Chen, Yu-Wen

2015-03-04

The impact of coadministration of transcutaneous electrical nerve stimulation (TENS) and diphenidol is not well established. Here we estimated the effects of diphenidol in combination with TENS on mechanical allodynia and tumor necrosis factor-α (TNF-α) expression. Using an animal chronic constriction injury (CCI) model, the rat was estimated for evidence of mechanical sensitivity via von Frey hair stimulation and TNF-α expression in the sciatic nerve using the ELISA assay. High frequency (100Hz) TENS or intraperitoneal injection of diphenidol (2.0μmol/kg) was applied daily, starting on postoperative day 1 (POD1) and lasting for the next 13 days. We demonstrated that both high frequency TENS and diphenidol groups had an increase in mechanical withdrawal thresholds of 60%. Coadministration of high frequency TENS and diphenidol gives better results of paw withdrawal thresholds in comparison with high frequency TENS alone or diphenidol alone. Both diphenidol and coadministration of high frequency TENS with diphenidol groups showed a significant reduction of the TNF-α level compared with the CCI or HFS group (P<0.05) in the sciatic nerve on POD7, whereas the CCI or high frequency TENS group exhibited a higher TNF-α level than the sham group (P<0.05). Our resulting data revealed that diphenidol alone, high frequency TENS alone, and the combination produced a reduction of neuropathic allodynia. Both diphenidol and the combination of diphenidol with high frequency TENS inhibited TNF-α expression. A moderately effective dose of diphenidol appeared to have an additive effect with high frequency TENS. Therefore, multidisciplinary treatments could be considered for this kind of mechanical allodynia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Use-Dependent Dendritic Regrowth Is Limited after Unilateral Controlled Cortical Impact to the Forelimb Sensorimotor Cortex

PubMed Central

Jones, Theresa A.; Liput, Daniel J.; Maresh, Erin L.; Donlan, Nicole; Parikh, Toral J.; Marlowe, Dana

2012-01-01

Abstract Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3–28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI. PMID:22352953

Risk scoring models for predicting peri-operative morbidity and mortality in people with fragility hip fractures: Qualitative systematic review.

PubMed

Marufu, Takawira C; Mannings, Alexa; Moppett, Iain K

2015-12-01

Accurate peri-operative risk prediction is an essential element of clinical practice. Various risk stratification tools for assessing patients' risk of mortality or morbidity have been developed and applied in clinical practice over the years. This review aims to outline essential characteristics (predictive accuracy, objectivity, clinical utility) of currently available risk scoring tools for hip fracture patients. We searched eight databases; AMED, CINHAL, Clinical Trials.gov, Cochrane, DARE, EMBASE, MEDLINE and Web of Science for all relevant studies published until April 2015. We included published English language observational studies that considered the predictive accuracy of risk stratification tools for patients with fragility hip fracture. After removal of duplicates, 15,620 studies were screened. Twenty-nine papers met the inclusion criteria, evaluating 25 risk stratification tools. Risk stratification tools considered in more than two studies were; ASA, CCI, E-PASS, NHFS and O-POSSUM. All tools were moderately accurate and validated in multiple studies; however there are some limitations to consider. The E-PASS and O-POSSUM are comprehensive but complex, and require intraoperative data making them a challenge for use on patient bedside. The ASA, CCI and NHFS are simple, easy and inexpensive using routinely available preoperative data. Contrary to the ASA and CCI which has subjective variables in addition to other limitations, the NHFS variables are all objective. In the search for a simple and inexpensive, easy to calculate, objective and accurate tool, the NHFS may be the most appropriate of the currently available scores for hip fracture patients. However more studies need to be undertaken before it becomes a national hip fracture risk stratification or audit tool of choice. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Adjuvant chemotherapy in elderly patients with primary breast cancer: are women ≥65 undertreated?

PubMed

Wallwiener, C W; Hartkopf, A D; Grabe, E; Wallwiener, M; Taran, F-A; Fehm, T; Brucker, S Y; Krämer, B

2016-08-01

To establish whether women over 65 years of age with newly diagnosed with breast cancer (BC) receive adjuvant chemotherapy less frequently than younger postmenopausal women and whether comorbidity influences this potential undertreatment. In a single-site, retrospective, comparative study, postmenopausal early stage BC patients treated between 01/2001 and 12/2005 at a major German university hospital were analyzed in two age Groups A and B (≥65 vs. <65 years) for initiation and completion of guideline-recommended adjuvant chemotherapy. Risk stratification was based on the 2005 St. Gallen Consensus Conference criteria. Comorbidity was parametrized using the Charlson Comorbidity Index (CCI). Analysis included 634 patients, 380 in Group A and 254 in Group B. Mean age (range) was 73 (65-94) and 61 (55-64) years, respectively. The proportion of patients from Group A given ≥3 cycles of chemotherapy was significantly decreased as compared to Group B. 52 % of patients with CCI <3 but only 20 % with CCI ≥3 were recommended to undergo chemotherapy (p < 0.001). Median follow-up [95 % confidence interval (CI)] was 85 (82-88) months. DFS was significantly shorter in patients aged ≥65 years as compared to younger postmenopausal patients (HR, 0.598; 95 % CI, 0.358-0.963; p = 0.048). Despite being high-risk patients, older women with early stage BC were often not given guideline-recommended chemotherapy. Higher recurrence rates compared with younger postmenopausal women suggest that older patients are undertreated. Treatment needs to be adapted to general health and tumor biology rather than age. More trials in elderly BC patients are needed.

Standard analgesics reverse burrowing deficits in a rat CCI model of neuropathic pain, but not in models of type 1 and type 2 diabetes-induced neuropathic pain.

PubMed

Rutten, Kris; Gould, Stacey A; Bryden, Luke; Doods, Henri; Christoph, Thomas; Pekcec, Anton

2018-09-17

Burrowing is a rodent behavior validated as a robust and reproducible outcome measure to infer the global effect of pain in several inflammatory pain models. However, less is known about the effect of analgesics on burrowing in neuropathic pain models and no studies have determined burrowing performance in models of diabetes-associated neuropathic pain. To compare the sensitivity of the burrowing assay in different neuropathic pain models: mononeuropathic pain and diabetic polyneuropathy. Burrowing performance was determined by the amount of substrate left in a hollow tube by rats with chronic constriction injury (CCI). In addition, burrowing performance, locomotion and pain development was assessed in the Zucker diabetic fatty (ZDF) rat model, resembling type-2 diabetes. Efficacy of clinically-active reference drugs (opioids, gabapentin and/or pregabalin) were investigated in these models. Burrowing behavior was additionally assessed in a second model, induced by streptozotocin (STZ) treatment, resembling type-1 diabetes. In the CCI model, moderate but consistent burrowing deficits were observed that persisted over a period of ≥20 days. Systemic administration of morphine, pregabalin and gabapentin reversed this deficit. In contrast, none of the reference drugs improved marked burrowing deficits detected in ZDF rats, and pregabalin did not reverse severe burrowing deficits observed in STZ rats. Burrowing performance cannot necessarily be used as pain-related readout across pain models and largely depends on the model used, at least in models of neuropathy. Specifically, analgesic drug effects might be masked by general diabetes-associated alteration of the animals' well-being, resulting in false negative outcomes. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

BCR-ABL1 transcript at 3 months predicts long-term outcomes following second generation tyrosine kinase inhibitor therapy in the patients with chronic myeloid leukaemia in chronic phase who failed Imatinib.

PubMed

Kim, Dennis D; Lee, Honggi; Kamel-Reid, Suzanne; Lipton, Jeffrey H

2013-03-01

The BCR-ABL1 transcript level at 3 months can predict long-term outcomes following frontline therapy with Imatinib or Dasatinib in chronic myeloid leukaemia (CML) patients. However, data is lacking for second-generation tyrosine kinase inhibitor (2GTKI) therapy after Imatinib failure. A total of 112 patients with CML in chronic phase receiving 2GTKI after Imatinib failure were reviewed. Treatment outcomes including complete cytogenetic (CCyR), major molecular (MMR) and molecular response 4.5 (4.5 log reduction of BCR-ABL1 transcript level, MR(4.5) ), treatment failure, progression-free and overall survival (OS) were compared according to BCR-ABL1 transcript levels at 3 or 6 months, divided into <1%(IS) , 1-10%(IS) and ≥ 10%(IS) . BCR-ABL1 transcript level at 3 months showed better correlation with OS (P < 0.001) than that at 6 months (P = 0.147). Better OS was also observed in the patients achieving <1%(IS) (100%) and 1-10%(IS) (100%) than those with ≥ 10%(IS) at 3 months (70.6%, P < 0.001). Those with <1%(IS) showed the best CCyR, MMR and MR(4.5) rates; 1-10%(IS) , intermediate; and ≥ 10%(IS) , the lowest CCyR, MMR and MR(4.5) rates. The group with <1%(IS) at 3 months maintained significantly lower BCR-ABL1 transcript level compared to other two groups. In conclusion, the BCR-ABL1 transcript level at 3 months is the most relevant surrogate for outcomes following 2GTKI therapy after Imatinib failure. © 2012 Blackwell Publishing Ltd.

Acute admissions to medical departments in Denmark: diagnoses and patient characteristics.

PubMed

Vest-Hansen, Betina; Riis, Anders Hammerich; Sørensen, Henrik Toft; Christiansen, Christian Fynbo

2014-09-01

Despite extensive research on individual diseases, population-based knowledge about reasons for acute medical admissions remains limited. Our aim was to examine primary diagnoses, Charlson Comorbidity Index (CCI) score, age, and gender among patients admitted acutely to medical departments in Denmark. In this population-based observational study, 264,265 acute medical patients admitted during 2010 were identified in the Danish National Registry of Patients (DNRP), covering all hospitals in Denmark. Reasons for acute admissions were assessed by primary diagnoses, grouped according to the International Classification of Diseases 10th edition. Additionally, the CCI score, age and gender were presented according to each diagnostic group. Two-thirds of the patients had one of the four following reasons for admission: cardiovascular diseases (19.3%), non-specific Z-diagnoses ("Factors influencing health status and contact with health services") (16.9%), infectious diseases (15.5%), and non-specific R-diagnoses ("Symptoms and abnormal findings, not elsewhere classified") (11.8%). In total, 45% of the patients had a CCI score of one or more and there was a considerable overlap between the patients' chronic diseases and the reason for admission. The median age of the study population was 64 years (IQR 47-77 years), ranging from 46 years (IQR 27-66) for injury and poisoning to 74 years (IQR 60-83) for hematological diseases. Gender representation varied considerably within the diagnostic groups, for example with male predominance in mental disorders (59.0%) and female predominance in diseases of the musculoskeletal system (57.8%). Our study identifies that acute medical patients often present with non-specific symptoms or complications related to their chronic diseases. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

In vitro and in vivo effects of a novel dimeric inhibitor of PSD-95 on excitotoxicity and functional recovery after experimental traumatic brain injury.

PubMed

Sommer, Jens Bak; Bach, Anders; Malá, Hana; Strømgaard, Kristian; Mogensen, Jesper; Pickering, Darryl S

2017-01-01

PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been evaluated in the treatment of traumatic brain injury (TBI) that has pathophysiological mechanisms in common with stroke. The aims of the current study were to assess the effects of a novel dimeric inhibitor of PSD-95, UCCB01-147, on histopathology and long-term cognitive outcome after controlled cortical impact (CCI) in rats. As excitotoxic cell death is thought to be a prominent part of the pathophysiology of TBI, we also investigated the neuroprotective effects of UCCB01-147 and related compounds on NMDA-induced cell death in cultured cortical neurons. Anesthetized rats were given a CCI or sham injury, and were randomized to receive an injection of either UCCB01-147 (10 mg/kg), the non-competitive NMDAR-receptor antagonist MK-801 (1 mg/kg) or saline immediately after injury. At 2 and 4 weeks post-trauma, spatial learning and memory were assessed in a water maze, and at 3 months, brains were removed for estimation of lesion volumes. Overall, neither treatment with UCCB01-147 nor MK-801 resulted in significant improvements of cognition and histopathology after CCI. Although MK-801 provided robust neuroprotection against NMDA-induced toxicity in cultured cortical neurons, UCCB01-147 failed to reduce cell death and became neurotoxic at high doses. The data suggest potential differential effects of PSD-95 inhibition in stroke and TBI that should be investigated further in future studies taking important experimental factors such as timing of treatment, dosage, and anesthesia into consideration. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis.

PubMed

Okamoto, Kohji; Suzuki, Kenji; Takada, Tadahiro; Strasberg, Steven M; Asbun, Horacio J; Endo, Itaru; Iwashita, Yukio; Hibi, Taizo; Pitt, Henry A; Umezawa, Akiko; Asai, Koji; Han, Ho-Seong; Hwang, Tsann-Long; Mori, Yasuhisa; Yoon, Yoo-Seok; Huang, Wayne Shih-Wei; Belli, Giulio; Dervenis, Christos; Yokoe, Masamichi; Kiriyama, Seiki; Itoi, Takao; Jagannath, Palepu; Garden, O James; Miura, Fumihiko; Nakamura, Masafumi; Horiguchi, Akihiko; Wakabayashi, Go; Cherqui, Daniel; de Santibañes, Eduardo; Shikata, Satoru; Noguchi, Yoshinori; Ukai, Tomohiko; Higuchi, Ryota; Wada, Keita; Honda, Goro; Supe, Avinash Nivritti; Yoshida, Masahiro; Mayumi, Toshihiko; Gouma, Dirk J; Deziel, Daniel J; Liau, Kui-Hin; Chen, Miin-Fu; Shibao, Kazunori; Liu, Keng-Hao; Su, Cheng-Hsi; Chan, Angus C W; Yoon, Dong-Sup; Choi, In-Seok; Jonas, Eduard; Chen, Xiao-Ping; Fan, Sheung Tat; Ker, Chen-Guo; Giménez, Mariano Eduardo; Kitano, Seigo; Inomata, Masafumi; Hirata, Koichi; Inui, Kazuo; Sumiyama, Yoshinobu; Yamamoto, Masakazu

2018-01-01

We propose a new flowchart for the treatment of acute cholecystitis (AC) in the Tokyo Guidelines 2018 (TG18). Grade III AC was not indicated for straightforward laparoscopic cholecystectomy (Lap-C). Following analysis of subsequent clinical investigations and drawing on Big Data in particular, TG18 proposes that some Grade III AC can be treated by Lap-C when performed at advanced centers with specialized surgeons experienced in this procedure and for patients that satisfy certain strict criteria. For Grade I, TG18 recommends early Lap-C if the patients meet the criteria of Charlson comorbidity index (CCI) ≤5 and American Society of Anesthesiologists physical status classification (ASA-PS) ≤2. For Grade II AC, if patients meet the criteria of CCI ≤5 and ASA-PS ≤2, TG18 recommends early Lap-C performed by experienced surgeons; and if not, after medical treatment and/or gallbladder drainage, Lap-C would be indicated. TG18 proposes that Lap-C is indicated in Grade III patients with strict criteria. These are that the patients have favorable organ system failure, and negative predictive factors, who meet the criteria of CCI ≤3 and ASA-PS ≤2 and who are being treated at an advanced center (where experienced surgeons practice). If the patient is not considered suitable for early surgery, TG18 recommends early/urgent biliary drainage followed by delayed Lap-C once the patient's overall condition has improved. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Comparison of Customized Cutting Block and Conventional Cutting Instrument in Total Knee Arthroplasty: A Randomized Controlled Trial.

PubMed

Tammachote, Nattapol; Panichkul, Phonthakorn; Kanitnate, Supakit

2018-03-01

Customized cutting block (CCB) was designed to ensure the accurate alignment of knee prostheses during total knee arthroplasty. Given the paucity of CCB efficacy data, we compare CCB with conventional cutting guide using a randomized controlled trial. One hundred eight osteoarthritic knee patients underwent total knee arthroplasty by one experienced surgeon were randomized to receive CCB (n = 54) or conventional cutting instrument (CCI) surgery (n = 54). The primary outcomes were limb alignment, prostheses position, and operative time. The secondary outcomes were hemodynamic alteration after surgery, functional outcomes (modified Western Ontario and McMaster University Osteoarthritis Index) and range of motion at 2 years after surgery. Mean hip-knee-ankle angle in the CCB group was 179.4° ± 1.8° vs 179.1° ± 2.4° in the CCI group, Δ = 0 (95% confidence interval [CI] -0.6 to 1.1, P = .55). Mean operative time was faster in the CCB arm: 93 ± 12 vs 104 ± 12 minutes, Δ = 11 (95% CI -16.7 to -7.2, P < .0001). There were no differences in hemodynamic parameters, mean blood loss (446 [CCB] vs 514 mL [CCI], Δ = -68 [95% CI -138 to 31 mL, P = .21]), postoperative hemoglobin changes, incidence of hypotension (systolic <90 mm Hg), oliguria, and rates of blood transfusion. Functional outcomes and range of motion were also similar. There was no improvement in alignment, hemodynamic changes, blood loss, and knee functional outcomes. CCB reduced surgical time by 11 minutes in our population. CCB cost-effectiveness should be further investigated. Copyright © 2017 Elsevier Inc. All rights reserved.

Comorbidity in acute pancreatitis relates to organ failure but not to local complications.

PubMed

Weitz, G; Woitalla, J; Wellhöner, P; Schmidt, K J; Büning, J; Fellermann, K

2016-03-01

Organ failure and local complications contribute to morbidity and mortality in acute pancreatitis. Comorbidity is known to be related to organ failure. The impact of comorbidity on local complications has not yet been delineated. Moreover, it is not clear if the outcome of first-attacks and acute-on-chronic episodes, respectively, differs from outcome in all episodes. Consecutive cases of confirmed acute pancreatitis in a four-year period were reviewed. Charlson comorbidity index (CCI), complications (organ failure and local complications), disease severity (according to the revised Atlanta Classification), need for intensive care, and mortality were derived from the charts. A total of 391 episodes of acute pancreatitis were included. Patients with organ failure were significantly older (P< 0.001) und had a higher CCI (P< 0.001) than patients without organ failure. Patients with and without local complications did not significantly differ in age or CCI. The complication rate of the entire cohort (n = 391; 47.1 %) was comparable with the complication rate of first-attacks (n = 269; 46.8 %) and acute-on-chronic episodes (n = 68; 47.1 %). The majority of the twelve deceased patients had been old and/or chronically ill. Six of these patients had an advanced malignant disease. Comorbidity and age clearly are contributors to organ failure and mortality. Local complications occur independently of age and concomitant diseases. The overall complication rate is not significantly influenced by preceding inflammation of the pancreas. To further improve care in patients with acute pancreatitis special attention should be given to old and multi-morbid patients. © Georg Thieme Verlag KG Stuttgart · New York.

Combined therapy with m-TOR-dependent and -independent autophagy inducers causes neurotoxicity in a mouse model of Machado-Joseph disease.

PubMed

Duarte-Silva, S; Silva-Fernandes, A; Neves-Carvalho, A; Soares-Cunha, C; Teixeira-Castro, A; Maciel, P

2016-01-28

A major pathological hallmark in several neurodegenerative disorders, like polyglutamine disorders (polyQ), including Machado-Joseph disease (MJD), is the formation of protein aggregates. MJD is caused by a CAG repeat expansion in the ATXN3 gene, resulting in an abnormal protein, which is prone to misfolding and forms cytoplasmic and nuclear aggregates within neurons, ultimately inducing neurodegeneration. Treatment of proteinopathies with drugs that up-regulate autophagy has shown promising results in models of polyQ diseases. Temsirolimus (CCI-779) inhibits the mammalian target of rapamycin (m-TOR), while lithium chloride (LiCl) acts by inhibiting inositol monophosphatase, both being able to induce autophagy. We have previously shown that chronic treatment with LiCl (10.4 mg/kg) had limited effects in a transgenic MJD mouse model. Also, others have shown that CCI-779 had mild positive effects in a different mouse model of the disease. It has been suggested that the combination of mTOR-dependent and -independent autophagy inducers could be a more effective therapeutic approach. To further explore this avenue toward therapy, we treated CMVMJD135 transgenic mice with a conjugation of CCI-779 and LiCl, both at concentrations known to induce autophagy and not to be toxic. Surprisingly, this combined treatment proved to be deleterious to both wild-type (wt) and transgenic animals, failing to rescue their neurological symptoms and actually exerting neurotoxic effects. These results highlight the possible dangers of manipulating autophagy in the nervous system and suggest that a better understanding of the potential disruption in the autophagy pathway in MJD is required before successful long-term autophagy modulating therapies can be developed. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of heavy metals on Cyanothece sp. CCY 0110 growth, extracellular polymeric substances (EPS) production, ultrastructure and protein profiles.

PubMed

Mota, Rita; Pereira, Sara B; Meazzini, Marianna; Fernandes, Rui; Santos, Arlete; Evans, Caroline A; De Philippis, Roberto; Wright, Phillip C; Tamagnini, Paula

2015-04-29

The effects of several heavy metals on the growth/survival, EPS production, ultrastructure and protein profiles of the highly efficient extracellular polymeric substances (EPS)-producer cyanobacterium Cyanothece sp. CCY 0110 were evaluated. Our results clearly show that each heavy metal affects the cells in a particular manner, triggering distinctive responses. Concerning chronic exposure, cells were more affected by Cu(2+) followed by Pb(2+), Cd(2+), and Li(+). The presence of metal leads to remarkable ultrastructural changes, mainly at the thylakoid level. The comparison of the proteomes (iTRAQ) allowed to follow the stress responses and to distinguish specific effects related to the time of exposure and/or the concentration of an essential (Cu(2+)) and a non-essential (Cd(2+)) metal. The majority of the proteins identified and with fold changes were associated with photosynthesis, CO2 fixation and carbohydrate metabolism, translation, and nitrogen and amino acid metabolism. Moreover, our results indicate that during chronic exposure to sub-lethal concentrations of Cu(2+), the cells tune down their metabolic rate to invest energy in the activation of detoxification mechanisms, which eventually result in a remarkable recovery. In contrast, the toxic effects of Cd(2+) are cumulative. Unexpectedly, the amount of released polysaccharides (RPS) was not enhanced by the presence of heavy metals. This work shows the holistic effects of different heavy metals on the cells of the highly efficient EPS-producer the cyanobacterium Cyanothece sp. CCY 0110. The growth/survival, EPS production, ultrastructure, protein profiles and stress response were evaluated. The knowledge generated by this study will contribute to the implementation of heavy-metal removal systems based on cyanobacteria EPS or their isolated polymers. Copyright © 2015. Published by Elsevier B.V.

Activation of GPR30 attenuates chronic pain-related anxiety in ovariectomized mice.

PubMed

Liu, Shui-bing; Tian, Zhen; Guo, Yan-yan; Zhang, Nan; Feng, Bin; Zhao, Ming-gao

2015-03-01

Estrogen regulates neuroendocrine and inflammatory processes that play critical roles in neuroinflammation, anxiety, and chronic pain. Patients suffering from chronic pain often complain of anxiety. However, limited information is available regarding the neural circuitry of chronic pain-related anxiety and the related function of estrogen. Hindpaw injection of complete Freund's adjuvant (CFA) and chronic constriction injury (CCI) of the sciatic nerve induced notable pain sensitization and anxiety-like behavior in ovariectomized (OVX) mice. We found that the level of G-protein-coupled receptor 30 (GPR30), a membrane estrogen receptor, was significantly increased in the basolateral amygdala (BLA) of ovariectomized (OVX) mice suffering from chronic inflammatory and neuropathic pain. Subcutaneous injection or BLA local infusion of the GPR30 agonist G1 significantly reduced anxiety-like behavior in CFA-injected and CCI-OVX mice; however, this treatment did not alter the nociceptive threshold. GPR30 knock down by shRNA in the BLA of OVX mice inhibited the anxiolytic effects of GPR30 activation. G1 administration reversed the upregulation of GluR1 subunit in AMPA and NR2A-containing NMDA receptors and the downregulation of GABAA receptors in the BLA of CFA-injected and CCI-OVX mice. Electrophysiological recording revealed that GPR30 activation could prevent imbalance between excitatory and inhibitory transmissions in the BLA synapses of CFA-injected OVX mice. In conclusion, GPR30 activation induced anxiolytic effects but did not affect the nociceptive threshold of mice under chronic pain. The anxiolytic effects of GPR30 were partially due to maintaining the balance between excitatory and inhibitory transmissions in the BLA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Risk Factors for Treatment Failure With the Adjustable Transobturator Male System Incontinence Device: Who Will Succeed, Who Will Fail? Results of a Multicenter Study.

PubMed

Friedl, Alexander; Mühlstädt, Sandra; Rom, Maximilian; Kivaranovic, Danijel; Mohammed, Nasreldin; Fornara, Paolo; Brössner, Clemens

2016-04-01

To identify risk factors for treatment failure of men with the adjustable transobturator male system (ATOMS) for treating stress urinary incontinence (SUI). Sixty-two patients with SUI after prostate surgery were provided with an ATOMS. The self-defined criteria for treatment failure (implant removal [A], no improvement or ≥3 pads/24 hours [B], and no improvement or ≥150 mL urine loss/24 hours [C]) were compared to anamnestic, clinical, and time-specific parameters: age, Charlson comorbidity index (CCI), urine culture (UC), previous ineffective implants, body mass index, radiotherapy, renal function (serum creatinine), smoker status, urethral strictures, SUI severity, surgery time, time to and season at implantation, and port system application. After a median follow-up of 17.7 months, 9 ATOMS (15%) were removed due to infection (8) or dysfunction (1); 23% and 16% had treatment failure of criteria B and C. Dry rate/overall success rate was 61%/87%. Age alone was no risk factor but the CCI and a positive UC were univariate significant predictors of the criteria A, B, and C. Besides, previous devices and renal failure were significantly associated with implant removal (A) and SUI severity with criterion C. In multivariate analysis, previous devices (P = .0163), positive UC (P = .0190), and SUI severity (P = .0123) were the strongest predictors of A, B, and C, respectively. A poor CCI, preoperative positive UC, severe SUI, and previous implants lead to more treatment failure and removal. Age, body mass index, radiotherapy, urethral strictures, current smoking, time-specific parameters, seasonality, and port system application did not influence the outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Use-dependent dendritic regrowth is limited after unilateral controlled cortical impact to the forelimb sensorimotor cortex.

PubMed

Jones, Theresa A; Liput, Daniel J; Maresh, Erin L; Donlan, Nicole; Parikh, Toral J; Marlowe, Dana; Kozlowski, Dorothy A

2012-05-01

Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3-28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI.

Voice emotion recognition by cochlear-implanted children and their normally-hearing peers

PubMed Central

Chatterjee, Monita; Zion, Danielle; Deroche, Mickael L.; Burianek, Brooke; Limb, Charles; Goren, Alison; Kulkarni, Aditya M.; Christensen, Julie A.

2014-01-01

Despite their remarkable success in bringing spoken language to hearing impaired listeners, the signal transmitted through cochlear implants (CIs) remains impoverished in spectro-temporal fine structure. As a consequence, pitch-dominant information such as voice emotion, is diminished. For young children, the ability to correctly identify the mood/intent of the speaker (which may not always be visible in their facial expression) is an important aspect of social and linguistic development. Previous work in the field has shown that children with cochlear implants (cCI) have significant deficits in voice emotion recognition relative to their normally hearing peers (cNH). Here, we report on voice emotion recognition by a cohort of 36 school-aged cCI. Additionally, we provide for the first time, a comparison of their performance to that of cNH and NH adults (aNH) listening to CI simulations of the same stimuli. We also provide comparisons to the performance of adult listeners with CIs (aCI), most of whom learned language primarily through normal acoustic hearing. Results indicate that, despite strong variability, on average, cCI perform similarly to their adult counterparts; that both groups’ mean performance is similar to aNHs’ performance with 8-channel noise-vocoded speech; that cNH achieve excellent scores in voice emotion recognition with full-spectrum speech, but on average, show significantly poorer scores than aNH with 8-channel noise-vocoded speech. A strong developmental effect was observed in the cNH with noise-vocoded speech in this task. These results point to the considerable benefit obtained by cochlear-implanted children from their devices, but also underscore the need for further research and development in this important and neglected area. PMID:25448167

Improvement in metabolic effects by dietary intervention is dependent on the precise nature of the developmental programming challenge.

PubMed

Bautista, C J; Guzmán, C; Rodríguez-González, G L; Zambrano, E

2015-08-01

Predisposition to offspring metabolic dysfunction due to poor maternal nutrition differs with the developmental stage at exposure. Post-weaning nutrition also influences offspring phenotype in either adverse or beneficial ways. We studied a well-established rat maternal protein-restriction model to determine whether post-weaning dietary intervention improves adverse outcomes produced by a deficient maternal nutritional environment in pregnancy. Pregnant rats were fed a controlled diet (C, 20% casein) during pregnancy and lactation (CC) or were fed a restricted diet (R, 10% casein isocaloric diet) during pregnancy and C diet during lactation (RC). After weaning, the offspring were fed the C diet. At postnatal day (PND) 70 (young adulthood), female offspring either continued with the C diet (CCC and RCC) or were fed commercial Chow Purina 5001 (I) to further divide the animals into dietary intervention groups CCI and RCI. Another group of mothers and offspring were fed I throughout (III). Offspring food intake was averaged between PND 95-110 and 235-250 and carcass and liver compositions were measured at PND 25 and 250. Leptin (PND 110 and 250) and serum glucose, triglycerides and cholesterol (PND 250) levels were measured. Statistical analysis was carried out using ANOVA. At PND 25, body and liver weights were similar between groups; however, CCC and RCC carcass protein:fat ratios were lower compared with III diet. At PND 110 and 250, offspring CCC and RCC had higher body weight, food intake and serum leptin compared with CCI and RCI. CCI had lower carcass fat and increased protein compared with CCC and improved fasting glucose and triglycerides. Adult dietary intervention partially overcomes adverse effects of programming. Further studies are needed to determine the mechanisms involved.

In vivo evaluation of the hippocampal glutamate, GABA and the BDNF levels associated with spatial memory performance in a rodent model of neuropathic pain.

PubMed

Saffarpour, S; Shaabani, M; Naghdi, N; Farahmandfar, M; Janzadeh, A; Nasirinezhad, F

2017-06-01

Patients with chronic pain usually suffer from learning and memory impairment which may significantly decrease their quality of life. Despite laboratory and clinical studies, the mechanism underlying this memory impairment remains elusive. We evaluated the effect of chronic pain on the glutamate and GABA levels and BDNF expression in the CA1 region of hippocampus as a possible explanation for memory impairment related to neuropathic pain. In this respect, 30 male rats were randomly allocated to 3 groups as control, sham and neuropathic. Neuropathic pain was induced by a chronic constriction injury of the sciatic nerve (CCI) and mechanical allodynia and the spatial memory was assessed using the Von Frey filaments and Morris water maze respectively. To determine the potential mechanisms, the in vivo extracellular levels of glutamate and γ-aminobutyric acid (GABA) were measured by microdialysis and the brain-derived neurotrophic factor (BDNF) expression was determined by using western blots technique in the hippocampus on days 14 and 21 post-CCI. We showed that CCI impaired spatial learning and memory in Morris water maze (MWM) task. BDNF expression level and glutamate concentration significantly decreased in rats with chronic constriction injury of the sciatic nerve (P<0.001, F=7.3, F=23.23). In addition, GABA increased in hippocampal CA1 region (P<0.001, F=39.2) when the pain threshold was minimum. Nevertheless, these changes reversed while pain was relieved spontaneously. Chronic pain induced by constriction of the sciatic nerve impairs the spatial learning and memory function in rats. This effect exerts through the increase in GABA concentration and decrease in the glutamate and BDNF levels in the CA1 region of the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

Dilantin therapy in an experimental model of traumatic brain injury: effects of limited versus daily treatment on neurological and behavioral recovery.

PubMed

Darrah, Shaun D; Darrah, Shaun H; Chuang, Jerry; Mohler, Laura M; Chen, Xiangbai; Cummings, Erin E; Burnett, Tiffany; Reyes-Littaua, M Christina; Galang, Gary N; Wagner, Amy K

2011-01-01

The mechanisms by which Dilantin confers anticonvulsant benefits may also be neuroprotective by attenuating the acute excitatory insult in cortical and subcortical structures when the drug is given in the acute phase after traumatic brain injury (TBI). However, when Dilantin is used for prolonged periods, we hypothesized that it may impede recovery, synaptic plasticity may be impaired, and neuroprotective benefits may be lost. As such, we assessed the effect of daily chronic administration (75 mg/kg day 0 followed by 50 mg/kg daily i.p.) and acute administration (75 mg/kg day 0 followed by 50 mg/kg i.p. day 1) of Dilantin in young adult male rats on motor performance, y-maze exploration, Morris Water Maze (MWM), hippocampal (HC) cell survival, contusion size, and regional expression of neuroplasticity markers after controlled cortical impact (CCI) injury. Chronic daily Dilantin administration resulted in beam walking impairments on day 6, whereas acute Dilantin administration resulted in beam walking impairments on days 3 and 4. Chronic Dilantin administration also resulted in worse MWM performance, more HC cell loss and no increases in neuroplasticity markers compared to rats with CCI receiving chronic vehicle. Conversely, rats receiving acute Dilantin administration exhibited more novel arm exploration in the y-maze, greater HC cell sparing, and greater growth-associated protein 43 (GAP-43) expression in the HC ipsilateral to the CCI, compared to injured rats receiving vehicle. MWM was not influenced by acute Dilantin administration. These results suggest that there are beneficial effects of limited acute Dilantin therapy after TBI, and that extended daily Dilantin therapy has deleterious effects on neural recovery. These findings support clinical guidelines for limited use of Dilantin in seizure prophylaxis after TBI.

Downregulation of spinal glutamate transporter EAAC1 following nerve injury is regulated by central glucocorticoid receptors in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Yang, Liling; Sung, Backil; Mao, Jianren

2006-01-01

Previous studies have shown that glucocorticoid receptors (GR) were upregulated, whereas glutamate transporters were downregulated, within the spinal cord dorsal horn after peripheral nerve injury. However, the relationship between the expression of spinal GR and glutamate transporter after nerve injury remains unknown. In the present study, we examined the hypothesis that central GR would regulate the expression of spinal glutamate transporter EAAC1 following chronic constriction nerve injury (CCI) in rats. CCI induced a significant downregulation of EAAC1 expression primarily within the ipsilateral spinal cord dorsal horn when examined on postoperative day 7 using both Western blot and immunohistochemistry. The downregulation of EAAC1 was significantly diminished after either the GR antagonist RU38486 (4 > 2 = 0.5 microg = vehicle) or a GR antisense oligonucleotide was administered intrathecally twice daily for postoperative day 1-6. Moreover, CCI induced a significant downregulation of nuclear factor kappaB (NF-kappaB) within the ipsilateral spinal cord dorsal horn, which also was attenuated by either RU38486 (4 > 2 = 0.5 microg = vehicle) or a GR antisense oligonucleotide. The immunohistochemical data indicated a pattern of colocalization between GR and EAAC1 as well as GR and NF-kappaB within the spinal cord dorsal horn. Since, NF-kappaB has been shown to regulate the expression of those cellular elements linked to inflammation and tissue injury and its activity can be negatively regulated by GR activation, these results suggest that spinal GR through NF-kappaB may play a significant role in the regulation of EAAC1 expression after peripheral nerve injury, a cellular pathway that may contribute to the development of neuropathic pain behaviors in rats.

[Transcultural adaptation of the Antifat Attitudes Test to Brazilian Portuguese].

PubMed

Obara, Angélica Almeida; Alvarenga, Marle Dos Santos

2018-05-01

Obese individuals are often blamed for their own condition and the targets of discrimination and prejudice. The scope of this study is to describe the cross-cultural adaptation to Brazilian Portuguese and the validation of the Antifat Attitudes Test - specifically developed for evaluation of negative attitudes toward the obese individual. The scale has 34 statements distributed in three subscales - Social/Character Disparagement (15 items), Physical/Romantic Unattractiveness (10 items) and Weight Control/Blame (9 items). The method involved the translation of the scale; evaluation of the conceptual, operational and item equivalence; evaluation of the semantic equivalence using the paired t test, the Pearson correlation coefficient and the intraclass correlation coefficient (ICC); internal consistency evaluation (Cronbach's alpha) and test-retest reliability (ICC) and Confirmatory Factor Analysis - after application in 340 college students in the area of health. The results showed good global internal consistency and reliability (α 0.85; CCI 0.83), and factor analysis showed that the original subscales can be kept in the adaptation, and therefore the scale adapted to the Brazilian-Portuguese version is valid and useful in studies to explore negative attitudes toward obese individuals.

KSC-2012-1322

NASA Image and Video Library

2012-02-14

COCOA BEACH, Fla. -- Ed Mango, program manager for NASA's Commercial Crew Program CCP, talks to industry partners and stakeholders during a preproposal conference at the Courtyard Marriott in Cocoa Beach, Fla. The meeting focused on information related to NASA's release of the Commercial Crew Integrated Capability CCiCap Announcement for Proposals on Feb. 7. More than 50 people from 25 aerospace companies attended the conference to find out what the space agency would be looking for in terms of milestones, funding, schedules, strategies, safety cultures, business modules and eventual flight certification standards of integrated crew space transportation systems. The goal of the CCiCap is to develop an indigenous U.S. transportation system that can safely, affordably and routinely fly to low Earth orbit destinations, including the International Space Station. Proposals are due March 23 and NASA plans to award multiple Space Act Agreements, valued from $300 million to $500 million each, toward the development of fully integrated commercial crew transportation systems in the summer of 2012. For more information, visit www.nasa.gov/commercialcrew Photo credit: Kim Shiflett

KSC-2012-1325

NASA Image and Video Library

2012-02-14

COCOA BEACH, Fla. -- Phil McAlister, NASA's director of Commercial Spaceflight Development, talks to industry partners and stakeholders during a preproposal conference at the Courtyard Marriott in Cocoa Beach, Fla. The meeting focused on information related to NASA's release of the Commercial Crew Integrated Capability CCiCap Announcement for Proposals on Feb. 7. More than 50 people from 25 aerospace companies attended the conference to find out what the space agency would be looking for in terms of milestones, funding, schedules, strategies, safety cultures, business modules and eventual flight certification standards of integrated crew space transportation systems. The goal of the CCiCap is to develop an indigenous U.S. transportation system that can safely, affordably and routinely fly to low Earth orbit destinations, including the International Space Station. Proposals are due March 23 and NASA plans to award multiple Space Act Agreements, valued from $300 million to $500 million each, toward the development of fully integrated commercial crew transportation systems in the summer of 2012. For more information, visit www.nasa.gov/commercialcrew Photo credit: Kim Shiflett

KSC-2012-1333

NASA Image and Video Library

2012-02-14

COCOA BEACH, Fla. -- Ed Mango, program manager for NASA's Commercial Crew Program CCP, talks to media during a preproposal conference at the Courtyard Marriott in Cocoa Beach, Fla. The meeting focused on information related to NASA's release of the Commercial Crew Integrated Capability CCiCap Announcement for Proposals on Feb. 7. More than 50 industry partners and stakeholders from 25 aerospace companies attended the conference to find out what the space agency would be looking for in terms of milestones, funding, schedules, strategies, safety cultures, business modules and eventual flight certification standards of integrated crew space transportation systems. The goal of the CCiCap is to develop an indigenous U.S. transportation system that can safely, affordably and routinely fly to low Earth orbit destinations, including the International Space Station. Proposals are due March 23 and NASA plans to award multiple Space Act Agreements, valued from $300 million to $500 million each, toward the development of fully integrated commercial crew transportation systems in the summer of 2012. For more information, visit www.nasa.gov/commercialcrew Photo credit: Kim Shiflett

KSC-2012-1326

NASA Image and Video Library

2012-02-14

COCOA BEACH, Fla. -- Ed Mango, program manager for NASA's Commercial Crew Program CCP, talks to industry partners and stakeholders during a preproposal conference at the Courtyard Marriott in Cocoa Beach, Fla. The meeting focused on information related to NASA's release of the Commercial Crew Integrated Capability CCiCap Announcement for Proposals on Feb. 7. More than 50 people from 25 aerospace companies attended the conference to find out what the space agency would be looking for in terms of milestones, funding, schedules, strategies, safety cultures, business modules and eventual flight certification standards of integrated crew space transportation systems. The goal of the CCiCap is to develop an indigenous U.S. transportation system that can safely, affordably and routinely fly to low Earth orbit destinations, including the International Space Station. Proposals are due March 23 and NASA plans to award multiple Space Act Agreements, valued from $300 million to $500 million each, toward the development of fully integrated commercial crew transportation systems in the summer of 2012. For more information, visit www.nasa.gov/commercialcrew Photo credit: Kim Shiflett

KSC-2012-1332

NASA Image and Video Library

2012-02-14

COCOA BEACH, Fla. -- Ed Mango, program manager for NASA's Commercial Crew Program CCP, talks to media during a preproposal conference at the Courtyard Marriott in Cocoa Beach, Fla. The meeting focused on information related to NASA's release of the Commercial Crew Integrated Capability CCiCap Announcement for Proposals on Feb. 7. More than 50 industry partners and stakeholders from 25 aerospace companies attended the conference to find out what the space agency would be looking for in terms of milestones, funding, schedules, strategies, safety cultures, business modules and eventual flight certification standards of integrated crew space transportation systems. The goal of the CCiCap is to develop an indigenous U.S. transportation system that can safely, affordably and routinely fly to low Earth orbit destinations, including the International Space Station. Proposals are due March 23 and NASA plans to award multiple Space Act Agreements, valued from $300 million to $500 million each, toward the development of fully integrated commercial crew transportation systems in the summer of 2012. For more information, visit www.nasa.gov/commercialcrew Photo credit: Kim Shiflett

KSC-2012-1330

NASA Image and Video Library

2012-02-14

COCOA BEACH, Fla. -- Ed Mango, program manager for NASA's Commercial Crew Program CCP, talks to media during a preproposal conference at the Courtyard Marriott in Cocoa Beach, Fla. The meeting focused on information related to NASA's release of the Commercial Crew Integrated Capability CCiCap Announcement for Proposals on Feb. 7. More than 50 industry partners and stakeholders from 25 aerospace companies attended the conference to find out what the space agency would be looking for in terms of milestones, funding, schedules, strategies, safety cultures, business modules and eventual flight certification standards of integrated crew space transportation systems. The goal of the CCiCap is to develop an indigenous U.S. transportation system that can safely, affordably and routinely fly to low Earth orbit destinations, including the International Space Station. Proposals are due March 23 and NASA plans to award multiple Space Act Agreements, valued from $300 million to $500 million each, toward the development of fully integrated commercial crew transportation systems in the summer of 2012. For more information, visit www.nasa.gov/commercialcrew Photo credit: Kim Shiflett

KSC-2012-1323

NASA Image and Video Library

2012-02-14

COCOA BEACH, Fla. -- Ed Mango, program manager for NASA's Commercial Crew Program CCP, talks to industry partners and stakeholders during a preproposal conference at the Courtyard Marriott in Cocoa Beach, Fla. The meeting focused on information related to NASA's release of the Commercial Crew Integrated Capability CCiCap Announcement for Proposals on Feb. 7. More than 50 people from 25 aerospace companies attended the conference to find out what the space agency would be looking for in terms of milestones, funding, schedules, strategies, safety cultures, business modules and eventual flight certification standards of integrated crew space transportation systems. The goal of the CCiCap is to develop an indigenous U.S. transportation system that can safely, affordably and routinely fly to low Earth orbit destinations, including the International Space Station. Proposals are due March 23 and NASA plans to award multiple Space Act Agreements, valued from $300 million to $500 million each, toward the development of fully integrated commercial crew transportation systems in the summer of 2012. For more information, visit www.nasa.gov/commercialcrew Photo credit: Kim Shiflett

KSC-2012-1331

NASA Image and Video Library

2012-02-14

COCOA BEACH, Fla. -- Ed Mango, program manager for NASA's Commercial Crew Program CCP, talks to media during a preproposal conference at the Courtyard Marriott in Cocoa Beach, Fla. The meeting focused on information related to NASA's release of the Commercial Crew Integrated Capability CCiCap Announcement for Proposals on Feb. 7. More than 50 industry partners and stakeholders from 25 aerospace companies attended the conference to find out what the space agency would be looking for in terms of milestones, funding, schedules, strategies, safety cultures, business modules and eventual flight certification standards of integrated crew space transportation systems. The goal of the CCiCap is to develop an indigenous U.S. transportation system that can safely, affordably and routinely fly to low Earth orbit destinations, including the International Space Station. Proposals are due March 23 and NASA plans to award multiple Space Act Agreements, valued from $300 million to $500 million each, toward the development of fully integrated commercial crew transportation systems in the summer of 2012. For more information, visit www.nasa.gov/commercialcrew Photo credit: Kim Shiflett

KSC-2012-1324

NASA Image and Video Library

2012-02-14

COCOA BEACH, Fla. -- Phil McAlister, NASA's director of Commercial Spaceflight Development, talks to industry partners and stakeholders during a preproposal conference at the Courtyard Marriott in Cocoa Beach, Fla. The meeting focused on information related to NASA's release of the Commercial Crew Integrated Capability CCiCap Announcement for Proposals on Feb. 7. More than 50 people from 25 aerospace companies attended the conference to find out what the space agency would be looking for in terms of milestones, funding, schedules, strategies, safety cultures, business modules and eventual flight certification standards of integrated crew space transportation systems. The goal of the CCiCap is to develop an indigenous U.S. transportation system that can safely, affordably and routinely fly to low Earth orbit destinations, including the International Space Station. Proposals are due March 23 and NASA plans to award multiple Space Act Agreements, valued from $300 million to $500 million each, toward the development of fully integrated commercial crew transportation systems in the summer of 2012. For more information, visit www.nasa.gov/commercialcrew Photo credit: Kim Shiflett

KSC-2013-3624

NASA Image and Video Library

2013-08-21

LAS CRUCES, N.M. – A thruster glows red during a hot-fire test for Boeing’s CST-100 spacecraft orbital maneuvering and attitude control OMAC system. During the tests at NASA’s White Sands Test Facility in Las Cruces, N.M., Boeing and partner Aerojet Rocketdyne tested two thrusters to demonstrate stable combustion and performance in a vacuum, simulating a space environment. Two additional thrusters were tested in a vacuum to demonstrate long-duration mission survivability. The 24 thrusters that compose the CST-100’s OMAC system will be jettisoned with the service module after the deorbit burn, prior to re-entry. The tests completed Milestone 9 of the company's funded Space Act Agreement with NASA’s Commercial Crew Program, or CCP, during the Commercial Crew Integrated Capability, or CCiCap, initiative. CCP is intended to lead to the availability of commercial human spaceflight services for government and commercial customers to low-Earth orbit. Future development and certification initiatives eventually will lead to the availability of human spaceflight services for NASA to send its astronauts to the International Space Station, where critical research is taking place daily. For more information about CCP, go to http://www.nasa.gov/commercialcrew. Photo credit: Boeing