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Antioxidant vitamins C, E and coenzyme Q10 vs Dexamethasone: comparisons of their effects in pulmonary contusion model
Mertol Gokce1,
Ozkan Saydam1,
Volkan Hanci2,
Murat Can3 &
Burak Bahadir4
Journal of Cardiothoracic Surgery volume 7, Article number: 92 (2012) Cite this article
The goal of our study is to evaluate the effects of antioxidant vitamins (vitamin C and E), Coenzyme Q10 (CoQ10) and dexamethasone (Dxm) in experimental rat models with pulmonary contusion (PC).
Rats were randomly divided into six groups. Except for the control, all subgroups had a moderate pulmonary contusion. Animals in the group I and group II received intraperitoneal saline, group III received 10mg.kg-1 CoQ10 group IV received 100mg.kg-1 vitamin C, group V received 150mg.kg-1 vitamin E, and group VI received 10mg.kg-1 Dxm. Blood gas analysis, serum nitric oxide (NO) and malondialdehyde (MDA) levels as well as superoxide dismutase (SOD) activity assays, bronchoalveolar lavage (BAL) fluid and histopathological examination were performed.
Administration of CoQ10 resulted in a significant increase in PaO2 values compared with the group I (p = 0.004). Levels of plasma MDA in group II were significantly higher than those in the group I (p = 0.01). Early administration of vitamin C, CoQ10, and Dxm significantly decreased the levels of MDA (p = 0.01). Lung contusion due to blunt trauma significantly decreased SOD activities in rat lung tissue compared with group I (p = 0.01). SOD levels were significantly elevated in animals treated with CoQ10, Vitamin E, or Dxm compared with group II (p = 0.01).
In our study, CoQ10, vitamin C, vitamin E and Dxm had a protective effect on the biochemical and histopathological outcome of PC after experimental blunt thorax trauma.
Pulmonary contusion (PC) is the most frequently diagnosed intrathoracic injury related to blunt chest trauma, affecting 17-25% of adult blunt chest trauma patients [1, 2]. It is also an independent risk factor for the development of pneumonia, severe clinical acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [1]. The exact mechanisms of PC due to blunt trauma are not yet understood. It may lead to a variety of pathophysiological alterations including inflammation, increased alveolo-capillary permeability, pulmonary oedema, ventilation/perfusion mismatching, increased intrapulmonary shunting, and a loss of compliance [3–8]. PC is revealed to be related to a progressive inflammatory response mediated by local and systemic immunological alterations [8–10]. Cytokines, reactive oxygen species (ROS), and proteolytic enzymes released from macrophages and leucocytes increase the alveolo- capillary membrane permeability and microvascular leakage [11, 12]. Although the standard treatment options for these patients remain largely supportive, such as supplemental oxygen, cardiopulmonary monitoring, analgesia and pulmonary hygiene, there is accumulating support for treating the activation of a secondary inflammatory response [6, 8–10]. Early supportive approaches, especially for moderate to severe patients with PC in intensive care units, are very important. To understand and evaluate the inflammatory process, antioxidant-oxidant mechanisms, and the effect of the anti-inflammatory drugs after blunt thorax trauma, many experimental animal trials have been conducted [13–16].
Animal experiments and clinical trials have shown that the administration of coenzyme Q10 (CoQ10), which has membrane stabilizing properties and acts as an antioxidant in both mitochondrial and lipid membranes, can inhibit the elevation of serum creatine kinase activity and lipid peroxidation and reduce exercise-induced muscular injuries [17–20]. Certain vitamins, including vitamin C and vitamin E, are also suggested to have strong free radical scavenging properties [21, 22]. The antioxidant drug Tempol®, antioxidant effectivity N-acetyl cystein (NAC) and dexamethasone (Dxm) were also used in experimental PC models [13, 16].
The goal of our study was to evaluate the effects of antioxidant vitamins and CoQ10 in experimental rat models with PC by using isolated blunt thorax trauma and to evaluate the biochemical and histopathological effects by comparing the effects of these antioxidants with the potent anti-inflammatory agent dexamethasone.
After the study was approved by the Animal Ethics Committee of Zonguldak Karaelmas University (ZKU) Medical School, 42 adult male Wistar–Albino rats weighting 450-550 g were randomly divided into six groups. All animals were housed in the ZKU Experimental Animals Research Unit in climate controlled rooms (24 ± 1°C) on a 12 h light–12 h dark cycle. Food and water were available ad libitum. They were fed with food pellets produced specially for experimental animals. Experiments were conducted according to the guiding principles for the care and use of laboratory animals (NIH publication No. 85-23, revised 1985).
Blunt chest trauma model
Lung contusion was induced using the model of isolated bilateral lung contusion described by Raghavendran et al.[14]. A hollow cylindrical weight (400 g) was dropped from a definite height (50 cm); it was encased in a vertical stainless steel tube that was positioned on a Lexon platform. This device was then suspended on Teflon guides in order to minimize friction and facilitate energy transfer. The platform was attached to a plastic protective shield that was in direct contact with the lateral aspect of the rat. This precordial shield was designed to protect the heart form contusion and thus directed the impact energy to the chest wall of the rats bilaterally. The impact energy created via this mechanism was calculated by using the equation E = mgh [E: energy; g: gravity (9.8 m/s2); h: height form the platform (50 cm); m: mass of the cylindrical weight (0.40 kg)]. The total energy transferred to the chest wall of the rats was calculated as 1.96 J.
Experimental protocol
Animals were randomly allocated into six groups: group I (Control, n = 7), group II (Sham = Contusion, n = 7), group III (Contusion + CoQ10, n = 7), group IV (Contusion + vitamin C, n = 7), group V (Contusion + vitamin E, n = 7) and group VI (Contusion + Dxm, n = 7). The rats were anesthetized with an intraperitoneal injection of 100 mg.kg-1 ketamine HCl (50 mg.ml-1, Ketalar®, Turkey). Blunt chest trauma was then performed. Analgesia was provided by morphine sulphate (0.05 mg.kg-1) administered intraperitoneally. Following the procedure, all subgroups were transferred to their cages. Rats were checked by observing breathing, nose bleeding, respiratory movements and cardiac rhythm. After 45 min. of observation, animals in groups I and II received intraperitoneal saline, group III was given 10 mg.kg-1 CoQ10, group IV was given 100 mg.kg-1 vitamin C, group V was given 150 mg.kg-1 vitamin E, and group VI was given 10 mg.kg-1 Dxm.
All subgroups were observed for 6 h in their cages. Thereafter, midsternotomy was performed on animals in all subgroups. Blood samples were collected from the descending aorta in a heparinized syringe followed by analysis with a blood gas analyzer. After the left main bronchus was clamped, bronchoalveolar lavage (BAL) of the right lung was performed with 2 ml of normal saline through a tracheal cannula. This was repeated three times; in total, 2 ml of lavage fluid was obtained. At the end of the BAL, the right lung was harvested and the upper lobe was fixed in 10% formaldehyde for histopathological examination; the remaining portion of the lung was stored at -20°C until further analysis.
Arterial blood gas measurements
Blood samples were collected from the descending aorta in a heparinized syringe during midsternotomy performed 6 h after blunt trauma. Analysis was performed by a blood gas analyzer (Cobas 221®; Roche, Mannheim, Germany) to assess and compare the effects of various drugs administered in the early period of blunt injury on pulmonary shunting.
Biochemical assay
Biochemical parameters were studied in the blood samples; the activity of superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) and nitric oxide (NO) were analyzed. High performance liquid chromatographic analysis was performed with an isocratic method using a Shimadzu HPLC system (Kyoto, Japan) and a commercial MDA kit (Immundiagnostik AG, Bensheim, Germany). Total SOD activity was determined according to the method from Sun et al.[23]. The principle of the method is based on the inhibition of nitroblue tetrazolium (NBT) reduction by the xanthine–xanthine oxidase system as a superoxide generator. One unit of SOD was defined as the enzyme amount causing 50% inhibition in the NBT reduction rate. Serum NO levels (nitrite + nitrate) were measured by a spectrophotometer at 545 nm (Shimadzu, Tokyo, Japan) after conversion of nitrate to nitrite by copperized cadmium granules [24]. Results are expressed μ mol/L for MDA, μmol/L for nitric oxide and U/ml for SOD.
PMNL count in BAL
One slide for cytologic examination was prepared from each BAL sample and stained with hematoxylin-eosin. Smears were then analyzed by using an image analysis program (Leica QWINPlus v. 3.1.0). Ten microscopic fields at x100 magnification were randomly selected. The polymorphonuclear cellularity was determined as the number of cells per 25000 μm2.
Histopathological examination
Lung tissue samples were fixed in 10% formalin immediately after removal, dehydrated in graded concentrations of ethanol, cleared in xylene and embedded in paraffin. At least eight tissue sections of 5-μm thickness were obtained and then stained with hematoxylin-eosin. The sections were examined under a light microscope by a pathologist in a blinded manner. All histopathological changes were documented in each lung tissue, including intra-alveolar haemorrhage, alveolar oedema, disruption and congestion and leukocyte infiltration. Alveolar oedema and congestion were scored on a scale from 0 to 3 where 0 = absence of pathology (<5% of maximum pathology), 1 = mild (<10%), 2 = moderate (15-20%), and 3 = severe (20-25%). Leukocyte infiltration was evaluated to determinate the severity of inflammation resulting from contusion. Each section was divided into 10 subsections, and leukocytic infiltration was examined in each of the subsections at a magnification of 400X with the following scale; 0: no extravascular leukocytes; 1: <10 leukocytes; 2: 10-45 leukocytes; 3: >45 leukocytes. The average of the numbers was used for comparison [25].
The primary outcome of this study was the determination of the PaO2 values. Sample size estimation was based on the standard deviation of a similar study performed by Türüt et al.[13].We used the PaO2 values of rats in control conditions (213.57 ± 26.34) determined by the same study (13). In order to detect a 20% change in PaO2 with an alpha error of 0.05 and a power of 95%, it was calculated that the sample size should be at least 7 rats per group.
Data are presented as means ± standard deviation. The Mann Whitney U test was used for statistical analysis. p < 0.05 was defined as the level of statistical significance. A commercial software package (SPSS 11.5 for Windows, SPSS Science, Chicago, IL) was used for data analysis.
Of the 42 animals subjected to blunt chest trauma, none of the rats died during the experiment. During the follow up period of contused rats, gross evaluation of the respiratory movements indicated a moderate bradypnea early after the trauma, but when the rats were transferred to the cages and supported with oxygen, respiratory rates reflected similar values compared with the control group. All rats exhibited similar behavior concerning mobilization and activity. Median sternotomy grossly indicated the effect of blunt trauma on the lungs; both lungs showed contused areas with a heterogeneous pattern.
Arterial blood gas analysis was assessed at 6 hours after blunt trauma. Results are shown in Table 1. All PaO2 values decreased significantly in group II as compared with the group I (p < 0.05). Administration of vitamin C, vitamin E and Dxm resulted in a slight increase in PaO2 values compared with the group II, but the difference was not statistically significant (p > 0.05). Administration of CoQ10 resulted in a significant increase in PaO2 values compared with group II (p = 0.004). PaCO2 levels significantly increased in group II compared with the group I (p = 0.01). Compared to group II, PaCO2 levels were significantly decreased in the group III, group IV, group V, and group VI (p < 0.05). All pH values significantly decreased in group II compared with the group I (p = 0.01).
Table 1 Comparison of blood gas analysis results obtained 6 h after contusion between the control, sham and drug-administered groups
pH values of arterial blood gases in all groups were higher than the group II. pH values in the group IV (p = 0.03), and group III (p = 0.03) were significantly higher than the group II. However pH values of group III, group V and group VI were significantly low compared with the group I (p < 0.05).
Biochemical results
Levels of plasma MDA (Table 2) in group II were significantly higher than those in the group I reflecting the significant lipid peroxidation that occurred with lung contusion after blunt trauma (p = 0.01). Early administration of vitamin C, CoQ10, and Dxm significantly decreased the levels of MDA (p = 0.01). No significant differences in MDA values were found between the group V and group II (p = 0.06).
Table 2 The activites of MDA, SOD and NO in serum
In group II, lung contusion due to blunt trauma, significantly decreased SOD activity in rat lung tissue compared with group I (p = 0.01). SOD levels were significantly elevated in the group III, group V, and group VI compared with group II (p = 0.01). No significant difference in SOD values was found between the group IV and group II (p = 0.06). In group II, the level of NO was higher than in the group I (p = 0.01). Early treatment with vitamin C, vitamin E, CoQ10 and Dxm decreased the NO levels significantly (p = 0.01).
Neutrophil count in BAL
Contusion resulted in a significant increase in the neutrophil population (p = 0.003). Dxm decreased the neutrophil population significantly in the BAL fluid of contused rats (p = 0.016) (Figure 1).
Comparison of BAL fluid neutrophil counts per mm3 in each group. Contusion resulted in a significant increase in neutrophil population (p = 0.003). Contusion-induced neutrophil increase was reduced significantly by Dxm. administration compared to sham group (p = 0.016). *: p < 0.01 compared Group I, Mann whitney U test. †: p < 0.05 compared Group II, Mann whitney U test. Group I: control. Group II: contusion (sham). Group III: contusion + CoQ10. Group IV: contusion + vitamin C. Group V: contusion + vitamin E. Group VI: contusion + dexamethasone.
Histopathological results
Scores of alveolar haemorrhage, oedema and disruption as well as leukocyte infiltration scores were significantly higher in group II compared to the group I (p = 0.001) (Table 3). In group III, CoQ10 administration, significantly improved the hemorrhage and oedema scores (p = 0.011) and the leukocyte infiltration scores (p = 0.002) compared to group II. There were no significant difference in the haemorrhage (p = 0.383) and leukocyte infiltration (p = 0.073) scores between the group II and group IV. There was no significant difference in the haemorrhage scores (p = 0.209), but there was a difference in the leukocyte infiltration scores (p = 0.004) between the group II and the group V. In group VI, Dxm administration significantly improved the haemorrhage and oedema scores (p = 0.017) as well as the leukocyte infiltration scores (p = 0.002) compared to the group II.
Table 3 Comparison of leukocyte infiltration and alveolar oedema/congestion scores of the lung tissue in each group
When the drug-administered groups were compared, no significant differences were found in haemorrhage and leucocyte infiltration scores (p > 0.05).
Microscopic findings in the lung specimens revealed normal lung parenchyma in the group I (Figure 2A). In contrast, rats in the group II had disruption of normal alveolar structure with severe congestion and haemorrhage associated with infiltrating leukocytes (Figure 2B). In the group IV and group V, the lungs of the contused rats exhibited moderate degrees of oedema and congestion (Figure 2C and 2D). Rats in the group VI and group III had significantly less leukocyte infiltration with relatively well- preserved alveolar histology compared to the group II (Figure 2E and 2F).
Microphotographs demonstrating (A) control group with normal pulmonary histology; (B) sham group displaying disruption of alveolar structure with extensive congestion, oedema, and hemorrhage; and decreased congestion, and oedema with relative preservation of alveolar histology in the treatment groups: (C) vitamin C, (D) Vitamin E (E), (E) Dxm and (F) CoQ 10 . Best improvement is appreciated in Dxm and CoQ10 group.
PC is the most frequently diagnosed injury due to blunt thorax trauma. Because approximately 1/3 of trauma patients admitted to hospitals have thorax trauma, it is an important cause of mortality and morbidity. About 25% of the patients require invasive mechanical ventilation [2, 4, 5, 7, 16]. With the development of possible new pharmacological agents and better resuscitation methods, the need for mechanical ventilation may be decreased and the prognosis of patients with PC may improve. For studying PC, various blunt thorax trauma models have been previously established. The local and systemic pathophysiological consequences of PC and the different treatment strategies to minimize the effects of this type of injury have been studied [8, 10–13, 26–29].
In our study, we used the rat model of lung contusion injury caused by external blunt thoracic trauma as described by Raghavendran et al.[14]. We generated and adapted the rat model mentioned above in order to constitute a moderate PC.
The effects of the PC depend on the extent of the injury. Direct injury causes pulmonary vascular damage with secondary alveolar haemorrhage, and thus the alveoli are poorly perfused. Afterwards, tissue inflammation develops and results in surrounding pulmonary oedema that leads to regional alterations in compliance and airway resistance causing V/Q mismatch. This manifests as a progressive deterioration of pulmonary gas exchange and P/F ratios [7]. Similar previous studies have been conducted to assess the severity of pulmonary shunting and arterial oxygenation in injured rats, revealing severe hypoxia early after induction of contusion. Although it was observed that arterial oxygenation was improved over time, levels persisted at the range of acute lung injury for 4-24 h following contusion [13, 30]. In our study, all PaO2 levels were decreased, and all PaCO2 levels were increased significantly at 6 h after contusion. We detected slight improvement in both PaO2 and PaCO2 levels due to the early administration of antioxidant vitamins (vitamin C, vitamin E), CoQ10 and Dxm. PC is associated with a leukocyte-mediated secondary inflammatory response leading to capillary leaking, interstitial oedema and protein extravasation [5, 7, 10, 12]. Strohmaier et al.[11] clearly demonstrated the importance of neutrophil influx in mediating lung injury. Alveolar levels of pro-inflammatory mediators like interleukins and TNF have been shown to rise precipitously after blunt lung injury [16]. It has been elucidated that PC is associated with a progressive inflammatory response mediated by local and systemic immunological alterations [8–13]. Macrophages and neutrophils, which are potentially involved in the inflammatory process, are activated after blunt trauma. Cytokines, reactive oxygen metabolites, and proteolytic enzymes are released by both leukocytes and macrophages.
This leads to increased alveolocapillary membrane permeability and microvascular leakage associated with the formation of alveolar oedema fluid, proteolytic and lipolytic enzymes, and reactive oxygens species (ROS) [11]. Alveolar macrophages can produce potent ROS, such as superoxide radicals and, consequently, peroxynitrite. Peroxynitrite can be produced by the reaction of NO with superoxide radicals and represents a highly oxidative species [30]. These ROS in turn are capable of initiating and promoting oxidative damage in the form of lipid peroxidation [18]. Some organs might prevent the damaging effects of the oxidant species through enzymatic and non-enzymatic antioxidant defenses. These defenses include enzymes, such as superoxide dismutase (SOD) and catalase [19]. Malondialdehyde (MDA) is a good indicator of free radical formation, and its elevation shows increased lipid peroxidation due to the effects of these radicals [25]. In our study, MDA levels showed significant increases after contusion, reflecting an indirect finding of oxidative damage. Similarly, NO levels were significantly elevated in the lung tissue. SOD activities were demonstrated to be decreased in the contused rats. These results suggest that oxidants and antioxidants participate in the mechanism of lung injury induced by PC.
The deleterious effects of the free radicals are determined by a delicate balance between the rate of their production and elimination by the different antioxidant systems. Beneficial effects of antioxidant molecules in experimental ALI, blunt trauma and PC models have been established in previous studies. [13, 16, 31–34]. Maxwell et al.[16] established the positive effects of the antioxidant drug Tempol® in a pig model with unilateral PC. Davis et al.[10] showed that systemic levels of prostacyclin and tromboxane elevate after PC. They also showed attenuation of pulmonary failure by pretreatment with indomethacin due to the effect of prostanoid inhibition. Koksel et al.[31] caused ALI in rats by intravenous administration of oleic acid and showed the positive effects of NAC, which has antioxidant properties. Türüt et al.[13] investigated the biochemical and histopathologic effects of dexamethasone, NAC and aprotinin in PC rat models. They reported that Dxm, NAC and aprotinin treatment have positive effects in bilateral PC, which activates an oxidant-antioxidant cascade.
CoQ10, a component of the mitochondrial electron transport chain, is a strong antioxidant that plays a role in membrane stabilization. Antioxidants inhibit lipid peroxidation by preventing a peroxidation chain reaction and/or picking up reactive oxygen derivatives. Endogenous antioxidants include mitochondrial cytochrome oxidase, SOD, catalase, glutathione peroxidase (GSH-Px), glutathione S-transferase, hydroperoxidase and CoQ. CoQ10 is the only antioxidant that is fat-soluble, synthesized endogenously and is present in tissues in active form (reduced) independently from diet [35]. It has been found in experimental studies that CoQ10 is effective in the treatment of ischemia reperfusion injury. Portakal et al.[36] found that CoQ10 has beneficial effects in the rat liver ischemia-reperfusion damage. Similary, Ostrowski et al.[37] suggested that CoQ10 has beneficial effects in cerebral ischemia. They also reported that CoQ10 reduced the cerebral ischemic lesion diameter in an animal model. Nonetheless, the effectiveness of CoQ10 in a trauma model has not been thoroughly studied. Kerimoglu et al.[38] has demonstrated that CoQ10 administration was beneficial after spinal cord trauma. Tran et al. [39] showed that pretreatment with Tempol® or CoQ10 decreased superoxide production, reduced the infarct size and normalized mitochondrial dysfunction in the gastrocnemius muscle after tourniquet-induced acute ischemia- reperfusion injury in mouse skeletal muscles. However, CoQ10 administration after lung injury in animal models has very rarely been studied. Lim et al.[40] demonstrated that CoQ10 reduced the increase in tumor necrosis factor-alpha (TNFα) and the injury-induced rise in peak airway pressure following lung injury models in rats. They concluded that CoQ10 may have a protective role in lung injury. They demonstrated that a high-dose of oral CoQ10 was well incorporated into plasma and lung tissue and, to a lesser extent, into the heart. Having shown that oral administration of CoQ10 provided substantial increases in plasma and lung tissue concentrations, the authors tested the benefits of these increases using an in situ lung injury model that incorporated physiological and biochemical measurements used by transplant clinicians to assess the function of the donor lung. The lung ischemia-reperfusion injury (IRI) model demonstrated both increased peak airway pressure, poor gas exchange and increased levels of TNFα. In this novel study of the effects of CoQ10 pre-dosing on lung IRI, there is evidence that oral administration of CoQ10 significantly attenuated the rise in cytokine TNFα but not IL-6, MDA and ATP. However, it did not provide sufficient clinical protection against IRI as judged by peak airway pressure and oxygen diffusion gradients [40]. However, there is no study evaluating the role of CoQ10 in a blunt chest trauma model. In our study, comparisons of MDA, SOD and NO levels measured after early administration of CoQ10 in experimental rat models were statistically significant. The serum MDA levels of the group that received CoQ10 were closest to the group I. These findings are similar to the previously published data studying the antioxidant properties of CoQ10[35–40]. Vitamin C is capable of scavenging oxygen-derived free radicals that are involved in the development or exacerbation of various diseases, including cancer, heart attack, arthritis and stroke [33]. Omeroglu et al.[34] administrated high doses of vitamin C to rat models with ruptured Achilles tendons and showed that a high dose vitamin C supplementation has positive effects on tendon healing by promoting early angiogenesis and increased collagen synthesis. Cristante et al.[41] demonstrated that vitamin C reduces the inflammatory response after spinal cord injury in rats. Additionally, Liao et al.[42] showed that early administration of vitamin C is effective for treating spinal cord injury in rats.
In our study, differences in MDA and NO levels after early administration of vitamin C in rats with blunt thorax trauma were found to be statistically significant compared to the group II. This result is consistent with previous studies demonstrating the antioxidant properties of vitamin C in PC [33, 34, 41, 42].
Vitamin E is the major lipophilic radical-scavenging antioxidant in vivo and protects humans from the oxidative stress mediated by active oxygen and nitrogen species [43].
Koc et al.[44] showed that vitamin E significantly decreased MDA levels, and thus, vitamin E may have a protective effect against spinal cord injury in rats due to its antioxidant properties. In a study comparing the effect of methylprednisolone with or without vitamin E in a rat model of spinal cord damage, the size of the ischemic area was smaller, and adrenaline, noradrenaline, and dopamine levels were lower in the group treated with methylprednisolone and vitamin E [45]. Cristante et al.[41] demonstrated that vitamin E reduces the inflammatory response after spinal cord injury in rats. Wigenstam et al.[46] has also demonstrated that vitamin E reduces acute inflammatory cell influx, suppresses collagen formation in lung tissue and protects against chemically induced lung injury.
In our study, SOD and NO levels in rats who received vitamin E were statistically significant compared to the group II. This result is concordant with the previously published data describing the antioxidant properties of vitamin E [41–46]. Dexamethasone (Dxm) was also used in experimental PC models [13, 16]. Türüt et al.[13] examined the biochemical and histopathologic effects of Dxm in a PC rat model and reported that Dxm has positive effects in bilateral PC through activation of an oxidant-antioxidant cascade.
In our study, MDA, SOD and NO levels in rats who received Dxm were statistically significant compared to the group II. The measured SOD and NO levels are the closest to the group I in our study.
Even though the beneficial effects of corticosteroids have been shown, these drugs have severe adverse effects, such as an increased risk of infection, fluid retention, increased blood pressure, high blood sugar, suppressed adrenal gland hormone production, weight gain, and loss of calcium from bones [47].
However, suitable doses and effective dose ranges of CoQ10 have not yet been identified. According to previous studies, 10 mg/kg CoQ10 was commonly administrated within one hour after injury in order to prevent ischemic damage [48]. In our study, we administrated 10 mg/kg CoQ10 to rat models immediately after blunt thorax trauma.
Histopathologic examination of lung tissues also supported the potential beneficial effects of the antioxidant vitamins C and E as well as Dxm and CoQ10. Parenchymal changes in the contused lungs were characterized by extensive haemorrhage with disruption of the alveoli, congestion, and alveolar oedema as well as increased leukocytic infiltration in the alveolar space. Although not statistically significant, vitamin C and vitamin E resulted in decreased haemorrhage, oedema and alveolar disruption. In addition, vitamin E significantly decreased leukocytic infiltration. On the other hand, administration of Dxm and CoQ10 subsequent to pulmonary contusion provided significant recovery. The most significant effects on haemorrhage, oedema and alveolar disruption were obtained with CoQ10, and dexamethasone resulted in the greatest decreases in leukocyte infiltration both in pulmonary tissue and BAL fluid. These results emphasize the antioxidant potential of the former and the anti-inflammatory property of the latter.
Finally, it appears that free oxygen radicals and lipid peroxidation play a role in PC after blunt thorax trauma. In our study, CoQ10, vitamin C, vitamin E and Dxm had protective effects on biochemical and histopathological outcomes of PC after experimental blunt thorax trauma. In particular, we have demonstrated that the best outcome was recorded in rats which were administered CoQ10 with respect to arterial oxygenation, MDA levels and histopathological outcome. Vitamin C and E are reliable and easy to administer and have been shown to have significant antioxidant effect. These results support the idea that early treatment with CoQ10, vitamin C, vitamin E, and dexamethasone may yield favorable effects on pulmonary pathophysiologic parameters of blunt thorax trauma patients.
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Shimomura Y, Suzuki M, Sugiyama S, Hanaki Y, Ozawa T: Protective effect of coenzyme Q10 on exercise-induced muscular injury. Biochem Biophys Res Commun. 1991, 176 (1): 349-355. 10.1016/0006-291X(91)90931-V.
Rose RC: Ascorbic acid metabolism in protection against free radicals: a radiation model. Biochem Biophys Res Commun. 1990, 169 (2): 430-436. 10.1016/0006-291X(90)90349-R.
Koul A, Bhatia V, Bansal MP: Effect of alpha-tochopherol on pulmonary antioxidant defence system and lipid peroxidation in cigarette smoke inhaling mice. BMC Biochem. 2001, 2: 14-10.1186/1471-2091-2-14.
Sun Y, Oberley LW, Li Y: A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988, 34: 497-500.
Cortas NK, Wakid NW: Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem. 1990, 36: 1440-1443.
Calikoglu M, Tamer L, Sucu N, Coskun B, Ercan B, Gul A, Calikoglu I, Kanik A: The effects of caffeic acid phenetyl ester on tissue damage in lung after hindlimb ischemia-reperfusion. Pharmacol Res. 2003, 48: 397-403. 10.1016/S1043-6618(03)00156-7.
Greenbery SM, Frishman WH: Coenzyme Q10: a new drug for myocardial ischemia?. Med Clin North Am. 1988, 72: 243-
Maxwell RA, Gibson JB, Fabian TC, Proctor KG: Resuscitation of severe chest trauma with four different hemoglobin-based oxygen-carrying solutions. J Trauma. 2000, 49: 200-209. 10.1097/00005373-200008000-00005.
Ischiropulos H, Zhu L, Beckman JS: Peroxynitrite formation from macrophage derived nitric oxide. Arch Biochem Biophys. 1992, 298 (2): 446-451. 10.1016/0003-9861(92)90433-W.
Wang ND, Stevens MH, Doty DB, Hammond EH: Blunt chest trauma: an experimental model for heart and lung contusion. J Trauma. 2003, 54: 744-748. 10.1097/01.TA.0000052362.40754.F2.
Raghavendran K, Davidson BA, Woytash JA, Helinski JD, Marschke CJ, Manderscheid P, Notter RH, Knight PR: The evolution of isolated bilateral lung contusion from blunt chest trauma in rats: cellular and cytokine responses. Shock. 2005, 24: 132-138. 10.1097/01.shk.0000169725.80068.4a.
Koksel O, Ozdulger A, Ercil M, Tamer L, Ercan B, Atik U, Cinel L, Cinel I, Kanik A: Effects of N-acetylcysteine on oxidant- antioxidant balance in oleic acid-induced lung injury. Exp Lung Res. 2004, 30 (6): 431-446. 10.1080/01902140490476319.
Koksel O, Cinel I, Tamer L, Cinel L, Ozdulger A, Kanik A, Ercan B, Oral U: N-Acetylcystein inhibits peroxynitrite- mediated damage in oleic acid-induced lung injury. Pulm Pharmacol Ther. 2004, 17: 263-270. 10.1016/j.pupt.2004.05.002.
Tsai PJ, Chen WY, Tzeng SF, Liang WM, Yang CS: Experimental spinal cord injury induced an increase of extracellular ascorbic acid concentration in anesthetized rats: a microdialysis study. Clin Chim Acta. 2005, 362 (1–2): 94-100.
Omeroğlu S, Peker T, Türközkan N, Omeroğlu H: High-dose vitamin C supplementation accelerates the Achilles tendon healing in healthy rats. Arch Orthop Trauma Surg. 2009, 129 (2): 281-286. 10.1007/s00402-008-0603-0.
Bentinger M, Brismar K, Dallner G: The antioxidant role of coenzyme Q. Mitochondrion. 2007, (Jun;Suppl): S41-S50.
Portakal O, Inal-Erden M: Effects of pentoxifylline and coenzyme Q10 in hepatic ischemia/reperfusion injury. Clin Biochem. 1999, 32 (6): 461-466. 10.1016/S0009-9120(99)00041-7.
Ostrowski RP: Effect of coenzyme Q10 on biochemical and morphological changes in experimental ischemia in the rat brain. Brain Res Bull. 2000, 53 (4): 399-407. 10.1016/S0361-9230(00)00406-8.
Kerimoglu A, Pasaoglu O, Kanbak G, Hanci V, Özdemir F, Atasoy MA: Efficiency of coenzyme Q10 at experimental spinal cord injury. Turkish Journal of Trauma & Emergency Surgery. 2007, 13 (2): 85-93.
Tran TP, Tu H, Pipinos II, Muelleman RL, Albadawi H, Li YL: Tourniquet-induced acute ischemia-reperfusion injury in mouse skeletal muscles: Involvement of superoxide. Eur J Pharmacol. 2011, 10;650 (1): 328-334. Epub 2010 Oct 29
Lim HK, Jayaweera S, Calderone A, Pepe S, Rosenfeldt FL, Marasco SF: Protective role of coenzyme Q10 in two models of rat lung injury. ANZ J Surg. 2010, 80 (4): 265-270. 10.1111/j.1445-2197.2009.05085.x.
Cristante AF, Barros Filho TE, Oliveira RP, Marcon RM, Rocha ID, Hanania FR, Daci K: Antioxidative therapy in contusion spinal cord injury. Spinal Cord. 2009, 47 (6): 458-463. 10.1038/sc.2008.155.
Liao JW, Song YM: Preliminary study of the effects of high-dose Vitamin C on acute spinal cord injury in rats. Sichuan Da Xue Xue Bao Yi Xue Ban. 2004, 35 (6): 854-857.
Niki E, Noguchi N: Dynamics of antioxidant action of vitamin E. Acc Chem Res. 2004, 37: 45-51. 10.1021/ar030069m.
Koc RK, Akdemir H, Karakücük EI, Oktem IS, Menkü A: Effect of methylprednisolone, tirilazad mesylate and vitamin E on lipid peroxidation after experimental spinal cord injury. Spinal Cord. 1999, 37 (1): 29-32. 10.1038/sj.sc.3100732.
Wigenstam E, Rocksén D, Ekstrand-Hammarström B, Bucht A: Treatment with dexamethasone or liposome-encapsuled vitamin E provides beneficial effects after chemical-induced lung injury. Inhal Toxicol. 2009, 21 (11): 958-964. 10.1080/08958370802596298.
Daneyemez M: Silicone rubber microangiography of injured acute spinal cord after treatment with methylprednisolone and vitamin E in rats. Spine. 1999, 24: 2201-2205. 10.1097/00007632-199911010-00005.
Dujovne CA, Azarnoff DL: Clinical complications of corticosteroid therapy: A selected review. Med Clin North Am. 1975, 57 (5): 1331-42.
Yokoyama K, Nakamura K, Nakamura K: Effect of coenzyme Q10 on superoxide production in rats with reperfusion injuries. Scand J Plast Reconstr Surg Hand Surg. 1999, 33: 1-5. 10.1080/02844319950159550.
Department of Thoracic Surgery, Karaelmas University Medical Faculty, Zonguldak, Turkey
Mertol Gokce
& Ozkan Saydam
Department of Anesthesiology and Intensive Care Medicine, Karaelmas University Medical Faculty, Zonguldak, Turkey
Volkan Hanci
Department of Biochemical, Karaelmas University Medical Faculty, Zonguldak, Turkey
Murat Can
Department of Pathology, Karaelmas University Medical Faculty, Zonguldak, Turkey
Burak Bahadir
Search for Mertol Gokce in:
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Correspondence to Mertol Gokce.
The author(s) (Gokce M; Saydam O, Hanci V, Can M, Bahadir B) declare that they have no competing interests.
Gokce M and Hanci V designed the research; Gokce M, Saydam O, Can M and Bahadir B performed the research; Hanci V, Can M and Bahadir B analyzed the data; Gokce M, Saydam O and Hanci V wrote the paper. All authors read and approved the final manuscript.
Gokce, M., Saydam, O., Hanci, V. et al. Antioxidant vitamins C, E and coenzyme Q10 vs Dexamethasone: comparisons of their effects in pulmonary contusion model. J Cardiothorac Surg 7, 92 (2012) doi:10.1186/1749-8090-7-92
Blunt Trauma
Blunt Chest Trauma
Pulmonary Contusion


86 Comments on "Awakening 1"
Tomb Raider status on this one.
whens the 3rd one of this come out?
It won't if you are on a cell phone or tablet, which is why there's a link to the mobile version.
Darn. I was hoping that they'd start kissing after being transformed.
Ditto on the hotter girl. Would not mind that change up every now and again.
I'm kinda curious now, are we going to get more gemstone animals like maybe ….. A topaz badger?
Defiantly Need a sequel !!!! Please !!


Join us on New Year's Eve to celebrate Sekhmet in fiery fashion!
Ntrt Sekhmet is the powerful one, she who loves Maat and abhors Isfet. Sekhmet was sent by Ra to punish the Kemau for turning their backs on the way of Maat. Her power and force reminds us that we will always reap what we sow. Using the power of Sekhmet to our benefit teaches us to channel her fire into the maintenance of Maat within and without. Sekhmet forces us to ask ourselves if we are contributing to divine order, or disrupting it.
The highlight of the evening is a fire ritual, the element that represents the passions of Sekhmet. As the flames are burning brightly, we release all of the troubles, pathologies, issues, fears, etc. that have kept us from reaching the peaks of success that we are capable of.
Dancing, celebrating, and communing with others of like mind and spirit.


Nearly 1,800 people died and 5,000 were injured in traffic accidents last year, an annual report showed yesterday.
Artist Riem Mony Silong dropped out of school in grade-four aged nine. Born into an impoverished family in Siem Reap, they could not afford to send him to public school, let alone provide him with art lessons.
Authorities in Poipet cracked down on two online gaming sites in "GOOD LUCK" on the morning of January 2 2019.
Phnom Penh: Preliminary reports say that the Royal Gendarmerie forces went to the "Dermo Clinic" beauty center, after claims a hidden camera was used to take pictures of customers and used to extort tens of thousands of dollars.
Cambodia has scheduled to host the 27th Annual Meeting of the Asia-Pacific Parliamentary Forum (APPF-27) from Jan. 14 to 17 in Siem Reap province under the theme "Strengthening Parliamentary Partnership for Peace, Security and Sustainable Development".
At least 27 nests of critically endangered bird species have been found the Siem Pang wildlife sanctuary in Stung Treng province, according to the BirdLife International Cambodia Programme.
Giant Ibis, vultures, and White-shouldered Ibis continue to be found in their natural habitats in Cambodia, according to BirdLife Cambodia.
A senior government official on Monday said that the amendment to Article 45 of the Law on Political Parties has reached its final stage and is merely awaiting the signature of King Norodom Sihamoni, leaving 118 politicians facing the dilemma as to whether to return to the political stage or not.


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Preview: Erie Commodores FC vs. FC Buffalo in the National Game of the Week
Saturday's match between Erie and Buffalo will feature one of the league's most established rivalries. It is a derby between two long-standing members of the NPSL and there's plenty of healthy banter between the clubs, supporters, and even owners.
"Rivalries are always good," Erie owner John Melody commented. "In Erie versus Buffalo this will be the 10th season of it. It's the first game you look for when the schedule comes out. They don't like us much and we are not too fond of them either. I'm not sure what the record over the years is, but it's easy enough to count the Buffalo wins."
Nicholas Mendola, co-owner of FC Buffalo, shared similar sentiments.
"All players need to know about the rivalry; they learn within moments of joining the club, whether from returning team members of our passionate supporters online. The distaste for Erie is visceral, and it extends from our fans to each member of our club. We have a terrific amount of respect for our fellow NPSL owner in John Melody, but we have nothing but dislike for his club."
All of the banter has led to amazing play on the pitch over the years, creating one of the country's most anticipated matchups and a favorite for fans of the East Conference.
Both teams are loaded with talent at every position and the rosters may not be fully complete just yet.
Goalkeeper Nicolau Neto, midfielder Cam Philpot, and forward Sam White have been leading the way for Erie this season. Neto has been absolutely incredible in goal and leads the team in saves. Philpot leads Erie in goals, while White has the team lead for assists.
This talented trio has already seen plenty of action, including a successful run in the U.S. Open Cup. Erie played two games in the Open Cup, winning the first on penalties against the Rochester River Dogz before bowing out to the USL's Pittsburgh Riverhounds in a 2-1 loss. The latter was against a full-time professional side and it was a match that could have gone either way, even in the final moments. Erie won their season opener against Syracuse FC 1-0.
FC Buffalo's preseason was wrecked by the weather so they were only able to play a single friendly, which ended in a scoreless draw. Buffalo lost their season opener 2-0 to Fort Pitt Regiment.
This is the first match this season where two of Buffalo's all-time greats are available from the opening whistle. Akean Shackleford, who flew in the day of their opener and came off the bench, scored seven goals in 11 matches during his first season with FCB. Captain Kendell McFayden, a former Rochester Rhinos striker, has 12 goals in 28 career matches for Buffalo. Whether Bayley Winkel is on the wing or at center mid, he'll be an important part of the attack, having worn the captain's armband in the opener. He's also coming off an All-Northeast Conference season at Robert Morris University. Euan Bauld from Cape Breton University has been a big part of FCB's early season at center back, and his college teammate and lifelong friend Lewis White is a spectacular left back. Jeremy Figler will start in goal, and he's a reliable veteran presence for Buffalo.
As you can see, fans and supporters will be treated to a great match.
"We know every Erie County Derby match is a physical, hot-blooded match," Mendola added. "We know Erie is a guaranteed tough 90-plus minutes, and they know we're the same. That said, both teams are early in their seasons and surely waiting out a few more international clearances. We expect our men to fight for every ball and do everything they can to extend our unbeaten rivalry run."
Melody isn't sure what to expect from the match-up. Anything could happen in such a heated derby.
"It's early in the season so we'd expect a cagey affair, but this game has the potential to break wide open. We've had three-goal wins, 3-3 and 0-0 ties and they have the odd win so who knows really."
There is one guarantee however. There will be plenty of entertaining and exciting soccer.
"We want to keep the ball and press hard when we don't have it," Mendola continued. "When we're at our best, we're not necessarily doing anything spectacular but the ball is headed to dangerous places."
Erie has found a style that works for the team over the years.
"Our style has changed little, but in 10 seasons we've adapted well to what's needed to be successful."
It's certain that the competition will be fierce between two clubs that have experienced tremendous success.
"The conference will be competitive, same as last year," Melody concluded. "We won the conference on goal difference and there wasn't a lot of points between Erie in first and Buffalo in fifth. The NPSL is tough with competitive games week in and week out."
Mendola agreed.
"We firmly believe that this is the toughest conference in the league, and there's isn't a day you can afford to let up."
Both teams are hoping to use this match to gain momentum in a run to win the conference title and qualify for the national playoffs and the Open Cup.
It's a certainty that fans and supporters will be treated to some incredible NPSL soccer on this holiday weekend.
Photo Credit: RJZ Photography and Jennifer White/Acacia Studios
Cosmos B Defeats TSF FC 5-0
Greater Binghamton FC Thunder Falls to Syracuse FC 7-1

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Marina Sirtis Was Almost Fired From 'Star Trek: The Next Generation' In The First Season
Posted August 27th, 2018 by Stuart Conover
It is hard to imagine Star Trek: The Next Generation' without Deanna Troi though Marina Sirtis has shared that she was almost cut from the show in the first season. It was something Sirtis suspected while the first season was in production and was later confirmed by Gene Roddenberry's wife, Majel Barrett. Barrett (who would go on to play Deanna's mother, Lwaxana Troi) eventually shared that the series creator felt that there was "one too many women" and that a psychologist was not needed on the series.
Roddenberry truly believed that humans would have worked past interpersonal conflicts by the 24th century and the profession would be highly outdated.
That seems like some wishful thinking these days.
Still, during the first season the only reason that Sirtis felt she was saved was because Denise Crosby quit her role as Lt. Tasha Yar at the end of the first season:
"I was very insecure in the first season because they were always writing me out of episodes and I went from being the favorite – because when I was cast, I knew I was their favorite. [Star Trek creator Gene Roddenberry] loved me, it was obvious I was their favorite – and it got to the point where if a producer saw me coming, they would turn around and walk away. So, I knew my job was on the line…I was on the bubble."
I'm sure anyone would feel great at their place of employment with that kind of a situation.
The show was far from the last time she almost lost her job as it also occurred during negotiations for one of the 'Star Trek' movies:
"When I was negotiating for Nemesis, they literally threatened to fire me and recast Troi. Well not actually recast, but they said 'We are going to fire you and hire Jeri Ryan. And I said 'Well Jeri Ryan won't do it for that money, that is for sure.'"
I hope that is the exact comeback she used to keep her job.
Are you happy that we were able to keep Marina Sirtis as Deanna Troi throughout 'Star Trek: The Next Generation'? Share your thoughts below!
Source: Trek Movie
Deanna Troi
Marina Sirtis
Star Trek TNG
Weekend Box Office (8/24-8/26): Audiences Are Crazy In Love With 'Crazy Rich Asians'; 'Happytime Murders'? More Like Crappytime Turders
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This trick will help you to Make Calls, Send and Receive SMS From Your Computer Using an Android Phone. The steps involved are simple and easy to understand.
There are many software to which allows you Make Calls, Send and Receive SMS From Your Computer Using an Android Phone. Of them the most user friendly being the AirDroid. So for this trick you will need to download the AirDroid. Then follow the following steps.
Download AirDroid on your Android phone.
Open the app on your Android phone.
The app will ask you to create an account, but it is not needed. Just tap the tiny Sign in later button at the bottom.
Now AirDroid will ask you for permission to show notifications on your computer in real time. Tap Enable.
This will take you to the system settings for access to notifications. Tap AirDroid Notification Mirror service.
A confirmation pop-up will appear. Tap OK.
Now hit the back button on your phone to return to AirDroid. The app will now display a URL – http://web.airdroid.com – on the phone.
Open the URL in any Web browser on your computer. You'll see a QR code in the browser window.
On AirDroid on your Android phone, tap the QR code image next to the URL. This will open the camera.
Point the camera at the QR code in the browser window on your computer. The Android app will vibrate when it has scanned the code.


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Q: How to prove the bijection from unit interval to unit-square constructed by Cantor is discontinuous? Can it be proved with mathematical analysis?

A: If the bijection were (bi)continuous, then the image of the boundary of the square (homeomorphic to a circle) would be a connected closed subset of the interval.  Such a subset is necessarily an interval itself.  But a circle and an interval have distinct fundamental groups: $\pi_1(I)=0$, while $\pi_1(S^1)=\mathbb Z$.  Since the fundamental group is a homeomorphism invariant, the result follows.

A: Here is a more elementary argument.  If there were a continuous bijection $f$ from the interval $[0,1]$ to the square, take the points $f(0)$ and $f(1)$ in the square.  They are necessarily distinct since $f$ is a bijection.  Now take two disjoint paths $\alpha$ and $\beta$ from $f(0)$ to $f(1)$ in the square. By the intermediate value theorem, the image of $\alpha$ in $[0,1]$ must be the entire interval $[0,1]$, and similarly for $\beta$.  Therefore $f$ is not bijective.  The contradiction proves the result.

A: If $f$ is a continuous and bijective function from the unit interval to the unit square it must map compact sets to compact sets. But all closed sets in the unit interval are compact so its maps all closed sets to closed sets. Equivalently it maps open sets to open sets. Thus its inverse $g$ must be continuous as well. Now use any of the other answers ruling out the existence of bicontinuous bijections.

A: Let $f$ be any continuous bijection from the unit interval to the unit square.
Since, $[0,1]$ is compact $f^{-1}$ will also be a continuous function.
Now consider any point $a$ belonging to $[0,1]$ such that $a$ is an interior point of $[0,1]$ i.e. $a$ belongs to $(0,1)$ then we look at its image $f(a)$. So deleting the point $a$ from $[0,1]$ will give us a disconnected set while its pre-image under $f^{-1}$ i.e. the $unit $ $square$ $-f(a)$ is clearly pathwise connected and hence connected.  (Since, in euclidean spaces pathwise connectedness is equivalent to connectedness).  So, it implies that $f^{-1}$ is a continuous function that maps a connected set to a disconnected set and hence contradiction.
So no bijection between the unit interval and the unit square can be continuous (in particular, cantor bijection!)

A: Note: This does not actually answer the question as stated, since it rules out the possibility of a homeomorphism, not a continuous bijection.
This proof if a variant of User72694's answer using $\pi_1$. Suppose that we had a homeomorphism from the square interval to the square.  We will first show that their is an interior point of the interval whose image is an interior point of the square. This is easy since any bijection, $\phi$ from the interval to the square restricts to a bijection of the form, $\bar{\phi}:(0,1)\to [0,1]^2-\{\phi(0),\phi(1)\}$. So pick an interior point of $\{\phi(0),\phi(1)\}$ and it's preimage will be an interior point of the interval. Denote the interior point of the interval by $x_0$. Then the bijection $\phi$ indices a bijection, $\hat{\phi}:[0,1]-\{x_0\}\to [0,1]^2-\{\phi(x_0)\}$, which is a homeomorphism if $\phi$ is. But then $[0,1]-\{x_0\}$ is disconnected and  $[0,1]^2-\{\phi(x_0)\}$ is connected, thus their can be no homeomorphism.
Note that this is a variant of the other proof since both proofs rely on some sort of connectivity.

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Home > Back Catalogue > DESIGN PORTRAIT
DESIGN PORTRAIT
Lancaster Road, W11
Never underestimate the determination of a Notting Hill homebuyer. While in the throes of negotiating this property, the vendor passed away and, having no descendants, left it to the Serbian Orthodox Church in Paris. The would-be buyers were not to be deterred, however, and continued the negotiations with the church, eventually employing French-speaking lawyers in England and even more lawyers in Paris. Finally, the property was theirs.
The next challenge for these new owners was to gain permission for the extensive renovations they planned. One of the key concepts was to add a mansard storey but this was bitterly opposed by the freeholder of the building. After a lot of tough negotiations, they eventually obtained permission and set about a five-month build using De Rosee Sa Architects. The result was a space that is entirely filled with light thanks to the large windows and the large skylight across the roof. Beautiful materials were also used, including Piedra de Burgos limestone and Carrara marble. De Rosee Sa then designed and commissioned custom-made furniture, including the dining room table, the coffee table, sofas and the side tables.
This beautiful flat is at the western end of Lancaster Road within moments of all that Notting Hill has to offer. Ladbroke Grove Underground station is minutes away and there was no excuse to miss workouts as Virgin Active was practically on the doorstep. When asked about their home, the owners replied, "At Lancaster Road, we aimed to create different atmospheres as you move through the property, unified by the herringbone floor and contemporary stair. We tried to introduce a bit of drama in the sombre cloakroom and the skylight above the shower." They certainly succeeded.
View De Rosee Sa Architects on the Domus Nova Architecture Guide


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Home » Lifestyle » Sophie, Countess of Wessex is 'leader' in marriage as Prince Edward takes 'low-key' role
Sophie, Countess of Wessex is 'leader' in marriage as Prince Edward takes 'low-key' role
Sophie, Countess of Wessex and Prince Edward have been married since 1999. Over the years, they have both stepped up to work on behalf of Queen Elizabeth II, 94.
Prince Edward is the son of the Queen which means he is used to being in the public eye.
Sophie, on the other hand, had a career in public relations before meeting the royal.
The pair dated for around six years before they married.
After the wedding, Sophie became a working member of the Royal Family and has appeared at numerous royal events ever since.
She has taken on increasing responsibilities and is comfortable attending official engagements by herself.
When Sophie and Prince Edward are seen together, body language expert Judi James commented on their relationship.
She claimed that Sophie appears happy to take a leading role.
"Sophie is clearly the team leader of the family," Judi told Express.co.uk.
"She takes what looks like the most active role, engaging and laughing across at others."
Prince Edward looks comfortable taking a step back and letting Sophie take control of their engagements, Judi suggested.
She claimed Prince Edward looks happy to wait on hand from directions from the Countess.
"Edward appears to be allowed to be a bit of an alpha presence, looking in control of the paperwork and pen and standing with his legs splayed in a bit of a power-pose," the expert continued.
"It's Sophie he keeps eye-checking as though waiting for instructions."
While Prince Edward has been in the public eye for his entire life, he seems happy to slip into the background with his wife.
The expert explained this is something both royals look comfortable with.
Judi claimed: "Edward's non-verbal signals suggest he's happily moved into a more low-key role in public.
"Sophie's confidence signals show her as being the more socially active one in the team dynamic.
"Sophie appears to enjoy stepping into the royal limelight but we never see any signs of vanity from her.
"Edward looks delighted to stand by his wife using glances of admiration and pride.
"He places his hands behind his back to suggest it's her show, but his overall mirroring of her mood and posture shows they share like-minded thinking."
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3 What Does the Thyroid Do?
4 How Many People Have Thyroid Problems?
What is thyroid cancer and how is is different from thyroid disease? Actress Katee Sackhoff discusses her battle with thyroid cancer with Progressive Health and how she manages to live normally. Read her fascinating story below.
When actress Katee Sackhoff went in for a routine check-up at age 27, she had no idea she was about to be diagnosed with thyroid cancer. Find out how this surprising disease changed her life and what steps she took to control her health after her thyroid surgery as well as the role of the thyroid and how you can detect thyroid problems in your own life.
Katee Sackhoff was already a famous actress when she was diagnosed with thyroid cancer at age 27. She discovered her condition with no previous knowledge or symptoms from the disease. During a routine check-up, her doctor felt a small lump and suggested a blood test. Within a few weeks, Katee had undergone surgery and underwent full treatment for the cancer.
Today, she is cancer-free and uses a combination of healthy living practices and traditional medicine to keep her hormones regulated despite the absence of a thyroid gland. She has found that with the right balance of holistic and traditional medical approaches, she is able to life a happy, healthy life.
Now, Katee keeps busy by starring as deputy Victoria "Vick" Moretti on the A&E series, "Longmire". She also recently starred with Vin Diesel in the film "Riddick." Progressive had the privilege of interviewing Katee Sackhoff in-person through video interview about her experiences with thyroid cancer. You can view the text of the interview below or watch the video to view Katee's responses.
What were the first symptoms that you noticed that make you suspect you had a medical condition? Were you surprised by your diagnosis, or did you suspect something was seriously wrong all along?
It did [surprise me], yeah. I was so lucky to be raised with a very safe environment and really didn't have anything health-wise or emotionally go wrong in my life for so many years. And when I was 27 I went in for my routine check-up with my gynecologist and she felt a lump in my neck in the thyroid, which is a little butterfly-shaped gland that's at the base of your neck, and through a bunch of blood tests after that realized that I had thyroid cancer. They took out the thyroid and I had a complete thyroidectomy at 28.
Did having thyroid cancer change your perspective on life?
I think the thing that changed my life so much was just the idea that life is very finite and cancer had touched me at what I thought was a very young age. Since then, I just take my thyroid medication on a daily basis and live a full, happy, healthy life that is relatively smooth at this point.
What health changes did you have to make as a result of your disease? Who was your biggest support during your illness and treatment? What support methods would you recommend to others facing thyroid disease or cancer?
During my treatment, my finance, who was my boyfriend at the time, was incredibly helpful. I would go into these appointments and not hear a word that the doctor was saying to me. I would walk out and we would go to lunch right afterwards and he would have all the information written down on a legal notepad that we had learned in the appointment.
And we would go over it again. And the thing that I learned during that process is that you really have to be your own advocate; you have to search for the answers that you are looking for, because a lot of times you need things explained in layman's terms actually, which I did, and it seems less daunting and it makes a lot more sense. So he was a tremendous help during that process.
But also, having and finding a good endocrinologist- I went through at least 2 to find one that actually spent time with me and made me feel safe.
Does your past condition impact your day-to-day life?
It did [in the beginning]. I tried to go to the support groups and see how people were doing and how not having a thyroid was affecting the function of their life. And then it was really hard for me to find a positive outlook after having a thyroidectimey, and I was so worried that I was going to a), be exhausted all the time or b), gain a substantial amount of weight- and I was really worried about that.
And what I found was that as long as I take my medication at the same time every day- within reason, I give myself a bit of a buffer- and go and get my blood tests quite a lot (I go about every 3 months just to make sure that my thyroid is functioning properly), then I really don't feel the fallout of not having a thyroid.
I've been too high and had massive panic attacks- that's how it presents itself in me; everybody is different- and then being too low and I could barely get out of bed, so it really is crucial to find that sweet spot, if you will.
What advice can you give to others facing thyroid disease or cancer? Was there any piece of advice that was particularly helpful to you during your treatment?
The thing that I want people to understand is something that was explained to me so many times, but I don't know if I quite heard at the time. Thyroid cancer is very treatable and you can live a full-functioning, happy, normal life without a thyroid. And you can actually do the same thing being hypo and hyper as well with the help of your endocrinologist and medication. But mostly that it doesn't have to be this massive change in your life and you can live a long, happy, healthy life with a thyroid disorder, for sure.
What would you tell people who think they might have a thyroid problem?
Go to thyroidawareness.com, which is an incredibly helpful website- all the information you need is there; and definitely if you don't feel well and you haven't felt well for a long period of time and there is really no other reason why, go and ask your doctor for a little [thyroid] blood test. A blood test can tell you if the function of your thyroid is right where it should be.
Many Americans are confused about what the thyroid actually does in the body. It is far more than simply a regulator for the metabolism. In fact, the hormones that the thyroid makes are involved in regulating nearly all organs and cells in the body. The thyroid controls body temperature, brain function, heart rate, bone strength, muscle health, and regulation of digestion. Clearly, the thyroid is one of the most important parts of the body- which is what makes thyroid disorders and thyroid cancer like Katee's so dangerous.
How Many People Have Thyroid Problems?
Experts are not sure how many people have thyroid problems- since many people can go for years without realizing they have a problem. However, it is estimated that about 30 million Americans have some kind of thyroid disease and that about 60 percent of cases are undiagnosed. As Katee pointed out, anyone who feels sluggish, tired, or simply "off" for no explainable reason should have their thyroid function checked.
Thyroid cancer is a fairly rare form of cancer. According to the American Cancer Society, about 60,000 Americans are diagnosed with thyroid cancer each year. About 1,500 people die from thyroid cancer each year. Thyroid cancer is highly treatable, because it is easy to detect in the early stages just like Katee's doctor was able to find her cancer early.
The reason thyroid cancer is easy to detect early is because one of the first signs of cancer is a swollen thyroid. Most doctors check the thyroid gland during well visits, which means that if you get regular well check-ups, you can easily detect any problems before they become major.
There is a difference between thyroid cancer and thyroid disease- although the two conditions are related. Thyroid cancer is a type of thyroid disease, but the key difference is that cancer is the uncontrolled growth of cells in the thyroid that can spread to other areas of the body. In other forms of thyroid disease (hyperthyroidism or hypothyroidism), the thyroid may swell and malfunction, but the disease is localized to the thyroid itself and will not spread.
While many people live for years with thyroid problems without even knowing there is a problem, there are serious health risks that thyroid diseases can cause. Thyroid cancer, for example, can spread and infect other areas of the body like the lymph nodes and brain. Other thyroid diseases can cause problems such as: increased bone density loss, cardiovascular disease, infertility, osteoporosis, stunted growth, mental diseases, infertility, hair and nail loss, and more. The best way to determine if you have a thyroid disorder is to have your thyroid tested with a simple blood test.
If you test your thyroid and you find that you don't have thyroid cancer- just a sluggish thyroid (far more common than an overactive thyroid), then there are many natural steps you can take to try to regulate your hormones on your own without using synthetic hormones. Synthetic thyroid hormones carry risks and side effects that can be damaging and unhealthy. Katee has faced some of these side effects herself.
Luckily, with the following three treatment methods, you can help regulate your thyroid hormones without taking synthetic thyroid hormones (or at least, for less time).
Exercise can boost your thyroid function. According to a 2005 study published in "Neuroendocrinology Letters," exercise benefited the production of T3 and T4 hormones. The researchers found that exercising at 70 percent of the maximum heart rate was the most beneficial for thyroid functioning.
You may be able to improve both overproduction and underproduction of thyroid hormones with diet. A thyroid diet simply reduces the amount of foods that interfere with hormone production and adds more foods that help regulate hormones.
Foods to avoid include: vegetable oils, sugar, processed grains, starches, and basic junk foods.
Foods to add include healthy fats like olive oil, omega-3 oils, and coconut oil; organic sources of protein; probiotics; and a wide variety of fruits and vegetables.
Many people who have thyroid disorders are deficient in B vitamins, minerals, and amino acids. By supplementing with these ingredients you can help boost your thyroid function and restore natural production levels without synthetic hormones. Try adding the following supplements to your daily routine: B Vitamins: B6, B1, B12, B5, B3, B2, B9. Minerals: Zinc, magnesium, selenium, iodine, copper, manganese. Amino Acids: Acetyl L-Tyrosine, L-Phenylalanine.
It is easy to get a simple blood test to check your thyroid. If you have a thyroid malfunction, like Katee Sackhoff, early intervention is key to finding the best treatment methods without harsh side effects. If you catch a thyroid disorder early enough; natural methods like exercise, supplements, and a healthy diet can reverse the condition and help you live a healthy, happy life.
If your condition goes on without diagnosis, however, it may take harsh synthetic hormones to restore balance in your body. There is no reason to delay. If you suspect a thyroid malfunction, get tested as soon as possible and do not wait to implement the above natural thyroid boosting methods to restore hormonal balance to every cell in your body and improve you overall health.


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Home > Blog > DATA Act > Statement by Data Transparency Coalition Executive Director Hudson Hollister on President Obama's Decision to Sign DATA Act
Statement by Data Transparency Coalition Executive Director Hudson Hollister on President Obama's Decision to Sign DATA Act
by Hudson Hollister on May 3, 2014
On Monday, the House of Representatives unanimously passed the DATA Act, following unanimous approval three weeks ago by the Senate. On Tuesday, the White House announced that President Obama will sign it.
The DATA Act's enactment will revolutionize federal spending. The federal government's antiquated document-based reporting apparatus will be transformed into an efficient flow of standardized, open data. Open spending data will become a public resource for citize
Addressing the Data Transparency Summit, April 29, 2014.
ns, watchdogs, and the tech industry.
Our nation leads the world in technological innovation. We will finally be able to apply our technical ingenuity to the inefficiencies of the federal government. The Data Transparency Coalition's members have demonstrated their ability to republish, analyze, and automate private-sector financial data. Now their solutions can transform the public sector too.
Open federal spending data will bring democratic accountability by expanding access to vital information about our government's actions and priorities. Open federal spending data will allow agencies and Congressional appropriators to deploy electronic management tools. Open federal spending data will automate compliance for grantees and contractors.
The DATA Act's chief champion in the House, Rep. Darrell Issa, estimates that one-third of the federal deficit is waste and fraud. The DATA Act will enable our government to deploy data analytics to illuminate and eliminate waste and fraud.
The federal government is already constitutionally obliged to report its expenditures. Under the DATA Act, technology will make sense of them.
Tuesday's Data Transparency Summit brought together all stakeholders to start transforming the largest, most complex organization in human history. Our Coalition will continue to light the way forward for the federal government. We will encourage the Treasury Department and the White House OMB to follow the intent of the DATA Act by adopting and implementing robust, nonproprietary, government-wide data standards.
President Obama's May 2013 Open Data Policy provides crucial context for the DATA Act's implementation by defining the essential characteristics of open data and by bringing together a community of practice that is now ready to focus its energies on federal spending data. The DATA Act builds on the President's earlier work, too: the new law amends and amplifies the Federal Funding Accountability and Transparency Act of 2006, a collaboration between Sens. Tom Coburn and Barack Obama.
We applaud the President's decision to sign the DATA Act. For both government transparency and the growing open data tech industry, the DATA Act will be President Obama's enduring legacy.
DATA Act Open Data


"I just love riding my bike, the countryside, being with those I love, just having fun enjoying life and being happy!"
Caring, sensitive, loyal and honest one man woman here. Independant and spirited yet friendly and can be shy at times.
"just me". . . . . . . . . . . . . nothing more, nothing less. . . . . . . . . . . . what you see is what you get lol!
local biking friends for rideouts and bike events. Enjoy meeting new people, going to biking events and riding my bike, having lots of laughs and generally enjoying life with my wonderful partner! Funny how life can be so randomly amazing when you least expect it! :). . one chance, one life. . . . . . . . . . . . enjoy. . . . . . I am 100% now!
Bone Head Idea - E Yorks.
Why do you ride a bike ?
matlock bath meet sunday 21st march?
Vertically challenged female seeks advice!
Creeps back in and pulls up a chair!


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Q: Mnemonic for remembering how to spell "mnemonic" It is ironic that the name of a mental device which is supposed to make our lives easier is itself so hard to spell. Is there a mnemonic for the spelling of mnemonic?

A: A collection of mnemonics for mnemonic from the web:

*

*Memorization's Not Easy; Memory Often Needs Initial Cues

*My Nanny Eats Mostly Old Noodles In Cans

*Memory Needs Every Means Of Naming It Correctly

*Mnemonics Neatly Eliminate Man's Only Nemesis - Insufficient Cerebral Storage

*Many Nuns Enjoy Monks Only Not In Convents

But I think the best is @Peter Taylor's simple suggestion to remember amnesia.

A: If it were a class of words you're talking about, I'd say a mnemonic would be useful. But as you are referring to a single instance, why create a mnemonic that you will have to remember (and may get wrong) to remember a single word? That adds an unnecessary burden (and abstraction) to the task.

A: It might help to associate it to a word which is related etymologically: amnesia.

A: Sure; repeat to yourself my niece is mnemonic.
This assumes that the mn is the source of difficulty and you don't need a mnemonic for the rest of the word.

A: Maybe try these to remember how to spell MNEMONICS:

*

*Men Never Eat Many Oysters Near Ice Cold Swamps

*Many New England Memories Of Nantuckett Ice Cold Shrimp

A: M N E M O N I C.
Two M's
Two N's
M always comes before N
Never a P!
Never a U!

A: My niece enjoys mnemonics only never in class.

A:
My nanny Eva makes oranges not inch closer.

It's a weird one, but that's how it got stuck in my head!

A: Angry at his last trickery, Seinfeld said: "Mmmm... Newman!"
A bit more in the scientific side: pneumatics, air brakes on buses, trucks and trains are examples of pneumatic systems.

A: My 11 year old has just been interviewing people for his English project on spelling strategies and just came up with what I thought was a good mnemonic for mnemonic-
Men Never Eat Marmalade On Nice Ice Creams

A: "mnemonic" is based on ancient Greek mnéme  μνήμη  meaning memory.  I'm no great specialist for old Greek so I'm not sure whether the m was really pronounced and I can't give information about the etymology of the word. I would guess something that is in the mind, memories you have in your head.

A: Hmmm? How to remember how to spell nemonic? (sic)
Hmmm! Spell phonetically by jogging your memory... mnemonic.


Every now and then, something happens in our culture that makes you think, "Wow, I'm so thankful I'm alive to experience this." A few quick examples include seeing Barack Obama win the presidency, last year's solar eclipse, and, oh yeah, these photos of Kendall Jenner and Bella Hadid leaving a Paris Fashion Week party with full wineglasses in their hands. There's art, my friends, and then there's art.
You laugh now, but someday you'll be glad to say, "Yup, I was there when Bella and Kendall decided they weren't finished with their wine and bravely took their glasses on the mean streets of Paris." Talk about heroic!
Of course, cameras were there to capture Hadid and Jenner's act of bravery. In the first photo below, you can practically hear Hadid (wearing Emilio Pucci) thinking to herself, "Maybe if I start talking about dirty sneakers again, no one will notice the wine in my hands." Meanwhile, Jenner (in Alexandre Vauthier) wants the world to know she took her booze to go. She's holding her wine proudly as if to say, "Let's raise a glass to every time Rob regifted my Christmas presents to Blac Chyna!"
Below, Hadid and Jenner are employing the classic, "Look down, and no one will see you" technique—something anyone who's snuck alcohol into a party knows all too well.
And here are their wine shenanigans from another angle, because why the hell not? I wonder what they're drinking! Pinot grigio? Chardonnay? A mix of both? Don't rule anything out! We already know from Keeping Up With the Kardashians that Jenner is a wine gal.
Whatever they're drinking, Kris Jenner is definitely proud.


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To learn more about the Academic Coaching program click here!


The overall job outlook for Sewing Machine Operator careers has been negative since 2004. Vacancies for this career have decreased by 39.37 percent nationwide in that time, with an average decline of 6.56 percent per year. Demand for Sewing Machine Operators is expected to go down, with an expected -6,130 jobs shed by 2018. This represents an annual decrease of 0.52 percent over the next few years.


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AMP Internal Page
The Center for Astrophysics | Harvard & Smithsonian Atomic & Molecular Physics division focuses on combined laboratory and theoretical studies of atomic and molecular processes; laboratory physics and astrophysics; atmospheric measurements; and atomic and molecular databases for astrophysics and atmospheric science.
Atomic & Molecular Physics (AMP) Research Activities
The full scientific potential of current and future generations of telescopes, across much of the electromagnetic spectrum from x-rays to radio waves, can be utilized fully only if the fundamental atomic and molecular physics data and their interpretation exist.
Research in the AMP division includes theoretical studies and laboratory and field measurements, which support astronomical observations at many wavelengths, address topics of astrophysical importance, and pursue related studies in fundamental physics and atmospheric science. Spin-offs from AMP research include current industrial, medical, communications, and environmental applications.
Studies of the processes of atomic, molecular, and optical physics and chemistry enable research in a number of astrophysics research areas.
Modeling of the chemistry of the early Universe clarifies the role molecules may have played in enabling the first generation of stars to form through gravitational collapse.
Calculations of molecule formation near supernovae and of the chemistry of interstellar clouds may explain a vast range of behavior in the Universe.
Analysis of spectroscopic observations being made with the instruments on board the Chandra X-ray Observatory enable AMP scientists to study the absorption of x-rays by atomic species. This research helps to explain the measured emissions of X-rays from comets and from the Jovian X-ray auroras over the polar caps.
AMP laboratory measurements coupled with radio astronomical investigations aim to understand the role of the chemical bond and organic chemistry in nature on a cosmic scale, and to determine the origin of the interstellar diffuse bands, the outstanding unsolved problem in astronomical spectroscopy.
AMP field measurements programs include satellite-based measurements of the Earth's atmosphere, to study the photochemistry of the stratospheric ozone layer, and the global distributions of atmospheric pollution in the lower atmosphere.
Practical applications of theoretical work in AMP include modeling of the emitted light from sodium high-pressure lamps; this has led to measurements in the AMP laboratory used to understand the characteristics of the atmospheres of brown dwarf stars and gas giant planets.
New Physics
The CfA | Harvard & Smithsonian is also at the forefront of developing and applying novel technologies to high-sensitivity searches for new physics. This emphasis makes the AMP division unique in its experimental and theoretical strength, as it operates at the forefront of atomic and molecular physics.
The program attracts leading scientists, who may not have an astrophysics background, to an environment where their skills can be applied both to cutting-edge topics in terrestrial physics as well as to astrophysics. As examples:
Theoretical studies in fundamental physics include the interactions between matter and anti-matter. Recently, the field ionization and velocity spectra of strongly magnetized antihydrogen atoms were characterized and interpreted in collaboration with the ATRAP experimental group in the Harvard Physics Department.
The Institute for Theoretical Atomic, Molecular, and Optical Physics (at the Observatory) is a leading center for research on physics at ultracold temperatures (emphasizing Bose-Einstein Condensation).
Theoretical work on nanodevices include proposed nanocentrifuges and stabilizers to damp turbulence in nanosystems.
AMP research on atomic clocks and quantum optics includes precise tests of fundamental symmetries of physics (Lorentz invariance) which also address questions about the origin and fate of the universe:
Measurements on low temperature collisions between hydrogen atoms contribute to the understanding of basic atomic processes.
Stored light experiments in quantum optics show that information encoded in a light pulse can be transferred to an atomic system and then retrieved coherently, with potential applications to quantum computing, communications, and cryptography.
Other applications of AMP measurements include the development and application of new tools for biomedical imaging, like the improved MRI of the lung, and understanding laboratory plasmas, e.g., controlled nuclear fusion.
The CfA also demonstrates its leadership in the compilation and administration of standard databases. For example, SAO's HITRAN (HIgh-resolution TRANmission molecular absorption database) is used for predicting and simulating transmission and emission of light in atmospheres. It is the world-standard reference database in molecular spectroscopy, with approximately 15,000 users worldwide. The journal article describing it is the most cited reference in the geosciences.
Visit the Data Archives Website
Atomic & Molecular Data
Solar and Stellar Atmospheres
Astrochemistry
Early Universe
Interstellar Medium and Molecular Clouds
Masers
Astro Combs
Laboratory Astrophysics
Division Administrator
Joseph Webber
Division Web Contact
James Babb
First Rocky Exoplanet Confirmed with NASA's JWST
A Leading Light in Atmospheric Science
New from JWST: An Exoplanet Atmosphere as Never Seen Before
Astronomers Warn of Risk of Misinterpreting JWST Planetary Signals
New Grant Supports Teen Air Quality Studies
Astronomers Detect Carbon Dioxide on Planet for the First Time with JWST
TEMPO Air Pollution Instrument Completes Satellite Integration
TEMPO Air Pollution Sensor Treks Toward Satellite Integration
Scientists Uncover Warehouse-Full of Complex Molecules Never before Seen in Space
HITRAN and HITEMP Database
With techniques developed in quantum mechanics, molecular spectra can be modeled by a set of discrete fundamental parameters. The knowledge of these reference molecular spectroscopic parameters is essential to correctly characterize constituents of their environments, model their spectra and atmospheric conditions. Physicists at the Center for Astrophysics | Harvard & Smithsonian maintain the HIgh-resolution TRANsmission (HITRAN) and HIgh TEMPerature (HITEMP) databases of molecular spectral parameters, along with the HITRAN Application Programming Interface (HAPI) which also enables one to access the database archive and process the data.
Telescopes and Instruments
Submillimeter Wave Astronomy Satellite
NASA's Submillimeter Wave Astronomy Satellite (SWAS) was a space observatory built to look for water and other molecules associated with life as we know it. During its seven years of operation, SWAS provided the first measure of the distribution of water in the Milky Way. Astronomers also used the observatory to make important discoveries about the interstellar clouds where new stars and planets are born, as well as observations of planets and comets within the Solar System. Center for Astrophysics | Harvard & Smithsonian scientists and engineers designed the telescope for SWAS, and the CfA hosted the operations center for the spacecraft. SWAS operated from 1998 through 2005, when it was put into hibernation mode.
Visit the SWAS Website
Tropospheric Emissions: Monitoring of Pollution (TEMPO)
Scientists study the atmospheres of many worlds with orbiting spacecraft, but Earth is the only planet where we can measure the effects of life — and of the negative impacts of civilization. When it is launched, NASA's Tropospheric Emissions: Monitoring of Pollution (TEMPO) observatory will measure air quality in North America from a geostationary satellite, specifically tracking air pollution in unprecedented detail. The scientific instrument development is led by scientists and engineers at the Center for Astrophysics | Harvard & Smithsonian and NASA's Langley Research Center.
Visit the TEMPO Website