BioMed Research International The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Age-Adjusted D-Dimer in the Prediction of Pulmonary Embolism: Does a Normal Age-Adjusted D-Dimer Rule Out PE? Thu, 19 Oct 2017 09:11:31 +0000 Risk assessment for pulmonary embolism (PE) currently relies on physician judgment, clinical decision rules (CDR), and D-dimer testing. There is still controversy regarding the role of D-dimer testing in low or intermediate risk patients. The objective of the study was to define the role of clinical decision rules and D-dimer testing in patients suspected of having a PE. Records of 894 patients referred for computed tomography pulmonary angiography (CTPA) at a University medical center were analyzed. The clinical decision rules overall had an ROC of approximately 0.70, while signs of DVT had the highest ROC (0.80). A low probability CDR coupled with a negative age-adjusted D-dimer largely excluded PE. The negative predictive value (NPV) of an intermediate CDR was 86–89%, while the addition of a negative D-dimer resulted in NPVs of 94%. Thus, in patients suspected of having a PE, a low or intermediate CDR does not exclude PE; however, in patients with an intermediate CDR, a normal age-adjusted D-dimer increases the NPV. Jacob Ortiz, Rabia Saeed, Christopher Little, and Saul Schaefer Copyright © 2017 Jacob Ortiz et al. All rights reserved. Healing and Antisecretory Effects of Aqueous Extract of Eremomastax speciosa (Acanthaceae) on Unhealed Gastric Ulcers Thu, 19 Oct 2017 08:52:49 +0000 Objective. This work investigated the healing and antisecretory effects of the aqueous extract of Eremomastax speciosa on “unhealed gastric ulcers” associated with gastric acid hypersecretion. Materials and Methods. “Unhealed gastric ulcers” were induced using indomethacin following the establishment of acetic-acid-induced chronic gastric ulcers. The extract (200 and 400 mg/kg, per os) was administered concomitantly with indomethacin (1 mg/kg, subcutaneously). The effects of the extract on both basal and histamine-stimulated gastric acid secretion were determined. Mucus secretion and oxidative stress parameters were measured, and histological assessment of ulcer healing was carried out. Results. The extract significantly promoted the healing process in rats subjected to “unhealed gastric ulcers” (82.4–88.5% healing rates). Treatment with the extract significantly reduced the basal (25.95–49.51% reduction rates) and histamine-stimulated (24.25–47.41%) acid secretions. The healing effect of the extract was associated with a significant () increase of mucus secretion and concentrations of antioxidant enzymes compared with the controls. The extract at the highest dose showed normalization of the mucosa, without glandular destruction and with the disappearance of fibrosis and lymphocyte infiltration. Conclusion. The abilities of the extract to increase mucus secretion, to reinforce antioxidant status, and to inhibit acid secretion would be some of the mechanisms by which this extract would accelerate the healing process in “unhealed gastric ulcers.” A. P. Amang, C. Mezui, G. T. Siwe, J. Emakoua, G. Mbah, E. Z. Nkwengoua, G. E. Enow-Orock, and P. V. Tan Copyright © 2017 A. P. Amang et al. All rights reserved. The Prognostic Value of Combined Smoking and Alcohol Consumption Habits for the Estimation of Cause-Specific Mortality in Middle-Age and Elderly Population: Results from a Long-Term Cohort Study in Lithuania Thu, 19 Oct 2017 08:35:52 +0000 Aim. To evaluate the prognostic value of combined smoking and alcohol consumption habits for the estimation of cause-specific mortality risk in middle-age and elderly population. Methods. The study presents data from the four surveys. A random sample of 6,729 subjects aged 35–64 years was selected for statistical analysis. During the follow-up of 31 years (1983–2014), there were 2,158 deaths from any cause. Multivariate Cox’s proportional hazards models were used to estimate hazard ratios (HR) for all-cause mortality and Competing Risk Regression analysis was used to estimate subdistribution hazard risk (SHR) for cause-specific mortality. Results. Smoking clearly increased the risk of all-cause mortality and mortality from cancer and cardiovascular disease (CVD), but alcohol use had little effect in men aged 35–64 years. However, heavy alcohol consumption (>14 units/week) increased the risk of all-cause mortality and mortality from external causes in the never-smokers men group who drank alcohol of 1–14 units/week (HR 2 = 1.57 and SHR 2 = 2.40, resp.). Conclusions. The smoking habits and alcohol consumption are modifiable risk factors, and thus efforts to support abstinence from alcohol and smoking use should be a public health priority. Dalia Luksiene, Abdonas Tamosiunas, Dalia Virviciute, and Ricardas Radisauskas Copyright © 2017 Dalia Luksiene et al. All rights reserved. Effect of a Carbohydrate-Rich Diet on Rat Detrusor Smooth Muscle Contractility: An Experimental Study Thu, 19 Oct 2017 07:36:51 +0000 Objectives. We aimed to investigate the effect of a carbohydrate-rich diet on detrusor contractility in rats. Materials and Methods. Sprague-Dawley rats were randomized into two groups. The control group received regular food and water. The study group received carbohydrate-rich diet for six weeks. The rats’ detrusor muscle was isolated for pharmacological and histopathological examinations. Results. In the control and study groups, mean body weights were 431.5 ± 27.6 g and 528.0 ± 36.2 g, respectively (p < 0.001). Electrical stimulation of the detrusor strips of the control group resulted in gradual contraction. A decreased contractile response was shown in the study group. Acetylcholine in 10-7-10-3 molar concentration produced a decreased contractile response in the study group, compared to the control group (p < 0.01). The study group showed marked subepithelial and intermuscular fibrosis in the bladder. Conclusion. Carbohydrate-rich diet causes marked subepithelial and extracellular fibrosis and changes in contractility in the detrusor within a six-week period. Changes have higher costs in therapeutic choices and correction of these changes remains difficult. Putting an end to carbohydrate-rich diet would seem to be more cost-effective than dealing with the effects of consuming it in high proportions which should be the national policy worldwide. Mustafa Suat Bolat, Sırrı S. Bilge, Ekrem Akdeniz, Onder Cinar, Fatih Firat, Arzu Erdal Agri, Mustafa Bakirtas, Omer Alici, and Fikret Erdemir Copyright © 2017 Mustafa Suat Bolat et al. All rights reserved. Acute Right Ventricular Dysfunction in Intensive Care Unit Thu, 19 Oct 2017 06:09:39 +0000 The role of the left ventricle in ICU patients with circulatory shock has long been considered. However, acute right ventricle (RV) dysfunction causes and aggravates many common critical diseases (acute respiratory distress syndrome, pulmonary embolism, acute myocardial infarction, and postoperative cardiac surgery). Several supportive therapies, including mechanical ventilation and fluid management, can make RV dysfunction worse, potentially exacerbating shock. We briefly review the epidemiology, pathophysiology, diagnosis, and recommendations to guide management of acute RV dysfunction in ICU patients. Our aim is to clarify the complex effects of mechanical ventilation, fluid therapy, vasoactive drug infusions, and other therapies to resuscitate the critical patient optimally. Juan C. Grignola and Enric Domingo Copyright © 2017 Juan C. Grignola and Enric Domingo. All rights reserved. Cryoablation of Primary Breast Cancer in Patients with Metastatic Disease: Considerations Arising from a Single-Centre Data Analysis Thu, 19 Oct 2017 00:00:00 +0000 Background. Patients presenting with stage IV breast cancer might benefit by removal of the primary tumor. We report our experience with CT-guided cryoablation of the primary tumor, with the aim of evaluating its role in this subgroup of patients. Patients and Methods. Data of 35 patients with mean age of 58 years with breast cancer at stage IV submitted to CT-guided cryoablation of the primary tumor between 2010 and 2016 were prospectively evaluated. All patients, except three, were preoperatively and postoperatively evaluated with breast MRI to assess the extent of tumor necrosis. Retreatment was performed in case of incomplete ablation. Results. Mean tumor size was 3.02 ± 1.4 cm. Six patients had multicentric disease. Complete tumor necrosis was 85.7% and 100% at 2-month and 6-month follow-up, respectively, as 5 patients with tumors > 3 cm required a redo cryoablation. No patient developed major complications. Minor side effects occurred in 30 patients (82%). All patients were discharged the same day of the procedure. During a mean follow-up of 46 months (range 3–84), 7 patients (20%) experienced local recurrences that were treated with redo cryoablation, and 7 (20%) died for disease progression. Conclusions. Our results suggest that cryoablation of the primary tumor is safe and effective in the treatment of patients presenting with stage IV breast cancer. Claudio Pusceddu, Luca Melis, Nicola Ballicu, Paolo Meloni, Valeria Sanna, Alberto Porcu, and Alessandro Fancellu Copyright © 2017 Claudio Pusceddu et al. All rights reserved. Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by Modulating Multiple Cell Cycle Regulators Thu, 19 Oct 2017 00:00:00 +0000 Platelets (PLTs) are produced by megakaryocytes (MKs) that completed differentiation and endomitosis. Endomitosis is an important process in which the cell replicates its DNA without cytokinesis and develops highly polyploid MK. In this study, to gain a better PLTs production, four small molecules (Rho-Rock inhibitor (RRI), nicotinamide (NIC), Src inhibitor (SI), and Aurora B inhibitor (ABI)) and their combinations were surveyed as MK culture supplements for promoting polyploidization. Three leukemia cell lines as well as primary mononuclear cells were chosen in the function and mechanism studies of the small molecules. In an optimal culture method, cells were treated with different small molecules and their combinations. The impact of the small molecules on megakaryocytic surface marker expression, polyploidy, proliferation, and apoptosis was examined for the best MK polyploidization supplement. The elaborate analysis confirmed that the combination of SI and RRI together with our MK induction system might result in efficient ploidy promotion. Our experiments demonstrated that, besides direct downregulation on the expression of cytoskeleton protein actin, SI and RRI could significantly enhance the level of cyclins through the suppression of p53 and p21. The verified small molecule combination might be further used in the in vitro PLT manufacture and clinical applications. Xiaojing Zou, Mingyi Qu, Fang Fang, Zeng Fan, Lin Chen, Wen Yue, Xiaoyan Xie, and Xuetao Pei Copyright © 2017 Xiaojing Zou et al. All rights reserved. Developmental Testicular Expression, Cloning, and Characterization of Rat HDAC6 In Silico Thu, 19 Oct 2017 00:00:00 +0000 We had previously reported presence of histone deacetylase 6 (HDAC6) in sperm and demonstrated its tubulin deacetylase activity and role in sperm motility in rat. In the present study we report its abundant expression in testis, epididymis, accessory sex organs, brain, and adrenal. In the testis, HDAC6 transcript and protein were observed throughout development. We therefore cloned the gene from rat testis using primers for hdac6 (accession number XM_228753.8) in order to determine the role of acetylation/deacetylation in spermatogenesis. The cloned rat hdac6 gene is ~3.5 kb with 28 exons and 1152 amino acids. We noted 4 single nucleotide polymorphisms (SNPs) on exons 2 (G/A), 5 (A/G), 7 (T/C), and 26 (G/T), respectively, in this sequence when compared to XM_228753.8. These were further validated at both cDNA and gene level. These SNPs resulted in 2 amino acids changes, namely, glycine → arginine and valine → phenylalanine at protein level. Cloned hdac6 overexpressed in HEK293T cells demonstrated significant overexpression by IIF. Alpha-tubulin acetylation analysis of the overexpressed cell lysate demonstrated that the protein was bioactive. This is the first study showing the ontogenic expression in the testis and reporting experimentally validated sequence of rat HDAC6 and its structural and functional annotation in silico. This sequence has been submitted to GenBank (Accession number Rattus KY009929.1). Pratibha Verma, Omshree Shetty, Sweta Parab, Karen Menezes, and Priyanka Parte Copyright © 2017 Pratibha Verma et al. All rights reserved. Biochemical and Genetical Responses of Phoenix dactylifera L. to Cadmium Stress Thu, 19 Oct 2017 00:00:00 +0000 The cadmium (Cd), a heavy metal, causes toxicity, which leads to hampering the growth and development of the plant. The molecular and biochemical approaches were used for the investigation of antioxidant system response and genotoxicity in date palm (Phoenix dactylifera L.) cv. Sagai in pot experiment having Cd. The root length was more affected than the shoot length as more accumulation of Cd occurs in roots. Fresh weights of root and shoot were reduced significantly in treated plants as compared to the control. The proline content was increased at low concentration of Cd (300 µM-CdCl2) than the medium and high concentrations (600 and 900 µM-CdCl2), respectively. The thiobarbituric acid reactive substances (TBARS) content was increased at 600 and 900 µM-CdCl2 compared to the plants treated at 300 µM-CdCl2 and controls. Antioxidant enzymatic assay was performed under Cd stress and compared with control plants. The catalase (CAT) and superoxide dismutase (SOD) activities were found to be high in plants treated with CdCl2 at 300 µM compared to at 600 and 900 µM-CdCl2, respectively. The genotoxicity of Cd was assessed using the inter-simple sequence repeat (ISSR) marker where all treated and control plants were clustered into three main groups based on genetic similarity. P. dactylifera plants were found to be more divergent at high Cd stress as compared to control and plants treated at low concentration of Cd. Fahad Al-Qurainy, Salim Khan, Mohamed Tarroum, Mohammad Nadeem, Saleh Alansi, and Aref Alshameri Copyright © 2017 Fahad Al-Qurainy et al. All rights reserved. Effect of Glycine, Pyruvate, and Resveratrol on the Regeneration Process of Postischemic Intestinal Mucosa Thu, 19 Oct 2017 00:00:00 +0000 Background. Intestinal ischemia is often caused by a malperfusion of the upper mesenteric artery. Since the intestinal mucosa is one of the most rapidly proliferating organs in human body, this tissue can partly regenerate itself after the onset of ischemia and reperfusion (I/R). Therefore, we investigated whether glycine, sodium pyruvate, and resveratrol can either support or potentially harm regeneration when applied therapeutically after reperfusion injury. Methods. I/R of the small intestine was initiated by occluding and reopening the upper mesenteric artery in rats. After 60 min of ischemia and 300 min of reperfusion, glycine, sodium pyruvate, or resveratrol was administered intravenously. Small intestine regeneration was analyzed regarding tissue damage, activity of saccharase, and Ki-67 positive cells. Additionally, systemic parameters and metabolic ones were obtained at selected periods. Results. Resveratrol failed in improving the outcome after I/R, while glycine showed a partial beneficial effect. Sodium pyruvate ameliorated metabolic acidosis, diminished histopathologic tissue injury, and increased cell proliferation in the small intestine. Conclusion. While glycine could improve in part regeneration but not proliferation, sodium pyruvate seems to be a possible therapeutic agent to facilitate proliferation and to support mucosal regeneration after I/R injury to the small intestine. Lisa Brencher, Frank Petrat, Katrin Stych, Tim Hamburger, and Michael Kirsch Copyright © 2017 Lisa Brencher et al. All rights reserved. Combined Treatment with an Anticoagulant and a Vasodilator Prevents Steroid-Associated Osteonecrosis of Rabbit Femoral Heads by Improving Hypercoagulability Thu, 19 Oct 2017 00:00:00 +0000 Steroid-associated osteonecrosis of the femoral head remains a challenging problem in orthopedics worldwide. One pathomechanism is ischemia of the femoral head, as a result of thrombus formation and vasoconstriction. The present study investigates the effects of combination prevention with enoxaparin and EGb 761 on steroid-associated ONFH in rabbits. Rabbits were randomly divided into 5 groups (control group, model group, enoxaparin group, ginkgo group, and combination group). With the exception of the control group, the groups of rabbits were modeled with lipopolysaccharide and methylprednisolone acetate. Starting with modeling, the enoxaparin group and ginkgo group were injected with 1 μg/kg/day enoxaparin subcutaneously and orally given 40 mg/kg/day EGb 761 for 4 weeks, respectively; the combination group received both treatments. After modeling for 6 weeks, the hematology data indicated prolonged PT and APTT in the three prevention groups. The micro-CT examination revealed higher bone density and better structure; histomorphometry revealed significant pathological changes. Immunohistochemistry revealed higher expression of BMP-2 and VEGF, thus revealing better osteogenesis and angiogenesis activities. Among the three prevention groups, the combination group had the most efficient results. In conclusion, the combined prevention with an anticoagulant and a vasodilator has the potential to decrease the incidence of steroid-associated ONFH in rabbits. Fang Cao, Ge Liu, Wei Wang, Benjie Wang, Xiaowei Wei, Faqiang Lu, Fan Yang, Kai Kang, Yongxuan Wang, Jiahui Yang, Kairong Qin, and Dewei Zhao Copyright © 2017 Fang Cao et al. All rights reserved. Long-Term Effectiveness of a Stress Management Intervention at Work: A 9-Year Follow-Up Study Based on a Randomized Wait-List Controlled Trial in Male Managers Wed, 18 Oct 2017 09:49:43 +0000 Objective. Short- and medium-term effectiveness (up to 3 years) of individual level stress management interventions (SMI) at work were demonstrated, yet long-term effectiveness remains unexplored. We therefore aimed to address this research gap. Methods. 94 male middle managers participated in a randomized wait-list controlled trial between 2006 and 2008 and in a post-trial-follow-up survey in 2015. During the first two years, all received an 18-hour psychotherapeutic SMI intervention which was based on the Effort-Reward Imbalance (ERI) model: tackling stressor on mismatch between effort and reward and promoting recovery on overcommitment. Work stress (i.e., ERI indicators) was the primary outcome, and the secondary outcome was depressive symptoms. The long-term effectiveness of the SMI was examined by mixed modeling, using an external control group (). Results. Effort and reward were substantially improved with significant intervention time interaction effects () compared to the external control group; effects on overcommitment and depressive symptoms were also significant ( and , resp.), though their trajectories in the intervention group were less sustainable. Conclusions. The effectiveness of this psychotherapeutic SMI at work based on the ERI model was observed over a 9-year period, particularly on the effort-reward ratio. Jian Li, Natalie Riedel, Amira Barrech, Raphael M. Herr, Birgit Aust, Kathrin Mörtl, Johannes Siegrist, Harald Gündel, and Peter Angerer Copyright © 2017 Jian Li et al. All rights reserved. Early Production of the Neutrophil-Derived Lipid Mediators LTB4 and LXA4 Is Modulated by Intracellular Infection with Leishmania major Wed, 18 Oct 2017 07:55:13 +0000 Recruitment of neutrophil granulocytes to sites of infectious tissue damage is an early event in innate immune responses. Following chemotactic signals neutrophils establish a first line of defense in a swarm-like manner. Intracellular pathogens such as Leishmania major can, however, evade neutrophil-mediated killing and survive inside neutrophils. To achieve this the parasites evolved potent evasion mechanisms. Since neutrophils are a major source of inflammation regulating lipid mediators, we hypothesized that intracellular infection modifies the release of pro- and anti-inflammatory lipid mediators like leukotriene B4 (LTB4) and lipoxin A4 (LXA4), respectively. In the present study, we demonstrated in vitro that L. major-infected primary human neutrophils release an increased amount of LTB4, whereas LXA4 liberation is reduced during the first hours of infection. To investigate whether lipid mediator modulation is a common feature in intracellular infections, we tested the impact of an infection with Anaplasma phagocytophilum. Similarly to L. major, neutrophil infection with A. phagocytophilum led to an enhanced release of LTB4 and decreased LXA4 production. Together, our findings indicate that intracellular infections modulate the lipid mediator profile of neutrophils. This effect is likely to contribute to the survival of the pathogens in neutrophils and to the outcome of the infections. Michael Plagge and Tamás Laskay Copyright © 2017 Michael Plagge and Tamás Laskay. All rights reserved. cAMP Response Element Binding Protein Expression in the Hippocampus of Rhesus Macaques with Chronic Ephedrine Addiction Wed, 18 Oct 2017 07:37:03 +0000 Background. Drug addiction is classified as a chronic relapse nature brain disease with complicated neurobiology mechanisms. There are an increasing number of researchers that are investigating the possible mechanisms for solving the thorny problem. Methods. The model of chronic addiction of rhesus monkey ephedrine was established, where changes in body weight and behavior were monitored. The expression of cAMP response element binding protein (CREB) in the hippocampus of rhesus monkeys was identified by real-time PCR and Western blot. Results. We were successful in establishing the chronic ephedrine addiction model in the rhesus macaques. They exhibited changes in body weight and behavior. Immunofluorescence showed that CREB was expressed in the nucleus of the hippocampus, and the expression of CREB mRNA and protein in the hippocampus were increased by real-time PCR and Western blot. The CREB positive expression in the hippocampus of the modeling group was significantly higher than in the control group. Conclusions. The changes of body weight and behavior of the rhesus monkeys after ephedrine chronic addiction were significant. The changes of CREB in the hippocampus of rhesus macaques with ephedrine chronic addiction are important molecular mechanisms, and the upregulation of CREB may be involved in the physiological pathology and behavior process in individuals with chronic ephedrine addiction. Zongbo Sun, Ye Ma, Shouxing Duan, Lei Xie, Junyao Lv, Jinzhuang Huang, Zhirong Lin, Ruiwei Guo, and Shuhua Ma Copyright © 2017 Zongbo Sun et al. All rights reserved. Body Posture Asymmetry in Prematurely Born Children at Six Years of Age Wed, 18 Oct 2017 07:04:06 +0000 Aims. The purpose of the study was to assess body posture asymmetries in the standing and sitting position in prematurely born children at six years of age. Study Design and Subjects. We measured trunk symmetry in coronal plane. The study was carried out in a group of 101 children, aged 6-7 years, mean age of 6.63, including 50 preterm children born at gestational age <32 weeks (preterm group) and 51 full-term children (control group). Outcome Measures. Trunk symmetry in coronal plane was measured using photogrammetric technique with Mora 4G CQ Elektronik. The subjects were examined in standing and sitting position. Statistical analyses were carried out using Shapiro-Wilk -test, Student’s -test, Mann–Whitney test, and Pearson’s chi-squared test. Statistical significance was assumed at . Results. No significant differences were found between the groups in the asymmetries identified in the relevant anthropometric points, relative to the position assumed during the examination or to the subjects’ sex. Conclusions. There are no significant differences in body posture in the coronal plane, between preterm children and full-term children. Premature birth does not have adverse effects related to body posture asymmetry in preterm children at the age of six. Katarzyna Walicka-Cupryś, Justyna Drzał-Grabiec, Maciej Rachwał, Paweł Piwoński, Lidia Perenc, Łukasz Przygoda, and Katarzyna Zajkiewicz Copyright © 2017 Katarzyna Walicka-Cupryś et al. All rights reserved. Therapy Effects of Wogonin on Ovarian Cancer Cells Wed, 18 Oct 2017 00:00:00 +0000 Background. Wogonin is a plant monoflavonoid and has been reported to induce apoptosis of cancer cells and show inhibitory effect on cancer cell growth. However, the detailed and underlying molecular mechanisms are not elucidated. In this study, we investigated the molecular and biological effects of wogonin in human ovarian A2780 cancer cells. Materials and Methods. We determined the effects of wogonin on the changes of cell cycling and apoptotic responses of cells. Western blot analysis was used to measure the effects of wogonin on protein expressions. Results. Our results showed that treatment with wogonin inhibited the cancer cell proliferation, decreased the percentage of G0/G1 subpopulation, and reduced invasiveness of A2780 cells. Exposure to wogonin also resulted in downregulated protein levels of estrogen receptor alpha (ER-α), VEGF, Bcl-2, and Akt and increased expressions of Bax and p53. In addition, exposure to wogonin increased caspase-3 cleavage and induced apoptosis in A2780 cells. Our study further showed that MPP, a specific ER-α inhibitor, significantly enhanced antitumor effects of wogonin in A2780 cells. Conclusion. Our results suggest a potential clinical impact of wogonin on management of ovarian cancer. Jiang Ruibin, Jin Bo, Wan Danying, Zhu Chihong, Feng Jianguo, and Gu Linhui Copyright © 2017 Jiang Ruibin et al. All rights reserved. Calcium Ionophore, Calcimycin, Kills Leishmania Promastigotes by Activating Parasite Nitric Oxide Synthase Wed, 18 Oct 2017 00:00:00 +0000 Leishmaniasis is an infectious disease caused by protozoan parasites of the genus Leishmania. There is no vaccine against human leishmaniasis and the treatment of the disease would benefit from a broader spectrum and a higher efficacy of leishmanicidal compounds. We analyzed the leishmanicidal activity and the mechanism of action of the calcium ionophore, calcimycin. L. major promastigotes were coincubated with calcimycin and the viability of the cells was assessed using resazurin assay. Calcimycin displayed dose-dependent effect with IC50 = 0.16 μM. Analysis of propidium iodide/LDS-751 stained promastigotes revealed that lower concentrations of calcimycin had cytostatic effect and higher concentrations had cytotoxic effect. To establish the mechanism of action of calcimycin, which is known to stimulate activity of mammalian constitutive nitric oxide synthase (NOS), we coincubated L. major promastigotes with calcimycin and selective NOS inhibitors ARL-17477 or L-NNA. Addition of these inhibitors substantially decreased the toxicity of calcimycin to Leishmania promastigotes. In doing so, we demonstrated for the first time that calcimycin has a direct leishmanicidal effect on L. major promastigotes. Also, we showed that Leishmania constitutive Ca2+/calmodulin-dependent nitric oxide synthase is involved in the parasite cell death. These data suggest activation of Leishmania nitric oxide synthase as a new therapeutic approach. Igor Grekov, António R. Pombinho, Tatyana Kobets, Petr Bartůněk, and Marie Lipoldová Copyright © 2017 Igor Grekov et al. All rights reserved. Gender Differences in the Progression of Experimental Chronic Kidney Disease Induced by Chronic Nitric Oxide Inhibition Wed, 18 Oct 2017 00:00:00 +0000 Chronic kidney disease (CKD) is considered a public health problem, assuming epidemic proportions worldwide. In this context, the preponderance of CKD prevalence in male over age-matched female patients is of note. In the present study, we investigated the impact of the gender on the development of experimental CKD induced by chronic nitric oxide (NO) inhibition in Wistar male and female rats through the administration of L-NAME. CKD model induced by L-NAME is characterized by systemic vasoconstriction, resulting in severe hypertension, albuminuria, renal ischemia, glomerulosclerosis, interstitial expansion, and macrophage infiltration. After 30 days of CKD induction, male NAME rats exhibited remarkable albuminuria, augmented cortical histological damage, interstitial inflammation, and fibrosis. Age-matched female NAME rats showed significantly lower albuminuria, diminished glomerular ischemia, and glomerulosclerosis, as well as a significant reduction in the expression of α-smooth muscle actin renal interstitial Ang II+ cells. Thus, the present study demonstrated that female rats submitted to the NAME model developed less severe CKD than males. Female renoprotection could be promoted by both the estrogen anti-inflammatory activity and/or by the lack of testosterone, related to renin-angiotensin-aldosterone system hyperactivation and fibrogenesis. However, the influence of sex hormones on the progression of CKD needs to be further investigated. Camilla Fanelli, Humberto Dellê, Rita Cassia Cavaglieri, Wagner Vasques Dominguez, and Irene L. Noronha Copyright © 2017 Camilla Fanelli et al. All rights reserved. Δ9-Tetrahydrocannabinol Prevents Cardiovascular Dysfunction in STZ-Diabetic Wistar-Kyoto Rats Wed, 18 Oct 2017 00:00:00 +0000 The aim of this study was to determine if chronic, low-dose administration of a nonspecific cannabinoid receptor agonist could provide cardioprotective effects in a model of type I diabetes mellitus. Diabetes was induced in eight-week-old male Wistar-Kyoto rats via a single intravenous dose of streptozotocin (65 mg kg−1). Following the induction of diabetes, Δ9-tetrahydrocannabinol was administered via intraperitoneal injection (0.15 mg kg−1 day−1) for an eight-week period until the animals reached sixteen weeks of age. Upon completion of the treatment regime, assessments of vascular reactivity and left ventricular function and electrophysiology were made, as were serum markers of oxidative stress and lipid peroxidation. Δ9-Tetrahydrocannabinol administration to diabetic animals significantly reduced blood glucose concentrations and attenuated pathological changes in serum markers of oxidative stress and lipid peroxidation. Positive changes to biochemical indices in diabetic animals conferred improvements in myocardial and vascular function. This study demonstrates that chronic, low-dose administration of Δ9-tetrahydrocannabinol can elicit antihyperglycaemic and antioxidant effects in diabetic animals, leading to improvements in end organ function of the cardiovascular system. Implications from this study suggest that cannabinoid receptors may be a potential new target for the treatment of diabetes-induced cardiovascular disease. Rebecca K. Vella, Douglas J. Jackson, and Andrew S. Fenning Copyright © 2017 Rebecca K. Vella et al. All rights reserved. Rheumatoid Arthritis Affecting the Upper Cervical Spine: Biomechanical Assessment of the Stabilizing Ligaments Wed, 18 Oct 2017 00:00:00 +0000 Diameters of anterior and posterior atlantodental intervals (AADI and PADI) are diagnostically conclusive regarding ongoing neurological disorders in rheumatoid arthritis. MRI and X-ray are mostly used for patients’ follow-up. This investigation aimed at analyzing these intervals during motion of cervical spine, when transverse and alar ligaments are damaged. AADI and PADI of 10 native, human cervical spines were measured using lateral fluoroscopy, while the spines were assessed in neutral position first, in maximal inclination second, and in maximal extension at last. First, specimens were evaluated under intact conditions, followed by analysis after transverse and alar ligaments were destroyed. Damage of the transverse ligament leads to an increase of the AADI’s diameter about 0.65 mm in flexion and damage of alar ligaments results in significant enhancement of 3.59 mm at mean. In extension, the AADI rises 0.60 mm after the transverse ligament was cut and 0.90 mm when the alar ligaments are damaged. After all ligaments are destroyed, AADI assessed in extension closely resembles AADI at neutral position. Ligamentous damage showed an average significant decrease of the PADI of 1.37 mm in the first step and of 3.57 mm in the second step in flexion, while it is reduced about 1.61 mm and 0.41 mm in the extended and similarly in the neutrally positioned spine. Alar and transverse ligaments are both of obvious importance in order to prevent AAS and movement-related spinal cord compression. Functional imaging is necessary at follow-up in order to identify patients having an advanced risk of neurological disorders. Carolin Meyer, Jan Bredow, Elisa Heising, Peer Eysel, Lars Peter Müller, and Gregor Stein Copyright © 2017 Carolin Meyer et al. All rights reserved. Isometric Tunnel Placement in Ulnar Collateral Ligament Reconstruction with Single CT Scan Wed, 18 Oct 2017 00:00:00 +0000 Background. Isometric tunnel placement for anterior bundle of the medial collateral ligament (MCL) reconstruction is mandatory for successful surgery. Purpose. This study aimed to demonstrate a useful method for identifying isometric tunnel placement using a single computed tomography (CT) scan. Study Design. Descriptive Laboratory Study. Methods. Five normal elbows were scanned at 4 different flexion angles at 45° increment. Three-dimensional models were analyzed using 2 different approaches: single and multiple CT scans methods. Ligament footprints in the humerus and the ulna were registered. Ligament length and isometric points were defined. The locations of the isometric points were imported into both methods to be compared. Results. There was no significant difference between 2 methods in calculating the length in every zone. There was also no significant difference in determining isometric ligament’s origin point, which is located approximately  mm and  mm for single and multiple CT, respectively, measured inferolaterally from medial epicondyle. Conclusions. A solid preoperative plan is critical when predicting tunnel locations due to the difficulty in finding isometric points and the individuality of optimal bone tunnel locations. Using single CT scan, optimal locations can be predicted with the same accuracy as a multiple CT scans with less radiation exposure. Erica Kholinne, Rizki Fajar Zulkarnain, Arnold Adikrishna, Bin Zhu, Han Pyo Hong, and In-Ho Jeon Copyright © 2017 Erica Kholinne et al. All rights reserved. Vertical-to-Horizontal Rotational Myocutaneous Flap for Repairing Cicatricial Lower Lid Ectropion: A Novel Surgical Technique Wed, 18 Oct 2017 00:00:00 +0000 Objective. To evaluate the efficacy and complications of a novel surgical technique for cicatricial lower lid ectropion that uses a vertical-to-horizontal (V-to-H) rotational myocutaneous flap procedure (Tsai procedure). Methods. We performed the V-to-H rotational myocutaneous flap procedure on 20 eyelids in 20 patients with mild to moderate cicatricial lower lid ectropion. A vertical myocutaneous flap was created from the anterior lamella of the vertical pedicle in the lateral third of the lower eyelid. Following a horizontal relaxing incision from the base of the flap, a vertical myocutaneous flap was created and rotated to horizontal. Two patients with combined cicatricial ectropion and paralytic lagophthalmos simultaneously underwent additional lateral tarsorrhaphy. Results. After a minimum follow-up period of 6 months, all patients showed good anatomical and functional improvement with decreased dependence on topical lubricants and a satisfactory cosmetic appearance. Two patients with combined cicatricial and paralytic ectropion had mild residual asymptomatic lagophthalmos. No patients required further revision surgery and there were no complications or recurrence. Conclusion. The V-to-H rotational myocutaneous flap technique was an effective and simple one-stage procedure for correcting cicatricial lower lid ectropion. It lengthened the anterior lamella and tightened horizontal eyelid laxity without the need for a free skin graft. Yu-Fan Chang, Chieh-Chih Tsai, Hui-Chuan Kau, and Catherine Jui-Ling Liu Copyright © 2017 Yu-Fan Chang et al. All rights reserved. High-Dose Compound Heat Map for 3D-Cultured Glioblastoma Multiforme Cells in a Micropillar and Microwell Chip Platform Wed, 18 Oct 2017 00:00:00 +0000 Glioblastoma multiforme (GBM) is recognized as the most common and lethal form of central nervous system cancer. To cure GBM patients, many target-specific chemotherapeutic agents have been developing. However, 2D monolayer cell-based toxicity and efficacy tests did not efficiently screen agents due to the pool reflection of in vivo microenvironments (cell-to-cell and cell-to-extracellular matrix interaction). In this study, we used a 3D cell-based, high-throughput screening method reflecting the microenvironments using a micropillar and microwell chip platform to draw a high-dose heat map of the cytotoxicity and efficacy of 70 compounds, with two DMSO controls. Moreover, the high-dose heat map model compared the responses of four 3D-cultured patient-derived GBM cells and astrocytes to high dosages of compounds with respect to efficacy and cytotoxicity, respectively, to discern the most efficacious drug for GBM. Among the 70 compounds tested, cediranib (a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases) exhibited the lowest cytotoxicity to astrocytes and high efficacy to GBM cells in a high-dose heat map model. Dong Woo Lee, Sang-Yun Lee, Il Doh, Gyu Ha Ryu, and Do-Hyun Nam Copyright © 2017 Dong Woo Lee et al. All rights reserved. Review of Natural Product-Derived Compounds as Potent Antiglioblastoma Drugs Wed, 18 Oct 2017 00:00:00 +0000 Common care for glioblastoma multiforme (GBM) is a surgical resection followed by radiotherapy and temozolomide- (TMZ-) based chemotherapy. Unfortunately, these therapies remain inadequate involving severe mortality and recurrence. Recently, new approaches discovering combinations of multiple inhibitors have been proposed along with the identification of key driver mutations that are specific to each patient. To date, this approach is still limited by the lack of effective therapy. Hopefully, novel compounds derived from natural products are suggested as potential solutions. Inhibitory effects of natural products on angiogenesis and metastasis and cancer suppressive effect of altering miRNA expression are provident discoveries. Angelica sinensis accelerates apoptosis by their key substances influencing factors of apoptosis pathways. Brazilin displays antitumor features by making influence on reactive oxygen species (ROS) intensity. Sargassum serratifolium, flavonoids, and so on have antimetastasis effect. Ficus carica controls miRNA that inhibits translation of certain secretory pathway proteins during the UPR. Serratia marcescens and patupilone (EPO 906) are physically assessed materials through clinical trials related to GBM progression. Consequently, our review puts emphasis on the potential of natural products in GBM treatment by regulating multiple malignant cancer-related pathway solving pending problem such as reducing toxicity and side effect. Moon Nyeo Park, Hyo Sook Song, Myungsun Kim, Min-Jung Lee, Whisung Cho, Hyun-Jin Lee, Cho-Hyun Hwang, Soojong Kim, Yechae Hwang, Beomku Kang, and Bonglee Kim Copyright © 2017 Moon Nyeo Park et al. All rights reserved. The Influence of Different Oregano Species on the Antioxidant Activity Determined Using HPLC Postcolumn DPPH Method and Anticancer Activity of Carvacrol and Rosmarinic Acid Wed, 18 Oct 2017 00:00:00 +0000 The aim of this study was to evaluate concentration-dependent antioxidant and anticancer activities of CA and RA in ethanol extracts of three different Oregano species (Origanum onites L., Origanum vulgare L., and Origanum vulgare ssp. hirtum). The study revealed the highest RA antioxidant activity in O. vulgare ssp. hirtum ( mmol/g) and the lowest in O. vulgare L. ( mmol/g) (). The highest CA amount was present in O. onites L., which was 1.8 and 4.7 times higher () than in O. vulgare ssp. hirtum and O. vulgare L., respectively. The anticancer activity was evaluated on human glioblastoma (U87) and triple-negative breast cancer (MDA-MB231) cell lines in vitro. RA anticancer activity was negligible. CA and the extracts were about 1.5–2 times more active against MDA-MB231 cell line () compared to U87 cell line. The anticancer activities of three tested extracts were similar against U87 cell line () but they had different activities against MDA-MB231 cell line. Juste Baranauskaite, Asta Kubiliene, Mindaugas Marksa, Vilma Petrikaite, Konradas Vitkevičius, Algirdas Baranauskas, and Jurga Bernatoniene Copyright © 2017 Juste Baranauskaite et al. All rights reserved. Modulating Neuroinflammation to Treat Neuropsychiatric Disorders Wed, 18 Oct 2017 00:00:00 +0000 Neuroinflammation is recognised as one of the potential mechanisms mediating the onset of a broad range of psychiatric disorders and may contribute to nonresponsiveness to current therapies. Both preclinical and clinical studies have indicated that aberrant inflammatory responses can result in altered behavioral responses and cognitive deficits. In this review, we discuss the role of inflammation in the pathogenesis of neuropsychiatric disorders and ask the question if certain genetic copy-number variants (CNVs) associated with psychiatric disorders might play a role in modulating inflammation. Furthermore, we detail some of the potential treatment strategies for psychiatric disorders that may operate by altering inflammatory responses. Franziska A. Radtke, Gareth Chapman, Jeremy Hall, and Yasir A. Syed Copyright © 2017 Franziska A. Radtke et al. All rights reserved. Preoperative C-Reactive Protein as a Risk Factor for Postoperative Delirium in Elderly Patients Undergoing Laparoscopic Surgery for Colon Carcinoma Wed, 18 Oct 2017 00:00:00 +0000 Background. Postoperative delirium (POD) is a very common complication in operative disciplines, especially in those elderly patients after cardiac surgery. This study aimed to investigate the relationship between C-reactive protein (CRP) and POD in elderly patients undergoing laparoscopic surgery for colon carcinoma. Methods. 160 elderly patients scheduled to undergo selective laparoscopic surgery for colon carcinoma were prospectively recruited in this present study. The preoperative demographic and medical characteristics, intraoperative variables, and postoperative complications were all recorded in detail. POD assessment was performed once a day for the first 3 days and at 7th day after surgery, respectively. CRP concentrations preoperatively and on postoperative days 1, 2, and 3 were measured by using human enzyme linked immunosorbent assay (ELISA). Results. Of all the 160 enrolled patients, 39 had suffered POD with a POD incidence of 24.4% within the first week after the operation. The univariate analysis and multiple logistic regression analysis suggested preoperative CRP concentrations as the only independent predicator for POD in patients undergoing laparoscopic surgery for colon carcinoma (OR: 5.87; 95% CI: 2.22–11.4; ). Conclusions. This present study highlighted the predictive role of preoperative CRP concentrations for POD in elderly patients undergoing laparoscopic surgery for colon carcinoma. Dong Xiang, Hailin Xing, Huiyu Tai, and Guozhu Xie Copyright © 2017 Dong Xiang et al. All rights reserved. Effects of rhBMP-2 Loaded Titanium Reinforced Collagen Membranes on Horizontal Bone Augmentation in Dogs Tue, 17 Oct 2017 09:52:11 +0000 The aim of this study was to evaluate the efficacy of growth factor loaded collagen membranes on new bone formation during horizontal bone augmentation. Mandibular defects (4 × 4 × 4 mm) were surgically prepared in six male beagle dogs, which were then protected with one of three types of membranes: (1) titanium mesh, (2) titanium reinforced collagen, or (3) rhBMP-2 loaded titanium reinforced collagen. Animals were euthanized 8 and 16 weeks after surgery, and nondecalcified specimens were prepared and histomorphologically investigated to determine the degree of osteogenesis. Data were analyzed with Friedman test. With respect to the degree of osteogenesis at earlier stage (8 weeks after surgery), there was significantly higher new bone ratio in rhBMP-2 loaded membrane group (). However, with respect to the long-term results (16 weeks after surgery), there were no significant differences among the three membranes (). Based on histomorphometric analysis, there were no significant differences in horizontal bone gaining ratio (). Ki-Sun Lee, Yu-Sung Jeon, Sang-Wan Shin, and Jeong-Yol Lee Copyright © 2017 Ki-Sun Lee et al. All rights reserved. Barcoding the Dendrobium (Orchidaceae) Species and Analysis of the Intragenomic Variation Based on the Internal Transcribed Spacer 2 Tue, 17 Oct 2017 08:58:17 +0000 Many species belonging to the genus Dendrobium are of great commercial value. However, their difficult growth conditions and high demand have caused many of these species to become endangered. Indeed, counterfeit Dendrobium products are common, especially in medicinal markets. This study aims to assess the suitability of the internal transcribed spacer 2 (ITS2) region as a marker for identifying Dendrobium and to evaluate its intragenomic variation in Dendrobium species. In total, 29,624 ITS2 copies from 18 species were obtained using 454 pyrosequencing to evaluate intragenomic variation. In addition, 513 ITS2 sequences from 26 Dendrobium species were used to assess its identification suitability. The highest intragenomic genetic distance was observed in Dendrobium chrysotoxum (0.081). The average intraspecific genetic distances of each species ranged from 0 to 0.032. Phylogenetic trees based on ITS2 sequences showed that most Dendrobium species are monophyletic. The intragenomic and intraspecies divergence analysis showed that greater intragenomic divergence is mostly correlated with larger intraspecific variation. As a major ITS2 variant becomes more common in genome, there are fewer intraspecific variable sites in ITS2 sequences at the species level. The results demonstrated that the intragenomic multiple copies of ITS2 did not affect species identification. Xiaoyue Wang, Xiaochen Chen, Pei Yang, Lili Wang, and Jianping Han Copyright © 2017 Xiaoyue Wang et al. All rights reserved. MRI-Based Estimation of Scalar Cochlear-Implant Electrode Position Tue, 17 Oct 2017 07:36:23 +0000 The position of the cochlear-implant electrode is important to audiological outcomes after cochlear implantation. The common technique to evaluate the intracochlear electrode’s position involves the use of ionized radiation in MSCT, DVT, or flat-panel tomography (FPT). Recent advances in knowledge regarding the handling of MRI artifacts in cochlear implantees indicate that estimating the intracochlear electrode’s position with an MRI could be possible. This study’s aim was to evaluate the ipsilaterally position of electrodes using MRI at 1.5 T. In a retrospective study of 10 implantees with postoperative need for MRI scanning, we evaluated the intrascalar electrode’s position using a T2-weighted sequence at 1.5 T. We compared the resulting estimate of the intracochlear position with the estimates from the postoperative FPT scan and the intraoperative NRT ratio. For each ear, the MRI-estimated scalar position corresponded with the estimated positions from the FPT and NRT ratio. For eight ears, a scala tympani’s position was observed in the MRI. In one case, an electrode scalar translocation was found. In one case, the scala vestibuli’s position was observed. Thus, MRI-based estimation of the scalar position of a cochlear-implant electrode is possible. Limitations to this method include implant-specific magnet and fixation configurations, which can cause complications. A. Stratmann, P. Mittmann, G. Rademacher, G. Grupe, S. Hoffmann, S. Mutze, A. Ernst, and I. Todt Copyright © 2017 A. Stratmann et al. All rights reserved.