bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed Development of Hemolytic Anemia with Fragmented Red Blood Cells and Cardiac and Renal Impairments after High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation for Malignant Lymphoma
Authors: Iioka Futoshi , Toda Yusuke , Nagai Yuya , Akasaka Takashi , Shimomura Daiki , Tsuda Katsuyo , Nakamura Fumihiko , Ohno Hitoshi
Published: October 2017

Among 42 consecutive patients with malignant lymphoma who underwent high-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (AHSCT), 5 developed hemolytic anemia with fragmented red blood cells (HA-FrRBCs) on days 87-125 (median 107) of AHSCT. Nadir Hb levels ranged between 5.0 and 6.4 g/dL with 2.2-5.6% FrRBCs. All patients developed grade ≥3 hypoxia and heart failure, and 4 developed grade ≥3 hypertension. The ejection fraction of the left ventricle assessed by echocardiography was significantly reduced in 3 patients. Peak creatinine levels were >4 times above the baseline and estimated glomerular filtration rates were reduced to <30 mL/min/1.73 m2. One patient received plasma exchange, while the remaining 4 responded to treatment with diuretics and cardiovascular agents. Hematological parameters normalized within a median duration of 91 days after the development of HA-FrRBCs. Renal and cardiac functions gradually improved, even though renal function did not return to the baseline. HA-FrRBCs associated with cardiac and renal impairments may represent a thrombotic microangiopathy syndrome and are a delayed complication of HDC/AHSCT. The close monitoring of laboratory abnormalities and persistent treatment with cardiovascular agents and diuretics are the mainstay for the management of this condition.
Impact of a pH 5 Oil-in-Water Emulsion on Skin Surface pH
Authors: Fürtjes Theresa , Weiss Katharina T. , Filbry Alexander , Rippke Frank , Schreml Stephan
Published: October 2017

Background: Human skin surface has a physiologically acidic pH (pHss). In cases of increased pHss, the acidity of the skin can be restored by topical formulations. We tested a pH 5 oil-in-water (O/W) emulsion for pHss regeneration and stabilization. Methods: We performed 2 experiments with 10 female study subjects in each. In both experiments, 2D imaging with luminescent sensor foils was used to determine pHss. Alkalization was reached by washing the volar forearm with a soap bar and warm running tap water for 20 min. Experiment 1: after defining the baseline pHss, we alkalized the respective area and measured pHss over a duration of 5 h, while applying emulsion every hour. Experiment 2: study subjects used the emulsion twice daily for 1 week. Then, pHss was measured before and after 5 min of washing a treated and an untreated area on the volar forearm. Results: (1) 5 h after alkalization, the treated arm showed a significantly lower pHss than the untreated one (5.87 ± 0.03 vs. 6.05 ± 0.03); (2) after washing, the treated area had a significantly lower pHss than controls (6.13 ± 0.03 vs. 6.27 ± 0.05). Conclusions: The tested pH 5 O/W emulsion seems to improve regeneration and stabilization of pHss.
Determination of the Influence of the Antiphlogistic Ingredients Panthenol and Bisabolol on the SPF Value in vivo
Authors: Werner Milena , Herling Marianne , Garbe Birgit , Theek Carmen , Tronnier Hagen , Heinrich Ulrike , Braun Nicole
Published: October 2017

Background: Today, the sun protection factor (SPF) value of sunscreen products is determined in vivo with a standardized protocol (EN ISO 24444:2010), and the measured SPF biological end point is the visible skin erythema. However, many of the sunscreen products currently available on the market have antiphlogistic ingredients, which may potentially result in an overestimated SPF of the sunscreen. Aims: To investigate the potential influence of the antiphlogistic ingredients panthenol and bisabolol in sunscreens on the determined SPF value in vivo. Methods: Formulations with different concentrations of the antiphlogistic ingredients bisabolol or panthenol were tested. As a reference, a base formulation (vehicle) without antiphlogistic ingredients was used. First, the SPF of the sunscreen formulas with and without antiphlogistic ingredients was analyzed in vitro. To investigate whether the antiphlogistic ingredient may suppress the inflammatory response to ultraviolet (UV) irradiation, the SPF was determined in vivo. Finally, selected formulations were also analyzed in an erythema model for testing formulations on UV-induced inflammation. Results: It could be confirmed that no differences between the formula with and that without the active antiphlogistic ingredients bisabolol or panthenol exist when measured in vitro. However, there was also no statistically significant difference in the erythemal response between the vehicle (without an antiphlogistic active ingredient) and the test formulations with different concentrations of the antiphlogistic active ingredients in the in vivo determination of the SPF. Evidence of anti-inflammatory activity of the sunscreen antiphlogistics bisabolol and panthenol was also not apparent in the UV model over a time course of 48 h. Conlusion: The antiphlogistic ingredients panthenol and bisabolol incorporated in the tested sunscreen formula do not interfere with erythema reddening and thus do not affect the SPF value in vivo.
Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature
Authors: Saxena Ashwini , Scaini Giselli , Bavaresco Daniela V. , Leite Camila , Valvassoria Samira S. , Carvalho André F. , Quevedo João
Published: October 2017

Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC. Moreover, we discuss the role of PKC on synaptogenesis and neuroplasticity in the context of BD. The recent development of animal models of BD, such as stimulant-treated and paradoxical sleep deprivation, and the ability to intervene pharmacologically provide further insights into the involvement of PKC in BD. In addition, the effect of PKC inhibitors, such as tamoxifen, in the resolution of manic symptoms in patients with BD further points in that direction. Furthermore, a wide variety of growth factors influence neurotransmission through several molecular pathways that involve downstream effects of PKC. Our current understanding identifies the PKC pathway as a potential therapeutic avenue for BD.
Basic in vitro Characterization of the Vasodilatory Potential of 2-Aminoethyl Nitrate Fixed-Dose Combinations with Cilostazol, Metoprolol and Valsartan
Authors: Oelze Matthias , Welschof Philipp , Knorr Maike , Tran Lan P. , Ullmann Elisabeth , Stamm Paul , Kröller-Schön Swenja , Jansen Thomas , Kopp Maximilian , Schulz Eberhard , Gori Tommaso , Burgin Karl , Scherhag Armin , Sartor Dirk , Münzel Thomas , Daiber Andreas
Published: October 2017

Background/Aims: 2-aminoethyl nitrate (CLC-1011) is a member of the class of organic nitrates that cause vasodilation by the generation of nitric oxide (•NO). These drugs are mainly used for the treatment of angina pectoris and ischemic heart disease. The aim of this study was to characterize the vasodilatory potency of this organic nitrate alone and in combination with clinically established cardiovascular drugs. Methods: Vasodilation by CLC-1011 was tested by isometric tension studies, either alone or combined with cilostazol, valsartan, and metoprolol. Induction of oxidative stress in isolated heart mitochondria was measured by enhanced chemiluminescence. Bioactivation of CLC-1011 in aortic tissue was measured by electron paramagnetic resonance spectroscopy using an iron-based spin trap for •NO. Results: We observed potent vasodilation by CLC-1011 and additive effects for all three drug combinations. In contrast to nitroglycerin (GTN), CLC-1011 did not stimulate mitochondrial oxidative stress. CLC-1011 was bioactivated to •NO in aortic tissue. Conclusion: In summary, the experiments described in this report demonstrate that CLC-1011 does not induce oxidative stress, is a more potent vasodilator than isosorbide-5-mononitrate and dinitrate ISDN, and displays synergistic vasodilation with other cardiovascular drugs. CLC-1011 fixed dose combinations could be used in the management of cardiovascular diseases.
The Clinical Characteristics and Prognostic Analysis of Status Epilepticus in Northeast China
Authors: Sun Lichao  , Han Chuntao  , Lin Weihong
Published: October 2017

Objective: Status epilepticus (SE) is a neurological emergency that may cause severe neurological deficiency and even death. The aim of this study was to analyze the clinical characteristics and prognosis of SE in northeast China. Additionally, the etiology and classification are discussed. Materials and Methods: We retrospectively collected the clinical profiles of patients diagnosed with SE in the Epilepsy Center of Jilin University between January 2011 and May 2015. The causes and clinical courses were investigated. The individuals were followed up by visit or telephone, and the prognoses were analyzed. Results: A total of 223 patients with SE were enrolled, including 134 cases with non-refractory SE (NRSE) and 89 cases with refractory or super-refractory SE (RSE/SRSE). Fifteen patients died during hospitalization, yielding a mortality of 6.73%; 11 of them succumbed to multiple organ dysfunction syndrome (MODS). Statistical analysis showed significant differences in age, family history of epilepsy, and the incidence of non-convulsive SE (NCSE) between the NRSE group and RSE/SRSE group (p < 0.05). We found no significant differences in the causes of SE (central nervous system infection, autoimmune encephalitis, and epilepsy) between these 2 groups. Conclusion: In northeast China, SE is associated with relatively lower mortality, and MODS is the major cause of death. Older age and NCSE are risk factors predicting potential progression to RSE. Central nervous system infection, autoimmune encephalitis, and epilepsy were common causes of SE, but there was no significant association between any of these causes and the occurrence of RSE.
X Chromosome Introgression and Recombination in the cephus Group of Cercopithecus Monkeys
Authors: Tosi Anthony J. , Hirai Hirohisa
Published: October 2017

A representative of Cercopithecus erythrotis was surveyed at a 9.3-kb region of the X chromosome. The data were compared against homologous sequences of closely related Cercopithecus monkeys including C. cephus, a species recently shown to have 2 polymorphic X-chromosomal lineages. Direct sequence comparisons and subsequent phylogenetic analyses revealed that synapomorphies in the first 4.3 kb cluster C. erythrotis with one C. cephus lineage, while synapomorphies in the latter 5.0 kb join it with the second C. cephus lineage. This pattern very likely reflects an ancestral episode of introgression from C. cephus into C. erythrotis followed by a recombination event. Similar groups of synapomorphies occur at different phylogenetic depths within the C. erythrotis/C. cephus/C. ascanius radiation and reveal new details in the evolutionary history of this 3-species clade.
The Epidemiology of Guillain-Barré Syndrome in Children under 15 Years Old in Southwest Iran
Authors: Momen Ali Akbar , Shakurnia Abdolhussein
Published: October 2017

Background: Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy, which has become the most common cause of acute flaccid paralysis. An accurate estimation of GBS occurrence would be useful for investigating the potential causal relationships between risk factors and GBS. The aim of the study was to analyze the incidence, annual time trend, and some epidemiological aspects of GBS in children in the Southwest of Iran. Methods: This was a retrospective study conducted by the Department of Pediatrics of Ahvaz Jundishapur University of Medical Sciences from January 2006 to December 2015. We extracted data from the national database of Acute Flaccid Paralysis Surveillance System. Results: A total of 184 subjects with GBS were assessed. The mean age of subjects was 5.43 ± 4.07 years. The average annual incidence rate of GBS was 1.51 per 100,000 children under 15 years old (95% CI: 1.29-1.73). There was no significant statistical difference in GBS incidence rate between girls and boys (p = 0.376). The highest and lowest proportions of the GBS occurrences were in autumn (32.2%) and summer (14.7%), respectively. Conclusions: The findings indicated that the annual incidence rate of GBS in this study was similar to those in other studies in this area.
Studying Kidney Disease Using Tissue and Genome Engineering in Human Pluripotent Stem Cells
Authors: Garreta Elena , González Federico , Montserrat Núria
Published: October 2017

Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying this complex multistep process. Based on this knowledge, the last 3 years have witnessed the development of a cohort of protocols allowing efficient differentiation of human pluripotent stem cells (hPSCs) towards defined kidney progenitor populations using two-dimensional (2D) culture systems or through generating organoids. Kidney organoids are three-dimensional (3D) kidney-like tissues, which are able to partially recapitulate kidney structure and function in vitro. The current possibility to combine state-of-the art tissue engineering with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9)-mediated genome engineering provides an unprecedented opportunity for studying kidney disease with hPSCs. Recently, hPSCs with genetic mutations introduced through CRISPR/Cas9-mediated genome engineering have shown to produce kidney organoids able to recapitulate phenotypes of polycystic kidney disease and glomerulopathies. This mini review provides an overview of the most recent advances in differentiation of hPSCs into kidney lineages, and the latest implementation of the CRISPR/Cas9 technology in the organoid setting, as promising platforms to study human kidney development and disease.
Efficacy in Treating Lung Metastasis of Invasive Breast Cancer with Functional Vincristine Plus Dasatinib Liposomes
Authors: Zeng Fan , Ju Rui-Jun , Liu Lei , Xie Hong-Jun , Mu Li-Min , Lu Wan-Liang
Published: October 2017

Background: The metastasis of breast cancer is the leading cause of death, while lung metastasis is a major clinical phenomenon in patients with invasive breast cancer. The current treatment option comprising surgery, radiation, and standard chemotherapy cannot achieve a satisfactory effect on the treatment of lung metastasis of breast cancer. In this study, we report the potential of preventing lung metastasis of invasive breast cancer using the newly developed functional vincristine plus dasatinib liposomes. Methods: The investigations were performed on invasive breast cancer MDA-MB-231 cells in vitro and in lung metastatic model of invasive breast cancer MDA-MB-231 cells in nude mice. Results: The functional drug liposomes were able to induce cell cycle arrest at G2/M phase, induce apoptosis, inhibit adhesion, migration, and invasion of breast cancer cells in vitro, and prevent lung metastasis of breast cancer in nude mice. Conclusion: These findings indicate a potential clinical use of functional vincristine plus dasatinib liposomes for treating metastatic breast cancer.
Nuclear Repositioning of the Non-Translocated HLXB9 Allele in the Leukaemia Cell Line GDM-1 Harbouring a t(6;7)(q23;q36)
Authors: Federico Concetta , Leotta Claudia G. , Bruno Francesca , Longo Anna M. , Owoka Temitayo , Tosi Sabrina , Saccone Salvatore
Published: October 2017

Transcriptionally active and inactive topologically associated domains (TADs) occupy different areas in the cell nucleus, and chromosomal rearrangements relocating TADs could determine ectopic expression of the repositioned genes. In this study, we investigated the HLXB9 gene in a myeloid leukaemia cell line, GDM-1, known to harbour a rearrangement involving chromosome 7 with a breakpoint distal to HLXB9, highly expressed in these cells. We used FISH to target the regions involved in the translocation and to distinguish the translocated chromosome from the non-translocated one in interphase nuclei. Two-dimensional analysis of the interphase FISH data indicated that the 2 HLXB9 alleles had a different localisation in the cell nuclei, with the translocated allele consistently positioned in the nuclear periphery and the normal one in the more internal portion of the nucleus, known as the transcriptionally active compartment. Our data may indicate that HLXB9 transcripts in the GDM-1 cell line do not arise from the allele located in rearranged chromosome 7, suggesting that regulation of gene expression in cancer cells harbouring chromosomal translocations might be more complex than previously thought, paving the path to further investigations on mechanisms of gene expression.
The RAPID Neuropsychological Test Battery for Subjects Aged 50–89: From Norms to Cognitive Profile
Authors: Sylvestre Géraldine , Mauny Frédéric , Lavaux Marie , Puyraveau Marc , Binetruy Mickael , Meyer Agatha , Vandel Pierre , Galmiche Jean , Chopard Gilles
Published: October 2017

Background/Aims: It is well established that healthy adults obtain low performances when simultaneously interpreting the results of multiple tests. The aim of this study was to estimate the proportion of French-speaking healthy older adults with low scores for the RAPID (Réseau d’Aide au diagnostic et à la PrIse en charge des Détériorations cognitives et de maladies neurologiques chroniques en Franche-Comté et au niveau national) battery test and consider different combinations of test scores within a specific domain and across different domains. Methods: The prevalence of low scores (i.e., ≤5th percentile) on the 14 RAPID primary measures was calculated from the RAPID normative sample (n = 476), based on 4 ages (50–89 years) and 3 levels of education. Results: A high percentage (40.1%) of the normative sample obtained at least one or more low scores (i.e., false positives). In contrast, the risk of having low scores was much less important (<2%) when considering the combinations of 2 test-scores. Conclusion: Low scores are very common in healthy older subjects and are thus not necessarily pathological or indicative of truly impaired functioning. The information derived from a cognitive profile may provide a greater clinical relevance in an individual, since very few of the healthy older adults obtained low scores on combinations of 2 test-scores.
Plaque-Type Syringoma: A Case Report
Authors: Rungananchai Chutima , Triwongwaranat Daranporn
Published: October 2017

Syringomas are benign appendageal tumors originated from eccrine ducts. The lesions usually present as multiple small, firm papules at lower eyelids and cheeks of women. Plaque-type syringoma is an infrequent form of syringoma and to date, 12 cases have been reported. Pathology demonstrated benign proliferation of eccrine ductal structures in the dermis with surrounding fibrotic stroma. We report the case of a 40-year-old Thai male with plaque-type syringomas at infraorbital areas.
Evaluation of Magnetic Resonance Imaging Safety and Imaging Issues Associated with the Occlusion Balloon Used during Fetoscopic Endoluminal Tracheal Occlusion
Authors: Victoria Teresa , Johnson Ann M. , Adzick N. Scott , Hedrick Holly L. , Shellock Frank G.
Published: October 2017

Introduction: Congenital diaphragmatic hernias can be successfully treated by fetoscopic tracheal occlusion (FETO), a minimally invasive procedure that may improve postnatal survival. The endoluminal balloon utilized for FETO contains a metallic component that may pose possible risks for the fetus and mother related to the use of magnetic resonance imaging (MRI). The objective of this study is to evaluate MRI-related imaging and safety issues (magnetic field interactions, heating, and artifacts) for the occlusion balloon used in FETO. Materials and Methods: Using well-established techniques, tests were performed to assess magnetic field interactions (translational attraction and torque) and MRI-related heating and artifacts that occurred when exposing the occlusion balloon typically used for FETO (Goldbal2, Balt, www.balt.fr) to a 3-T magnet. MRI-related heating was determined by placing the occlusion balloon in a gelled-saline-filled, head-torso phantom and conducting MRI at relatively high, whole-body-averaged specific absorption rate (2.9 W/kg) for 15 min. Artifacts were measured in association with the use of T1-weighted, spin-echo and gradient-echo pulse sequences. Results: The balloon displayed minor magnetic field interactions and physiologically inconsequential heating (highest temperature rise: 0.1°C above background). Artifacts extended approximately 10 mm from the occlusion balloon on the gradient-echo pulse sequence, suggesting that anatomy located at a position greater than this distance may be visualized on MRI. Discussion: In this paper, we demonstrate that the risks of performing MRI at 3 T or less in a patient who has this occlusion balloon in place are acceptable (or MR conditional, using current terminology).
Omission of a Bladder Flap during Cesarean Birth in Primiparous Women
Authors: Aslan Cetin Berna , Aydogan Mathyk Begum , Barut Sibel , Zindar Yelda , Seckin Kerem Doga , Kadirogullari Pinar
Published: October 2017

Aims: Creation of a bladder flap has traditionally been an integral surgical step of Cesarean birth, and the practicality of such a procedure to create a bladder flap is still highly debated. Methods: A total of 208 patients undergoing a primary cesarean birth were randomized. Group 1 (bladder flap) had 101 patients and group 2 (omission of a bladder flap) had 100 patients. The primary outcome was the total operating time and secondary outcomes were postoperative urinary symptoms, bladder injury, postoperative urinary retention, and postoperative residual urine volume. Results: No significant differences were found among groups in terms of mean total operating time and mean skin incision-to-delivery time. No bladder injury occurred in either group. Postoperative urine retention observed in the bladder flap group was 2%. The postoperative residual urine volume was significantly more in the bladder flap group compared to the non-bladder flap group (24.5 ± 2.8 vs. 16.2 ± 1.4 mL). The number of patients with dysuria was significantly higher in the bladder flap group (42 vs. 13%). Conclusions: The creation of a bladder flap during cesarean birth does not have an effect on intraoperative results and operation time, but it is associated with short-term urinary complaints, such as postoperative urinary retention and dysuria.
Chronic Toxicity Test in Cynomolgus Monkeys For 98 Days with Repeated Intravenous Infusion of Cynomolgus Umbilical Cord Mesenchymal Stem Cells
Authors: He Jie , Ruan Guang-ping , Yao Xiang , Liu Ju-fen , Zhu Xiang-qing , Zhao Jing , Pang Rong-qing , Li Zi-an , Pan Xing-hua
Published: October 2017

Background/Aims: Stem cell-based therapy is attractive in many clinical studies, but current data on the safety of stem cell applications remains inadequate. This study observed the safety, immunological effect of cynomolgus monkey umbilical cord mesenchymal stem cells (mUC-MSCs) injected into cynomolgus monkeys, in order to evaluate the safety of human umbilical cord mesenchymal stem cells (hUC-MSCs) prepared for human clinical application. Methods: Eighteen cynomolgus monkeys were divided into three groups. Group 1 is control group, Group 2 is low-dose group, Group 3 is high-dose group. After repeated administrations of mUC-MSCs, cynomolgus monkeys were observed for possible toxic reactions. Results: During the experiment, no animal died. There were no toxicological abnormalities in body weight, body temperature, electrocardiogram, coagulation and pathology. In the groups 2 and 3, AST and CK transiently increased, and serum inorganic P slightly decreased. All animals were able to recover at 28 days after the infusion was stopped. In the groups 2 and 3, CD3+ and IL-6 levels significantly increased, and recovery was after 28 days of infusion. There were no obvious pathological changes associated with the infusion of cells in the general and microscopic examinations. Conclusions: The safe dosage of repeated intravenous infusion of mUC-MSCs in cynomolgus monkeys is 1.0 × 107/kg, which is 10 times of that in clinical human use.
Resveratrol Inhibits the Epidermal Growth Factor-Induced Migration of Osteoblasts: the Suppression of SAPK/JNK and Akt
Authors: Kawabata Tetsu , Tokuda Haruhiko , Fujita Kazuhiko , Kainuma Shingo , Sakai Go , Matsushima-Nishiwaki Rie , Kozawa Osamu , Otsuka Takanobu
Published: October 2017

Background/Aims: Resveratrol is a polyphenol enriched in the skins of grapes and berries, that shows various beneficial effects for human health. In the present study, we investigated the mechanism behind the epidermal growth factor (EGF)-induced migration of osteoblast-like MC3T3-E1 cells, and the effect of resveratrol on this cell migration. Methods: The cell migration was examined using Boyden chamber, and phosphorylation of each kinase was analyzed by Western blotting. Results: The EGF-induced migration was suppressed by PD98059, an inhibitor of MEK1/2, as well as SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of SAPK/JNK, and deguelin, an inhibitor of Akt. In contrast, rapamycin, an inhibitor of upstream kinase of p70 S6 kinase, and fasudil, an inhibitor of Rho-kinase, hardly affected the migration. Resveratrol significantly reduced the EGF-induced migration in a dose-dependent manner. SRT1720, an SIRT1 activator, suppressed the migration by EGF. In addition, resveratrol markedly attenuated the EGF-induced phosphorylation of SAPK/JNK and Akt without affecting the phosphorylation of p44/p42 MAP kinase or p38 MAP kinase. The phosphorylation of SAPK/JNK and Akt induced by EGF was down-regulated by SRT1720. Conclusion: Our results strongly suggest that resveratrol reduces the EGF-stimulated migration of osteoblasts via suppression of SAPK and Akt, and that the inhibitory effect of resveratrol is mediated in part via SIRT1.
Overexpression of LncRNA PVT1 Predicts Advanced Clinicopathological Features and Serves as an Unfavorable Risk Factor for Survival of Patients with Gastrointestinal Cancers
Authors: Liu Fangteng , Dong Qing , Huang Jun
Published: October 2017

Background/Aims: Many studies have reported that PVT1 played important roles in diverse cancer types. But the systematic analysis of PVT1 in gastrointestinal cancers has not been inspected. Thus, we aimed to investigate clinical value of the long noncoding RNA PVT1 (lncRNA) expression in digestive system cancers. Methods: Eligible studies were collected from a number of databases (PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure and Wanfang database). Pooled hazard ratio (HR) or odds ratio (OR) with 95 % confidence interval (95 % Cl) were applied to assess the clinical significance of PVT1. Results: Data from 15 articles were included with a total of 2585 patients. Elevated PVT1 expression were significantly related to poor overall survival (OS) [HR = 1.86, 95% CI (1.44, 2.28); p<0. 0001] in digestive system cancers. The same association was also observed between PVT1 expression with outcomes, including disease free survival (DFS), disease specific survival (DSS) and relapse free survival (RFS). The lncRNA PVT1 could also be predicative for some clinicopathological features. Conclusions: This meta-analysis revealed that PVT1 may serve as a prognostic predictor and pathological biomarker in digestive system cancers.
Remote Limb Ischaemic Postconditioning Protects Against Myocardial Ischaemia/Reperfusion Injury in Mice: Activation of JAK/STAT3-Mediated Nrf2-Antioxidant Signalling
Authors: Gao Sumin , Zhan Leyun , Yang Zhengchao , Shi Ruili , Li Haobo , Xia Zhengyuan , Yuan Shiying , Wu Qing-ping , Wang Tingting , Yao Shanglong
Published: October 2017

Background: This study aimed to evaluate the protective effect and mechanisms of remote limb ischaemic postconditioning (RIPostC) against myocardial ischaemia/reperfusion (IR) injury. Methods: Male mice underwent 45 min of coronary artery occlusion followed by 2 h of reperfusion. RIPostC was achieved by three cycles of 5 min of ischaemia and 5 min of reperfusion in the left hind limb at the start of the reperfusion period. After 2 h of cardiac reperfusion, myocardial infarct size, cardiac enzyme release, apoptosis and oxidative stress were assessed. Protein expression and phosphorylation were measured by Western blotting. Results: RIPostC significantly decreased cardiac IR injury, as reflected by reduced infarct size and cellular apoptosis (22.9 ± 3.3% vs 40.9 ± 6.2% and 13.4% ± 3.1% vs 26.2% ± 3.1%, respectively, both P < 0.01) as well as plasma creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) release (21.97 ± 4.08 vs 35.86 ± 2.91 ng/ml and 6.17 ± 0.58 vs 8.37 ± 0.89 U/ml, respectively, both P < 0.01) compared with the IR group. RIPostC significantly increased the phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.01). In addition, RIPostC elevated the nuclear translocation of Nrf2 and the expression of HO-1 and reduced myocardial oxidative stress (P < 0.05). Interestingly, pretreatment with the JAK/STAT3 inhibitor AG490 blocked the cardioprotective effect of RIPostC accompanied by decreased phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.05), decreased nuclear translocation of Nrf2 and expression of HO-1, as well as increased oxidative stress (P < 0.05). Conclusion: RIPostC attenuates apoptosis and protects against myocardial IR injury, possibly through the activation of JAK/STAT3-mediated Nrf2-antioxidant signalling.
MiR-26a Mediates Ultraviolet B-Induced Apoptosis by Targeting Histone Methyltransferase EZH2 Depending on Myc Expression
Authors: Zhang Ting , Qian Hua , Hu Cui , Lu Hui , Li Ji-Bing , Wu Ya-Fen , Li Wei
Published: October 2017

Background/Aims: Ultraviolet B (UVB) damage is the most essential etiological factor in skin carcinogenesis, and apoptosis leads to the efficient elimination of UVB-damaged cells. However, the mechanisms underlying resistance to UVB-induced apoptosis remain unclear. Methods: HaCaT and A431 cells were used in the present study. Quantitative real-time PCR, single cell PCR, and western blotting were used to examine cancer-related gene expression at the mRNA and protein levels. Results: We report that miR-26a, which is upregulated upon UVB irradiation, promotes UVB-induced apoptosis in HaCaT cells by targeting the histone methyltransferase EZH2. Moreover, the UVB/miR-26a/EZH2 regulatory axis largely depends on the MYC expression level. Interestingly, treatment with EZH2 inhibitors significantly enhanced UVB-induced apoptosis. Conclusion: miR-26a/EZH2 might be potential targets for skin cancer prevention and therapy.
Heparan Sulfate and Chondroitin Sulfate Glycosaminoglycans Are Targeted by Bleomycin in Cancer Cells
Authors: Li Xiulian , Lan Ying , He Yanli , Liu Yong , Luo Heng , Yu Haibo , Song Ni , Ren Sumei , Liu Tianwei , Hao Cui , Guo Yunliang , Zhang Lijuan
Published: October 2017

Background/Aims: Bleomycin is a clinically used anti-cancer drug that produces DNA breaks once inside of cells. However, bleomycin is a positively charged molecule and cannot get inside of cells by free diffusion. We previously reported that the cell surface negatively charged glycosaminoglycans (GAGs) may be involved in the cellular uptake of bleomycin. We also observed that a class of positively charged small molecules has Golgi localization once inside of the cells. We therefore hypothesized that bleomycin might perturb Golgi-operated GAG biosynthesis. Methods: We used stable isotope labeling coupled with LC/MS analysis of GAG disaccharides simultaneously from bleomycin-treated and non-treated cancer cells. To further understand the cytotoxicity of bleomycin and its relationship to GAGs, we used sodium chlorate to inhibit GAG sulfation and commercially available GAGs to compete for cell surface GAG/bleomycin interactions in seven cell lines including CHO745 defective in both heparan sulfate and chondroitin sulfate biosynthesis. Results: we discovered that heparan sulfate GAG was significantly undersulfated and the quantity and disaccharide compositions of GAGs were changed in bleomycin-treated cells in a concentration- and time-dependent manner. We revealed that bleomycin-induced cytotoxicity was directly related to cell surface GAGs. Conclusion: GAGs were targeted by bleomycin both at cell surface and at Golgi. Thus, GAGs might be the biological relevant molecules that might be related to the bleomycin-induced fibrosis in certain cancer patients, a severe side effect with largely unknown molecular mechanism.
Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study
Authors: Venter Chantelle , Oberholzer Hester Magdalena , Bester Janette , van Rooy Mia-Jeanne , Bester Megan Jean
Published: October 2017

Background/Aims: Heavy metal pollution is increasing in the environment, contaminating water, food and air supplies. This can be linked to many anthropogenic activities. Heavy metals are absorbed through the skin, inhalation and/or orally. Irrespective of the manner of heavy metal entry in the body, the blood circulatory system is potentially the first to be affected following exposure and adverse effects on blood coagulation can lead to associated thrombotic disease. Although the plasma levels and the effects of cadmium (Cd) and chromium (Cr) on erythrocytes and lymphocytes have been described, the environmental exposure to heavy metals are not limited to a single metal and often involves metal mixtures, with each metal having different rates of absorption, different cellular, tissue, and organ targets. Therefore the aim of this study is to investigate the effects of the heavy metals Cd and Cr alone and whether Cr synergistically increases the effect of Cd on physiological important processes such as blood coagulation. Methods: Human blood was exposed to the heavy metals ex vivo, and thereafter morphological analysis was performed with scanning electron- and confocal laser scanning microscopy (CLSM) in conjunction with thromboelastography®. Results: The erythrocytes, platelets and fibrin networks presented with ultrastructural changes, including varied erythrocytes morphologies, activated platelets and significantly thicker fibrin fibres in the metal-exposed groups. CLSM analysis revealed the presence of phosphatidylserine on the outer surface of the membranes of the spherocytic erythrocytes exposed to Cd and Cr alone and in combination. The viscoelastic analysis revealed only a trend that indicates that clots that will form after heavy metal exposure, will likely be fragile and unstable especially for Cd and Cr in combination. Conclusion: This study identified the blood as an important target system of Cd and Cr toxicity.
Serum and Glucocorticoid Inducible Kinase 1-Sensitive Survival, Proliferation and Migration of Rhabdomyosarcoma Cells
Authors: Schmid Evi , Stagno Matias Julian , Yan Jing , Schleicher Sabine , Yu Willi , Honisch Sabina , Lang Florian , Fuchs Jörg , Seitz Guido
Published: October 2017

Background/Aims: Rhabdomyosarcoma, the most common pediatric soft tissue sarcoma, may show an intrinsic refractoriness to standard chemotherapy in advanced tumor stages, which is associated with poor prognosis. Cellular mechanisms conferring tumor cell survival and therapy resistance in many tumor types include the serum & glucocorticoid inducible kinase (SGK) 1 pathway, a kinase expressed ubiquitously with particularly strong expression in skeletal muscle and some tumor types. The present study explored whether SGK1 is expressed in rhabdomyosarcoma and, if so, whether this kinase impacts on tumor cell survival, proliferation and migration. Multiple in vitro techniques were used to study the role of SGK1 in rhabdomyosarcoma. Methods: The Gene Chip® Human Genome U133 Plus 2.0 Array were employed to examine SGK1 transcriptional activity in healthy muscle and rhabdomyosarcoma tissue. SGK1 transcript levels were quantified in rhabdomyosarcoma cell lines RD (embryonal subtype) and RH30 (alveolar subtype) by RT-PCR, cell viability was measured using MTT assays. Clonal cell growth was assessed via colony forming assays and migration experiments were performed in a transwell system. Results: SGK1 is expressed in embryonal and alveolar rhabdomyosarcoma tissue samples and in RD and RH30 rhabdomyosarcoma cell lines. Administration of EMD638683 – an inhibitor specific for SGK1 - decreased viability of RD and RH30 cells, enhanced the effects of the cytotoxic drug doxorubicin leading to reduced migration and decreased cell proliferation. Conclusions: SGK1 is expressed in rhabdomyosarcoma cells where it contributes to survival, therapy resistance, cell proliferation and migration. Thus, SGK1 inhibitors may be considered a therapeutic option for the treatment of therapy-resistant rhabdomyosarcoma.
Clinical Outcomes and Predictors of Satisfaction in Patients with Improved Lithium Disilicate All-Ceramic Crowns
Authors: Samer Mazin Saleh , Faraz Qahtani , Al-Dubai Sami Abdo Radman , Vohra Fahim , Abdullah Hadijah , Taiyeb-Ali Tara Bai , Saub Roslan
Published: October 2017

Objectives: The aim of this study was to determine the clinical outcomes and predictors of satisfaction in patients with lithium disilicate (LD) ceramic crowns. Subjects and Methods: Clinical outcomes were assessed in 47 patients with 88 LD crowns using modified United States Public Health Service (USPHS) evaluation criteria and survival rates. The questionnaire for predictors included 3 aspects: (a) sociodemographic characteristics, (b) oral health habits (tooth brushing frequency, flossing frequency, and dental visits), and (c) satisfaction of the restorations (aesthetics, function, fit, cleansability, and chewing ability of the crowns, and overall satisfaction). Frequency distributions were computed using univariate and multivariate analysis. The Student t test and analysis of variance (ANOVA) were used to compare means across variables. Correlation analysis was done to assess the association between continuous variables. Results: The age of crowns was 34.7 ± 9.7 months. The survival rate was 96.6% at 35.9 ± 9.2 months. There was a significant association between successful crown function and oral hygiene measures: tooth brushing (p˂ 0.001), dental visits (p = 0.006), and flossing (p = 0.009). A strong negative correlation was observed between aesthetic satisfaction (r = -0.717, p˂ 0.001) and chewing ability (r = -0.639, p˂ 0.001) with crown age. The linear regression model was significant for all predictors (p < 0.05) except overall satisfaction (p > 0.05). Conclusion: The LD crowns had long survival rates of 96.6% up to 35.9 ± 9.2 months and provided satisfactory clinical performance (low risk of failure). Oral hygiene habits such as brushing, flossing, and regular dental visits influenced patient satisfaction with LD crowns.
МОДЕЛЬ ФОРМУВАННЯ ДОСЛІДНИЦЬКОЇ КОМПЕТЕНТНОСТІ МАЙБУТНІХ ФЕЛЬДШЕРІВ У ПРОЦЕСІ ВИВЧЕННЯ БІОЛОГІЧНИХ ДИСЦИПЛІН
Authors: Moseychuk A. R.
Published: October 2017

Мета дослідження. – науково обґрунтувати модель формування дослідницької компетентності майбутніх фельдшерів у процесі вивчення біологічних дисциплін.Матеріали та методи дослідження. Формування дослідницької компетентності майбутніх фельдшерів у процесі вивчення біологічних дисциплін не стихійний, а керований і регульований процес, результативність та успішність якого залежать від визначених педагогічних умов, які  реалізовано через засоби, методи і форми навчального процесу. Групи методів склали: методи, що формують науковий світогляд майбутніх фельдшерів і здійснюють обмін інформацією (бесіда, диспут, есе); методи, що організують дослідницьку діяльність майбутніх фельдшерів і стимулюють її мотиви (дослід, інструктаж, дослідницькі завдання, ділова гра, проектний метод, кейс-метод); методи, що надають допомогу майбутнім фельдшерам здійснювати рефлексію їх дослідницької діяльності (індивідуальна бесіда, есе). Основними формами організації навчання виступили: лекції, семінари-дискусії, лабораторно-дослідні заняття, олімпіади, круглий стіл, конференція, майстер-клас, самостійна робота, практика, робота у науковому гуртку, індивідуальні консультації.Результати й обговорення. Дослідницька компетентність забезпечує безперервний саморозвиток особистості протягом всього життя у соціальній та професійній сферах завдяки системним трансдисциплінарним знанням методології та парадигматики наукового дослідження, вмінню всебічно, критично, економно опрацьовувати найновішу інформацію та мобільно використовувати її для розв’язання професійних задач Аналіз педагогічної літератури засвідчує, що процес моделювання широко застосовується в педагогіці і дидактиці. При цьому моделюванню підлягає як зміст освіти, так і навчальна діяльність. Для відображення цілісної картини досліджуваного процесу розроблено структурно-змістову модель формування дослідницької компетентності майбутніх фельдшерів у процесі вивчення біологічних дисциплін.   Розробляючи педагогічну модель, дійшли висновку, що проблема формування дослідницької компетентності майбутніх фельдшерів у процесі вивчення  біологічних дисциплін є складною і різнобічною, яку потрібно розглядати з позицій системного та компетентнісного наукових підходівВисновки. Моделювання процесу формування дослідницької компетентності відповідно до концепцій системного та компетентнісного підходів забезпечить позитивну динаміку рівнів сформованості дослідницької компетентності майбутніх фельдшерів. Подальший науковий пошук спрямовано на визначення ефективності розробленої моделі та педагогічних умов формування дослідницької компетентності майбутніх фельдшерів у процесі вивчення біологічних дисциплін.
ВПРОВАДЖЕННЯ ДИСТАНЦІЙНОЇ ОСВІТИ НА КАФЕДРІ СІМЕЙНОЇ МЕДИЦИНИ І ТЕРАПІЇ
Authors: Zhdan V. N. , Babanina M. Y. , Tkachenko M. V. , Volchenko G. V. , Kitura E. M. , Shylkina L. M. , Lebed V. G.
Published: October 2017

Мета дослідження – аналіз педагогічної ефективності курсів передатестаційного циклу для лікарів з фаху “Загальна практика – сімейна медицина”, що проводилися на базі кафедри сімейної медицини і терапії навчально-наукового інституту післядипломної освіти та на філії кафедри у м. Кременчук.Матеріали та методи дослідження. Оцінка ефективності використаних педагогічних технологій проводилася наприкінці циклу шляхом проведення тестування за допомогою ліцензованої комп’ютерної програми “Elex” (пропонувалося 150 питань 2-3 рівня складності з відповідного фаху) і шляхом перевірки опанування практичних навичок згідно зі стандартизованими картами практичних навичок та підведення підсумків з анонімним анкетуванням. Важливою особливістю навчального процесу в галузі післядипломної медичної освіти також є тісне поєднання теоретичної та практичної підготовки фахівців, тому велике значення має саме комплексність навчання: використання дистанційних форм на етапі теоретичної підготовки та  відпрацювання практичних навичок на клінічних базах стажування. Це є переконливим поясненням наявності заочної частини навчання та пояснює перевагу дистанційної освіти, коли слухачі віддалені від бази навчального закладу. Дистанційні форми освіти не можуть існувати самостійно та використовуються у поєднанні з класичними формами навчання.Результати й обговорення. Показана ефективність використання дистанційних форм навчання за даними результатів тестування та опанування практичних навичок.Висновки. Дистанційна освіта на післядипломному етапі навчання лікарів-інтернів та лікарів-курсантів є самостійна цілеспрямована робота з використанням сучасних інформаційних технологій, ефективність якої залежить від методологічно структурованого викладачем процесу та інформаційно-комунікаційних можливостей вищого навчального закладу. Надані рекомендації щодо впровадження елементів дистанційного навчання в практику роботи Навчально-наукового інституту післядипломної освіти.
АНАЛІЗ ВІТЧИЗНЯНОГО ТА ЗАРУБІЖНОГО ДОСВІДУ ПІДГОТОВКИ МЕДИЧНИХ СЕСТЕР
Authors: Slavopas V. A.
Published: October 2017

Мета дослідження – проаналізувати відмінності у підготовці та практичній діяльності медичних сестер в Україні та за кордоном, запропонувати шляхи покращення якості підготовки медичних сестер.Матеріали та методи дослідження. Об’єктом дослідження є підготовка майбутніх медичних сестер  в Україні та за кордоном. У дослідженні використані методики теоретичного аналізу.Результати й обговорення. В Україні функції медичної сестри обмежені виконанням призначень лікаря. У лікувально-профілактичних закладах країн Європи та в США медичні сестри працюють за принципами медсестринського процесу, який передбачає їх самостійність. Рівень теоретичної та практичної підготовки майбутніх медичних сестер за кордоном значно вищий, оскільки вони наділені ширшими повноваженнями та виконують складні маніпуляції. Тому виникає необхідність покращити якість підготовки та посилити роль медичних сестер в Україні, відповідно до міжнародних стандартів.Висновок. Сучасна модель підготовки передбачає, що медична сестра – це фахівець з професійною освітою, має право на самостійне виконання своїх функцій та здійснює медсестринський процес, тому в нашій державі повинні бути змінені основні підходи до підготовки та практичної діяльності медичних сестер відповідно до міжнародних стандартів.
Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association
Authors: Lui George K. , Saidi Arwa , Bhatt Ami B. , Burchill Luke J. , Deen Jason F. , Earing Michael G. , Gewitz Michael , Ginns Jonathan , Kay Joseph D. , Kim Yuli Y. , Kovacs Adrienne H. , Krieger Eric V. , Wu Fred M. , Yoo Shi-Joon
Published: October 2017

Life expectancy and quality of life for those born with congenital heart disease (CHD) have greatly improved over the past 3 decades. While representing a great advance for these patients, who have been able to move from childhood to successful adult lives in increasing numbers, this development has resulted in an epidemiological shift and a generation of patients who are at risk of developing chronic multisystem disease in adulthood. Noncardiac complications significantly contribute to the morbidity and mortality of adults with CHD. Reduced survival has been documented in patients with CHD with renal dysfunction, restrictive lung disease, anemia, and cirrhosis. Furthermore, as this population ages, atherosclerotic cardiovascular disease and its risk factors are becoming increasingly prevalent. Disorders of psychosocial and cognitive development are key factors affecting the quality of life of these individuals. It is incumbent on physicians who care for patients with CHD to be mindful of the effects that disease of organs other than the heart may have on the well-being of adults with CHD. Further research is needed to understand how these noncardiac complications may affect the long-term outcome in these patients and what modifiable factors can be targeted for preventive intervention.