bluuebunny/crossref_metadata_2025 huggingface dataset:
Conductive Education as a Method of Stroke Rehabilitation: A Single Blinded Randomised Controlled Feasibility Study
Authors: Bek Judith , Brown Melanie R. , Jutley-Neilson Jagjeet , Russell Nicholas C. C. , Huber Pia A. J. , Sackley Catherine M.
Published: June 2016

Background.Conductive Education for stroke survivors has shown promise but randomised evidence is unavailable. This study assessed the feasibility of a definitive randomised controlled trial to evaluate efficacy.Methods.Adult stroke survivors were recruited through local community notices. Those completing the baseline assessment were randomised using an online program and group allocation was independent. Intervention group participants received 10 weekly 1.5-hour sessions of Conductive Education at the National Institute of Conductive Education in Birmingham, UK. The control group participants attended two group meetings. The study evaluated the feasibility of recruitment procedures, delivery of the intervention, retention of participants, and appropriateness of outcome measures and data collection methods. Independent assessments included the Barthel Index, the Stroke Impact Scale, the Timed Up and Go test, and the Hospital Anxiety and Depression Scale.Results.Eighty-two patients were enrolled; 77 completed the baseline assessment (46 men, mean age 62.1 yrs.) and were randomised. 70 commenced the intervention (n=37) or an equivalent waiting period (n=33). 32/37 completed the 10-week training and 32/33 the waiting period. There were no missing items from completed questionnaires and no adverse events.Discussion.Recruitment, intervention, and assessment methods worked well. Transport issues for intervention and assessment appointments require review.Conclusion.A definitive trial is feasible. This trial is registered withISRCTN84064492.
Efficiency on the Use of Radiation and Corn Yield under Three Densities of Sowing
Authors: Morales-Ruiz A. , Loeza-Corte J. M. , Díaz-López E. , Morales-Rosales E. J. , Franco-Mora O. , Mariezcurrena-Berasaín M. D. , Estrada-Campuzano G.
Published: June 2016

Aiming to evaluate sowing densities and efficiency of radiation use, six corn genotypes, three from open pollination (“Amarillo Almoloya,” “Cacahuacintle,” and “Jiquipilco”) and three hybrids (“Z-60,” “Condor,” and “H-50”), were sown at densities of 6.9, 7.8, and 8.9 plants m−2, under a split plot design, within a factorial arrangement of treatments during three years (2008, 2009, and 2010). Evaluated variables were yield, harvest index, biomass production, attenuation coefficient, and radiation use efficiency. Results indicate that 2008 was the best year because yield, biomass, and radiation use efficiency were 1132.6, 3505 gm−2, and 0.79 g MJ−1, respectively. “Jiquipilco” was the genotype that exhibited the best adaptability to climatic conditions of the zone; thus, it is recommended to be grown on the studied zone.
Effectively Screening for Coronary Artery Disease in Patients Undergoing Orthotopic Liver Transplant Evaluation
Authors: Lee Bryan C. , Li Feng , Hanje Adam J. , Mumtaz Khalid , Boudoulas Konstantinos D. , Lilly Scott M.
Published: June 2016

Coronary artery disease (CAD) is prevalent in patients with end-stage liver disease and associated with poor outcomes when undergoing orthotopic liver transplantation (OLT); however, noninvasive screening for CAD in this population is less sensitive. In an attempt to identify redundancy, we reviewed our experience among patients undergoing CAD screening as part of their OLT evaluation between May 2009 and February 2014. Demographic, clinical, and procedural characteristics were analyzed. Of the total number of screened patients (n=132), initial screening was more common via stress testing (n=100; 75.8%) than coronary angiography (n=32; 24.2%). Most with initial stress testing underwent angiography (n=52; 39.4%). Among those undergoing angiography, CAD was common (n=31; 23.5%). Across the entire cohort the number of traditional risk factors was linearly associated with CAD, and those with two or more risk factors were found to have CAD by angiography 50% of the time (OR 1.92; CI 1.07–3.44,p=0.026). Our data supports that CAD is prevalent among pre-OLT patients, especially among those with 2 or more risk factors. Moreover, we identified a lack of uniformity in practice and the need for evidence-based and standardized screening protocols.
Hepatectomy Based on Future Liver Remnant Plasma Clearance Rate of Indocyanine Green
Authors: Uchida Yuichiro , Furuyama Hiroaki , Yasukawa Daiki , Nishino Hiroto , Ando Yasuhisa , Hata Toshiyuki , Machimoto Takafumi , Yoshimura Tsunehiro
Published: June 2016

Background. Hepatectomy, an important treatment modality for liver malignancies, has high perioperative morbidity and mortality rates. Safe, comprehensive criteria for selecting patients for hepatectomy are needed. Since June 2011, we have used a cut-off value of ≧ 0.05 for future liver remnant plasma clearance rate of indocyanine green as a criterion for hepatectomy. The aim of this study was to verify the validity of this criterion. Methods. From June 2011 to December 2015, 212 hepatectomies were performed in Tenri Yorozu Hospital. Of these 212 patients, 107 who underwent preoperative computed tomography imaging volumetry, indocyanine green clearance test, and hepatectomy (excluding partial resection or enucleation) were retrospectively analyzed. Results. There was no postoperative mortality. Posthepatectomy liver failure occurred in 59 patients (55.1%) (International Study Group of Liver Surgery Grade A: 43 cases (40.2%), Grade B: 16 cases (15.0%), and Grade C: no cases). Operative morbidity greater than Clavien-Dindo Grade 3 occurred in 23 patients (21.5%). A low future liver remnant plasma clearance rate of indocyanine green was a good predictor for Grade B cases (area under curve = 0.804; 95% confidence interval, 0.712–0.895). Conclusion. Liver remnant plasma clearance rate of indocyanine green is a valid criterion for hepatectomy.
Synergistic Effects of Sulfated Polysaccharides from Mexican Seaweeds against Measles Virus
Authors: Morán-Santibañez Karla , Cruz-Suárez Lucia Elizabeth , Ricque-Marie Denis , Robledo Daniel , Freile-Pelegrín Yolanda , Peña-Hernández Mario A. , Rodríguez-Padilla Cristina , Trejo-Avila Laura M.
Published: June 2016

Sulfated polysaccharides (SPs) extracted from five seaweed samples collected or cultivated in Mexico (Macrocystis pyrifera,Eisenia arborea,Pelvetia compressa,Ulva intestinalis, andSolieria filiformis) were tested in this study in order to evaluate their effect on measles virusin vitro. All polysaccharides showed antiviral activity (as measured by the reduction of syncytia formation) and low cytotoxicity (MTT assay) at inhibitory concentrations. SPs fromEisenia arboreaandSolieria filiformisshowed the highest antiviral activities (confirmed by qPCR) and were selected to determine their combined effect. Their synergistic effect was observed at low concentrations (0.0274 μg/mL and 0.011 μg/mL ofE. arboreaandS. filiformisSPs, resp.), which exhibited by far a higher inhibitory effect (96% syncytia reduction) in comparison to the individual SP effects (50% inhibition with 0.275 μg/mL and 0.985 μg/mL ofE. arboreaandS. filiformis, resp.). Time of addition experiments and viral penetration assays suggest that best activities of these SPs occur at different stages of infection. The synergistic effect would allow reducing the treatment dose and toxicity and minimizing or delaying the induction of antiviral resistance; sulfated polysaccharides of the tested seaweed species thus appear as promising candidates for the development of natural antiviral agents.
Research on the Calibration Method of Micro Inertial Measurement Unit for Engineering Application
Authors: Xu Yun , Wang Yu , Su Yan , Zhu Xinhua
Published: June 2016

With rapid development of micro fabrication technology, the production level of micro inertial devices has increased, which promoted the performance improvement of Micro Inertial Measurement Unit (MIMU). Measurement precision of MIMU is one of the most significant indexes, especially for the application of the guided spinning projectiles. In order to improve the measurement precision of MIMU, this paper presents a novel calibration method. The calibration model is established and the derivation for parameters estimation has been introduced. By the multirate tests and multiposition tests, all the parameters in the calibration model can be well estimated. Verification experiment shows that the proposed method has the same compensation effect as the traditional method, but it can alleviate the computing burden for the system. Thus the proposed method will have a wide application prospect for the future engineering calibration.
Cardiac Effects of Thyrotropin Oversuppression with Levothyroxine in Young Women with Differentiated Thyroid Cancer
Authors: Hong Kyung-Soon , Son Jung-Woo , Ryu Ohk Hyun , Choi Moon-Gi , Hong Ji Yeon , Lee Seong Jin
Published: June 2016

Background. We investigated the cardiac effects of TSH (thyroid-stimulating hormone) oversuppression in women with thyroidectomized differentiated thyroid cancer (DTC) during levothyroxine suppression therapy.Methods. Fourteen young female patients with DTC were enrolled. The duration of TSH-suppressive therapy was 5 to 9 years. They satisfied the following criteria: (1) a serum level of TSH < 0.1 mU/L in the intermediate-risk or TSH < 0.3 mU/L in the low-recurrence-risk group and (2) having been receiving a fixed dose of LT4 before the study. Controls matched for age, sex, and body mass index (BMI) were compared in terms of the levels of serum free T4, free T3, TSH, plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and cardiac functions and structures.Results. DTC patients and control subjects were well matched in heart rate and blood pressure. There were marked differences in serum TSH (P=0.001) and free T4 (P=0.002). However, there were no differences between the groups in serum free T3 and plasma NT-pro-BNP. Furthermore, there were nonsignificant differences in cardiac functions and structures between the groups.Conclusions. This study shows that TSH suppression therapy in women with DTC may be safe with respect to cardiac functions and structures despite intermittent oversuppression of TSH during long-term suppressive therapy.Trial Registration. This trial is registered with clinicaltrials.gov identifierNCT02645786.
miR-214 and miR-148b Targeting Inhibits Dissemination of Melanoma and Breast Cancer
Authors: Orso Francesca , Quirico Lorena , Virga Federico , Penna Elisa , Dettori Daniela , Cimino Daniela , Coppo Roberto , Grassi Elena , Elia Angela Rita , Brusa Davide , Deaglio Silvia , Brizzi Maria Felice , Stadler Michael B. , Provero Paolo , Caselle Michele , Taverna Daniela
Published: June 2016

miR-214 and miR-148b have been proposed to antagonize the effects of each other in enabling or blocking metastasis, respectively. In this study, we provide evidence deepening their role and interrelationship in the process of metastatic dissemination. Depleting miR-214 or elevating miR-148b blocked the dissemination of melanoma or breast cancer cells, an effect that could be accentuated by dual alteration. Mechanistic investigations indicated that dual alteration suppressed passage of malignant cells through the blood vessel endothelium by reducing expression of the cell adhesion molecules ITGA5 and ALCAM. Notably, transendothelial migration in vitro and extravasation in vivo impaired by singly alternating miR-214 or miR-148b could be overridden by overexpression of ITGA5 or ALCAM in the same tumor cells. In clinical specimens of primary breast cancer or metastatic melanoma, we found a positive correlation between miR-214 and ITGA5 or ALCAM along with an inverse correlation of miR-214 and miR-148b in the same specimens. Our findings define an antagonistic relationship of miR-214 and miR-148b in determining the dissemination of cancer cells via tumor–endothelial cell interactions, with possible implications for microRNA-mediated therapeutic interventions aimed at blocking cancer extravasation. Cancer Res; 76(17); 5151–62. ©2016 AACR.
Tumor Suppressor HIPK2 Regulates Malignant Growth via Phosphorylation of Notch1
Authors: Ann Eun-Jung , Kim Mi-Yeon , Yoon Ji-Hye , Ahn Ji-Seon , Jo Eun-Hye , Lee Hye-Jin , Lee Hyun-Woo , Kang Hyeok-Gu , Choi Dong Wook , Chun Kyung-Hee , Lee Ji Shin , Choi Cheol Yong , Ferrando Adolfo A. , Lee Keesook , Park Hee-Sae
Published: June 2016

The receptor Notch1 plays an important role in malignant progression of many cancers, but its regulation is not fully understood. In this study, we report that the kinase HIPK2 is responsible for facilitating the Fbw7-dependent proteasomal degradation of Notch1 by phosphorylating its intracellular domain (Notch1-IC) within the Cdc4 phosphodegron motif. Notch1-IC expression was higher in cancer cells than normal cells. Under genotoxic stress, Notch1-IC was phosphorylated constitutively by HIPK2 and was maintained at a low level through proteasomal degradation. HIPK2 phosphorylated the residue T2512 in Notch1-IC. Somatic mutations near this residue rendered Notch1-IC resistant to degradation, as induced either by HIPK2 overexpression or adriamycin treatment. In revealing an important mechanism of Notch1 stability, the results of this study could offer a therapeutic strategy to block Notch1-dependent progression in many types of cancer. Cancer Res; 76(16); 4728–40. ©2016 AACR.
Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer
Authors: Hall Zoe , Ament Zsuzsanna , Wilson Catherine H. , Burkhart Deborah L. , Ashmore Tom , Koulman Albert , Littlewood Trevor , Evan Gerard I. , Griffin Julian L.
Published: June 2016

MYC-mediated pathogenesis in lung cancer continues to attract interest for new therapeutic strategies. In this study, we describe a transgenic mouse model of KRAS-driven lung adenocarcinoma that affords reversible activation of MYC, used here as a tool for lipidomic profiling of MYC-dependent lung tumors formed in this model. Advanced mass spectrometric imaging and surface analysis techniques were used to characterize the spatial and temporal changes in lipid composition in lung tissue. We found that normal lung tissue was characterized predominantly by saturated phosphatidylcholines and phosphatidylglycerols, which are major lipid components of pulmonary surfactant. In contrast, tumor tissues displayed an increase in phosphatidylinositols and arachidonate-containing phospholipids that can serve as signaling precursors. Deactivating MYC resulted in a rapid and dramatic decrease in arachidonic acid and its eicosanoid metabolites. In tumors with high levels of MYC, we found an increase in cytosolic phospholipase A2 (cPLA2) activity with a preferential release of membrane-bound arachidonic acid, stimulating the lipoxygenase (LOX) and COX pathways also amplified by MYC at the level of gene expression. Deactivating MYC lowered cPLA2 activity along with COX2 and 5-LOX mRNA levels. Notably, inhibiting the COX/5-LOX pathways in vivo reduced tumor burden in a manner associated with reduced cell proliferation. Taken together, our results show how MYC drives the production of specific eicosanoids critical for lung cancer cell survival and proliferation, with possible implications for the use of COX and LOX pathway inhibitors for lung cancer therapy. Cancer Res; 76(16); 4608–18. ©2016 AACR.
Eritoran Suppresses Colon Cancer by Altering a Functional Balance in Toll-like Receptors That Bind Lipopolysaccharide
Authors: Kuo Wei-Ting , Lee Tsung-Chun , Yu Linda Chia-Hui
Published: June 2016

Colorectal carcinogenesis is affected by overexpression of the lipopolysaccharide (LPS) receptors CD14 and TLR4, which antagonize each other by affecting epithelial cell proliferation and apoptosis. Eritoran is an investigational drug for sepsis treatment that resembles the lipid A moiety of LPS and therefore acts as a TLR4 inhibitor. In the present study, we explored the potential therapeutic uses and mechanisms of action of eritoran in reducing colon cancer progression. Eritoran administration via intracolonic, intragastric, or intravenous routes significantly reduced tumor burden in a chemically induced mouse model of colorectal carcinoma. Decreased proliferation and increased apoptosis were observed in mouse tumor cells after eritoran treatment. In vitro cultures of mouse primary tumor spheroids and human cancer cell lines displayed increased cell proliferation and cell-cycle progression following LPS challenge. This effect was inhibited by eritoran and by silencing CD14 or TLR4. In contrast, apoptosis induced by eritoran was eliminated by silencing CD14 or protein kinase Cζ (PKCζ) but not TLR4. Lastly, LPS and eritoran caused hyperphosphorylation of PKCζ in a CD14-dependent and TLR4-independent manner. Blocking PKCζ activation by a Src kinase inhibitor and a PKCζ-pseudosubstrate prevented eritoran-induced apoptosis. In summary, our work offers a preclinical proof of concept for the exploration of eritoran as a clinical treatment, with a mechanistic rationale to reposition this drug to improve the management of colorectal cancer. Cancer Res; 76(16); 4684–95. ©2016 AACR.
Eosinophilic Esophagitis: Impact of Latest Insights Into Pathophysiology on Therapeutic Strategies
Authors: Schoepfer Alain , Safroneeva Ekaterina , Straumann Alex
Published: June 2016

Eosinophilic esophagitis (EoE) has been defined as a ‘chronic, immune/antigen-mediated, esophageal disease, characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation'. A peak value of ≥15 eosinophils/high power field has been defined as histologic diagnostic cutoff. Other conditions associated with esophageal eosinophilia, such as gastro-esophageal reflux disease, PPI-responsive esophageal eosinophilia or Crohn's disease, need to be ruled out before EoE can be diagnosed. Males are affected more frequently than females and most of the patients have concomitant allergies. Currently, the EoE prevalence is about 1 of 2,000 inhabitants in Westernized countries. The first EoE patients were described only 2 decades ago. Despite this short period, considerable progress has been made regarding the understanding of the pathophysiology, natural history, assessment of disease activity and with respect to evaluating different therapeutic options. Untreated EoE can lead to esophageal remodeling with reduced compliance and stricture formation, which represents the main risk factor for food bolus impactions. The therapeutic options can be summarized with the 3 D's, which stand for drugs, diets and dilation. Of note, as of yet, there is no EoE-specific drug that has been approved by regulatory authorities. This is, among other reasons, related to the lack of validated outcome measurement instruments until recently. Swallowed topical steroids such as budesonide or fluticasone represent the standard of care for treating symptomatic pediatric and adult EoE patients with inflammatory activity. Several trials have already evaluated different biologic therapies, such as anti-interleukin-5 or anti-IgE. Further studies are on the way. As a non-pharmacologic alternative, different dietary regimens exist. Dilation can offer long-lasting symptomatic response in case of stricturing EoE but does not have any impact on the underlying inflammation. This review highlights the latest insights regarding pathophysiology and its impact regarding current and future therapeutic strategies.
Endoscopic Resection and Radiofrequency Ablation for Early Esophageal Neoplasia
Authors: Belghazi Kamar , Bergman Jacques , Pouw Roos E.
Published: June 2016

Background: In the last few decades, endoscopic treatment of early neoplastic lesions in the esophagus has established itself as a valid and less invasive alternative to surgical resection. Endoscopic resection (ER) is the cornerstone of endoscopic therapy. Next to the curative potential of ER, by removing neoplastic lesions, ER may also serve as a diagnostic tool. The relatively large tissue specimens obtained with ER enable accurate histological staging of a lesion, allowing for optimal decision-making for further patient management. ER was pioneered in Japan, mainly for the resection of gastric lesions and squamous esophageal neoplasia, and also Western countries have been increasingly implementing ER in the treatment of early gastroesophageal neoplasia, mostly associated with Barrett's esophagus (BE). In BE, however, there is still a risk of metachronous lesions in the remainder of the Barrett's after focal ER. Additional treatment of all Barrett's mucosa is therefore advised. Currently, the most effective method for this is by using radiofrequency ablation (RFA). This review will provide an overview of indications for ER and RFA. Key Messages and Conclusions: Endoscopic management of early esophageal neoplasia is a safe and valid alternative to surgery and is nowadays the treatment of choice. ER is the mainstay of endoscopic management of early esophageal neoplasia since it allows for removal of neoplastic lesions and provides a large tissue specimen for histological evaluation. In case of early neoplasia in BE, focal ER should be complemented by eradication of the remaining Barrett's mucosa. RFA has proven to be a safe and effective modality to achieve complete eradication of Barrett's mucosa.
From Reflux Esophagitis to Esophageal Adenocarcinoma
Authors: Souza Rhonda F.
Published: June 2016

Reflux esophagitis causes Barrett's metaplasia, an abnormal esophageal mucosa predisposed to adenocarcinoma. Medical therapy for reflux esophagitis focuses on decreasing gastric acid production with proton pump inhibitors. We have reported that reflux esophagitis in a rat model develops from a cytokine-mediated inflammatory injury, not from a caustic chemical (acid) injury. In this model, refluxed acid and bile stimulate the release of inflammatory cytokines from esophageal squamous cells, recruiting lymphocytes first to the submucosa and later to the luminal surface. Emerging studies on acute reflux esophagitis in humans support this new concept, suggesting that reflux-induced cytokine release may be a future target for medical therapies. Sometimes, reflux esophagitis heals with Barrett's metaplasia, a process facilitated by reflux-related nitric oxide (NO) production and Sonic Hedgehog (Hh) secretion by squamous cells. We have shown that NO reduces expression of genes that promote a squamous cell phenotype, while Hh signaling induces genes that mediate the development of the columnar cell phenotypes of Barrett's metaplasia. Agents targeting esophageal NO production or Hh signaling conceivably could prevent the development of Barrett's esophagus. Persistent reflux promotes cancer in Barrett's metaplasia. We have reported that acid and bile salts induce DNA damage in Barrett's cells. Bile salts also cause NF-κB activation in Barrett's cells, enabling them to resist apoptosis in the setting of DNA damage and likely contributing to carcinogenesis. Oral treatment with ursodeoxycholic acid prevents the esophageal DNA damage and NF-κB activation induced by toxic bile acids. Altering bile acid composition might be another approach to cancer prevention.
Failed Eradication for Helicobacter pylori. What Should Be Done?
Authors: Mégraud Francis
Published: June 2016

Failed eradication of Helicobacter pylori occurs when the antibiotic concentration at the site where H. pylori is located is lower than the minimal inhibitory concentration of the antibiotic for this bacterium. The main reason for this is the acquisition of resistance; and in the context of the most common treatment, the main reason is the acquisition of resistance to clarithromycin. Several options can then be followed. The most rational option is to use a tailored therapy, that is, to look for clarithromycin resistance either by culture plus antibiogram or by a molecular method. The standard triple therapy is used only in the case of clarithromycin susceptibility. In case of resistance or if an empiric treatment must be given, a good option is to use a bismuth-based quadruple therapy. If unavailable, clarithromycin-based quadruple therapies can be used either as sequential or ‘concomitant' or hybrid. The limit, especially for concomitant therapy, is the use of clarithromycin, which will be inactive in about 2/3 of the cases, adding to cost and adverse events. Recently, the dual therapy proton pump inhibitor-amoxicillin has been revisited especially in the Far East, and increasing the dose and the frequency of administration gives excellent results.
Development of Pancreatic Cancer: Targets for Early Detection and Treatment
Authors: Lerch Markus M. , Mayerle Julia , Mahajan Ujjwal , Sendler Matthias , Weiss F. Ulrich , Aghdassi Ali , Moskwa Patryk , Simon Peter
Published: June 2016

Background: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer death worldwide and compared to other malignancies its share in cancer mortality is expected to rise further. This is due to a lack of sensitive diagnostic tools that would permit earlier detection in a potentially curable stage and the very slow progress in finding effective drug treatments for pancreatic cancer. Key Messages: Aside from genetic predispositions and environmental agents, chronic pancreatitis is by far the greatest risk factor for PDAC. It also shares several etiological factors with pancreatic cancer and represents its most challenging differential diagnosis. Biomarkers that can distinguish between chronic pancreatitis and PDAC may therefore be suitable for the latter's early detection. Moreover, targeting the natural history of chronic pancreatitis would be one approach to prevent PDAC. Targeting tumor-cell signaling directly by interfering with receptor tyrosine kinases has shown some efficacy, although the results in clinical trials were less encouraging than for other cancers. Other compounds developed have targeted the formation of extracellular matrix around the tumor, the proteolytic activity in the tumor environment, histone deacetylases, hedgehog signaling and heat shock proteins, but none has yet found its way into routine patient care. Attempts to individualize treatment according to the tumor's somatic mutation profile are novel but so far impractical. Conclusions: Progress in the treatment of pancreatic cancer has been exceedingly slow and mostly dependent on improved pharmaceutical preparations or combinations of established chemotherapeutic agents. The promise of major breakthroughs implied in targeting tumor signal transduction events has so far not materialized.
Modern Management of Irritable Bowel Syndrome: More Than Motility
Authors: Tack Jan , Vanuytsel Tim , Corsetti Maura
Published: June 2016

In the treatment of irritable bowel syndrome (IBS), loperamide seems efficacious for diarrhea and ispaghula for constipation, while musculotropic spasmolytics may relieve abdominal pain. Antidepressants were found to be efficacious for abdominal pain, but their tolerance may be problematic and the therapeutic effect varied largely between trials. While meta-analyses suggest efficacy of probiotics as a group, the quality of the trials is often suboptimal and there is large variability. Lubiprostone, a chloride channel activator, and linaclotide, a guanylyl cyclase-C agonist, showed favorable effects on multiple symptoms in IBS with constipation. For IBS with diarrhea (IBS-D), the 5-HT3 receptor antagonist ramosetron showed efficacy in men and women, but is currently only approved in Japan. A multicenter study with the anti-emetic 5-HT3 receptor antagonist ondansetron showed efficacy on stool pattern in IBS-D. The poorly absorbable antibiotic rifaximin and eluxadoline, a mu opioid receptor agonist and delta antagonist, both showed efficacy in phase III trials in IBS-D and were approved by the FDA. Eluxadoline was associated with increased occurrence of sphincter of Oddi spasm and biliary pancreatitis. The non-pharmacological treatment of IBS, with dietary interventions (mainly gluten elimination and low FODMAP (fructose, oligo-, di-, monosaccharides and polyols)) has received a lot of attention lately. While responder rates vary across studies, perhaps based on regional variations in dietary intake of FODMAPs, the dietary approach seems to have acquired recognition as a valid therapeutic alternative. Long-term studies and comparative studies with pharmacotherapy, as well as elucidation of the underlying mechanisms of action, are needed.
Protein-DNA Interactions at the Opossum Npt2a Promoter are Dependent upon NHERF-1
Authors: Clark Barbara J. , Murray Rebecca D. , Salyer Sarah A. , Tyagi Samuel C. , Arumugam Cibi , Khundmiri Syed J. , Lederer Eleanor D.
Published: June 2016

Background/Aims: Phosphate homeostasis is controlled by the renal reabsorption of Pi by the type IIa sodium phosphate cotransporter, Npt2a, which is localized in the proximal tubule brush border membrane. Regulation of Npt2a expression is a key control point to maintain phosphate homeostasis with most studies focused on regulating protein levels in the brush border membrane. Molecular mechanisms that control Npt2a mRNA, however, remain to be defined. We have reported that Npt2a mRNA and protein levels correlate directly with the expression of the Na+/H+ exchanger regulatory factor 1 (NHERF-1) using opossum kidney (OK) cells and the NHERF-1-deficient OK-H cells. The goal of this study was to determine whether NHERF-1 contributes to transcriptional and/or post-transcriptional mechanisms controlling Npt2a mRNA levels. Methods: Npt2a mRNA half-life was compared between OK and NHERF-1 deficient OK-H cell lines. oNpt2a promoter-reporter gene assays and electrophoretic mobility shift assays (EMSA) were used identify a NHERF-1 responsive region within the oNpt2a proximal promoter. Results: Npt2a mRNA half-life is the same in OK and OK-H cells. The NHERF-1 responsive region lies within the proximal promoter in a region that contains a highly conserved CAATT box and G-rich element. Specific protein-DNA complex formation with the CAATT element is altered by the absence of NHERF-1 (OK v OK-H EMSA) although NHERF-1 does not directly contribute to complex formation. Conclusion: NHERF-1 helps maintain steady-state Npt2a mRNA levels in OK cells through indirect mechanisms that help promote protein-DNA interactions at the Npt2a proximal promoter.
Amlodipine and Atorvastatin Improved Hypertensive Cardiac Remodeling through Regulation of MMPs/TIMPs in SHR Rats
Authors: Lu Jingchao , Hao Jie , Du Hong , Xiao Bing , Li Yue , Yang Xiuchun , Cui Wei
Published: June 2016

Background: MMPs/TIMPs system is well known to play important roles in pressure overload-induced cardiac remodeling, and Amlodipine and Atorvastatin have been showed to exert favourable protective effects on cardiovascular disease, however, it is not clear whether Amlodipine and Atorvastatin can improve hypertensive cardiac remodeling and whether the MMPs/TIMPs system is involved. The present study aims to answer these questions. Methods: 36 weeks old male spontaneous hypertension (SHR) rats were randomly divided into four groups: 1). SHR control group, 2). Amlodipine alone (10 mg/kg/d) group, 3). Atorvastatin alone (10 mg/kg/d) group, 4).Combination of Amlodipine and Atorvastatin (10 mg/kg/d for each) group. Same gender, weight and age of Wistar-Kyoto (WKY) rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The blood pressure and left ventricle mass index were measured. Enzyme activity of MMP-2 and MMP-9 was assessed with Gelatin zymography. MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA and protein expression was studied by RT-PCR and Western blot. Single factor ANOVA and LSD-t test were used in statistical analysis. Results: Treatment with Amlodipine alone or combination with atorvastatin significantly decreased blood pressure, left ventricle mass index in SHR rats (P < 0.05 for both). Compared with WKY rats, the myocardial levels of MMP-2, MMP-9 mRNA, protein and enzyme activity were significantly increased (P<0.05). Amlodipine alone, Atorvastatin alone, and combination of the two all reduced MMP-2 and MMP-9 mRNA, protein and enzyme activity, with the best effects seen in the combination. Compared with WKY rats, the myocardial levels of TIMP-1 mRNA and protein were significantly increased (P<0.05), however, there was no difference in levels of TIMP-2. Neither Amlodipine alone, Atorvastatin alone, nor combination of the two drugs significantly affect the expression of TIMP-1 or TIMP-2. Conclusion: Amlodipine and Atorvastatin could improve ventricular remodeling in SHR rats through intervention with the imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 system.
Upregulation of Periostin Prevents High Glucose-Induced Mitochondrial Apoptosis in Human Umbilical Vein Endothelial Cells via Activation of Nrf2/HO-1 Signaling
Authors: Zhong Zhi-ying , Tang Yu
Published: June 2016

Background/Aims: High glucose-induced oxidative damage to endothelial cells plays a central role in the pathogenesis of diabetic vascular complications. This study was undertaken to explore the role of periostin in high glucose-induced endothelial cell apoptosis and associated molecular mechanisms. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (33.3 mmol/L) and examined for the expression of periostin. The effects of periostin upregulation on high glucose-induced apoptosis, mitochondrial dysfunction, and reactive oxygen species (ROS) production were determined. The activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) by periostin was checked. HO-1 knockdown experiments were done to confirm its role in the action of periostin in high glucose-exposed HUVECs. Results: High glucose significantly upregulated the expression of periostin in HUVECs. Enforced expression of periostin attenuated high glucose-induced apoptosis in HUVECs, as determined by TUNEL staining and caspase-3 activity assay. Periostin overexpression prevented loss of Δψm, release of mitochondrial cytochrome c, and dysregulation of Bcl-2 and Bax in high glucose-exposed HUVECs. Periostin upregulation suppressed high glucose-induced ROS generation and activated the Nrf2/HO-1 signaling. HO-1 silencing restored high glucose-induced ROS generation and apoptotic response in periostin-overexpressing HUVECs. Conclusion: Periostin mitigates high glucose-induced mitochondrial apoptosis in endothelial cells, via activation of Nrf2/HO-1 signaling and reduction of ROS formation. Further studies are warranted to explore the therapeutic potential of periostin in diabetic vascular complications.
Modified Hand-Assisted Retroperitoneoscopic Living Donor Nephrectomy with a Mini-Open Muscle Splitting Gibson Incision
Authors: Zhu Yi-Chen , Lin Jun , Guo Yu-Wen , Zhang Lei , Zhu Xi , Tian Ye
Published: June 2016

Background: We aimed to confirm the advantages of a modified hand-assisted retroperitoneoscopic living donor nephrectomy (HARPLDN) compared to the performance of standard retroperitoneoscopic living donor nephrectomy (RPLDN). Methods: One hundred twenty-eight consecutive surgical cases were categorized into 2 groups, one receiving standard RPLDN (group 1) and one receiving modified HARPLDN (group 2). Perioperative factors of both groups were evaluated retrospectively, including donors' demographics, overall operating time, warm ischemia time (WIT), graft vessel length, blood loss, complications, pain visual analogue scale (VAS) scores, hospital stay, and matched recipients' perioperative outcomes. One-year follow-up data were also examined. Results: The standard RPLDN group (n = 44) and modified HARPLDN group (n = 84) had comparable age, gender, and body mass index. The RPLDN group donors had longer operative time, shorter vein length and longer WIT than the modified HARPLDN (all p < 0.001). RPLDN had higher VAS scores (p < 0.001), longer carminative time (p = 0.002) and higher morphine requirement (p = 0.039) than the modified HARPLDN. No complications occurred in either group. All recipients and grafts had survived at 1-year follow-up. Conclusion: The modified HARPLDN technique is safe and effective for living donor nephrectomy and has shorter operating time, shorter WIT and better pain control. Further study is required to evaluate donors' long-term quality of life and recipients' long-term outcomes.
Topical Corticosteroid Concerns in Dermatological Outpatients: A Cross-Sectional and Interventional Study
Authors: Müller Simon M. , Tomaschett Dominique , Euler Sebastian , Vogt Deborah R. , Herzog Lisa , Itin Peter
Published: June 2016

Background/Aims: Topical corticosteroid concerns (TCC) are an important issue in patients with atopic dermatitis, leading to non-adherence with poor disease control and increased health care costs. However, neither the prevalence of TCC in a more comprehensible dermatological population nor the impact of patient information on topical corticosteroids given by clinicians is known. Therefore, we assessed the prevalence, characteristics, and sources of TCC in a dermatological population and the impact of written and oral patient information on TCC. Methods: A total of 643 outpatients with various skin diseases answered a 12-item questionnaire while waiting for the doctor's visit. Patients with TCC quantified their concerns on a discrete visual analogue scale before and after patient information, which consisted of written and oral information about topical corticosteroids (TCS) given by dermatologists. Results: The prevalence of TCC was 41.5%, and that of TCC-related non-adherence was 28.3%. TCC was positively associated with age <60 years, female gender, use of complementary and alternative medicine (CAM) and non-physician health care profession. The leading concerns were skin atrophy, systemic effects, and impairment of the immune system. The most frequent sources of TCC were negative reports by media, family, or friends. Both written and oral patient information significantly reduced TCC. The number needed to benefit from patient information was approximately 2. Non-responders were more often female, TCS-inexperienced, and users of CAM with an intermediate level of education. Conclusions: TCC are highly prevalent in dermatological patients. Patient information may lower TCC in almost every second patient.
Implementation of the German Mammography Screening Program (German MSP) and First Results for Initial Examinations, 2005-2009
Authors: Malek Daniela , Kääb-Sanyal Vanessa
Published: June 2016

Background: The German Mammography Screening Program (German MSP) is population-based and intended for women aged 50-69 years (approximately 10.5 million). The program started in 2005 and was implemented within 5 years. This article describes the implementation, structure, and screening process, and presents the results of initial examinations for the prevalence phase. Methods: Data were collected annually from invitation centers (invitation, attendance), screening units (performance, outcomes), and cancer registries (incidence). Results: In 2009, 92% of all annually eligible women were invited; 50% of the annually eligible population participated. The total cancer detection rate in the period of 2005-2009 was 8.1/1,000; the corresponding recall rate was 5.9%. 19.6% of detected cancers were ductal carcinoma in situ; 76.7% of invasive cancers were ≤ 20 mm in size, 30.2% were ≤ 10 mm, and 75.3% were node-negative. During the implementation period, incidence increased by 37 and 56% in the old and new federal states, respectively. Incidence rates decreased following the prevalence phase. Conclusion: The German MSP was successfully implemented. The results of the prevalence phase meet the target values of the European guidelines. Proper functioning of the program is also verified by its effects on breast cancer incidence. To draw reliable conclusions regarding the long-term effects of the program, results from the routine screening rounds have to be awaited.
Equestrian-Related Traumatic Brain Injury in the Pediatric Population
Authors: Nguyen Ha Son , Lew Sean
Published: June 2016

Background: Equestrian activities can be undertaken for competition or leisure. Accidents can lead to bodily injuries. In particular, traumatic brain injury (TBI) can be devastating. Limited data exist regarding the pediatric population with respect to patterns of injury and related neurosurgical intervention. Methods: We retrospectively reviewed data for all pediatric patients diagnosed with equestrian-related injuries with neurological injuries from 2005 through June 2015. Results: Nine patients (1 male and 8 females) had neurological injuries. Their mean age was 10.4 years (range 2.9-16.8 years). Intracranial pathologies ranged from small punctate hemorrhages to large surgical extra-axial hematomas. Five patients also had concurrent skull fractures; 2 exhibited open lesions. Two patients required a decompressive craniotomy with placement of an external ventricular drain. Three patients exhibited other minor injuries; none had thoracic/abdominal/pelvic injuries. At discharge, all had good recovery; 1 patient who had a craniotomy did have a persistent right third-nerve palsy. Conclusion: Equestrian activities can present with dangerous and unpredictable situations, which can lead to profound neurological injury. Caution should be observed for all involved members, as both riders and nonriders are susceptible to harm. Protective gear (such as helmets), adequate training, and extensive experience are encouraged.
Comparison of Two Different Methods Used for Semen Evaluation: Analysis of Semen Samples from 1,055 Men
Authors: Dinçer Murat , Kucukdurmaz Faruk , Salabas Emre , Ortac Mazhar , Aktan Gulsan , Kadioglu Ates
Published: June 2016

The aim of this study was to evaluate whether there is a difference between gravimetrically and volumetrically measured semen samples and to assess the impact of semen volume, density, and sperm count on the discrepancy between gravimetric and volumetric methods. This study was designed in an andrology laboratory setting and performed on semen samples of 1,055 men receiving infertility treatment. Semen volume was calculated by gravimetric and volumetric methods. The total sperm count, semen density and sperm viability were also examined according to recent version of World Health Organization manual. The median values for gravimetric and volumetric measurements were 3.44 g and 2.96 ml respectively. The numeric difference in semen volume between 2 methods was 0.48. The mean density of samples was 1.01 ± 0.46 g/ml (range 0.90-2.0 g/ml). The numeric difference between 2 methods gets higher as semen volume increases (p < 0.001). Gravimetric and volumetric semen volume measurements were strongly correlated for all samples and for each subgroup of semen volume, semen density and sperm count, with minimum correlation coefficient of 0.895 (p < 0.001). In conclusion, the gravimetric measurement provides higher results than volumetric one and numeric differences between 2 methods increase as semen volume increases. However, further studies are needed to offer the use of gravimetrical method, which was thought to minimize laboratory errors, particularly for a high amount of semen samples.
MicroRNAs in Pathogenesis of Acute Kidney Injury
Authors: Liu Zhiwen , Wang Shixuan , Mi Qing-Sheng , Dong Zheng
Published: June 2016

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression mainly by repressing their target gene translation. A large spectrum of human diseases is associated with significant changes in miRNAs. Many miRNAs are induced in diseases, whereas some others are downregulated. The significance of miRNAs has been demonstrated in renal development and physiology, and in major kidney diseases such as acute kidney injury (AKI). Recent studies have further implicated specific miRNAs in the pathogenesis of AKI. miRNAs also have the potential to become new diagnostic biomarkers of AKI. Further investigation will identify the key pathogenic miRNAs in various types of AKI and test miRNA-based therapeutics and diagnosis.
Berücksichtigung von Wechsel- und Nebenwirkungen bei pflanzlichen Arzneimitteln in deutschen S3-Leitlinien der AWMF
Authors: Klose Petra , Kraft Karin , Lauche Romy , Cramer Holger , Dobos Gustav , Langhorst Jost
Published: June 2016

Pflanzliche Arzneimittel haben in der medizinischen Versorgung im deutschsprachigen Raum eine lange Tradition, werden aber bei der Erstellung medizinischer Leitlinien selten berücksichtigt. In einer Vorstudie wurde von unserer Arbeitsgruppe aufgearbeitet, in welchem Ausmaß sie in den aktuellen interdisziplinär, evidenz- und konsensusbasiert erstellten S3-Leitlinien der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) Beachtung gefunden haben. Ziel der jetzigen Studie war es, zu analysieren, inwieweit Neben- bzw. Wechselwirkungen von pflanzlichen Arzneimitteln in diesen S3-Leitlinien diskutiert werden. Im Januar 2015 wurden 134 S3-Leitlinien gezählt und analysiert. 27,6% (n = 37) weisen insgesamt 194 Statements unter dem Begriff «Phytotherapie» auf. Hinweise zu Neben- und Wechselwirkungen finden sich in 28,4% der Statements (n = 55), die bei 13,9% (n = 27) durch Literatur belegt werden. 14 dieser Statements betreffen Nahrungsergänzungsmittel und Ähnliches, 11 sind pauschale Aussagen zur Phytotherapie, 7 fassen mindestens 2 Arzneipflanzen pauschal zusammen. Damit weisen nur 23 Statements auf Neben- bzw. Wechselwirkungen von einzelnen Arzneipflanzen hin, 14 davon sind mit Literaturstellen belegt. Diese Ergebnisse entsprechen bei Weitem nicht den geforderten Standards der AWMF. Dafür verantwortlich sind insbesondere unpräzise Begrifflichkeiten sowie eine unzureichende Systematik bei der Suche nach wissenschaftlicher Evidenz für die Unbedenklichkeit von Arzneipflanzen-Zubereitungen. Die Gesellschaft für Phytotherapie kann hier einen wichtigen Beitrag zur Qualitätsverbesserung leisten.
Phenotyping Adults with Non-Cystic Fibrosis Bronchiectasis: A 10-Year Cohort Study in a French Regional University Hospital Center
Authors: Buscot Matthieu , Pottier Héloïse , Marquette Charles-Hugo , Leroy Sylvie
Published: June 2016

Background: Data concerning phenotypes in bronchiectasis are scarce. Objective: The aim of this study was to describe the clinical, functional and microbiological phenotypes of patients with bronchiectasis. Methods: A monocentric retrospective study in a university hospital in France was conducted over 10 years (2002-2012). Non-cystic fibrosis patients with tomographic confirmation of bronchiectasis were included. The clinical, functional and microbiological data of patients were analyzed relying on the underlying etiology. Results: Of the 311 included patients, an etiology was found for 245 of them. At the time of diagnosis, the median age was 61 years and the mean FEV1 was 63% of predicted. The main causes of bronchiectasis were post-infectious (50%, mostly related to tuberculosis), chronic obstructive pulmonary disease (COPD; 13%) and idiopathic (11%). Other causes were immune deficiency (6%), asthma (4%), autoimmunity (3%), tumor (2%) and other causes (4%). The comparison of phenotypic traits shows significant differences between COPD, congenital and idiopathic groups in term of sex (p = 0.0175), tobacco status (p < 0.0001), FEV1 (p = 0.0412) and age at diagnosis (p < 0.001), Pseudomonas aeruginosa (PA) colonization (p = 0.0276) and lobectomy (0.0093). Functional follow-up was available in 30% of patients with a median duration of 2.7 years. Presence of PA was associated with a lower median FEV1 at diagnosis (43% p < 0.003) but not with a faster rate of decline in FEV1. Conclusion: Distinctive clinical, functional and microbiological features were found for idiopathic, congenital and COPD-related bronchiectasis. A prospective follow-up of these subgroups is necessary to validate their relevance in the management of bacterial colonization and specific complications of these bronchiectases.