bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Cardiovascular Tissue Components for the Diagnosis of Coronary Vulnerable Plaque from Intravascular Ultrasound Images
Authors: Lee Ju Hwan , Hwang Yoo Na , Kim Ga Young , Shin Eun Seok , Kim Sung Min
Published: February 2017

The purpose of this study was to characterize cardiovascular tissue components and analyze the different tissue properties for predicting coronary vulnerable plaque from intravascular ultrasound (IVUS) images. For this purpose, sequential IVUS image frames were obtained from human coronary arteries using 20 MHz catheters. The plaque regions between the intima and media-adventitial borders were manually segmented in all IVUS images. Tissue components of the plaque regions were classified into having fibrous tissue (FT), fibrofatty tissue (FFT), necrotic core (NC), or dense calcium (DC). The media area and lumen diameter were also estimated simultaneously. In addition, the external elastic membrane (EEM) was computed to predict the vulnerable plaque after the tissue characterization. The reliability of manual segmentation was validated in terms of inter- and intraobserver agreements. The quantitative results found that the FT and the media as well as the NC would be good indicators for predicting vulnerable plaques in IVUS images. In addition, the lumen was not suitable for early diagnosis of vulnerable plaque because of the low significance compared to the other vessel parameters. To predict vulnerable plaque rupture, future study should have additional experiments using various tissue components, such as the EEM, FT, NC, and media.
An Integrated Approach Identifies Mediators of Local Recurrence in Head and Neck Squamous Carcinoma
Authors: Citron Francesca , Armenia Joshua , Franchin Giovanni , Polesel Jerry , Talamini Renato , D'Andrea Sara , Sulfaro Sandro , Croce Carlo M. , Klement William , Otasek David , Pastrello Chiara , Tokar Tomas , Jurisica Igor , French Deborah , Bomben Riccardo , Vaccher Emanuela , Serraino Diego , Belletti Barbara , Vecchione Andrea , Barzan Luigi , Baldassarre Gustavo
Published: February 2017

Purpose: Head and neck squamous cell carcinomas (HNSCCs) cause more than 300,000 deaths worldwide each year. Locoregional and distant recurrences represent worse prognostic events and accepted surrogate markers of patients' overall survival. No valid biomarker and salvage therapy exist to identify and treat patients at high-risk of recurrence. We aimed to verify if selected miRNAs could be used as biomarkers of recurrence in HNSCC.

Experimental Design: A NanoString array was used to identify miRNAs associated with locoregional recurrence in 44 patients with HNSCC. Bioinformatic approaches validated the signature and identified potential miRNA targets. Validation experiments were performed using an independent cohort of primary HNSCC samples and a panel of HNSCC cell lines. In vivo experiments validated the in vitro results.

Results: Our data identified a four-miRNA signature that classified HNSCC patients at high- or low-risk of recurrence. These miRNAs collectively impinge on the epithelial–mesenchymal transition process. In silico and wet lab approaches showed that miR-9, expressed at high levels in recurrent HNSCC, targets SASH1 and KRT13, whereas miR-1, miR-133, and miR-150, expressed at low levels in recurrent HNSCC, collectively target SP1 and TGFβ pathways. A six-gene signature comprising these targets identified patients at high risk of recurrences, as well. Combined pharmacological inhibition of SP1 and TGFβ pathways induced HNSCC cell death and, when timely administered, prevented recurrence formation in a preclinical model of HNSCC recurrence.

Conclusions: By integrating different experimental approaches and competences, we identified critical mediators of recurrence formation in HNSCC that may merit to be considered for future clinical development. Clin Cancer Res; 23(14); 3769–80. ©2017 AACR.
Improvement of a ‘Leaky' Intestinal Barrier
Authors: Stange Eduard F.
Published: February 2017

In Crohn's disease, the mucus layer appears to be defective in terms of low defensin levels and lack of antibacterial activity. These deficiencies actually explain the Montreal phenotypes and the stable localization of disease in the terminal ileum with low α-defensins from Paneth cells and/or low β-defensins in colonic disease, respectively. Conversely, in ulcerative colitis (UC) the defensin production is normal or even induced, but the mucus layer is thinner and patchy, more in the liquid form and also chemically altered so that antibacterial peptides are not retained and lost into the luminal bacterial bulk. Therefore, both barrier problems allow slow bacterial attachment and invasion, ultimately triggering the massive response of adaptive immunity and tissue destruction. Therefore, leakiness should refer to the antibacterial barrier and not to the general barrier against small molecules, such as mannitol or lactulose, which are not antigenic. The most promising approach in UC seems to be the use of probiotics or the natural compound lecithin as a stabilizer of mucus structure to enhance the barrier. While a phase II study has yielded positive results, the results of the ongoing phase III study are eagerly awaited. It is quite possible that the protective effect of smoking in UC is related to mucus production in the colon also, but this is not an option. Another alternative would be to shift cell differentiation in the colon towards goblet cell; the relevant differentiation factors are known. In Crohn's disease, the direct oral application of defensins might be effective if release and binding to the mucus are achieved. In the experimental colitis model, this works quite well. In conclusion, in a situation where enthusiasm about so-called biologics is declining due to loss of response over time, searching for the primary defects in inflammatory bowel disease and treating them may well be worthwhile, although it is unlikely to provide rapid relief.
Real-Life Efficacy, Immunogenicity and Safety of Biosimilar Infliximab
Authors: Vegh Zsuzsanna , Kurti Zsuzsanna , Lakatos Peter L.
Published: February 2017

Recently, the use of biosimilar infliximab (IFX) in the treatment of inflammatory bowel diseases has become widespread in some European and non-European countries. Data on the efficacy, safety and immunogenicity from real-life cohorts are accumulating. The first reports showed similar outcomes in the induction and maintenance of remission, mucosal healing, safety and immunogenicity profile to the originator IFX. In the present review, we aimed to summarize the existing knowledge on the efficacy, safety and immunogenicity profile of biosimilar IFX reported from real-life cohorts.
Prognostic Value of the Delivery Dialysis Dose on Twice-Weekly Hemodialysis Patients
Authors: Fan Qichen , Yan Yucheng , Gu Leyi , He Liqun , Chen Nan , Jiang Gengru , Yuan Li , Xue Jun , Zhang Yun , Ma Jun , Jin Huimin , Yuan Weijie , Guo Zhiyong , Guo Lili , Wang Niansong , Zhang Wei , Ye Zhibin , Mao Peiju , Pi Xiaoling , Lu Renhua , Zhu Mingli , Zhang Weiming , Ni Zhaohui , Qian Jiaqi , Pang Huihua
Published: February 2017

Background: Few studies have evaluated the prognostic value of dialysis dose in twice-weekly hemodialysis (HD). A single-pool Kt/V (spKt/V) over 1.70 may benefit patients receiving twice-weekly maintenance HD. Methods: This is a multicenter randomized controlled trial performed on 163 patients from 17 dialysis centers in Shanghai who were allocated to high- (n = 98) and standard-dose groups (n = 65) and followed through 96 weeks of study period. Therapeutic approaches were given to increase spKt/V to over 1.70 in the high-dose group. Data were collected every 12-24 weeks. The primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACEs) occurrence, and secondary outcomes included residual kidney function (RKF) and health-related quality of life (HR-QOL). Results: The spKt/V in high-dose and standard-dose groups were 1.80 ± 0.23 and 1.55 ± 0.19, respectively, after an 8-week intervention (p < 0.001). At the end of the study, SF-36 physical function and total score in high-dose group were 82 (69-90) and 74 (47-84), respectively, both of which were higher than those in the standard-dose group. Decline in urine volume was observed in both groups with no significant difference (p = 0.431). No difference was found in overall survival between the 2 groups (p = 0.580). The 1-year MACE-free survival for high-dose group was 84.49%, better than 76.72% for standard-dose group (p = 0.029). Conclusions: Higher spKt/V is also associated with MACE-free survival and better HR-QOL, especially in physical function aspect for twice-weekly dialysis patients. Increasing spKt/V over 1.70 in twice-weekly HD population does not cause loss of RKF.
Ein beidseitig ausgeprägtes Embryotoxon posterius und eine neonatale Cholestase sind charakteristische Befunde beim Alagille-Syndrom
Authors: Lorenz Birgit
Published: February 2017

Hintergrund: Das Alagille-Syndrom ist eine autosomal-dominante Erkrankung, die durch neonatale Cholestase, typische Facies und kardiale Anomalien gekennzeichnet ist. Charakteristische okuläre Anomalien sind Embryotoxon posterius, Irisstroma-Hypoplasie mit Mosaikmuster, Mikrocornea, papilläre Drusen und Retinopathia pigmentosa. Wir legen hier den zweiten Bericht zur okulären Pathologie in zwei Fällen des Alagille-Syndroms vor. Methoden: Makroskopische und histologische Untersuchung von Präparaten von vier Augen zweier Patienten. Ergebnisse: In beiden Fällen liegt ein Embryotoxon posterius vor; in Fall 1 mit Iris-Prozessbildung bis zum Embryotoxon. Fall 1 wies ein deutlich anomales Irisstroma mit ausgeprägter Spaltbildung zwischen anteriorem und posteriorem Stroma auf. In Fall 2 war Vakuolenbildung mit Spitzenmuster zu beobachten. Schlussfolgerungen: Das Alagille-Syndrom ist primär eine hepatische Erkrankung, weist jedoch auch mehrere charakterische okuläre Krankheitsmerkmale auf, insbesondere Embryotoxon posterius. Dies und die Anomalien des Irisstromas könnten auf die fehlerhafte Migration von Neuralleistenzellen infolge der Mutation des Jagged-1-Gens zurückzuführen sein, die das Alagille-Syndrom verursacht. Patienten mit Alagille-Syndrom werden selten einer okulären Autopsie unterzogen. Die Ergebnisse dieser Untersuchung könnten zum besseren Verständnis der Pathophysiologie der okulären Anomalien bei dieser Erkrankung beitragen.
Efficacy of Second-Line Bevacizumab-Containing Chemotherapy for Patients with Metastatic Colorectal Cancer following First-Line Treatment with an Anti-Epidermal Growth Factor Receptor Antibody
Authors: Hasegawa Hiroko , Taniguchi Hiroya , Mitani Seiichiro , Masuishi Toshiki , Komori Azusa , Narita Yukiya , Kadowaki Shigenori , Ura Takashi , Ando Masashi , Yatabe Yasushi , Muro Kei
Published: February 2017

Objective: Anti-epidermal growth factor receptor (EGFR) antibodies and bevacizumab are commonly used, sequentially, as palliative chemotherapies for patients with metastatic colorectal cancer. However, little is known about the efficacy of second-line treatments containing bevacizumab after first-line treatment with an anti-EGFR antibody. Methods: We retrospectively reviewed 128 patients who received second-line bevacizumab-containing chemotherapy and evaluated the effect of prior use of anti-EGFR antibody on the efficacy of the second-line treatment. Results: As first-line treatments, 35 of these patients received only cytotoxic chemotherapy (cohort A), 58 received bevacizumab-containing chemotherapy (cohort B), and 35 received anti-EGFR-containing chemotherapy (cohort C). The median progression-free survival (PFS) with the second-line bevacizumab-containing therapy was 8.3 months in cohort C, 6.9 months in cohort A (hazard ratio [HR], 1.43; 95% confidence interval [CI], 0.83-2.51), and 5.6 months in cohort B (HR, 1.95; 95% CI, 1.18-3.22). Multivariate analysis showed that PFS in cohort C was the same as that in cohort A, but better than that in cohort B. The overall response rate in cohort C (25.7%) was also similar to that in cohort A (20.0%), but better than that in cohort B (10.3%). Conclusions: Prior use of anti-EGFR antibody did not adversely affect the efficacy of subsequent bevacizumab-containing chemotherapy.
Treatment Options in Colorectal Liver Metastases: Hepatic Arterial Infusion
Authors: Zervoudakis Alice , Boucher Taryn , Kemeny Nancy E.
Published: February 2017

Background: The liver is the most common site for metastases from colorectal cancer (CRC) with the majority of these patients having unresectable disease. Methods: This is a retrospective review of studies using hepatic arterial infusion (HAI) therapy to treat liver metastasis from CRC. A PubMed search of randomized controlled trials and retrospective studies from 2006 to present was conducted using the search terms ‘hepatic arterial infusion (HAI) therapy', ‘colorectal cancer', and ‘treatment of liver metastases'. Results: The first randomized studies comparing HAI to systemic therapy with 5-fluorouracil/leucovorin produced significantly higher response rates of 41 versus 14%. Systemic therapy has improved with the addition of irinotecan and oxaliplatin; however, the responses with HAI and these modern agents have also increased, with responses as high as 80%. For patients with wild-type KRAS, HAI and systemic therapy produced a median survival of 68 months. In patients with refractory disease, response rates are in the 30% range with a median survival of 20 months. Adjuvant HAI after liver resection has shown an increase of hepatic disease-free survival and overall disease-free survival when compared to systemic therapy alone in three of four randomized trials. A recent update of the adjuvant trials after liver resection at Memorial Sloan Kettering Cancer Center has shown a 5-year survival of 78%. Conclusion: HAI therapy has a role in treating hepatic metastases from CRC in both the resectable and unresectable setting.
Thermal Ablation in the Management of Colorectal Cancer Patients with Oligometastatic Liver Disease
Authors: Petre Elena Nadia , Sofocleous Constantinos
Published: February 2017

Background: Surgical resection of limited colorectal liver disease improves long-term survival and can be curative in a subset of selected cases. Image-guided percutaneous ablation therapies have emerged as safe and effective alternative options for selected patients with unresectable colorectal liver metastases (CLM) that can be ablated with margins. Ablation causes focal destruction of tissue and has increasingly been shown to provide durable eradication of tumors. Methods: A selective review of literature was conducted in PubMed, focusing on recent studies reporting on the safety, efficacy, and long-term outcomes of percutaneous ablation modalities in the treatment of CLM. The present work gives an overview of the different ablation techniques, their current clinical indications, and reported outcomes from most recently published studies. The ‘test of time' concept for using ablation as a first local therapy is also described. Results: There are several thermal ablative tools currently available, including radiofrequency ablation (RFA), microwave ablation, and cryoablation. Most data to date originated from the application of RFA. Adjuvant thermal ablation in the treatment of oligometastatic colon cancer liver disease offers improved oncologic outcomes. The ideal CLM amenable to percutaneous ablation is a solitary tumor with the largest diameter up to 3 cm that can be completely ablated with a sufficient margin. 5-year overall survival rates up to 70% after ablation of unresectable CLM have been reported. Pathologic confirmation of complete tumor necrosis with margins over 5 mm provides best long-term local tumor control by thermal ablation. Conclusion: Current evidence suggests that percutaneous ablation as adjuvant to chemotherapy improves oncologic outcomes of patients with CLM. For small tumors that can be ablated completely with clear margins, percutaneous ablation may offer outcomes similar to those of surgery.
Endoscopic Characteristics, Risk Grade, and Prognostic Prediction in Gastrointestinal Stromal Tumors of the Small Bowel
Authors: Nakano Arihiro , Nakamura Masanao , Watanabe Osamu , Yamamura Takeshi , Funasaka Kohei , Ohno Eizaburo , Kawashima Hiroki , Miyahara Ryoji , Goto Hidemi , Hirooka Yoshiki
Published: February 2017

Background/Aims: Balloon-assisted endoscopy allows us to diagnose gastrointestinal (GI) stromal tumors (GISTs) in the small bowel including endoscopic ultrasonography and taking biopsy. The aim of this study was to retrospectively clarify clinical and endoscopic characteristics of small bowel GISTs using double-balloon endoscopy (DBE). Methods: We reviewed 25 patients who underwent DBE and were diagnosed with GISTs. The risk of GISTs was stratified using the National Institute of Health (NIH) consensus criteria. We evaluated the available DBE route, the diagnostic yield of biopsy examination, and the relationship between endoscopic characteristics and recurrence-free survival (RFS). Results: Of all 25 patients, 23 had any endoscopic findings related to GIST. They were detected using the antegrade approach in 91.3%. GISTs were classified into high risk (n = 7), intermediate risk (n = 4), low risk (n = 10), and very low risk (n = 4) based on surgical specimens. The diagnostic result of biopsy was 46.7% (7/15), but it was difficult to predict the NIH risk group. Endoscopic characteristics were not associated with RFS. The NIH risk group was significantly associated with RFS. Conclusions: Antegrade DBE was preferable for exploring small bowel GIST, but the diagnostic ability of biopsy examination was limited.
Altersbedingte echte Exfoliation der Linsenkapsel: Ergebnisse der Phakoemulsifikationsoperation
Authors: Ng Alex Lap Ki , Marcet Marcus M. , Lai Jimmy S.M. , Yeung Jane C.C.
Published: February 2017

Die echte Exfoliation der kristallinen Linse, historisch gesehen ein bei den Glasbläsern beobachtetes Phänomen, beinhaltet eine Aufspaltung oder Abschilferung der Kapsel. Wir haben die Phakoemulsifikationsaufzeichnungen eines einzelnen Chirurgen im Hinblick auf Patienten mit echter Exfoliation der Linsenkapsel überprüft. Die Inzidenz in unserer Serie betrug 2,2% (6 von 278 Fällen). Das Durchschnittsalter betrug 85 Jahre. Bei allen Patienten verlief die Phakoemulsifikation erfolgreich, was auf die genaue Feststellung der Erkrankung und entsprechende chirurgische Planung zurückzuführen sein könnte. Unsere Erkenntnisse unterstützen die Auffassung, dass echte Exfoliation möglicherweise häufiger mit fortgeschrittenem Alter assoziiert ist als mit Infrarotstrahlung. Übersetzung aus Case Rep Ophthalmol 2015;6:401-407 (DOI: 10.1159/000442345)
Similarities and Differences in Autoimmune Hepatitis Epidemiology between East and West: Autoimmune Hepatitis in East Asia, Southeast Asia, and South Asia
Authors: Enomoto Hirayuki , Nishiguchi Shuhei
Published: February 2017

Background: Autoimmune hepatitis (AIH) is a relatively rare disease that can develop regardless of age or ethnicity. However, its clinical features differ between eastern and western populations due to several heterogeneous genetic and environmental factors. We herein report the clinical characteristics of AIH patients in East Asia, Southeast Asia, and South Asia. Summary and Key Messages: The prevalence of AIH in eastern countries is considered to be lower than in western countries. Although a few young patients with type 2 AIH have been observed in South Asia, most patients in Asia are middle-aged women with type 1 AIH who respond well to steroid-based immunosuppressive therapy. Human leukocyte antigen DR4 is suggested to be an influential factor in the genetic background of AIH patients in Asia, particularly in East Asia. Notably, AIH may be induced by some societal- or culture-associated medicines, including herbal medicines. The IAIHG (International Autoimmune Hepatitis Group) scoring systems are generally accepted as the standard diagnostic methods for AIH in Asian countries. The results of repeated nationwide surveys in Japan suggest that the clinical features of AIH patients in East Asia are changing, with IgG levels and rates of anti-nuclear antibody positivity decreasing.
Should We Change the Initial Treatment of Renal or Retroperitoneal Abscess in High Risk Patients?
Authors: Yamamichi Fukashi , Shigemura Katsumi , Kitagawa Koichi , Arakawa Soichi , Tokimatsu Issei , Fujisawa Masato
Published: February 2017

Introduction: This study examined the risk factors for initial treatment failure in renal or retroperitoneal abscess as a multicenter study. Materials and Methods: This retrospective analysis investigated consecutive patients with renal or retroperitoneal abscess who were hospitalized in Japan. The outcomes of these patients were classified into “cured” and “failure or recurrence.” The potential clinical risk factors examined were abscess size, diabetes mellitus, major organ failure, laboratory data, fever, drainage, and causative organisms, for instance. Results: Of the 74 patients, 40 (54.1%) were diagnosed with renal abscess and 34 (45.9%) with retroperitoneal abscess, 51 (68.9%) were cured by initial treatments, and 23 (31.1%) underwent failure or relapse; 33 (44.6%) were men and 41 (55.4%) were women. In detail, 36 patients were cured by conservative therapy only. Our multivariate analysis data showed that renal failure was the only significant factor for initial treatment failure (p = 0.0281). Conclusions: Our multivariate analysis showed that renal failure was a significant risk factor for initial treatment failure or recurrence.
Kataraktchirurgie und Augeninnendruck
Authors: Melancia Diana , Abegão Pinto Luis , Marques-Neves Carlos
Published: February 2017

Die Kataraktoperation ist eine der am häufigsten durchgeführten Operationen in den Industrieländern. Neben ihrer signifikanten Auswirkung auf die Sehschärfe wird der Phakoemulsifikation auch eine potenzielle Intraokulardruck(IOD)-senkende Wirkung zugeschrieben. Während die aktuelle Evidenzlage auf eine insgesamt signifikante und anhaltende IOD-Senkung nach Kataraktoperationen hindeutet, ist noch unklar, welche spezifischen okulären Merkmale dazu beitragen könnten vorherzusagen, welche Patienten wahrscheinlich von diesem IOD-senkenden Effekt profitieren würden. Dies bei Glaukompatienten klar zu benennen ist jedoch wichtig, wenn die Kataraktoperation einen Platz in der Behandlung des Glaukoms erhalten soll. Die vorliegende Arbeit gibt einen Überblick über die Literatur zu diesem Thema und geht darauf ein, welche Mechanismen der IOD-Senkung zugrunde liegen und welche Patientengruppen mit höherer Wahrscheinlichkeit im Hinblick auf die IOD-Senkung von diesem Eingriff profitieren könnten, um so letztlich zur Optimierung der Versorgung der steigenden Zahl der Patienten beizutragen, bei denen gleichzeitig Glaukom und Katarakt vorliegen. Übersetzung aus Ophthalmic Res 2015;53:141-148 (DOI:10.1159/000377635)
DHA Reduces Oxidative Stress after Perinatal Asphyxia: A Study in Newborn Piglets
Authors: Solberg Rønnaug , Longini Mariangela , Proietti Fabrizio , Perrone Serafina , Felici Cosetta , Porta Alessio , Saugstad Ola Didrik , Buonocore Giuseppe
Published: February 2017

Background: Perinatal hypoxic-ischemic brain damage is a major cause of acute mortality and chronic neurological morbidity in infants and children. Oxidative stress due to free radical formation and the initiation of abnormal oxidative reactions appears to play a key role. Docosahexanoic acid (DHA), a main component of brain membrane phospholipids, may act as a neuroprotectant after hypoxia-ischemia by regulating multiple molecular pathways and gene expression. Objectives: The aims of this study were to test the hypothesis that DHA provides significant protection against lipoperoxidation damage in the cerebral cortex and hippocampus in a neonatal piglet model of severe hypoxia-reoxygenation. Methods: Newborn piglets, Noroc (LYLD), were subjected to severe global hypoxia. One group was resuscitated with ambient air (21% group, n = 11) and another also received 5 mg/kg of DHA 4 h after the end of hypoxia (21% DHA group, n = 10). After 9.5 h, tissues from the prefrontal cortex and hippocampus were sampled and the levels of isoprostanes, neuroprostanes, neurofurans, and F2-dihomo-isoprostanes were determined by the liquid chromatography triple quadrupole mass spectrometry technique. Results: Lipid peroxidation biomarkers were significantly lower in both the cortex and hippocampus in the DHA-treated group compared with the untreated group. Conclusions: The present study demonstrates that DHA administration after severe hypoxia in newborn piglets has an antioxidative effect in the brain, suggesting a protective potential of DHA if given after injuries to the brain.
Breast-Conserving Surgery Under Local Anesthesia in Elderly Patients with Severe Cardiorespiratory Comorbidities: A Hospital-Based Case-Control Study
Authors: Karanlik Hasan , Kılıç Berkay , Yıldırım Ilknur , Bademler Süleyman , Ozgur Ilker , Ilhan Burak , Onder Semen
Published: February 2017

Introduction: We report the feasibility and safety of local anesthesia (LA) in patients having breast-conserving surgery (BCS). Methods: 37 patients with American Society of Anesthesiologists (ASA) score of 4 having BCS under LA and 54 age-matched subjects with ASA score of 3-4 having BCS under general anesthesia (GA) were included. Patients were retrospectively evaluated for the follow-up duration, duration of surgery, postoperative satisfaction scores (1-10), complication and survival time for locoregional recurrence and overall survival rates. Results: The mean follow-up duration was 55.09 ± 13.49 months (range 38-104) in GA group, and 58.7 ± 15.5 months (range 20-99) in LA group. There was a significant difference in the duration of surgery (p < 0.001). In the LA group, 5 patients (13.5%) had minor complications including seroma, wound infection or hematoma, whereas 6 patients (11.1%) had minor complications in the GA group (p > 0.05). The re-excision rate due to positive tumor margins was 5.4% (2 patients) in the LA group and 5.5% in the GA group, respectively. The locoregional recurrence-free survival and overall survival rate was not different between 2 groups (p = 0.192, p = 0.93). Conclusion: BCS under LA seemed to be effective and safe in selected high-risk elderly patients.
Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the GLA Gene Associated with the Classical Phenotype of Fabry Disease
Authors: Azevedo Olga , Gago Miguel , Miltenberger-Miltenyi Gabriel , Gaspar Paulo , Sousa Nuno , Cunha Damião
Published: February 2017

We report on the clinical, biochemical, and genetic findings of a large family with the classical phenotype of Fabry disease due to the novel nonsense mutation c.607G>T (p.E203X) of the GLA gene, which occurs in the active site of the α-galactosidase A enzyme. This report highlights that (i) Fabry disease diagnosis should be considered in all cases of unexplained left ventricular hypertrophy (LVH), even in its milder forms; (ii) a complete evaluation of patients with unexplained LVH is important to find diagnostic red flags of treatable causes of LVH, such as Fabry disease; (iii) cascade family screening is paramount to the earlier diagnosis and treatment of other affected family members; and (iv) the Fabry disease phenotype is highly variable in heterozygote females, even within the same family.
In the Wake of Systolic Blood Pressure Intervention Trial: New Targets for Improving Hypertension Management in Chronic Kidney Disease?
Authors: Tyson Crystal C. , Coffman Thomas M.
Published: February 2017

Systolic Blood Pressure Intervention Trial (SPRINT) was a multicenter randomized controlled trial showing the significant benefit of intensive reduction of blood pressure to a target of 120 mm Hg in individuals with hypertension and elevated cardiovascular risk. Because SPRINT includes the largest cohort of adults with chronic kidney disease (CKD) to be prospectively studied in a hypertension intervention trial, it has particular relevance to the field of nephrology. Here, we review the findings of SPRINT and assess their potential impact on guidelines for treatment of hypertension in patients with CKD. We believe that the data from SPRINT will support a recommendation for lowering blood pressure targets to 120 mm Hg in a substantial segment of adults with CKD.
Cancer Stem Cells in Prostate Cancer: Implications for Targeted Therapy
Authors: Leão Ricardo , Domingos Célia , Figueiredo Arnaldo , Hamilton Robert , Tabori Uri , Castelo-Branco Pedro
Published: February 2017

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the second most common cause of cancer-related mortality among men in the developed world. Conventional anti-PCa therapies include surgery, radiation, hormonal ablation, and chemotherapy. Despite increasing efforts, these therapies are not effective for patients with advanced and/or metastatic disease. In most cases, cancer therapies fail due to an incomplete depletion of tumor cells, resulting in tumor relapse. The cancer stem cell (CSC) hypothesis is an emerging model that explains many of the molecular characteristics of oncological disease as well as the tendency of cancers to relapse, metastasize, and develop resistance to conventional therapies. CSCs are a reservoir of cancer cells that exhibit properties of self-renewal and the ability to reestablish the heterogeneous tumor cell population. The existence of PCa stem cells offers a theoretical explanation for many uncertainties regarding PCa and also for treatment resistance and disease progression once clinical cure is achieved. Therapies targeting CSCs might therefore lead to more effective cancer treatments, divergent from a traditional anti-proliferative approach, based on tumor bulk reduction accompanied by CSC-specific inhibition. Here, we focus on reviewing the historical perspective as well as concepts regarding stem cells and CSCs in PCa. In addition, we will report possible strategies and new clinical approaches that address the CSC-based concept of tumorigenesis in PCa.
Solifenacin in the Elderly: Results of an Observational Study Measuring Efficacy, Tolerability and Cognitive Effects
Authors: Hampel Christian , Betz Dietmar , Burger Maximilian , Nowak Christoph , Vogel Monika
Published: February 2017

Introduction: The study aimed to evaluate the efficacy and safety of solifenacin in older patients with overactive bladder (OAB). Materials and Methods: Observational data on patients aged ≥70 years and the prescribed flexible dose of solifenacin for OAB were collected at 294 offices of German general practitioners. Baseline and week 12 data included type and severity of OAB symptoms, adverse events, quality of life, and change in cognitive function per Mini Mental State Examination (MMSE). Results: Mean age of 774 patients was 78 ± 6 years. A decrease was observed in all OAB symptoms including a reduction of urinary urgency and micturition, each by 4 episodes per 24 h. No change in mean MMSE scores was apparent at week 12. Adverse events and treatment discontinuations were low at 5.8 and 0.5%, respectively. Conclusion: Solifenacin was well-tolerated while OAB symptoms declined at week 12. No relevant effect of solifenacin on cognitive function was observed in this elderly population.
Therapeutic Advances and New Directions for Triple-Negative Breast Cancer
Authors: Andreopoulou Eleni , Kelly Catherine M. , McDaid Hayley M.
Published: February 2017

Triple-negative breast cancer (TNBC) is a molecularly diverse grouping with poor prognosis for which chemotherapy remains the foundation of treatment. The molecular heterogeneity of the disease rationalizes its diverse biological behavior and differential response to treatment. Estimates of up to 20% of patients diagnosed have germline mutations in DNA-damage repair-pathway genes, namely BRCA1 and 2, and this can be used to select patients likely to respond to platinums and/or inhibitors of poly(ADP-ribose) polymerase (PARP). Similar strategies can be utilized in other subtypes of TNBC that have ‘BRCA-like' tumor biology due to the presence of mutations in alternate DNA-damage repair genes. The diverse biological behavior of TNBC and its variable response to chemotherapy were largely decoded following genotyping studies that enabled the identification of distinct molecular subtypes, such that the biological and genetic heterogeneity of the disease could be understood. This subsequently enabled the identification of therapeutic ‘vulnerabilities' for each subtype that encompass biological processes including proliferation, DNA repair, apoptosis, angiogenesis, immune modulation, and invasion and metastasis. To expedite the development of therapies for high-risk, early-stage breast cancer, we have adopted novel trial designs and re-defined endpoints as surrogates of clinical outcomes. The purpose of this review is to highlight the current standard and experimental treatment options for TNBC.
Late-Onset Inadvertent Bleb Formation following Pars Plana M3 Molteno Implant Tube Obstruction
Authors: Abdul-Rahman Anmar M. , Molteno Anthony
Published: February 2017

Purpose: To report a case of inadvertent bleb formation presenting 18 months after pars plana M3 Molteno implant tube obstruction in a patient with mixed mechanism glaucoma. Materials and Methods: An 84-year-old Caucasian male with mixed mechanism glaucoma underwent slit-lamp examination, gonioscopy, colour anterior segment photography and anterior segment optical coherence tomography (AS-OCT). Results: An inadvertent bleb developed 18 months after pars plana implant tube re-positioning with a 6/0 Vicryl tie ligature. The bleb was located in the area anterior to the implant plate; it was characterised by a thin, transparent, avascular and multi-cystic wall, with a visible stoma at the posterior edge of the bleb. The bleb was functioning as demonstrated by an intraocular pressure of 6 mm Hg at presentation and a punctate fluorescein uptake pattern of the bleb wall. The bleb over the plate of the Molteno implant was non-functioning, likely secondary to tube obstruction by vitreous in the early postoperative period. AS-OCT showed a tract from the anterior chamber commencing at an entry wound through a corneal tunnel to the posterior stoma at the base of the inadvertent bleb. Conclusions: We hypothesise that the pathophysiologic factors resulting in an inadvertent bleb are a result of a combination of apoptosis, late-onset wound dehiscence and internal gaping of a centrally placed corneal wound. In addition, aqueous hydrodynamic factors may play a role.
Analysis of Long Non-Coding RNA Expression of Lymphatic Endothelial Cells in Response to Type 2 Diabetes
Authors: Qi Min , Zhou Qiuhong , Zeng Weiqi , Shen Minxue , Liu Xiaomin , Luo Chang , Long Jing , Chen Wangqing , Zhang Jianglin , Yan Siyu
Published: February 2017

Background: Recent evidence has indicated that long non-coding RNA (lncRNA) is involved in the pathogenesis of type 2 diabetes, but nothing is known about lncRNA expression changes of lymphatic endothelial cells in response to type 2 diabetes. Methods: The GSE38396 dataset was downloaded from the Gene Expression Omnibus database and the probe sets of Human Gnome U133 Plus2.0 microarray were annotated for lncRNA. Differentially expressed lncRNAs between diabetic and non-diabetic lymphatic endothelial cells were calculated. Results: Compared with lymphatic endothelial cells in non-diabetic patients, 31 lncRNAs were down-regulated and 79 lncRNAs were up-regualted in lymphatic endothelial cells of type 2 diabetic patients. Several known lncRNAs were found, such as H19, GAS5, UCA1, CRNDE, GAS5, and LINC00312. Co-expression network of differentially expressed lncRNAs and mRNAs were constructed. Based on genomic regions of these lncRNAs, we found that binding sites of MAF and TCF3 were enriched and these lncRNAs may be related to insulin reporter signaling pathway and response to insulin stimulus. Conclusions: In a word, we found a set of lncRNAs were differentially expressed in lymphatic endothelial cells in response to type 2 diabetes and these lncRNAs may be involved in the pathogenesis of diabetes-related complications.
A Serous Cystic Neoplasm of the Pancreas Coexisting with High-Grade Pancreatic Intraepithelial Neoplasia Mimicking an Intraepithelial Papillary Mucinous Neoplasm: A Case Report
Authors: Kawanishi Aya , Hirabayashi Kenichi , Kono Hirotaka , Takanashi Yumi , Hadano Atsuko , Kawashima Yohei , Ogawa Masami , Kawaguchi Yoshiaki , Yamada Misuzu , Nakagohri Toshio , Nakamura Naoya , Mine Tetsuya
Published: February 2017

Serous cystic neoplasms of the pancreas are rare exocrine pancreatic neoplasms, most of which are benign and do not communicate with the pancreatic duct. Pancreatic intraepithelial neoplasm (PanIN) is considered a precursor of ductal adenocarcinoma that is microscopically recognized in pancreatic ducts. A 67-year-old Japanese woman presented with a 10-mm multilocular cystic lesion at the pancreatic body. Magnetic resonance pancreatography showed stenosis of the main pancreatic duct at the pancreatic body and dilatation of the distal side of the main pancreatic duct. Furthermore, communication between the cystic lesion and the main pancreatic duct was suspected based on magnetic resonance pancreatography findings. Distal pancreatectomy was performed under the preoperative diagnosis of intraductal papillary mucinous neoplasm. Histologically, the cystic lesion was lined with a non-atypical cuboidal or flat epithelium with clear cytoplasm and was thus diagnosed as a serous cystic neoplasm. High-grade PanIN lesions with stromal fibrosis were observed at the main and branch pancreatic ducts. Histological examination revealed no communication between the serous cystic neoplasm and the pancreatic ducts. Immunohistochemically, the epithelium of the serous cystic neoplasm showed positive anti-von Hippel-Lindau antibody staining, whereas the epithelium of the PanIN showed negative staining. A serous cystic neoplasm coexisting with another pancreatic neoplasm is rare. When dilatation of the main or branch pancreatic ducts coexists with a serous cystic neoplasm, as in this case, the lesion clinically mimics an intraductal papillary mucinous neoplasm.
“Nabucco” by Giuseppe Verdi: A Case of Delirium in an Italian Romantic Opera
Authors: Cambioli Luca , Bava Mattia , Bellelli Giuseppe , Clerici Massimo , Cesana Giancarlo , Riva Michele Augusto
Published: February 2017

Italian operas can provide relevant information on the medical knowledge during the Romantic Age, especially in the field of neuroscience. One of the most renowned operas, “Nabucco” by Giuseppe Verdi (1813-1901) may provide us with some information on the state of knowledge on neuropsychiatric diseases in the first part of the nineteenth century. The main character of this opera, the Assyrian king Nabucco suffers from delirium. Psychic signs and symptoms attributed to Nabucco in Verdi's opera could have been influenced by a better knowledge of neuropsychiatric diseases in the nineteenth century. Furthermore, the representation of Nabucco's mental illness in the opera could also have been influenced by direct experiences of Verdi himself, who seems to have suffered from recurrent depressive episodes in that period, and for the rest of his life.
Stimulation of Phospholipid Scrambling of the Erythrocyte Membrane by 9-Cis-Retinoic Acid
Authors: Abed Majed , Alzoubi Kousi , Lang Florian , Al Mamun Bhuayn Abdulla 
Published: February 2017

Background/Aims: The endogenous retinoid 9-cis-retinoic acid has previously been shown to trigger apoptosis in a wide variety of cells including several tumor cells and has thus been suggested for the treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms participating in the accomplishment of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i) and formation of ceramide. The present study explored, whether 9-cis-retinoic acid induces eryptosis and whether the effect involves Ca2+ and/or ceramide. Methods: Flow cytometry was employed to estimate erythrocyte volume from forward scatter, phosphatidylserine exposure at the cell surface from annexin-V-binding, [Ca2+]i from Fluo3-fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was quantified from hemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to 9-cis-retinoic acid (≥ 0.5 µg/ml) significantly increased the percentage of annexin-V-binding cells and significantly decreased forward scatter. Exposure to 9-cis-retinoic acid (≥ 0.5 µg/ml) significantly increased Fluo3-fluorescence, and the effect of 9-cis-retinoic acid on annexin-V-binding was significantly blunted by removal of extracellular Ca2+. Exposure to 9-cis-retinoic acid (1 µg/ml) further significantly increased the ceramide abundance at the erythrocyte surface and significantly increased hemolysis. Conclusions: 9-cis-retinoic acid triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part downstream of Ca2+ and ceramide.
Contribution of p62 to Phenotype Transition of Coronary Arterial Myocytes with Defective Autophagy
Authors: Bao Junxiang , Li Guangbi , Yuan Xinxu , Li Pin-Lan , Gulbins Erich
Published: February 2017

Background: Autophagy disorder contributes to dedifferentiation of arterial smooth muscle cells, but the mechanisms are poorly understood. Here, we sought to investigate the role of scaffolding adaptor p62/SQSTM1 (p62) in phenotype switching of mouse coronary arterial myocytes (CAMs) induced by CD38 gene deficiency or lysosomal dysfunction which blocks autophagic flux in the cells. Methods: Protein expression was measured by western blot analysis and immunofluorescent staining. Cell cycle and proliferation rate were analyzed by flow cytometry and MTS assay respectively. mRNA abundance was tested by qRT-PCR. Results: CD38 gene deficiency or bafilomycin A1 (baf), a selective lysosomal inhibitor treatment increased proliferation rate and vimentin expression in CAMs which was prevented by p62 gene silencing. Cell percentage in G2/M and G0/G1 phase was decreased and increased by CD38 deficiency or baf treatment, respectively which was accompanied by accrual of cyclin-dependent kinase 1 (CDK1) protein. Although free ubiquitin content was increased, the colocalization of it to CDK1 was markedly decreased in CD38-/- or baf treated CAMs. Furthermore, the changes in both cell cycle and CDK1 ubiquitinylation could be restored by p62 gene silencing. Conclusion: The results suggest in CD38-/- or baf treated CAMs, p62 accumulation promotes phenotype transition and proliferation by accelerating cell cycle progress through G2/M which might relate to the compromised ubiquitinylation and degradation of CDK1.
Epigenetic Alterations in Cellular Immunity: New Insights into Autoimmune Diseases
Authors: Wang Zijun , Lu Qianjin , Wang Zhihui
Published: February 2017

Epigenetic modification is an additional regulator in immune responses as the genome-wide profiling somehow fails to explain the sophisticated mechanisms in autoimmune diseases. The effect of epigenetic modifications on adaptive immunity derives from their regulations to induce a permissive or negative gene expression. Epigenetic events, such as DNA methylation, histone modifications and microRNAs (miRNAs) are often found in T cell activation, differentiation and commitment which are the major parts in cellular immunity. Recognizing the complexity of interactions between epigenetic mechanisms and immune disturbance in autoimmune diseases is essential for the exploration of efficient therapeutic targets. In this review, we summarize a list of studies that indicate the significance of dysregulated epigenetic modifications in autoimmune diseases while focusing on T cell immunity.
Novel Discrete Components based Speed Controller for Induction Motor
Authors: Attia Hussain , Sagafinia Ali
Published: February 2017

This paper presents an electronic design based on general purpose discrete components for speed control of a single phase induction motor drive. The MOSFETs inverter switching is controlled using Sampled Sinusoidal Pulse Width Modulation (SPWM) techniques with V/F method based on Voltage Controlled Oscillator (VCO). The load power is also controlled by a novel design to produce a suitable SPWM pulse. The proposed electronic system has ability to control the output frequency with flexible setting of lower limit to less than 1 Hz and to higher frequency limits to 55 Hz. Moreover, the proposed controller able to control the value of load voltage to frequency ratio, which plays a major parameter in the function of IM speed control. Furthermore, the designed system is characterized by easy manufacturing and maintenance, high speed response, low cost, and does not need to program steps as compared to other systems based on Microcontroller and digital signal processor (DSP) units. The complete proposed electronic design is made by the software of NI Multisim version 11.0 and all the internal sub-designs are shown in this paper. Simulation results show the effectiveness of electronic design for a promising of a high performance IM PWM drive.
Modeling and Simulation of Induction Motor based on Finite Element Analysis
Authors: Bensalem Yemna , Naceur Abdelkrim Mohamed
Published: February 2017

This paper presents the development of a co-simulation platform of induction motor (IM). For the simulation, a coupled model is introduced which contains the control, the power electronics and also the induction machine. Each of these components is simulated in different software environments. So, this study provides an advanced modeling and simulation tools for IM which integrate all the components into one common simulation platform environment. In this work, the IM is created using Ansys-Maxwell based on Finite Element Analysis (FEA), whereas the power electronic converter is developed in Ansys-Simplorer and the control scheme is build in MATLAB-Simulink environment. Such structure can be useful for accurate design and allows coupling analysis for more realistic simulation. This platform is exploited to analyze the system models with faults caused by failures of different drive’s components. Here, two studies cases are presented: the first is the effects of a faulty device of the PWM inverter, and the second case is the influence of the short circuit of two stator phases. In order to study the performance of the control drive of the IM under fault conditions, a co-simulation of the global dynamic model has been proposed to analyze the IM behavior and control drives. In this work, the co-simulation has been performed; furthermore the simulation results of scalar control allowed verifying the precision of the proposed FEM platform.
Fuzzy Gain-scheduling Proportional–integral Control for Improving the Speed Behavior of a Three-phases Induction Motor
Authors: Othmani Hichem , Mezghani D. , Mami A.
Published: February 2017

In this article, we have set up a vector control law of induction machine where we tried different type of speed controllers. Our control strategy is of type Field Orientated Control (FOC). In this structure we designed a Fuzzy Gain-Scheduling Proportional–Integral (Pi) controller to obtain best result regarding the speed of induction machine. At the beginning we designed a Pi controller with fixed parameters. We came up to these parameters by identifying the transfer function of this controller to that of Broïda (second order transfer function). Then we designed a fuzzy logic (FL) controller. Based on simulation results, we highlight the performances of each controller. To improve the speed behaviour of the induction machine, we have designend a controller called “Fuzzy Gain-Scheduling Proportional–Integral controller” (FGS-PI controller) which inherited the pros of the aforementioned controllers. The simulation result of this controller will strengthen its performances.