bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Stable Coronary Artery Disease and In Vivo Thrombin Generation
Authors: Valente-Acosta Benjamin , Baños-González Manuel Alfonso , Peña-Duque Marco Antonio , Martínez-Ríos Marco Antonio , Quintanar-Trejo Leslie , Aptilon-Duque Gad , Flores-García Mirthala , Cruz-Robles David , Cardoso-Saldaña Guillermo , de la Peña-Díaz Aurora
Published: August 2016

Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinical evidence shows that thrombin generation is enhanced in atherosclerosis, but its role as a risk factor for coronary atherosclerotic burden has not been proven in coronary artery disease (CAD) stable patients.Objectives. To evaluate the association between TAT levels and homocysteine levels and the presence of coronary artery disease diagnosed by coronary angiography in patients with stable CAD.Methods and Results. We included 95 stable patients admitted to the Haemodynamics Department, including 63 patients with significant CAD and 32 patients without. We measured the thrombin-antithrombin complex (TAT) and homocysteine concentrations in all the patients. The CAD patients exhibited higher concentrations of TAT (40.76 μg/L versus 20.81 μg/L,p=0.002) and homocysteine (11.36μmol/L versus 8.81μmol/L,p<0.01) compared to the patients without significant CAD. Specifically, in patients with CAD+ the level of TAT level was associated with the severity of CAD being 36.17 ± 24.48 μg/L in the patients with bivascular obstruction and 42.77 ± 31.81 μg/L in trivascular coronary obstruction,p=0.002.Conclusions. The level of in vivo thrombin generation, quantified as TAT complexes, is associated with the presence and severity of CAD assessed by coronary angiography in stable CAD patients.
In VitroGrowth Inhibitory Activities of Natural Products from Irciniid Sponges against Cancer Cells: A Comparative Study
Authors: BenRedjem Romdhane Yosr , Elbour Monia , Carbone Marianna , Ciavatta Maria Letizia , Gavagnin Margherita , Mathieu Véronique , Lefranc Florence , Ktari Leila , Ben Mustapha Karim , Boudabous Abdellatif , Kiss Robert , Mollo Ernesto
Published: August 2016

Marine sponges of the Irciniidae family contain both bioactive furanosesterterpene tetronic acids (FTAs) and prenylated hydroquinones (PHQs). Both classes of compounds are known for their anti-inflammatory, antioxidant, and antimicrobial properties and known to display growth inhibitory effects against various human tumor cell lines. However, the different experimental conditions of the reportedin vitrobioassays, carried out on different cancer cell lines within separate studies, prevent realistic actual discrimination between the two classes of compounds from being carried out in terms of growth inhibitory effects. In the present work, a chemical investigation of irciniid sponges from Tunisian coasts led to the purification of three known FTAs and three known PHQs. Thein vitrogrowth inhibitory properties of the six purified compounds have been evaluated in the same experiment in a panel of five human and one murine cancer cell lines displaying various levels of sensitivity to proapoptotic stimuli. Surprisingly, FTAs and PHQs elicited distinct profiles of growth inhibitory-responses, differing by one to two orders of magnitude in favor of the PHQs in all cell lines. The obtained comparative results are discussed in the light of a better selection of drug candidates from natural sources.
Intraperitoneal Hemorrhage in a Pregnant Woman with Hyperemesis Gravidarum: Vitamin K Deficiency as a Possible Cause
Authors: Baba Yosuke , Morisawa Hiroyuki , Saito Koyomi , Takahashi Hironori , Rifu Kazuma , Matsubara Shigeki
Published: August 2016

Hyperemesis gravidarum can cause various vitamin deficiencies. Vitamin K deficiency can lead to coagulopathy or hemorrhagic diathesis. A nulliparous Japanese woman with hyperemesis gravidarum at 105/7weeks was admitted with giant myoma, intestinal obstruction, and abdominal pain. Treatment for a degenerative myoma was instituted with intravenous antibiotics. The abdominal pain ameliorated, but intestinal obstruction persisted. At 166/7weeks, we performed laparotomy for release of intestinal obstruction, when intraabdominal bleeding of 110 mL existed. Blood tests revealed coagulopathy secondary to vitamin K deficiency. The coagulopathy responded to intravenous vitamin K injection. Coagulopathy due to vitamin K deficiency can occur with hyperemesis gravidarum, and coexisting intestinal obstruction and broad-spectrum antibiotics can aggravate the deficiency.
Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation
Authors: McCoy Kathleen L.
Published: August 2016

Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents. Abundant evidence indicates that cannabinoids modulate immune responses. An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors. Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells. Cannabinoids suppress Toll-like receptor-mediated inflammatory responses. However, the relationship between the endocannabinoid system and innate immune system may not be one-sided. Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids. Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses. Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases. This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them.
Necessity of Microdissecting Different Tumor Components in Pulmonary Tumor Pyrosequencing
Authors: Qin Dahui , Zheng Zhong , Shen Shanxiang , Smith Prudence , Khalil Farah K.
Published: August 2016

Microdissection is a useful method in tissue sampling prior to molecular testing. Tumor heterogeneity imposes new challenges for tissue sampling. Different microdissecting methods have been employed in face of such challenge. We improved our microdissection method by separately microdissecting the morphologically different tumor components. This improvement helped the pyrosequencing data analysis of two specimens. One specimen consisted of both adenocarcinoma and neuroendocrine components. When both tumor components were sequenced together for KRAS (Kirsten rat sarcoma viral oncogene homolog) gene mutations, the resulting pyrogram indicated that it was not a wild type, suggesting that it contained KRAS mutation. However, the pyrogram did not match any KRAS mutations and a conclusion could not be reached. After microdissecting and testing the adenocarcinoma and neuroendocrine components separately, it was found that the adenocarcinoma was positive for KRAS G12C mutation and the neuroendocrine component was positive for KRAS G12D mutation. The second specimen consisted of two morphologically different tumor nodules. When microdissected and sequenced separately, one nodule was positive for BRAF (v-raf murine sarcoma viral oncogene homolog B1) V600E and the other nodule was wild type at the BRAF codon 600. These examples demonstrate that it is necessary to microdissect morphologically different tumor components for pyrosequencing.
Future Changes in Drought Characteristics under Extreme Climate Change over South Korea
Authors: Lee Joo-Heon , Kwon Hyun-Han , Jang Ho-Won , Kim Tae-Woong
Published: August 2016

This study attempts to analyze several drought features in South Korea from various perspectives using a three-month standard precipitation index. In particular, this study aims to evaluate changes in spatial distribution in terms of frequency and severity of droughts in the future due to climate change, using IPCC (intergovernmental panel on climate change) GCM (general circulation model) simulations. First, the Mann-Kendall method was adopted to identify drought trends at the five major watersheds. The simulated temporal evolution of SPI (standardized precipitation index) during the winter showed significant drying trends in most parts of the watersheds, while the simulated SPI during the spring showed a somewhat different feature in the GCMs. Second, this study explored the low-frequency patterns associated with drought by comparing global wavelet power, with significance test. Future spectra decreased in the fractional variance attributed to a reduction in the interannual band from 2 to 8 years. Finally, the changes in the frequency and the severity under climate change were evaluated through the drought spell analyses. Overall features of drought conditions in the future showed a tendency to increase (about 6%) in frequency and severity of droughts during the dry season (i.e., from October to May) under climate change.
Convergence of Laguerre Impulse Response Approximation for Noninteger Order Systems
Authors: Bania Piotr , Baranowski Jerzy , Zagórowska Marta
Published: August 2016

One of the most important issues in application of noninteger order systems concerns their implementation. One of the possible approaches is the approximation of convolution operation with the impulse response of noninteger system. In this paper, new results on the Laguerre Impulse Response Approximation method are presented. Among the others, a new proof ofL1convergence of approximation is given, allowing less strict assumptions. Additionally, more general results are given including one regarding functions that are in the joint part ofL1andL2spaces. The method was also illustrated with examples of use: analysis of “fractional order lag” system, application to noninteger order filters design, and parametric optimization of fractional controllers.
Selective and Accurate Determination Method of Propofol in Human Plasma by Mixed-Mode Cation Exchange Cartridge and GC-MS
Authors: Pyo Jae Sung
Published: August 2016

A gas chromatography-mass spectrometry (GC-MS) method for the determination of propofol in human plasma has been developed and validated. Propofol was extracted from human plasma by using mixed-mode cation exchange/reversed-phase (MCX) cartridges. As propofol easily volatilizes during concentration, 100% methanol was injected directly into GC-MS to elute propofol. Despite avoiding concentration process of the eluted solution, lower limit of quantization (LLOQ) of propofol was 25 ng/mL. The validated method exhibited good linearity (R2=0.9989) with accuracy and precision −5.8%~11.7% and 3.7%~11.6%, respectively. The other validation parameters, recovery and matrix effect, ranged from 96.6% to 99.4% and 95.3% to 101.4%, respectively. Propofol standard was quantified to evaluate possible loss due to the concentration processes, nitrogen gas and centrifugal vacuum. These two concentration processes resulted in notable decrease in the quantity of propofol, signifying avoiding any concentration processes during propofol quantification. Also, to confirm suitability of the developed method, authentic human plasma samples were analyzed. The selective assay method using MCX cartridge and GC-MS facilitated quantification of propofol in plasma sample accurately by preventing any losses due to the concentration processes.
Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung über die Lebensspanne
Authors: Christiansen Hanna
Published: August 2016

Die Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) ist eine Störung mit Beginn in der Kindheit und Jugend. Die Persistenzraten für das Erwachsenenalter liegen allerdings zwischen 20 bis über 80%. Demnach handelt es sich um eine chronische Störung, die über die Lebensspanne hinweg zu erheblichen Beeinträchtigungen führen kann. In diesem Übersichtsartikel werden zunächst die Symptomatik, Klassifikation, Komorbidität und Epidemiologie der Störung dargestellt, wobei auf Unterschiede in den verschiedenen Lebensphasen (Kindes-, Jugend- und Erwachsenenalter) eingegangen wird. Daran anschließend wird die ADHS als Entwicklungsstörung dargestellt und mögliche Entwicklungspfade und Risikofaktoren werden beschrieben. Abschließend werden diagnostische und therapeutische Ansätze in den unterschiedlichen Lebensphasen vorgestellt.
PAH-Therapie bei Patienten mit schwerer PH und milder bis moderater COPD
Authors: Krüger Stefan
Published: August 2016

Hintergrund: Das Outcome von Patienten mit schwerer pulmonaler Hypertonie (PH) in Verbindung mit einer chronisch-obstruktiven Lungenerkrankung (COPD) ist dürftig. Eine spezifische Behandlung der PH könnte den klinischen und hämodynamischen Status dieser Patienten verbessern, dabei jedoch potenziell die arterielle Blutgaszusammensetzung verschlechtern. Ziele: In unsere Studie wurden retrospektiv 28 Patienten mit schwerer präkapillärer PH (mittlerer Pulmonalarteriendruck >35 mmHg) in Verbindung mit milder bis moderater COPD [Einsekundenkapazität (FEV1) >50% des Sollwerts] eingeschlossen. Alle Patienten hatten im Rahmen einer Monotherapie oder Zwei- bzw. Dreifach-Kombinationstherapie eine spezifische Behandlung der pulmonal-arteriellen Hypertonie (PAH) erhalten. Methoden: In unserer monozentrischen Studie werteten wir retrospektiv 537 Rechtsherzkatheterisierungen (RHK) aus, die zwischen Januar 2004 und Juni 2014 bei COPD-Patienten erfolgt waren. Vor der RHK wurden jeweils eine Echokardiografie, umfassende Blutuntersuchungen, Lungenfunktionstests und eine hochauflösende Computertomografie durchgeführt. Für die RHK wurde bei allen Patienten ein Swan-Ganz-Katheter verwendet. Ergebnisse: Die Patienten, die mit spezifischen PAH-Medikamenten behandelt worden waren, zeigten langfristig im Vergleich zu Studienbeginn eine signifikante Verbesserung des Herzindex (2,5 ± 0,7 L/min/m2 zu Studienbeginn vs. 3,2 ± 0,6 L/min/m2 nach 6/12 Monaten; p = 0,003) sowie eine langfristige Abnahme des Lungengefäßwiderstands (8,4 ± 4,2 Wood-Einheiten bei Studienbeginn vs. 5 ± 1,7 Wood-Einheiten nach 6/12 Monaten; p = 0,008). Nach 3-monatiger Behandlung war ein leichter Rückgang des arteriellen Sauerstoffdrucks (PaO2) zu verzeichnen (-2,4 ± 7,21 mmHg; p = 0,066). 12 Patienten (42,8%) verstarben während der im Median 3 Jahre langen Nachbeobachtung (alle Todesursachen zusammengenommen). Schlussfolgerung: Dieser vorläufige Bericht legt nahe, dass der Einsatz spezifischer PH-Medikamente bei schwerer PH in Verbindung mit milder bis moderater COPD Verbesserungen bei pulmonal-hämodynamischen Parametern bewirken kann, einhergehend mit einer Verschlechterung des PaO2, die keine klinisch Bedeutung aufwies und bei keinem der Patienten zum Abbruch der PAH-Therapie führte. Übersetzung aus Respiration 2016;91:9-17 (DOI:10.1159/000441304)
Nutzen einer Cyclophosphamid-Pulstherapie bei interstitiellen Lungenerkrankungen
Authors: Drakopanagiotakis Fotios
Published: August 2016

Hintergrund: Unter interstitiellen Lungenerkrankungen (interstitial lung diseases; ILD) versteht man eine Gruppe von Erkrankungen, die durch progressive Abnahme der Lungenfunktion gekennzeichnet sind. Eine Stabilisierung der Lungenfunktion unter intermittierender intravenöser Gabe von Cyclophosphamid wurde bei Patienten mit systemischer Sklerose nachgewiesen; entsprechende Daten von ILD-Patienten hingegen sind rar. Ziel: Retrospektive Nutzenbewertung einer Cyclophosphamid-Pulstherapie bei ILD. Methoden: Wir analysierten retrospektiv alle Patienten, die zwischen 2002 und 2012 in unserem Zentrum intravenös mit Cyclophosphamid behandelt wurden. Lungenfunktion, Überlebensstatus und Zytologie der Bronchiallavage wurden für einen Nachbeobachtungszeitraum von 18 Monaten erfasst. Ergebnisse: 26 Patienten mit idiopathischer Lungenfibrose, 6 mit lymphozytärer interstitieller Pneumonie (LIP), 8 mit unspezifischer idiopathischer interstitieller Pneumonie (NSIP), 7 mit ILD in Assoziation mit rheumatoider Arthritis und 7 mit (pANCA + ILD) für perinukleäre anti-neutrophile zytoplasmatische Antikörper positiver ILD (pANCA + ILD) wurden eingeschlossen. Patienten mit LIP und NSIP hatten die besten Überlebenswerte, diejenigen mit pANCA+ ILD die schlechtesten. In der Gesamtkohorte stellten wir im Jahr vor der Behandlung einen signifikant stärkeren Rückgang der Gesamtlungenkapazität fest als im Jahr nach der Behandlung. Schlussfolgerungen: Diese retrospektive Analyse zur Behandlung mit Cyclophosphamid zeigt eine Stabilisierung der Lungenfunktion bei den meisten Patienten mit fibrosierenden ILD-Formen; prospektive Studien bei klar definierten Diagnosen werden jedoch noch dringend benötigt. Übersetzung aus Respiration 2016;91:296-301(DOI:10.1159/000445031)
Ingenol Mebutate for Recalcitrant Chronic Actinic Cheilitis
Authors: Tzika Evangelia , Masouyé Isabelle , Mühlstädt Michael , Laffitte Emmanuel
Published: August 2016

We present the case of a healthy 76-year-old man with a whitish, hyperkeratotic lesion of the lower lip diagnosed as actinic cheilitis (AC) previously treated with classic red light photodynamic therapy 5 years ago. Initial treatment with 5% imiquimod cream - also with intensified application - failed. After 2 cycles thrice daily, consecutive applications of 150 μg/g ingenol mebutate gel at 3 weeks' interval, the lesions cleared completely. Surprisingly, no pustular or crusting reaction or other side effect occurred contrary to expectation. Remission was stable for 10 months, when recurrence occurred. Ingenol mebutate proved to be a feasible and safe treatment in this otherwise refractory case of AC.
Ingenol Mebutate 500 μg for Treatment of the Scalp in Refractory Field Cancerization
Authors: Gaide Olivier , Clayton Helena , Girardin Marie , Kuonen Francois
Published: August 2016

Patients suffering from chronic lymphocytic leukemia often develop actinic keratosis (AK) and squamous cell carcinoma in sun-exposed areas. In these particular patients, who have a suboptimal immune function, AK treatment can be particularly challenging. We report the case of a patient who failed to respond to most AK treatments, including 5-FU, imiquimod and photodynamic therapy, but responded to ingenol mebutate. We started with 3 applications of 150 μg/g (registered treatment of the scalp) and also 2 applications of 500 μg/g (registered in for trunk and extremities). Both treatments were well tolerated, but only the latter led to significant clinical success. This suggests that 500 μg/g of ingenol mebutate may represent an interesting therapeutic option in patients with mild immunosuppression.
Ingenol Mebutate vs. Daylight Photodynamic Therapy in a Kidney Transplant Recipient
Authors: Mühlstädt Michael
Published: August 2016

We present the case of a 73-year-old male patient who had received a first renal transplant at 36 years and a second one at the age of 55 years. He is currently under immunosuppression with everolimus 2.5 mg/day and prednisone 5 mg/day. The patient presented with multiple actinic keratoses on both cheeks and the forehead and received treatment by ingenol mebutate 150 µg/g gel daily on 3 consecutive days on his right cheek and methyl aminolevulinate (MAL) photodynamic therapy activated by daylight (MAL-dPDT) on the forehead and the left cheek. MAL-dPDT treatment proved a feasible, repeatable, physician-directed method of treating field cancerization with limited morbidity for a period of 6 days. Treatment with ingenol mebutate gel was a feasible, possibly self-directed method of treating field cancerization with limited morbidity for 10 days in this immunosuppressed patient. Both treatments showed similar efficacy. At the time of treatment, the MAL daylight PDT ran at 3 times the cost of ingenol mebutate gel.
Sexual Health and Quality of Life Assessment among Ovarian Cancer Patients during Chemotherapy
Authors: Domenici Lavinia , Palaia Innocenza , Giorgini Margherita , Piscitelli Valerio Piacentino , Tomao Federica , Marchetti Claudia , Di Donato Violante , Perniola Giorgia , Musella Angela , Monti Marco , Muzii Ludovico , Benedetti Panici Pierluigi
Published: August 2016

Background: During the last decades many successful efforts have been made in order to increase life expectancy in ovarian cancer (OC) patients. However, just a few studies have investigated the impact of OC on quality of life (QoL) and sexual function in OC cases during treatment. Objective: The aim of this study was to evaluate the QoL and sexual function of OC patients during chemotherapy (CT). Patients and Methods: Forty-nine subjects were enrolled and filled in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OV28, Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) questionnaires. The results were evaluated globally and consequently stratified into several groups: single surgery versus multiple surgeries, age ≤48 years versus >48 years, and first-line CT versus multiple lines of CT. Results: Menopause-related symptoms, body image and attitude toward the disease were significantly worse during first-line CT (p = 0.018, p = 0.029 and p = 0.006, respectively). Sexual outcomes resulted in better scores in younger patients in all questionnaires (FSFI: p = 0.001; FSDS: p = 0.048; specific EORTC QLQ-OV28 items: p = 0.022). Scores concerning body image, attitude toward the disease and CT-associated symptoms resulted worse in patients after the first surgery (p = 0.017, p = 0.002 and p = 0.012, respectively). Conclusion: Our study confirms that OC has a detrimental impact on QoL and intimacy, particularly in younger patients, during the first course of CT and after the first cytoreductive surgery.
Developmental Origins of Disease - Crisis Precipitates Change
Authors: Reichetzeder Christoph , Dwi Putra Sulistyo Emantoko , Li Jian , Hocher Berthold
Published: August 2016

The concept of developmental origins of diseases has gained a huge interest in recent years and is a constantly emerging scientific field. First observations hereof originated from epidemiological studies, linking impaired birth outcomes to adult chronic, noncommunicable disease. By now there is a considerable amount of both epidemiological and experimental evidence highlighting the impact of early life events on later life disease susceptibility. Albeit far from being completely understood, more recent studies managed to elucidate underlying mechanisms, with epigenetics having become almost synonymous with developmental programming. The aim of this review was to give a comprehensive overview of various aspects and mechanisms of developmental origins of diseases. Starting from initial research foci mainly centered on a nutritionally impaired intrauterine environment, more recent findings such as postnatal nutrition, preterm birth, paternal programming and putative interventional approaches are summarized. The review outlines general underlying mechanisms and particularly discusses mechanistic explanations for sexual dimorphism in developmental programming. Furthermore, novel hypotheses are presented emphasizing a non-mendelian impact of parental genes on the offspring's phenotype.
Matrix Metalloproteinase Neutrophil Gelatinase-Associated Lipocalin Complex Predicts Atrial Fibrillation Recurrence after Electrical Cardioversion in Obese Patients
Authors: Mlodawska Elzbieta , Tomaszuk-Kazberuk Anna , Lopatowska Paulina , Waszkiewicz Ewa , Bachorzewska-Gajewska Hanna , Malyszko Jolanta , Michniewicz Ewelina , Dobrzycki Slawomir , Musial Wlodzimierz Jerzy
Published: August 2016

Background: There is not much data on matrix metalloproteinase neutrophil gelatinase-associated lipocalin (MMP-NGAL) complex in patients with atrial fibrillation (AF). Aim: The aim of the study was to assess the value of MMP-NGAL complex in predicting AF recurrence after electrical cardioversion. Methods: The serum levels of NGAL, cystatin C, interleukin-6, high-sensitivity C-reactive protein, copeptin, MMP-NGAL complex, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase 1, Von Willebrand factor, B-type natriuretic peptide and the urinary level of NGAL were evaluated before cardioversion. Results: A total of 83 patients with persistent AF were enrolled in the study. Left atrial diameter (LA) ≥4.5 cm was significantly associated with AF recurrence at follow-up (p = 0.009). In selected 39 obese patients, MMP-NGAL complex was associated with AF recurrence (p = 0.03). If the concentration of MMP-NGAL complex increased by 1 ng/ml, the odds of AF recurrence increased by 4% (OR 1.04; CI: 1.00-1.08; p = 0.03). MMP-NGAL complex did not correlate with AF recurrence in patients with a first episode of AF, in patients ≥65 years of age and in patients with a LA ≥4.5 cm or with chronic kidney disease. Conclusions: It is known that the greater the BMI at baseline, the higher the likelihood of progression from paroxysmal to permanent AF. However, European Society of Cardiology (ESC) guidelines do not consider obese patients a population with a low likelihood of success of cardioversion. That is why we need a sensitive marker to predict sinus rhythm maintenance in such a population. We found that MMP-NGAL complex may predict AF recurrence after successful cardioversion in obese patients.
Complementary and Alternative Medicine Use Among Chronically Ill Adolescents from 2 German Birth Cohorts
Authors: Italia Salvatore , Brüske Irene , Heinrich Joachim , Berdel Dietrich , von Berg Andrea , Lehmann Irina , Standl Marie , Wolfenstetter Silke Britta
Published: August 2016

Background: Pediatric use of complementary and alternative medicine (CAM) is popular in Europe, and utilization may be even more prevalent in chronically ill children/adolescents. This study's aim is to assess CAM use among adolescents with chronic conditions. Methods: Data on drug utilization (past 4 weeks) and consultation with CAM providers (past year) were collected using a self-administered questionnaire from 4,677 adolescents from the German GINIplus/LISAplus birth cohorts. All reported drugs were classified into therapeutic categories (conventional drugs, homeopathy, herbal drugs, etc.). Additionally, participants were asked to list any chronic diseases (that were parent-reported, physician-verified diagnoses such as allergies, atopic dermatitis, asthma, or other chronic diseases) that they had had over the previous 5 years. Results: Compared with the total sample, drug utilization in general (60.1% vs. 41.1%), homeopathy use (11.1% vs. 8.1%), and consultation with CAM providers (16.9% vs. 10.9%) was significantly more prevalent among chronically ill adolescents. However, chronically ill adolescents used relatively (proportion of the defined therapeutic category among all drugs used) more conventional drugs than healthy adolescents. Conclusion: Compared with healthy adolescents, CAM use is more prevalent among adolescents with chronic conditions. Nevertheless, CAM may predominantly be used as a complementary treatment option rather than substituting conventional drugs.
Inhibition of mTOR's Catalytic Site by PKI-587 Is a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease
Authors: Freitag Helma , Christen Friederike , Lewens Florentine , Grass Irina , Briest Franziska , Iwaszkiewicz Sara , Siegmund Britta , Grabowski Patricia
Published: August 2016

Background: The characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, the current therapy options are not satisfactory. PKI-587 is a highly potent, novel dual inhibitor of PI3K and mTORC1/C2. Aim: We assessed the effects of PKI-587 in different GEP-NEN tumor models, including the poorly differentiated cell line LCC-18, and compared them with those of the established mTORC1 inhibitor everolimus. Methods: We treated BON, QGP-1, KRJ-I, and LCC-18 cell lines with increasing concentrations of the inhibitor PKI-587, and compared the results with those of everolimus and DMSO. We assessed the impact of the treatments on viability (WST-1 assay), on apoptotic processes (caspase 3/7 assay, JC-1), and on cell cycle regulation (flow cytometry). We determined alterations in signaling mediators by phosphor-specific Western blot analysis and conducted multiplexed gene expression analysis (nCounter® technology). Results: In all cell lines, PKI-587 dose-dependently inhibited proliferation, whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest and induction of apoptosis and successfully suppressed activity of the direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT, and PI3K pathway genes after treatment. Treatment-dependent and cell line-characteristic effects on AKT/Rb/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this paper. Conclusion: PI3K/mTOR dual targeting is a promising new therapeutic approach in neuroendocrine tumor disease that should be evaluated in further clinical trials.
The Effect of Problem-Based Learning on Improvement of the Medical Educational Environment: A Systematic Review and Meta-Analysis
Authors: Qin Yongjie , Wang Yungui , Floden Robert E.
Published: August 2016

Objectives: The aim of this study was to evaluate the effect of problem-based learning on improving the medical educational environment. Materials and Methods: All relevant studies on problem-based learning and the medical educational environment were searched for in PubMed, the Education Resources Information Center (ERIC) catalogue, Google Scholar, China National Knowledge Infrastructure (CNKI) and WanFang Data (WF) databases for material dating from 1969 to May 2015 without any language limitation. Six randomized controlled trials of problem-based learning compared to traditional lecture-based learning were included. The Cochrane risk of bias tool was used to assess the quality of the included studies. Review Manager (Revman) version 5.3 software was used for data analysis. The effect size of the improvement on the medical educational environment was calculated as the mean difference and 95% confidence interval. Heterogeneity was evaluated with Cochrane's χ2 test and I2. Publication bias was assessed by funnel plot, Begg's rank correlation test, and Egg's linear regression test. Results: The six included studies were at low risk of bias in all domains except for three that were at high risk of bias in the domain of allocation concealment. The pooled effect size showed that problem-based learning was better than lecture-based learning in improving the medical educational environment, as measured by the Dundee Ready Education Environment Measure (DREEM), with statistically significant differences. No significant publication bias was observed. The sensitivity analysis showed that the result was reliable. Conclusions: This study showed that problem-based learning was able to improve the medical educational environment as measured by DREEM. However, further studies with larger sample sizes and high-quality data are needed.
O Movimento Bibliográfico: organização do conhecimento no contexto da modernidade
Authors: Mendes Luciana Corts
Published: August 2016

Através de levantamento, revisão e análise bibliográficos, o artigo explora os objetivos e propostas de organização da informação desenvolvidos pelo Movimento Bibliográfico e indica sua influência na Ciência da Informação. O movimento caracterizava-se por sua pluralidade e buscava responder às alterações no mundo informacional decorrentes da modernidade. Apesar de sua especificidade histórica, esse movimento compartilha com a Ciência da Informação o ideário informacional moderno e a relação deste com a cultura. Conclui-se que a cultura da informação contemporânea e aquela do movimento pesquisado apresentam diferenças, porém se entrelaçam.
A Bibliografia Nacional Brasileira: histórico, reflexões e inflexões
Authors: Juvêncio Carlos Henrique , Rodrigues Georgete Medleg
Published: August 2016

A Bibliografia Nacional tem papel de destaque como instrumento de pesquisa e memória da produção intelectual da sociedade. No âmbito de sua construção, este trabalho busca refazer a trajetória histórica de tal instrumento de controle bibliográfico no Brasil a partir do século XIX até os dias atuais tomando como norte a sua importância enquanto inventário da memória intelectual nacional. Utiliza como fonte de pesquisa documentos e publicações sobre o tema de diferentes épocas e em diferentes contextos, sobretudo, publicações destacadas por Edson Nery da Fonseca em suas mais diversas pesquisa sobre o tema. Problematiza a institucionalização da Bibliografia, enquanto disciplina, no país e sua contribuição para a construção da(s) bibliografia(s) nacional(is). Também visa elucidar os papéis exercidos por diferentes instituições ao longo da história como responsáveis pela construção de tal instrumento. Conclui que a Bibliografia Brasileira jamais foi construída plenamente e sempre foi perene frente à necessidade de constante atualização, além de não se tratar de uma política sólida de construção da memória nacional.
Confusa e irritante multidão de livros: relações entre o contexto histórico-informacional da Europa Moderna e a estrutura documentária de Bibliotheca Universalis, de Conrad Gesner
Authors: Araujo Andre Vieira de Freitas , Crippa Giulia
Published: August 2016

A Imprensa teve como um dos seus mais significativos impactos a vasta, intensa e acelerada produção de bibliografias, como meios de registro, organização, seleção, disponibilização e mediação de documentos. Entre as inúmeras conseqüências da Imprensa está a necessidade de se operar a chamada explosão informacional -  fenômeno investigado, do ponto de vista histórico-cultural, por autores como Peter Burke e Ann Blair. A partir desta paisagem, o artigo busca estabelecer relações entre o contexto histórico-informacional da Europa Moderna e Bibliotheca Universalis, de Conrad Gesner (Séc. XVI). Bibliotheca arrola aspectos da cultura manuscrita e impressa e traz implicitamente uma profunda reflexão descritiva e semântica sobre os documentos e os saberes, conforme se evidencia nos estudos de Alfredo Serrai e Fiammetta Sabba. O “gesto bibliográfico” gesneriano é mais do que uma resposta a confusa et noxia illa librorum multitude (“confusa e irritante multidão de livros”, que hoje nos remete ao sentido da denominada information overload): é a força que arquiteta a própria Bibliografia enquanto disciplina.
Entre arte, técnica e tecnologia: algumas considerações sobre a bibliografia e seus gestos
Authors: Crippa Giulia
Published: August 2016

O trabalho propõe uma discussão acerca do conceito de “gesto bibliográfico”, buscando defini-lo em relação às definições de técnica e de tecnologia. Busca entender o âmbito dos fazeres do que chamamos bibliografia, na medida em que essa se torna fazer biblioteconômico, explicitando e organizando suas ferramentas. O cerne da discussão individualiza duas operações diferentes, uma de natureza técnica e outra tecnológica. Sem uma clara fronteira hierárquica entre especulação e aplicação, entre ciência e técnica, é preciso estruturar o discurso das práticas bibliográficas lá onde ainda ele não se articula em teoria. Trata-se de um trabalho de natureza bibliográfica que discute os conceitos, em uma perspectiva histórica, utilizando autores que refletiram sobre essas questões, principalmente Herbert Marcuse, Michel Foucault e Michel de Certau. Com efeito, a tecnologia, entendida como sistema organizado de aparatos a serem utilizados graças a competências técnicas, é um processo que se desenvolve principalmente a partir da Idade Moderna e a bibliografia, entendida como conjunto de práticas ligadas ao fazer também se desenvolve no mesmo eixo temporal. O perfil de autonomia alcançado pela tecnologia, principalmente no campo da informação, produz um conjunto de problemas para o desenvolvimento da bibliografia, que buscaremos individualizar. Nossa proposta é recuperar uma ideia de bibliografia como técnica que se identifica como gesto que produz expressão cultural.
Natureza e origem da Bibliografia: uma perspectiva disciplinar para contemporaneidade
Authors: Sabba Fiammetta
Published: August 2016

O trabalho propõe o estudo da Bibliotheca Universalis de Conrad Gesner através da tipologia de fontes de informação utilizadas pelo autor em sua composição e de sua representatividade bibliográfica em relação à cultura escrita disponível na época. Com base nisso, propõe medir o grau de ‘universalidade’ da obra na perspectiva da meta desejada e dos instrumentos a sua disposição. Para isso, se elabora um percurso de revisão das fontes utilizadas por Gesner, que variam entre catálogos editoriais, catálogos de bibliotecas e, ainda, bibliografias propriamente ditas, fontes obtidas, na maioria das vezes, ao longo de viagens realizadas pelo autor. Se destaca assim, na reconstituição desse percurso de pesquisa de Gesner, a atualidade de seu projeto bibliográfico, fundamentado no princípio de registrar o patrimônio escrito, de classificá-lo e identificar aquilo que ainda precisava se tornar público. Desenvolve-se, ainda, uma discussão que visa mostrar afinidades e paralelismos entre as necessidades de uma construção ‘semântica’ da informação nos nossos tempos e a atualidade do Método Gesneriano para tanto.
Modernidade: uma impressão
Authors: Saldanha Gustavo Silva
Published: August 2016

Da Gramatologia de Derrida à Arqueologia dos Saberes de Foucault, um pensamento filosófico-bibliográfico se consolida, mas tem seu nascimento nas primeiras “aparições” da filosofia ocidental, nas disputas entre parmenídicos e heraclitianos, entre sofistas e socráticos, entre uma cultura clássica e o helenismo. Um certo metaforismo do livro, colaborador direto da construção conceitual de “modernas” concepções de mundo, desde os gregos, se apresenta à história do pensamento. O conceito de “gramatização” tem aqui papel preponderante: ele relaciona objetivamente as transformações do pensamento junto das transformações da linguagem. A proposta desta reflexão filosófica é discutir a relação ubíqua, em um longo decurso histórico, das conexões subjacentes entre uma teoria conhecimento e uma teoria bibliográfica, que “desemboca” atualmente nos discursos tecidos entre tecnologia e linguagem, os quais resultam, por sua vez, na centralidade do papel da Bibliografia, como gesto, arte, ciência. A inflexão histórica tem papel preponderante aqui não por conta da demarcação de uma historiografia das tecnologias da linguagem, mas na possibilidade de realização de suturas no tempo-espaço de afirmação de um ethos bibliográfico que está costurado na passagem das culturas nômades para uma racionalidade sedentária, dependente de memórias estáveis. Deste modo, de uma teoria do conhecimento como “transformação moderna” do pensamento anti-mitológico na Antiguidade (pré-século V antes de Cristo), às novas tecnologias da linguagem pós-1960, uma epistemologia prática, ou seja, uma teoria bibliográfica do conhecimento se estabelece lentamente, constituindo uma episteme distinta em paralelo à história do próprio projeto histórico do pensamento filosófico
Cardiac Magnetic Resonance–Measured Left Atrial Volume and Function and Incident Atrial Fibrillation
Authors: Habibi Mohammadali , Samiei Sanaz , Ambale Venkatesh Bharath , Opdahl Anders , Helle-Valle Thomas M. , Zareian Mytra , Almeida Andre L.C. , Choi Eui-Young , Wu Colin , Alonso Alvaro , Heckbert Susan R. , Bluemke David A. , Lima João A.C.
Published: August 2016

Background—

Early detection of structural changes in left atrium (LA) before atrial fibrillation (AF) development could be helpful in identification of those at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the association of LA volume and function, and incident AF in a multiethnic population free of clinical cardiovascular diseases.

Methods and Results—

In a case–cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants randomly selected from the whole MESA cohort. Participants were followed up for 8 years. Incident AF cases had a larger LA volume and decreased passive, active, and total LA emptying fractions and peak global LA longitudinal strain (peak LA strain) at baseline. In multivariable analysis, elevated LA maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01–1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence interval, 0.48–0.96), and passive and total LA emptying fractions (hazard ratio for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40–0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95% confidence interval, 0.52–0.95), but not active LA emptying fraction, were associated with incident AF.

Conclusions—

Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population. Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development.
Comparison of Fractional Flow Reserve Assessment With Demand Stress Myocardial Contrast Echocardiography in Angiographically Intermediate Coronary Stenoses
Authors: Wu Juefei , Barton David , Xie Feng , O’Leary Edward , Steuter John , Pavlides Gregory , Porter Thomas R.
Published: August 2016

Background—

Real-time myocardial contrast echocardiography (RTMCE) directly measures capillary flow (CBF), which in turn is a major regulator of coronary flow and resistance during demand or hyperemic stress. Although fractional flow reserve (FFR) was developed to assess the physiological relevance of an epicardial stenosis, it assumes maximal microvascular vasodilation and minimal resistance during vasodilator stress. Therefore, we sought to determine the relationship between CBF assessed with RTMCE during stress echocardiography and FFR in intermediate coronary lesions.

Methods and Results—

Sixty-seven vessels with 50% to 80% diameter stenoses by quantitative coronary angiography in 58 consecutive patients were examined with FFR and RTMCE (mean age, 60±13 years). RTMCE was performed using an incremental dobutamine (n=32) or exercise (n=26) stress protocol, and myocardial perfusion was assessed using a continuous infusion of ultrasound contrast. The presence or absence of inducible perfusion defects and wall motion abnormalities were correlated with FFR. Mean percent diameter stenosis was 60±9%. Eighteen stenoses (27%) had an FFR ≤ 0.8. Although 17 of the 18 stenoses that were FFR+ had abnormal CBF during RTMCE, 28 of the 49 stenoses (57%) that were FFR had abnormal CBF, and 24 (49%) had abnormal wall motion in the corresponding coronary artery territory during stress echocardiography.

Conclusions—

In a significant percentage of intermediate stenoses with normal FFR values, CBF during demand stress is reduced, resulting in myocardial ischemia.
Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis
Authors: Treibel Thomas A. , Fontana Marianna , Gilbertson Janet A. , Castelletti Silvia , White Steven K. , Scully Paul R. , Roberts Neil , Hutt David F. , Rowczenio Dorota M. , Whelan Carol J. , Ashworth Michael A. , Gillmore Julian D. , Hawkins Philip N. , Moon James C.
Published: August 2016

Background—

Calcific aortic stenosis (cAS) affects 3% of individuals aged >75 years, leading to heart failure and death unless the valve is replaced. Wild-type transthyretin cardiac amyloid is also a disorder of ageing individuals. Prevalence and clinical significance of dual pathology are unknown. This study explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial biopsy, its imaging phenotype and prognostic significance.

Methods and Results—

A total of 146 patients with severe AS requiring surgical valve replacement underwent cardiovascular magnetic resonance and intraoperative biopsies; 112 had cAS (75±6 years; 57% men). Amyloid was sought histologically using Congo red staining and then typed using immunohistochemistry and mass spectrometry; patients with amyloid underwent clinical evaluation including genotyping and
99m
TC-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) bone scintigraphy. Amyloid was identified in 6 of 146 patients, all with cAS and >65 years (prevalence 5.6% in cAS >65). All 6 patients had wild-type transthyretin amyloid (mean age 75 years; range, 69–85; 4 men), not suspected on echocardiography. Cardiovascular magnetic resonance findings were of definite cardiac amyloidosis in 2, but could be explained solely by AS in the other 4. Postoperative DPD scans demonstrated cardiac localization in all 4 patients who had this investigation (2 died prior). At follow-up (median, 2.3 years), 50% with amyloid had died (versus 7.5% in cAS; 6.9% in age >65 years). In univariable analyses, the presence of transthyretin amyloidosis amyloid had the highest hazard ratio for death (9.5 [95% confidence interval, 2.5–35.8];
P
=0.001).

Conclusions—

Occult wild-type transthyretin cardiac amyloid had a prevalence of 6% among patients with AS aged >65 years undergoing surgical aortic valve replacement and was associated with a poor outcome.
Description of a new species of Priolepis (Perciformes: Gobiidae) from the Red Sea, a new record of Priolepis compita, and a distributional range extension of Trimma fishelsoni
Authors: BOGORODSKY SERGEY V. , SUZUKI TOSHIYUKI , MAL AHMAD O.
Published: August 2016

A new species of Reefgoby, Priolepis melanops, is described from Al Lith, central Saudi Arabian coast of the Red Sea, on the basis of a single adult specimen. It is a distinctive species, and can distinguish from its congeners by the following characters: dorsal-fin rays VI + I,9, no elongate spines in first dorsal fin; anal-fin rays I,8; pectoral-fin rays 14–15, all unbranched; longitudinal scale series 25; no scales on the head or predorsal midline, sides of the nape scaled; a developed transverse pattern of the sensory papillae below the eye; fifth pelvic-fin ray unbranched, its length 47% length of fourth ray; body and most of head brownish orange, densely covered with melanophores; snout, lips, chin and chest black; iris black; fins translucent with narrow black stripe along base of each dorsal fin. Placement of the new species in Priolepis is based on the presence of characteristics currently associated with Priolepis rather than with Trimma. An individual of Priolepis compita Winterbottom was photographed in very shallow water on a reef flat at Sharm el Sheikh, at the entrance of the Gulf of Aqaba, and represents a new record for the Red Sea. The endemic Red Sea species Trimma filamentosus Winterbottom and T. fishelsoni Goren, previously know as far south as Jeddah, were collected at Al Lith, central Saudi Arabia, and represents the southernmost record for both species. Variation of P. compita and T. fishelsoni is noted and the cephalic sensory system of the latter is described for the first time. In addition, we report that records of Trimma tevegae Cohen & Davis from the Red Sea are based on misidentification. A key to distinguish the species of Priolepis and Trimma known from the Red Sea is provided.