bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat-Wave Events in Spain: Air Mass Analysis and Impacts on7Be Concentrations
Authors: Hernández-Ceballos M. A. , Brattich E. , Cinelli G.
Published: June 2016

The present paper describes and characterizes the air mass circulation during the heat-wave events registered during the period 2005–2014 over Spain, paying special attention to the role of the Saharan circulations. Backward trajectories at 500, 1500, and 3000 m in Seville (south), Madrid (centre), and Bilbao (north) during the thirteen heat-wave events identified are analysed. Finally, the impact of the heat-wave events and of each advection pattern on7Be activity concentrations is also analysed. The heat-wave events are characterized roughly by western, southern, and nearby advections, with a higher frequency of the first two types. The analysis shows an increase of African air masses with height, presenting a different spatial impact over Spain, with a decreasing occurrence and a decrease in the simultaneous occurrence percentage from south to north. On average, the7Be activity concentrations during these events show an increase of concentrations in central (21%) and southern (18%) areas and a decrease in northern (13%) Spain. This increase is not associated with Saharan air masses but instead with the arrival of distant westerly air masses.
The Chaotic Attractor Analysis of DJIA Based on Manifold Embedding and Laplacian Eigenmaps
Authors: Song Xiaohua , Niu Dongxiao , Zhang Yulin
Published: June 2016

By using the techniques of Manifold Embedding and Laplacian Eigenmaps, a novel strategy has been proposed in this paper to detect the chaos of Dow Jones Industrial Average. Firstly, the chaotic attractor of financial time series is assumed to lie on a low-dimensional manifold that is embedded into a high-dimensional Euclidean space. Then, an improved phase space reconstruction method and a nonlinear dimensionality reduction method are introduced to help reveal the structure of the chaotic attractor. Next, the empirical study on the financial time series of Dow Jones Industrial Average shows that there exists an attractor which lies on a manifold constructed by the time sequence of Moving average convergence divergence; finally, Determinism Test, Poincaré section, and translation analysis are used as test approaches to prove both whether it is a chaos and how it works.
Euterpe edulis Extract but Not Oil Enhances Antioxidant Defenses and Protects against Nonalcoholic Fatty Liver Disease Induced by a High‐Fat Diet in Rats
Authors: Freitas Rodrigo Barros , Novaes Rômulo Dias , Gonçalves Reggiani Vilela , Mendonça Bianca Gazolla , Santos Eliziária Cardoso , Ribeiro Andréia Queiroz , Lima Luciana Moreira , Fietto Luciano Gomes , Peluzio Maria do Carmo Gouveia , Leite João Paulo Viana
Published: June 2016

We investigated the effects of E. edulis bioproducts (lyophilized pulp [LEE], defatted lyophilized pulp [LDEE], and oil [EO]) on nonalcoholic fatty liver disease (NAFLD) induced by a high‐fat diet (HFD) in rats. All products were chemically analyzed. In vivo, 42 rats were equally randomized into seven groups receiving standard diet, HFD alone or combined with EO, LEE, or LDEE. After NAFLD induction, LEE, LDEE, or EO was added to the animals’ diet for 4 weeks. LEE was rich in polyunsaturated fatty acids. From LEE degreasing, LDEE presented higher levels of anthocyanins and antioxidant capacity in vitro. Dietary intake of LEE and especially LDEE, but not EO, attenuated diet‐induced NAFLD, reducing inflammatory infiltrate, steatosis, and lipid peroxidation in liver tissue. Although both E. edulis bioproducts were not hepatotoxic, only LDEE presented sufficient benefits to treat NAFLD in rats, possibly by its low lipid content and high amount of phenols and anthocyanins.
An Approach for Integrated Analysis of Human Factors in Remote Handling Maintenance
Authors: Guo Jianwen , Sun Zhenzhong , He Jiaxin , Jia Xuejun , Li Hongjuan , Yan Xiaohui , Chen Haibin , Tang Hong , Wu GuoHong
Published: June 2016

Considering dangerous environmental conditions, maintenance of radioactive equipment can be performed by remote handling maintenance (RHM) system. The RHM system is a sophisticated man-machine system. Therefore, human factors analysis is an inevitable aspect considered in guaranteeing successful and safe task performance. This study proposes an approach for integrated analysis of human factors in RHM so as to make the evaluating process more practical. In the approach, indicators of accessibility, health safety, and fatigue are analyzed using virtual human simulation technologies. The human error factors in the maintenance process are analyzed using the human error probability (HEP) based on the success likelihood index method- (SLIM-) analytic hierarchy process (AHP). The psychological factors level of maintenance personnel is determined with an expert scoring. The human factors for the entire RHM system are then evaluated using the interval method. An application example is present, and the application results show that the approach can support the evaluation of the human factors in RHM.
Stress Fracture and Nonunion of Coronoid Process in a Gymnast
Authors: Hetling T. , Bourban P. , Gojanovic B.
Published: June 2016

Background. Gymnasts have high mechanical loading forces of up to 14 times body weight. Overuse lesions are typical in wrists and stress fractures in the olecranon, while isolated fractures of the coronoid process are uncommon. We present a case of retraumatized nonunion stress fracture of the ulnar coronoid process.Case Description. A 19-year-old gymnast presented with elbow pain after training. Imaging confirmed an old fracture of the coronoid process. We describe a 6-month multiphase return to competition rehabilitation program, which allowed him to compete pain-freely.Literature Review. Acute and overuse injuries in gymnasts are known but no nonunion of the coronoid process has been described before. Only one case of stress fracture of coronoid process in a gymnast was reported.Purpose and Clinical Relevance. We could successfully and conservatively return to sport a reactivated nonunion of a stress fracture of the coronoid process.
Transcriptomics: A Step behind the Comprehension of the Polygenic Influence on Oxidative Stress, Immune Deregulation, and Mitochondrial Dysfunction in Chronic Kidney Disease
Authors: Granata Simona , Dalla Gassa Alessandra , Bellin Gloria , Lupo Antonio , Zaza Gianluigi
Published: June 2016

Chronic kidney disease (CKD) is an increasing and global health problem with a great economic burden for healthcare system. Therefore to slow down the progression of this condition is a main objective in nephrology. It has been extensively reported that microinflammation, immune system deregulation, and oxidative stress contribute to CKD progression. Additionally, dialysis worsens this clinical condition because of the contact of blood with bioincompatible dialytic devices. Numerous studies have shown the close link between immune system impairment and CKD but most have been performed using classical biomolecular strategies. These methodologies are limited in their ability to discover new elements and enable measuring the simultaneous influence of multiple factors. The “omics” techniques could overcome these gaps. For example, transcriptomics has revealed that mitochondria and inflammasome have a role in pathogenesis of CKD and are pivotal elements in the cellular alterations leading to systemic complications. We believe that a larger employment of this technique, together with other “omics” methodologies, could help clinicians to obtain new pathogenetic insights, novel diagnostic biomarkers, and therapeutic targets. Finally, transcriptomics could allow clinicians to personalize therapeutic strategies according to individual genetic background (nutrigenomic and pharmacogenomic). In this review, we analyzed the available transcriptomic studies involving CKD patients.
Designing the Adaptive Tracking Controller for Uncertain Fully Actuated Dynamical Systems with Additive Disturbances Based on Sliding Mode
Authors: Van Chi Nguyen
Published: June 2016

This paper addresses the problem of adaptive tracking control for uncertain fully actuated dynamical systems with additive disturbance (FDSA) based on the sliding mode. We use the adaptive mechanism to adjust the uncertain parameters in sliding mode control law which can be switched to two modes depending on the sliding surface. By choosing appropriately the parameters in control law, the desired transient time can be obtained without effects of uncertain parameters and additive disturbances. The chattering phenomenon can be minimized by a chosen constant. This control method is applied to the angles tracking control of the twin rotor multi-input multi-output system (TRMS) which have nonlinear characteristics, the input torque disturbances and the coupling between the horizontal and vertical movements. The simulation and experimental results are presented that validate the proposed solution.
The Role of Proliferation in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer: A Gene Expression–Based Meta-Analysis
Authors: Stover Daniel G. , Coloff Jonathan L. , Barry William T. , Brugge Joan S. , Winer Eric P. , Selfors Laura M.
Published: June 2016

Purpose: To provide further insight into the role of proliferation and other cellular processes in chemosensitivity and resistance, we evaluated the association of a diverse set of gene expression signatures with response to neoadjuvant chemotherapy (NAC) in breast cancer.

Experimental Design: Expression data from primary breast cancer biopsies for 1,419 patients in 17 studies prior to NAC were identified and aggregated using common normalization procedures. Clinicopathologic characteristics, including response to NAC, were collected. Scores for 125 previously published breast cancer–related gene expression signatures were calculated for each tumor.

Results: Within each receptor-based subgroup or PAM50 subtype, breast tumors with high proliferation signature scores were significantly more likely to achieve pathologic complete response to NAC. To distinguish “proliferation-associated” from “proliferation-independent” signatures, we used correlation and linear modeling approaches. Most signatures associated with response to NAC were proliferation associated: 90.5% (38/42) in ER+/HER2− and 63.3% (38/60) in triple-negative breast cancer (TNBC). Proliferation-independent signatures predictive of response to NAC in ER+/HER2− breast cancer were related to immune activity, while those in TNBC comprised a diverse set of signatures, including immune, DNA damage, signaling pathways (PI3K, AKT, Ras, and EGFR), and “stemness” phenotypes.

Conclusions: Proliferation differences account for the vast majority of predictive capacity of gene expression signatures in neoadjuvant chemosensitivity for ER+/HER2− breast cancers and, to a lesser extent, TNBCs. Immune activation signatures are proliferation-independent predictors of pathologic complete response in ER+/HER2− breast cancers. In TNBCs, significant proliferation-independent signatures include gene sets that represent a diverse set of cellular processes. Clin Cancer Res; 22(24); 6039–50. ©2016 AACR.
Targeting Androgen Receptor Aberrations in Castration-Resistant Prostate Cancer
Authors: Sharp Adam , Welti Jonathan , Blagg Julian , de Bono Johann S.
Published: June 2016

Androgen receptor (AR) splice variants (SV) have been implicated in the development of metastatic castration-resistant prostate cancer and resistance to AR targeting therapies, including abiraterone and enzalutamide. Agents targeting AR-SV are urgently needed to test this hypothesis and further improve the outcome of patients suffering from this lethal disease. Clin Cancer Res; 22(17); 4280–2. ©2016 AACR.

See related article by Yang et al., p. 4466
Plk1 Inhibitors in Cancer Therapy: From Laboratory to Clinics
Authors: Gutteridge Rosie Elizabeth Ann , Ndiaye Mary Ann , Liu Xiaoqi , Ahmad Nihal
Published: June 2016

Polo-like kinase 1 (Plk1) overexpression has been shown to occur in a wide range of tumors, prompting research and development of Plk1 inhibitors as a means of cancer treatment. This review discusses recent advances in the development of Plk1 inhibitors for cancer management. Plk1 inhibition has been shown to cause mitotic block and apoptosis of cells with higher mitotic index and therefore higher Plk1 expression. The potential of Plk1 inhibitors as cancer therapeutics has been widely investigated. However, a complete understanding of Plk1 biology/mechanism is yet to be fully achieved. Resistance to certain chemotherapeutic drugs has been linked to Plk1 overexpression, and Plk1-mediated mitotic events such as microtubule rearrangement have been found to reduce the efficacy of chemotherapeutic agents. The Plk1 inhibitor volasertib has shown considerable promise in clinical studies, having reached phase III trials. However, preclinical success with Plk1 inhibitors has not translated well into clinical success. In our view, combined therapies targeting other relevant pathways together with Plk1 may be vital to combat issues observed with monotherapy, especially resistance. In addition, research should also be directed toward understanding the mechanisms of Plk1 and designing additional next generations of specific, potent Plk1 inhibitors to target cancer. Mol Cancer Ther; 15(7); 1427–35. ©2016 AACR.
New Biology to New Treatment of Helicobacter pylori-Induced Gastric Cancer
Authors: Peek Jr. Richard M.
Published: June 2016

Background:Helicobacter pylori is a bacterial carcinogen that is supposed to have the highest known level of risk for the development of gastric cancer, a disease that claims hundreds of thousands of lives per year. Approximately 89% of the global gastric cancer burden and 5.5% of malignancies worldwide are attributed to H. pylori-induced inflammation and injury. However, only a fraction of colonized persons ever develop neoplasia, and disease risk involves well-choreographed interactions between pathogen and host, which are dependent upon strain-specific bacterial factors, host genotypic traits, and/or environmental conditions. Key Messages: One H. pylori strain-specific virulence determinant that augments the risk for gastric cancer is the cag pathogenicity island, a secretion system that injects the bacterial oncoprotein CagA into host cells. Host polymorphisms within genes that regulate immunity and oncogenesis also heighten the risk for gastric cancer, in conjunction with H. pylori strain-specific constituents. Further, conditions such as iron deficiency and high salt intake can influence H. pylori phenotypes that lower the threshold for disease. Conclusions: Delineation of bacterial, host, and environmental mediators that augment gastric cancer risk has profound ramifications for both physicians and biomedical researchers as such findings will not only focus prevention approaches that target H. pylori-infected human populations at increased risk for stomach cancer, but will also provide mechanistic insights into inflammatory carcinomas that develop beyond the gastric niche.
Gut and Liver in Vasculitic Disorders
Authors: Müller-Ladner Ulf
Published: June 2016

Background: Although the gastrointestinal (GI) tract including its related organs is not generally regarded as one of the primary organ systems of primary and secondary vasculitic disorders, there are numerous mechanisms of these diseases operative in or around the different structures and compartments of the GI tract. Key Messages: A majority of the respective clinical symptoms and problems are linked to an alteration of (peri)vascular homeostasis. Alteration of perivascular matrix metabolism can also affect the functional integrity and motility of the GI tract. Apart from the specific GI phenomena of the individual diseases as outlined in detail in this review, the epidemiology of GI involvement follows in general the characteristics of the respective underlying systemic disease. In addition, gender and age do neither influence the occurrence nor the severity of the GI manifestations significantly. With respect to clinical symptoms, vasculitides may result in abdominal pain, bleeding, ileus, intestinal necrosis and hematochezia because of reduced blood flow and hyper-acute occlusion in the antiphospholipid syndrome. Small-bowel involvement in vasculitic entities can cause pseudoobstruction, obstruction, malabsorption and bacterial overgrowth. Laboratory parameters can point to specific diseases but are frequently nonspecific. Thus, if biopsy fails or in unclear endoscopic situations, a variety of imaging techniques including Doppler ultrasound, abdominal CT, MRI and angiography are used and required for identification and localization of the underlying disease. Therapeutic strategies in vasculitides usually include corticosteroids and immunosuppressants, for example, cyclophosphamide in granulomatosis with polyangiitis and in panarteriitis nodosa but also biologics such as rituximab in ANCA-associated vasculitides. Virostatic drugs including interferon-α and ribavirin can be used in hepatitis B- and C-triggered vasculitides such as panarteriitis nodosa and hepatitis C-associated cryoglobulinemia. Conclusions: Immediate diagnostic and therapeutic steps of action need to be performed if vasculitis of the GI tract is suspected in order to avoid irreversible damage to organs and to improve the well-being and life of the affected patient.
Predicting Therapeutic Response by in vivo Molecular Imaging in Inflammatory Bowel Diseases
Authors: Atreya Raja , Neurath Markus F.
Published: June 2016

Background: Different invasive and non-invasive imaging modalities are indispensable tools in the management of inflammatory bowel disease (IBD) patients. Standard imaging procedures like white light endoscopy or MRI are used to define gut inflammation based on structural changes and altered morphology of the mucosa. Nevertheless, it has thus far not been possible to analyse biological processes at the cellular level, which drive intestinal inflammation in IBD patients. The recent advent of molecular imaging in the field of IBD has opened new promising avenues to allow personalized medicine approaches based on in vivo-detected molecular findings. Key Messages: Recent clinical studies have attempted to address the issue of predicting therapeutic response to anti-tumor necrosis factor (TNF) treatment in IBD patients based on the molecular mechanism of action of these agents and corresponding in vivo assessment of mucosal immune responses. Several experimental studies have indicated that one of the main functions of efficacious anti-TNF therapy in IBD is the induction of intestinal cell apoptosis. Fittingly, a corresponding molecular-imaging study using single-photon emission CT for the localization and quantification of cell apoptosis, demonstrated that induction of mucosal T-cell apoptosis correlated with the therapeutic response to anti-TNF therapy in Crohn's disease patients. There was moreover a predictive capacity regarding therapeutic efficacy. As the main biological properties of anti-TNF antibodies in IBD are mediated through binding to membrane-bound TNF (mTNF) expressing intestinal cells, another study used molecular imaging for in vivo visualization of these cells via fluorescent anti-TNF antibodies to predict therapeutic efficacy of these agents. It could be shown that patients with high amounts of mTNF positive cells showed significantly better response rates compared to patients with low amounts of mTNF positive cells. Conclusion: In vivo molecular imaging in IBD has the potential to have an impact on our current treatment approaches and may allow us to individualize specific therapies based on molecular level analysis.
Angiotensin II Enhances Proliferation and Inflammation through AT1/PKC/NF-κB Signaling Pathway in Hepatocellular Carcinoma Cells
Authors: Ji Yuanyuan , Wang Zhidong , Li Zongfang , Zhang Aijun , Jin Yaofeng , Chen Haiyan , Le Xiaofeng
Published: June 2016

Background/Aims: The pathogenesis of hepatocellular carcinoma (HCC) is mainly characterized by persistent cycles of liver injury, inflammation, and compensatory hepatocyte proliferation. Angiotensin II (Ang II) behaves as an endogenous pro-inflammatory molecule playing a significant role in HCC, however, the molecular link between Ang II, proliferation and inflammation remains unclear. Methods: Human HCC cell lines (HepG-2, SMMC-7721, MHCC97-H) were incubated with Ang II at the indicated concentrations for 24, 48, 72 h. MTT, BrdU ELISA, plate colony formation assay, immunohistochemistry, ELISA, small-interfering RNA(siRNA) transfection, quantitative real-time PCR and western blot were applied to assess their functional, morphological and molecular mechanisms in HCC cell lines. Results: High expression of Ang II type 1 receptor (AT1) and low expression of AT2 in HCC cells and tissues were found. Next, Ang II could significantly enhance cell growth and proliferation. Albeit Ang II slightly increased the percentage of HCC cells in the G0/G1 phase using flow cytometry analysis, no statistically significant alterations were shown. Further studies suggested that Ang II could directly induce proliferation associated proteins C-myc and proliferating cell nuclear antigen (PCNA) expressions, and inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) productions in HCC cells. Interestingly, blocking AT1 and AT1 siRNA evidently inhibited Ang II-induced cell proliferation and inflammatory responses in HCC cells. More importantly, these effects may be mediated by AT1/PKC/NF-κB signaling pathway in HCC cell lines. Conclusions: The results propose that Ang II/AT1/PKC/NF-κB signaling pathway is necessary for proliferation and inflammation of HCC cells, which increases our understanding of the pathogenesis and provides clues for developing new strategies against Ang II-related progress of HCC.
Morphine Postconditioning Protects against Reperfusion Injury via Inhibiting JNK/p38 MAPK and Mitochondrial Permeability Transition Pores Signaling Pathways
Authors: Chen Zuolei , Zhang Xuewei , Liu Yingzhi , Liu Zhongkai
Published: June 2016

Background: The purpose of this study was to determine whether c-jun NH2 amino-terminal kinases (JNK) and p38 mitogen-activated protein kinases (MAPK) were involved in morphine postconditioning (MpostC). Methods: The isolated rat hearts were randomly assigned into one of the following groups. Hearts in the time control (TC) group were constantly perfused for 105min. Hearts in the ischemia-reperfusion (I/R) group were subjected to 45 min of ischemia followed by 1 h of reperfusion. MpostC was induced by 10 min of morphine administration at the onset of reperfusion. Anisomycin (an activator of JNK/p38 kinases) was administered with or without morphine during the first 10 min of reperfusion following the 45 min of ischemia. Mitochondria and cytosolic proteins were prepared to detect mitochondrial permeability transition (MPT) and cytochrome C (Cyt-c) respectively. Results: MpostC markedly reduced infarct size (IS/AAR), CK-MB release, and improved cardiac function recovery. However, these protective effects were partly abolished in the presence of anisomycin. I/R significantly increased the phosphorylation of JNK and p38 kinases, mitochondrial permeability transition (MPT) opening and Cyt-c release, while these effects were partly abolished by MpostC. The inhibitory effects of MpostC on the phosphorylation of JNK/p38 kinases, MPT opening and Cyt-c release were totally reversed by Anisocycin, which, used individually, did not show any influence on perfusion injury. Conclusions: These findings suggest that MpostC protects isolated rat hearts against reperfusion injury via inhibiting JNK/p38 MAPKs and mitochondrial permeability transition pores signaling pathways.
Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation In Vivo
Authors: Zhang Qingbin , Chen Liming , Si Zhihua , Bu Haoran , Narasimhulu Chandrakala A. , Song Xueling , Cui Ming-Yu , Liu Hang , Lu Tiewei , He Guanglong , Parthasarathy Sampath , Cui Lianqun , Liu Zhenguo , Cui Yuqi
Published: June 2016

Background/Aims: Oxidized low-density lipoprotein (ox-LDL) is a major component of hyperlipidemia and contributes to atherosclerosis. Endothelial progenitor cells (EPCs) play an important role in preventing atherosclerosis and notably decreased in hyperlipidemia. Ox-LDL and ox-LDL-related reactive oxygen species (ROS) have deleterious effects on EPCs. Probucol as an antioxidant and anti-inflammatory drug reduces ROS production. The present study was to determine if probucol could protect EPCs from ox-LDL in vivo and to investigate the potential mechanisms. Methods: ox-LDL was injected into male C57BL/6 mice for 3 days with or without probucol treatment with PBS as control. Bone marrow (BM) fluid, serum, circulating mononuclear cells (MNCs) and EPCs were collected for analysis. Results: the increased extracellular ROS in BM, serum and blood intracellular ROS production in the mice with ox-LDL treatment in association with a significant reduction of circulating MNCs and EPCs were restored with Probucol treatment. A significant increase in the serum ox-LDL and C-reactive protein and decrease in superoxide dismutase and circulating MNCs and EPCs were observed in hyperlipidemic patients that were effectively reversed with probucol treatment. Conclusion: these data suggested that probucol could protect EPCs from ox-LDL through inhibition of ROS production in vivo.
Crystal-Associated Colitis with Ulceration Leading to Hematochezia and Abdominal Pain
Authors: Desai Meeta , Reiprich Aaron , Khov Nancy , Yang Zhaohai , Mathew Abraham , Levenick John
Published: June 2016

Lower GI bleeding is a common cause for hospitalization in adults. Medication-associated mucosal injury is an important clinical entity that can result in significant morbidity and mortality. We present the case of a 45-year-old woman with a 3-month history of intermittent abdominal cramping and rectal bleeding. Her medical history was extensive and included end-stage renal disease and a remote history of endometrial carcinoma that was treated with radiation. Initial workup was concerning for ischemic and radiation colitis, however, histology was most consistent with acute inflammation and ulceration associated with crystal fragments. Sevelamer and cholestyramine are commonly used ion-exchange resins that have been associated with mucosal damage. Both medications were discontinued and her symptoms resolved. Our case highlights an underrecognized but important cause of hematochezia.
Breast Tuberculosis after Chest Trauma - a Case Report and Review of the Literature
Authors: Perrone Claudio , Altieri Alfonso M. , D''Antonio Salvatore , Leonetti Clara , Alma Mario G.
Published: June 2016

Background: Breast involvement of tuberculosis (TB) is well known but uncommon. It can resemble other diseases, including breast cancer, and diagnosis is quite difficult. So, when facing a breast lesion, a possible tubercular etiology should always be born in mind, relying on qualified laboratories to confirm the diagnosis. Case Report: We describe a 42-year-old woman with a mammary fistula complicating a post-traumatic lump. A critical analysis of the diagnostic process was performed together with a review of the literature, also considering the potential role of trauma in inducing such a rare complication.
Relevanz für Patienten - Naturheilkunde und Komplementärmedizin in medizinischen Leitlinien
Authors: Kaltz Birgit , Sander Cornelia
Published: June 2016

Leitlinien und Patientenleitlinien sind für Patienten von großer Bedeutung. Dies wird hier am Beispiel der chronisch entzündlichen Darmerkrankung dargestellt, wobei der Fokus auf dem Bereich Naturheilkunde und Komplementärmedizin sowie dem Wunsch der Patienten nach qualitätsgesicherten Informationen liegt. Im vorliegenden Beitrag wird auch auf die Forschung im Bereich Komplementär- und Alternativmedizin und die Unterstützungsmöglichkeiten durch den Selbsthilfeverband Deutsche Morbus Crohn / Colitis ulcerosa Vereinigung eingegangen.
Task Force - «Naturheilkunde und Komplementärmedizin in medizinischen Leitlinien»
Authors: Langhorst Jost
Published: June 2016

Im Rahmen der aktuellen Wissenschaftskultur stellt das Bestreben, die evidenzbasierte Naturheilkunde in die Leitlinien zu integrieren, eine besondere Herausforderung dar. In Deutschland werden medizinische Leitlinien primär von den wissenschaftlichen medizinischen Fachgesellschaften und deren Dachgesellschaft, der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. (AWMF), entwickelt und verbreitet. Bisher wird das große klinische Potential von Naturheilkunde und Komplementärmedizin an vielen Stellen nur unzureichend berücksichtigt. Mit der Aufnahme der Gesellschaft für Phytotherapie (GPT) in die AWMF wurde im Jahr 2013 ein neues Kapitel in der Leitlinienarbeit der von der Rut- und Klaus-Bahlsen-Stiftung geförderten Arbeitsgruppe «Naturheilkunde und Komplementärmedizin in medizinischen Leitlinien» aufgeschlagen. Die Bestrebung, Naturheilkunde und Komplementärmedizin fester in der konventionellen medizinischen Versorgung in Deutschland zu etablieren, bekommt damit weiter Auftrieb. Durch die Förderung der Rut- und Klaus-Bahlsen-Stiftung wurden die Mitarbeit oder Unterstützung bei bisher mehr als 20 nationalen und internationalen Leitlinien, die Erstellung von 8 Cochrane-Reviews, 4 davon federführend, und von 40 systematischen Reviews und Meta-Analysen in internationalen Peer-Review-Zeitschriften möglich. Erst durch die konsequente Ausweitung und Vollendung der begonnenen Arbeit wird eine Rückentwicklung (und Rückabwicklung) im Feld der Leitlinienarbeit unmöglich gemacht und damit die Anerkennung von Naturheilkunde und Komplementärmedizin im Fächerkanon weiter gestärkt.
Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer
Authors: Barroso-Sousa Romualdo , Shapiro Geoffrey I. , Tolaney Sara M.
Published: June 2016

Clinical and preclinical data support a significant role for inhibitors of the cyclin-dependent kinases (CDKs) 4 and 6 in the treatment of patients with breast cancer. Recently, based on data showing improvement in progression-free survival, the use of palbociclib (Ibrance; Pfizer, Inc.) in combination with endocrine agents was approved to treat patients with hormone receptor-positive advanced disease. Importantly, 2 other CDK4/6 inhibitors, abemaciclib (LY2835219; Lilly) and ribociclib (LEE011; Novartis), are in the late stage of clinical development. In this review, we will focus on clinical data on these 2 new drugs, highlighting their differences compared to palbociclib in terms of single-agent activity, central nervous system penetration, and common adverse events. In addition, we will present the ongoing clinical trials and discuss future directions in the field.
Palbociclib: First CDK4/6 Inhibitor in Clinical Practice for the Treatment of Advanced HR-Positive Breast Cancer
Authors: Ettl Johannes
Published: June 2016

Palbociclib is the first inhibitor of the cyclin-dependent kinases (CDK) 4 and 6 to be introduced into clinical practice. Preclinical investigations led to its clinical development in advanced hormone receptor (HR)-positive breast cancer. To date, 2 significant clinical trials have been fully published. In this article, the results of these trials and their clinical relevance for the management of HR-positive advanced breast cancer are discussed.
Inter-Rater Reliability of Neck Reflex Points in Women with Chronic Neck Pain
Authors: Weinschenk Stefan , Göllner Richard , Hollmann Markus W. , Hotz Lorenz , Picardi Susanne , Hubbert Katharina , Strowitzki Thomas , Meuser Thomas ,   for the Heidelberg University Neural Therapy Education and Research Group (The HUNTER group)h
Published: June 2016

Background: Neck reflex points (NRP) are tender soft tissue areas of the cervical region that display reflectory changes in response to chronic inflammations of correlated regions in the visceral cranium. Six bilateral areas, NRP C0, C1, C2, C3, C4 and C7, are detectable by palpating the lateral neck. We investigated the inter-rater reliability of NRP to assess their potential clinical relevance. Methods: 32 consecutive patients with chronic neck pain were examined for NRP tenderness by an experienced physician and an inexperienced medical student in a blinded design. A detailed description of the palpation technique is included in this section. Absence of pain was defined as pain index (PI) = 0, slight tenderness = 1, and marked pain = 2. Findings were evaluated either by pair-wise Cohen's kappa (ĸ) or by percentage of agreement (PA). Results: Examiners identified 40% and 41% of positive NRP, respectively (PI > 0, physician: 155, student: 157) with a slight preference for the left side (1.2:1). The number of patients identified with >6 positive NRP by the examiners was similar (13 vs. 12 patients). ĸ values ranged from 0.52 to 0.95. The overall kappa was ĸ = 0.80 for the left and ĸ = 0.74 for the right side. PA varied from 78.1% to 96.9% with strongest agreement at NRP C0, NRP C2, and NRP C7. Inter-rater agreement was independent of patients' age, gender, body mass index and examiner's experience. Conclusion: The high reproducibility suggests the clinical relevance of NRP in women.
Analysis of the Factors Affecting Surgical Success of Implants Placed in Iranian Warfare Victims
Authors: Jafarian Mohammad , Bayat Mohammad , Pakravan Amir-Hossein , Emadi Naghmeh
Published: June 2016

Objective: The aim was to evaluate the survival time and success rates of dental implants in warfare victims and factors that affect implant success. Subjects and Methods: This retrospective study involved 250 Iranian warfare victims who received dental implants from 2003 to 2013. Patients' demographic characteristics, as well as the brand, diameter, length, location and failure rate of the implants were retrieved from patients' dental records and radiographs. The associations between these data and the survival rate were analyzed. Statistical analysis was carried out with χ2 and log-rank tests. Results: Overall, out of the 1,533 dental implants, 61 (4%) failed. The maxillary canine area had the highest failure rate [9 of 132 implants (6.8%)], while the mandibular incisor region had the least number of failures [3 of 147 implants (2.0%)] and the longest survival time (approximately 3,182 days). Maxillary canine areas had the shortest survival (about 2,996 days). The longest survival time was observed in implants with 11 mm length (3,179.72 ± 30.139 days) and 3.75-4 mm diameter (3,131.161 ± 35.96 days), and the shortest survival was found in implants with 11.5 mm length (2,317.79 ± 18.71 days) and 6.5 mm diameter (2,241.45 ± 182.21 days). Moreover, implants with 10 mm length (10.7%) and 5.5-6 mm diameter (22.2%) had the highest failure rate; however, the least failure rate occurred when the implants were 11.5 mm in length (1.9%) and 3-3.5 mm in diameter (3.1%). Conclusions: The brand, length and diameter of implants affected the survival time, failure rate and time to failure. The location of the implant was not statistically significant regarding the mentioned factors, although it has clinical significance.
Evaluation of the xTAG Gastrointestinal Pathogen Panel Assay for the Detection of Enteric Pathogens in Kuwait
Authors: Albert Manuel John , Rotimi Vincent Olubunmi , Iqbal Jamshed , Chehadeh Wassim
Published: June 2016

Objective: To evaluate the utility of the Luminex xTAG gastrointestinal pathogen panel (GPP) assay in the detection of enteric pathogens from diarrheal stool samples in Kuwait. Materials and Methods: The Luminex xTAG GPP assay was used according to the manufacturer's instructions to evaluate single diarrheal stool samples from 109 hospitalized patients at Mubarak Al-Kabeer Hospital, Kuwait, from March 2014 to June 2015. The assay procedure involved nucleic acid extraction from stool samples, amplification of the target by reverse transcriptase polymerase chain reaction, hybridization of the amplified target by probe, detection of the target by the Luminex instrument and computerized data analysis. Conventional microbiological assays were used as the gold standard for comparison. Results: From the 109 diarrheal stool samples, 20 (18.4%) pathogens were detected by the xTAG GPP assay compared to 10 (9.2%) pathogens using conventional assays. Both methods detected 3 Salmonella spp., 3 Clostridium difficile, 2 rotavirus and 2 norovirus. In addition, the xTAG GPP assay detected 1 Shigella sp., 6 Campylobacter spp., 1 Cryptosporidium sp. and 2 Giardia lamblia which were missed by conventional assays. Conclusions: In this study, xTAG GPP detected twice as many pathogens as the conventional assays. We recommend the introduction of this assay in routine diagnostic laboratories for a rapid and better diagnosis and treatment of diarrheal disease.
Comparison of the Nerve Conduction Parameters in Proximally and Distally Located Muscles Innervated by the Bundles of Median and Ulnar Nerves
Authors: Ongun Nedim , Oguzhanoglu Attila
Published: June 2016

Objective: The aim of this study was to investigate and compare the conduction parameters of nerve bundles of median and ulnar nerves that innervate proximal and distal muscles. Subjects and Methods: Thirty male and 30 female healthy volunteers between 18 and 70 years of age were enrolled in the study. The conduction parameters were recorded from the proximally located flexor carpi ulnaris, pronator teres and the flexor carpi radialis muscles to the distally located abductor digiti minimi and abductor pollicis brevis muscles for the ulnar and median nerves. Each nerve was stimulated at the region above the elbow and at the axillary region separately. The Student t test was used for statistical analysis, and Levene's test was used to assess whether or not the group variances exhibited a uniform distribution. Results: The conduction velocities were faster (78.27 ± 6.55 vs. 67.83 ± 6.76 m/s, and 74.57 ± 5.66 and 74.23 ± 5.88 vs. 66.38 ± 6.85 m/s) and the durations of compound muscle action potential (CMAP) response were longer (15.65 ± 2.43 vs. 13.55 ± 1.78 ms, and 16.38 ± 2.39 and 16.04 ± 2.34 vs. 13.40 ± 1.79 ms) in proximally located muscles than in distally located muscles that are innervated either by ulnar or median nerves (p < 0.001). However, the CMAP amplitudes were smaller (2.52 ± 1.16 vs. 5.81 ± 3.13 mV, and 2.90 ± 1.20 and 3.59 ± 1.66 vs. 6.88 ± 2.77 mV) in proximal muscles than in distal muscles (p < 0.001). There was no significant difference (p > 0.05) between males and females regarding conduction velocities and CMAP amplitudes recorded from proximal and distal muscles. Conclusion: Proximal muscles innervated by median or ulnar nerves had lower CMAP amplitude values, longer CMAP durations and higher conduction velocities than distal muscles. These findings could reveal a temporal dispersion and phase cancellation due to desynchronized conduction during nerve stimulation.
Whole-Exome Molecular Autopsy After Exertion-Related Sudden Unexplained Death in the Young
Authors: Anderson Jason H. , Tester David J. , Will Melissa L. , Ackerman Michael J.
Published: June 2016

Background—

Targeted postmortem genetic testing of the 4 major channelopathy-susceptibility genes (
KCNQ1
,
KCNH2
,
SCN5A
, and
RYR2
) have yielded putative pathogenic mutations in ≤30% of autopsy-negative sudden unexplained death in the young (SUDY) cases with highest yields derived from the subset of exertion-related SUDY. Here, we evaluate the role of whole-exome sequencing in exertion-related SUDY cases.

Methods and Results—

From 1998 to 2010, 32 cases of exertion-related SUDY were referred by Medical Examiners for a cardiac channel molecular autopsy. A mutational analysis of the major long-QT syndrome–susceptibility genes (
KCNQ1
,
KCNH2
, and
SCN5A
) and catecholaminergic polymorphic ventricular tachycardia–susceptibility gene (
RYR2
) identified a putative pathogenic mutation in 11 cases. Whole-exome sequencing was performed on the remaining 21 targeted gene–negative SUDY cases. After whole-exome sequencing, a gene-specific surveillance of all genes (N=100) implicated in sudden death was performed to identify putative pathogenic mutation(s). Three of these 21 decedents had a clinically actionable, pathogenic mutation (CALM2-F90L, CALM2-N98S, and PKP2-N634fs). Of the 18 remaining cases, 7 hosted at least 1 variant of unknown significance with a minor allele frequency <1:20 000. The overall yield of pathogenic mutations was higher among decedents aged 1 to 10 years (10/11, 91%) than those aged 11 to 19 years (4/21, 19%,
P
=0.0001).

Conclusions—

Molecular screening in this clinical scenario is appropriate with a pathogenic mutation detection rate of 44% using direct DNA sequencing followed by whole-exome sequencing. Only 5 of the 100 interrogated sudden death genes hosted actionable pathogenic mutations for more than one third of these exertion-related, autopsy-negative SUDY cases.
Treatment Gaps in Adults With Heterozygous Familial Hypercholesterolemia in the United States
Authors: deGoma Emil M. , Ahmad Zahid S. , O’Brien Emily C. , Kindt Iris , Shrader Peter , Newman Connie B. , Pokharel Yashashwi , Baum Seth J. , Hemphill Linda C. , Hudgins Lisa C. , Ahmed Catherine D. , Gidding Samuel S. , Duffy Danielle , Neal William , Wilemon Katherine , Roe Matthew T. , Rader Daniel J. , Ballantyne Christie M. , Linton MacRae F. , Duell P. Barton , Shapiro Michael D. , Moriarty Patrick M. , Knowles Joshua W.
Published: June 2016

Background—

Cardiovascular disease burden and treatment patterns among patients with familial hypercholesterolemia (FH) in the United States remain poorly described. In 2013, the FH Foundation launched the Cascade Screening for Awareness and Detection (CASCADE) of FH Registry to address this knowledge gap.

Methods and Results—

We conducted a cross-sectional analysis of 1295 adults with heterozygous FH enrolled in the CASCADE-FH Registry from 11 US lipid clinics. Median age at initiation of lipid-lowering therapy was 39 years, and median age at FH diagnosis was 47 years. Prevalent coronary heart disease was reported in 36% of patients, and 61% exhibited 1 or more modifiable risk factors. Median untreated low-density lipoprotein cholesterol (LDL-C) was 239 mg/dL. At enrollment, median LDL-C was 141 mg/dL; 42% of patients were taking high-intensity statin therapy and 45% received >1 LDL-lowering medication. Among FH patients receiving LDL-lowering medication(s), 25% achieved an LDL-C <100 mg/dL and 41% achieved a ≥50% LDL-C reduction. Factors associated with prevalent coronary heart disease included diabetes mellitus (adjusted odds ratio 1.74; 95% confidence interval 1.08–2.82) and hypertension (2.48; 1.92–3.21). Factors associated with a ≥50% LDL-C reduction from untreated levels included high-intensity statin use (7.33; 1.86–28.86) and use of >1 LDL-lowering medication (1.80; 1.34–2.41).

Conclusions—

FH patients in the CASCADE-FH Registry are diagnosed late in life and often do not achieve adequate LDL-C lowering, despite a high prevalence of coronary heart disease and risk factors. These findings highlight the need for earlier diagnosis of FH and initiation of lipid-lowering therapy, more consistent use of guideline-recommended LDL-lowering therapy, and comprehensive management of traditional coronary heart disease risk factors.
Sex‐Based Disparities in Incidence, Treatment, and Outcomes of Cardiac Arrest in the United States, 2003–2012
Authors: Kim Luke K. , Looser Patrick , Swaminathan Rajesh V. , Horowitz James , Friedman Oren , Shin Ji Hae , Minutello Robert M. , Bergman Geoffrey , Singh Harsimran , Wong S. Chiu , Feldman Dmitriy N.
Published: June 2016

Background

Recent studies have shown improving survival after cardiac arrest. However, data regarding sex‐based disparities in treatment and outcomes after cardiac arrest are limited.

Methods and Results

We performed a retrospective analysis of all patients suffering cardiac arrest between 2003 and 2012 using the Nationwide Inpatient Sample database. Annual rates of cardiac arrest, rates of utilization of coronary angiography/percutaneous coronary interventions/targeted temperature management, and sex‐based outcomes after cardiac arrest were examined. Among a total of 1 436 052 discharge records analyzed for cardiac arrest patients, 45.4% (n=651 745) were females. Women were less likely to present with ventricular tachycardia/ventricular fibrillation arrests compared with men throughout the study period. The annual rates of cardiac arrests have increased from 2003 to 2012 by 14.0% (
P
trend
<0.001) and ventricular tachycardia/ventricular fibrillation arrests have increased by 25.9% (
P
trend
<0.001). Women were less likely to undergo coronary angiography, percutaneous coronary interventions, or targeted temperature management in both ventricular tachycardia/ventricular fibrillation and pulseless electrical activity/asystole arrests. Over a 10‐year study period, there was a significant decrease in in‐hospital mortality in women (from 69.1% to 60.9%,
P
trend
<0.001) and men (from 67.2% to 58.6%,
P
trend
<0.001) after cardiac arrest. In‐hospital mortality was significantly higher in women compared with men (64.0% versus 61.4%; adjusted odds ratio 1.02,
P
<0.001), particularly in the ventricular tachycardia/ventricular fibrillation arrest cohort (49.4% versus 45.6%; adjusted odds ratio 1.11,
P
<0.001).

Conclusions

Women presenting with cardiac arrests are less likely to undergo therapeutic procedures, including coronary angiography, percutaneous coronary interventions, and targeted temperature management. Despite trends in improving survival after cardiac arrest over 10 years, women continue to have higher in‐hospital mortality when compared with men.
Predictors of Restenosis Following Carotid Angioplasty and Stenting
Authors: Zapata-Arriaza Elena , Moniche Francisco , González Alejandro , Bustamante Alejandro , Escudero-Martínez Irene , De la Torre Laviana Francisco Javier , Prieto María , Mancha Fernando , Montaner Joan
Published: June 2016

Background and Purpose—

Restenosis after carotid angioplasty (with or without stent) is associated with increased rate of stroke and death. Our aim was to determine risk and predictive factors related to carotid restenosis post carotid angioplasty and its association to recurrent cerebrovascular events.

Methods—

All consecutive patients with carotid stenosis treated with angioplasty (n=1060) in a single University Hospital were included (from 2002 to 2013). Follow-up was done prospectively evaluating restenosis, ipsilateral stroke, or death. Restenosis was defined as a narrowing of ≥70% of a previously treated vessel evaluated by ultrasonography.

Results—

Of the 1060 patients treated, 9.2% (97) of patients experienced restenosis during follow up (median 12 [9–32] months). Occurrence of restenosis was associated with ipsilateral stroke during follow-up (
P
=0.049). After Cox regression analysis, hypertension (hazard ratio, 6.2 [1.9–19.9];
P
=0.002), impaired vasoreactivity (hazard ratio, 1.7 [1.09–2.8];
P
=0.019), and angioplasty without stent (hazard ratio, 2.9 [1.2–6.8];
P
=0.012) were independent risk predictors of >70% restenosis.

Conclusions—

Carotid restenosis after carotid angioplasty is associated with ipsilateral stroke occurrence. In our sample, hypertension, angioplasty without stent, and impaired vasoreactivity identify patients at high risk of restenosis and could help to select patients for follow-up ultrasonography imaging.