bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Elevated CO2, O3, and UV Radiation on Soils
Authors: Formánek Pavel , Rejšek Klement , Vranová Valerie
Published: February 2014

In this work, we have attempted to review the current knowledge on the impact of elevated CO2, O3, and UV on soils. Elevated CO2increases labile and stabile soil C pool as well as efficiency of organic pollutants rhizoremediation and phytoextraction of heavy metals. Conversely, both elevated O3and UV radiation decrease inputs of assimilates to the rhizosphere being accompanied by inhibitory effects on decomposition processes, rhizoremediation, and heavy metals phytoextraction efficiency. Contrary to elevated CO2, O3, or UV-B decreases soil microbial biomass, metabolisable C, and soil Ntcontent leading to higher C/N of soil organic matter. Elevated UV-B radiation shifts soil microbial community and decreases populations of soil meso- and macrofauna via direct effect rather than by induced changes of litter quality and root exudation as in case of elevated CO2or O3. CO2enrichment or increased UV-B is hypothesised to stimulate or inhibit both plant and microbial competitiveness for soluble soil N, respectively, whereas O3favours only microbial competitive efficiency. Understanding the consequences of elevated CO2, O3, and UV radiation for soils, especially those related to fertility, phytotoxins inputs, elements cycling, plant-microbe interactions, and decontamination of polluted sites, presents a knowledge gap for future research.
Impact of STAT/SOCS mRNA Expression Levels after Major Injury
Authors: Brumann M. , Matz M. , Kusmenkov T. , Stegmaier J. , Biberthaler P. , Kanz K.-G. , Mutschler W. , Bogner V.
Published: February 2014

Background. Fulminant changes in cytokine receptor signalling might provoke severe pathological alterations after multiple trauma. The aim of this study was to evaluate the posttraumatic imbalance of the innate immune system with a special focus on theSTAT/SOCSfamily.Methods. 20 polytraumatized patients were included. Blood samples were drawn 0 h–72 h after trauma; mRNA expression profiles of IL-10, STAT 3, SOCS 1, and SOCS 3 were quantified by qPCR.Results. IL-10 mRNA expression increased significantly in the early posttraumatic period. STAT 3 mRNA expressions showed a significant maximum at 6 h after trauma. SOCS 1 levels significantly decreased 6 h–72 h after trauma. SOCS 3 levels were significantly higher in nonsurvivors 6 h after trauma.Conclusion. We present a serial, sequential investigation in human neutrophil granulocytes of major trauma patients evaluating mRNA expression profiles of IL-10, STAT 3, SOCS 1, and SOCS 3. Posttraumatically, immune disorder was accompanied by a significant increase of IL-10 and STAT 3 mRNA expression, whereas SOCS 1 mRNA levels decreased after injury. We could demonstrate that death after trauma was associated with higher SOCS 3 mRNA levels already at 6 h after trauma. To support our results, further investigations have to evaluate protein levels of STAT/SOCS family in terms of posttraumatic immune imbalance.
Multiple Multilateral Coronary-Cameral Fistulae in a Patient with Minor Cardiac Venous System
Authors: Markota Darko , Prskalo Zrinko , Markota Ivica , Starcevic Boris , Maskovic Josip , Tomic Monika , Brizic Ivica
Published: February 2014

A 40-year-old man was hospitalized in the coronary care unit with chest pain and abnormal electrocardiogram. Twenty days earlier, the patient underwent laparoscopic gallbladder surgery. Due to chest pain and ischemic ECG changes, patient was subjected to coronary angiography. The selective coronary angiography revealed multiple multilateral fistulae arising from the left anterior descending artery, circumflex artery, and the right coronary artery draining to the left ventricle. Multislice computed tomography showed hypoplastic coronary sinus and minor cardiac venous system.
A New High-Order Stable Numerical Method for Matrix Inversion
Authors: Haghani F. Khaksar , Soleymani F.
Published: February 2014

A stable numerical method is proposed for matrix inversion. The new method is accompanied by theoretical proof to illustrate twelfth-order convergence. A discussion of how to achieve the convergence using an appropriate initial value is presented. The application of the new scheme for finding Moore-Penrose inverse will also be pointed out analytically. The efficiency of the contributed iterative method is clarified on solving some numerical examples.
A Compact Planar UWB Antenna with Triple Controllable Band-Notched Characteristics
Authors: Abdelhalim Chaabane , Farid Djahli
Published: February 2014

A modified compact planar ultrawideband (UWB) monopole antenna with triple controllable band-notched characteristics is presented in this paper. The proposed antenna consists of a modified stair cased V-shaped radiating element and partial ground plane. The triple band-notched characteristics are achieved by embedding two different vertical up C-shaped slots with a vertical down C-shaped slot in the radiating patch and in the ground plane, respectively. Besides, the bandwidth of each rejected band can be independently controlled by adjusting the dimensions of the corresponding band notched structure. The proposed antenna with rejected bands characteristics is successfully simulated, prototyped, and measured. The measured results show that the antenna operates until upper 11 GHz for voltage standing wave ratio (VSWR) is less than 2, and exhibits bands rejection of 1.6–2.66 GHz (49.76%), 3-4 GHz (28.57%), and 5.13–6.03 GHz (16.12%). Moreover, the proposed antenna shows a near omnidirectional radiation patterns, stable peak gain, and with small group delay and transfer function variation on the whole UWB frequency range except in the notched frequency bands, which makes it suitable for being used in the future UWB applications.
Further Studies on Arcanobacterium phocisimile: a Novel Species of Genus Arcanobacterium
Authors: Sammra Osama , Balbutskaya Anna , Hijazin Muaz , Nagib Samy , Alber Jörg , Lämmler Christoph , Abdulmawjood Amir , Prenger-Berninghoff Ellen , Timke Markus , Kostrzewa Markus , Siebert Ursula
Published: February 2014

Arcanobacterium phocisimile, a newly described species with the type strain A. phocisimile 2698T isolated from a vaginal swab of a harbour seal and four additional A. phocisimile strains also isolated from four harbour seals could reliably be identified by phenotypic properties, by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), and by sequencing the genomic targets 16S rDNA and 16S-23S rDNA intergenic spacer region and the genes rpoB and gap. The A. phocisimile strains investigated in the present study were isolated together with several other bacterial species indicating that the pathogenic importance of A. phocisimile remains unclear. However, the detection of peptidic spectra by MALDI-TOF MS and the presented phenotypic and genotypic approach might help to identify A. phocisimile in future.
The Occurrence ofblaCTX-M,blaSHV, andblaTEMGenes in Extended-Spectrumβ-Lactamase-Positive Strains ofKlebsiella pneumoniae,Escherichia coli, andProteus mirabilisin Poland
Authors: Ojdana Dominika , Sacha Paweł , Wieczorek Piotr , Czaban Sławomir , Michalska Anna , Jaworowska Jadwiga , Jurczak Anna , Poniatowski Bogusław , Tryniszewska Elżbieta
Published: February 2014

Bacteria belonging to theEnterobacteriaceaefamily that produce extended-spectrumβ-lactamase (ESBL) enzymes are important pathogens of infections. Increasing numbers of ESBL-producing bacterial strains exhibiting multidrug resistance have been observed. The aim of the study was to evaluate the prevalence ofblaCTX-M,blaSHV, andblaTEMgenes among ESBL-producingKlebsiella pneumoniae,Escherichia coli, andProteus mirabilisstrains and to examine susceptibility to antibiotics of tested strains. In our study, thirty-six of the tested strains exhibitedblaCTX-Mgenes(blaCTX-M-15,blaCTX-M-3,blaCTX-M-91, andblaCTX-M-89). Moreover, twelve ESBL-positive strains harboredblaSHVgenes(blaSHV-18,blaSHV-7,blaSHV-2, andblaSHV-5), and the presence of ablaTEMgene(blaTEM-1)in twenty-five ESBL-positive strains was revealed. AmongK. pneumoniaethe multiple ESBL genotype composed ofblaCTX-M-15, blaCTX-M-3, blaSHV-18, blaSHV-7, blaSHV-2, andblaSHV-5genes encoding particular ESBL variants was observed. Analysis of bacterial susceptibility to antibiotics revealed that, amongβ-lactam antibiotics, the most effective againstE. colistrains was meropenem (100%), whereasK. pneumoniaewere completely susceptible to ertapenem and meropenem (100%), andP. mirabilisstrains were susceptible to ertapenem (91.7%). Moreover, among non-β-lactam antibiotics, gentamicin showed the highest activity toE. coli(91.7%) and ciprofloxacin the highest toK. pneumoniae(83.3%).P. mirabilisrevealed the highest susceptibility to amikacin (66.7%).
Challenges in the Smart Grid Applications: An Overview
Authors: Bari Ataul , Jiang Jin , Saad Walid , Jaekel Arunita
Published: February 2014

The smart grid is expected to revolutionize existing electrical grid by allowing two-way communications to improve efficiency, reliability, economics, and sustainability of the generation, transmission, and distribution of electrical power. However, issues associated with communication and management must be addressed before full benefits of the smart grid can be achieved. Furthermore, how to maximize the use of network resources and available power, how to ensure reliability and security, and how to provide self-healing capability need to be considered in the design of smart grids. In this paper, some features of the smart grid have been discussed such as communications, demand response, and security. Microgrids and issues with integration of distributed energy sources are also considered.
Impact of an Anticaries Mouthrinse onIn VitroRemineralization and Microbial Control
Authors: Sun Frank C. , Engelman E. Eric , McGuire James A. , Kosmoski Gabrielle , Carratello Lauren , Ricci-Nittel Danette , Zhang Jane Z. , Schemehorn Bruce R. , Gambogi Robert J.
Published: February 2014

Objective. The objective of this research was to evaluate the caries control potential of a new fluoride mouthrinse that also contained antimicrobial agents and a biofilm disrupting agent using differentin vitromodels.Methods. Fourin vitrostudies were conducted to assess the performance of this three pronged approach to caries control: (1) traditional enamel fluoride uptake, (2) surface microhardness study using pH cycling model and subsequent fluoride uptake, (3) a salivary biofilm flow-through study to determine the anti-microbial activity, and (4) a single species biofilm model measuring effect on biofilm matrix disruption.Results. The data showed that a LISTERINE rinse with fluoride, essential oils and xylitol was superior in promoting enamel fluoride uptake and in enhancing antimicrobial activity over traditional commercially available fluoridated products. An increase of the surface microhardness was observed when the LISTERINE rinse was used in combination with fluoridated toothpaste versus the fluoridated toothpaste alone. Finally, it was demonstrated that xylitol solutions disrupted and reduced the biovolume of biofilm matrix of matureStreptococcus mutans.Conclusion. Thesein vitrostudies demonstrated that a fluoride mouthrinse with antimicrobial agent and biofilm matrix disrupting agent provided multifaceted and enhanced anti-caries efficacy by promoting remineralization, reducing acidogenic bacteria and disrupting biofilm matrix.
A New Pull-Out Technique for In-Place Estimation of Concrete Compressive Strength
Authors: Latte Bovio F. , Latte Bovio G. , Brencich A. , Cassini G. , Pera D. , Riotto G.
Published: February 2014

A new type of postinstalled wedge anchor (B15G) is presented. A refined geometry of the anchor bolt and a careful choice of all the technical details allow the insert to work also in tensile stress states and to avoid much of the practical uncertainties that affect the commonly used procedures. The calibration of the procedure has been performed on 3 classes of concrete and for 5 stress distributions (medium and low compression, vanishing stress states, inhomogeneous compressive stresses, and inhomogeneous tensile stresses). It has been found that the correlation curves, pull-out force versus compressive strength, are not linear and depend on the stress state; besides, the statistical scattering of the calibration tests never exceeds 7-8% of the average values.
A Randomized Trial to Increase Colonoscopy Screening in Members of High-Risk Families in the Colorectal Cancer Family Registry and Cancer Genetics Network
Authors: Lowery Jan T. , Horick Nora , Kinney Anita Y. , Finkelstein Dianne M. , Garrett Kathleen , Haile Robert W. , Lindor Noralane M. , Newcomb Polly A. , Sandler Robert S. , Burke Carol , Hill Deirdre A. , Ahnen Dennis J.
Published: February 2014

Background: Individuals with a strong family history of colorectal cancer have significant risk for colorectal cancer, although adherence to colonoscopy screening in these groups remains low. This study assessed whether a tailored telephone counseling intervention can increase adherence to colonoscopy in members of high-risk families in a randomized, controlled trial.

Methods: Eligible participants were recruited from two national cancer registries if they had a first-degree relative with colorectal cancer under age 60 or multiple affected family members, which included families that met the Amsterdam criteria for hereditary non-polyposis colon cancer (HNPCC), and if they were due for colonoscopy within 24 months. Participants were randomized to receive a tailored telephone intervention grounded in behavioral theory or a mailed packet with general information about screening. Colonoscopy status was assessed through follow-up surveys and endoscopy reports. Cox proportional hazards models were used to assess intervention effect.

Results: Of the 632 participants (ages 25–80), 60% were female, the majority were White, non-Hispanic, educated, and had health insurance. Colonoscopy adherence increased 11 percentage points in the tailored telephone intervention group, compared with no significant change in the mailed group. The telephone intervention was associated with a 32% increase in screening adherence compared with the mailed intervention (HR, 1.32; P = 0.01).

Conclusions: A tailored telephone intervention can effectively increase colonoscopy adherence in high-risk persons. This intervention has the potential for broad dissemination to healthcare organizations or other high-risk populations.

Impact: Increasing adherence to colonoscopy among persons with increased colorectal cancer risk could effectively reduce incidence and mortality from this disease. Cancer Epidemiol Biomarkers Prev; 23(4); 601–10. ©2014 AACR.
Omacetaxine: A Protein Translation Inhibitor for Treatment of Chronic Myelogenous Leukemia
Authors: Gandhi Varsha , Plunkett William , Cortes Jorge E.
Published: February 2014

Chronic myelogenous leukemia (CML) is driven by the Bcr-Abl fusion protein, which is a result of a (9;22) chromosomal translocation. Imatinib, dasatinib, and nilotinib (tyrosine kinase inhibitors, TKI) have revolutionized how CML is treated. Although the majority of patients respond to these kinase inhibitors, a subset becomes resistant to these therapeutics. Synribo (omacetaxine mepesuccinate) was recently approved by the U.S. Food and Drug Administration for Philadelphia-positive CML either in the chronic or the accelerated phase whose disease failed two prior TKIs. With omacetaxine 1.25 mg/m2 twice daily for 14 days during induction and for 7 days during maintenance, a major cytogenetic response occurred in 20% of patients in the chronic phase and major hematologic response in 27% of patients in the accelerated phase. Laboratory investigations unraveled the mechanism of action and effectiveness of this agent. Bcr-Abl protein is intrinsically programmed to turn over with a short half-life that makes it susceptible to protein translation inhibitors. Omacetaxine (homoharringtonine) inhibits total protein biosynthesis by binding to A-site cleft of ribosomes. As a corollary to this action, there is a diminution of short-lived proteins, such as Bcr-Abl, followed by cell death. Approval of this first-in-class protein translation inhibitor opens up new avenues for its use in other diseases as well as mechanism-based combinations. Clin Cancer Res; 20(7); 1735–40. ©2014 AACR.
Wilhelm Erb's Years in Leipzig (1880-1883) and Their Impact on the History of Neurology
Authors: Steinberg Holger , Wagner Armin
Published: February 2014

Background: Between 1880 and 1883, the famous German neurologist Wilhelm Erb was appointed Professor of Special Pathology at Leipzig University and Head of the Medical Outpatient Department. Summary: Besides the favourable clinical conditions, it was first and foremost the access to large numbers of patients that enabled him to both establish a new, juvenile form of progressive muscular atrophy and to classify various forms of muscular atrophies already discovered into a new clinical entity which he called dystrophia muscularis progressiva. Key Messages: His summarising these different forms of muscular atrophies into one group is the most long-lasting outcome of Erb's years in Leipzig. The access to large numbers of different patients at the Medical Outpatient Department, on the one hand, and the dynamics of Leipzig's neurosciences, in particular the so-called ‘Leipzig Nervous Circle', on the other, had a lasting impact on Erb and definitely gave him other valuable insights, such as the thought that tabes dorsalis must have been caused by a syphilitic infection.
Pioneering the Concepts of Stereognosis and Polyradiculoneuritis: Octave Landry (1826-1865)
Authors: Walusinski Olivier
Published: February 2014

Octave Landry was one of a long list of fine 19th century clinicians who died very young and whose discoveries in physiology and descriptions of new clinical pictures helped found current-day neurology. In 1852, Landry proposed a new take on the physiology of sensation which laid the ground for the concepts of proprioception and stereognosis. He also described the clinical picture of a rapidly progressing ascending paralysis, which in 1859 prefigured Guillain-Barré syndrome. In discussing his very active life, we will mention the hydrotherapies in fashion at the time and the pleasures of Parisian society. Landry's career was also marked by terrible cholera epidemics, one of which killed him at age 39, in the prime of his working life as a devoted physician.
Multivalent Choline Dendrimers Increase Phagocytosis of Streptococcus pneumoniae R6 by Microglial Cells
Authors: Ribes Sandra , Riegelmann Jörn , Redlich Sandra , Maestro Beatriz , de Waal Bas , Meijer E.W. , Sanz Jesús M. , Nau Roland
Published: February 2014

Background: Pneumococcal virulence factors common to all serotypes, such as choline-binding proteins (CBPs), are promising therapeutic targets in pneumococcal infections. We studied the effect of a choline dendrimer with maximized binding affinity/specificity for CBPs on microglia-mediated pneumococcal phagocytosis. Methods: Pneumoccocal cultures were exposed to dendrimers containing 8 choline end groups or amino groups as controls, either from the beginning of bacterial growth or at the late exponential phase. The effect of long/short co-incubation was assessed in terms of bacterial morphological changes and increase in bacterial uptake by primary microglial cultures. Results: Inhibiting CBPs by micromolar concentrations of a choline dendrimer caused the formation of long pneumococcal chains that were readily phagocytosed by microglia. Enhanced phagocytosis was dendrimer dose-dependent. Long bacteria-dendrimer co-incubation (14 h) resulted in a higher bacterial uptake than short co-incubation (2 h; p < 0.001). Conclusions: Multivalent dendrimers containing choline end groups are promising antimicrobial agents for the management of pneumococcal diseases.
Artificial Nutrition and Intestinal Mucosal Barrier Functionality
Authors: Anastasilakis Chrysostomos D. , Ioannidis Orestis , Gkiomisi Athina I. , Botsios Dimitrios
Published: February 2014

The gastrointestinal tract has a major role in digestion and absorption of nutrients while playing a leading role in defense of the body. It forms a shield against the invasion of various microorganisms or their products (e.g. antigens, toxins) and therefore it is important to establish its integrity and functionality. That depends on the route of administration and the composition of the artificial nutrition. This study concentrates on the influences of different kinds of artificial nutrition in the functionality of the intestinal mucosal barriers. It seems that full macromolecular solutions of enteral nutrition ensure an adequate mucous immune response, while a lack of nutritional stimulus in the lumen leads rapidly to a dysfunction of gastric-associated lymphatic tissue and mucosal immune system. This dysfunction renders the patients susceptible to infections in distant organs, hospital pneumonia, and multiorgan failure of non-infectious etiology. In patients with indication of total parenteral nutrition administration, addition of bombesin or glutamine preserves mucosal immune response and may limit the adverse effects.
Diagnostic Accuracy Measures
Authors: Eusebi Paolo
Published: February 2014

Background: An increasing number of diagnostic tests and biomarkers have been validated during the last decades, and this will still be a prominent field of research in the future because of the need for personalized medicine. Strict evaluation is needed whenever we aim at validating any potential diagnostic tool, and the first requirement a new testing procedure must fulfill is diagnostic accuracy. Summary: Diagnostic accuracy measures tell us about the ability of a test to discriminate between and/or predict disease and health. This discriminative and predictive potential can be quantified by measures of diagnostic accuracy such as sensitivity and specificity, predictive values, likelihood ratios, area under the receiver operating characteristic curve, overall accuracy and diagnostic odds ratio. Some measures are useful for discriminative purposes, while others serve as a predictive tool. Measures of diagnostic accuracy vary in the way they depend on the prevalence, spectrum and definition of the disease. In general, measures of diagnostic accuracy are extremely sensitive to the design of the study. Studies not meeting strict methodological standards usually over- or underestimate the indicators of test performance and limit the applicability of the results of the study. Key Messages: The testing procedure should be verified on a reasonable population, including people with mild and severe disease, thus providing a comparable spectrum. Sensitivities and specificities are not predictive measures. Predictive values depend on disease prevalence, and their conclusions can be transposed to other settings only for studies which are based on a suitable population (e.g. screening studies). Likelihood ratios should be an optimal choice for reporting diagnostic accuracy. Diagnostic accuracy measures must be reported with their confidence intervals. We always have to report paired measures (sensitivity and specificity, predictive values or likelihood ratios) for clinically meaningful thresholds. How much discriminative or predictive power we need depends on the clinical diagnostic pathway and on misclassification (false positives/negatives) costs.
Migraine Headache Triggered Specifically by Sunlight: Report of 16 Cases
Authors: Tekatas Aslan , Mungen Bulent
Published: February 2014

Migraine headaches may take place due to various triggering factors. One or more triggering factors can be detected in a migraine patient. To our knowledge, a factor that is known to trigger migraine attacks in a patient does not cause headache each time the patient is exposed to it. Migraine headaches also can be experienced without these factors. Here, we describe a case series of 16 sunlight-induced migraine patients. Records of patients admitted to Firat University Faculty of Medicine Clinic of Neurology with a complaint of headache between January 2001 and June 2010 were scanned. Among those patients, the ones suffering headaches after being exposed to sunlight were examined comprehensively. Nine patients were female and 7 were male. Fourteen patients had the characteristics of migraine without aura, while 2 patients had the characteristics of migraine with aura. The mean times to headache onset after sunlight exposure were 5-10 min in summer and 60 min in winter. Migraine headaches can be triggered by many different causes. We view sunlight as a single triggering factor which should be questioned in migraine patients.
Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX Trial): Rationale and Design
Authors: Hoffmann Kristine , Frederiksen Kristian S. , Sobol Nanna Aue , Beyer Nina , Vogel Asmus , Simonsen Anja Hviid , Johannsen Peter , Lolk Annette , Terkelsen Ole , Cotman Carl W. , Hasselbalch Steen G. , Waldemar Gunhild
Published: February 2014

Background: Exercise is hypothesized to improve cognition, physical performance, functional ability and quality of life, but evidence is scarce. Previous studies were of short duration, often underpowered and involving home-based light exercise programs in patients with undefined dementia. The aim of the ADEX (‘Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: the Effect of Physical Exercise') trial is to establish whether aerobic exercise is effective in improving cognition as well as in reducing the prevalence of psychiatric symptoms among patients with Alzheimer's disease (AD). Methods: The ADEX study is a multicenter, single-blind, randomized trial with two arms: an intervention group attending 16 weeks of continuously supervised moderate-to-high intensity aerobic exercise and a control group receiving usual care. We plan to recruit 192 patients with mild AD. The primary outcome measure is change from baseline in cognitive performance at 16 weeks (as measured by the Symbol Digit Modalities test). Conclusions: To our knowledge this is the first large-scale controlled study to investigate the effects of supervised moderate aerobic exercise on cognition in patients with AD. Recruitment began in January 2012 and results are expected to be available in 2014. We summarize the methodological challenges we and other studies have faced in this type of complex multicenter intervention with unique challenges to study design.
Current Options for the Management of Aneurysmal Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: A Comprehensive Review of the Literature
Authors: Dabus Guilherme , Nogueira Raul G.
Published: February 2014

Objectives: Cerebral vasospasm is one of the leading causes of morbi-mortality following aneurysmal subarachnoid hemorrhage. The aim of this article is to discuss the current status of vasospasm therapy with emphasis on endovascular treatment. Methods: A comprehensive review of the literature obtained by a PubMed search. The most relevant articles related to medical, endovascular and alternative therapies were selected for discussion. Results: Current accepted medical options include the oral nimodipine and ‘triple-H' therapy (hypertension, hypervolemia and hemodilution). Nimodipine remains the only modality proven to reduce the incidence of infarction. Although widely used, ‘triple-H' therapy has not been demonstrated to significantly change overall outcome after cerebral vasospasm. Indeed, both induced hypervolemia and hemodilution may have deleterious effects, and more recent physiologic data favor normovolemia with induced hypertension or optimization of cardiac output. Endovascular options include percutaneous transluminal balloon angioplasty (PTA) and intra-arterial (IA) infusion of vasodilators. Multiple case reports and case series have been encountered in the literature using different drug regimens with diverse mechanisms of action. Compared with PTA, IA drug infusion has the advantages of distal penetration and a better safety profile. Its main disadvantages are the more frequent need for repeat treatments and its systemic hemodynamic repercussions. Alternative options using intraventricular/cisternal drug therapy and flow augmentation strategies have also shown possible benefits; however, their use is not yet as well established. Conclusion: Blood pressure or cardiac output optimization should be the mainstay of hyperdynamic therapy. Endovascular treatment appears to have a positive impact on neurological outcome compared with the natural history of the disease. The role of intraventricular therapy and flow augmentation strategies in association with medical and endovascular treatment may, in the future, play a growing role in the management of patients with severe refractory vasospasm.
Research on Neonatal Microbiomes: What Neonatologists Need to Know
Authors: Sherman Michael P. , Minnerly John , Curtiss William , Rangwala Shaukat , Kelley Scott T.
Published: February 2014

The aim of this article is to educate neonatal caregivers about metagenomics. This scientific field uses novel and ever changing molecular methods to identify how infants become colonized with microbes after birth. Publications using metagenomics appear infrequently in the neonatal literature because clinicians are unaccustomed to the analytical techniques, data interpretation, and illustration of the results. This review covers those areas. After a brief introduction of neonatal citations forthcoming from metagenomic studies, the following topics are covered: (1) the history of metagenomics, (2) a description of current and emerging instruments used to define microbial populations in human organs, and (3) how extensive databases generated by genome analyzers are examined and presented to readers. Clinicians may feel like they are learning a new language; however, they will appreciate this task is essential to understanding and practicing neonatal medicine in the future.
Colorectal Cancer: Basic and Translational Research
Authors: Zhou J.J. , Zheng S.
Published: February 2014

Background: Colorectal cancer (CRC) still accounts for high mortality and morbidity of cancer patients worldwide. Early detection screening and therapeutic management of CRC are still traditional, with some important progress including cetuximab, microsatellite instability and the concept of CRC intrinsic subtypes. Summary: Most achievements are derived from translational cancer research. Translational cancer research attempts to better understand the heterogeneity of human cancer and further turn discoveries into benefits for cancer patients. The four basic strategies of translational research can be depicted as (a) biomarker discovery, (b) identification in xenografts, (c) population-based verification and (d) clinical validation. Key Message Translational research has led to significant benefits in the screening and management of patients with colorectal cancer, such as the identification of responders to cetuximab therapy, and the application of microsatellite instability and intrinsic subtyping of colorectal cancers towards personalized therapy. Practical Implications The process of translational research involves four basic strategies: (a) biomarker discovery, (b) identification of the biomarkers in xenografts, (c) population-based verification and (d) clinical validation. Several prognostic biomarkers, namely SPARCL1, HMGA2, RRM2 and SOX2, have been successfully identified following these strategies. To address the problem of treatment failure, therapy should be adapted to the molecular phenotype and colorectal cancer intrinsic subtype of the tumor. A case in point is the presence of mutated KRAS, which can be used to identify non-responders to cetuximab therapy. Likewise, microsatellite instability is a strong predictor of response to fluorouracil-based adjuvant chemotherapy in stage II and III colon cancer. A comprehensive classification of the intrinsic subtypes of colorectal cancer not only enhances our understanding of response to therapy and prognosis, but also enables treatment to be tailored to the individual patient.
Pancreatic Cancer: Clinical Significance of Biomarkers
Authors: Ohuchida Kenoki , Ohtsuka Takao , Mizumoto Kazuhiro , Hashizume Makoto , Tanaka Masao
Published: February 2014

Background: Improvement in the prognosis of patients with pancreatic cancer, novel effective screening and diagnostic strategies and treatments are needed. Recent advances in the understanding of pancreatic carcinogenesis and tumor microenvironment have allowed identification of biomarkers for screening, diagnosis and prediction of cancer treatments, including novel therapies targeting specific cancer or stromal cell subpopulations. Personalized therapy in pancreatic cancer is also promising as several drugs such as S1, capecitabine and gemcitabine reportedly have significant therapeutic effects. Predictive markers are thus needed to select patients most likely to benefit from therapies based on gemcitabine or other drugs. Summary: We review the clinical significance of promising screening, diagnostic, predictive and prognostic biomarkers based on genetic and epigenetic alterations and microRNA abnormalities in pancreatic cancer. We also review new types of biomarkers based on stromal cells, such as pancreatic stellate cells, in the microenvironment of pancreatic cancer. Key Message Recent advances in our understanding of pancreatic carcinogenesis and the tumor microenvironment have enabled the identification of biomarkers that can be used for screening, diagnosis and prediction of therapeutic response, including the response to novel agents targeting specific cancer cell subpopulations. Practical Implications Although genetic mutations (found in K-ras, p53and p16INK4A) as well as high levels of telomerase activity are frequently associated with pancreatic cancer, their applicability as biomarkers for clinical use has not yet been established. Microarray studies have identified several proteins related to pancreatic cancer. Several of these molecules, such as S100P, MUC1 and MUC5AC, can be quantified in plasma and other body fluids, indicating their utility as potential biomarkers. Research on gemcitabine resistance has uncovered several candidate markers, including genes related to the metabolism and transport of gemcitabine, which may provide a means for identifying those patients who will not benefit from gemcitabine therapy. MicroRNA (miRNA) profiling has revealed an array of miRNAs that are differentially expressed: for example, miR-142-5p and miR-204 may be predictors of response to gemcitabine-based therapy in patients with resected pancreatic cancer. Molecules secreted by pancreatic stellate cells, such as CD10 and CD271, could provide novel targets for the cell-specific management of pancreatic cancer. The use of duodenal juice provides a promising new approach in pancreatic cancer screening.
Epidemiology of Multiple Sclerosis in Iran: A Systematic Review
Authors: Etemadifar Masoud , Sajjadi Sepideh , Nasr Zahra , Firoozeei Toktam Sadat , Abtahi Seyed-Hossein , Akbari Mojtaba , Fereidan-Esfahani Mahboobeh
Published: February 2014

Background: There is a wide variation in the prevalence of multiple sclerosis (MS) in different geographical regions and the epidemiology of MS in Iran has been a major topic of concern during the last decade. Several population-based studies have shown a sharp increase in the prevalence and incidence of MS in this region. In this study, for the first time, the aim was to provide a comprehensive review regarding the incidence and prevalence of MS across Iran. Methods: A comprehensive literature search was performed using PubMed, Embase, and Web of Science. We also did a manual search of reference lists from primary articles and relevant reviews. Databases of ongoing research and unpublished literature were also searched. Results: A total of 22 relevant studies were reviewed and 11 studies met the inclusion criteria. Incidence data were found in 5 studies and ranged from 0.68 to 9.1/100,000 per year in the Iranian population. Prevalence was reported in all studies and ranged from 5.3 to 74.28/100,000 with the higher prevalence among females (female/male ratio ranged from 1.8 to 3.6). The most prevalent subtype of MS was the relapsing-remitting form (65.8-87.8%). The sensory disturbance was the most initial presentation. Conclusion: The incidence and prevalence of MS in Iran has been increasing rapidly, especially in females. Future research should focus on determining the epidemiological features of MS in the neglected provinces with different ethnicities. Such an effort along with further research towards improvement of data on previously studied areas can enable a field to be opened up to identify the patterns of MS in varied genetic backgrounds and environments of Iran.
Effect of in utero Exposure to Antiepileptic Drugs on Cognitive Function in Children
Authors: Vashishth Kanupriya , Singh Rahul , Medhi Bikash
Published: February 2014

Epilepsy, being one of the most common neurological disorders, has raised concerns in developed and developing countries. Due to its heterogeneous pathophysiology and different cellular, molecular and genetic mechanisms, it is becoming a threat worldwide. Despite wide availability of antiepileptic drugs (AEDs), epilepsy still remains a major cause of morbidity and mortality among the pediatric and geriatric populations. Commonly available AED therapies include sodium and calcium channel blockers, GABA agonists, and potassium channel activists. Along with beneficial effects, AEDs have been known to cause teratogenic responses, learning disabilities, malfunctions of different organs, and drug-induced syndrome. Nowadays, AED-related cognitive impairment is emerging as a serious condition, affecting children born to epileptic women.
The Placental Exposome: Placental Determinants of Fetal Adiposity and Postnatal Body Composition
Authors: Lewis R.M. , Demmelmair H. , Gaillard R. , Godfrey K.M. , Hauguel-de Mouzon S. , Huppertz B. , Larque E. , Saffery R. , Symonds M.E. , Desoye G.
Published: February 2014

Offspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on placental function. High plasma levels of particular nutrients in obese and diabetic mothers are likely to be the important drivers of nutrient transfer to the fetus, resulting in excess fat accretion. However, not all offspring of obese and diabetic mothers are born large for gestational age and the explanation may involve the regulation of placental nutrient transfer required for fetal growth. The placenta integrates maternal and fetal signals across gestation in order to determine nutrient transfer rate. Understanding the nature of these signals and placental responses to them is key to understanding the pathology of both fetal growth restriction and macrosomia. The overall effects of the maternal environment on the placenta are the product of its exposures throughout gestation, the ‘placental exposome'. Understanding these environmental influences is important as exposures early in gestation, for instance causing changes in the function of genes involved in nutrient transfer, may determine how the placenta will respond to exposures later in gestation, such as to raised maternal plasma glucose or lipid concentrations. Longitudinal studies are required which allow investigation of the influences on the placenta across gestation. These studies need to make full use of developing technologies characterising placental function, fetal growth and body composition. Understanding these processes will assist in the development of preventive strategies and treatments to optimise prenatal growth in those pregnancies at risk of either excess or insufficient nutrient supply and could also reduce the risk of chronic disease in later life.
Antipsychotic Discontinuation in Patients with Dementia: A Systematic Review and Meta-Analysis of Published Randomized Controlled Studies
Authors: Pan Yi-Ju , Wu Chi-Shin , Gau Susan Shur-Fen , Chan Hung-Yu , Banerjee Sube
Published: February 2014

Background: There is a lack of clarity in the literature on the impact of antipsychotic discontinuation in dementia. Method: We conducted a systematic review and meta-analysis of published randomized controlled studies comparing the effects of antipsychotic discontinuation versus continuation in dementia. MEDLINE, EMBASE, PsycInfo, Cochrane Library and CINAHL were searched. Severity change of behavioral and psychological symptoms of dementia (BPSD) was the primary outcome. Results: Ten studies were included in the systematic review and 9 studies in the meta-analysis. The results showed that the antipsychotic discontinuation group had no statistically significant difference in BPSD severity change compared to the continuation group (n = 214, standardized mean difference: 0.19, 95% CI: -0.20 to 0.58). Secondary outcome analyses revealed that the discontinuation group included a statistically significantly higher proportion of subjects whose BPSD severity worsened (n = 366, risk ratio: 1.78, 95% CI: 1.31-2.41). Although not statistically significant, the discontinuation group appeared to have higher early study termination rates and a lower mortality during follow-up. Conclusions: This meta-analysis showed that antipsychotic discontinuation resulted in no statistically significant difference in BPSD severity change, early study terminations and mortality. However, a statistically significantly higher proportion of subjects with BPSD worsened in this group compared to the continuation group. Further studies are needed to explore the effects of antipsychotic discontinuation on BPSD.
Advances in Meta-Analysis: Examples from Internal Medicine to Neurology
Authors: Copetti Massimiliano , Fontana Andrea , Graziano Giusi , Veneziani Federica , Siena Federica , Scardapane Marco , Lucisano Giuseppe , Pellegrini Fabio
Published: February 2014

Objective: We review the state of the art in meta-analysis and data pooling following the evolution of the statistical models employed. Methods: Starting from a classic definition of meta-analysis of published data, a set of apparent antinomies which characterized the development of the meta-analytic tools are reconciled in dichotomies where the second term represents a possible generalization of the first one. Particular attention is given to the generalized linear mixed models as an overall framework for meta-analysis. Bayesian meta-analysis is discussed as a further possibility of generalization for sensitivity analysis and the use of priors as a data augmentation approach. Results: We provide relevant examples to underline how the need for adequate methods to solve practical issues in specific areas of research have guided the development of advanced methods in meta-analysis. Conclusions: We show how all the advances in meta-analysis naturally merge into the unified framework of generalized linear mixed models and reconcile apparently conflicting approaches. All these complex models can be easily implemented with the standard commercial software available.
Overview of Systematic Reviews and Meta-Analyses of Acupuncture for Stroke
Authors: Zhang Jun-huai , Wang Deren , Liu Ming
Published: February 2014

Background: We aimed to systematically overview published systematic reviews and meta-analyses in order to identify whether and when acupuncture is an effective treatment for stroke and stroke-related disorders. We also hoped to identify the best directions for future research in this area. Methods: Systematic reviews and meta-analyses of randomized controlled trials (RCTs) and quasi-RCTs evaluating the efficacy of acupuncture to treat stroke or stroke-related conditions were included. Electronic searches were conducted in the Cochrane Database of Systematic Reviews, Ovid MEDLINE, CINAHL, Ovid EMBASE, EBSCO Allied and Complementary Medicine (AMED) database, Chinese Biological Medicine Database, and Chinese National Knowledge Infrastructure Database. Two authors independently assessed the compliance of studies with eligibility criteria, and extracted data from included studies. The quality of systematic reviews was assessed according to the Overview Quality Assessment Questionnaire. Results: A total of 24 systematic reviews were included, of which 4 (16.7%) were Cochrane systematic reviews and 20 (83.3%) were non-Cochrane reviews. Acupuncture was analyzed as an acute stroke intervention in 3 reviews (12.5%), as an approach to stroke rehabilitation in 6 (25%), and as an intervention to treat various stroke-related disorders in the remaining 15 (62.5%). Reviews analyzing death or dependency/disability as the primary outcome reported no statistically significant difference between acupuncture and nonacupuncture control treatments. In contrast, reviews in which the outcome was improvement in global neurological deficit scores or performance on the video-fluoroscopic swallowing study test or water-swallowing test often reported that acupuncture was superior to control treatment. The quality of 10 reviews was ‘poor', 6 reviews were ‘moderate' and 8 were ‘good'. Conclusions: The available evidence suggests that acupuncture may be effective for treating poststroke neurological impairment and dysfunction such as dysphagia, although these reported benefits should be verified in large, well-controlled studies. On the other hand, the available evidence does not clearly indicate that acupuncture can help prevent poststroke death or disability, or ameliorate other aspects of stroke recovery, such as poststroke motor dysfunction. These findings suggest that researchers should focus on the potential application of acupuncture to treat poststroke neurological impairment and dysfunction and on the development of more precise tools to assess these improvements after stroke.
Pancreatic Hepatoid Carcinoma: A Review of the Literature
Authors: Marchegiani Giovanni , Gareer Haytham , Parisi Alice , Capelli Paola , Bassi Claudio , Salvia Roberto
Published: February 2014

Background: Hepatoid carcinomas (HCs) are extrahepatic neoplasms exhibiting features of hepatocellular tumors in terms of morphology and immunohistochemistry. They have been described in several organs, most notably in the stomach and ovary. They can present in pure forms or in association with other morphological aspects, such as endocrine tumors or ductal adenocarcinomas. The aim of this review is to describe aspects of hepatoid adenocarcinoma of the pancreas with regard to epidemiology, diagnosis, and treatment. Methods: The PubMed database was searched for publications addressing hepatoid adenocarcinoma of the pancreas. We have searched for articles including the following keywords: ‘pancreatic hepatoid carcinoma', ‘ectopic liver cancer' and ‘rare pancreas neoplasm' published to date. As references, we used case reports and review articles. Results: Pancreatic forms of HCs are extremely uncommon: only 22 cases have been reported. Conclusions: The possibility of an HC of the pancreas should be considered in the differential diagnosis of an uncommon pathological mass of the pancreas. Treatment seems to be related to the association with other neoplasms, tumor extension at the time of diagnosis and the possibility to perform a radical resection. The common embryologic origin of the pancreas and liver, together with peculiar environmental factors, may explain the development of pancreatic HCs.