bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusual presentation of PRES in the postnatal period
Authors: O'Kane Miriam , Elhalwagy Hosam , Kumar Sathish , Badawi Claire
Published: July 2014

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity, associated with a vast array of medical conditions and a variety of presenting symptoms. There is a characteristic pattern of radiographic features alongside suggestive clinical manifestations, which lead to a diagnosis of PRES. This report describes the case of a 39 years old, previously normotensive woman, who presented on day 7 postpartum with generalised tonic clonic seizures, reduced conscious level and a history of blurred vision and headache. She was treated immediately as eclamptic and transferred to the intensive care unit for stabilisation. Following an inconclusive CT result, an MRI was performed 2 days after presentation, which demonstrated white matter changes consistent with those found in PRES. She made a full recovery and a repeat MRI scan 7 weeks later showed no progression of the lesions noted on the original scan.
Guidance for laboratories performing molecular pathology for cancer patients
Authors: Cree Ian A , Deans Zandra , Ligtenberg Marjolijn J L , Normanno Nicola , Edsjö Anders , Rouleau Etienne , Solé Francesc , Thunnissen Erik , Timens Wim , Schuuring Ed , Dequeker Elisabeth , Murray Samuel , Dietel Manfred , Groenen Patricia , Van Krieken J Han
Published: July 2014

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here.
Forensic veterinary pathology, today's situation and perspectives
Authors: Ottinger T. , Rasmusson B. , Segerstad C. H. A. , Merck M. , Goot F. V. D. , Olsén L. , Gavier‐Widén D.
Published: July 2014

To investigate the current status of forensic veterinary pathology, a survey was composed directed at pathology laboratories and institutes, mostly in Europe. The questions included number of and type of cases, resources available, level of special training of the investigating pathologists and the general view on the current status and future of the discipline. The surveys were sent to 134 laboratories and were returned by 72 respondents of which 93 per cent work on forensic pathology cases. The results indicate scarcity of training opportunities and special education, and insufficient veterinary‐specific reference data and information on forensic analyses. More cooperation with human forensic pathology was desired by many respondents, as was more interaction across country borders.
CLASSIFICATION PERFORMANCE OF MULTILAYER PERCEPTRONS WITH DIFFERENT RISK FUNCTIONALS
Authors: SILVA LUÍS M. , SANTOS JORGE M. , MARQUES DE SÁ JOAQUIM
Published: July 2014

In the present paper, we assess the performance of information-theoretic inspired risk functionals in multilayer perceptrons with reference to the two most popular ones, Mean Square Error and Cross-Entropy. The information-theoretic inspired risks, recently proposed: HS and HR2 are, respectively, the Shannon and quadratic Rényi entropies of the error; ZED is a risk reflecting the error density at zero errors; EXP is a generalized exponential risk, able to mimic a wide variety of risk functionals, including the information-thoeretic ones. The experiments were carried out with multilayer perceptrons on 35 public real-world datasets. All experiments were performed according to the same protocol. The statistical tests applied to the experimental results showed that the ubiquitous mean square error was the less interesting risk functional to be used by multilayer perceptrons. Namely, mean square error never achieved a significantly better classification performance than competing risks. Cross-entropy and EXP were the risks found by several tests to be significantly better than their competitors. Counts of significantly better and worse risks have also shown the usefulness of HS and HR2 for some datasets.
DESIGN OF BESSEL LOW PASS FILTER USING DGS WITH IMPROVED CHARACTERISTICS FOR RF/MICROWAVE APPLICATIONS
Authors: Kumar Ashwani , Verma A. K. , Chaudhari Nainu P.
Published: July 2014

We report a synthesis process to design the defected ground structure (DGS)-based Bessel lowpass filter (LPF). For 5-pole LPF at fc = 2.5 GHz, its selectivity is 10.6 dB/GHz and for the DGS-based Butterworth LPF it is 12.6 dB/GHz. For the lumped elements Bessel LPF, it is only 4.84 dB/GHz. Its 20 dB rejection bandwidth is 13.1 GHz and impedance matching BW is 76%, as against 88.8% for Butterworth LPF. At fc = 7.5 GHz, the 5-pole DGS Bessel LPF has selectivity 7 dB/GHz, 20 dB rejection BW is 13 GHz and 10 dB return loss (RL) BW in passband is 4.86 GHz (64.8%) with less than 7.9 pS group delay (GD) variation. In case of a bulky mixed microstrip-waveguide (MMW) 5-pole Bessel LPF at 7.5 GHz [W. Menzel and F. Boigelsack, 29th European Microwave Conference, Munich (1999), pp. 191–194.], reported results are: sharpness of cut-off 1.48 dB/GHz, 10 dB RL BW and GD variation are 48% and 4 pS, respectively. The improved performance the DGS-based Bessel LPF can find applications in high speed data communication, front-end of a wideband communication system and in a power amplifier, by improving the selectivity, suppression of harmonics and linear distortion.
How to distinguish a molecule from an 'elementary' particle?
Authors: Dai L. Y. , Shi M. , Tang G. Y. , Zheng H. Q.
Published: July 2014

We discuss how to use Morgan's pole counting rule to distinguish a molecular state from an 'elementary' particle. As two examples we focus on X(3872) and f0(980) particles. A molecule may be generated from a meson loop bubble chain, and an 'elementary' particle is related to an explicit interaction field in the effective lagrangian and propagates with a Breit–Wigner propagator. For X(3872) it is found that the data favor the 'elementary' particle explanation. For f0(980) the study becomes much more difficult, since highly nonperturbative dynamics is involved. A unitarization model analysis suggests that f0(980)'s property is quite exotic. Unlike other light scalars, it does not behave like a [Formula: see text] state, and could be interpreted as a molecule.
Ab initio no core full configuration approach for light nuclei
Authors: Kim Youngman , Shin Ik Jae , Maris Pieter , Vary James P. , Forssén Christian , Rotureau Jimmy
Published: July 2014

Comprehensive understanding of the structure and reactions of light nuclei poses theoretical and computational challenges. Still, a number of ab initio approaches have been developed to calculate the properties of atomic nuclei using fundamental interactions among nucleons. Among them, we work with the ab initio no core full configuration (NCFC) method and ab initio no core Gamow Shell Model (GSM). We first review these approaches and present some recent results.
Progress in resolving charge symmetry violation in nucleon structure
Authors: Young R. D. , Shanahan P. E. , Thomas A. W.
Published: July 2014

Recent work unambiguously resolves the level of charge symmetry violation in moments of parton distributions using (2 + 1)-flavor lattice QCD. We introduce the methods used for that analysis by applying them to determine the strong contribution to the proton–neutron mass difference. We also summarize related work which reveals that the fraction of baryon spin which is carried by the quarks is in fact structure-dependent rather than universal across the baryon octet.
Duplicate sampling and the retention of archival diamond drill-core: no longer a contradiction
Authors: Stanley Cliff
Published: July 2014

Geoscientists undertaking mineral exploration sometimes are provided with historic geological and geochemical information about a prospective mineral deposit that they would like to use in a modern mineral resource assessment. Unfortunately, these historic datasets may lack critical information describing the quality of the data, such as duplicate samples, that are required under today’s disclosure regulations. As a result, geoscientists sometimes need to generate such data quality information after the fact (
a posteriori
). This contribution describes how duplicate samples can be obtained from historic drill-core to provide an unbiased assessment of grade and measurement error, as well as ensuring equivalent geostatistical ‘support’ in all samples, while at the same time retaining at least one quarter of the drill-core in archive for all sample intervals. It also describes an alternative method that can be applied to unsampled drill-core (
a priori
) to acquire unbiased grade and measurement error estimates, ensure equal sample support, while at the same time retaining half of the drill-core in archive.
Programming Urban-Area Applications by Exploiting Public Transportation
Authors: Harnie Dries , Boix Elisa Gonzalez , D’hondt Theo , Meuter Wolfgang De
Published: July 2014

The evolution of smartphones has given rise to urban-area applications: applications that communicate in a city by means of the public (moving) infrastructure (e.g., buses and trams). In this setting, applications need to communicate with and discover each other using intermediaries that move around the city and transfer data between them. This requires programmers to scatter code that deals with routing messages to the correct place and deal with network failures all over their programs. Our approach allows the programmer to specify urban-area applications in a high-level manner without the burden of directly encoding communication using intermediaries. We present this as a translation from a high-level object-oriented programming paradigm to a low-level communication mechanism. This translation allows the programmer to restrict routing of messages to, for example, a certain number of hops, geographic areas, or even types of carrier devices. In addition, we show how high-level group messaging can be efficiently represented in the low-level communication. Finally, we document our experiences in setting up a small-scale real-world urban-area application.
Some definite integrals containing the Tree T function
Authors: Corless Robert M. , Hu Junrui , Jeffrey D. J.
Published: July 2014

We consider, from a symbolic point of view, a pair of definite integrals containing Lambert
W
, recently considered from a numerical point of view by Walter Gautschi. We transform the integrals to a shape that can be integrated in special cases by a computer-algebra system or by using tables of integrals, such as Prudnikov et al.
What's in a name?
Authors: Salvo Michael
Published: July 2014

By describing cultural usability work as "information architecture," I knew I would be waging a continuous rearguard battle with database designers. Eventually the cost of bickering over turf outweighed the clarity the term brought, even considering its lineage. Richard Saul Wurman first recognized
Information Anxiety
in the late 1980s and described those working as
Information Architects
in the 1990s. Here, I remind readers that Wurman goes by the nickname "Ted." Wurman's vision of widespread attention to Technology, Education, and Design resulting in the popular TED talks---although he has an uneasy relationship with his own creation. "When he speaks about TED Talks, he clearly struggles to identify with the organisation today and is adamant that it has lost its vision." [http://www.universityobserver.ie/2012/10/31/interview-richard-saul-wurman-ted-talks/] At our current moment of media convergence, it helps to remember that the 20 minute flipped pedagogical lecture itself is the result of thirty years of dedication to disseminating disruptive ideas. If Ted Wurman can let TED go, I can let go of Information Architecture.
Letting context speak
Authors: Carlson Clinton , Peake Whitney , Joiner Jeff
Published: July 2014

This paper discusses how co-creative, design-led, and user-centered design methods are being utilized to gain insight into the factors that influence the communication of food recalls. It looks at the role of designer and public in these methods and considers the value of these methods for other settings.
A detailed, conductance-based computer model of intrinsic sensory neurons of the gastrointestinal tract
Authors: Chambers Jordan D. , Bornstein Joel C. , Gwynne Rachel M. , Koussoulas Katerina , Thomas Evan A.
Published: July 2014

Intrinsic sensory neurons (ISNs) of the enteric nervous system respond to stimuli such as muscle tension, muscle length, distortion of the mucosa, and the chemical content in the lumen. ISNs form recurrent networks that probably drive many intestinal motor patterns and reflexes. ISNs express a large number of voltage- and calcium-gated ion channels, some of which are modified by inflammation or repeated physiological stimuli, but how interactions between different ionic currents in ISNs produce both normal and pathological behaviors in the intestine remains unclear. We constructed a model of ISNs including voltage-gated sodium and potassium channels, N-type calcium channels, big conductance calcium-dependent potassium (BK) channels, calcium-dependent nonspecific cation channels (NSCa), intermediate conductance calcium-dependent potassium (IK) channels, hyperpolarization-activated cation ( Ih) channels, and internal calcium dynamics. The model was based on data from the literature and our electrophysiological studies. The model reproduced responses to short or long depolarizing current pulses and responses to long hyperpolarizing current pulses. Sensitivity analysis showed that Ih, IK, NSCa, and BK have the largest influence on the number of action potentials observed during prolonged depolarizations. The model also predicts that changes to the voltage of activation for Ih have a large influence on excitability, but changes to the time constant of activation for Ih have a minor effect. Our model identifies how interactions between different iconic currents influence the excitability of ISNs and highlights an important role for Ih in enteric neuroplasticity resulting from disease.
Acute cardiopulmonary effects induced by the inhalation of concentrated ambient particles during seasonal variation in the city of São Paulo
Authors: de Brito Jôse Mára , Macchione Mariângela , Yoshizaki Kelly , Toledo-Arruda Alessandra Choqueta , Saraiva-Romanholo Beatriz Mangueira , Andrade Maria de Fátima , Mauad Thaís , Rivero Dolores Helena Rodriguez Ferreira , Saldiva Paulo Hilário Nascimento
Published: July 2014

Ambient particles may undergo modifications to their chemical composition as a consequence of climatic variability. The determination of whether these changes modify the toxicity of the particles is important for the understanding of the health effects associated with particle exposure. The objectives were to determine whether low levels of particles promote cardiopulmonary effects, and to assess if the observed alterations are influenced by season. Mice were exposed to 200 μg/m3 concentrated ambient particles (CAPs) and filtered air (FA) in cold/dry and warm/humid periods. Lung hyperresponsiveness, heart rate, heart rate variability, and blood pressure were evaluated 30 min after each exposure. After 24 h, blood and tissue samples were collected. During both periods (warm/humid and cold/dry), CAPs induced alterations in red blood cells and lung inflammation. During the cold/dry period, CAPs reduced the mean corpuscular volume levels and increased erythrocytes, hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width coefficient variation levels compared with the FA group. Similarly, CAPs during the warm/humid period decreased mean corpuscular volume levels and increased erythrocytes, hemoglobin, hematocrit, and red cell distribution width coefficient variation levels compared with the FA group. CAPs during the cold/dry period increased the influx of neutrophils in the alveolar parenchyma. Short-term exposure to low concentrations of CAPs elicited modest but significant pulmonary inflammation and, to a lesser extent, changes in blood parameters. In addition, our data support the concept that changes in climate conditions slightly modify particle toxicity because equivalent doses of CAPs in the cold/dry period produced a more exacerbated response.
Cerebral blood flow velocity underestimates cerebral blood flow during modest hypercapnia and hypocapnia
Authors: Coverdale Nicole S. , Gati Joseph S. , Opalevych Oksana , Perrotta Amanda , Shoemaker J. Kevin
Published: July 2014

To establish the accuracy of transcranial Doppler ultrasound (TCD) measures of middle cerebral artery (MCA) cerebral blood flow velocity (CBFV) as a surrogate of cerebral blood flow (CBF) during hypercapnia (HC) and hypocapnia (HO), we examined whether the cross-sectional area (CSA) of the MCA changed during HC or HO and whether TCD-based estimates of CBFV were equivalent to estimates from phase contrast (PC) magnetic resonance imaging. MCA CSA was measured from 3T magnetic resonance images during baseline, HO (hyperventilation at 30 breaths/min), and HC (6% carbon dioxide). PC and TCD measures of CBFV were measured during these protocols on separate days. CSA and TCD CBFV were used to calculate CBF. During HC, CSA increased from 5.6 ± 0.8 to 6.5 ± 1.0 mm2 ( P < 0.001, n = 13), while end-tidal carbon dioxide partial pressure (PetCO2) increased from 37 ± 3 to 46 ± 5 Torr ( P < 0.001). During HO, CSA decreased from 5.8 ± 0.9 to 5.3 ± 0.9 mm2 ( P < 0.001, n = 15), while PetCO2 decreased from 36 ± 4 to 23 ± 3 Torr ( P < 0.001). CBFVs during baseline, HO, and HC were compared between PC and TCD, and the intraclass correlation coefficient was 0.83 ( P < 0.001). The relative increase from baseline was 18 ± 8% greater ( P < 0.001) for CBF than TCD CBFV during HC, and the relative decrease of CBF during HO was 7 ± 4% greater than the change in TCD CBFV ( P < 0.001). These findings challenge the assumption that the CSA of the MCA does not change over modest changes in PetCO2.
Diagnostic Utility of Broad Range Bacterial 16S rRNA Gene PCR with Degradation of Human and Free Bacterial DNA in Bloodstream Infection Is More Sensitive Than an In-House Developed PCR without Degradation of Human and Free Bacterial DNA
Authors: Rogina Petra , Skvarc Miha , Stubljar David , Kofol Romina , Kaasch Achim
Published: July 2014

We compared a commercial broad range 16S rRNA gene PCR assay (SepsiTest) to an in-house developed assay (IHP). We assessed whether CD64 index, a biomarker of bacterial infection, can be used to exclude patients with a low probability of systemic bacterial infection. From January to March 2010, 23 patients with suspected sepsis were enrolled. CD64 index, procalcitonin, and C-reactive protein were measured on admission. Broad range 16S rRNA gene PCR was performed from whole blood (SepsiTest) or blood plasma (IHP) and compared to blood culture results. Blood samples spiked withStaphylococcus aureuswere used to assess sensitivity of the molecular assaysin vitro. CD64 index was lower in patients where possible sepsis was excluded than in patients with microbiologically confirmed sepsis (P=0.004). SepsiTest identified more relevant pathogens than blood cultures (P=0.008); in three patients (13%) results from blood culture and SepsiTest were congruent, whereas in four cases (17.4%) relevant pathogens were detected by SepsiTest only.In vitrospiking experiments suggested equal sensitivity of SepsiTest and IHP. A diagnostic algorithm using CD64 index as a decision maker to perform SepsiTest shows improved detection of pathogens in patients with suspected blood stream infection and may enable earlier targeted antibiotic therapy.
Immature Stages and Life Cycle of the Wasp Moth,Cosmosoma auge(Lepidoptera: Erebidae: Arctiinae) under Laboratory Conditions
Authors: León-Finalé Gunnary , Barro Alejandro
Published: July 2014

Cosmosoma auge(Linnaeus 1767) (Lepidoptera: Erebidae) is a Neotropical arctiid moth common in Cuban mountainous areas; however, its life cycle remains unknown. In this work,C. augelife cycle is described for the first time; also, immature stages are described using a Cuban population. Larvae were obtained from gravid wild females caught in Viñales National Park and were fed with fresh leaves of its host plant, the climbing hempweedMikania micranthaKunth (Asterales: Asteraceae), which is a new host plant record. Eggs are hemispherical and hatching occurred five days after laying. Larval period had six instars and lasted between 20 and 22 days. First and last larval stages are easily distinguishable from others. First stage has body covered by chalazae and last stage has body covered by verrucae as other stages but has a tuft on each side of A1 and A7. Eggs and larvae features agree with Arctiinae pattern. Pupal stage lasted eight days, and, in general, females emerge before males as a result of pupal stage duration differences between sexes.
Utilization of Zinc Dust for a Core Monomer 2-Bromo-3-hexylthien-5-ylzinc Bromide: Its Synthesis and Application for the Preparation of Regioregular Poly(3-hexylthiophene)
Authors: Kim Seung-Hoi
Published: July 2014

The oxidative insertion of readily available zinc dust into the carbon-bromine bond of 2,5-dibromo-3-hexylthiophene was efficiently achieved to provide 2-bromo-3-hexylthien-5-ylzinc bromide (I), which was utilized for the preparation of highly regioregular poly(3-hexylthiophene) (P3HT) in the presence of catalytic amounts of Ni-catalyst.
Automated Measurement of Volumetric Mammographic Density: A Tool for Widespread Breast Cancer Risk Assessment
Authors: Brand Judith S. , Czene Kamila , Shepherd John A. , Leifland Karin , Heddson Boel , Sundbom Ann , Eriksson Mikael , Li Jingmei , Humphreys Keith , Hall Per
Published: July 2014

Introduction: Mammographic density is a strong risk factor for breast cancer and an important determinant of screening sensitivity, but its clinical utility is hampered due to the lack of objective and automated measures. We evaluated the performance of a fully automated volumetric method (Volpara).

Methods: A prospective cohort study included 41,102 women attending mammography screening, of whom 206 were diagnosed with breast cancer after a median follow-up of 15.2 months. Percent and absolute dense volumes were estimated from raw digital mammograms. Genotyping was performed in a subset of the cohort (N = 2,122). We examined the agreement by side and view and compared density distributions across different mammography systems. We also studied associations with established density determinants and breast cancer risk.

Results: The method showed good agreement by side and view, and distributions of percent and absolute dense volume were similar across mammography systems. Volumetric density was positively associated with nulliparity, age at first birth, hormone use, benign breast disease, and family history of breast cancer, and negatively with age and postmenopausal status. Associations were also observed with rs10995190 in the ZNF365 gene (P < 1.0 × 10−6) and breast cancer risk [HR for the highest vs. lowest quartile, 2.93; 95% confidence interval, 1.73–4.96 and 1.63 (1.10–2.42) for percent and absolute dense volume, respectively].

Conclusions: In a high-throughput setting, Volpara performs well and in accordance with the behavior of established density measures.

Impact: Automated measurement of volumetric mammographic density is a promising tool for widespread breast cancer risk assessment. Cancer Epidemiol Biomarkers Prev; 23(9); 1764–72. ©2014 AACR.
Metabolic Health Reduces Risk of Obesity-Related Cancer in Framingham Study Adults
Authors: Moore Lynn L. , Chadid Susan , Singer Martha R. , Kreger Bernard E. , Denis Gerald V.
Published: July 2014

Background: It is unknown whether the risk for obesity-related cancers differs between metabolically unhealthy and healthy overweight/obese adults.

Methods: Data on body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and random blood glucose in Framingham Heart Study adults (n = 3,763) ages 55 to 69 years were used to estimate risks of obesity-related cancers (n = 385), including postmenopausal breast, female reproductive, colon, liver, gallbladder, pancreas, and kidney cancers, as well as esophageal adenocarcinomas. Multivariable-adjusted Cox proportional hazards models were used to estimate risk for obesity-related cancers associated with body fat and metabolic health (as defined by glucose levels) among subjects in three risk groups (vs. referent group with normal weight/normal glucose): normal weight/elevated glucose, overweight/normal glucose, and overweight/elevated glucose.

Results: Overweight adults [BMI ≥ 25 or WHtR ≥ 0.51 (men) and ≥0.57 (women)] with elevated glucose (≥125 mg/dL) had a statistically significant 2-fold increased risk of developing obesity-related cancer, whereas overweight adults with normal glucose had a 50% increased risk. Normal-weight adults with elevated glucose had no excess cancer risk. The effects of BMI and WHtR were independent of one another. Finally, overweight women with elevated blood glucose had a 2.6-fold increased risk [95% confidence interval (CI), 1.4–4.9] of female reproductive (cervical, endometrial, uterine cancers) and postmenopausal breast cancers, whereas overweight women with normal glucose levels had only a 70% increased risk (95% CI, 1.1–2.5).

Conclusion: These results suggest that cancer risk may be lower among metabolically healthy overweight/obese older adults than among overweight/obese adults with metabolic dysfunction.

Impact: Metabolic dysfunction and obesity act synergistically to increase cancer risk. Cancer Epidemiol Biomarkers Prev; 23(10); 2057–65. ©2014 AACR.
Smoking Status and Prevalence of Upper Gastrointestinal Disorders
Authors: Esmaillzadeh Ahmad , Keshteli Ammar Hassanzadeh , Tabesh Marjan , Feizi Awat , Adibi Peyman
Published: July 2014

Background: Lifestyle and environmental factors affecting upper gastrointestinal (GI) disorders are different in developing countries than those in developed nations. Objective: This study aimed to examine the association between smoking status and upper GI disorders among a large group of the Iranian adult population. Methods: This cross-sectional study was conducted among 1,933 adult men in Isfahan, Iran. Smoking status was assessed by a self-administered questionnaire. Required information on GI health was collected through the use of the validated ROME III questionnaire. Individuals who reported having heartburn sometimes, often, or always in the last 3 months were considered as having epidemiologic gastroesophageal reflux disease (GERD), and those who reported having heartburn often or always were considered as having clinical GERD. Subjects who reported having functional dyspepsia (FD) symptoms (based on the ROME III criteria) sometimes, often, or always in the last 3 months were considered as having epidemiologic FD, and those who reported having these disorders often or always were considered as having clinical FD. Results: Smoking was prevalent among 7.8% of the study population. FD and GERD was prevalent among 12.6% (n = 244) and 22.3% (n = 432), respectively. Smoking was not associated with GERD by either the epidemiologic or clinical definition. Although the association between smoking and FD (epidemiologic definition) was not statistically significant, smokers had an 83% higher risk of suffering from clinical FD compared with nonsmokers after taking potential confounders into account [odds ratio (OR) = 1.83, 95% CI: 1.12-3.00; p = 0.01]. Smokers had a 57% higher risk for epidemiologic postprandial fullness (OR = 1.57, 95% CI: 1.05-2.33; p = 0.02) and a 92% higher risk for clinical epigastric pain compared with nonsmokers (OR = 1.92, 95% CI: 1.02-3.62; p = 0.04). We found no significant association between smoking and severity of upper GI disorders. Conclusion: This large population-based study indicated that smoking was not associated with GERD and epidemiologic FD. However, smoking was significantly associated with clinical FD, postprandial fullness, and epigastric pain.
Controversies in Colorectal Cancer Screening
Authors: Pox Christian P.
Published: July 2014

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide and a good candidate for screening programmes. However, there is controversy concerning which of the available screening tests should be used. Summary: There is general agreement that screening for CRC in the asymptomatic population should begin at the age of 50. Several different screening methods are available which can be separated into those that mainly detect cancers: faecal occult blood tests [guaiac (FOBT) and immunochemical (FIT)], genetic stool tests, blood tests and the M2-pyruvate kinase (M2-PK) test. Methods that detect cancers and polyps are colonoscopy, sigmoidoscopy, CT-colonography (CT-C) and colon capsule endoscopy. The only tests for which a reduction in CRC mortality compared to no screening have been proven in randomized trials are FOBT and sigmoidoscopy. Several trials suggest that FIT are superior to FOBT in terms of detection rates of cancers and advanced adenomas and possibly compliance. There is indirect evidence suggesting efficacy of colonoscopy as a screening test. The role of CT-C is controversial. There is data suggesting a good sensitivity for neoplasia >9 mm with a lower sensitivity for smaller neoplasia. However, radiation exposure is considered a major limitation in some countries. Unresolved questions include the lesion cut-off for referral to colonoscopy and work-up of extracolonic findings. For other methods, like genetic stool testing using newer markers, blood tests, capsule endoscopy and M2-PK, there is currently insufficient data on screening of the asymptomatic population. Key Messages: Colorectal screening is recommended and should be performed in the form of an organized programme. If detection of early-stage cancers is the aim of a screening programme, FIT seem to be superior to FOBT. If detection and removal of adenomas is the aim of a screening programme, endoscopic methods seem to be good alternatives. Sigmoidoscopy is easier to perform but will likely only have an effect on distal cancers. Colonoscopy is more invasive but enables inspection of the whole colon. The role of CT-C, capsule endoscopy, genetic stool tests, blood tests and M2-PK is currently unknown.
Horrifying Basal Cell Carcinoma: Cytological, Immunohistochemical, and Ultrastructural Findings
Authors: Kinoshita Yuichi , Takasu Kosho , Yoshizawa Katsuhiko , Emoto Yuko , Yuki Michiko , Yuri Takashi , Shikata Nobuaki , Tsubura Airo
Published: July 2014

Basal cell carcinoma (BCC) is a slow-growing and frequently occurring tumor of the eyelids. Among BCC cases, there is a subtype of aggressive cases called horrifying BCC (HBCC). There are also rare BCC cases that show neuroendocrine differentiation. Here, we describe a case of HBCC with neuroendocrine differentiation. The patient, a 41-year-old woman, presented with abnormal left eye tearing and left cheek pain. On computed tomography imaging, a tumor that extended to the left orbit was detected in the left cheek. On cytological examination of fine-needle aspiration (FNA) samples, the tumor cells were observed as sheet-like clusters and single bare nuclei with a clear background; peripheral palisading was not clearly seen. On examination of the biopsy specimen taken after FNA, the tumor was found to be composed of cancer cell nests with scattered peripheral palisading in the dermis. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7 and CD56 and were negative for CK20, synaptophysin, and chromogranin A. Membrane-bound dense-core granules were detected on ultrastructural study. A HBCC case with neuroendocrine differentiation has not been previously reported. The correlation between the presence of neuroendocrine differentiation in HBCC and patient prognosis should be further studied.
Hemorrhagic Macular Infarction after Intravitreal Bevacizumab for Chronic Multifocal Central Serous Chorioretinopathy
Authors: Kelkar Aditya , Gandhi Poonam , Amoaku Winfried , Kelkar Jai , Kelkar Shreekant , Raut Priyanka , Shah Rachana
Published: July 2014

We hereby report a case of hemorrhagic macular infarction after intravitreal bevacizumab for chronic multifocal central serous chorioretinopathy (CSC). Issues regarding safety and adverse effects of bevacizumab are discussed. To the best of our knowledge, this is the first reported case of hemorrhagic macular infarction after intravitreal bevacizumab for chronic multifocal CSC.
Role of Flow-Sensitive microRNAs in Endothelial Dysfunction and Atherosclerosis
Authors: Kumar Sandeep , Kim Chan Woo , Simmons Rachel D. , Jo Hanjoong
Published: July 2014

Atherosclerosis preferentially occurs in arterial regions exposed to disturbed flow, in part, due to alterations in gene expression. MicroRNAs (miRNAs) are small, noncoding genes that post-transcriptionally regulate gene expression by targeting messenger RNA transcripts. Emerging evidence indicates that alteration of flow conditions regulate expression of miRNAs in endothelial cells both in vitro and in vivo. These flow-sensitive miRNAs, known as mechano-miRs, regulate endothelial gene expression and can regulate endothelial dysfunction and atherosclerosis. MiRNAs such as, miR-10a, miR-19a, miR-23b, miR-17–92, miR-21, miR-663, miR-92a, miR-143/145, miR-101, miR-126, miR-712, miR-205, and miR-155, have been identified as mechano-miRs. Many of these miRNAs were initially identified as flow sensitive in vitro and were later found to play a critical role in endothelial function and atherosclerosis in vivo through either gain-of-function or loss-of-function approaches. The key signaling pathways that are targeted by these mechano-miRs include the endothelial cell cycle, inflammation, apoptosis, and nitric oxide signaling. Furthermore, we have recently shown that the miR-712/205 family, which is upregulated by disturbed flow, contributes to endothelial inflammation and vascular hyperpermeability by targeting tissue inhibitor of metalloproteinase-3, which regulates metalloproteinases and a disintegrin and metalloproteinases. The mechano-miRs that are implicated in atherosclerosis are termed as mechanosensitive athero-miRs and are potential therapeutic targets to prevent or treat atherosclerosis. This review summarizes the current knowledge of mechanosensitive athero-miRs and their role in vascular biology and atherosclerosis.
Retinal Vasculopathy Is Reduced by Dietary Salt Restriction
Authors: Deliyanti Devy , Armani Roksana , Casely David , Figgett William A. , Agrotis Alex , Wilkinson-Berka Jennifer L.
Published: July 2014

Objective—

Neovascularization and vaso-obliteration are vision-threatening events that develop by interactions between retinal vascular and glial cells. A high-salt diet is causal in cardiovascular and renal disease, which is linked to modulation of the renin–angiotensin–aldosterone system. However, it is not known whether dietary salt influences retinal vasculopathy and if the renin–angiotensin–aldosterone system is involved. We examined whether a low-salt (LS) diet influenced vascular and glial cell injury and the renin–angiotensin–aldosterone system in ischemic retinopathy.

Approach and Results—

Pregnant Sprague Dawley rats were fed LS (0.03% NaCl) or normal salt (0.3% NaCl) diets, and ischemic retinopathy was induced in the offspring. An LS diet reduced retinal neovascularization and vaso-obliteration, the mRNA and protein levels of the angiogenic factors, vascular endothelial growth factor, and erythropoietin. Microglia, which influence vascular remodeling in ischemic retinopathy, were reduced by LS as was tumor necrosis factor-α. Macroglial Müller cells maintain the integrity of the blood–retinal barrier, and in ischemic retinopathy, LS reduced their gliosis and also vascular leakage. In retina, LS reduced mineralocorticoid receptor, angiotensin type 1 receptor, and renin mRNA levels, whereas, as expected, plasma levels of aldosterone and renin were increased. The aldosterone/mineralocorticoid receptor–sensitive epithelial sodium channel alpha (ENaCα), which is expressed in Müller cells, was increased in ischemic retinopathy and reduced by LS. In cultured Müller cells, high salt increased ENaCα, which was prevented by mineralocorticoid receptor and angiotensin type 1 receptor blockade. Conversely, LS reduced ENaCα, angiotensin type 1 receptor, and mineralocorticoid receptor expression.

Conclusions—

An LS diet reduced retinal vasculopathy, by modulating glial cell function and the retinal renin–angiotensin–aldosterone system.
Haploinsufficiency of the Insulin-Like Growth Factor-1 Receptor Enhances Endothelial Repair and Favorably Modifies Angiogenic Progenitor Cell Phenotype
Authors: Yuldasheva Nadira Y. , Rashid Sheikh Tawqeer , Haywood Natalie J. , Cordell Paul , Mughal Romana , Viswambharan Hema , Imrie Helen , Sukumar Piruthivi , Cubbon Richard M. , Aziz Amir , Gage Matthew , Mbonye Kamatamu Amanda , Smith Jessica , Galloway Stacey , Skromna Anna , Scott D. Julian A. , Kearney Mark T. , Wheatcroft Stephen B.
Published: July 2014

Objectives—

Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair.

Approach and Results—

We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R
+/−
). Endothelial regeneration after arterial injury was accelerated in IGF1R
+/−
mice. Although the yield of angiogenic progenitor cells was lower in IGF1R
+/−
mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R
+/−
bone marrow–derived CD117
+
cells into wild-type mice. IGF1R
+/−
cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation.

Conclusions—

Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow–derived CD117
+
cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury.
F-Actin–Anchored Focal Adhesions Distinguish Endothelial Phenotypes of Human Arteries and Veins
Authors: van Geemen Daphne , Smeets Michel W.J. , van Stalborch Anne-Marieke D. , Woerdeman Leonie A.E. , Daemen Mat J.A.P. , Hordijk Peter L. , Huveneers Stephan
Published: July 2014

Objective—

Vascular endothelial–cadherin- and integrin-based cell adhesions are crucial for endothelial barrier function. Formation and disassembly of these adhesions controls endothelial remodeling during vascular repair, angiogenesis, and inflammation. In vitro studies indicate that vascular cytokines control adhesion through regulation of the actin cytoskeleton, but it remains unknown whether such regulation occurs in human vessels. We aimed to investigate regulation of the actin cytoskeleton and cell adhesions within the endothelium of human arteries and veins.

Approach and Results—

We used an ex vivo protocol for immunofluorescence in human vessels, allowing detailed en face microscopy of endothelial monolayers. We compared arteries and veins of the umbilical cord and mesenteric, epigastric, and breast tissues and find that the presence of central F-actin fibers distinguishes the endothelial phenotype of adult arteries from veins. F-actin in endothelium of adult veins as well as in umbilical vasculature predominantly localizes cortically at the cell boundaries. By contrast, prominent endothelial F-actin fibers in adult arteries anchor mostly to focal adhesions containing integrin-binding proteins paxillin and focal adhesion kinase and follow the orientation of the extracellular matrix protein fibronectin. Other arterial F-actin fibers end in vascular endothelial–cadherin-based endothelial focal adherens junctions. In vitro adhesion experiments on compliant substrates demonstrate that formation of focal adhesions is strongly induced by extracellular matrix rigidity, irrespective of arterial or venous origin of endothelial cells.

Conclusions—

Our data show that F-actin–anchored focal adhesions distinguish endothelial phenotypes of human arteries from veins. We conclude that the biomechanical properties of the vascular extracellular matrix determine this endothelial characteristic.
Incremental Prognostic Significance of the Elevated Levels of Pentraxin 3 in Patients With Heart Failure With Normal Left Ventricular Ejection Fraction
Authors: Matsubara Junichi , Sugiyama Seigo , Nozaki Toshimitsu , Akiyama Eiichi , Matsuzawa Yasushi , Kurokawa Hirofumi , Maeda Hirofumi , Fujisue Koichiro , Sugamura Koichi , Yamamoto Eiichiro , Matsui Kunihiko , Jinnouchi Hideaki , Ogawa Hisao
Published: July 2014

Background

Pentraxin 3 (
PTX
3) is a novel inflammatory marker produced by various cell types including those of the vasculature and the heart. The relationship between inflammatory markers and prognosis of patients with heart failure with normal ejection fraction (
HFNEF
) remains unknown. We investigated whether plasma
PTX
3 levels can predict future cardiovascular events in patients with
HFNEF
.

Methods and Results

Plasma PTX3, high‐sensitivity C‐reactive protein, and B‐type natriuretic peptide levels were measured prospectively in 360 stable patients with HFNEF. The subsequent incidence of cardiovascular events, including cardiovascular death, nonfatal myocardial infarction (MI), unstable angina pectoris, nonfatal ischemic stroke, hospitalization for heart failure decompensation, and coronary revascularization, was determined. During a mean 30‐month follow‐up, 106 patients experienced cardiovascular events. These events were more frequent in patients with high plasma PTX3 levels (>3.0 ng/
mL
) than low levels (≤3.0 ng/
mL
). Multivariable Cox hazard analysis showed that PTX3 (hazard ratio: 1.16; 95% CI: 1.05 to 1.27;
P
<0.01) and B‐type natriuretic peptide (hazard ratio: 1.08; 95% CI: 1.03 to 1.14;
P
<0.001), but not high‐sensitivity C‐reactive protein levels, were significant predictors of future cardiovascular events. Multivariable Cox analysis with the forced inclusion model, including 5 previously identified prognostic factors, found that PTX3 was a significant predictor of cardiovascular events (hazard ratio: 1.16; 95% CI: 1.06 to 1.27;
P
<0.01). The C‐statistics for cardiovascular events substantially increased from 0.617 to 0.683 when PTX3 was added to the 5 previously identified prognostic factors.

Conclusions

High plasma
PTX
3 levels, but not other inflammatory markers, are correlated with future cardiovascular events in patients with
HFNEF
.
PTX
3 may be a useful biomarker for assessment of risk stratification in
HFNEF
.

Clinical Trial Registration

URL
:
http://www.umin.ac.jp
; Unique identifier:
UMIN
000002170.
Mammalian Target of Rapamycin Cell Signaling Pathway Contributes to the Protective Effects of Ischemic Postconditioning Against Stroke
Authors: Xie Rong , Wang Peng , Cheng Michelle , Sapolsky Robert , Ji Xunming , Zhao Heng
Published: July 2014

Background and Purpose—

Whether the mammalian target of rapamycin (mTOR) pathway is protective against brain injury from stroke or is detrimental is controversial, and whether it is involved in the protective effects of ischemic postconditioning (IPC) against stroke is unreported. Our study focuses on the protective role of mTOR against neuronal injury after stroke with and without IPC.

Methods—

We used both an in vitro oxygen–glucose deprivation model with a mixed neuronal culture and hypoxic postconditioning, as well as an in vivo stroke model with IPC. Rapamycin, a specific pharmacological inhibitor of mTOR, and mTOR short hairpin RNA lentiviral vectors were used to inhibit mTOR activity. A lentiviral vector expressing S6K1, a downstream molecule of mTOR, was used to confirm the protective effects of mTOR. Infarct sizes were measured and protein levels were examined by Western blot.

Results—

We report that stroke resulted in reduced levels of phosphorylated proteins in the mTOR pathway, including S6K1, S6, and 4EBP1, and that IPC increased these proteins. mTOR inhibition, both by the mTOR inhibitor rapamycin and by mTOR short hairpin RNA, worsened ischemic outcomes in vitro and in vivo and abolished the protective effects of hypoxic postconditioning and IPC on neuronal death in vitro and brain injury size in vivo. Overexpression of S6K1 mediated by lentiviral vectors significantly attenuated brain infarction.

Conclusions—

mTOR plays a crucial protective role in brain damage after stroke and contributes to the protective effects of IPC.
α4 Integrin Is a Regulator of Leukocyte Recruitment After Experimental Intracerebral Hemorrhage
Authors: Hammond Matthew D. , Ambler William G. , Ai Youxi , Sansing Lauren H.
Published: July 2014

Background and Purpose—

Intracerebral hemorrhage (ICH) is swiftly followed by an inflammatory response. A key component of this response is the recruitment of leukocytes into the brain, which promotes neurological injury in rodent models. However, the mechanisms by which leukocytes transmigrate across the endothelium into the injured brain are unclear. The present study examines leukocyte adhesion molecules (α4 integrin, L-selectin, and αLβ2 integrin) on 4 leukocyte subtypes to determine which are important for leukocyte recruitment after ICH.

Methods—

We used the blood injection mouse model of ICH, whereby 25 μL of blood was injected into the striatum. Flow cytometry was used to quantify leukocyte populations and adhesion molecule expression in brain and blood. An α4 integrin–blocking antibody was administered to evaluate the contribution of α4 integrin in leukocyte migration and neurological injury.

Results—

α4 integrin was elevated on all leukocyte populations in brain after ICH, whereas L-selectin was unchanged and αLβ2 was increased only on T cells. Antagonism of α4 resulted in decreased leukocyte transmigration and lessened neurobehavioral disability.

Conclusions—

α4 integrin is an important cell adhesion molecule involved in neuroinflammation after ICH.