bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies to Optimize Dual Antiplatelet Therapy After Coronary Artery Stenting in Acute Coronary Syndrome
Authors: Paravattil Bridget , Elewa Hazem
Published: June 2017

The use of aspirin and a P2Y12 receptor antagonist as dual antiplatelet therapy (DAPT) has become the treatment of choice in patients with acute coronary syndrome (ACS) and percutaneous coronary intervention to prevent recurrent thrombotic events. Although DAPT is beneficial for most patients, few patients still experience recurrent thrombotic events and increased bleeding episodes. This article reviews current literature to identify various approaches that may enhance the DAPT benefit-risk ratio in patients with ACS. Three strategies addressed in this article include the following—(1) use of more potent antiplatelet agents other than clopidogrel; (2) addition of direct oral anticoagulants (DOACs) to DAPT; and (3) optimizing DAPT duration. Although the use of prasugrel or ticagrelor improves treatment efficacy, their use has been associated with increased risk of bleeding compared to clopidogrel. The combination of DOACs and DAPT may not be the most viable strategy because of its limited cardiovascular benefits and increased bleeding risks. The optimal duration of DAPT duration remains controversial. Most guidelines recommend 6 to 12 months of DAPT, whereas emerging studies have shown benefit for both shorter and longer duration of treatment. Risk stratification tools such as the DAPT score may play a role in individualizing DAPT duration according to patient’s ischemic and bleeding risks.
The Role of Vitamins and Minerals on the Immune System
Authors: Alpert Patricia T.
Published: June 2017

It has long been recognized that individuals living in poverty who suffer from malnutrition are more susceptible to infections and certain diseases due to deficiencies in macronutrients such as proteins, lipids, and carbohydrates. More recently, it has come to light that micronutrients such as several vitamins and minerals also play major roles in boosting the immune system to protect against certain infections, inflammation, and possibly some cancers. This article discusses the various immune boosting properties of several micronutrients.
Rapid and sensitive insulated isothermal PCR for point-of-need feline leukaemia virus detection
Authors: Wilkes Rebecca P , Anis Eman , Dunbar Dawn , Lee Pei-Yu A , Tsai Yun-Long , Lee Fu-Chun , Chang Hsiao-Fen G , Wang Hwa-Tang T , Graham Elizabeth M
Published: June 2017

Objectives

Feline leukaemia virus (FeLV), a gamma retrovirus, causes diseases of the feline haematopoietic system that are invariably fatal. Rapid and accurate testing at the point-of-need (PON) supports prevention of virus spread and management of clinical disease. This study evaluated the performance of an insulated isothermal PCR (iiPCR) that detects proviral DNA, and a reverse transcription (RT)-iiPCR that detects both viral RNA and proviral DNA, for FeLV detection at the PON.

Methods

Mycoplasma haemofelis, feline coronavirus, feline herpesvirus, feline calicivirus and feline immunodeficiency virus were used to test analytical specificity. In vitro transcribed RNA, artificial plasmid, FeLV strain American Type Culture Collection VR-719 and a clinical FeLV isolate were used in the analytical sensitivity assays. A retrospective study including 116 clinical plasma and serum samples that had been tested with virus isolation, real-time PCR and ELISA, and a prospective study including 150 clinical plasma and serum samples were implemented to evaluate the clinical performances of the iiPCR-based methods for FeLV detection.

Results

Ninety-five percent assay limit of detection was calculated to be 16 RNA and five DNA copies for the RT-iiPCR, and six DNA copies for the iiPCR. Both reactions had analytical sensitivity comparable to a reference real-time PCR (qPCR) and did not detect five non-target feline pathogens. The clinical performance of the RT-iiPCR and iiPCR had 98.82% agreement (kappa[κ] = 0.97) and 100% agreement (κ = 1.0), respectively, with the qPCR (n = 85). The agreement between an automatic nucleic extraction/RT-iiPCR system and virus isolation to detect FeLV in plasma or serum was 95.69% (κ = 0.95) and 98.67% (κ = 0.85) in a retrospective (n = 116) and a prospective (n = 150) study, respectively.

Conclusions and relevance

These results suggested that both RT-iiPCR and iiPCR assays can serve as reliable tools for PON FeLV detection.
A four-node quadrilateral element for vibration and damping analysis of sandwich plates with viscoelastic core
Authors: Ren Shanhong , Zhao Guozhong
Published: June 2017

Constrained layer damping treatments have been widely used as an effective way for vibration control and noise reduction of thin-walled plates and shells. Despite extensive application in vibration and damping analysis of sandwich plates with viscoelastic core, the rectangular element is challenged by irregular structural forms in practical engineering. In this paper, a three-layer four-node quadrilateral element with seven degrees of freedom at each node is presented. Compared with classical rectangular element, the four-node quadrilateral element has stronger adaptability in complex structural forms and boundary conditions. Based on the layer-wise theory where the constrained layer and the base layer meet Kirchhoff theory and the viscoelastic layer satisfies first-order shear deformation theory, the finite element formulation of the sandwich plate with viscoelastic core is derived by the Hamilton principle in variational form and based on the generalization of the discrete Kirchhoff Quadrilateral plate element. The complex modulus model is employed to describe the viscoelastic core of sandwich plates, allowing for the material’s frequency dependent characteristics. The natural frequencies and associated modal loss factors are computed based on the complex eigenvalue problems. The frequency dependent characteristic of the viscoelastic core is considered and an iterative procedure is introduced to solve the nonlinear eigenvalue problem. At last, six verification numerical examples that include three sandwich beam-plates and three sandwich plates are provided to compare present method with experiment, analytical method, Galerkin method, finite element methods and commercial software (NASTRAN). The results show that the proposed finite element can accurately and efficiently simulate the sandwich plates treated with constrained layer damping with a variety of structural forms and boundary conditions.
Functional Budd-Chiari Syndrome Associated With Severe Polycystic Liver Disease
Authors: de Menezes Neves Precil Diego Miranda , Balbo Bruno Eduardo Pedroso , Watanabe Elieser Hitoshi , Rocha-Santos Vinicius , Andraus Wellington , D’Albuquerque Luiz Augusto Carneiro , Onuchic Luiz Fernando
Published: June 2017

A 50-year-old woman with end-stage renal disease secondary to autosomal dominant polycystic kidney disease was referred to a quaternary care center due to significantly increased abdominal girth. Her physical examination revealed tense ascites and abdominal collateral veins. A 10-L paracentesis improved abdominal discomfort and disclosed a transudate, suggestive of portal hypertension. A computed tomographic scan revealed massive hepatomegaly caused by multiple cysts of variable sizes, distributed throughout all hepatic segments. Contrast-enhanced imaging uncovered extrinsic compression of hepatic and portal veins, resulting in functional Budd-Chiari syndrome and portal hypertension. Although image-guided drainage followed by sclerosis of dominant cysts could potentially lead to alleviation of the extrinsic compression, the associated significant risk of cyst hemorrhage and infection precluded this procedure. In this scenario, the decision was to submit the patient to a liver-kidney transplantation. After 1 year of this procedure, the patient maintains normal liver and kidney function and refers significant improvement in quality of life.
Corrigendum to: “Effectiveness of a multidimensional web-based intervention program to change Brazilian health practitioners’ attitudes toward the lesbian, gay, bisexual and transgender population”
Authors: Costa Angelo Brandelli , Pase Paola Fagundes , de Camargo Eric Seger , Guaranha Camila , Caetano Adriano Henrique , Kveller Daniel , da Rosa Filho Heitor Thomé , Catelan Ramiro Figueiredo , Koller Silvia Helena , Nardi Henrique Caetano
Published: June 2017

Corrigendum to: J Health Psychol DOI 10.1177/1359105316628748

Unfortunately, the online published article has an error in one of the analyses. On page 365, fifth paragraph, the corrected statistical report is (Δ 1.66, 95% CI [3.32, .01], t (305) = –1.98, p<.05), not (Δ 1.66, 95% CI [3.32, .01], t (305) = –1.66, p <.05).

In spite of this correction, there is no change in the direction of the test and therefore in the interpretation of this result.
How Precise Are Preinterventional Measurements Using Centerline Analysis Applications? Objective Ground Truth Evaluation Reveals Software-Specific Centerline Characteristics
Authors: Hoegen Philipp , Wörz Stefan , Müller-Eschner Matthias , Geisbüsch Philipp , Liao Wei , Rohr Karl , Schmitt Matthias , Rengier Fabian , Kauczor Hans-Ulrich , von Tengg-Kobligk Hendrik
Published: June 2017

Purpose: To evaluate different centerline analysis applications using objective ground truth from realistic aortic aneurysm phantoms with precisely defined geometry and centerlines to overcome the lack of unknown true dimensions in previously published in vivo validation studies. Methods: Three aortic phantoms were created using computer-aided design (CAD) software and a 3-dimensional (3D) printer. Computed tomography angiograms (CTAs) of phantoms and 3 patients were analyzed with 3 clinically approved and 1 research software application. The 3D centerline coordinates, intraluminal diameters, and lengths were validated against CAD ground truth using a dedicated evaluation software platform. Results: The 3D centerline position mean error ranged from 0.7±0.8 to 2.9±2.5 mm between tested applications. All applications calculated centerlines significantly different from ground truth. Diameter mean errors varied from 0.5±1.2 to 1.1±1.0 mm among 3 applications, but exceeded 8.0±11.0 mm with one application due to an unsteady distortion of luminal dimensions along the centerline. All tested commercially available software tools systematically underestimated centerline total lengths by −4.6±0.9 mm to −10.4±4.3 mm (maximum error −14.6 mm). Applications with the highest 3D centerline accuracy yielded the most precise diameter and length measurements. Conclusion: One clinically approved application did not provide reproducible centerline-based analysis results, while another approved application showed length errors that might influence stent-graft choice and procedure success. The variety and specific characteristics of endovascular aneurysm repair planning software tools require scientific evaluation and user awareness.
Analysis of cyclic load die forming for woven jute fabric 3D reinforcement polymeric composites
Authors: El Messiry Magdi , Mohamed Abeer
Published: June 2017

2D fabrics are used widely and to good effect as a reinforcement for many planer composites and simple curved structures, i.e. a cylindrical arc. There are, however, manufacturing difficulties in the formation of composite structures which are curved across two axes, i.e. a bowl shape. This can be addressed by manufacturing “3D” fabric preforms; however, this requires complex machinery and is slow and expensive. It is, therefore, desirable to form complex curved shapes from planer textile structures; this is either done by cutting a net shape from the textile and placing it on a mold or by using force to stretch the fabric to the mold. These methods, however, result in discontinuous reinforcement or poor distribution of phases, respectively. Wrinkling of the fabric during formation will increase the possibility of composite failure under loading because of the presence of rich fiber or resin areas. A new method was suggested to manufacture 3D shapes from 2D fabric through the application of cyclic loading on the 2D fabric under a continuous hot air till the final fabric prepreg bagging form is reached. The composite fabrication process was completed in two steps: imposing dynamic bagging of the chemically treated 2D Jute fabric with 16% sodium hydroxide in slack form to fit the die final shape prior to the infusing of the resin accompanied by pressing two halves of the mold. A proto-type setup was designed to study the two-step fabrication method for various shapes of 3D fabric reinforcement.
Short-Term Motor Learning and Retention During Visually Guided Walking in Persons With Multiple Sclerosis
Authors: McGowan Kayla , Gunn Shaila M. , Vorobeychik Galina , Marigold Daniel S.
Published: June 2017

Background. The ability to adapt, a form of short-term motor learning, and retain this adaptation, is essential for rehabilitation and for day-to-day living. Yet little research is available on this topic in persons with multiple sclerosis (PwMS), particularly in relation to complex walking tasks. Objective. To determine the ability of PwMS to learn and retain a novel relationship between visual input and motor output—or visuomotor map—during visually guided walking. Methods. Nineteen PwMS and 17 healthy controls performed a precision walking task while adapting to prism lenses that altered the normal visuomotor map on 1 day, and again after a 1-week delay. The task required individuals to walk and step onto 2 targets without stopping. To quantify motor performance, we determined foot placement error relative to the targets. Results. PwMS with mild disability and healthy controls attenuated foot placement error over repeated trials when exposed to the novel mapping and demonstrated a similar rate and magnitude of adaptation in the first learning session. Both groups equally retained the adaptation 1 week later, reflected by reduced foot placement error and a faster rate of error reduction in that session. Conclusion. PwMS can learn and retain a novel visuomotor mapping during a precision-based walking task. This suggests that PwMS with mild disability have the capacity for short-term motor learning and retention, indicating that neural plasticity is preserved.
Vitamin K2 can suppress the expression of Toll-like receptor 2 (TLR2) and TLR4, and inhibit calcification of aortic intima in ApoE-/- mice as well as smooth muscle cells
Authors: Wang Zhaojun , Wang Zhongqun , Zhu Jie , Long Xinguang , Yan Jinchuan
Published: June 2017

Background and objectives

Vascular calcification is a common complication in atherosclerosis. Accumulating evidence showed that Toll-like receptors (TLRs) mediate pro-inflammatory and atherosclerosis. Recent studies demonstrated that vascular calcification is one of the detrimental effects of vitamin K (Vit K) antagonists. However, the effects of Vit K on the expression of TLR2 and 4 and intimal calcification in artery remained unidentified.

Methods and results

Eighteen ApoE-/- mice were randomly divided into model group, Vit K-treated group, and control group. The mice of model and Vit K-treated group were fed with high-fat diet, while control group mice were fed with normal diet. Mice of Vit K-treated group were administered orally with vitamin K2 (40 mg.kg−1.day−1) for 12 weeks. Twelve weeks later the aortic sections of mice were acquired and stained with hematoxylin and eosin and von Kossa, respectively. Calcium content and activity of alkaline phosphatase (ALP) at aortic tissues were measured. The expression levels of TLR2 and TLR4 in aorta sections were detected by immunohistochemisty and RT-PCR, respectively. The effects of Vit K on cellular calcification were further studied in A7r5 SMCs. Results demonstrated that high-fat diet induced typical atherosclerosis with intimal calcification in ApoE-/- mice, while in Vit K-treated group atherosclerosis and calcium deposits were not serious; Vit K2 also inhibited cellular calcification in A7r5 SMCs. Quantitative analysis showed that calcium and ALP activity at aortic tissues in the Vit K-treated mice were significantly lower than that of the model group ( P < 0.01); Compared to the control group, the expression levels of TLR2 and TLR4 in the model group were significantly higher ( P < 0.05), while in Vit K-treated group the levels of TLR2 and 4 were significantly lower than that in the model group. Furthermore, the content of calcium was positively related to the expression levels of TLR2 and TLR4 mRNA at aortic tissues ( r = 0.77 and r = 0.79, respectively, both P < 0.001).

Conclusion

VitK2 can inhibit intimal calcification of aortic artery induced by high-fat diet in ApoE-/- mice and A7r5 SMCs calcification induced by β-sodium glycerophosphate, and meanwhile can reduce the expression of TLR2 and TLR4. These results suggested that the effects of VitK2 on vascular calcification may be associated with the expression of TLR2 and TLR4.
Poly (I:C) and hyaluronic acid directly interact with NLRP3, resulting in the assembly of NLRP3 and ASC in a cell-free system
Authors: Kaneko Naoe , Ito Yuki , Iwasaki Tomoyuki , Takeda Hiroyuki , Sawasaki Tatsuya , Migita Kiyoshi , Agematsu Kazunaga , Koga Tomohiro , Kawakami Atsushi , Yachie Akihiro , Yoshiura Koh-ichiro , Morikawa Shinnosuke , Kurata Mie , Masumoto Junya
Published: June 2017

In the NLR family, pyrin domain containing 3 (NLRP3) is an intracellular pattern recognition receptor that activates pro-caspase-1, leading to IL-1β and IL-18 processing and activation in a large complex called the NLRP3 inflammasome. Since various pathogens or endogenous metabolites have been reported to stimulate NLRP3 inflammasome, the interaction between NLRP3 and ASC induced by these stimulants may be an attractive drug target for NLRP3-related diseases, called inflammasomopathies. However, the endogenous ligand that directly interacts with NLRP3, leading to binding to ASC, remains unclear. Therefore, we developed a cell-free system consisting of NLRP3, ASC, and pro-caspase-1 or ASC and NLRP3 with an amplified luminescent proximity homogeneous assay (ALPHA). ALPHA signals of the interaction between NLRP3 and ASC were not enhanced following an incubation without any ligand, whereas strong ALPHA signals for the interaction between NLRP3 and ASC and between NLRP3 and pro-caspase-1 with the adaptor ASC were observed upon an incubation with poly (I:C) and hyaluronic acid (HA). Poly (I:C) and HA both directly interacted with NLRP3 within a specific concentration. These results suggest that NLRP3 directly interacts with intrinsic RNA and HA, which is followed by the activation of NLRP3 inflammasome, and the cell-free system consisting of NLRP3 and ASC, or NLRP3, ASC, and pro-caspase-1 may be a useful tool for elucidating the pathogenesis of inflammasomopathies and developing target therapeutics.
Differential involvement of reactive oxygen species in a mouse model of capsaicin-induced secondary mechanical hyperalgesia and allodynia
Authors: La Jun-Ho , Wang Jigong , Bittar Alice , Shim Hyun Soo , Bae Chilman , Chung Jin Mo
Published: June 2017

Intradermally injected capsaicin induces secondary mechanical hyperalgesia and allodynia outside the primary (i.e., capsaicin-injected) site. This secondary mechanical hypersensitivity is attributed to central sensitization in which reactive oxygen species (ROS) play a key role. We examined whether ROS would be differentially involved in secondary mechanical hyperalgesia and allodynia using a mouse intraplantar capsaicin injection model. In mice, capsaicin-induced secondary mechanical hyperalgesia outlasted its allodynia counterpart. Unlike the hyperalgesia, the allodynia was temporarily abolished by an anesthetic given at the capsaicin-injected site. The ROS scavenger phenyl-N-tert-butylnitrone slowed the development of both secondary mechanical hyperalgesia and allodynia when administered before intraplantar capsaicin injection, whereas it inhibited only the allodynia when administered after capsaicin had already induced secondary mechanical hyperalgesia and allodynia. Intrathecal injection of the ROS donor KO2 induced both mechanical hyperalgesia and allodynia with the former outlasting the latter. Metformin, an activator of redox-sensitive adenosine monophosphate-activated protein kinase, selectively inhibited capsaicin-induced secondary mechanical allodynia and intrathecal KO2-induced mechanical allodynia. These results suggest that ROS is required for rapid activation of central sensitization mechanisms for both secondary mechanical hyperalgesia and allodynia after intraplantar capsaicin injection. Once activated, the mechanism for the hyperalgesia is long-lasting without being critically dependent on ongoing afferent activities arising from the capsaicin-injected site and the continuous presence of ROS. On the contrary, the ongoing afferent activities, ROS presence and adenosine monophosphate-activated protein kinase inhibition are indispensable for the maintenance mechanism for capsaicin-induced secondary mechanical allodynia.
The invisible structures of anarchy: Gender, orders, and global politics
Authors: Sjoberg Laura
Published: June 2017

This article argues anarchy is undertheorized in International Relations, and that the undertheorization of the concept of anarchy in International Relations is rooted in Waltz’s original discussion of the concept as equal to the invisibility of structure, where the lack of exogenous authority is not just a feature of the international political system but the salient feature. This article recognizes the international system as anarchical but looks to theorize its contours—to see the invisible structures that are overlaid within international anarchy, and then to consider what those structures mean for theorizing anarchy itself. It uses as an example the various (invisible) ways that gender orders global political relations to suggest that anarchy in the international arena is a place of multiple orders rather than of disorder. It therefore begins by theorizing anarchy with orders in global politics, rather than anarchy as necessarily substantively lacking orders. It then argues that gender orders global politics in various ways. It concludes with a framework for theorizing order within anarchy in global politics.
A content analysis of the consumer-facing online information about My Health Record: Implications for increasing knowledge and awareness to facilitate uptake and use
Authors: Walsh Louisa , Hill Sophie , Allan Meredith , Balandin Susan , Georgiou Andrew , Higgins Isabel , Kraal Ben , McCarthy Shaun , Hemsley Bronwyn
Published: June 2017

Background:

Low health literacy, low levels of positive belief and privacy and security concerns have been identified as a significant barrier to personal electronic health record uptake and use. An important tool for overcoming these barriers is the consumer-facing information which accompanies the system. My Health Record (MyHR) is the Australian national e-health record system, for which a large suite of online resources exists to facilitate consumer registration and use. This study uses a number of different measures of health resource quality to assess the MyHR online consumer-facing information and identify any gaps or areas for improvement.

Objective:

To analyse the quality and content of the online consumer-facing resources which support the uptake and use of MyHR.

Method:

Australian information resources aimed at healthcare consumers about the MyHR were included in this study. A comprehensive search using Internet search engines was conducted to locate all online consumer-facing resources about MyHR from both government and non-government sources. Readability (measured by Flesch–Kincaid grade level), year of publication/review, publishing organisation type, presentation style, linked websites, target audience, and themes were identified as important measures of health information quality, and these were recorded and reported on for each resource.

Results:

Eighty resources met the inclusion criteria. The mean Flesch–Kincaid grade level was 11.8. Most resources were created by Australian government sources ( n = 55), and the most common target audience was the general public ( n = 65). Registration ( n = 51), privacy/security ( n = 49), and benefits of use ( n = 46) were the most common resource themes.

Conclusion:

The authors identified a number of gaps and areas for improvement in the provision of consumer-facing information about MyHR. Readability is too high for the general Australian population, and there are few translated resources, which means that the information provided does not cater to people with low literacy levels, communication disability, and/or difficulties in understanding written English. The target audiences for resources do not reflect priority groups that were identified during the MyHR development processes. There are also gaps in information provision about how consumers can use MyHR as a tool to meaningfully engage with health professionals and services to support their own person-centred care.
Do the New FDA Guidance Documents Help Improving Performance of Blood Glucose Monitoring Systems Compared With ISO 15197?
Authors: Freckmann Guido , Baumstark Annette , Pleus Stefan
Published: June 2017

Recently, the Food and Drug Administration (FDA) published guidance documents for point-of-care testing (POCT) and over-the-counter (OTC) blood glucose monitoring systems (BGMS). These are expected to improve weaknesses of the already established ISO 15197:2013 standard accuracy evaluation for OTC BGMS; however, the proposed criteria and procedures rather raise new questions. As an example, the OTC guidance stipulates tighter accuracy criteria in the low glycemic range than the POCT guidance for no obvious reason. Furthermore, a clear definition of requirements for the reference method is missing under consideration of the strict accuracy criteria. External surveillance of BGMS after introduction to the market is an issue that is addressed neither in the FDA documents, nor in ISO 15197, but in the Clinical and Laboratory Standards Institute (CLSI) guideline POCT12-A3.
The Temporal Stability of In-Group Favoritism Is Mostly Attributable to Genetic Factors
Authors: Lewis Gary J. , Bates Timothy C.
Published: June 2017

Twin studies of in-group favoritism have reported roughly equal influences of genetic and environmental factors. All, however, have solely relied on cross-sectional approaches, leaving open the question of whether genetic and environmental factors have similar roles on stability and change for in-group favoritism across time. While in-group favoritism is commonly perceived to reflect environmental influences, stable environmental effects are rare for psychological traits, thus suggesting that genetic influences may play the major role in the stability of favoritism. Here, we used addressed this issue using a 10-year (two waves) longitudinal twin design. In-group favoritism showed high rank-order stability ( r = .67). Seventy four percent of this rank-order stability was attributable to genes. A broadly similar pattern was observed for race, ethnic, and religious favoritism. By contrast, changes in favoritism almost entirely reflected nonshared environmental influences. These findings indicate that environmental influences underpin change in favoritism, while the stability of favoritism mostly reflects genetic influences.
Physical Androgyny and Categorization Difficulty Shape Political Conservatives’ Attitudes Toward Transgender People
Authors: Stern Chadly , Rule Nicholas O.
Published: June 2017

Researchers have recently begun to examine how categorization processes impact social evaluations. In two studies, we examined how sex categorization influences attitudes toward transgender individuals. We found that people evaluated transgender individuals more negatively if they possessed physically androgynous (vs. sex-typical) characteristics because they struggled to identify their sex. These relationships were stronger among political conservatives compared to individuals with more liberal political views. These findings provide new insights for research on attitudes toward gender minorities and for the role of political ideology in social judgments.
Comparison of two-dimensional strain analysis using vendor-independent and vendor-specific software in adult and pediatric patients
Authors: Anwar Shafkat , Negishi Kazuaki , Borowszki Allen , Gladding Patrick , Popović Zoran B , Erenberg Francine , Thomas James D
Published: June 2017

Introduction

Two-dimensional strain analysis is a powerful analysis modality, however, clinical utilization has been limited by variability between different analysis systems and operators. We compared strain in adults and children using vendor-specific and vendor-independent software to evaluate variability.

Methods

One hundred and ten subjects (50/110 pediatric, 80/110 normal left ventricular function) had echocardiograms with a General Electric ultrasound scanner between September 2010 and January 2012. Left ventricular longitudinal strain was derived with EchoPAC (General Electric, v10.8.1), a vendor-specific software, and Velocity Vector Imaging (Siemens, v3.5), which is vendor-independent. Three independent readers analyzed all the echocardiograms yielding 330 datasets.

Results

Mean left ventricular global longitudinal Lagrangian strain was −18.1 ± SD 4.4% for EchoPAC and −15.3 ± SD 4.1% for Velocity Vector Imaging. Velocity Vector Imaging yielded lower absolute global longitudinal Lagrangian strain by mean 2.9 (±SD 2.7, p < 0.0001), and lower regional longitudinal strain. These differences persisted in normal subjects versus those with cardiomyopathy. Longitudinal strain differences were slightly higher in the pediatric cohort. There was no significant difference in inter-observer longitudinal strain and a small difference in intra-observer strain between analysis systems. On repeat measurements, a significant change in global longitudinal Lagrangian strain occurred after the difference exceeded 3–5 strain points for EchoPAC and Velocity Vector Imaging, respectively.

Conclusion

Velocity Vector Imaging produces lower left ventricular longitudinal strain values versus EchoPAC for the same echo images. Both systems have similar inter-observer variability, Velocity Vector Imaging slightly higher intra-observer variability. A statistically significant change in global longitudinal Lagrangian strain occurs with changes >3–5 strain points on repeat measurements. Strain values between the systems are not interchangeable.
Quality of life in patients with established rheumatoid arthritis: A phenomenographic study
Authors: Malm Karina , Bergman Stefan , Andersson Maria LE , Bremander Ann , Larsson Ingrid
Published: June 2017

Objective:

Patients with rheumatoid arthritis perceive reduced quality of life in several domains, such as physical health, level of independence, environment and personal beliefs, compared with the healthy population. There is an increasing interest in quality of life in clinical and medical interventions. Few studies have explored patients’ individual conceptions of quality of life, and interviews can thus complement quantitative studies. There is a need for a deeper understanding of the patients’ experiences of quality of life, with regard to living with a long-term condition such as rheumatoid arthritis. The aim of this study was to explore the variation of ways in which patients with established rheumatoid arthritis understand the concept of quality of life.

Methods:

The study had a qualitative design with a phenomenographic approach, which was used to describe variations in how individuals experience their quality of life. The study is based on interviews with 22 patients with established rheumatoid arthritis enrolled in the BARFOT (better anti-rheumatic pharmacotherapy) study.

Results:

The concept of quality of life could be understood in three different ways: (1) independence in terms of physical functioning and personal finances, (2) empowerment in how to manage life and (3) participation as an experience of belonging in a social context.

Conclusion:

The different conceptions of quality of life reflect the complexity in the concept, including physical, psychological and social aspects. This complexity is important to have in mind when health professionals support patients in enhancing their quality of life.
Bifurcated BACH2 control coordinates mantle cell lymphoma survival and dispersal during hypoxia
Authors: Zhang Han , Chen Zheng , Miranda Roberto N. , Medeiros L. Jeffrey , McCarty Nami
Published: June 2017

Key Points

Downregulation of BACH2 increases MCL proliferation, dispersal, and drug resistance. Distinct crosstalk between BACH2 and HIF-1α under different physiological conditions modifies MCL properties.
Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia
Authors: Stein Eytan M. , DiNardo Courtney D. , Pollyea Daniel A. , Fathi Amir T. , Roboz Gail J. , Altman Jessica K. , Stone Richard M. , DeAngelo Daniel J. , Levine Ross L. , Flinn Ian W. , Kantarjian Hagop M. , Collins Robert , Patel Manish R. , Frankel Arthur E. , Stein Anthony , Sekeres Mikkael A. , Swords Ronan T. , Medeiros Bruno C. , Willekens Christophe , Vyas Paresh , Tosolini Alessandra , Xu Qiang , Knight Robert D. , Yen Katharine E. , Agresta Sam , de Botton Stephane , Tallman Martin S.
Published: June 2017

Key Points

Enasidenib, a selective inhibitor of mutant IDH2 enzymes, was safe and well tolerated in patients with IDH2-mutated myeloid malignancies. Enasidenib induced hematologic responses in patients with relapsed/refractory AML in this dose-escalation and expansion study.
Functional Characterization of Xenopus Thyroid Hormone Transporters mct8 and oatp1c1
Authors: Mughal Bilal B , Leemans Michelle , Lima de Souza Elaine C , le Mevel Sébastien , Spirhanzlova Petra , Visser Theo J , Fini Jean-Baptiste , Demeneix Barbara A
Published: June 2017

Xenopus is an excellent model for studying thyroid hormone signaling as it undergoes thyroid hormone–dependent metamorphosis. Despite the fact that receptors and deiodinases have been described in Xenopus, membrane transporters for these hormones are yet to be characterized. We cloned Xenopus monocarboxylate transporter 8 (mct8) and organic anion-transporting polypeptide 1C1 (oatpc1c1), focusing on these two transporters given their importance for vertebrate brain development. Protein alignment and bootstrap analysis showed that Xenopus mct8 and oatp1c1 are closer to their mammalian orthologs than their teleost counterparts. We functionally characterized the two transporters using a radiolabeled hormones in vitro uptake assay in COS-1 cells. Xenopus mct8 was found to actively transport both T3 and T4 bidirectionally. As to the thyroid precursor molecules, diiodotyrosine (DIT) and monoiodotyrosine (MIT), both human and Xenopus mct8, showed active efflux, but no influx. Again similar to humans, Xenopus oatp1c1 transported T4 but not T3, MIT, or DIT. We used reverse transcription quantitative polymerase chain reaction and in situ hybridization to characterize the temporal and spatial expression of mct8 and oatp1c1 in Xenopus. Specific expression of the transporter was observed in the brain, with increasingly strong expression as development progressed. In conclusion, these results show that Xenopus thyroid hormone transporters are functional and display marked spatiotemporal expression patterns. These features make them interesting targets to elucidate their roles in determining thyroid hormone availability during embryonic development.
Biological Evaluation of a Fluorescent-Imaging Agent for Medullary Thyroid Cancer in an Orthotopic Model
Authors: Rossfeld Kara K , Justiniano Steven E , Ding Haiming , Gong Li , Kothandaraman Shankaran , Sawant Dwitiya , Saji Motoyasu , Wright Chadwick L , Kirschner Lawrence S , Ringel Matthew D , Tweedle Michael F , Phay John E
Published: June 2017

Context

The primary and definitive treatment of medullary thyroid cancer (MTC) is surgical resection. Recurrent or residual disease is typically a result of incomplete surgical removal.

Objective

Our objective is to develop a compound that assists in intraoperative visualization of cancer, which would have the potential to improve surgical cure rates and outcomes.

Results

We report the biological characterization of Compound-17, which is labeled with IRdye800, allowing fluorescent visualization of MTC mouse models. We found that the agent has high affinity for two human MTC cell lines (TT and MZ-CRC1) in vitro and in vivo. We further tested the affinity of the compound in a newly developed MTC orthotopic xenograft model and found that Compound-17 produces fluorescent signals within MTC-derived orthotopic xenografts in comparison with a sequence-jumbled control compound and surrounding normal tissues.

Conclusions

Compound-17 is a unique and effective molecule for MTC identification that may have therapeutic potential.
Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity
Authors: Timper Katharina , Brüning Jens C.
Published: June 2017

The ‘obesity epidemic’ represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies. The CNS plays a pivotal role in the regulation of energy and glucose homeostasis. Distinct neuronal cell populations, particularly within the arcuate nucleus of the hypothalamus, sense the nutrient status of the organism and integrate signals from peripheral hormones including pancreas-derived insulin and adipocyte-derived leptin to regulate calorie intake, glucose metabolism and energy expenditure. The arcuate neurons are tightly connected to other specialized neuronal subpopulations within the hypothalamus, but also to various extrahypothalamic brain regions, allowing a coordinated behavioral response. This At a Glance article gives an overview of the recent knowledge, mainly derived from rodent models, regarding the CNS-dependent regulation of energy and glucose homeostasis, and illustrates how dysregulation of the neuronal networks involved can lead to overnutrition and obesity. The potential impact of recent research findings in the field on therapeutic treatment strategies for human obesity is also discussed.
Induced pluripotent stem cell models of lysosomal storage disorders
Authors: Borger Daniel K. , McMahon Benjamin , Roshan Lal Tamanna , Serra-Vinardell Jenny , Aflaki Elma , Sidransky Ellen
Published: June 2017

Induced pluripotent stem cells (iPSCs) have provided new opportunities to explore the cell biology and pathophysiology of human diseases, and the lysosomal storage disorder research community has been quick to adopt this technology. Patient-derived iPSC models have been generated for a number of lysosomal storage disorders, including Gaucher disease, Pompe disease, Fabry disease, metachromatic leukodystrophy, the neuronal ceroid lipofuscinoses, Niemann-Pick types A and C1, and several of the mucopolysaccharidoses. Here, we review the strategies employed for reprogramming and differentiation, as well as insights into disease etiology gleaned from the currently available models. Examples are provided to illustrate how iPSC-derived models can be employed to develop new therapeutic strategies for these disorders. We also discuss how models of these rare diseases could contribute to an enhanced understanding of more common neurodegenerative disorders such as Parkinson’s disease, and discuss key challenges and opportunities in this area of research.
A dosimetric parameter to limit chest wall toxicity in SABR of NSCLC
Authors: Jumeau Raphaël , Filion Édith , Bahig Houda , Vu Toni , Lambert Louise , Roberge David , Doucet Robert , Campeau Marie-Pierre
Published: June 2017

Objective:

Chest wall (CW) toxicity (rib fracture and/or pain) is a recognized complication of stereotactic ablative radiotherapy (SABR) for non-small-cell lung cancer. The aim of this study was to evaluate the frequency of CW toxicity following SABR and to propose a new dosimetric parameter.

Methods:

We reviewed the charts and SABR plans from patients treated for T1–T2N0 peripheral non-small-cell lung cancer between 2009 and 2015. The CW structure was created through a 3-cm expansion of the lung. The median dose delivered to the planning target volume was 60 Gy. SABR was delivered in three fractions for patients with CW V  30 < 30 cm3. If the CW V  30 exceeded 30 cm3, five fractions were used, and the plan was optimized based on CW V  37 (biologically equivalent to the V  30 of three-fraction plans).

Results:

In 6 years, 361 lesions from 356 patients were treated (3 fractions: 297; 5 fractions: 64). The median follow-up was 16 months. 23 patients (6.5%) developed CW toxicity after a median time of 10 months following treatment. The mean CW V  30/V  37 was 21 cm3 for patients with CW toxicity and 17 cm3 for patients without toxicity (p < 0.05). The 2-year local control and the CW toxicity rates were similar, whether patients received three or five fractions (97% vs 96% and 7% vs 5%).

Conclusion:

When the CW V  30 is >30 cm3, altered fractionation combined with V  37 optimization can limit CW toxicity.

Advances in knowledge:

The CW V  37 is a suggested dosimetric parameter adapted to fractionation that may potentially limit CW toxicity after lung SABR.
Endovascular Treatment of Renal Arteriovenous Fistula with N-Butyl Cyanoacrylate (NBCA)
Authors: Kuklik Ewa , Sojka Michał , Karska Klaudia , Szajner Maciej
Published: June 2017

Background: Renal arteriovenous malformation (RAVM) is a rare disease. The causes of pathological connections between renal arteries may be congenital or iatrogenic – mainly as a consequence of a biopsy or due to renal carcinomas and postinflammatory changes. Computed tomography, ultrasound Doppler and angiography are the main diagnostic tools used for the detection of RAVMs.

Case Report: The aim of this study is to present a case of endovascular treatment of RAVM with a mixture of NBCA and lipiodol. A 29-year-old woman was suffering from drug-resistant hypertension secondary to RAVM. The malformation was embolized using NBCA mixed with lipiodol. The postoperative course was uneventful. A follow-up angio-CT, performed 3 months and one year after the procedure, showed a complete occlusion of the RAVM.

Conclusions: NBCA can be used alone to embolize RAVMs. Procedures involving a combination of NBCA and lipiodol are difficult and should be performed by experienced specialists.
Η χρήση του edmodo στη διδασκαλία των Αρχαίων Ελληνικών στην Α΄ Λυκείου
Authors: Λύχνου Ευτέρπη
Published: June 2017

Η νέα κοινωνική πραγματικότητα οδηγεί προοδευτικά το εκπαιδευτικό μας σύστημα σε επαναπροσδιορισμό των εκπαιδευτικών αναγκών και στόχων, σε αναζήτηση νέων εκπαιδευτικών εργαλείων, μεθόδων και τεχνικών. Το σχολείο καλείται να ανταποκριθεί στα νέα δεδομένα της ψηφιακής εποχής ,στις νέες εκπαιδευτικές προκλήσεις. Την κοινωνία των πολιτών, την κοινωνία της γνώσης στην οποία ζούμε δεν μπορεί να την επιδιώξει ο μελλοντικός πολίτης, αν δεν τη βιώσει στο σχολικό περιβάλλον. Στα πλαίσια αυτά εντάσσεται η χρήση της διαδικτυακής εκπαιδευτικής πλατφόρμας του Εdmodo, η οποία αρχικά χρησιμοποιήθηκε από τους καθηγητές τηςπληροφορικής, αλλά στη συνέχεια φάνηκε ότι μπορεί να αποτελέσει ένα χώρο δράσης και εργασίας και για τα γλωσσικά μαθήματα, όπως είναι τα αρχαία ελληνικά. Στόχος του παρόντος άρθρου είναι να παρουσιαστεί σε γενικές γραμμές η χρήση της πλατφόρμας Edmodo στο μάθημα της αρχαίας ελληνικής γλώσσας σε πραγματική τάξη Α΄ Λυκείου του Γυμνασίου-Λ.Τ. Παξών. Παράλληλα παρουσιάζονται οι λόγοι που οδήγησαν στην αναζήτηση ενός τέτοιου εργαλείου και στην επιλογή του συγκεκριμένου, καθώς και οι εκτιμήσεις στις οποίες κατέληξαν οι εκπαιδευτικοί, οι μαθητές και οι γονείς που το αξιοποίησαν.
Early embryo mortality in natural human reproduction: What the data say
Authors: Jarvis Gavin E.
Published: June 2017

How many human embryos die between fertilisation and birth under natural conditions? It is widely accepted that natural human embryo mortality is high, particularly during the first weeks after fertilisation, with total prenatal losses of 70% and higher frequently claimed. However, the first external sign of pregnancy occurs two weeks after fertilisation with a missed menstrual period, and establishing the fate of embryos before this is challenging. Calculations are additionally hampered by a lack of data on the efficiency of fertilisation under natural conditions. Four distinct sources are used to justify quantitative claims regarding embryo loss: (i) a hypothesis published by Roberts & Lowe inTheLancet is widely cited but has no practical quantitative value; (ii) life table analyses give consistent assessments of clinical pregnancy loss, but cannot illuminate losses at earlier stages of development; (iii) studies that measure human chorionic gonadotrophin (hCG) reveal losses in the second week of development and beyond, but not before; and (iv) the classic studies of Hertig and Rock offer the only direct insight into the fate of human embryos from fertilisation under natural conditions. Re-examination of Hertig’s data demonstrates that his estimates for fertilisation rate and early embryo loss are highly imprecise and casts doubt on the validity of his numerical analysis. A recent re-analysis of hCG study data concluded that approximately 40-60% of embryos may be lost between fertilisation and birth, although this will vary substantially between individual women. In conclusion, natural human embryo mortality is lower than often claimed and widely accepted. Estimates for total prenatal mortality of 70% or higher are exaggerated and not supported by the available data.
Make Room! Make Room! A Note on Sequential Spinoffs and Acquisitions
Authors: Bennett Victor Manuel , Feldman Emilie R.
Published: June 2017

In this study, we identify a novel pattern of deal-making activity—spinoffs followed by acquisitions—that has yet to be analyzed in the corporate strategy literature. We present a set of descriptive results showing that firms undertake spinoffs followed by acquisitions at a rate that is too high to be attributable to random chance. We also find that the acquired businesses are typically more closely related to these companies’ remaining operations than are the spun-off subsidiaries, a pattern that is common across companies with different characteristics. Together, these results suggest that firms may use sequential spinoffs and acquisitions to achieve ongoing synergies and improve the allocation of managerial attention within their organizations. We conclude by discussing how our work contributes to ongoing conversations in corporate strategy about patterns of acquisitions and divestitures, resource redeployment, reconfiguration, and firm scope.
Review of European Thyroid Association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumours
Authors: Fadeyev Valentin V.
Published: June 2017

Тиреотоксикоз в большинстве случаев обусловлен аутоиммунными заболеваниями щитовидной железы или многоузловым токсическим зобом; крайне редко его причиной являются ТТГ-секретирующие аденомы гипофиза (ТТГ-омы). Эти опухоли характеризуются высоким уровнем циркулирующих тиреоидных гормонов в сочетании с отсутствием подавления или повышенным уровнем ТТГ. Неправильная диагностика ТТГ-ом зачастую является причиной неоправданных тиреоидэктомий или проведения терапии радиоактивным йодом, что в свою очередь сопровождается существенным увеличением размера опухоли гипофиза. Диагноз может быть подтвержден при помощи определения уровня ТТГ на фоне супрессивной терапии L-Т3 или в тесте с тиреолиберином. Эти тесты в комбинации с МРТ гипофиза и генетическим исследованием лежат в основе дифференциальной диагностики ТТГ-ом и синдромов резистентности к тиреоидным гормонам. Методом выбора в лечении ТТГ-ом является хирургическая транссфеноидальная аденомэктомия. При невозможности проведения или неэффективности оперативного лечения эффективным методом нормализации продукции ТТГ в 90% случаев является назначение аналогов соматостатина.