bluuebunny/crossref_metadata_2025 huggingface dataset:
Oestrogen upregulates the expression levels and functional activities of duodenal mucosal CFTR and SLC26A6
Authors: Jin Hai , Wen Guorong , Deng Shili , Wan Shuo , Xu Jingyu , Liu Xuemei , Xie Rui , Dong Hui , Tuo Biguang
Published: September 2016

New Findings

What is the central question of this study?

Duodenal ulcer is a common disease. A sex‐based difference in the incidence of duodenal ulcer has long been observed clinically, but the cause is unclear.

What is the main finding and its importance?

Duodenal mucosal bicarbonate secretion is the most important protective factor in duodenal mucosa against acid‐induced damage. The cystic fibrosis transmembrane conductance regulator (CFTR) and the solute‐linked carrier 26 gene family A6 (SLC26A6) are two key bicarbonate transport proteins that mediate duodenal mucosal bicarbonate secretion. We demonstrate that endogenous oestrogen upregulates the expression levels and functional activities of duodenal mucosal CFTR and SLC26A6, which contributes to the sex difference in the prevalence of duodenal ulcer.

The incidence of duodenal ulcer is markedly lower in women than men, but the cause of the sex difference is not clear. The cystic fibrosis transmembrane conductance regulator (CFTR) and the solute‐linked carrier 26 gene family A6 (SLC26A6) are two key bicarbonate transport proteins that mediate duodenal mucosal bicarbonate secretion, which is an important protective factor against acid‐induced duodenal injury. The aim of this study was to investigate the effect of oestrogen on the expressions and functional activities of CFTR and SLC26A6 in duodenal mucosa. We found that the expression levels of duodenal CFTR and SLC26A6 were markedly higher in young (20‐ to 30‐year‐old) women than in young men and old (60‐ to 70‐year‐old) women and men. The expression levels of CFTR and SLC26A6 in young women were markedly higher in preovulatory phases than in premenstrual phases, which was consistent with the changes of serum estradiol concentrations. Further results showed that duodenal CFTR and SLC26A6 expression levels in female mice were markedly decreased after ovariectomy, and supplementation with estradiol reversed the changes in CFTR and SLC26A6. 17β‐Estradiol increased CFTR and SLC26A6 expression levels of human duodenocytes in experiments in vitro. Functional experiments showed that basal and forskolin‐ and prostaglandin E2‐stimulated duodenal bicarbonate secretion in ovariectomized mice was markedly decreased and, likewise, supplementation with 17β‐estradiol reversed the changes. In conclusion, endogenous oestrogen upregulates the expressions and functional activities of CFTR and SLC26A6 in duodenal mucosa, which could contribute to protection of the duodenum and explain the sex difference in the prevalence of duodenal ulcer.
Role of respiratory changes in the modulation of arterial pressure in rats submitted to sino‐aortic denervation
Authors: Amorim Mateus R. , Bonagamba Leni G. H. , Souza George M. P. R. , Moraes Davi J. A. , Machado Benedito H.
Published: September 2016

New Findings

What is the central question of this study?

The arterial baroreflex regulates arterial pressure within a narrow range of variation. After sino‐aortic denervation (SAD), rats show a large increase in arterial pressure variability, but mean arterial pressure levels remain similar to those of control rats. Considering that breathing influences the control of arterial pressure, the question is: to what extent does SAD cause changes in breathing?

What is the main finding and its importance?

Removal of arterial baroreceptors produced changes in breathing in rats, marked by a reduction in respiratory frequency, but not hypertension. These findings are indicative of a possible interaction of respiratory and autonomic neural mechanisms in the regulation of arterial pressure after SAD.

Sino‐aortic denervated (SAD) rats exhibit a mean arterial pressure (MAP) similar to that of control rats. Given that respiration modulates MAP, we hypothesized that conscious SAD rats show respiratory changes associated with the normal MAP. In this study, we evaluated the cardiovascular and respiratory activities and arterial blood gases in control and SAD rats. Male juvenile Wistar rats (postnatal day 19–21) were submitted to SAD, sham surgery or selective removal of the carotid bodies (CBX), and the three groups were evaluated 10 days after the surgery (SAD, n = 21; Sham, n = 18; and CBX, n = 13). The MAP in Sham, SAD and CBX groups was similar (P > 0.05), but the variability of MAP was significantly higher in SAD than in Sham and CBX rats (P < 0.0001). The duration of expiration and inspiration increased in SAD rats compared with Sham and CBX rats, which resulted in a reduced respiratory frequency and minute ventilation (P < 0.05). The arterial partial pressure of O2 and the haemoglobin saturation were reduced in SAD and CBX compared with Sham rats, whereas the arterial partial pressure of CO2 was increased in SAD compared with Sham rats. The short‐ and long‐term respiratory variability were significantly higher in SAD than in Sham and CBX rats (P < 0.05). In addition, the reductions in MAP during deep breaths were greater in SAD than in Sham and CBX rats (P < 0.0001). The data show that SAD rats exhibit respiratory changes, which may be one of the compensatory mechanisms associated with the maintenance of normal levels of MAP in the absence of arterial baroreceptors.
Improving and accelerating the differentiation and functional maturation of human stem cell‐derived neurons: role of extracellular calcium and GABA
Authors: Kemp Paul J. , Rushton David J. , Yarova Polina L. , Schnell Christian , Geater Charlene , Hancock Jane M. , Wieland Annalena , Hughes Alis , Badder Luned , Cope Emma , Riccardi Daniela , Randall Andrew D. , Brown Jonathan T. , Allen Nicholas D. , Telezhkin Vsevolod
Published: September 2016

Neurons differentiated from pluripotent stem cells using established neural culture conditions often exhibit functional deficits. Recently, we have developed enhanced media which both synchronize the neurogenesis of pluripotent stem cell‐derived neural progenitors and accelerate their functional maturation; together these media are termed SynaptoJuice. This pair of media are pro‐synaptogenic and generate authentic, mature synaptic networks of connected forebrain neurons from a variety of induced pluripotent and embryonic stem cell lines. Such enhanced rate and extent of synchronized maturation of pluripotent stem cell‐derived neural progenitor cells generates neurons which are characterized by a relatively hyperpolarized resting membrane potential, higher spontaneous and induced action potential activity, enhanced synaptic activity, more complete development of a mature inhibitory GABAA receptor phenotype and faster production of electrical network activity when compared to standard differentiation media. This entire process – from pre‐patterned neural progenitor to active neuron – takes 3 weeks or less, making it an ideal platform for drug discovery and disease modelling in the fields of human neurodegenerative and neuropsychiatric disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease and Schizophrenia.

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A Novel Sequential Multi-Objective Optimization Using Anchor Points in the Design Space of Global Variables
Authors: Zhou Jianhua , Li Mian , Xu Min
Published: September 2016

Multi-objective problems are encountered in many engineering applications and multi-objective optimization (MOO) approaches have been proposed to search for Pareto solutions. Due to the nature of searching for multiple optimal solutions, the computational efforts of MOO can be a serious concern. To improve the computational efficiency, a novel efficient sequential MOO (S-MOO) approach is proposed in this work, in which anchor points in the design space for global variables are fully utilized and a data set for global solutions is generated to guide the search for Pareto solutions. Global variables refer to those shared by more than one objective or constraint, while local variables appear only in one objective and corresponding constraints. As a matter of fact, it is the existence of global variables that leads to couplings among the multiple objectives. The proposed S-MOO breaks the couplings among multiple objectives (and constraints) by distinguishing the global variables, and thus all objectives are optimized in a sequential manner within each iteration while all iterations can be processed in parallel. The computational cost per produced Pareto point is reduced and a well-spread Pareto front is obtained. Six numerical and engineering examples including two three-objective problems are tested to demonstrate the applicability and efficiency of the proposed approach.
Architecture, Performance, and Investment in Product Development Networks
Authors: Yassine Ali A. , Naoum-Sawaya Joe
Published: September 2016

Firms engaging in product development (PD) face the imperative problem of allocating scarce development resources to a multitude of opportunities. In this paper, we propose a mathematical formulation to optimize PD investment or resource allocation decisions. The model maximizes the performance of a product under development, based on its architecture and the firm's available resource, by choosing the optimal resource allocation across product modules and design rules that govern the relationships between these modules. Results based on a comprehensive experiment (with various architectural patterns, escalating number of dependencies, and different problem sizes) shed light on three important hypotheses. First, product architecture affects resource allocation decisions and ultimately product performance. The second hypothesis tests whether modular or integral architectures can attain higher performance levels based on our formulation. A third hypothesis states that there is a shift in the temporal allocation of resources from design rules to individual modules, thus supporting the move from integral to modular architectures as the product evolves across multiple generations. Finally, the model and the experimental results provide design and managerial insights to both development engineers and managers. Specifically, for development engineers, the model and its analysis provide guidance for selecting the product architecture which leads to maximum performance. For development managers, the model and its analysis assist in deciding the optimal budget proportions to be allocated to modules and to design rules, given a fixed architecture and budget.
Experimental Study of Channel Driven Cavity Flow for Fluid–Structure Interaction
Authors: Kwon Y. W. , Arceneaux S. M.
Published: September 2016

An experimental setup was designed and fabricated for the channel driven cavity flow in order to provide benchmark data for validation of any numerical analysis program for solving fluid–structure interaction (FSI) problems. The channel driven cavity flow is a modification from the lid-driven cavity flow. To provide the fluid–structure interaction, the bottom face of the cavity is a deformable flat plate. All other boundaries are rigid. The fluid motion inside the cavity is driven by the flow through a narrow channel topside of the cavity. To establish suitable boundary conditions for numerical analyses of the experiment, the inlet of the channel has a given fluid velocity, while its outlet has a known pressure. Water is used as the fluid in this study. Multiple strain gages and laser displacement sensors were used to measure dynamic responses of the plate attached at the bottom of the cavity.
Analytical Inverse Solution of Eigenstrains and Residual Fields in Autofrettaged Thick-Walled Tubes
Authors: Ali Faghidian S.
Published: September 2016

The smoothed inverse eigenstrain method is revisited for the reconstruction of residual fields and eigenstrains from limited strain measurements within axially symmetric tubes. The application of the present approach is successfully demonstrated for two cases of analytical solution and experimental measurements. The well-known advantage of the smoothed inverse eigenstrain approach is that it not only minimizes the deviation of measurements from the model predictions but also will result in an inverse solution satisfying all of the continuum mechanics requirements. As a result, less number of experimental measurements is required to reconstruct the complete residual fields. Consequently, the distribution of residual stresses is obtained without requiring the details of the hardening behavior of the material. Furthermore, the eigenstrain field is inversely determined satisfying the total strain compatibility equations, and a closed form analytical solution is presented for the distribution of eigenstrains.
A Nonclassical Finite Element Approach for the Nonlinear Analysis of Micropolar Plates
Authors: Ansari R. , Shakouri A. H. , Bazdid-Vahdati M. , Norouzzadeh A. , Rouhi H.
Published: September 2016

Based on the micropolar elasticity theory, a size-dependent rectangular element is proposed in this article to investigate the nonlinear mechanical behavior of plates. To this end, a novel three-dimensional formulation for the micropolar theory with the capability of being used easily in the finite element approach is developed first. Afterward, in order to study the micropolar plates, the obtained general formulation is reduced to that based on the Mindlin plate theory. Accordingly, a rectangular plate element is developed in which the displacements and microrotations are estimated by quadratic shape functions. To show the efficiency of the developed element, it is utilized to address the nonlinear bending problem of micropolar plates with different types of boundary conditions. It is revealed that the present finite element formulation can be efficiently employed for the nonlinear modeling of small-scale plates by considering the micropolar effects.
Novel electron monochromator for high resolution imaging and spectroscopy
Authors: Mankos Marian , Shadman Khashayar , Kolarik Vladimir
Published: September 2016

A mirror electron monochromator has been developed for reducing the energy spread of commonly used high brightness electron sources from the characteristic range of 0.3–1 eV to values below 100 meV. The monochromator utilizes mirror optics and thereby exploits the symmetry inherent in reversing the electron trajectory to monochromatize the primary beam with a knife edge instead of a conventional slit. The performance of the key electron-optical components of the monochromator has been simulated. These components include the combination of an electron mirror with a magnetic prism array. In initial testing, the monochromator has demonstrated the ability to reduce the energy spread of a 5 keV electron beam that was generated by a Schottky electron emitter from its initial value of 0.65–0.75 eV to 180 meV with an exit beam current exceeding 1 nA and to 100 meV with an exit beam current of 50 pA. Here, the attainable energy resolution was found to be limited by the noise on the power supply. The monochromator is designed to attach to scanning and transmission electron microscopes thus making them suitable for enhancing the study of the structure, composition, and bonding states of new materials at the nanoscale. For scanning electron microscopy, the monochromator will increase the spatial resolution of the acquired images of specimens, in particular, at low landing energies where the chromatic aberrations become dominant. For transmission electron microscopy, the monochromator will refine the spectra extracted from electron spectrometers, where the energy spread of the electron source limits the achievable energy resolution.
A substructuring approach for modeling the acoustic scattering from stiffened submerged shells coupled to non-axisymmetric internal structures
Authors: Meyer Valentin , Maxit Laurent , Audoly Christian
Published: September 2016

The scattered pressure from a stiffened axisymmetric submerged shell impinged by acoustic plane waves has been investigated experimentally, analytically and through numerical models. In the case where the shell is periodically stiffened, it is shown that helical, Bragg, and Bloch-Floquet waves can propagate. The influence of non-axisymmetric internal frames on these scattering phenomena is nevertheless not well known, as it can considerably increase the computational cost. To overcome this issue, the condensed transfer function (CTF) method, which has been developed to couple subsystems along linear junctions in the case of a mechanical excitation, is extended to acoustical excitations. It consists in approximating transfer functions on the junctions and deducing the behavior of the coupled system using the superposition principle and the continuity equations at the junctions. In particular, the CTF method can be used to couple a dedicated model of an axisymmetric stiffened submerged shell with non-axisymmetric internal structures modeled by the finite element method. Incident plane waves are introduced in the formulation and far-field reradiated pressure is estimated. An application consisting of a stiffened shell with curved plates connecting the ribs is considered. Supplementary Bloch-Floquet trajectories are observed in the frequency-angle spectrum and are explained using a simplified interference model.
Sparse spatial spectral estimation in directional noise environment
Authors: Yang Long , Yang Yixin , Wang Yong
Published: September 2016

White Gaussian noise assumption is widely used in the field of spatial spectral estimation. But, the practical ambient noise usually does not satisfy this assumption, which may seriously affect the performance of direction of arrival estimation. This letter presents a linear noise model that can provide a more complete description of the practical ambient noise field, and then proposes a directional noise field sparse spectrum fitting (DN-SpSF) algorithm to estimate the spatial spectral in a directional noise field. Simulations and experimental results demonstrate the good performance of the DN-SpSF algorithm in a spatially directional noise environment.
Class I HLA haplotypes form two schools that educate NK cells in different ways
Authors: Horowitz Amir , Djaoud Zakia , Nemat-Gorgani Neda , Blokhuis Jeroen , Hilton Hugo G. , Béziat Vivien , Malmberg Karl-Johan , Norman Paul J. , Guethlein Lisbeth A. , Parham Peter
Published: September 2016

Individuals heterozygous for HLA haplotypes have increased NK cell diversity because of distinct education pathways.
EyeOpener
Authors: Shu Zhixin , Shechtman Eli , Samaras Dimitris , Hadap Sunil
Published: September 2016

Closed eyes and look-aways can ruin precious moments captured in photographs. In this article, we present a new framework for automatically editing eyes in photographs. We leverage a user’s personal photo collection to find a “good” set of reference eyes and transfer them onto a target image. Our example-based editing approach is robust and effective for realistic image editing. A fully automatic pipeline for realistic eye editing is challenging due to the unconstrained conditions under which the face appears in a typical photo collection. We use crowd-sourced human evaluations to understand the aspects of the target-reference image pair that will produce the most realistic results. We subsequently train a model that automatically selects the top-ranked reference candidate(s) by narrowing the gap in terms of pose, local contrast, lighting conditions, and even expressions. Finally, we develop a comprehensive pipeline of three-dimensional face estimation, image warping, relighting, image harmonization, automatic segmentation, and image compositing in order to achieve highly believable results. We evaluate the performance of our method via quantitative and crowd-sourced experiments.
On Well-Founded Set-Inductions and Locally Monotone Operators
Authors: Bogaerts Bart , Vennekens Joost , Denecker Marc
Published: September 2016

In the past, compelling arguments in favour of the well-founded semantics for autoepistemic logic have been presented. In this article, we show that for certain classes of theories, this semantics fails to identify the unique intended model. We solve this problem by refining the well-founded semantics. We develop our work in approximation fixpoint theory, an abstract algebraical study of semantics of nonmonotonic logics. As such, our results also apply to logic programming, default logic, Dung’s argumentation frameworks, and abstract dialectical frameworks.
Mediterranean Biomes: Evolution of Their Vegetation, Floras, and Climate
Authors: Rundel Philip W. , Arroyo Mary T.K. , Cowling Richard M. , Keeley Jon E. , Lamont Byron B. , Vargas Pablo
Published: September 2016

Mediterranean-type ecosystems (MTEs) are located today in southwestern Australia, the Cape Region of South Africa, the Mediterranean Basin, California, and central Chile. These MTEs possess the highest levels of plant species richness in the world outside of the wet tropics. These ecosystems include a variety of vegetation structures that range from the iconic mediterranean-type shrublands to deciduous and evergreen woodlands, evergreen forests, and herblands and grasslands. Sclerophyll vegetation similar to today's mediterranean-type shrublands was already present on oligotrophic soils in the wet and humid climate of the Cretaceous, with fire-adapted Paleogene lineages in southwestern Australia and the Cape Region. The novel mediterranean-type climate (MTC) seasonality present since the middle Miocene has allowed colonization of MTEs from a regional species pool with associated diversification. Fire persistence has been a primary driving factor for speciation in four of the five regions. Understanding the regional patterns of plant species diversity among the MTEs involves complex interactions of geologic and climatic histories for each region as well as ecological factors that have promoted diversification in the Neogene and Quaternary. A critical element of species richness for many MTE lineages has been their ability to speciate and persist at fine spatial scales, with low rates of extinction.
Credit Default Swaps: Past, Present, and Future
Authors: Augustin Patrick , Subrahmanyam Marti G. , Tang Dragon Y. , Wang Sarah Q.
Published: September 2016

Credit default swaps (CDS) have grown to be a multi-trillion-dollar, globally important market. The academic literature on CDS has developed in parallel with the market practices, public debates, and regulatory initiatives in this market. We selectively review the extant literature, identify remaining gaps, and suggest directions for future research. We present a narrative including the following four aspects. First, we discuss the benefits and costs of CDS, emphasizing the need for more research in order to better understand the welfare implications. Second, we provide an overview of the postcrisis market structure and the new regulatory framework for CDS. Third, we place CDS in the intersection of law and finance, focusing on agency conflicts and financial intermediation. Last, we examine the role of CDS in international finance, especially during and after the recent sovereign credit crises.
Functions, Regulation, and Therapeutic Implications of the ATR Checkpoint Pathway
Authors: Yazinski Stephanie A. , Zou Lee
Published: September 2016

The ATR (ATM and rad3-related) pathway is crucial for proliferation, responding to DNA replication stress and DNA damage. This critical signaling pathway is carefully orchestrated through a multistep process requiring initial priming of ATR prior to damage, recruitment of ATR to DNA damage lesions, activation of ATR signaling, and, finally, modulation of ATR activity through a variety of post-translational modifications. Following activation, ATR functions in several vital cellular processes, including suppression of replication origin firing, promotion of deoxynucleotide synthesis and replication fork restart, prevention of double-stranded DNA break formation, and avoidance of replication catastrophe and mitotic catastrophe. In many cancers, tumor cells have increased dependence on ATR signaling for survival, making ATR a promising target for cancer therapy. Tumor cells compromised in DNA repair pathways or DNA damage checkpoints, cells reliant on homologous recombination, and cells with increased replication stress are particularly sensitive to ATR inhibition. Understanding ATR signaling and modulation is essential to unraveling which tumors have increased dependence on ATR signaling as well as how the ATR pathway can best be exploited for targeted cancer therapy.
Sperm Meets Egg: The Genetics of Mammalian Fertilization
Authors: Bianchi Enrica , Wright Gavin J.
Published: September 2016

Fertilization is the culminating event of sexual reproduction, which involves the union of the sperm and egg to form a single, genetically distinct organism. Despite the fundamental role of fertilization, the basic mechanisms involved have remained poorly understood. However, these mechanisms must involve an ordered schedule of cellular recognition events between the sperm and egg to ensure successful fusion. In this article, we review recent progress in our molecular understanding of mammalian fertilization, highlighting the areas in which genetic approaches have been particularly informative and focusing especially on the roles of secreted and cell surface proteins, expressed in a sex-specific manner, that mediate sperm-egg interactions. We discuss how the sperm interacts with the female reproductive tract, zona pellucida, and the oolemma. Finally, we review recent progress made in elucidating the mechanisms that reduce polyspermy and ensure that eggs normally fuse with only a single sperm.
Theorizing Transnational Legal Ordering
Authors: Shaffer Gregory
Published: September 2016

This article categorizes three approaches to theorizing transnational legal ordering that respectively address private legal ordering; provide a framework for the study of the interaction of lawmaking and practice at the transnational, national, and local levels; and reconfigure the concept of law. The first approach develops theories of private legal ordering, involving lawmaking, adjudication, and enforcement through nonstate actors and institutions. The second approach provides a theoretical framework for sociolegal study of the transnational processes through which legal norms are constructed, flow, and settle across national borders. The third develops theory to critique and reformulate the concept of law in transnational terms that include nonstate processes.
Modeling Viral Spread
Authors: Graw Frederik , Perelson Alan S.
Published: September 2016

The way in which a viral infection spreads within a host is a complex process that is not well understood. Different viruses, such as human immunodeficiency virus type 1 and hepatitis C virus, have evolved different strategies, including direct cell-to-cell transmission and cell-free transmission, to spread within a host. To what extent these two modes of transmission are exploited in vivo is still unknown. Mathematical modeling has been an essential tool to get a better systematic and quantitative understanding of viral processes that are difficult to discern through strictly experimental approaches. In this review, we discuss recent attempts that combine experimental data and mathematical modeling in order to determine and quantify viral transmission modes. We also discuss the current challenges for a systems-level understanding of viral spread, and we highlight the promises and challenges that novel experimental techniques and data will bring to the field.
Sodium Valproate Exacerbating an Underlying Disorder of Fatty Acid Metabolism
Authors: Bellinge Jamie , Herath Sanjaya , Sonigra Dharmesh
Published: September 2016

We describe a 29-year-old female who presented with rhabdomyolysis shortly after starting a course of sodium valproate. A thorough investigation revealed a likely mitochondrial origin inducing this susceptibility. An underlying mitochondrial disorder should be considered in all patients who present with undifferentiated disease whilst taking sodium valproate.
Mother-Infant Face-to-Face Interaction: The Communicative Value of Infant-Directed Talking and Singing
Authors: Arias Diana , Peña Marcela
Published: September 2016

Background: Across culture, healthy infants show a high interest in infant-directed (ID) talking and singing. Despite ID talking and ID singing being very similar in physical properties, infants differentially respond to each of them. The mechanisms underpinning these different responses are still under discussion. Methods: This study explored the behavioral (n = 26) and brain (n = 14) responses from 6- to 8-month-old infants to ID talking and ID singing during a face-to-face mother-infant interaction with their own mother. Behavioral response was analyzed from offline video coding, and brain response was estimated from the analysis of electrophysiological recordings. Results: We found that during ID talking, infants displayed a significantly higher number of visual contacts, vocalizations, and body movements than during ID singing. Moreover, only during ID talking were the number of visual contacts and vocalizations positively correlated with the number of questions and pauses in the mother's speech. Conclusions: Our results suggest that ID talking provides infants with specific cues that allow them not only to react to mother stimulation, but also to act toward them, displaying a rudimentary version of turn-taking behavior. Brain activity partially supported that interpretation. The relevance of our results for bonding is discussed.
Bilateral Necrotizing Fasciitis of the Foot Associated with Group B Streptococcus
Authors: Fukuda Keitaro , Ryujin Misao , Sakio Reiko , Fukuzumi Satoshi , Omae Takanori , Hayakawa Kazuhito
Published: September 2016

Necrotizing fasciitis (NF) is a severe bacterial infection involving fascia and subcutaneous tissue. It generally affects upper or lower extremities unilaterally, and there are few reports of bilateral-extremity NF. Here, we report a case of a 43-year-old male with type 1 diabetes who had NF on the left foot and subsequently developed NF on the other foot 1 week later. The patient survived with antimicrobial therapy and bilateral below-knee amputation. As group B streptococcus (GBS) was isolated by blood culture and culture of excised tissues of both feet, bilateral GBS NF of the foot was diagnosed. GBS is a rare causative pathogen in NF; however, there have been two case reports of bilateral GBS NF of an extremity in which NF appeared on the opposite extremity 1 week after the primary site infection, as in our case. GBS was isolated from cultures of blood and excised tissues of both extremities in both cases. Together, these observations suggest that GBS has a potential to cause secondary NF at remote sites by hematogenous dissemination with approximately 1 week delay and thereby lead to bilateral NF.
Clinical Recommendations for the Use of Donepezil 23 mg in Moderate-to-Severe Alzheimer's Disease in the Asia-Pacific Region
Authors: Sabbagh Marwan , Han SeolHeui , Kim SangYun , Na Hae-Ri , Lee Jae-Hong , Kandiah Nagaendran , Phanthumchinda Kammant , Suthisisang Chuthamanee , Senanarong Vorapun , Pai Ming-Chyi , Narilastri Diatri , Sowani Ajit M. , Ampil Encarnita , Dash Amitabh ,   for the Asia-Pacific Expert Panel (APEX) for Donepezil 23 mg
Published: September 2016

Background: The ‘Asia-Pacific Expert Panel (APEX) for donepezil 23 mg' met in November 2015 to review evidence for the recently approved high dose of donepezil and to provide recommendations to help physicians in Asia make informed clinical decisions about using donepezil 23 mg in patients with moderate-to-severe Alzheimer's disease (AD). Summary: In a global phase III study (study 326) in patients with moderate-to-severe AD, donepezil 23 mg/day demonstrated significantly greater cognitive benefits versus donepezil 10 mg/day, with a between-treatment difference in mean change in the Severe Impairment Battery score of 2.2 points (p < 0.001) in the overall population and 3.1 points (p < 0.001) in patients with advanced AD. A subanalysis of study 326 demonstrated that the benefits and risks associated with donepezil 23 mg/day versus donepezil 10 mg/day in Asian patients with moderate-to-severe AD were comparable to those in the global study population. Key Message: Donepezil 23 mg is a valuable treatment for patients with AD, particularly those with advanced disease. The APEX emphasized the importance of patient selection (AD severity, tolerability of lower doses of donepezil, and absence of contraindications), a stepwise titration strategy for dose escalation, and appropriate monitoring and counseling of patients and caregivers in the management of patients with AD.
An Atrophic Plaque with Arborizing Vessels
Authors: Villarreal-Martinez Alejandra , Chavez-Alvarez Sonia , Herz-Ruelas Maira , Miranda-Maldonado Ivette , Vázquez-Martinez Osvaldo
Published: September 2016

Dermatofibromas are a common finding in the daily clinical practice. Most lesions are found incidentally or because patients seek medical attention due to the aspect of the lesion. Rare variants of dermatofibroma such as aneurismatic or atrophic dermatofibroma can be encountered simultaneously; thus, these combined features may raise the possibility of other diagnoses to be considered. By providing diverse clinical and dermoscopic examples of dermatofibromas, we may prevent misdiagnosing these lesions. This case illustrates how two rare variants of dermatofibroma can coexist. Clinical presentation of dermatofibromas may vary greatly, and it is essential for dermatologists to recognize them clinically and dermoscopically before obtaining histopathological diagnosis.
Ponatinib Induces a Persistent Molecular Response and Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia with a T315I Mutation following Early Relapse after Allogeneic Transplant
Authors: Renzi Daniela , Marchesi Francesco , De Angelis Gottardo , Elia Loredana , Salvatorelli Emanuela , Gumenyuk Svitlana , Palombi Francesca , Pisani Francesco , Romano Atelda , Spadea Antonio , Papa Elena , Canfora Marco , Arcese William , Mengarelli Andrea ,   for the Rome Transplant Network
Published: September 2016

We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment.
A Case of Intussusception Associated with Pneumatosis Cystoides Intestinalis
Authors: Fujiya Taku , Iwabuchi Masahiro , Sugimura Mikako , Ukai Katsuaki , Tadokoro Keiichi
Published: September 2016

Pneumatosis cystoides intestinalis (PCI) is an uncommon disease that generally lacks symptoms and is rarely associated with intussusception. A 29-year-old man visited our hospital for right upper abdominal pain. Computed tomography (CT) scan revealed multiple air-filled cysts along the intestinal wall and a pseudokidney sign in the transverse colon. A gastrographin enema examination showed a so-called crab finger appearance and multiple elevated translucency in the transverse colon. From these findings, the diagnosis of intussusception associated with PCI was made. The enema and manipulative reduction improved the intussusception. Comparing the enema findings before and after the reduction, we thought that mobile cecum could play an important role in the intussusception. Colonoscopy was performed after the reduction and showed multiple elevated lesions in the ascending colon, which were similar to cluster of grapes. The CT scan of the next day revealed no recurrence of the intussusception, and the patient has not had symptoms of recurrence ever since.
The Diagnosis and Manifestations of Liver Injury Secondary to Off-Label Androgenic Anabolic Steroid Use
Authors: Cabb Elena , Baltar Shanna , Powers David Wes , Mohan Karthik , Martinez Antonio , Pitts Eric
Published: September 2016

Drug-induced liver injury (DILI) presents as a broad spectrum of adverse drug reactions which can range from a mild elevation in liver enzymes to fulminant liver failure. The primary goal is to identify DILI early when the patient’s liver enzymes are elevated and to discontinue the offending agent as soon as possible to prevent further injury. Herbal, dietary supplements and anabolic steroids represent a significant component of the drugs thought to cause DILI in the United States. Unlike all other drugs known to cause DILI, these drugs fall into a category of injury that is neither intrinsic nor idiosyncratic due to overlapping characteristics between the two. Here, we present a case of the off-label use of androgenic anabolic steroids inducing liver injury. A combination of clinical, laboratory, and histologic workup eventually led to the diagnosis of DILI. This can be a diagnostic challenge for practitioners. The American College of Gastroenterology (ACG) published guidelines to aid the clinician in diagnosing DILI. Proving that an episode of liver injury is caused by a drug is difficult in many cases as it requires the exclusion of alternative etiologies. Some of the variables include temporal association, clinical-biochemical features, type of injury (hepatocellular and/or cholestatic), extrahepatic features, and the likelihood that a given agent is the culprit based on its known manifestations with prior cases. This case illustrates the utility of the diagnostic tools used for DILI as recommended by the ACG, along with a supplemental histopathologic diagnosis.
Epidemiology of Amyotrophic Lateral Sclerosis: A Population-Based Study in Israel
Authors: Weil Clara , Zach Neta , Rishoni Shay , Shalev Varda , Chodick Gabriel
Published: September 2016

Background: Globally, the annual incidence and prevalence of amyotrophic lateral sclerosis (ALS) are estimated at 1.9 and 4.5 per 100,000 population, respectively. This study is aimed at describing the epidemiology of ALS in Israel in a real-world setting. Methods: A retrospective study was performed using the databases of Maccabi Healthcare Services (MHS), a 2-million-member health maintenance organization in Israel. The study included all MHS adults diagnosed with ALS between 1997 and 2013. In 2013, characteristics of ALS patients were compared to those of age-sex-matched patients without ALS. Survival after ALS diagnosis was assessed until death and until tracheostomy or death (follow-up through 2014). Results: In 2013 (n = 158), the prevalence of ALS was 8.1 per 100,000 population in MHS. In 1997-2013, a total of 375 ALS patients were diagnosed, corresponding to an average annual incidence of 1.8 per 100,000 population in MHS. The median survival from diagnosis to death was 3.5 years (95% CI 2.9-4.1), with approximately 28% surviving at least 10 years. Median tracheostomy-free survival was 2.5 years (95% CI 2.1-2.9). Conclusions: Results suggest that there is a relatively high prevalence of ALS in Israel. Further research is needed to investigate factors that may contribute to the survival of patients with ALS in Israel.
Medical Photography: Documentation, Art, and the Expression of Human Emotions
Authors: Aberer Elisabeth , Stieber Werner , Homayoon Donja , Fink-Puches Regina , Lichen Roland , Salmhofer Wolfgang , Gruber-Wackernagel Alexandra , Aberer Werner
Published: September 2016

Medical photography is the state of the art for the documentation of dermatological disease. Experienced photographers take pictures of the most typical skin lesions in order to assist the clinician in assessing disease morphology and activity. In this study, we present 6 individuals with a variety of dermatoses and the expression of the patients’ emotions. The patients were asked to show their diseased skin and to present typically involved areas in the respective disease. The feelings expressed by their body movements and positions are viewed and interpreted. The patients’ history will be reported retrospectively. The aim of the report is to show that the art of medical photography does not only document skin lesions but also the disease burden and the associated impairment of quality of life. Moreover, dermatologic photography is a sensitive intervention for patients viewed in the light of teaching and patient care.
Cerebral Cavernous Malformation: A Portuguese Family with a Novel CCM1 Mutation
Authors: Marto João Pedro , Gil Inês , Calado Sofia , Viana-Baptista Miguel
Published: September 2016

Introduction: Cerebral cavernous malformation (CCM) is a vascular disorder characterized by the presence of central nervous system cavernomas. In familial forms, mutations in three genes (CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10) were identified. We describe a Portuguese family harboring a novel CCM1 mutation. Case Presentation: The proband is a woman who at the age of 55 years started to have complex partial seizures and episodic headache. Although nothing was found during her neurological examination, brain MRI showed bilateral, supra- and infratentorial cavernomas. She had a sister who, at the age 61 years, suffered a tonic-clonic seizure. Neurological examination was normal and imaging investigation demonstrated a right frontal intracerebral hemorrhage and multiple cavernomas. In the following years, she suffered several complex partial seizures and had a new intracerebral hemorrhage located in the right temporal lobe. Genetic analysis was performed and a novel nucleotide substitution, i.e. c.1927C>T (p.Gln643*) within the exon 17 of the CCM1 gene, was detected in both sisters. The substitution encodes a stop codon, with a consequent truncated KRIT1 protein, therefore supporting its pathogenic role. Further affected family members were detected, suggesting an autosomal dominant pattern of inheritance. Conclusion: We report a Portuguese family with a novel CCM1 (KRIT1) mutation – c.1927C>T (p.Gln643*). A better knowledge of the phenotype-genotype correlation is needed to improve the management of CCM patients.
Lazer, Turismo e Espaço Urbano: a reconversão portuária na cidade de Santa Fé, Argentina
Authors: França Jéssika Paiva
Published: September 2016

Este artigo é resultante de um estágio realizado no ano de 2014 na Universidade Nacional del Litoral, na cidade de Santa Fé na Argentina em parceria com a Universidade de São Paulo e financiamentoda instituição SANTANDER. Tem como objetivo, o estudo da área portuária da cidade de Santa Fé que foi transformada em um complexo de lazer e turismo seguindo uma tendência internacional de reconfiguração de espaços waterfronts (frente de águas). A metodologia envolveu pesquisa bibliográfica e realização de entrevista semiestruturada junto à secretaria de planejamento urbano da cidade. Os resultados apontam que a área portuária no ano de 2004 passou por um processo de reconversão de suas funções, objetivando o atendimento a uma política de planejamento estratégico de cidade, em busca da retomada do papel de centralidade. Ao seu término é traçada uma reflexão sobre a postura assumida pelos gestores públicos na cidade contemporânea e o peso destinado a atividade turística enquanto viés de desenvolvimento econômico local. A reconversão portuária em Santa Fé está baseada em um modelo internacional de planejamento urbano e utilização de espaços em frentes de água para fins de lazer e turismo, viabilizados através de parceria estabelecida entre os setores público e o privado.
Luz, Câmera... Segmentação: uma proposta de turismo cinematográfico para a cidade de Niterói-RJ
Authors: Duarte Rômulo , Fonseca Filho Ari da Silva
Published: September 2016

O turismo cinematográfico é um segmento do mercado turístico, no qual o turista viaja motivado a conhecer um local após tê-lo visto em alguma produção audiovisual, em especial, no cinema. Essas produções podem ser filmes minisséries, seriados ou as novelas. Nesse sentido, o objetivo geral do artigo é apresentar o potencial da cidade de Niterói-RJ para o desenvolvimento do turismo cinematográfico. Os objetivos específicos são: destacar a relação entre o turismo e o audiovisual; apresentar a cidade de Niterói como um destino cinematográfico; e construir um catálogo de locações, que contemple os atrativos que expressam a identidade da cidade. A metodologia consistiu de um levantamento de atrativos turísticos da cidade; levantamento de informações sobre estes; e visitas aos locais para a realização do registro fotográfico e observação sobre possíveis locações para produções audiovisuais. Como principal resultado dessa pesquisa, tem-se a catalogação dos atrativos da cidade organizados na forma de um catálogo de locações, cujo objetivo é apresentar o potencial para produção audiovisual que a cidade tem.
O Planejamento Estratégico para Implantação da Sustentabilidade na Copa do Mundo FIFA 2014 no Brasil
Authors: Gomes Borges da Silva Elaine
Published: September 2016

Esta pesquisa descritiva traz a análise documental do planejamento estratégico para a aplicação do conceito de sustentabilidade na Copa do Mundo FIFA 2014. Por meio deste estudo descobriu-se que o evento deveria estar em consonância com as políticas públicas do governo federal vigentes à época de 2012, além de primar pelos aspectos ambientais na execução das obras das instalações esportivas e seu entorno. Verificou-se que para que o evento estivesse em concordância às recomendações e requerimentos da entidade FIFA deveria ser seguido o check-list para obtenção da certificação LEED, ser avaliada a emissão de gases de efeito estufa em complementaridade a outras ações em prol da garantia da qualidade de vida da sociedade e do meio ambiente e que ao final deveria ser publicado um relatório de sustentabilidade daquele evento que deverá ser um paradigma para a sustentabilidade em eventos futuros. As conclusões desse estudo revelam que a dimensão ambiental da sustentabilidade é prioridade para os organizadores desse megaevento.
Patrimônio Histórico Ambiental: diagnósticos para criação de unidade de conservação e orientações para o uso público do Jardim Botânico de Ouro Preto-MG
Authors: Machado Simone Fernandes , Chaves Valéria da Conceição , Fonseca Filho Ricardo Eustáquio
Published: September 2016

No final do século XVIII, na antiga Vila Rica (MG), foi definido um espaço, que em 1840, passou a abrigar uma escola de ensino prático de agricultura, transformando-se no Jardim Botânico de Ouro Preto-MG. Atualmente o local está sendo pleiteando para a criação de uma Unidade de Conservação (UC) Estadual. O presente trabalho foi realizado como parte dos estudos para avaliar a possibilidade de criação de uma nova UC nesta área em consonância com a Lei Federal nº. 9.985, de 18/07/2000. Para tanto, foram realizadas as seguintes etapas: revisão bibliográfica; levantamentos de dados secundários e primários provenientes de cinco visitas in loco, realizadas em novembro de 2014; análise de 40 entrevistas, realizadas com representantes institucionais, moradores e lideranças comunitárias formais e informais, de Ouro Preto. Como resultado obteve-se uma análise preliminar dos impactos e oportunidades oferecidas na criação da UC e o apontamento de sugestões para o estabelecimento da mesma. O estudo propôs ainda algumas orientações para o manejo da UC, através do desenvolvimento dos atrativos turísticos de base comunitária, que contam com elementos de referência histórica, cultural e ecoturística, propiciando a preservação do meio ambiente e o resgate da memória cultural e da identidade regional.