bluuebunny/crossref_metadata_2025 huggingface dataset:
Histamine-mediated potentiation of transient receptor potential (TRP) ankyrin 1 and TRP vanilloid 4 signaling in submucosal neurons in patients with irritable bowel syndrome
Authors: Balemans D. , Aguilera-Lizarraga J. , Florens M. V. , Jain P. , Denadai-Souza A. , Viola M. F. , Alpizar Y. A. , Van Der Merwe S. , Vanden Berghe P. , Talavera K. , Vanner S. , Wouters M. M. , Boeckxstaens G. E.
Published: January 2019

Previously, we showed histamine-mediated sensitization of transient receptor potential (TRP) vanilloid 1 (TRPV1) in patients with irritable bowel syndrome (IBS). Sensitization of TRP ankyrin 1 (TRPA1) and TRP vanilloid 4 (TRPV4) are also involved in aberrant pain perception in preclinical models of somatic pain. Here, we hypothesize that in parallel with TRPV1, histamine sensitizes TRPA1 and TRPV4, contributing to increased visceral pain in patients with IBS. Rectal biopsies were collected from patients with IBS and healthy subjects (HS) to study neuronal sensitivity to TRPA1 and TRPV4 agonists (cinnamaldehyde and GSK1016790A) using intracellular Ca2+ imaging. In addition, the effect of supernatants of rectal biopsies on patients with IBS and HS was assessed on TRPA1 and TRPV4 responses in murine dorsal root ganglion (DRG) sensory neurons. Finally, we evaluated the role of histamine and histamine 1 receptor (H1R) in TRPA1 and TRPV4 sensitization. Application of TRPA1 and TRPV4 agonists evoked significantly higher peak amplitudes and percentage of responding submucosal neurons in biopsies of patients with IBS compared with HS. In HS, pretreatment with histamine significantly increased the Ca2+ responses to cinnamaldehyde and GSK1016790A, an effect prevented by H1R antagonism. IBS supernatants, but not of HS, sensitized TRPA1 and TRPV4 on DRG neurons. This effect was reproduced by histamine and prevented by H1R antagonism. We demonstrate that the mucosal microenvironment in IBS contains mediators, such as histamine, which sensitize TRPV4 and TRPA1 via H1R activation, most likely contributing to increased visceral pain perception in IBS. These data further underscore H1R antagonism as potential treatment for IBS.

NEW & NOTEWORTHY We provide evidence for histamine-mediated transient receptor potential (TRP) ankyrin 1 and TRP vanilloid 4 sensitization in irritable bowel syndrome (IBS) via histamine 1 receptor (H1R) activation, most likely contributing to increased visceral pain perception. Our results reveal a general role of sensory TRP channels as histamine effectors in the pathophysiology of IBS and provide novel mechanistic insights into the therapeutic potential of H1R antagonism in IBS.
Evaluating physiological signal salience for estimating metabolic energy cost from wearable sensors
Authors: Ingraham Kimberly A. , Ferris Daniel P. , Remy C. David
Published: January 2019

Body-in-the-loop optimization algorithms have the capability to automatically tune the parameters of robotic prostheses and exoskeletons to minimize the metabolic energy expenditure of the user. However, current body-in-the-loop algorithms rely on indirect calorimetry to obtain measurements of energy cost, which are noisy, sparsely sampled, time-delayed, and require wearing a respiratory mask. To improve these algorithms, the goal of this work is to predict a user’s steady-state energy cost quickly and accurately using physiological signals obtained from portable, wearable sensors. In this paper, we quantified physiological signal salience to discover which signals, or groups of signals, have the best predictive capability when estimating metabolic energy cost. We collected data from 10 healthy individuals performing 6 activities (walking, incline walking, backward walking, running, cycling, and stair climbing) at various speeds or intensities. Subjects wore a suite of physiological sensors that measured breath frequency and volume, limb accelerations, lower limb EMG, heart rate, electrodermal activity, skin temperature, and oxygen saturation; indirect calorimetry was used to establish the ‘ground truth’ energy cost for each activity. Evaluating Pearson’s correlation coefficients and single and multiple linear regression models with cross validation (leave-one- subject-out and leave-one- task-out), we found that 1) filtering the accelerations and EMG signals improved their predictive power, 2) global signals (e.g., heart rate, electrodermal activity) were more sensitive to unknown subjects than tasks, while local signals (e.g., accelerations) were more sensitive to unknown tasks than subjects, and 3) good predictive performance was obtained combining a small number of signals (4–5) from multiple sensor modalities.

NEW & NOTEWORTHY In this paper, we systematically compare a large set of physiological signals collected from portable sensors and determine which sensor signals contain the most salient information for predicting steady-state metabolic energy cost, robust to unknown subjects or tasks. This information, together with the comprehensive data set that is published in conjunction with this paper, will enable researchers and clinicians across many fields to develop novel algorithms to predict energy cost from wearable sensors.
Raman Spectroscopic Characterization of Endodontic Biofilm Matrices
Authors: Ramirez-Mora Tatiana , Dávila-Pérez Claudia , Torres-Méndez Fernando , Valle-Bourrouet Grettel
Published: January 2019

Endodontic persistent infections are often mediated by bacterial biofilms. This mode of bacterial growth is characterized by the presence of a matrix mainly composed of extracellular polymeric substances (EPSs) that protect the encased microorganisms. To establish better control and disinfection protocols, elucidation of the main components of biofilm matrices present in endodontic infections is required. The aim of the present study was to characterize the principal components ofE. faecalis,A. naeslundii, and dual-species biofilm matrices by means of Raman spectroscopy and confocal scanning laser microscopy (CSLM) techniques. The total biomass of biofilms was quantified via crystal violet assays, and the monospecies biofilms showed higher biomass than the dual-species biofilms. Raman spectroscopy and confocal laser scanning microscopy were used to identify the biochemical composition and structure of the biofilm matrices. Spectra originating from the biofilms of two endodontic pathogens show the presence of carbohydrates, proteins, fatty acids, and nucleic acids in all samples; however, variation in the levels of expression of these biomolecules allows spectroscopic differentiation of the biofilms using principal component analysis. This study is the first attempt to identify the composition of monospecies and dual-species biofilms of endodontic origin. Our data provides an important approach to the understanding of molecular dynamics of endodontic infections.
Verapamil Attenuated Prediabetic Neuropathy in High-Fat Diet-Fed Mice through Inhibiting TXNIP-Mediated Apoptosis and Inflammation
Authors: Xu Lingling , Lin Xiaopu , Guan Meiping , Zeng Yanmei , Liu Yingshan
Published: January 2019

Diabetic neuropathy (DN) is a common and severe complication of diabetes mellitus. There is still a lack of an effective treatment to DN because of its complex pathogenesis. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of thioredoxin, has been shown to be associated with diabetic retinopathy and nephropathy. Herein, we aim to investigate the role of TXNIP in prediabetic neuropathy and therapeutic potential of verapamil which has been shown to inhibit TXNIP expression. The effects of mediating TXNIP on prediabetic neuropathy and its exact mechanism were performed using high-fat diet- (HFD-) induced diabetic mice and palmitate-treated neurons. Our results showed that TXNIP upregulation is associated with prediabetic neuropathy in HFD-fed mice. TXNIP knockdown improved DN in HFD-induced prediabetic mice. Mechanistically, increased TXNIP in dorsal root ganglion is transferred into the cytoplasm and shuttled to the mitochondria. In cytoplasm, TXNIP binding to TRX1 results in the increased oxidative stress and inflammation. In mitochondria, TXNIP binding to TRX2 induced mitochondria dysfunction and apoptosis. TXNIP isolated from TRX2 then shuttles to the cytoplasm and binds to NLRP3, resulting in further increased TXNIP-NLRP3 complex, which induced the release of IL-1β and the development of inflammation. Thus, apoptosis and inflammation of dorsal root ganglion neuron eventually cause neural dysfunction. In addition, we also showed that verapamil, a known inhibitor of calcium channels, improved prediabetic neuropathy in the HFD-fed mice by inhibiting the upregulation of TXNIP. Our finding suggests that TXNIP might be a potential target for the treatment of neuropathy in prediabetic patients with dyslipidemia.
Characterization of Kenyan Honeys Based on Their Physicochemical Properties, Botanical and Geographical Origin
Authors: Warui Mary Wanjiru , Hansted Lise , Gikungu Mary , Mburu John , Kironchi Geoffrey , Bosselmann Aske Skovmand
Published: January 2019

Properties and composition of honey are essential in providing information regarding their quality as well as in their differentiation based on production region characteristics, e.g., floral sources. This paper presents physicochemical properties and floral sources (botanical origin) of 21 honey samples obtained from arid and semiarid areas of Kenya, specifically, West Pokot, Baringo, and Kitui Counties. Physicochemical parameters which were analyzed to determine honey quality included moisture content, hydroxymethylfurfural (HMF), diastase activity, free acidity, and electrical conductivity. Values of these parameters were compared with those of the existing local, regional, and international standards for honey. Melissopalynological analysis (pollen analysis) was also carried out to provide information on botanical origin of the honeys. Results showed mean parameter values of moisture, 16.34%; HMF, 23.28 mg/kg; diastase activity, 10.67 Schade units; free acidity, 22.95 meq/kg; and electrical conductivity, 0.40 mS/cm. Free acidity and electrical conductivity values of honey samples obtained from West Pokot were significantly lower than the values of honeys from Baringo and Kitui. Eighteen (18) honey samples had all parameter values within the limits set in the East African, Codex Alimentarius, and the European Union directive standards for honey. Results also showed a total of 29 pollen types in the honey samples analyzed, and Acacia spp. was the predominant pollen type in 4 of the 21 honey samples. Findings of this study showed that Kenyan origin honeys can tap into the existing regional and international markets based on their quality which can be attributed to their botanical origin. Results of this study also suggested that honey producers have undertaken appropriate measures in honey harvesting, processing, handling, and storage. However, there is a need to build capacity of producers whose honey were of unacceptable quality. This would involve training on proper honey production, processing, and handling practices as well establishment of honey collection and processing centres at the local level in order to improve honey quality. This will enhance access to existing honey markets. Conservation of bee floral sources would also be needed to maintain honey quality.
A Strong Impact of Soil Tetracycline on Physiology and Biochemistry of Pea Seedlings
Authors: Margas Małgorzata , Piotrowicz-Cieślak Agnieszka I. , Michalczyk Dariusz J. , Głowacka Katarzyna
Published: January 2019

Antibiotics are a new type of contaminants found in the environment. They are increasingly used in farm animal production systems and may accumulate in crops, limiting the plant growth rate and nutritive value. The aim of this study was to determine the effects of tetracycline (TC) on physiological and biochemical properties of pea seedlings. The presence of TC in the soil during 24 hours did not result in any distinct changes of the seedlings. However, after five days (120 h) of soil TC action, the seedling appearance and metabolic activities were significantly affected. Leaves lost their green coloration as a result of a 38% degradation of their chlorophyll. Total protein was isolated from shoots of pea grown for 120 h in TC-supplemented perlite (250 mg × L−1) or perlite with no TC (control plants). The 2D electrophoretic maps of proteins from non-TC shoots contained 326 spots, whereas maps of shoot proteins from TC-treated seedlings contained only 316 spots. The identity of 26 proteins was determined. The intensity of most proteins (62%) increased. This was particularly visible with diphosphate kinase, superoxide dismutase [Cu-Zn], peroxiredoxin, and glutathione S-transferase. A distinctly increased quantity of a protein involved in photosynthesis (photosystem II stability/assembly factor HCF136) was also noted. One protein was detected only in shoots of TC-treated plants (as opposed to controls); however, it could not be identified. Moreover, at the highest concentration of TC (250 mg × L−1 of perlite), a sharp increase in free-radical content was observed along with the amount of callose deposited in vascular bundles of leaves and roots and the occurrence of masses of dead cells in roots. It was found, therefore, that tetracycline which has been known for inhibiting predominantly the attachment of aminoacyl-tRNA to the ribosomal acceptor in bacteria can disturb diverse metabolic pathways in plants.
In Vitro Antimicrobial Activity Screening of Ethanol Extract of Lavandula stoechas and Investigation of Its Biochemical Composition
Authors: Canlı Kerem , Yetgin Ali , Benek Atakan , Bozyel Mustafa Eray , Murat Altuner Ergin
Published: January 2019

The aim of this study was to test antimicrobial activity of ethanol extract of Lavandula stoechas against 22 bacteria and 1 yeast. Also, biochemical composition of the extract was investigated. A wide range of Gram-positive, Gram-negative microorganisms, and multidrug resistant bacteria were selected to test the antimicrobial activity. As a result, the extract is observed to contain fenchone (bicyclo[2.2.1]heptan-2-one, 1,3,3-trimethyl-, (1R)-) and camphor (+)-2-bornanone) as major components and showed antimicrobial activity against all studied microorganisms except Escherichia coli ATCC 25922 and Klebsiella pneumoniae. The results of the study present that L. stoechas is active against MDR strains too.
Efficient Techniques for Solution of Complex Computational Tasks in Building Physics
Authors: Kočí Václav , Maděra Jiří , Krejčí Tomáš , Kruis Jaroslav , Černý Robert
Published: January 2019

Various simplification or optimization techniques are sought that reduce demands of computational modeling on time or computing power while keeping a sufficient level of accuracy. In this paper, determination of hygrothermal performance of a brick block is presented using two homogenization techniques based on different principles. While the computational homogenization technique uses a multiscale method realized on the master/slave computer system, the materials homogenization comes out from the effective media theory (EMT), and after the determination of effective material properties, the whole isotropic problem can be transformed to one dimension. Contrary to most applications of EMT, free parameters of mixing formulas are not determined based on an experimental measurement of a single material property but on a complex hygrothermal performance of the element where the distribution of moisture and temperature over a reference year is taken into account. The calculated results from both techniques are compared with results obtained by high‐performance computing without any computational simplifications. For materials homogenization, the best results are achieved when k = 0.9 in Lichtenecker’s mixing rule is assumed, which corresponds to a nearly parallel arrangement of the block. The root mean square error (RMSE) of relative humidity (RH) and temperature distribution is only 0.992% and 0.566°C, respectively. This is even better than the results of computational homogenization (RMSE: 1.502% of RH and 0.629°C). Besides obtaining sufficiently precise results, a significant time‐saving is achieved, accounting for more than 99%, while being solved on a single‐processor computer.
Trend Analysis and Comprehensive Evaluation of Green Production Principal Component of Thermal Power Unit Based on ANP-MEEM Model
Authors: Tan Zhongfu , Tan Qingkun , Ju Liwei , Yang Shenbo , Cheng Huangfu , Ma Jiale
Published: January 2019

Low-emission environmental protection concept once it replaced the low-carbon energy transformation concept, to a certain extent, disrupted the core direction of energy transformation. This paper takes the green development of electric power as the research direction, the thermal power unit is the green source control point of electricity, and the green production of the thermal power unit is the research target; based on the actual research data and the actual data, the comprehensive evaluation of the green production of a thermal power generating unit in a city is carried out by means of ANP, matter-element extension model, and principal component analysis. This paper not only reflects the quantification of green benefits in each year, but also achieves the comparison of green achievements and the analysis of increasing losses in the data years. Furthermore, the indexes of annual increase and loss of the index system are analyzed and filtered. The indexes of strong contribution index and short board of barrel are found out, and the dimension reduction management of green production of thermal power unit is realized.
Geometric Asian Options Pricing under the Double Heston Stochastic Volatility Model with Stochastic Interest Rate
Authors: Zhong Yanhong , Deng Guohe
Published: January 2019

This paper presents an extension of double Heston stochastic volatility model by incorporating stochastic interest rates and derives explicit solutions for the prices of the continuously monitored fixed and floating strike geometric Asian options. The discounted joint characteristic function of the log‐asset price and its log‐geometric mean value is computed by using the change of numeraire and the Fourier inversion transform technique. We also provide efficient approximated approach and analyze several effects on option prices under the proposed model. Numerical examples show that both stochastic volatility and stochastic interest rate have a significant impact on option values, particularly on the values of longer term options. The proposed model is suitable for modeling the longer time real‐market changes and managing the credit risks.
Dynamical Analysis of a Stochastic Multispecies Turbidostat Model
Authors: Mu Yu , Li Zuxiong , Xiang Huili , Wang Hailing
Published: January 2019

A stochastic turbidostat system in which the dilution rate is subject to white noise is investigated in this paper. First of all, sufficient conditions of the competitive exclusion among microorganisms are obtained by employing the techniques of stochastic analysis. Furthermore, the results demonstrate that the competition among microorganisms and stochastic disturbance will affect the dynamical behaviors of microorganisms. Finally, the theoretical results obtained in this contribution are illustrated by numerical simulations.
Towards the Thousandth CubeSat: A Statistical Overview
Authors: Villela Thyrso , Costa Cesar A. , Brandão Alessandra M. , Bueno Fernando T. , Leonardi Rodrigo
Published: January 2019

CubeSats have become an interesting innovation in the space sector. Such platforms are being used for several space applications, such as education, Earth remote sensing, science, and defense. As of May 31st, 2018, 855 CubeSats had been launched. Remote sensing application is the main sector in which CubeSats are being used, corresponding to about 45% of all applications. This fact indicates the commercial potential of such a platform. Fifty eight countries have already been involved with developing CubeSats. The most used CubeSat configuration is 3U (about 64%), followed by 1U (18%), while 6U platforms account for about 4%. In this paper, we present an analysis of the current situation regarding CubeSats worldwide, through the use of a dataset built to encompass information about these satellites. The overall success rate of the CubeSat missions is increasing over time. Moreover, considering CubeSat missions as a Bernoulli experiment, and excluding launch failures, the current success rate was estimated, as a parameter of a binomial distribution, to be about 75%. By using a logistic model and considering that the launchings keep following the current tendency, one can expect that one thousand CubeSats will be launched in 2021, within 95% certainty.
Value of Time to Positivity of Blood Culture in Children with Bloodstream Infections
Authors: Pan Fen , Zhao Wantong , Zhang Hong
Published: January 2019

Objective. This study was to investigate the microbiological characteristics and the relationship between the time to positivity (TTP) of blood cultures and different bacterial species and to assess the clinical value of TTP in children with bloodstream infections (BSIs). Methods. The TTP of all the blood cultures from children with suspected BSIs was retrospectively collected in 2016. The microbiological characteristics and the relationship between the TTP of blood cultures and different bacterial species were also analyzed. Results. A total of 808 strains were isolated from 15835 blood cultures collected, and 145 (17.9%) were Gram-negative, 636 (78.7%) were Gram-positive, and 27 (3.3%) were fungi. The bacteria were divided into definite pathogens (174), possible pathogens (592), fungi (27), and contaminants (15). The average TTP of all positive blood cultures was 30.97 and ranged from 3.23 h to 92.73 h. The TTP of Gram-negative strains was significantly shorter than that of Gram-positive strains (P<0.001) and fungi (P = 0.032). The mean TTP for E. coli (15.60 h) was shortest within the group of Gram-negative isolates, and the mean TTP for Streptococcus (17.34 h) within the group of Gram-positive isolates. Significant difference of the TTP was detected in methicillin-resistant vs methicillin-susceptible S. aureus, extended-spectrum beta-lactamases (ESBLs) positive vs negative Enterobacteriaceae, and extensive drug-resistant and non-XDR A. baumannii. The median TTP in patients with BSI was significantly shorter than in those without it (P<0.001). ROC curve analysis indicated that the TTP cutoff value of CoNS, S. aureus, E. coli, and K. pneumoniae was 22.72 h, 19.6 h, 18.58 h, and 16.43 h, respectively, with most sensitive and specific predictor of BSIs. Conclusions. Our data acknowledged that TTP is a valuable index for the early prognosis of BSIs. TTP not only provides additional utility as a general predictor of bacteria with smear result but also provides the implication of drug-resistant organisms.
Treatment of Atypical Bifid Mandibular Condyle Associated with Ankylosis of the Temporomandibular Joint
Authors: Miranda Katheleen , Carneiro André Sander , Gerber Jennifer Tsi , Weiss Suyany Gabriely , Klüppel Leandro Eduardo , Scariot Rafaela
Published: January 2019

Introduction. The bifid mandibular condyle (BMC) is an unusual temporomandibular joint (TMJ) disorder with controversial etiology. The association of this entity with ankylosis is rare. Objective. The objective of the present study is to report a case of BMC with associated TMJ ankylosis in a patient with no history of trauma and/or infection. Case Report. A 17-year-old male patient sought care reporting pain on the right TMJ region and mastication difficulty due to a severe limitation of mouth opening. In the clinic and imaging examinations, a 15 mm mouth opening and BMC associated with ankylotic mass of the right TMJ were observed, besides a facial asymmetry with chin deviation to the right. The proposed treatment plan was condylectomy on the right side, bilateral coronectomy, and genioplasty, so the chin lateral deviation could be corrected, under general anesthesia. The patient remains under clinical and imaging follow-up of two years with functional stability and no signs of relapse of the ankylosis. Conclusion. The association of BMC with ankylosis is an atypical entity which must be diagnosed and treated early to prevent aesthetic and functional damages to the patient.
Conformable Integral Inequalities of the Hermite-Hadamard Type in terms of GG- and GA-Convexities
Authors: Khurshid Yousaf , Adil Khan Muhammad , Chu Yu-Ming
Published: January 2019

In the article, we present several conformable fractional integrals’ versions of the Hermite-Hadamard type inequalities for GG- and GA-convex functions and provide their applications in special bivariate means.
The Full Spectrum of Infective Endocarditis: Case Report and Review
Authors: Rali Aniket S. , Al-Kofahi Mejalli , Patel Nilay , Wiele Benjamin , Shah Zubair , Nath Jayant
Published: January 2019

Over the past five decades, the incidence of intravenous drug use- (IVDU-) associated infective endocarditis (IE) has been on the rise in North America. Classically, IVDU has been thought to affect right-sided valves. However, in recent times a more variable presentation of IVDU-associated IE has been reported. Here, we report a case of a patient with a known history of IVDU who presented with clinical symptoms concerning for right- as well as left-sided endocarditis. In addition, we also discuss what should be considered adequate evaluation for patients with suspected endocarditis, and more specifically, what should be the role of transesophageal echocardiography in patients with IE noted on transthoracic echocardiography.
Investigation of Safety Profile of Four Copaifera Species and of Kaurenoic Acid by Salmonella/Microsome Test
Authors: Damasceno Jaqueline Lopes , Arnet Yadira Fernández , Fortunato Giovanna Capaldi , Girotto Luiza , Marena Gabriel Davi , Rocha Beatriz Patti , Resende Flávia Aparecida , Ambrosio Sergio Ricardo , Veneziani Rodrigo Cássio Sola , Bastos Jairo Kenupp , Martins Carlos Henrique Gomes
Published: January 2019

Trees of the Copaifera genus are native to the tropical regions of Latin America and Western Africa. Copaifera sp is widely used as a popular medicine and it has various ethnopharmacological indications, including gonorrhea, bronchitis, asthma, skin ulcers, ulcers, sore throat, uterine infections, general inflammations, cancer, and leishmanioses. Kaurenoic acid is a naturally occurring diterpene found in Copaifera and has been used as an anti-inflammatory, treatment of ulcer, leishmaniasis, and cancer. Bearing in mind the fact that the Ames test is an excellent tool to assess the safety of extracts, oils, and phytochemicals isolated from medicinal plants, from it, we evaluate the mutagenic potential of four species, between oleoresins (C. oblongifolia; C. langsdorffii) and leaves extracts (C. lucens; C. multijuga), of the Copaifera genus and also of kaurenoic acid, which is one of its major compounds. The results showed that the Copaifera spp. and kaurenoic acid did not induce an increase in the number of revertant colonies, without mutagenic effect in experiments, in the all concentrations evaluated by Ames test. The results obtained in our study support the safe use of the Copaifera genus medicinal plants selected and of kaurenoic acid.
Potential Involvement of BIRC5 in Maintaining Pluripotency and Cell Differentiation of Human Stem Cells
Authors: Gil-Kulik Paulina , Krzyżanowski Arkadiusz , Dudzińska Ewa , Karwat Jolanta , Chomik Piotr , Świstowska Małgorzata , Kondracka Adrianna , Kwaśniewska Anna , Cioch Maria , Jojczuk Mariusz , Nogalski Adam , Kocki Janusz
Published: January 2019

The BIRC5 gene encodes a survivin protein belonging to class III of inhibitors of apoptosis, IAP. This protein serves a dual role. First, it regulates cell death, and second, it is an important regulator of mitosis progression, although its physiological regulatory function has not been fully understood. Many studies have shown and confirmed that survivin is practically absent in mature tissues in nature, while its overexpression has been reported in many cancerous tissues. There is little information about the significance of BIRC5 expression in normal adult human stem cells. This paper presents the study and analysis of survivin expression at the transcription level using qPCR method, in hematopoietic stem cells from peripheral blood mobilized with a granulocyte growth factor, adherent cells derived from the umbilical cord, and normal bone marrow stem cells. The expression of this gene was also examined in the blood of normal healthy individuals. The results of the analysis have shown that the more mature the cells are, the lower the expression of the BIRC5 gene is. The lowest expression has been found in peripheral blood cells, while the highest in normal bone marrow cells. The more the CD34+ and CD105 cells in the tested material are, the higher the BIRC5 expression is. Stem cells from cell culture show higher BIRC5 expression. The study confirms the involvement of BIRC5 from the IAP family in many physiological processes apart from apoptosis inhibition. The possible effect of BIRC5 on cell proliferation; involvement in cell cycle, cell differentiation, survival, and maintenance of stem cells; and the possible effect of IAP on the antineoplastic properties of mesenchymal stem cells have been demonstrated. Our research suggests that BIRC5 may be responsible for the condition of stem cell pluripotency and its high expression may also be responsible for the dedifferentiation of tumor cells.
Serrated Lesions of the Colon-Rectum: A Focus on New Diagnostic Tools and Current Management
Authors: Cassese Gianluca , Amendola Alfonso , Maione Francesco , Giglio Mariano Cesare , Pagano Gianluca , Milone Marco , Aprea Giovanni , Luglio Gaetano , De Palma Giovanni Domenico
Published: January 2019

Prompt diagnosis and correct management of the so called “serrated lesions” (SLs) of the colon-rectum are generally considered of crucial importance in the past years, mainly due to their histological heterogeneity and peculiar clinical and molecular patterns; sometimes, they are missed at conventional endoscopy and are possibly implicated in the genesis of interval cancers. The aim of this review is to focus on the diagnostic challenges of serrated lesions, underlying the role of both conventional endoscopy and novel technologies. We will show how an accurate and precise diagnosis should immediately prompt the most appropriate therapy other than defining a proper follow-up program. It will be emphasized how novel endoscopic techniques may provide better visualization of mucosal microsurface structures other than enhancing the microvascular architecture, in order to better define and characterize specific patterns of mucosal lesions of the gastrointestinal tract. Standard therapy of SLs of the colon-rectum is still very debated, also due to the relatively lack of studies focusing on treatment issues. The high risk of incomplete resection, together with the high rate of postcolonoscopy interval cancers, suggests the need of an extra care when facing this kind of lesions. Given this background, we will outline useful technical tips and tricks in the resection of SLs, taking aspects such as the size and location of the lesions, as well as novel available techniques and technologies, other than future perspectives, including confocal laser endomicroscopy into consideration. Follow-up of SLs is another hot topic, also considering that their clinical impact has been misunderstood for a long time. The incidence of the so called interval colorectal cancer underlines how some weaknesses exist in current screening and follow-up programs. Considering the lack of wide consensus for the management of some SLs, we will try to summarize and clarify the best strategies for their optimal management.
Overlooked Fracture of the Inferior Scapular Angle Treated Conservatively
Authors: Ogawa Kiyohisa , Inokuchi Wataru , Honma Takayuki
Published: January 2019

Isolated fracture of the inferior scapular angle is extremely rare. We present the case of a 20-year-old female with persistent periscapular pain and a winged scapula caused by delayed union of an inferior scapular angle (ISA) fracture. Ten months previously, the patient had a car accident while seated in the left rear passenger seat. The patient visited an orthopedic clinic where a surgeon diagnosed left shoulder contusion without any abnormal radiographic findings. The left arm was kept in a sling for 2 months, as left arm elevation caused severe pain in the upper back. After sling removal, the dull pain around the left scapula continued. The patient presented at our clinic because her mother had noticed the deformity of her back. Radiographs showed a small bony fragment in the ventral side of the ISA. Computed tomography revealed a narrow gap between the ISA and the fragment. The patient’s symptoms resolved with conservative treatment that consisted of relative rest for 2 months and subsequent reinforcement exercises of the serratus anterior for 2 months.
Naïve T-cell Deficits at Diagnosis and after Chemotherapy Impair Cell Therapy Potential in Pediatric Cancers
Authors: Das Rajat K. , Vernau Lauren , Grupp Stephan A. , Barrett David M.
Published: January 2019

Translational data on chimeric antigen receptor (CAR) T-cell trials indicate that the presence of naïve T cells in the premanufacture product is important to clinical response and persistence. In anticipation of developing CAR trials for other tumors, we investigated the T-cell distribution from children with solid tumors and lymphomas at diagnosis and after every cycle of chemotherapy. We found that patients with T cells enriched for naïve and stem central memory cells expanded well in vitro, but the majority of tumor types showed chemotherapy-related depletion of early lineage cells with a corresponding decline in successful ex vivo stimulation response. Unexpectedly, many pediatric patients with solid tumors had low numbers of naïve T cells prior to any therapy. These data indicate the ex vivo manufacture of CAR T cells may need to be customized based on the nature of T cells available in each disease type.

Significance:

Cumulative chemotherapy cycles deplete naïve T cells in many pediatric cancer regimens, reducing expansion potential associated with successful adoptive cellular therapies. Naïve T-cell deficits can be seen at diagnosis as well, implying immune deficits that exist prior to chemotherapy, which may also affect the development of immune-based therapies.

See related commentary by Leick and Maus, p. 466.

This article is highlighted in the In This Issue feature, p. 453
Splenic Injury with Subsequent Pleural Effusion: An Underreported Complication of Colonoscopy
Authors: Suliman Idrees , Guirguis John , Chyshkevych Iryna , Dabage Nemer F.
Published: January 2019

Colorectal cancer is a leading cause of morbidity and mortality worldwide. As such, there are recognized guidelines in the screening of this preventable cancer. There are differences in opinion regarding screening recommendations between the European and United States Cancer Prevention Societies. Screening colonoscopy is an option for routine screening for colorectal cancer in asymptomatic adults. It is a day procedure that is conducted both in hospital and specialized outpatient endoscopy suites. Serious harm is in the region of 3 per 1,000 examinations [Am J Gastroenterol. 2016 Aug; 111(8): 1092–101]. Splenic injury is a rare complication of colonoscopy whose frequency is unclear. Conservative management of splenic injury is desirable in order to preserve immunocompetence. We present a case in which a previously healthy 59-year-old female developed a splenic injury and later pleural effusion after screening colonoscopy.
Iodine-125 Episcleral Plaque Brachytherapy for AJCC T4 Posterior Uveal Melanoma: Clinical Outcomes in 158 Patients
Authors: King Benjamin A. , Awh Caroline , Gao Brad T. , Wang Jiajing , Kocak Mehmet , Morales-Tirado Vanessa M. , Ballo Matthew T. , Wilson Matthew W.
Published: January 2019

Background/Aims: The aim of this study is to report the burden of ocular morbidity following iodine-125 episcleral plaque brachytherapy (EPBT) in the treatment of American Joint Committee on Cancer (AJCC) T4-staged posterior uveal melanoma (PUM). Methods: Clinical records of patients with T4-staged PUM treated with 125I EPBT were analyzed for incidence of treatment failure and radiation-induced complications. Results: Cumulative incidence of local treatment failure was 9% (95% CI 5–15%) at 5 years and was associated with decreased tumor height (HR = 0.78; p = 0.01). Cumulative incidence of enucleation at 5 years was 21% and was correlated with worsening baseline visual acuity (HR = 1.42; p = 0.05). Increasing patient age was associated with higher rates of vitreous hemorrhage (HR = 1.03; p = 0.02) and cataract surgery (HR = 1.05; p < 0.001). Increased tumor height was associated with higher rates of neovascular glaucoma (HR = 1.16; p = 0.03) and vitreous hemorrhage (HR = 1.23; p < 0.001). Conclusion: 125I EPBT is an effective treatment for T4-staged PUM and achieves high rates of local control. Treatment failure appears to be more common among minimally elevated tumors. Other causes of ocular morbidity were associated with increasing tumor height, patient age, and baseline visual acuity.
Reconstructed Human Epidermis Predicts Barrier-Improving Effects of Lactococcus lactis Emulsion in Humans
Authors: Hausmann Christian , Hertz-Kleptow Dominique , Zoschke Christian , Wanjiku Barbara , Wentzien-Odenthal Alexandra , Kerscher Martina , Schäfer-Korting Monika
Published: January 2019

Background/Aims: The skin provides protection against chemical, physical, and biological stressors, yet the skin morphology changes over the course of life. These changes might affect the skin barrier function and facilitate the onset of age-related diseases. Since orally applied lactic acid bacteria ameliorate signs of aged and atopic skin, we investigated the effects of a topically applied Lactococcus lactis emulsion. Methods: In a blinded, randomized, vehicle-controlled trial, we studied topical Lactococcus effects both in vitro and in 20 healthy female volunteers. Commercially available reconstructed human epidermis (RHE) was treated for 4 days (once daily) and volar forearms were treated for 30 days (twice daily). Results: Lactococcus formulations improve the skin barrier in RHE as shown by increased filaggrin and human β-defensin-2 expression as well as by the 23% declined mean apparent permeability coefficients for caffeine. A reduction of 18% in transepidermal water loss confirms this effect in humans. Moreover, Lactococcus emulsion optimized skin hydration and surface pH. Skin irritation was not detected. Conclusions: Lactococcus emulsion improved the skin barrier function with good biocompatibility. Moreover, our study exemplifies the translational predictive capacity of testing on RHE with respect to Lactococcus emulsion.
Evaluating Patient Brain and Behavior Pathways to Caregiver Health in Neurodegenerative Diseases
Authors: Hua Alice Y. , Wells Jenna L. , Haase Claudia M. , Chen Kuan-Hua , Rosen Howard J. , Miller Bruce L. , Levenson Robert W.
Published: January 2019

Background: Caregivers of patients with neurodegenerative diseases are at heightened risk for serious health problems, but health differences between individual caregivers abound. Aims: To determine whether atrophy in patient brains could be used to identify caregivers at heightened risk for health problems and which patient variables mediate this relationship. Methods: In 162 patient-caregiver dyads, we assessed patient atrophy using structural MRI, caregiver health, and patient behavior and cognitive symptoms. Results: Patient atrophy in the right insula and medial frontal gyrus was associated with worse caregiver health; this relationship was partially mediated by patient neuropsychiatric symptoms, and assessing atrophy in these regions improved predictions of poor caregiver health above and beyond patient behavioral symptoms. Conclusions: This study shows the value of patients’ brain data in identifying caregivers at risk for becoming sick themselves.
GNAQ and PMS1 Mutations Associated with Uveal Melanoma, Ocular Surface Melanosis, and Nevus of Ota
Authors: Toomey Christopher B. , Fraser Kyle , Thorson John A. , Goldbaum Michael H. , Lin Jonathan H.
Published: January 2019

G protein mutations are common in uveal melanomas, and the vast majority target amino acid residue Q209 in either GNAQ or GNA11. The GNAQ R183Q mutation is found in a small fraction of uveal melanomas. We report a patient with an unusual presentation of uveal melanoma arising at an early age in the setting of congenital skin and ocular surface melanosis. A 34-year-old Hispanic female with congenital bilateral nevus of Ota and ocular surface melanosis presented with progressive loss of visual acuity and was found to have a juxtapapillary uveal melanoma. She was treated with brachytherapy, but the tumor relapsed. She underwent enucleation that revealed mixed spindle and epithelioid uveal melanoma cells with no extraocular or lymphovascular spread. Next-generation sequencing performed on DNA isolated from the enucleation specimen identified a GNAQ R183Q mutation and a PMS1 truncation mutation. Cytogenetic profiling revealed no monosomy 3. These findings raise the possibility that uveal melanomas bearing G protein R183 mutations may have distinct clinicopathologic profiles compared to those with Q209 mutations. Furthermore, this is the first reported case of a mutation in the mismatch repair gene PMS1 associated with uveal melanoma.
Clinical Outcomes of ABO-Incompatible Kidney Transplantation in Patients with End-Stage Kidney Disease due to Diabetes Nephropathy
Authors: Uchida Junji , Kosoku Akihiro , Kabei Kazuya , Nishide Shunji , Shimada Hisao , Iwai Tomoaki , Kuwabara Nobuyuki , Naganuma Toshihide , Maeda Keiko , Kumada Norihiko , Takemoto Yoshiaki , Nakatani Tatsuya
Published: January 2019

Background: Diabetes nephropathy is one of the most common causes of end-stage kidney disease (ESKD) worldwide. The data are clear that kidney transplantation is superior to remaining on dialysis for patients with diabetes. However, there have been no reports on ABO-incompatible kidney transplantation in patients with ESKD due to diabetes nephropathy. Patients and Methods: We conducted a retrospective, observational study to investigate the clinical outcomes of ABO-incompatible kidney transplantation for patients with pre-existing diabetes nephropathy at our institution from April 2011 to October 2017. A total of 14 recipients were enrolled in this study. Results: All 14 patients underwent successful kidney transplantation. Both overall patient and graft survival rates were 100, 89.9, and 89.9% at 1, 3, and 5 years, respectively. One patient died 20 months after transplantation with a functioning graft due to pancreas cancer. Two of the 14 patients (14.3%) developed biopsy-proven acute cellular rejection during the follow-up period. The median observation period was 32.0 months (range 5–83 months). Conclusion: ABO-incompatible kidney transplantation may be an acceptable renal replacement therapy for ESKD patients with diabetes.
Characteristics and Predictive Factor of Helicobacter pylori-Associated Functional Dyspepsia in Japanese Patients
Authors: Kawamura Yurika , Funaki Yasushi , Yoshimine Takashi , Tamura Yasuhiro , Yamamoto Sayuri , Izawa Shinya , Hayakawa Toshihiko , Ebi Masahide , Murotani Kenta , Ogasawara Naotaka , Sasaki Makoto , Kasugai Kunio
Published: January 2019

Background/Aim: Helicobacter pylori (HP) eradication therapy was first recommended as pharmacotherapy for functional dyspepsia (FD). However, the mechanism and effect of eradication on FD symptom improvement have not been fully investigated. This study aimed to investigate the pathology of patients with HP-associated FD, and predictive factors for HP-associated FD. Methods: Ninety-seven patients with chronic gastritis caused by HP infection were divided into the group with FD symptoms and the group ­without FD symptoms. Patient backgrounds, QOL, gastric mucosal atrophy severity, and serum pepsinogen (PG) value were compared between the 2 groups. Twelve months after eradication, those factors were evaluated between HP-associated FD and HP-non-associated FD, and predictive factors of HP-associated FD were analyzed. Results: The FD-positive group existed in 45 (46.3%) out of 97 patients. Twelve months after eradication, there were 34 patients (75.6%) in the HP-associated FD. The mean PG I value in the HP-associated FD was significantly lower than that in the HP-non-associated FD, while the PG II values in the HP-associated FD tended to be lower than those in the HP-non-associated FD. QOL in the HP-associated FD significantly improved after HP eradication. On multivariate logistic regression analysis, it was found that PG II value was a significant predictive factor for FD symptom improvement in the HP-associated FD. Conclusion: HP eradication is an effective initial therapy for FD. PG II value is considered a predictive factor for FD symptom improvement through HP eradication.
An Atypical Presentation of Acute Macular Neuroretinopathy after Non-Ocular Trauma
Authors: Kuriakose Robin K. , Chin Eric K. , Almeida David R.P.
Published: January 2019

Purpose: Acute macular neuroretinopathy (AMN) is a rare clinical entity with an uncertain etiology. We report an atypical case presenting with retinal hemorrhages (RH) and cotton-wool spots (CWS) following non-ocular trauma. Observations: A 49-year-old male presented with an acute onset of a paracentral scotoma in his left eye, immediately following a motor vehicle accident 1 day prior. Fundus findings revealed a unilateral nasal petalloid perifoveal lesion with the tip pointing toward the fovea associated with CWS and RH. Optical coherence tomography demonstrated disruption of the ellipsoid zone. Symptoms and exam findings improved at 2-week follow-up without any intervention, consistent with the natural history of the disease process. Conclusion: We report a rare case of AMN following non-ocular trauma with the unique fundus findings of CWS and RH. This presentation supports the role of ischemia in the retinal deep capillary plexus, of which trauma contributed to the pathophysiological process. Summary: AMN is a rare condition whose pathophysiological process remains speculative. We report an atypical case of AMN, which supports the role of trauma in the pathophysiology of deep retinal capillary plexus compromise.
The Effects of Oxytocin on Withdrawal, Craving and Stress Response in Heroin-Dependent Patients: A Randomized, Double-Blind Clinical Trial
Authors: Moeini Mina , Omidi Abdoallah , Sehat Mojtaba , Banafshe Hamid Reza
Published: January 2019

Opioid dependence is an increasing clinical and public health problem. Current pharmacotherapies have limited efficacy and cause serious side effects. Increasing bodies of evidences suggest the neuropeptide, oxytocin (OT), as a potential treatment for drug abuse disorders. The current study was designed to evaluate the effect of OT on withdrawal, craving and anxiety scores, cortisol and dehydroepiandrosterone sulphate (DHEAS) blood level in heroin-dependent male patients. This randomized, double-blind placebo-controlled clinical trial was conducted on 58 males with opioid dependence by Abstinence Center of Addictive People in Iran. The participants were randomly allocated to receive intranasal OT (single dose; 40 IU, n = 29) or placebo (n = 29). Heroine withdrawal, craving and anxiety scores were measured using the Opioid Withdrawal Scale, Visual Analogue Scale and (Desire for Drug Questionnaire), and Hamilton checklist respectively. The cortisol and DHEAS levels at baseline and different post-intervention time were measured using a competitive immunoanalysis method. Acute OT administration reduced craving and withdrawal scores but did not change anxiety significantly. Single dose of OT decreased the level of cortisol and improved the cortisol/DHEAS ratio in the heroin users during abstinence (p < 0.01). These results suggest that OT may be useful in the attenuation of craving, withdrawal symptom in heroin-dependent patients and might be considered a new potential treatment for heroin dependence where positive effects of OT on stress-related hormones may be involved in this effect of OT.