bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of simvastatin in different concentrations on free radicals in A‐2058 human melanoma malignum cells—EPR studies
Authors: Zdybel Magdalena , Chodurek Ewa , Pilawa Barbara
Published: September 2018

The influence of concentration of simvastatin (SIM) on free radicals in A‐2058 human melanoma malignum cells was studied. The proliferation assay for melanoma A‐2058 cells with SIM in concentration range from 0.1 to 20 µM was performed. SIM in the concentrations of 0.1, 0.3, and 1 μM only slightly changed the growth of A‐2058 cells, but the growth of the cells considerably decreased for higher concentrations of SIM. Free radicals in the cells were examined by an X‐band (9.3 GHz) electron paramagnetic resonance (EPR) spectroscopy. o‐Semiquinone free radicals with g‐factors in the range of 2.0060 to 2.0065 were found in A‐2058 cells. The asymmetric broad EPR spectra with linewidths (ΔBpp) from 0.87 to 1.25 mT were measured. The fast spin‐lattice relaxation processes characterized all the tested cells. The free radical concentrations in the all A‐2058 cells cultured with SIM were lower than in the control cells. The quenching of free radicals in A‐2058 cells depended on concentration of SIM. This effect was the weakest for concentration of SIM of 3 μM. The strongest decrease of free radical concentration caused SIM in concentration of 1 μM.
Tissue protein and lipid alterations in response to metallic impaction
Authors: Seidman Shari A. , Johnson Natasha A. , Arbelo Ulises , Aribindi Katyayini , Bhattacharya Sanjoy K
Published: September 2018

Tissue response to metallic contact and injury remains poorly understood at the level of proteins and lipid changes. We used corneas as a model system (bovine, porcine [n = 300 each], and human corneas [n = 6]) to characterize proteomic and lipidomic reactions to metallic exposure (impaction with iron). We also made a limited investigation into protein extractability and profile changes due to copper, and lead exposure as well. We identified selected proteins after trypsin digestion using an LCQ Deca XP and lipids using a TSQ Quantum Access Max mass spectrometer, respectively. Our findings indicate that iron impaction to corneal tissue results in cleavage of 1‐phosphatidylinositol‐4,5‐bisphosphate phosphodiesterase beta‐2 variant (PLCB2; 134 kDa) into a 36 kDa species and presence of the epithelial layer is necessary for this cleavage. Penetration of the cornea with other metals (copper and lead) resulted in lower protein extractability from corneal tissue compared with controls but not distinct changes in PLCB2. The changes in protein profiles were unique to the type of metal used for impaction. The depth of injury negatively affected protein extractability and profile compared with controls. These changes were also dependent on several other factors in a complex manner. Iron impaction of corneal tissue for 24 hours results in cleavage of PLCB2 commensurate with significant changes in phosphatidylinositols but not phosphatidylcholines or other phospholipids.
Inhibition of miR146b‐5p suppresses CT‐guided renal cell carcinoma by targeting TRAF6
Authors: Meng Gaopei , Li Guoce , Yang Xue , Xiao Na
Published: September 2018

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. Due to the lack of early symptoms, diagnosis of RCC usually occurs at late stages or after cancer metastasis leading to poor prognosis. Therefore, it is crucial to study early molecular mechanisms and biomarkers. Previous studies have suggested that microRNAs are involved in RCC initiation and development, making them a good candidate for early diagnosis and therapy. MiR146b‐5P plays important roles in the progression of multiple cancers including thyroid cancer, pancreatic cancer, cervical cancer. However, it is not clear whether and how miR146b‐5P is involved in RCC. In this study, we aimed to investigate the function of miR146b‐5P in RCC. We examined the expression levels of miR146b‐5p in renal cancer tissue and cell lines. We also explored the effects of blocking miR146b‐5p in renal tumor growth and inflammatory signaling. Finally, we determined if miR146b‐5p regulates tumorigenesis through TRAF6. We found that miR146b‐5p levels were significantly increased in renal cancer tissue and renal cancer cells. Blocking miR146b‐5p suppressed renal tumor growth and enhanced inflammatory response through increased TRAF6 expression. These effects were eliminated in TRAF6 knockout mice. Our results suggest that enhanced miR146b‐5p expression may be a biomarker for RCC and modulating miR146b‐5p and TRAF6 levels represent a potential therapeutic strategy for RCC.
MiR‐125b suppresses the carcinogenesis of osteosarcoma cells via the MAPK‐STAT3 pathway
Authors: Xiao Tao , Zhou You , Li Hui , Xiong Liang , Wang Jing , Wang Zhi‐Hua , Liu Li‐Hong
Published: September 2018

The microRNA (miRNA) miR‐125b is abnormally expressed in many different types of tumors, including osteosarcoma (OS). How aberrantly expressed miR‐125b participates in regulating the initiation and progression of OS is still poorly understood. In the current study, we found that in OS, miR‐125b can suppress the expression of MAP kinase kinase 7 (MKK7), which can dephosphorylate and inactivate signal transducer and activator of transcription 3 (STAT3). We also identified an elevated expression level of MKK7 in OS and an association between MKK7 expression and poor prognosis. Further, miR‐125b inhibited OS cell proliferation and invasion by targeting and downregulating MKK7 in vitro and suppressed tumor formation in vivo. Moreover, using Western blot analysis, we preliminarily proved that the activation (phosphorylation) of STAT3 was regulated by MKK7 at the epigenetic level. MKK7 was overexpressed in OS and associated with poor clinical results. The miR‐125b‐MAPK‐STAT3 axis may be one of the mechanisms of OS oncogenesis and a potential target for the treatment of OS.
Bisphenol A stimulates steroidogenic acute regulatory protein expression via an unknown mechanism in adrenal cortical cells
Authors: Medwid Samantha , Guan Haiyan , Yang Kaiping
Published: September 2018

Bisphenol A (BPA) is one of the most widespread endocrine disrupting chemicals in the environment. Exposure to BPA is known to be associated with disruption of steroidogenesis in reproductive tissues, but little is known about its effects on the adrenal gland. We previously showed that prenatal BPA exposure resulted in elevated plasma corticosterone levels concomitant with increased adrenal levels of steroidogenic acute regulatory protein (StAR), the rate‐limiting step in steroidogenesis, in adult female mouse offspring. However, the molecular mechanisms underlying the BPA‐induced StAR protein expression in the adrenal gland remain unknown. Therefore, the current study was designed to address this important question using the human cortical cell line, H295A cells, as an in vitro model system. We found that: (1) BPA increased StAR protein levels in a dose‐dependent manner; (2) both estrogen receptor alpha (ERα)‐ and ERβ‐specific agonists mimicked while the ER antagonist ICI abrogated the stimulatory effects of BPA on StAR protein levels; and (3) BPA did not alter StAR messenger RNA, 37kDa preprotein or protein half‐life. Taken together, these findings demonstrate that BPA increases StAR protein levels through an unknown mechanism independent of StAR gene transcription, translation, and protein half‐life. Furthermore, such effects are likely mediated by ERα and/or ERβ.
Increasing maternal age of blastocyst affects on efficient derivation and behavior of mouse embryonic stem cells
Authors: Assadollahi Vahideh , Fathi Fardin , Abdi Mohammad , Khadem Erfan Mohamad Bager , Soleimani Farzad , Banafshi Omid
Published: September 2018

Mouse embryonic stem cells (mESCs) have the capability to undergo unlimited cell division and differentiate into derivatives of all three embryonic germ layers. These fundamental features enable mESCs to potentially be appropriate, efficient models for biological and medical research. Therefore, it is essential to produce high‐performance mESCs. In the current study, we have produced mESCs from blastocysts that developed from fertilized oocytes of 2 (2‐C57)‐, 4 (4‐C57)‐, and 6 (6‐C57)‐month‐old C57BL/6 mice. A comparison of isolated stem cells was done from the viewpoint of the efficiency of mESC derivation, self‐renewal, and their differentiation capacity. All generated mESCs showed a similar expression of the molecular markers protein of pluripotency and AP activity. In the 3i medium, there was a significant decrease in undifferentiated marker genes expression in the 2‐C57 cells compared with the other two groups (
P < 0.05) but developmental genes significantly increased in the 4‐C57 and 6‐C57 cells compared with the 2‐C57 cells (
P < 0.05). The differentiation capacity into three germ layers through the embryoid body formation and percentage of cell lines with normal numbers of chromosomes reduced with increased maternal age. The highest DT and highest percentage of cells in the S phase belonged to 2‐C57 cells. These data demonstrated that blastocysts which developed from fertilized oocytes of 2‐, 4‐, and 6‐month‐old C57BL/6 mice can generate pluripotent stem cells, and suggested that both the efficiency of mESC isolation and the behavior of these isolated mESCs including pluripotency, self‐renewal, cell cycle, and DT changed with increasing maternal age.
Retracted: MicroRNA‐520a‐3p suppresses epithelial–mesenchymal transition, invasion, and migration of papillary thyroid carcinoma cells via the JAK1‐mediated JAK/STAT signaling pathway
Authors: Bi Chang‐Long , Zhang Ying‐Qi , Li Bo , Guo Min , Fu Yi‐Li
Published: September 2018

Papillary thyroid cancer (PTC) is a kind of thyroid cancer and frequently presents with epithelial–mesenchymal transition (EMT). MicroRNAs (miRNAs) were previously reported to be associated with PTC. Thus, this study aims to define the role of microRNA‐520a‐3p (miR‐520a‐3p) in PTC through the JAK/STAT signaling pathway by targeting
JAK1. The PTC and normal thyroid tissues of 137 PTC patients were collected. First of all, the expression pattern of miR‐520a‐3p, JAK1, JAK2, STAT3, E‐cadherin, and vimentin in PTC was identified. The relationship between miR‐520a‐3p and
JAK1 was predicted and analyzed. And a series of miR‐520a‐3p mimic or inhibitor, or siRNA
JAK1 introduced into PTC cells were applied to examine the effect of miR‐520a‐3p on PTC cell viability, migration, invasion, cell cycle, apoptosis, and EMT. Meanwhile, the regulatory effect of miR‐520a‐3p and
JAK1 on the JAK/STAT signaling pathway was also determined. The expression of
JAK1,
JAK2,
STAT3, and vimentin increased yet miR‐520a‐3p and E‐cadherin decreased in PTC tissue.
JAK1 was negatively regulated by miR‐520a‐3p. Functionally, EMT induction was prevented by miR‐520a‐3p upregulation through downregulating
JAK1. When upregulating miR‐520a‐3p or silencing
JAK1 in PTC cells, PTC cell viability, migration, and invasion were inhibited yet cell apoptosis promoted with cells arrested at G1 phase, indicating that miR‐520a‐3p prevented PTC progression by downregulating
JAK1. Moreover, miR‐520a‐3p elevation or
JAK1 inhibition inactivated the JAK/STAT signaling pathway. Collectively, miR‐520a‐3p prevents cancer progression through inactivating the JAK/STAT signaling pathway by downregulating
JAK1 in PTC.
Cucurbitacin B suppresses proliferation of pancreatic cancer cells by ceRNA: Effect of miR‐146b‐5p and lncRNA‐AFAP1‐AS1
Authors: Zhou Jingkai , Liu Mei , Chen Yanan , Xu Shansen , Guo Yingjie , Zhao Limei
Published: September 2018

Cucurbitacin B (CuB) is a natural tetracyclic triterpene product that displays antitumor activity against a wide variety of cancers. In this study, we explored the antipancreatic cancer activity of CuB via the inhibition of expression of the cancer‐related long noncoding RNA, actin filament‐associated protein 1‐antisense RNA 1 (AFAP1‐AS1). CuB arrested pancreatic cancer (PC) cells in the G2/M cell cycle phase by suppressing the expression of AFAP1‐AS1. Insights into the mechanisms of competing endogenous RNAs (ceRNAs) gained from bioinformatics analysis and luciferase activity assays showed that the epidermal growth factor receptor (EGFR) and AFAP1‐AS1 directly compete for miR‐146b‐5p binding. CuB‐induced high miR‐146b‐5p expression and inhibited the expression of AFAP1‐AS1. In summary, reducing the expression of endogenous AFAP1‐AS1 effectively increased the available concentration of miR‐146b‐5p in PC, whereas miR‐146b‐5p overexpression prevented the expression of endogenous AFAP1‐AS1. In particular, we hypothesized that AFAP1‐AS1 might act as a ceRNA, effectively becoming a sponge for miR‐146b‐5p, thereby activating the expression of the EGFR. Thus, CuB suppresses the proliferation, in vitro and in vivo, of PC cells through the ceRNA effect of AFAP1‐AS1 on miR‐146b‐5p.
Phospholipase D: A new mediator during high phosphate‐induced vascular calcification associated with chronic kidney disease
Authors: Skafi Najwa , Abdallah Dina , Soulage Christophe , Reibel Sophie , Vitale Nicolas , Hamade Eva , Faour Wissam , Magne David , Badran Bassam , Hussein Nader , Buchet Rene , Brizuela Leyre , Mebarek Saida
Published: September 2018

Vascular calcification (VC) is the pathological accumulation of calcium phosphate crystals in one of the layers of blood vessels, leading to loss of elasticity and causing severe calcification in vessels. Medial calcification is mostly seen in patients with chronic kidney disease (CKD) and diabetes. Identification of key enzymes and their actions during calcification will contribute to understand the onset of pathological calcification. Phospholipase D (PLD1, PLD2) is active at the earlier steps of mineralization in osteoblasts and chondrocytes. In this study, we aimed to determine their effects during high‐phosphate treatment in mouse vascular smooth muscle cell line MOVAS, in the ex vivo model of the rat aorta, and in the in vivo model of adenine‐induced CKD. We observed an early increase in PLD1 gene and protein expression along with the increase in the PLD activity in vascular muscle cell line, during calcification induced by ascorbic acid and β‐glycerophosphate. Inhibition of PLD1 by the selective inhibitor VU0155069, or the pan‐PLD inhibitor, halopemide, prevented calcification. The mechanism of PLD activation is likely to be protein kinase C (PKC)‐independent since bisindolylmaleimide X hydrochloride, a pan‐PKC inhibitor, did not affect the PLD activity. In agreement, we found an increase in Pld1 gene expression and PLD activity in aortic explant cultures treated with high phosphate, whereas PLD inhibition by halopemide decreased calcification. Finally, an increase in both
Pld1 and
Pld2 expression occurred simultaneously with the appearance of VC in a rat model of CKD. Thus, PLD, especially PLD1, promotes VC in the context of CKD and could be an important target for preventing onset or progression of VC.
An Integrated Population Pharmacokinetic Analysis to Characterize Levonorgestrel Pharmacokinetics After Different Administration Routes
Authors: Reinecke Isabel , Hofmann Birte , Mesic Emir , Drenth Henk‐Jan , Garmann Dirk
Published: September 2018

To compare the pharmacokinetics (PK) of the progestin levonorgestrel for various routes of administration, an integrated population PK analysis was performed. This analysis integrated data from 10 clinical pharmacology studies and resulted in a single, comprehensive population PK model (and its applications) describing the PK of levonorgestrel and its variability for 6 levonorgestrel‐containing contraceptives: 3 intrauterine systems (IUSs; levonorgestrel [LNG]‐IUS 20 [Mirena®], LNG‐IUS 12 [Kyleena®], and LNG‐IUS 8 [Jaydess®/Skyla®]); 2 oral contraceptives (the progestin‐only pill [Microlut®/Norgeston®] and the combined oral contraceptive [Miranova®]); and a subdermal implant (Jadelle®). The levonorgestrel‐containing contraceptives administered orally or as an implant act mainly via their systemic (unbound) levonorgestrel exposure, whereas levonorgestrel administered via an IUS is released directly into the uterine cavity, resulting in lower systemic levonorgestrel concentrations. The integrated population PK analysis revealed that the combined oral contraceptive led to the highest levonorgestrel exposure, followed by the progestin‐only pill and the implant, which led to similar levonorgestrel exposure, and the IUSs, which led to the lowest levonorgestrel exposure (in decreasing order: LNG‐IUS 20, LNG‐IUS 12, and LNG‐IUS 8). The difference was even more distinct at the end of the indicated duration of use of 3 years (LNG‐IUS 8) and 5 years (LNG‐IUS 20 and LNG‐IUS 12). Comparing the 3 IUSs and the implant, in vivo release rates were highest for the implant, followed by LNG‐IUS 20, then LNG‐IUS 12, and were lowest for LNG‐IUS 8. This is in line with the comparison of the total levonorgestrel concentrations.
What Interactions between Financial Globalization and Instability?—Growth in Developing Countries
Authors: Gaies Brahim , Goutte Stephane , Guesmi Khaled
Published: September 2018

This paper tests the effects of the impact of financial globalization on economic growth, examining its interaction with financial instability for a sample of 72 developing countries over the period 1972–2011, using dynamic panel estimator ‘two‐step Generalized Method of Moments’ (two‐step system GMM). The main results of the paper are the following: (i) financial instability and indebtedness‐globalization decrease growth; (ii) financial globalization and investment‐globalization increase growth; (iii) indebtedness‐globalization increases the effect of financial instability on growth; (iv) investment‐globalization decreases the effect of financial instability on growth; and (vi) financial globalization decreases the effect of financial instability on growth. These results are robust in a set of tests consisting of the insertion of alternative variables of financial instability, the inclusion of new control variables, inter alia an indicator of banking crises, using different time periods, and changing of the composition of the sample. © 2018 John Wiley & Sons, Ltd.
Nickel and arsenite‐induced differential oxidative stress and antioxidant responses in two Anabaena species
Authors: Prajapati Rajesh , Yadav Shivam , Atri Neelam
Published: September 2018

In recent years, release of chemical pollutants has increased due to anthropogenic activities. Heterocystous filamentous cyanobacteria constitute dominant paddy microflora and are excellent biofertilizers augmenting rice productivity. Cyanobacteria are frequently exposed to toxic metals, nickel and arsenic are one of the major toxicants present. We exposed two species of diazotrophic cyanobacteria Anabaena sp. PCC 7120 and Anabaena doliolum, to sub‐lethal concentrations (15.0 and 9.0 μM) of Ni2+ and (17.0 and 11 mM) of arsenite (AsIII) and analyzed at different days of treatments (0, 1, 7, and 15 days) for oxidative damage and antioxidative biomarkers. Lipid peroxidation was enhanced (1.5‐ to 2.5‐fold increase in MDA content), indicating damaging effects of Ni2+ and As(III) on membrane. Although Ni2+ and As(III), both induced oxidative stress in both species, Anabaena PCC 7120 experienced less stress than A. doliolum. This could be explained by a higher activity of antioxidant enzymes catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR) in Anabaena PCC 7120 (4.6‐, 2.0‐ and 1.4‐fold [Ni2+] 3.2‐, 2.5‐, and 2.08‐fold [As]) compared to A. doliolum (4.2‐, 2.5‐, and 1.3‐fold [Ni2+] and 3.2‐, 3.33‐, and 1.8‐fold [As]). Moreover, superoxide dismutase registered less inhibition in Anabaena sp. PCC 7120 (1.5 and 1.8) compared to A. doliolum (1.8 and 2.3) under Ni2+ and As(III) stress. In addition to, IBR revealed that As(III) imposes severe impact on both strain, however, A. doliolum suffers most. Therefore, the study demonstrates interspecies variation in survival strategy of two Anabaena species and difference in potential of two different toxicants to produce oxidative stress.
In situ surface‐enhanced Raman spectroscopic monitoring electrochemical and surface plasmon resonance synergetic catalysis on dehydroxylation of PHTP at Ag electrodes
Authors: Li Xu , Zhang Chenjie , Wu Qian , Zhang Jing , Xu Minmin , Yuan Yaxian , Yao Jianlin
Published: September 2018

Surface plasmon resonance (SPR)‐driven heterogeneous catalytic reactions have attracted considerable interests. However, the application of SPR was restricted in few types of surface reaction; the extension of SPR‐catalyzed reaction still remains significant challenge. The introduction of additional external fields is expected to generate the synergetic effect for improving the performance of SPR catalytic reaction. Herein, the roughened Ag electrode played as a substrate for introducing the second external field, that is, electrochemical control. A probe molecule, p‐hydroxythiophenol (PHTP), was preanchored onto Ag electrodes and surface‐enhanced Raman spectroscopy was employed to monitor the surface processes. It demonstrated that the PHTP underwent the dehydroxylation reaction to produce the thiophenol (TP) by the appropriate excitation line and potentials. It disappeared on Ag roughened electrodes without electrochemical control or on a smooth charged surface attached with shell‐isolated nanoparticles. It suggested that the dehydroxylation reaction was contributed by the synergetic effects of localized SPR and applied potential. The results revealed that the efficiency of dehydroxylation was critically depended on wavelength and power of laser, potential, as well as solution pH. The hydrogen sources were essential for dehydroxylation and protonated hydroxyl group promoted the process for producing TP, thus, the dehydroxylation of PHTP was more favorable in acidic solution than that in a neutral case, while it was inhibited completely in alkaline environment. With the appropriate potential, the size of the nanostructures on Ag electrode surface and the corresponding surface plasmon band resulted in the higher efficiency with matched laser wavelength at about 532 nm. The synergetic effects of SPR and potential allowed the extension of the SPR catalysis to a new catalogue of surface reaction, that is, dehydroxylation. It was beneficial to develop the SPR catalysis as a promising approach in the surface chemistry.
Raman and time of flight secondary ion mass spectrometry investigation answers specific conservation questions on Bosch painting Saint Wilgefortis Triptych
Authors: Sodo Armida , Tortora Luca , Biocca Paola , Casanova Municchia Annalaura , Fiorin Enrico , Ricci Maria Antonietta
Published: September 2018

Raman spectroscopy and time of flight secondary ion mass spectrometry (ToF‐SIMS) were used to answer conservation questions left open after the preliminary analysis performed by the restoration team on the Bosch painting Saint Wilgefortis Triptych, within the project “Bosch in Venice.” In this work, we present the results obtained by combining these two techniques on five cross sections, concerning a detailed study of pigments and bindings degradation processes, the identification of organic components (binders/lakes), and the characterization of restoration products. Raman measurements show the presence of degradation products, such as calomel on the red pigment cinnabar, calcium‐oxalate, in particular weddellite, localized in a not original external layer, and finally lead soaps in several layers of the investigated samples. Although the detection of lead soaps suggests the use of oils as binders, Raman spectroscopy has given no conclusive information about such binders, neither on the possible presence of red lakes, suggested by independent UV observations. Complementary ToF‐SIMS investigations have instead revealed the presence of lead palmitate and stearate in the painting layers along with miristic, palmitic, oleic, and stearic acids, thus confirming the use of an oil medium, likely linseed oil. Additionally, ToF‐SIMS shows the presence of polydimethylsiloxane, likely from a previous restoration treatment in the 1990s, in the external layer of the investigated cross sections. Due to experimental difficulties during the analysis of the red lake, we can only hypothesize the presence of alizarin.
Plant antimicrobial polyphenols as potential natural food preservatives
Authors: Bouarab Chibane Lynda , Degraeve Pascal , Ferhout Hicham , Bouajila Jalloul , Oulahal Nadia
Published: September 2018

BACKGROUND

The growing demand for natural food preservatives in the last decade has promoted investigations on their application for preserving perishable foods. In this context, the present review is focused on discussing the prospective application of plant extracts containing phenolics or isolated plant phenolics as natural antimicrobials in foods. Plant essential oils are outside the scope of this review since utilization of their antimicrobial activity for food preservation has been extensively reviewed.

RESULTS

Although the exact antimicrobial mechanisms of action of phenolic compounds are not yet fully understood, it is commonly acknowledged that they have diverse sites of action at the cellular level. Antimicrobial phenolics can be added directly to the formulation of perishable food products or incorporated into food‐contact materials to release them in the immediate zone of perishable foods. Edible coatings or active food packaging materials can thus be used as carriers of plant bioactive compounds.

CONCLUSION

These materials could be an interesting delivery system to improve the stability of phenolics in foods and to improve the shelf life of perishable foods. This review will thus provide an overview of current knowledge of the antimicrobial activity of phenolic‐rich plant extracts and of the promises and limits of their exploitation for the preservation of perishable foods. © 2018 Society of Chemical Industry
Definition of a new type of tourism niche—The geriatric tourism
Authors: Tsartsara Stella Ioannis
Published: September 2018

In this paper, a new type of tourism, the geriatric tourism, will be initiated for further research as a separate niche from health, medical, or wellness tourism, and it will be proven that the most relevant active and healthy ageing and well‐being products are touching upon more aspects than just wellness.

Geriatric tourism does not exist in bibliography nor to the market as such. The innovative approach to the sales of the geriatric tourism packages is in the fact that geriatric tourism is promoted as a holistic approach of hospitality and possibly but not necessarily, long term type of care to a person with multiple morbidity, frailty, and possibly mild cognitive impairment while holidaying, however not for cure nor for care but for leisure.

We will also prove that the term “senior traveller” based on any age limit above 50 years is not truly representative for any traveller's segment, as the same lifestyle criteria for the intention to buy a certain tourism product also apply to other age segments as well. And that the only classification of the tourism segments above 65 years as geriatric for the purpose of travel organization and management rather than marketing can occur when the chronic conditions due to ageing are causing impairment to a geriatric patient after chronicity onset but who has not nonetheless lost desire to accumulate life experiences. This classification of the undistinguished so far segment to a geriatric one presupposes the existence of a support system at the destination, which is not the same as that of the medical or health tourism offer with the intend to cure, but rather this of a long‐term care service.
Cerebral and Extracerebral Vasoreactivity in Patients With Different Clinical Manifestations of Cerebral Small‐Vessel Disease: Data From the Significance of Hemodynamic and Hemostatic Factors in the Course of Different Manifestations of Cerebral Small‐Vessel Disease Study
Authors: Staszewski Jacek , Skrobowska Ewa , Piusińska‐Macoch Renata , Brodacki Bogdan , Stępień Adam
Published: September 2018

Objectives

Endothelial dysfunction has been implicated in the pathogenesis of cerebral small‐vessel disease (SVD). Little is known about the relationship between SVD and measures of endothelium‐dependent vasodilatation and cerebral vasomotor reactivity. The aim of this study was to evaluate cerebral and extracerebral endothelial dysfunction in patients with different manifestations of SVD and to assess the relationship between endothelial dysfunction and radiologic markers of SVD.

Methods

The vasomotor reactivity reserve (VMRr), breath‐holding index (BHI) of the middle cerebral arteries, and brachial artery flow‐mediated dilatation (FMD) were measured with ultrasound techniques in 90 patients (30 in each group) older than 60 years with extensive white matter lesions (Fazekas grade ≥ 2) with a history of lacunar stroke, vascular dementia, or parkinsonism and 30 individuals with normal magnetic resonance imaging findings (control group). All groups were matched for age, sex, hypertension, and diabetes.

Results

The mean age ± SD (71.8 ± 3.4 versus 71.7 ± 3.4 years), sex distribution, and prevalence of the main vascular risk factors were similar in the SVD and control groups. The VMRr (56.6% ± 18.3% versus 77.1% ± 16.9%), BHI (0.8 ± 0.3 versus 1.1 ± 0.4), and FMD (5.8% ± 4 versus 12.1% ± 5.2%) were severely impaired in the SVD groups compared to the control group (P < .01). The vascular responses to all tests was similar in the SVD groups, but they were significantly decreased in patients with severe white matter lesions, marked brain atrophy, and enlarged perivascular spaces.

Conclusions

This study was the first that simultaneously evaluated cerebral and extracerebral vasodilator responses in a well‐phenotyped cohort of patients with lacunar stroke, vascular dementia, or parkinsonism. The VMRr, BHI, and FMD were more severely impaired in patients with SVD, regardless of its clinical manifestation, than in control participants. All measures were significantly lower in patients with severe white‐matter lesions, brain atrophy, or enlarged perivascular spaces.
Contribution of the Fetal Cardiac Axis and V‐Sign Angle in First‐Trimester Screening for Major Cardiac Defects
Authors: Zheng Ming M. , Tang Hui R. , Zhang Yan , Ru Tong , Li Jie , Xu Bi Y. , Xu Yan , Hu Ya L.
Published: September 2018

Objective

To estimate the potential value of fetal assessment for the cardiac axis (CAx) and V‐sign angle (VSA) in the first trimester in the prediction of fetal major cardiac defects.

Methods

A cohort study was conducted from December 2015 to June 2016. Patients with singleton pregnancies and crown‐rump length from 45 to 84 mm were recruited to undergo nuchal translucency sonography. The CAx on the 4‐chamber view and the VSA on the 3‐vessel and trachea view with Doppler mapping were measured. The estimated performance of different combinations of increased fetal nuchal translucency, CAx, and VSA in screening for major cardiac defects was examined.

Results

The study population of fetuses included 30 fetuses with major cardiac defects and 1538 normal fetuses. The CAx and VSA were 30° to 60° and 30° to 40°, respectively, according to the 2.5th and 97.5th percentiles in normal fetuses. When cases of isolated septal wall defects and an isolated right aortic arch were excluded, nuchal translucency above the 95th percentile, an abnormal CAx, and an abnormal VSA were observed in 63.3% (19 of 30), 63.3% (19 of 30), and 66.7% (20 of 30) of fetuses with major cardiac defects, respectively, and in 4.6% (71 of 1538), 2.0% (30 of 1538), and 5.6% (86 of 1538) of those without cardiac defects. Either an abnormal CAx or VSA was found in 93.3% (28 of 30) of the fetuses with cardiac defects and in 7.3% (113 of 1538) of those without cardiac defects.

Conclusion

Assessment of the CAx and VSA is helpful in defining a population at risk for major cardiac defects in the first trimester.
Trends in Medical Claims and Utilization of Limited Ultrasonography Among Emergency Physicians and Radiologists Within a Large Health Plan Provider
Authors: Bergmann Kelly R. , Reardon Robert F. , Flores Glenn , Whitcomb Valerie , Christensen Eric W. , Watson Dave , Kharbanda Anupam
Published: September 2018

Objectives

The goal of this study was to evaluate trends in medical claim submissions for limited ultrasound studies performed (1) during emergency department (ED) encounters and (2) by ED providers compared to radiologists.

Methods

We conducted a retrospective, descriptive study using medical claims data from Medica Health Plans from January 1, 2011 to December 31, 2015. Current procedural terminology codes were abstracted for limited ultrasound applications performed during an ED visit and further stratified by studies performed by ED providers compared with radiologists. We excluded claims for which we could not determine provider specialty.

Results

We identified 42,576 encounters with limited US claims, of which, 32,666 were submitted by ED providers (N = 9649) or radiologists (N = 23,017). Among ED providers, there was a significant linear increase in the annual number of claims for retroperitoneal (P < .001) and nonlinear increases for thoracic, soft tissue, cardiac, transvaginal genitourinary (GU) and transabdominal GU claims (all P < .001). Compared with radiologists, there was a linear increase in the annual proportion of claims submitted for retroperitoneal (P = .023), transabdominal GU (P = .003), and transvaginal GU (P < .001) studies by ED providers. There was a nonlinear decrease in the annual proportion of limited abdomen claims (P < .001) submitted by ED providers compared with radiologists.

Conclusions

Using data from a large health plan provider, we show that medical claims for many limited ultrasound studies are increasing among ED providers. Compared with radiologists, ED providers are increasingly submitting claims for retroperitoneal, soft tissue, and transabdominal GU studies.
Development of a survival animal model for subglottic stenosis
Authors: Schweiger Cláudia , Hart Catherine K. , Tabangin Meredith E. , Cohen Aliza P. , Roetting Nicholas J. , DeMarcantonio Michael , Becker Elise , Ward Jonette A. , de Alarcón Alessandro
Published: September 2018

Objective

To develop a reproducible survival animal model for subglottic stenosis.

Study Design

Prospective study.

Methods

We evaluated five methods of inducing airway injury in 30 New Zealand white rabbits to produce a subglottic stenosis model. Experimental groups comprised: group 1 (n = 5), which underwent 4‐hour intubation; group 2 (n = 5), which underwent induced subglottic injury with a nylon brush; group 3 (n = 10), which underwent subglottic injury with a nylon brush, followed by 4‐hour intubation; group 4 (n = 5), which underwent subglottic injury with Bugbee cautery in 50% of the subglottic circumference, followed by 4‐hour intubation; and group 5 (n = 5), which underwent subglottic injury with Bugbee cautery in 75% of the subglottic circumference, followed by 4‐hour intubation. Five animals were used as controls. Endoscopy of the airway and sacrifice of animals were planned at an interval of 14 days postinjury. Histologic measurements were analyzed.

Results

No animals in groups 1 or 2 developed stenosis. In group 3, 50% of animals developed symptomatic grade 3 subglottic and tracheal stenosis, necessitating early endoscopy and sacrifice in three animals. Four animals in group 4 developed grade 1 subglottic stenosis, and four in group 5 developed grade 2 subglottic stenosis. Histologic measurements of lumen areas within each of these two groups were similar; all animals survived the follow‐up period.

Conclusion

We successfully developed a reproducible survival model for induced subglottic stenosis using a combination of cautery‐induced subglottic injury followed by 4‐hour intubation. This model lays the foundation for future studies that evaluate endoscopic interventions for the management of subglottic stenosis.

Level of Evidence

NA Laryngoscope, 129:989–994, 2019
Facial Palsy‐Specific Quality of Life in 920 Patients: Correlation With Clinician‐Graded Severity and Predicting Factors
Authors: Tavares‐Brito Joana , van Veen Martinus M. , Dusseldorp Joseph R. , Bahmad Fayez , Hadlock Tessa A.
Published: September 2018

Objectives

To investigate the correlation between facial palsy severity and quality of life in a broad cohort of facial palsy patients and to elucidate factors that influence this relationship.

Study Design

Retrospective study.

Methods

Records of patients presenting with a clinician‐graded facial function (eFACE) and facial palsy‐specific quality‐of‐life patient‐reported outcome measure (FaCE) scale from the same moment were reviewed. Multiple linear regression was performed to study the effect of various variables on FaCE total score.

Results

A total of 920 of 1,304 patients were included, 59.9% female with a mean (standard deviation) age of 48.6 (16.7) years and a median (interquartile range palsy duration of 9.6 [2.2; 42.2] months. A multiple linear regression model predicting FaCE total score was established, finding 10 significant variables: eFACE; viral, malignant, and congenital etiologies; overweight status; anxiety; chronic pain; previous treatment; radiotherapy; and duration of palsy (R2 = 0.261, P < 0.001). Gender, age, laterality, surgical etiology, depression, and timing of evaluation (at initial intake or at follow up) were not found to predict FaCE total scores.

Conclusion

A correlation between facial palsy severity and quality of life was found in a large cohort of patients comprising various etiologies. Additionally, novel factors that predict quality of life in facial palsy were revealed. This information may help specialists to predict which facial palsy patients are at higher risk of a poorer quality of life, regardless of severity.

Level of Evidence

4 Laryngoscope, 129:100–104, 2019
Endoscopic resection of a chorda tympani schwannoma: A novel approach for an exceedingly rare entity
Authors: Schwam Zachary G. , Kaul Vivian Z. , Wanna George B.
Published: September 2018

We present a novel approach for a rare chorda tympani schwannoma. A case report as well as special considerations in all phases of care are reviewed. Laryngoscope, 129:1188–1190, 2019
Changes in Cerebral Hemodynamics in Patients With Cirrhosis After Liver Transplantation
Authors: Macías‐Rodríguez Ricardo Ulises , Ruiz‐Margáin Astrid , Cantú‐Brito Carlos , Flores‐Silva Daniel Fernando , García‐Flores Octavio René , Cubero Francisco Javier , Larrieta‐Carrasco Elena , Torre Aldo
Published: September 2018

Improvement in cognitive function after orthotopic liver transplantation (LT) has been demonstrated in the acute setting immediately after LT and in acute liver failure. However, the longterm changes in cerebral hemodynamics after LT remain unexplored. Therefore, we aimed to evaluate the longterm changes in cerebral hemodynamics of patients with cirrhosis after LT. In this prospective cohort study, we performed transcranial Doppler ultrasonography (TCD) measuring the pulsatility index (PI), resistance index (RI), and breath‐holding index (BHI) to evaluate cerebrovascular structural integrity and reactivity, respectively, in both middle cerebral arteries before and after LT. Neuropsychometric tests and West‐Haven criteria were used for hepatic encephalopathy (HE) characterization. Interleukin 6 and tumor necrosis factor α plasma levels were measured. Descriptive statistics and Wilcoxon’s test were used. There were 27 patients who were included. Median follow‐up after LT was 6 months, mean age before LT was 46.3 ± 10.3 years, the main etiology was hepatitis C virus (59%), and most of the patients were Child‐Pugh B (15/27). Model for End‐Stage Liver Disease (MELD) score was 16 ± 7.5, MELD‐Na was 19.3 ± 7.1, Psychometric Hepatic Encephalopathy Score was –3.48 ± 3.66, and critical flicker fusion (CFF) was 40.28 ± 5.70 Hz. Before LT, 17/27 patients had HE and 11/27 ascites. A decrease of 20.8% and 13.5% in PI and RI was observed after LT (P < 0.001, both), together with an increase in BHI (32.4%, P = 0.122). These changes in cerebral hemodynamics paralleled those in systemic inflammation. Clinical improvement in cognition was observed in all patients with overt HE after LT. In conclusion, these results show a significant improvement in cerebral hemodynamics after LT, obtained through TCD, indicating less arterial cerebral vasoconstriction together with a decrease in systemic inflammation. Changes in cerebral vasoconstriction can be the basis for the improvement in cognitive function after LT in the long term.
De Novo Malignancies Screening After Liver Transplantation for Alcoholic Liver Disease: A Comparative Opportunistic Study
Authors: Renaud Laurence , Hilleret Marie‐Noëlle , Thimonier Elsa , Guillaud Olivier , Arbib Francois , Ferretti Gilbert , Jankowski Adrien , Chambon‐Augoyard Christine , Erard‐Poinsot Domitille , Decaens Thomas , Boillot Olivier , Leroy Vincent , Dumortier Jérôme
Published: September 2018

Patients having received a liver transplantation (LT) for alcoholic liver disease (ALD) have a high risk of de novo malignancies, especially in the upper aerodigestive tract and lungs due to their smoking and alcohol history. The aim of this retrospective study was to compare a group of patients transplanted for ALD who continue to smoke and who were included in an intensive screening program for tobacco‐related cancers implemented at the Grenoble University Hospital and a group of similar patients followed according to usual practice (chest computed tomography [CT] scan every 5 years) at the Edouard Herriot Hospital in Lyon. The intensive screening program consisted of an annual checkup, including a clinical examination by an otorhinolaryngologist, a chest CT scan, and an upper digestive endoscopy. A total of 147 patients were included: 71 patients in Grenoble and 76 patients in Lyon. The cumulative incidence of a first tobacco‐related cancer was 12.3% at 3 years, 20.6% at 5 years, 42.6% at 10 years, and 64.0% at 15 years. A curative treatment was possible in 80.0% of the patients in Grenoble versus 57.9% in Lyon (P = 0.068). The rates of curative treatment were 63.6% versus 26.3% (P = 0.062) for lung cancers, 100.0% versus 87.5% (P = 0.498) for lip‐mouth‐pharynx and larynx cancers, and 66.7% versus 100.0% (P = 1) for esophageal cancers, respectively. In addition, for lung cancers, regardless of study group, 68.7% received a curative treatment when the diagnosis was made by CT scan screening versus 14.3% when it was made because of symptoms (P = 0.008). In conclusion, our study strongly confirms the high rate of tobacco‐related de novo malignancies in LT patients for ALD and suggests that the screening of lung cancer by annual chest CT scan could significantly increase the rate of curative treatment.
Piecewise smooth localized solutions of Liénard‐type equations with application to NLSE
Authors: Das Prakash Kumar , Mandal Supriya , Panja Madan M.
Published: September 2018

In this work, the rapidly convergent approximation method (RCAM) followed by appropriate modifications is applied to obtain piecewise smooth solutions and conserved quantities of a Liénard‐type equation and some important nonlinear partial differential equations reducible to former one. Explicit parameter dependence of the solution has been sensibly used to determine parameter dependence of the constant of the motion as well as the domain in the parameter space for which the piecewise smooth solution is bounded. Solution of Liénard‐type equation is then used to find piecewise smooth traveling wave solutions and corresponding conserved quantities of nonlinear Schrödinger equation. These findings affirm the efficiency of the RCAM for analytical exercise of variety of nonlinear systems of ordinary/partial differential equations appear as mathematical model of physical processes.
Examining contradictory evidence on racial/ethnic differences in perceived need for behavioral health treatment
Authors: Breslau Joshua , Stein Bradley D. , Burns Rachel M. , Collins Rebecca L. , Han Bing , Yu Hao , Mojtabai Ramin
Published: September 2018

Objectives

The study aims to investigate apparently contradictory evidence regarding racial/ethnic differences in perceived need for behavioral health treatment in two prominent surveys of the U.S. population, the National Comorbidity Survey Replication (NCS‐R) and the National Survey of Drug Use and Health (NSDUH).

Methods

The two surveys were compared with respect to two components of perceived need: service use and perceived need among the untreated. Logistic regression models were estimated to adjust comparisons for demographic characteristics. Comparisons were conducted in samples representing the entire population, without selection on a mental health assessment, and for samples meeting criteria for lifetime major depression.

Results

The surveys are concordant with respect to racial/ethnic differences in service use and discordant with respect to perceived need among the untreated. For instance, among untreated individuals, the odds of perceiving a need for treatment are significantly higher in Blacks than Whites in the NCS‐R (OR = 1.8, 95% CI [1.1, 2.9]) but do not differ between these groups in the NSDUH (OR = 0.9, 95% CI [0.7, 1.2]). Temporal trends do not appear to explain this discordance.

Conclusion

Assessments of racial/ethnic differences in perceived need among untreated individuals are affected by methodological differences across surveys. Resolving contradictory evidence is critical to efforts to reduce racial/ethnic disparities.
Detection of microscopic diffusion anisotropy in human cortical gray matter in vivo with double diffusion encoding
Authors: Lawrenz Marco , Finsterbusch Jürgen
Published: September 2018

Purpose

To detect microscopic diffusion anisotropy in human cortical gray matter in vivo with double diffusion encoding experiments.

Methods

Double diffusion encoding experiments were performed on a 3 T whole‐body MR system using echo‐planar imaging. Angular double diffusion encoding measurements were acquired with 8 × 8 and 12 × 12 planar direction combinations and were analyzed in three regions of interest containing white matter, mostly cortical gray matter, and one having significant contributions from cerebrospinal fluid. Inversion with variable recovery times served to estimate and eliminate white matter partial volume effects. To investigate the influence of magnetic field inhomogeneities, experiments with gradient offsets and cross‐term compensated diffusion weightings were performed. The MA index, a rotationally invariant measure of the microscopic diffusion anisotropy, was determined from measurements with 96 direction combinations.

Results

The angular signal modulation in the gray matter region of interest has two components, one being consistent, inter alia, with cross terms with field inhomogeneities while the other represents a signal difference between parallel/antiparallel and orthogonal direction combinations, ie, the fingerprint of microscopic diffusion anisotropy. Based on the amplitudes and their dependency on the inversion time, white matter partial volumes can be excluded as the sole source for this modulation, providing strong evidence for the detection of microscopic diffusion anisotropy in cortical gray matter. MA maps of healthy volunteers show considerably lower values in cortical gray matter compared with white matter.

Conclusion

Microscopic diffusion anisotropy can be measured in human cortical brain matter, which could help to characterize the microstructure of healthy and pathological tissue.
Use of Intradialytic Parenteral Nutrition in Patients Undergoing Hemodialysis
Authors: Sarav Menaka , Friedman Allon N.
Published: September 2018

Intradialytic parenteral nutrition (IDPN) is a form of supplemental nutrition used to treat patients with malnutrition who receive hemodialysis. Once the diagnosis of malnutrition is made in such patients, encouragement of oral intake is the first‐line treatment. If this fails, then enteral or parenteral nutrition may be needed. This review examines the literature on the use of IDPN and summarizes the current recommendations. There is considerable controversy over indications and benefits of IDPN, and well‐controlled, long‐term studies are needed to help tease out these issues. In the interim, clinical judgment should be used when considering IDPN for individual patients.