bluuebunny/crossref_metadata_2025 huggingface dataset:
Anxiety affects disability and quality of life in patients with painful diabetic neuropathy
Authors: Geelen C.C. , Smeets R.J.E.M. , Schmitz S. , van den Bergh J.P. , Goossens M.E.J.B. , Verbunt J.A.
Published: June 2017

Background

Painful diabetic neuropathy (PDN) is known to negatively affect psychosocial functioning as expressed by enhanced levels of anxiety and depression. The aim of this study was to specify diabetes and pain‐related fears.

Methods

This questionnaire‐based cross‐sectional study included 154 patients with PDN (mean age 65.7 ± 6.6 years). Correlation analyses corrected for age, gender, pain intensity, pain duration and insulin treatment were performed to assess the associations of fear of hypoglycaemia (Hypoglycaemia Fear Survey, HFS), kinesiophobia (Tampa Scale of Kinesiophobia, TSK), fear of pain (Pain Anxiety Symptom Scale, PASS‐20), fear of falling (Falls Efficacy Scale‐I, FES‐I), fear of fatigue (Tampa Scale of Fatigue, TSF) and fear of negative evaluation (Brief Fear of Negative Evaluation Scale, BFNE), with quality of life (QoL) (Norfolk Quality of Life Questionnaire, Diabetic Neuropathy Version, QOL‐DN) and disability (Pain Disability Index, PDI), respectively.

Results

In univariate analyses, all fears were independently associated with QOL‐DN and PDI (p < 0.001 for all variables). Linear regression models including all fears and confounders, showed that pain intensity, pain duration and FES‐I were significantly associated with QOL‐DN (R2 = 0.603). Pain intensity, male gender and FES‐I were significantly associated with PDI (R2 = 0.526).

Conclusions

After controlling for confounders, levels of pain intensity, duration of pain and fear of falling were negatively associated with QoL in patients with PDN. Pain intensity, male gender and fear of falling were positively associated with disability. Specifying fears enables us to identify potential targets for behavioural interventions that aim to improve psychosocial well‐being in patients with PDN.

Significance

This study shows that patients with PDN suffer from various fears, which should enable us to design a treatment strategy that directly targets these fears, hereby improving physical and psychosocial well‐being in these patients.
A compact and facile microfluidic droplet creation device using a piezoelectric diaphragm micropump for droplet digital PCR platforms
Authors: Okura Naoaki , Nakashoji Yuta , Koshirogane Toshihiro , Kondo Masaki , Tanaka Yugo , Inoue Kohei , Hashimoto Masahiko
Published: June 2017

We have exploited a compact and facile microfluidic droplet creation device consisting of a poly(dimethylsiloxane) microfluidic chip possessing T‐junction channel geometry, two inlet reservoirs, and one outlet reservoir, and a piezoelectric (PZT) diaphragm micropump with controller. Air was evacuated from the outlet reservoir using the PZT pump, reducing the pressure inside. The reduced pressure within the outlet reservoir pulled oil and aqueous solution preloaded in the inlet reservoirs into the microchannels, which then merged at the T‐junction, successfully forming water‐in‐oil emulsion droplets at a rate of ∼1000 per second with minimal sample loss. We confirmed that the onset of droplet formation occurred immediately after turning on the pump (<1 s). Over repeated runs, droplet formation was highly reproducible, with droplet size purity (polydispersity, <4%) comparable to that achieved using other microfluidic droplet preparation techniques. We also demonstrated single‐molecule PCR amplification in the created droplets, suggesting that the device could be used for effective droplet digital PCR platforms in most laboratories without requiring great expense, space, or time for acquiring technical skills.
Gravel‐bed river evolution in earthquake‐prone regions subject to cycled hydrographs and repeated sediment pulses
Authors: An Chenge , Cui Yantao , Fu Xudong , Parker Gary
Published: June 2017

Sediment often enters rivers in the form of sediment pulses associated with landslides and debris flows. This is particularly so in gravel‐bed rivers in earthquake‐prone mountain regions, such as Southwest China. Under such circumstances, sediment pulses can rapidly change river topography and leave the river in repeated states of gradual recovery. In this paper, we implement a one‐dimensional morphodynamic model of river response to pulsed sediment supply. The model is validated using data from flume experiments, so demonstrating that it can successfully reproduce the overall morphodynamics of experimental pulses. The model is then used to explore the evolution of a gravel‐bed river subject to cycled hydrographs and repeated sediment pulses. These pulses are fed into the channel in a fixed region centered at a point halfway down the calculational domain. The pulsed sediment supply is in addition to a constant sediment supply at the upstream end. Results indicate that the river can reach a mobile‐bed equilibrium in which two regions exist within which bed elevation and surface grain size distribution vary periodically in time. One of these is at the upstream end, where a periodic discharge hydrograph and constant sediment supply are imposed, and the other is in a region about halfway down the channel where periodic sediment pulses are introduced. Outside these two regions, bed elevation and surface grain size distribution reach a mobile‐bed equilibrium that is invariant in time. The zone of fluctuation‐free mobile‐bed equilibrium upstream of the pulse region is not affected by repeated sediment pulses under the scenarios tested, but downstream of the pulse region, the channel reaches different fluctuation‐free mobile‐bed equilibriums under different sediment pulse scenarios. The vertical bed structure predicted by the simulations indicates that the cyclic variation associated with the hydrograph and sediment pulses can affect the substrate stratigraphy to some depth. Copyright © 2017 John Wiley & Sons, Ltd.
Improving power for rare‐variant tests by integrating external controls
Authors: Lee Seunggeun , Kim Sehee , Fuchsberger Christian
Published: June 2017

Due to the drop in sequencing cost, the number of sequenced genomes is increasing rapidly. To improve power of rare‐variant tests, these sequenced samples could be used as external control samples in addition to control samples from the study itself. However, when using external controls, possible batch effects due to the use of different sequencing platforms or genotype calling pipelines can dramatically increase type I error rates. To address this, we propose novel summary statistics based single and gene‐ or region‐based rare‐variant tests that allow the integration of external controls while controlling for type I error. Our approach is based on the insight that batch effects on a given variant can be assessed by comparing odds ratio estimates using internal controls only vs. using combined control samples of internal and external controls. From simulation experiments and the analysis of data from age‐related macular degeneration and type 2 diabetes studies, we demonstrate that our method can substantially improve power while controlling for type I error rate.
Dike distribution density: Method for quantitative mine targets prediction in the South Alatao Mountains area, NW China
Authors: Guo Jing , Luo Zhaohua , Yu Shengyao , Santosh M. , Li Yunshuai
Published: June 2017

The correlation between dike density and regional‐scale mineralization indicates a fundamental criterion for ore‐forming process. Here, a novel dike distribution density method is formulated for evaluating this correlation and exploring mine targets quantitatively. Three parameters (dike density, dike orientation scatter degree and dike fractal dimension) are proposed to express the degree of irregularity and complexity of dike distribution patterns. This method is applied to the South Alatao Mountains area (China), where the dike swarms show regionally well‐developed density gradients and the mineral deposits are spatially associated with abundant dike swarms. On the basis of this quantitative dike distribution density method, 60% of the deposit targets are delineated in this area. This result indicates that the method is an effective quantification tool for prospecting mine targets. The dike distribution density method is applicable for areas where abundant regional‐scale dike swarms and mineralization occur. It should be considered as an effective and complimentary technique for the common mine prospectivity analysis.
Vascular risk factors in older patients with depression: outcome of electroconvulsive therapy versus medication
Authors: Spaans Harm‐Pieter , Kok Rob M. , Bouckaert Filip , Van Den Berg Julia F. , Tunney Orlaith C. , Sienaert Pascal , Verwijk Esmée , Kho King H. , Stek Max L.
Published: June 2017

Objective

Research suggests that in depression, vascular burden predicts a lower efficacy for medication (MED) and a more favourable outcome for electroconvulsive therapy (ECT). Therefore, we investigated the influence of the following vascular risk factors (VRF): hypercholesterolemia, hypertension, smoking, diabetes mellitus, cardiovascular disease, and cerebral vascular accident/transient ischemic attack, on remission from major depression after ECT versus MED.

Methods

The study sample consisted of 81 inpatients with a DSM‐IV unipolar major depression diagnosis (mean age 72.2 years, SD = 7.6, mean Montgomery–Åsberg Depression Rating Scale score 32.9, SD = 6.2) participating in a randomized controlled trial comparing nortriptyline versus venlafaxine and 43 inpatients (mean age 73.7 years, SD = 7.5, mean Montgomery–Åsberg Depression Rating Scale score 30.6, SD = 7.1) from an randomized controlled trial comparing brief pulse versus ultrabrief pulse ECT. The presence of VRF was established from the medical records. The remission rate of patients with VRF was compared with those of patients without VRF.

Results

The remission rate was 58% (19/33) in the ECT group with ≥1 VRF and 32% (23/73) in the MED group with ≥1 VRF (χ2 = 6.456, p = 0.011). Comparing patients with no VRF versus ≥1 VRF, the remission rate decreased from 80 to 58% (χ2 = 1.652, p = 0.276) in ECT patients and from 38 to 32% (χ2 = 0.119, p = 0.707) in MED patients. Applying different cut‐offs for the number of VRFs yielded the same trends. Logistic regression revealed no interaction between VRF and treatment condition.

Conclusion

The superior efficacy of ECT over pharmacotherapy in major depression in older age was independent of the presence of VRF. Copyright © 2017 John Wiley & Sons, Ltd.
Mapping the order and pattern of brain structural MRI changes using change‐point analysis in premanifest Huntington's disease
Authors: Wu Dan , Faria Andreia V. , Younes Laurent , Mori Susumu , Brown Timothy , Johnson Hans , Paulsen Jane S. , Ross Christopher A. , Miller Michael I. ,   the PREDICT‐HD Investigators and Coordinators of the Huntington Study Group
Published: June 2017

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that progressively affects motor, cognitive, and emotional functions. Structural MRI studies have demonstrated brain atrophy beginning many years prior to clinical onset (“premanifest” period), but the order and pattern of brain structural changes have not been fully characterized. In this study, we investigated brain regional volumes and diffusion tensor imaging (DTI) measurements in premanifest HD, and we aim to determine (1) the extent of MRI changes in a large number of structures across the brain by atlas‐based analysis, and (2) the initiation points of structural MRI changes in these brain regions. We adopted a novel multivariate linear regression model to detect the inflection points at which the MRI changes begin (namely, “change‐points”), with respect to the CAG‐age product (CAP, an indicator of extent of exposure to the effects of CAG repeat expansion). We used approximately 300 T1‐weighted and DTI data from premanifest HD and control subjects in the PREDICT‐HD study, with atlas‐based whole brain segmentation and change‐point analysis. The results indicated a distinct topology of structural MRI changes: the change‐points of the volumetric measurements suggested a central‐to‐peripheral pattern of atrophy from the striatum to the deep white matter; and the change points of DTI measurements indicated the earliest changes in mean diffusivity in the deep white matter and posterior white matter. While interpretation needs to be cautious given the cross‐sectional nature of the data, these findings suggest a spatial and temporal pattern of spread of structural changes within the HD brain.Hum Brain Mapp 38:5035–5050, 2017. ©2017 Wiley Periodicals, Inc.
Using event related potentials to investigate visual aesthetic perception of product appearance
Authors: Ding Yi , Guo Fu , Hu Mingcai , Cao Yaqin
Published: June 2017

Visual aesthetic directly affects the user's purchase decision and results from the user's analysis and judgment after perceiving product appearance. Therefore, understanding the neural mechanisms of visual experience is critical for product design. This study combined subjective evaluation with ERPs (event‐related potentials) to investigate the user's aesthetic experience as evoked by smartphones. A visual aesthetic scale was constructed, and the results from the questionnaire were used to verify the reliability of the aesthetic scale. Before the ERPs experiment was constructed, smartphones were divided into higher visual aesthetic and lower visual aesthetic based on subjective evaluation according to the aesthetic scale. An amended oddball paradigm was then used in the ERPs experiment. Landscapes were presented as rare targets, while smartphone pictures were presented as frequent nontarget stimuli. The ERPs were then averaged separately for each aesthetic type. Two negative components were recorded and compared with respect to two aesthetic types on the participants’ prefrontal, frontal, and central sites. The smartphone pictures with lower scores of visual aesthetic elicited larger amplitudes of N100/N200 than those with higher scores according to the within‐subjects, repeated‐measures analysis of variance. The exploring of neural responses correlated with visual aesthetic can provide an accurate method of measuring the user's perception and can help marketers know which product gives the user a higher visual aesthetic experience. The difference of ERPs may be taken as an evaluating indicator of product design.
1‐cyclohexyl‐x‐methoxybenzene derivatives, novel psychoactive substances seized on the internet market. Synthesis and in vivo pharmacological studies in mice
Authors: Fantinati Anna , Ossato Andrea , Bianco Sara , Canazza Isabella , De Giorgio Fabio , Trapella Claudio , Marti Matteo
Published: June 2017

Introduction

Among novel psychoactive substances notified to EMCDDA and Europol were 1‐cyclohexyl‐x‐methoxybenzene stereoisomers (ortho, meta, and para). These substances share some structural characteristics with phencyclidine and tramadol. Nowadays, no information on the pharmacological and toxicological effects evoked by 1‐cyclohexyl‐x‐methoxybenzene are reported. The aim of this study was to investigate the effect evoked by each one stereoisomer on visual stimulation, body temperature, acute thermal pain, and motor activity in mice.

Methods

Mice were evaluated in behavioral tests carried out in a consecutive manner according to the following time scheme: observation of visual placing response, measures of core body temperature, determination of acute thermal pain, and stimulated motor activity.

Results

All three stereoisomers dose‐dependent inhibit visual placing response (rank order: meta > ortho > para), induce hyperthermia at lower and hypothermia at higher doses (meta > ortho > para) and cause analgesia to thermal stimuli (para > meta = ortho), while they do not alter motor activity.

Conclusions

For the first time, this study demonstrates that systemic administration of 1‐cyclohexyl‐x‐methoxybenzene compounds markedly inhibit visual response, promote analgesia, and induce core temperature alterations in mice. This data, although obtained in animal model, suggest their possible hazard for human health (i.e., hyperthermia and sensorimotor alterations). In particular, these novel psychoactive substances may have a negative impact in many daily activities, greatly increasing the risk factors for workplace accidents and traffic injuries.
4,4′‐Dimethylaminorex (“4,4′‐DMAR”; “Serotoni”) misuse: A Web‐based study
Authors: Loi Barbara , Zloh Mire , De Luca Maria Antonietta , Pintori Nicholas , Corkery John , Schifano Fabrizio
Published: June 2017

Background

4,4′‐DMAR (4,4′‐dimethylaminorex; “Serotoni”) is a potent stimulant drug that has recently been associated with a number of fatalities in Europe. Over the last few years, online communities have emerged as important resources for disseminating levels of technical knowledge on novel psychoactive substances.

Objective

Analysing the information provided by the fora communities on 4,4′‐DMAR use, additionally critical reviewing the available evidence‐based literature on this topic.

Methods

Different website drug fora were identified. A critical review of the existing evidence‐based literature was undertaken. Individuation and analysis of qualitative data from the identified website fora were performed.

Results

The combined search results identified six website fora from which a range of qualitative data on recurring themes was collected. These themes included routes of administration and doses; desired effects; adverse effects; comparison with other drugs; association with other drugs; medications self‐administered to reverse 4,4′‐DMAR action; overall impression; and provision of harm‐reduction advice.

Conclusions

Although being characterized by a number of methodological limitations, the social networks' Web monitoring approach (netnography) may be helpful to better understand some of the clinical and psychopharmacological issues pertaining to a range of novel psychoactive substances, including 4,4′‐DMAR, for which only extremely little, if any, scientific knowledge is available.
Intended and unintended use of cathinone mixtures
Authors: Guirguis Amira , Corkery John Martin , Stair Jacqueline Leslie , Kirton Stewart Brian , Zloh Mire , Schifano Fabrizio
Published: June 2017

Introduction

Cathinones are one of the most popular categories of new psychoactive substances (NPS) consumed. Cathinones have different pharmacological activities and receptor selectivity for monoamine transporters based on their chemical structures. They are incorporated into NPS mixtures and used with other NPS or ‘traditional’ drugs. Cathinone use represents significant health risks to individuals and is a public health burden.

Methods

Evidence of poly‐NPS use with cathinones, seizure information, and literature analyses results on NPS mixtures was systematically gathered from online database sources, including Google Scholar, Scopus, Bluelight, and Drugs‐Forum.

Results and discussion

Results highlight the prevalence of NPS with low purity, incorporation of cathinones into NPS mixtures since 2008, and multiple members of the cathinone family being present in individual UK‐seized samples. Cathinones were identified as adulterants in NPS marketed as being pure NPS, drugs of abuse, branded products, herbal blends, and products labelled “not for human consumption.” Toxicity resulting from cathinone mixtures is unpredictable because key attributes remain largely unknown. Symptoms of intoxication include neuro‐psychological, psychiatric, and metabolic symptoms. Proposed treatment includes holistic approaches involving psychosocial, psychiatric and pharmacological interventions.

Conclusion

Raising awareness of NPS, education, and training of health care professionals are paramount in reducing harms related to cathinone use.
The use of supplements and performance and image enhancing drugs in fitness settings: A exploratory cross‐sectional investigation in the United Kingdom
Authors: Mooney Roisin , Simonato Pierluigi , Ruparelia Risha , Roman‐Urrestarazu Andres , Martinotti Giovanni , Corazza Ornella
Published: June 2017

Objective

The strive for perfection is prevalent in the fitness industry. This study aimed to explore the use of products to enhance performance alongside exposure to exercise addiction, appearance anxiety and self‐esteem in fitness settings.

Methods

An online survey was prepared and piloted before wider dissemination in fitness clubs via snowballing and selected mailing lists. A list of commonly used products, including Performance and Image Enhancing Drugs (PIEDs) was provided. Exercise addiction (Exercise Addiction Inventory; EAI), anxiety levels (Appearance Anxiety Inventory; AAI) and their self‐esteem (Rosenberg's Self‐Esteem Scale; RSE) were also measured.

Results

377 questionnaires were completed. A significant number of participants declared the use products either to lose weight (16%) or to reach their fitness goals (41%). The Internet played a major role in both the supply of information and the provision of the enhancement products (33.7%) and side effects were reported (10.5%). Only a limited number of participants sought a medical opinion about taking products (5.1%). EAI scores were high (m=20.02 ± 4.1), AAI (m=15.98 ± 4.8) showed an intermediate level of anxiety, while self‐esteem was low (RSE m=12.59 ± 2.2).

Conclusion

This pilot study identified the emergence of a new drug trend in fitness settings and showed a potential relationship to exercise addiction, anxiety disorders and low self‐esteem. The Internet played a crucial role in disseminating often untested products, including PIEDs without medical supervision and unwanted side‐effects were reported. More studies in the field are required in order to safeguard public health and inform policy making.
Patterns of use and toxicity of new para‐halogenated substituted cathinones: 4‐CMC (clephedrone), 4‐CEC (4‐chloroethcatinone) and 4‐BMC (brephedrone)
Authors: Grifell Marc , Ventura Mireia , Carbón Xoán , Quintana Pol , Galindo Liliana , Palma Álvaro , Fornis Ivan , Gil Cristina , Farre Magi , Torrens Marta
Published: June 2017

Objective

This paper aims to present results of the analysis of clephedrone (4‐CMC), 4‐chloroethcathinone (4‐CEC), and brephedrone (4‐BMC) on recreational drug markets and a systematic review of all the available information concerning these substances.

Material and methods

Samples collected by the drug checking service of the Spanish harm reduction NGO—Energy Control were analyzed and systematic research was conducted. Between June 2014 and October 2016, 1,471 samples with at least one NPS were analyzed, 397 of which contained cathinones.

Results

Clephedrone was found in 29 samples, brephedrone in 8, and both were present in 2 samples. 4‐Chloroethcathinone was detected in 5 samples. Eleven out of the 47 purchased samples (23.4%) were tested to contain the substance the user expected. Samples received were mainly sold as 3‐MMC, MDMA, ketamine, and other cathinones. No literature on the effects or toxicity of these substances was found; the only information available was on internet fora. On many posts, users exhibit concerns about potential toxicity and side effects of using these substances.

Conclusion

Since the emergence of these substances could prove to be the next step to the cat‐and‐mouse game existing between drug producers and legislation, further clinical and epidemiological research should be carried out in order to build evidence to support policy for public health issues.
Assessing the effect of D59P mutation in the DE loop region in amyloid aggregation propensity of β2‐microglobulin: A molecular dynamics simulation study
Authors: Narang Simranjeet S. , Shuaib Suniba , Goyal Deepti , Goyal Bhupesh
Published: June 2017

Dialysis‐related amyloidosis (DRA) is a severe condition characterized by the accumulation of amyloidogenic β2‐microglobulin (β2m) protein around skeletal joints and bones. The recent studies highlighted a critical role of the DE loop region for β2m stability and amyloid aggregation propensity. Despite significant efforts, the molecular mechanism of enhanced aggregation due to D59P mutation in the DE loop region remain elusive. In the present study, explicit‐solvent molecular dynamics (MD) simulations were performed to examine the key changes in the structural and dynamic properties of wild type (wt) β2m upon D59P mutation. MD simulations reveal a decrease in the average number of hydrogen bonds in the loop regions on D59P mutation that enhances conformational flexibility, which lead to higher aggregation propensity of D59P as compare to wt β2m. The principal component analysis (PCA) highlight that D59P covers a larger region of phase space and display a higher trace value than wt β2m, which suggest an overall enhancement in the conformational flexibility. D59P display two minimum energy basins in the free energy landscape (FEL) that are associated with thermodynamically less stable conformational states as compare to single minimum energy basin in wt β2m. The present study provides theoretical insights into the molecular mechanism behind the higher aggregation propensity of D59P as compare to wt β2m.
Diet and cancer prevention: Dietary compounds, dietary MicroRNAs, and dietary exosomes
Authors: Banikazemi Zarrin , Haji Hemat Aghagolzadeh , Mohammadi Mohsen , Taheripak Gholamreza , Iranifar Elmira , Poursadeghiyan Mohsen , Moridikia Abdullah , Rashidi Bahman , Taghizadeh Mohsen , Mirzaei Hamed
Published: June 2017

Cancer is one of main health public problems worldwide. Several factors are involved in beginning and development of cancer. Genetic and internal/external environmental factors can be as important agents that effect on emerging and development of several cancers. Diet and nutrition may be as one of important factors in prevention or treatment of various cancers. A large number studies indicated that suitable dietary patterns may help to cancer prevention or could inhibit development of tumor in cancer patients. Moreover, a large numbers studies indicated that a variety of dietary compounds such as curcumin, green tea, folat, selenium, and soy isoflavones show a wide range anti‐cancer properties. It has been showed that these compounds via targeting a sequence of cellular and molecular pathways could be used as suitable options for cancer chemoprevention and cancer therapy. Recently, dietary microRNAs and exosomes have been emerged as attractive players in cancer prevention and cancer therapy. These molecules could change behavior of cancer cells via targeting various cellular and molecular pathways involved in cancer pathogenesis. Hence, the utilization of dietary compounds which are associated with powerful molecules such as microRNAs and exosomes and put them in dietary patterns could contribute to prevention or treatment of various cancers. Here, we summarized various studies that assessed effect of dietary patterns on cancer prevention shortly. Moreover, we highlighted the utilization of dietary compounds, dietary microRNAs, and dietary exosomes and their cellular and molecular pathways in cancer chemoprevention.
Long noncoding RNA BDNF‐AS inversely regulated BDNF and modulated high‐glucose induced apoptosis in human retinal pigment epithelial cells
Authors: Li Yanyan , Xu Feng , Xiao Hanyan , Han Feng
Published: June 2017

In this study, we characterized the functional role of long noncoding RNA (lncRNA), brain derived neurotrophic factor anti‐sense (BDNF‐AS) in regulating D‐glucose‐induced (DGI) apoptosis in human retinal pigment epithelial (RPE) cells. Human RPE cell line, ARPE‐19 cells were cultured in vitro and treated with various concentrations of D‐glucose for 24 h. A TUNEL assay was applied with immunohistochemical and quantitative approaches to assess the apoptotic effect of D‐glucose. Under the condition of 50 mM D‐glucose, qPCR was used to assess gene expression of BDNF and BDNF‐AS in ARPE‐19 cells. Using siRNA transfection, BDNF‐AS was endogenously knocked down in ARPE‐19 cells. The effects of BDNF‐AS downregulation on DGI apoptosis and BDNF expression were assessed by TUNEL assay, qPCR, and Western blot, respectively. Furthermore, in BDNF‐AS‐downregulated ARPE‐19 cells, secondary siRNA transfection was conducted to knock down endogenous BDNF expression. Its effect on BDNF‐AS‐associated apoptotic regulation was further evaluated. High concentrations of D‐glucose induced significant apoptosis in ARPE‐19 cells in vitro. With treatment of 50 mM D‐glucose, BDNF was markedly downregulated whereas BDNF‐AS upregulated in ARPE‐19 cells. SiRNA‐mediated BDNF‐AS downregulation ameliorated DGI apoptosis and upregulated BDNF in ARPE‐19 cells. In addition, inhibiting BDNF reversed the protective effect of BDNF‐AS downregulation on DGI apoptosis. Our results suggest that BDNF‐AS, through inverse regulation of BDNF, might play a critical role in the process of DGI apoptosis in diabetic retinopathy.
Obacunone causes sustained expression of MKP‐1 thus inactivating p38 MAPK to suppress pro‐inflammatory mediators through intracellular MIF
Authors: Gao Yuan , Hou Rui , Liu Fen , Liu Haibo , Fei Qiaoling , Han Yixin , Cai Runlan , Peng Cheng , Qi Yun
Published: June 2017

Obacunone (OBA) is a highly oxygenated triterpenoid with various pharmacological activities. In this study, we explored its anti‐inflammatory effect and underlying mechanisms in LPS‐activated macrophages. Our data showed that OBA potently decreased pro‐inflammatory mediators (eg, NO, IL‐6, IL‐1β, and MCP‐1) at the transcriptional and translational levels without cytotoxicity. A mechanism study showed that OBA significantly suppressed p38‐mediated AP‐1 signaling by stabilizing the mRNA of mitogen‐activated protein kinase phosphatase 1 (MKP‐1), thus prolonging the expression time of the MKP‐1 protein. Next, we used computational target‐fishing technology to predict the possible target of OBA. Only one potential target, macrophage migration inhibitory factor (MIF), was presented. Experimentally, the interaction between OBA and MIF was also confirmed. By using an anti‐mouse MIF antibody, extracellular MIF (exMIF) was neutralized. Our results showed that autocrine MIF had slight influence on the pro‐inflammatory mediator production. Correspondingly, the anti‐inflammatory activity of OBA was also not affected. Accordingly, we knocked down the MIF gene in RAW 264.7 cells and obtained stable MIF deficient cells MIF(−), in which the effects of OBA on p38 phosphorylation, AP‐1 activation, and pro‐inflammatory mediator production in response to LPS nearly disappeared. In contrast to MIF(+) cells, the MKP‐1 protein expression time of the MIF(−) cells was markedly prolonged. We conclude that OBA exerts its anti‐inflammatory effect by targeting intracellular MIF (inMIF) inhibition to regulate the MKP‐1/p38/AP‐1 pathway. Our findings also provide a chain of evidence that the inhibition of inMIF, rather than exMIF, may become a novel target for inflammation.
Diagnostic reliability of Architect anti‐HCV assay: Experience of a tertiary care hospital in India
Authors: Fletcher Gnanadurai John , Raghavendran Anantharam , Sivakumar Jayashree , Samuel Prasanna , Abraham Priya
Published: June 2017

Background & Aims

Anti‐HCV assays are prone to false positive results. Thus, accurate detection of HCV infection is critical for the timely therapeutic management. This study ascertained the reliability of Architect anti‐HCV assay (Abbott) and to estimate the agreement of this assay with Ortho HCV 3.0 ELISA Test System with Enhanced SAVe (Ortho), HCV Tri‐dot (Tri‐dot) and HCV‐PCR in a tertiary care setting.

Methods

A total of 78 788 consecutive sera were routinely screened for anti‐HCV antibodies using Architect. All repeatedly reactive anti‐HCV sera (n=1000) and anti‐HCV negative sera (n=300) were tested in Ortho and in Tri‐dot assays. Representative proportions of sera (n=500) with various signal‐to‐cut‐off (S/Co) ratio were also compared with HCV‐PCR.

Results

When Architect was compared with Ortho, Tri‐dot, and HCV‐PCR, the level of agreement as assessed by kappa were .26, .16, and .27 respectively. Using Latent class analysis (LCA), we found that sensitivity and specificity were 100% and 36.1% for Architect, 93.8% and 100% for Ortho and 63.8% and 100% for Tri‐dot respectively. The median S/CO ratio of Architect and Ortho anti‐HCV assays were significantly different between HCV‐PCR positive and negative results (P<.0001). Furthermore, Architect S/CO ratio of >8 showed higher accuracy indices in both anti‐HCV assays.

Conclusions

Architect can be used as a screening assay because of its high sensitivity, high throughput, and short turnaround time. However, S/Co ratios of ≥1 to <8 in Architect necessitates HCV PCR to identify current infection and or EIA to distinguish true positivity from false biological positivity.
Ptn functions downstream of C/EBPβ to mediate the effects of cAMP on uterine stromal cell differentiation through targeting Hand2 in response to progesterone
Authors: Yu Hai‐Fan , Tao Ran , Yang Zhan‐Qing , Wang Kai , Yue Zhan‐Peng , Guo Bin
Published: June 2017

Ptn is a pleiotropic growth factor involving in the regulation of cellular proliferation and differentiation, but its biological function in uterine decidualization remains unknown. Here, we showed that Ptn was highly expressed in the decidual cells, and could induce the proliferation of uterine stromal cells and expression of Prl8a2 and Prl3c1 which were two well‐established differentiation markers for decidualization, suggesting an important role of Ptn in decidualization. In the uterine stromal cells, progesterone stimulated the expression of Ptn accompanied with an accumulation of intracellular cAMP level. Silencing of Ptn impeded the induction of progesterone and cAMP on the differentiation of uterine stromal cells. Administration of PKA inhibitor H89 resulted in a blockage of progesterone on Ptn expression. Further analysis evidenced that regulation of progesterone and cAMP on Ptn was mediated by C/EBPβ. During in vitro decidualization, knockdown of Ptn could weaken the up‐regulation of Prl8a2 and Prl3c1 elicited by C/EBPβ overexpression, while constitutive activation of Ptn reversed the repressive effects of C/EBPβ siRNA on the expression of Prl8a2 and Prl3c1. Meanwhile, Ptn might mediate the regulation of C/EBPβ on Hand2 which was a downstream target of Ptn in the differentiation of uterine stromal cells. Attenuation of Ptn or C/EBPβ by specific siRNA blocked the stimulation of Hand2 by progesterone and cAMP. Collectively, Ptn may play a vital role in the progesterone‐induced decidualization pathway.
The advantages of live/real‐time three‐dimensional echocardiograhy in the assessment of left ventricular myxoma, which causes partial left ventricular outflow tract obstruction
Authors: Kalkan Ali Kemal , Uygur Begum , Karakayalı Muammer , Kadirogulları Ersin , Erturk Mehmet
Published: June 2017

Myxomas are the most common cardiac primary tumors; however, left ventricular myxomas are extremely rare. We describe a young female patient with a giant left ventricular myxoma causing partial obstruction of the left ventricular outflow tract, who underwent successful surgical resection. Real‐time three‐dimensional echocardiography yielded incremental value to two‐dimensional echocardiography by allowing better assess of the true size, extent, attachment, and morphology of the tumor. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:273–277, 2018
Early Activation of MAPK and Apoptosis in Nutritive Embryos of Calyptraeid Gastropods
Authors: Lesoway Maryna P. , Collin Rachel , Abouheif Ehab
Published: June 2017

Investigation of alternative phenotypes, different morphologies produced by a single genome, has contributed novel insights into development and evolution. Yet, the mechanisms underlying developmental switch points between alternative phenotypes remain poorly understood. The calyptraeid snailsCrepidula navicellaandCalyptraea lichenproduce two phenotypes: viable and nutritive embryos, where nutritive embryos arrest their development after gastrulation and are ingested by their viable siblings as a form of intracapsular nutrition. Here, we investigate the activity of mitogen‐activated protein kinase (MAPK, ERK1/2) and apoptosis during early cleavage. MAPK and apoptosis, found in a previous transcriptomic study, are known to be involved in organization of other spiralian embryos and nutritive embryo development, respectively. In the modelCrepidula fornicata, MAPK activation begins at the 16‐cell stage. In contrast, we discovered inC. navicellaandC. lichenthat many embryos begin MAPK activation at the one‐cell stage. A subset of embryos shows a similar pattern of MAPK activation toC. fornicataat later stages. In all stages where MAPK is detected, the activation pattern is highly variable, frequently occurring in all quadrants or in multiple tiers of cells. We also detected apoptosis in cleaving embryos, whileC. fornicataandCrepidula lessoni, which do not produce nutritive embryos, show no signs of apoptosis during cleavage. Our results show that MAPK and apoptosis are expressed during early development in species with nutritive embryos, and raises the possibility that these processes may play a role and even interact with one another in producing the nutritive embryo phenotype.
Sustained secretion of anti‐tumor necrosis factor α monoclonal antibody from ex vivo genetically engineered dermal tissue demonstrates therapeutic activity in mouse model of rheumatoid arthritis
Authors: Zafir‐Lavie Inbal , Miari Reem , Sherbo Shay , Krispel Simi , Tal Osnat , Liran Atar , Shatil Tamar , Badinter Felix , Goltsman Haim , Shapir Nir , Benhar Itai , Neil Garry A. , Panet Amos
Published: June 2017

Background

Rheumatoid arthritis (RA) is a symmetric inflammatory polyarthritis associated with high concentrations of pro‐inflammatory, cytokines including tumor necrosis factor (TNF)‐α. Adalimumab is a monoclonal antibody (mAb) that binds TNF‐α, and is widely used to treat RA. Despite its proven clinical efficacy, adalimumab and other therapeutic mAbs have disadvantages, including the requirement for repeated bolus injections and the appearance of treatment limiting anti‐drug antibodies. To address these issues, we have developed an innovative ex vivo gene therapy approach, termed transduced autologous restorative gene therapy (TARGT), to produce and secrete adalimumab for the treatment of RA.

Methods

Helper‐dependent (HD) adenovirus vector containing adalimumab light and heavy chain coding sequences was used to transduce microdermal tissues and cells of human and mouse origin ex vivo, rendering sustained secretion of active adalimumab. The genetically engineered tissues were subsequently implanted in a mouse model of RA.

Results

Transduced human microdermal tissues implanted in SCID mice demonstrated 49 days of secretion of active adalimumab in the blood, at levels of tens of microgram per milliliter. In addition, transduced autologous dermal cells were implanted in the RA mouse model and demonstrated statistically significant amelioration in RA symptoms compared to naïve cell implantation and were similar to recombinant adalimumab bolus injections.

Conclusions

The results of the present study report microdermal tissues engineered to secrete active adalimumab as a proof of concept for sustained secretion of antibody from the novel ex vivo gene therapy TARGT platform. This technology may now be applied to a range of antibodies for the therapy of other diseases.
Making sense of organizational change: Is hindsight really 20/20?
Authors: Gover Laura , Duxbury Linda
Published: June 2017

This qualitative study explores the conceptual links between 2 different approaches to managerial cognition, sensemaking and cognitive bias, in the context of organizational change. A longitudinal case study utilizing both real‐time assessments and retrospective sensemaking data from interviews with 26 hospital employees at 3 points in time was undertaken. Patterns related to individuals' retrospective accounts and real‐time assessments were identified and used to construct 4 prototypical narratives. Data analysis revealed that organizational change was not a markedly negative experience for most informants, which is contrary to the prevailing theme in the literature. This and other findings are discussed in terms of sensemaking and cognitive bias. This study makes 2 contributions to our understanding of how individual's experience and make sense of organizational change over time as (a) little is known about how the process of change unfolds over time at the individual level and (b) extant research has not investigated the extent to which individuals' retrospective sensemaking about organizational change reflects or diverges from their real‐time assessments over the course of the change. More broadly, the study provides insights and focused advice for management researchers regarding the use of retrospective data to understand individuals' perceptions of situations that have already occurred.
Does homesickness undermine the potential of job resources? A perspective from the work–home resources model
Authors: Du Danyang , Derks Daantje , Bakker Arnold B. , Lu Chang‐qin
Published: June 2017

Rapid economic development in recent decades has resulted in a considerable increase in the number of people working far away from their home locations. Homesickness is a common reaction to the separation from home. Our research uses the work–home resources model to explain how the experience of homesickness can undermine the positive effect of job resources on job performance (i.e., task performance and safety behavior). In addition, we hypothesize that emotional stability and openness are key resources that can buffer the negative interference of homesickness with the job resources–performance relationship. We conducted two studies to test our hypotheses. Study 1 was a two‐wave longitudinal study using a migrant manufacturing worker sample. In this study, homesickness was measured at the between‐person level, and performance was measured three months later. Study 2 was a daily diary study conducted in a military trainee sample. In this study, homesickness was measured at the within‐person level to capture its fluctuations over 20 days, and daily job performance was assessed using supervisor ratings. Both studies showed evidence of the hypothesized moderating effect of homesickness and three‐way interaction effects of job resources, homesickness, and key resources (i.e., emotional stability and openness) on task performance and safety behavior.
Evaluation of NCEP‐2 and CFSR reanalysis seasonal temperature data in China using detrended fluctuation analysis
Authors: Zhao Shanshan , He Wenping , Jiang Yundi
Published: June 2017

ABSTRACT

In the present study, the performance of the National Centers for Environmental Prediction/Department of Energy (NCEP/DOE) Atmospheric Model Intercomparison Project (AMIP‐II) reanalysis (NCEP‐2) and NCEP Climate Forecast System Reanalysis (CFSR) seasonal temperature data for China was quantitatively evaluated by using detrended fluctuation analysis. The results indicate that the quality of the NCEP‐2 temperature data is the highest in autumn, while the quality of CFSR data set is the highest in summer. Both the quality of NCEP‐2 and that of CFSR temperature data is the lowest in winter. The quality is very low in eastern Tibetan Plateau and most of Xinjiang at a significance level of 0.05 for the NCEP‐2 and CFSR reanalysis temperature data including three elements: the daily average temperature (Tmean), the daily maximum temperature (Tmax) and the daily minimum temperature (Tmin). The performance of the NCEP‐2 Tmean data is poorer than those of the NCEP‐2 Tmax and Tmin data for all four seasons, while the performance of CFSR Tmean is better than that of CFSR Tmax and Tmin for all four seasons. In addition, the NCEP‐2 Tmax, Tmin and CFSR Tmean, Tmax data perform well in most of central and eastern China for all four seasons. The quality of the CFSR Tmean is better than that of the NCEP‐2 Tmean for all four seasons. However, the NCEP‐2 Tmax and Tmin data have higher credibility than that of the CFSR Tmax and Tmin data for all four seasons. Therefore, it is important to consider the reliability of the NCEP‐2 and CFSR daily temperature reanalysis data in different districts and seasons when drawing conclusions from the different reanalysis data.
Synoptic conditions leading to extremely warm periods in Western Iran
Authors: Darand M. , Garcia‐Herrera R. , Asakereh H. , Amiri R. , Barriopedro David
Published: June 2017

ABSTRACT

The purpose of this study is the characterization of the synoptic circulation patterns leading to extremely warm periods (EWPs) over the Kurdistan province of Iran. Daily maximum temperature data from 27 meteorological stations were used for the period 1962–2012. Data were interpolated to a 6 × 6 km grid using the geospatial Kriging method. EWPs were defined as a period of at least 6 consecutive days with maximum temperature above the local daily‐based 95th percentile of the 1971–2000 period, with additional criteria for spatial extension. The identified EWPs are distributed through the whole year, with maximum frequencies in winter and summer. Interestingly, the decade 1988–1997 did not record any extreme episode and summer extremes were recorded only before 1983. The associated synoptic patterns were classified into four clusters by applying the Ward's hierarchical clustering method to sea level pressure and Z500 data. Four clusters are identified: two represent warm periods in winter, one those occurring spring, especially in March, and another one mainly reflecting summer heat waves. In general, it is found that EWPs are associated with statistically significant anomalies in regional circulation. A deep trough of geopotential height in 500 hPa over North Africa and a ridge directly over the study area were the more important causes for the occurrence of EWPs. Other synoptic configurations that favour extreme periods in winter and summer include, respectively, the northward expansion of the Sudan low pressure with an associated southerly wind advection and the persistence of anticyclonic circulation at all tropospheric levels enhancing subsidence and adiabatic heating. The spring pattern is the most frequent one (nearly 48% of all cases) and reflects a southeastward extension of the subpolar low pressure that leads to the displacement of the Siberian high to south and southwestern Asia and the accompanied northward expansion of the Sudan low.
Assessing the climatic and environmental impacts of mid‐tropospheric anticyclones over Alaska
Authors: McLeod Jordan T. , Ballinger Thomas J. , Mote Thomas L.
Published: June 2017

ABSTRACT

Ongoing climatic and cryospheric changes observed throughout the greater Alaska region are interconnected and often linked to oceanic and atmospheric patterns and processes that operate on varying spatiotemporal scales. To evaluate the long‐term, mid‐tropospheric circulation field across Alaska, and possible connections to climate and environmental change in the Pacific sector of the Arctic, the Alaska Blocking Index (ABI) is developed over the domain (54°–76°N, 125°–180°W) using daily gridded 500 hPa geopotential height fields derived from the ERA‐40 (1958–1978) and ERA‐Interim (1979–2014) data sets, 1958–2014. Climatological characteristics of the seasonal and annual ABI conditions are evaluated and periods of prevalent blocking conditions are identified and subsequently linked to possible local and large‐scale forcing mechanisms. The ABI has exhibited positive trends during all seasons and annually since 1979. Many of the extreme high ABI values occurred since 2000, including the highest annual values in 2013 and 2014. Anomalous blocking patterns in all seasons are associated with diminished snow depth and sea‐ice cover, positive near‐surface air temperature anomalies, and anticyclonic flows of heat and moisture across the domain. The ABI is also shown to differ from the long‐term variability and atmospheric circulation responses associated with phases of the Pacific–North American pattern and Pacific Decadal Oscillation, revealing some notable spatial and temporal disconnects between the region‐centric, high‐latitude blocking flow and some of the predominant modes of sea surface temperature and middle tropospheric circulation variability in the Northern Hemisphere.