Data on social media use related to age, gender and trust constructs of integrity, competence, concern, benevolence and identification

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Gillian Warner-Søderholm, Andy Bertsch, Annika Søderholm
This article contains data collected from self-report surveys of respondents to measure 1) social media usage, 2) age, 3) gender and 4) trust, measured within five major trust constructs of a) Integrity, b) Competence, c) Concern, d) Benevolence and e) Identification. The data includes all instruments used, SPSS syntax, the raw survey data and descriptive statistics from the analyses. Raw data was entered into SPSS software and scrubbed using appropriate techniques in order to prepare the data for analysis. We believe that our dataset and instrument may give important insights related to computers in human behavior, and predicting trust antecedents in social media use such as age, gender, number of hour online and choice of content provider. We have also created a parsimonious five factor trust instrument developed from the extant literature for future research. Hence, this newly developed trust instrument can be used to measure trust not only in social media, but also in other areas such as healthcare, economics and investor relations, CSR, management and education. Moreover, the survey items developed to measure social media use are concise and may be applied to measure social media use in other contexts such as national cultural differences, marketing and tourism. For interpretation and discussion of the data and constructs, please see original article entitled "Who trusts social media" (Warner-Søderholm et al., 2018) [1].



https://ift.tt/2Jap1EG

Transcription profile data of phorbol esters biosynthetic genes during developmental stages in Jatropha curcas

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Nurul Jadid, Rizal Kharisma Mardika, Kristanti Indah Purwani, Erlyta Vivi Permatasari, Indah Prasetyowati, Mohammad Isa Irawan
Jatropha curcas is currently known as an alternative source for biodiesel production. Beside its high free fatty acid content, J. curcas also contains typical diterpenoid-toxic compounds of Euphorbiaceae plant namely phorbol esters. This article present the transcription profile data of genes involved in the biosynthesis of phorbol esters at different developmental stages of leaves, fruit, and seed in Jatropha curcas. Transcriptional profiles were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). We used two genes including GGPPS (Geranylgeranyl diphospate synthase), which is responsible for the formation of common diterpenoid precursor (GGPP) and CS (Casbene Synthase), which functions in the synthesis of casbene. Meanwhile, J. curcas Actin (ACT) was used as internal standard. We demonstrated dynamic of GGPPS and CS expression among different stage of development of leaves, fruit and seed in Jatropha.



https://ift.tt/2EaSMRO

Key gene co-expression modules and functional pathways involved in the pathogenesis of Graves’ disease

Publication date: Available online 31 March 2018
Source:Molecular and Cellular Endocrinology
Author(s): Xiaoqing Shao, Bin Wang, Kaida Mu, Ling Li, Qian Li, Weiwei He, Qiuming Yao, Xi Jia, Jin-an Zhang
Graves' disease (GD) is a common autoimmune thyroid disease characterized by positive thyroid stimulating hormone receptor antibody. To better understand its molecular pathogenesis, we adopted the weighted gene co-expression network analysis to reveal co-expression modules of key genes involved in the pathogenesis of GD, protein-protein interaction network analysis to identify the hub genes related to GD development and functional analyses to explore their possible functions. Our results showed that 1) a total of 2667 differentially expressed genes in our microarray study and 16 different gene co-expression modules were associated with GD, and 2) the most significant module was associated with the percentage of macrophages, T follicular helper cells and CD4⁺ memory T cells and mainly enriched in immune regulation and immune response. Overall, our study reveals several key gene co-expression modules and functional pathways involved in GD, which provides some novel insights into the pathogenesis of GD.



https://ift.tt/2Eb9Kzs

Maternal lipopolysaccharide exposure results in glucose metabolism disorders and sex hormone imbalance in male offspring

Publication date: Available online 1 April 2018
Source:Molecular and Cellular Endocrinology
Author(s): Mei Zhao, Li Yuan, Man-man Yuan, Li-li Huang, Chang Su, Yuan-hua Chen, Yu-ying Yang, Yan Hu, De-xiang Xu
An adverse intrauterine environment may be an important factor contributing to the development of type 2 diabetes in later life. The present study investigated the longitudinal effects of maternal lipopolysaccharide (LPS) exposure during the third trimester on glucose metabolism and sex hormone balance in the offspring. Pregnant mice were intraperitoneally injected with LPS (50 μg/kg) daily from gestational day (GD) 15 to GD17. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were assessed at postnatal day (PND) 60 and PND120. Sex hormones, their receptors, and metabolic enzymes (aromatase) were measured in male offspring at different phases of development (PND14: juvenile; PND35: adolescence; PND60: adulthood; and PND120: middle age). LPS-exposed male offspring exhibited glucose intolerance and insulin resistance by GTT and ITT at middle age, accompanied by an increase in fasting blood glucose and reductions in serum insulin levels and hepatic phosphorylated (p) -AKT/AKT ratio. However, glucose intolerance and insulin resistance were not observed in LPS-exposed female offspring. Maternal LPS exposure upregulated hepatic aromatase proteins and mRNA levels in male offspring at all time points. At adolescence, the testosterone/estradiol ratio (T/E2) was markedly reduced in LPS-exposed male offspring. Moreover, maternal LPS exposure significantly increased hepatic estrogen receptor (ER) α expressions and decreased hepatic androgen receptor (AR) expressions in male offspring. At adulthood, maternal LPS exposure increased serum estradiol levels, decreased serum testosterone levels and elevated hepatic ERβ expressions in male offspring. In conclusion, maternal LPS exposure upregulated aromatase expressions, followed by a reduction in the T/E2 ratio and an alteration in sex hormone receptor activity, which might be involved in the development of glucose metabolism disorders in middle-aged male offspring. This study provides a novel clue and direction to clarify the pathogenesis of maternal infection-related diabetes in male offspring.



https://ift.tt/2H0mEn9

Brief Clinical Report: Hypophosphatasia—Diagnostic Considerations and Treatment Outcomes in an Infant

Hypophosphatasia (HPP) is a rare, inherited metabolic bone disorder characterized by low serum alkaline phosphatase activity and impaired bone mineralization. Clinical manifestations and severity of symptoms vary widely in HPP, ranging from in utero death to isolated dental manifestations in adults. Treatment with enzyme replacement therapy has been reported to improve outcomes in perinatal, infantile, and childhood forms of HPP. Here, we present a case of a boy with poor linear growth, mild limb bowing, and radiographic rickets who was diagnosed with HPP before 6 months of age. Treatment with enzyme replacement therapy was initiated at 7 months of age, after which significant improvements in radiographic findings and linear growth were demonstrated. This case highlights several important challenges in the diagnosis, classification, and management of HPP.

https://ift.tt/2GDJGCD

A Rare Case of Lemierre-Like Syndrome: A Case Report and Literature Review

Lemierre's syndrome (LS) is a serious rare complication of oropharyngeal infections. It is characterized by thrombosis of internal jugular vein that rapidly progresses into sepsis and is typically caused by anaerobes. Most of the reported cases have been linked to Fusobacterium necrophorum; however, there are a handful of reported cases due to aerobes. It is primarily the disease of healthy young adults and can present in school-aged children. The early recognition and treatment of this complication results in resolution of the illness; nevertheless, there have been some concerns about chronic venous insufficiency as a long-term complication. We report a case of a 6-year-old boy, who presented with fever and headache with a history of sore throat. His blood culture was positive for group A Streptococcus (GAS) and was subsequently found to have internal jugular vein, sigmoid, and transverse sinus vein thrombosis.

https://ift.tt/2uDRGP6

Infectious Aortitis: A Life-Threatening Endovascular Complication of Nontyphoidal Salmonella Bacteremia

A 65-year-old Japanese man living in the United States presented with pyrexia and chills associated with intermittent lower abdominal and back pain for 5 days. He denied recent travel, rash, diarrhea, or rectal bleeding. Physical examination revealed spiking pyrexia, and routine laboratory tests revealed mild leukocytosis and neutrophilia. Abdominal CT with contrast showed findings highly compatible with aortitis. Comprehensive autoimmune evaluation was negative. Salmonella enterica serotype Enteritidis was isolated from blood cultures. IV antibiotics were administered, but the patient continued to experience low-grade pyrexia and mild leukocytosis, and follow-up abdominal CT showed progressive aortic inflammation. The patient therefore underwent resection of the affected aortic segment with in-situ graft replacement and lifelong suppressive antibiotics. The patient is asymptomatic with no complications at 18 weeks of follow-up. This case report illustrates that patients with infectious aortitis from nontyphoidal Salmonella may (1) present with nonspecific and nonlocalizing symptoms and signs except for sepsis; (2) have diagnostic blood cultures and abdominal CT findings; and (3) typically require aggressive, prolonged IV antibiotic therapy and surgery for potential cure of this life-threatening infection.

https://ift.tt/2J939cF

A Large Grade 5 Mobile Aortic Arch Atheromatous Plaque: Cause of Cerebrovascular Accident

Aortic atheromas (aortic atheromatous plaques) are defined by an irregular thickening of the intima ≥2 mm, and a complex plaque is defined as a protruding atheroma ≥4 mm with or without an attached mobile component. Stroke incidence is approximately 25% in patients with mobile plaques of the aortic arch and 2% in patients with quiescent nonmobile plaques. Antiplatelet agents, oral anticoagulants, and statins have been suggested in the management of atheromas. We present an 80-year-old male, with non-ST-segment elevation myocardial infarction (NSTEMI) and chronic dysarthria, found to have an acute cerebrovascular accident (CVA) secondary to embolism from a large 12 mm aortic arch plaque, treated medically with oral antiplatelet therapy, anticoagulation, and statin therapy.

https://ift.tt/2E91lNd

A numerical simulation study on the impact of smoke aerosols from Russian forest fires on the air pollution over Asia

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Qingzhe Zhu, Yuzhi Liu, Rui Jia, Shan Hua, Tianbin Shao, Bing Wang
Serious forest fires were observed over Siberia, particularly in the vast area between Lake Baikal and the Gulf of Ob, during the period of 18–27 July 2016 using Moderate Resolution Imaging Spectroradiometer (MODIS) data. The Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) satellite simultaneously detected a multitude of smoke aerosols surrounding the same area. Combing a Lagrangian Flexible Particle dispersion model (FLEXPART) executed using the Weather Research and Forecasting (WRF) model output, the transport of smoke aerosols and the quantification of impact of Russian forest fires on the Asia were investigated. From model simulations, two transport paths were determined for the smoke plumes from the Russian forest fires. The first path was directed southwestward from Russia to Central Asia and eventually Xinjiang Province of China, furthermore, the second path was directed southeastward through Mongolia to Northeast China. The FLEXPART-WRF model simulations also revealed that the smoke aerosol concentrations entering the Central Asia, Mongolia and Northern China were approximately 60–300 μg m⁻³, 40–250 μg m⁻³ and 5–140 μg m⁻³, respectively. Meanwhile, the aerosol particles from these forest fires have an impact on the air quality in Asia. With the arrival of smoke aerosols from the Russian forest fires, the near-surface PM10 concentrations over Altay, Hulunbuir and Harbin increased to 61, 146 and 42 μg m⁻³, respectively. In conclusion, smoke aerosols from Russian forest fires can variably influence the air quality over Central Asia, Mongolia and Northern China.



https://ift.tt/2Im4R9t

Development of the “Recovery from Eating Disorders for Life” Food Guide (REAL Food Guide) - a food pyramid for adults with an eating disorder

Abstract

Background

There is limited evidence to inform nutrition and dietetic interventions for individuals with eating disorders even though it is recommended as an essential part of multidisciplinary management. There is minimal guidance, an absence of standardised nutrition educational material, and no research on how best to educate patients on healthy eating and how to achieve nutrition adequacy. Therefore the REAL Food Guide was developed.

Methods

The REAL Food Guide is a pyramid with four layers and key nutrition messages beside each layer that was conceived to address gaps in nutrition education and intervention for individuals with eating disorders. Written and verbal consumer feedback was obtained from consumers receiving treatment regarding the acceptability and usefulness of the REAL Food Guide. A unique database was developed to reflect the types of foods and realistic portion sizes that patients are likely to select. This database was used for nutrition modelling to assess the nutrition adequacy of three meal patterns (meat containing, vegetarian and semi-vegan) for both weight maintenance and weight regain. Each meal pattern was compared to the Nutrient Reference Values for Australia and New Zealand.

Results

Nutritional analysis demonstrated nutritional adequacy of meal patterns for energy, macronutrients and most micronutrients when the recommended number of serves from the REAL Food Guide were assessed. All meal patterns were adequate in micronutrients except for the semi-vegan meal pattern that was inadequate in vitamin D. Feedback from individuals with eating disorders demonstrates the nutrition education tool was acceptable to them as they felt it was more helpful for their recovery than general nutrition guidelines.

Conclusion

The REAL Food Guide is a comprehensive and user-friendly guide that clinicians can use to educate patients about components of a balanced and healthy diet. The guide can educate all eating disorder clinicians, including those who are new to the field, about the basics of nutrition. Clinicians using the guide can be confident that, if followed, patient's energy and nutritional requirements will be met and important nutrition education messages are reinforced, that are tailored to the beliefs and concerns of individuals with eating disorders.

https://ift.tt/2Gr85Ms

Low expression of B-Cell-Associated protein 31 is associated with unfavorable prognosis in human colorectal cancer

Publication date: Available online 31 March 2018
Source:Pathology - Research and Practice
Author(s): Chong Ma, Ri-Ming Jin, Ke-Ji Chen, Tao Hao, Bao-Song Li, Da-Hua Zhao, Hong Jiang
Colorectal cancer (CRC) is one of the most common cancers worldwide. B cell-associated protein 31 (BAP31) was shown to participate in the apoptosis, and to be an immunotherapy target and a, prognostic factor for cancer, but its role in CRC has not been elucidated. In this study, we examined the expression of BAP31 in CRC to evaluate its prognostic values. We investigated the BAP31 expression level in 142 tissues (108 CRC and 17 paired human adjacent normal mucosa, and 17 liver metastatic CRC tissues) from 108 patients, using tissue microarray-based immunohistochemistry. We further investigated the association between BAP31 expression and overall survival (OS) and disease-free survival (DFS) in 77 CRC patients using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were applied to evaluate the potential prognostic value of BAP31 in CRC patients. BAP31 expression level was significantly increased in CRC tissues (p = 0.0014) and liver metastatic CRC tissues (p < 0.0001) compared with corresponding adjacent normal mucosa. BAP31 expression was also significantly increased in liver metastatic CRC tissues compared with corresponding primary CRC tissues (p = 0.0116). Kaplan-Meier analyses showed that CRC patients with low BAP31 expression had significantly lower survival rate (p = 0.001) and lower disease-free survival rate (P = 0.009). Furthermore, multivariate Cox analysis showed that BAP31 was an independent prognostic factor for OS (hazard ratio = 0.410, 95% confidence interval = 0.195–0.862, p = 0.019).ConclusionsOur study demonstrated that BAP31 is a potential prognostic marker for CRC patients after surgery.



https://ift.tt/2uGXPtW

Highly sensitive detection and mutational analysis of lung cancer circulating tumor cells using integrated combined immunomagnetic beads with a droplet digital PCR chip

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Wanlei Gao, Ting Huang, Haojun Yuan, Jun Yang, Qinghui Jin, Chunping Jia, Guoxin Mao, Jianlong Zhao
Circulating tumor cells (CTCs) have become an important biomarker for liquid biopsy to monitor tumor progression and indicate response to therapies. Many epithelial cellular adhesion molecule (EpCAM) dependent CTC isolation methods have been developed, which have a limitation for low EpCAM expressed tumor cells. In an effort to overcome these drawbacks, we developed combined immunomagnetic beads (EpCAM, Mucin1 and epidermal growth factor receptor) to sensitively isolate CTCs for immunofluorescence analysis and genetic characterization. With this combined immunomagnetic beads, 93.35% H446 cells from spiked blood sample can be recovered. We were able to detect CTCs in 127 among 143 patients included in the study (88.8%). Some CTC clusters were captured with the combined magnetic beads system. In 17 of them, CTCs after chemotherapy significantly decreased compared to that before chemotherapy (4.42 (± 3.94) vs. 12 (± 7)/mL, P = 0.002). For subsequent genetic characterization of CTCs, 2 of 6 samples, using a droplet digital PCR (ddPCR) chip, have detectable EGFR L858R mutation in the cells enriched with the combined immunomagnetic beads. In conclusion, this method integrating the combined immunomagnetic beads and the ddPCR chip for CTCs detection can be of potential application in terms of diagnosis, therapeutic evaluation and personalized medicine in lung cancer.

Graphical abstract

https://ift.tt/2GJcfi0

Characterization of an array of honeys of different types and botanical origins through fluorescence emission based on LEDs

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Miguel Lastra-Mejías, Albertina Torreblanca-Zanca, Regina Aroca-Santos, John C. Cancilla, Jesús.G. Izquierdo, José S. Torrecilla
A set of 10 honeys comprising a diverse range of botanical origins have been successfully characterized through fluorescence spectroscopy using inexpensive light-emitting diodes (LEDs) as light sources. It has been proven that each LED-honey combination tested originates a unique emission spectrum, which enables the authentication of every honey, being able to correctly label it with its botanical origin. Furthermore, the analysis was backed up by a mathematical analysis based on partial least square models which led to a correct classification rate of each type of honey of over 95%. Finally, the same approach was followed to analyze rice syrup, which is a common honey adulterant that is challenging to identify when mixed with honey. A LED-dependent and unique fluorescence spectrum was found for the syrup, which presumably qualifies this approach for the design of uncomplicated, fast, and cost-effective quality control and adulteration assessing tools for different types of honey.

Graphical abstract

https://ift.tt/2GJ4hVW

Comparative evaluation of seven commercial products for human serum enrichment/depletion by shotgun proteomics

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Salvatore Pisanu, Grazia Biosa, Laura Carcangiu, Sergio Uzzau, Daniela Pagnozzi
Seven commercial products for human serum depletion/enrichment were tested and compared by shotgun proteomics. Methods were based on four different capturing agents: antibodies (Qproteome Albumin/IgG Depletion kit, ProteoPrep Immunoaffinity Albumin and IgG Depletion Kit, Top 2 Abundant Protein Depletion Spin Columns, and Top 12 Abundant Protein Depletion Spin Columns), specific ligands (Albumin/IgG Removal), mixture of antibodies and ligands (Albumin and IgG Depletion SpinTrap), and combinatorial peptide ligand libraries (ProteoMiner beads), respectively. All procedures, to a greater or lesser extent, allowed an increase of identified proteins. ProteoMiner beads provided the highest number of proteins; Albumin and IgG Depletion SpinTrap and ProteoPrep Immunoaffinity Albumin and IgG Depletion Kit resulted the most efficient in albumin removal; Top 2 and Top 12 Abundant Protein Depletion Spin Columns decreased the overall immunoglobulin levels more than other procedures, whereas specifically gamma immunoglobulins were mostly removed by Albumin and IgG Depletion SpinTrap, ProteoPrep Immunoaffinity Albumin and IgG Depletion Kit, and Top 2 Abundant Protein Depletion Spin Columns. Albumin/IgG Removal, a resin bound to a mixture of protein A and Cibacron Blue, behaved less efficiently than the other products.

Graphical abstract

https://ift.tt/2GFBBNL

The facile approaches to asymmetric modification of glassy biconical microchannel wall with silver, copper or gold

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Fengxia Chang, Yang Yang, Xia Xie, Meixian Li, Zhiwei Zhu
The modification of inner surface has significant influence in the properties of the nano or microchannel based on various materials, especially for the ionic current rectification (ICR) that arises from the selective interaction between ions in solution and the inner surface. Herein, we demonstrate a simple strategy to asymmetrically modify the inner wall of a glassy biconical microchannel with silver, copper or gold by means of silver mirror reaction and polydopamine platform, respectively. And the bidirectional ionic current rectification phenomena were observed in all of the modified biconical microchannels. All of the modification methods are simple, facile and low-cost, and can be applied in the modification of other glassy pipettes.

Graphical abstract

https://ift.tt/2uzwsC3

Simultaneous voltammetry detection of dopamine and uric acid in human serum and urine with a poly(procaterol hydrochloride) modified glassy carbon electrode

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Dexian Kong, Qizhao Zhuang, Yejian Han, Lanping Xu, Zeming Wang, Lili Jiang, Jinwei Su, Chun-Hua Lu, Yuwu Chi
In the present study, procaterol hydrochloride (ProH) was successfully electropolymerized onto a glass carbon electrode (GCE) with simply cyclic voltammetry scans to construct a poly(procaterol hydrochloride) (p-ProH) membrane modified electrode. Compared with the bare GCE, much higher oxidation peak current responses and better peak potentials separation could be obtained for the simultaneous oxidation of dopamine (DA) and uric acid (UA), owning to the excellent electrocatalytic ability of the p-ProH membrane. And it's based on that a square wave voltammetry (SWV) method was developed to selective and simultaneous measurement of DA and UA. Under the optimum conditions, the linear dependence of oxidation peak current on analyte concentrations were found to be 1.0–100 μmol/L and 2–100 μmol/L, giving detection limits of 0.3 μmol/L and 0.5 μmol/L for DA and UA, separately. The as prepared modified electrode shows simplicity in construction with the merits of good reproducibility, high stability, passable selectivity and nice sensitivity. Finally, the proposed p-ProH membrane modified electrode was successfully devoted to the detection of DA and UA in biological fluids such as human serum and urine with acceptable results.

Graphical abstract

https://ift.tt/2uGUWt6

The polystyrene-divinylbenzene stationary phase hybridized with oxidized nanodiamonds for liquid chromatography

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Zhongping Huang, Peng Yao, Qiulian Zhu, Lili Wang, Yan Zhu
A novel polystyrene-divinylbenzene microspheres hybridized with oxidized nanodiamonds (PS-DVB-OND) was synthesized by the method of seed swelling and polymerization. The oxidized nanodiamonds (OND) were characterized by Fourier transform infrared (FTIR) spectra, X-ray phtoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), X-ray diffraction (XRD). PS-DVB-OND particles were characterized by scanning electron microscopy (SEM) and transmission electron microscope (TEM). The result suggested that OND were successfully embedded into the polymer microspheres with the diameter of 6 ± 2 µm. Compared to polystyrene-divinylbenzene (PS-DVB) microspheres, PS-DVB-OND microspheres could tolerate higher pressure. The PS-DVB-OND microspheres were used as stationary phase of reversed-phase liquid chromatography directly and anion-exchangers after further quaternized with methylamine and 1,4-butanediol diglycidyl ether. Reversed-phase liquid chromatographic performance of PS-DVB-OND beads was investigated through separating six benzenes such as toluene, benzaldehyde, phenol, benzoic acid, 1,4-hydroquinone and methyl p-hydroxybenzoate. Inorganic anions such as F^-, Cl^-, NO2^-, Br^-, NO3^-, HPO4^2- and SO4^2-, were baseline separated on the anion exchangers of PS-DVB-OND microspheres. The result suggested that the prepared PS-DVB-OND microspheres have the potential as liquid chromatographic stationary phase under high pressure and extremely pH conditions.

Graphical abstract

https://ift.tt/2uEmZtb

Simultaneous competitive and sandwich formats multiplexed immunoassays based on ICP-MS detection

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Yuqing Zhang, Gongwei Sun, Yi Zhang, Biao Huang, Zhi Xing, Sichun Zhang, Xinrong Zhang
Inductively Coupled Plasma Mass Spectrometry (ICP-MS) based immunoassay method has been proposed in multiple immunoassays but has not been used in competitive and sandwich formats immunoassay simultaneously. The two immunoassays were usually conducted separately in clinical field depending on the size and the amount of binding sites of targets. We proposed an immunoassay method based on magnetic beads and ICP-MS detection that could be suitable for both small and large molecules. The functionalized magnetic beads were added to capture the immune complex after immune reaction. In this way, thyrotropin and free thyroid hormone can be captured, separated and then detected according to the elemental tags by ICP-MS simultaneously. The new method was evaluated by comparing the results with time resolved fluorescence immunoassays (TRFIA). The dynamic ranges of TSH and FT4 were 0.16–105 mU/L and 3.5–65 pmol/L, respectively. The limits of detections were 0.06 mU/L for TSH and 1.59 pmol/L for FT4. And the relative standard deviations (RSD) of TSH and FT4 were 4.64% at 2.5 mU/L and 1.87% at 5.85 pmol/L. This immunoassay method enables the determination of small and large biomolecules simultaneously via competitive and sandwich immunoassay formats.

Graphical abstract

https://ift.tt/2uJ9eJR

Multiple roles of lymphatic vessels in tumor progression

Qiaoli Ma | Lothar C Dieterich | Michael Detmar

https://ift.tt/2pTZNlS

Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering

May Daher | Katayoun Rezvani

https://ift.tt/2GspGzm

Plasticity and biological diversity of myeloid derived suppressor cells

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Kerem Ben-Meir, Nira Twaik, Michal Baniyash
Myeloid derived suppressor cells (MDSCs) are immature myeloid cells characterized by diverse phenotypes and functions. They impair effector functions of immune cells and promote tumor growth, angiogenesis, and tissue damage. In pathologies characterized by chronic inflammation, MDSCs are arrested in their immature state and migrate from the bone marrow to the periphery and to the site of inflammation, where they mediate immunosuppression. When reaching new environments, which exhibit a different array of cytokines, chemokines, and pro-inflammatory mediators, MDSCs sense and adapt to the altered micro-environment by virtue of acquiring different suppressive features/functions that involve changing their cell fate, surface receptors, metabolism and intracellular as well as secreted molecules. This review summarizes some of the latest publications highlighting various layers of MDSC plasticity in relation to different pathologies. We discuss treatments capitalizing on MDSC plasticity aimed at combating MDSCs or manipulating their suppressive activity for improved therapy.



https://ift.tt/2GZpQ2g

The safety and risk factors of revision adenoidectomy in children and adolescents: A nationwide retrospective population-based cohort study

To investigate the safety of adenoidectomy and risk factors of re-adenoidectomy, and intend to provide evidence-based information to clinicians for further consideration.

https://ift.tt/2pWg8pW

Multimodality Surgical Approach in Management of Laryngotracheal Stenosis

Introduction. Postintubation laryngotracheal stenosis requires a precise diagnosis and an experienced operator in both endoscopic and surgical treatment. This report presents surgically treated cases of laryngotracheal stenosis secondary to long-term intubation/tracheostomy with review of the literature. Materials and Methods. In this retrospective study, we present 5 cases (a 23-year-old male, 13-year-old male, 22-year-old male, 19-year-old male, and 33-year-old female) of postintubation/tracheostomy laryngotracheal (glottic/subglottic) stenosis in the years 2016 and 2017. Each patient was managed differently. Intubation characteristics, localization of stenosis, surgical technique and material, postoperative complications, and survival of patients were recorded. Results. The site of stenosis was in the subglottis in 4 patients and glottis in 1 patient. The mean length of the stenosis was greater in the postintubation group. Postintubation stenosis had a mean duration of intubation of 6.8 days, compared to 206.25 days of cannulation following tracheostomies. Each patient underwent an average of 2 procedures during their treatment course. One patient underwent open surgical anastomosis because of recurrent subglottic stenosis after multiple treatments. Phonation improved immediately in almost all except in the patient who underwent only endoscopic dilatation. Discussion. The reasons for laryngeal stenosis and its delayed diagnosis have been reviewed from the literature. Suture tension should be appropriate, and placement of the suture knot outside the trachea minimizes formation of granulation tissue. The published reports suggest that resection by endoscopy with laser and open technique resection and primary anastomosis are the best treatment modality so far as the long-term results are concerned. Conclusion. Resection of stenotic segment by open surgical anastomosis and laser-assisted resection is a safe option for the treatment of subglottic stenosis following intubation without the need for repeated dilation. Endoscopic dilation can be reserved for unfit patients.

https://ift.tt/2GMy4xf

Spinal Accessory Nerve Duplication: A Case Report and Literature Review

Aim of the present study is to expand our knowledge of the anatomy of the 11th cranial nerve and discuss the clinical importance and literature pertaining to accessory nerve duplication. We present one case of duplicated spinal accessory nerve in a patient undergoing neck dissection for oral cavity cancer. The literature review confirms the extremely rare diagnosis of a duplicated accessory nerve. Its clinical implication is of great importance. From this finding, a further extension to our knowledge of the existing anatomy is proposed.

https://ift.tt/2uCOanZ

EEG-based neglect assessment: A feasibility study

Publication date: Available online 31 March 2018
Source:Journal of Neuroscience Methods
Author(s): Aya Khalaf, Jessica Kersey, Safaa Eldeeb, Gazihan Alankus, Emily Grattan, Laura Waterstram, Elizabeth Skidmore, Murat Akcakaya
BackgroundSpatial neglect (SN) is a neuropsychological syndrome that impairs automatic attention orienting to stimuli in the contralesional visual space of stroke patients. SN is commonly assessed using paper and pencil tests. Recently, computerized tests have been proposed to provide a dynamic assessment of SN. However, both paper- and computer-based methods have limitations.New methodElectroencephalography (EEG) shows promise for overcoming the limitations of current assessment methods The aim of this work is to introduce an objective passive BCI system that records EEG signals in response to visual stimuli appearing in random locations on a screen with a dynamically changing background. Our preliminary experimental studies focused on validating the system using healthy participants with intact brains rather than employing it initially in more complex environments with patients having cortical lesions. Therefore, we designed a version of the test in which we simulated SN by hiding target stimuli appearing on the left side of the screen so that the subject's attention is shifted to the right side.ResultsResults showed that there are statistically significant differences between EEG responses due to right and left side stimuli reflecting different processing and attention levels towards both sides of the screen. The system achieved average accuracy, sensitivity and specificity of 74.24%, 75.17% and 71.36% respectively.Comparison with existing methodsThe proposed test can examine both presence and severity of SN, unlike traditional paper and pencil tests and computer-based methods.ConclusionsThe proposed test is a promising objective SN evaluation method.



https://ift.tt/2GomJE9

Methodology and effects of repeated intranasal delivery of DNSP-11 in awake Rhesus macaques

Publication date: Available online 31 March 2018
Source:Journal of Neuroscience Methods
Author(s): M.J. Stenslik, A. Evans, F. Pomerleau, R. Weeks, P. Huettl, E. Foreman, J. Turchan-Cholewo, A. Andersen, W.A. Cass, Z. Zhang, R.C. Grondin, D.M. Gash, G.A. Gerhardt, L.H. Bradley
BackgroundTo determine if the intranasal delivery of neuroactive compounds is a viable, long-term treatment strategy for progressive, chronic neurodegenerative disorders, such as Parkinson's disease (PD), intranasal methodologies in preclinical models comparable to humans are needed.New MethodWe developed a methodology to evaluate the repeated intranasal delivery of neuroactive compounds on the non-human primate (NHP) brain, without the need for sedation. We evaluated the effects of the neuroactive peptide, DNSP-11 following repeated intranasal delivery and dose-escalation over the course of 10-weeks in Rhesus macaques. This approach allowed us to examine striatal target engagement, safety and tolerability, and brain distribution following a single ¹²⁵I-labeled DNSP-11 dose.ResultsOur initial data support that repeated intranasal delivery and dose-escalation of DNSP-11 resulted in bilateral, striatal target engagement based on neurochemical changes in DA metabolites-without observable, adverse behavioral effects or weight loss in NHPs. Furthermore, a ¹²⁵I-labeled DNSP-11 study illustrates diffuse rostral to caudal distribution in the brain including the striatum-our target region of interest.Comparison with Existing MethodsThe results of this study are compared to our experiments in normal and 6-OHDA lesioned rats, where DNSP-11 was repeatedly delivered intranasally using a micropipette with animals under light sedation.ConclusionsThe results from this proof-of-concept study support the utility of our repeated intranasal dosing methodology in awake Rhesus macaques, to evaluate the effects of neuroactive compounds on the NHP brain. Additionally, results indicate that DNSP-11 can be safely and effectively delivered intranasally in MPTP-treated NHPs, while engaging the DA system.



https://ift.tt/2IjzThY

Automatic cardiac cycle determination directly from EEG-fMRI data by multi-scale peak detection method

Publication date: Available online 31 March 2018
Source:Journal of Neuroscience Methods
Author(s): Chung-Ki Wong, Qingfei Luo, Vadim Zotev, Raquel Phillips, Kam Wai Clifford Chan, Jerzy Bodurka
BackgroundIn simultaneous EEG-fMRI, identification of the period of cardioballistic artifact (BCG) in EEG is required for the artifact removal. Recording the electrocardiogram (ECG) waveform during fMRI is difficult, often causing inaccurate period detection.New MethodSince the waveform of the BCG extracted by independent component analysis (ICA) is relatively invariable compared to the ECG waveform, we propose a multiple-scale peak-detection algorithm to determine the BCG cycle directly from the EEG data. The algorithm first extracts the high contrast BCG component from the EEG data by ICA. The BCG cycle is then estimated by band-pass filtering the component around the fundamental frequency identified from its energy spectral density, and the peak of BCG artifact occurrence is selected from each of the estimated cycle.ResultsThe algorithm is shown to achieve a high accuracy on a large EEG-fMRI dataset. It is also adaptive to various heart rates without the needs of adjusting the threshold parameters. The cycle detection remains accurate with the scan duration reduced to half a minute. Additionally, the algorithm gives a figure of merit to evaluate the reliability of the detection accuracy.Comparison with ExistingethodThe algorithm is shown to give a higher detection accuracy than the commonly used cycle detection algorithm fmrib_qrsdetect implemented in EEGLAB.ConclusionsThe achieved high cycle detection accuracy of our algorithm without using the ECG waveforms makes possible to create and automate pipelines for processing large EEG-fMRI datasets, and virtually eliminates the need for ECG recordings for BCG artifact removal.



https://ift.tt/2GmKSed

Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats

Publication date: June 2018
Source:Biomaterials, Volume 168
Author(s): Rui Li, Yiyang Li, Yanqing Wu, Yingzheng Zhao, Huanwen Chen, Yuan Yuan, Ke Xu, Hongyu Zhang, Yingfeng Lu, Jian Wang, Xiaokun Li, Xiaofeng Jia, Jian Xiao
Peripheral nerve injury (PNI) is a major burden to society with limited therapeutic options, and novel biomaterials have great potential for shifting the current paradigm of treatment. With a rising prevalence of chronic illnesses such as diabetes mellitus (DM), treatment of PNI is further complicated, and only few studies have proposed therapies suitable for peripheral nerve regeneration in DM. To provide a supportive environment to restore structure and/or function of nerves in DM, we developed a novel thermo-sensitive heparin-poloxamer (HP) hydrogel co-delivered with basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in diabetic rats with sciatic nerve crush injury. The delivery vehicle not only had a good affinity for large amounts of growth factors (GFs), but also controlled their release in a steady fashion, preventing degradation in vitro. In vivo, compared with HP hydrogel alone or direct GFs administration, GFs-HP hydrogel treatment is more effective at facilitating Schwann cell (SC) proliferation, leading to an increased expression of nerve associated structural proteins, enhanced axonal regeneration and remyelination, and improved recovery of motor function (all p < 0.05). Our mechanistic investigation also revealed that these neuroprotective and neuroregenerative effects of the GFs-HP hydrogel may be associated with activations of phosphatidylinositol 3 kinase and protein kinase B (PI3K/Akt), janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways. Our work provides a promising therapy option for peripheral nerve regeneration in patients with DM.



https://ift.tt/2H1t31s

Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats

Publication date: June 2018
Source:Biomaterials, Volume 168
Author(s): Rui Li, Yiyang Li, Yanqing Wu, Yingzheng Zhao, Huanwen Chen, Yuan Yuan, Ke Xu, Hongyu Zhang, Yingfeng Lu, Jian Wang, Xiaokun Li, Xiaofeng Jia, Jian Xiao
Peripheral nerve injury (PNI) is a major burden to society with limited therapeutic options, and novel biomaterials have great potential for shifting the current paradigm of treatment. With a rising prevalence of chronic illnesses such as diabetes mellitus (DM), treatment of PNI is further complicated, and only few studies have proposed therapies suitable for peripheral nerve regeneration in DM. To provide a supportive environment to restore structure and/or function of nerves in DM, we developed a novel thermo-sensitive heparin-poloxamer (HP) hydrogel co-delivered with basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in diabetic rats with sciatic nerve crush injury. The delivery vehicle not only had a good affinity for large amounts of growth factors (GFs), but also controlled their release in a steady fashion, preventing degradation in vitro. In vivo, compared with HP hydrogel alone or direct GFs administration, GFs-HP hydrogel treatment is more effective at facilitating Schwann cell (SC) proliferation, leading to an increased expression of nerve associated structural proteins, enhanced axonal regeneration and remyelination, and improved recovery of motor function (all p < 0.05). Our mechanistic investigation also revealed that these neuroprotective and neuroregenerative effects of the GFs-HP hydrogel may be associated with activations of phosphatidylinositol 3 kinase and protein kinase B (PI3K/Akt), janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways. Our work provides a promising therapy option for peripheral nerve regeneration in patients with DM.



https://ift.tt/2H1t31s

A Systematic Review to Explore the Feasibility of a Behavioural Sleep Intervention for Insomnia in Children with Neurodevelopmental Disorders: A Transdiagnostic Approach

Children with neurodevelopmental disorders (NDD) are at high risk for sleep problems, especially insomnia. It is currently not known whether behavioural sleep interventions developed for typically developing (TD) children are effective for children with NDD, and if interventions need to be modified for each diagnostic group. The aim of this systematic review was to identify and evaluate commonalities, trends in outcomes, and the methodological quality of parent-delivered behavioural sleep interventions for children with NDD, specifically Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Cerebral Palsy, and Fetal Alcohol Spectrum Disorder.

https://ift.tt/2pVoDkr

Safety and Efficacy of a Halobetasol/Tazarotene Fixed Combination in the Treatment of Moderate-to-Severe Plaque Psoriasis: Results of two Phase 3 randomized controlled trials

Topical corticosteroids are the mainstay of psoriasis treatment; long-term safety concerns limit use. Combination with tazarotene may optimize efficacy, minimizing safety/tolerability concerns, In patients with moderate-to-severe plaque psoriasis treated with HP/TAZ lotion, improvement is noted within 2 weeks with few adverse effects observed after 8 weeks., HP/TAZ lotion may provide a realistic topical option for psoriasis management

https://ift.tt/2J9TjHF

Effects of left dlPFC modulation on social cognitive processes following food sampling

Publication date: 1 July 2018
Source:Appetite, Volume 126
Author(s): Peter A. Hall, Cassandra J. Lowe, Adrian B. Safati, Huaqi Li, Emilia B. Klassen, Amer M. Burhan
BackgroundThe dorsolateral prefrontal cortex (dlPFC) plays a central role in the inhibition of eating, but also the modulation of conscious thought processes that might precede, accompany or follow initial food tasting. The latter might be particularly important to the extent that post-tasting cognitions may drive prolonged eating beyond the satiety point. However, we know very little about the effect of the dlPFC on conation following initial food sampling. This investigation compared the effects of dlPFC attenuation using repetitive transcranial magnetic stimulation (rTMS) on social cognition following (Study 1) and prior to (Study 2) a food consumption opportunity.MethodsIn Study 1, participants (N = 21; Mage = 21 years) were randomized to active or sham continuous theta-burst stimulation (cTBS; an inhibitory variant of rTMS) targeting the left dlPFC followed by an interference task. Participants subsequently completed measures of attitudes, norms and perceived control following a mock taste test. In Study 2, (N = 36, Mage = 21 years) a second sample of right handed participants (N = 37; Mage = 21 years) were assigned to active or sham cTBS, followed by an interference task and two measures of attitudes (implicit and explicit), both assessed prior to the same taste test paradigm.ResultsIn Study 1, findings revealed a reliable effect of cTBS on post-tasting attitudes (t(1,19) = 3.055, p = .007; d = 1.34), such that attitudes towards calorie dense snack foods were significantly more positive following active stimulation than following sham stimulation. Similar effects were found for social norms (t(1,19) = 3.024, p = .007, d = 1.31) and perceived control (t(1,20) = 19.247, p < .001, d = 0.50). In Study 2, no effects of cTBS were observed on pre-consumption attitudes, despite reliable effects on interference scores and subsequent consumption.ConclusionsThe left dlPFC may selectively modulate facilitative social cognition following initial food sampling (but not pre-consumption).



https://ift.tt/2pQm8kf

Observance du traitement de fond dans l’asthme persistant de l’adulte en pratique courante

Publication date: Available online 30 March 2018
Source:Revue des Maladies Respiratoires
Author(s): P. Devillier, C. Ghasarossian, P. Terrioux, M. Schiratti, E. Leutenegger
IntroductionL'objectif de cette étude était d'évaluer, en pratique courante, par une méthode originale, l'observance du traitement de fond de patients asthmatiques.MéthodesCette étude observationnelle a été conduite en France auprès de patients adultes traités depuis au moins trois mois pour asthme persistant. L'observance était évaluée d'après les données du relevé de consommation (RC) de l'assurance maladie, par quantification de la concordance entre prescription et délivrance des traitements en pharmacie, et par l'autoquestionnaire validé de Morisky.RésultatsQuatre-vingt-un médecins qualifiés en pneumologie ou généralistes ont inclus 488 patients, d'âge moyen de 51 ans avec 55 % de femmes. Le RC était disponible pour 35 % des patients, mais le questionnaire de Morisky (85 % des patients) montrait une observance similaire entre les patients avec ou sans RC. Le taux de bons observants (observance ≥80 %) était de 51 % selon le RC et de 38 % selon le questionnaire de Morisky. Parmi les facteurs classiquement prédictifs, seule l'obésité était retrouvée chez les mauvais observants (19 % vs 7 %, p<0,05), qui présentaient une symptomatologie plus marquée et un taux de non-contrôle plus important (21,7 % vs 5,7 %, p<0,01).ConclusionsLe RC s'est avéré un outil utile pour obtenir une mesure quantitative de l'observance en pratique courante.IntroductionThe aim of the study was to assess, compliance with maintenance treatment in patients with persistent asthma in clinical practice.MethodsThis observational, cross-sectional, prospective, multicenter study was conducted in metropolitan France on patients with persistent asthma under the care of a representative sample of general practitioners and pneumologists. Compliance was determined via access to the Health Insurance database allowing comparison between the actual consumption of medications and the corresponding theoretical consumption related to prescription. Additional compliance data were obtained using the validated Morisky questionnaire.ResultsEighty one physicians included 488 patients, mean age of 51 years, 55% women. The statement of consumption (SC) was available for 35% of patients however the Morisky questionnaire (present for 85% of patients) showed a similar compliance between patients with or without SC. The good compliance rate (compliance ≥80%) was observed in 51% based on the SC and in 38% based on the Morisky questionnaire. Among possible predictive factors, only obesity was associated with a bad compliance (19% vs 7%, P<0.05). Patients with poor compliances displayed more severe symptoms and a higher rate of non-control (21.7% vs 5.7%, P<0.01).ConclusionsThe statement of consumption is a useful tool to provide quantitative measurement of compliance in daily practice.



https://ift.tt/2uCC9in

Oxidatively-induced DNA damage and base excision repair in euthymic patients with bipolar disorder

Publication date: Available online 30 March 2018
Source:DNA Repair
Author(s): Deniz Ceylan, Gamze Tuna, Güldal Kirkali, Zeliha Tunca, Güneş Can, Hidayet Ece Arat, Melis Kant, Miral Dizdaroglu, Ayşegül Özerdem
Oxidatively-induced DNA damage has previously been associated with bipolar disorder. More recently, impairments in DNA repair mechanisms have also been reported. We aimed to investigate oxidatively-induced DNA lesions and expression of DNA glycosylases involved in base excision repair in euthymic patients with bipolar disorder compared to healthy individuals. DNA base lesions including both base and nucleoside modifications were measured using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry with isotope-dilution in DNA samples isolated from leukocytes of euthymic patients with bipolar disorder (n = 32) and healthy individuals (n = 51). The expression of DNA repair enzymes OGG1 and NEIL1 were measured using quantitative real-time polymerase chain reaction. The levels of malondialdehyde were measured using high performance liquid chromatography. Seven DNA base lesions in DNA of leukocytes of patients and healthy individuals were identified and quantified. Three of them had significantly elevated levels in bipolar patients when compared to healthy individuals. No elevation of lipid peroxidation marker malondialdehyde was observed. The level of OGG1 expression was significantly reduced in bipolar patients compared to healthy individuals, whereas the two groups exhibited similar levels of NEIL1 expression. Our results suggest that oxidatively-induced DNA damage occurs and base excision repair capacity may be decreased in bipolar patients when compared to healthy individuals. Measurement of oxidatively-induced DNA base lesions and the expression of DNA repair enzymes may be of great importance for large scale basic research and clinical studies of bipolar disorder.



https://ift.tt/2H47AF6

Activation of the Monocytic α7 Nicotinic Acetylcholine Receptor Modulates Oxidative Stress and Inflammation-associated Development of Coronary Artery Spasm via a p38 MAP-Kinase signaling-dependent pathway

Publication date: Available online 31 March 2018
Source:Free Radical Biology and Medicine
Author(s): Ming-Yow Hung, Yi-Hong Wu, Oluwaseun Adebayo Bamodu, Xi Chen, Yen-Kuang Lin, Patrick Hu, Nen-Chung Chang, Jong-Hwei Su Pang, Chi-Tai Yeh
ObjectiveSmoking and high-sensitivity C-reactive protein (hs-CRP) are risk factors for coronary artery spasm (CAS), which is characterized by the increased interleukin-6 (IL-6) level and monocyte counts; however, limited data are available regarding the role of cigarette-embedded nicotine in the modulation of monocytic inflammatory activity in CAS.ApproachWe investigated and elucidated the putative roles and associations of nicotine, monocytic IL-6, α7 nicotinic acetylcholine receptor (α7-nAChR), and CRP in CAS development.ResultsWe demonstrated that a significantly increased α7-nAChR (p = 0.001) and IL-6 (p = 0.0036) messenger RNA (mRNA) expression in the serum of patients with CAS. Serum hs-CRP levels exhibited a strong positive correlation with the monocytic mRNA expression of α7-nAChR (r = 0.71, p < 0.001) and IL-6 (r = 0.49, p =0.006). The α7-nAChR and IL-6 expression levels of the CAS group were also positively correlated (r = 0.63, p < 0.001). Compared with the untreated controls, THP-1 cells and patient-derived monocytes treated with different concentrations of CRP displayed significantly increased expression levels of α7-nAChR mRNA and protein (p = 0.0054), in a dose-dependent manner. We also demonstrated that compared with the IL-6 expression elicited by CRP alone (p = 0.0489), the CRP-induced rise in monocytic IL-6 mRNA and protein expression in the presence of nicotine (p = 0.0002), is mediated by α7-nAChR activation and the deregulation of the human p38 mitogen-activated protein kinases (MAPK) signaling pathway.ConclusionsOur data demonstrate that the elevated monocytic IL-6 and α7-nAChR mRNA and protein expression levels are associated with the interaction between nicotine and CRP positively modulates CAS development. Our study suggests the potential role of α7-nAChR mRNA and/or protein expression as a diagnostic biomarker for CAS.

Graphical abstract

https://ift.tt/2J8Vb33

Designing Aptamers which Respond to Intracellular Oxidative Stress and Inhibit Aggregation of Mutant Huntingtin

Publication date: Available online 30 March 2018
Source:Free Radical Biology and Medicine
Author(s): Kinjal A. Patel, Thulasi Kolluri, Swati Jain, Ipsita Roy
Targeted expression of a therapeutic agent is a major bottleneck in designing a drug delivery system. Protein aggregation and elevated oxidative stress are associated with the onset of many neurodegenerative disorders, including Huntington's disease (HD). An oxidative stress-inducible promoter, i.e. Thioredoxin 2, was employed to design a sensor for protein aggregation. RNA aptamers specific for mutant huntingtin were expressed only in cells where aggregation of mutant huntingtin occurred. A nine-fold increase in RNA expression was seen when aptamer sequences were cloned under the Trx2 promoter. Expression of aptamer resulted in reduced protein aggregation and decreased oxidative stress, which, in turn, reduced the expression of aptamers by two-fold. Reduction in aggregation led to increased cell survival. The aptamers were not expressed in cells expressing wild-type huntingtin in the soluble form. This rational and simple design will allow the use of this construct for the targeted expression of other therapeutic nucleic acid molecules as well.

Graphical abstract

https://ift.tt/2E6tGnf

NADPH-dependent and -independent Disulfide Reductase Systems

Publication date: Available online 30 March 2018
Source:Free Radical Biology and Medicine
Author(s): Colin G. Miller, Arne Holmgren, Elias S.J. Arnér, Edward E. Schmidt
Over the past seven decades, research on autotrophic and heterotrophic model organisms has defined how the flow of electrons ("reducing power") from high-energy inorganic sources, through biological systems, to low-energy inorganic products like water, powers all of Life's processes. Universally, an initial major biological recipient of these electrons is nicotinamide adenine dinucleotide-phosphate, which thereby transits from an oxidized state (NADP⁺) to a reduced state (NADPH). A portion of this reducing power is then distributed via the cellular NADPH-dependent disulfide reductase systems as sequential reductions of disulfide bonds. Along the disulfide reduction pathways, some enzymes have active sites that use the selenium-containing amino acid, selenocysteine, in place of the common but less reactive sulfur-containing cysteine. In particular, the mammalian/metazoan thioredoxin systems are usually selenium-dependent as, across metazoan phyla, most thioredoxin reductases are selenoproteins. Among the roles of the NADPH-dependent disulfide reductase systems, the most universal is that they provide the reducing power for the production of DNA precursors by ribonucleotide reductase (RNR). Some studies, however, have uncovered examples of NADPH-independent disulfide reductase systems that can also support RNR. These systems are summarized here and their implications are discussed.

Graphical abstract

https://ift.tt/2E9uKGI

Editorial Board

Publication date: April 2018
Source:Free Radical Biology and Medicine, Volume 118





https://ift.tt/2J8V6fL

Clinical and Prognostic Significance of CSF Opening and Closing Pressures in Pediatric Pseudotumor Cerebri Syndrome

Publication date: Available online 30 March 2018
Source:Pediatric Neurology
Author(s): Shannon J. Beres, Claire A. Sheldon, Chantal J. Boisvert, Christina L. Szperka, Grace L. Paley, Evanette K. Burrows, Marianne R. Chilutti, Geraldine W. Liu, Shana E. McCormack, Grant T. Liu
BACKGROUNDThe purpose of this study was to determine the prognostic utility of closing pressure and volume of cerebrospinal fluid (CSF) removed with respect to papilledema resolution and headache improvement in pediatric pseudotumor cerebri syndrome (PTCS).STUDY DESIGNThis is a retrospective observational study of 93 children with definite PTCS. The primary outcome measure was time to resolution of papilledema and the secondary outcome measure was time to resolution of headache.RESULTSThere were no significant differences in gender, age, or BMI-Z observed between subjects with (N=35) and without (N=58) documented closing pressure. The median time to resolution of papilledema was not statistically different between the children above or equal to and those below the closing pressure median (170 mm of CSF, n=31, p = 0.391) or the volume of CSF removed median (16ml, n=19, p=0.155). There was no statistically significant difference detected in days of headache when comparing the children with opening pressure above and equal to the median (400 mm of CSF) from those below (n=44, p= 0.634).CONCLUSIONSNo significant association between closing pressure, or amount of CSF removed, and time to resolution of papilledema in pediatric PTCS was detected. The diagnostic and therapeutic purposes of either measuring the closing pressure or maximizing the volume of CSF removed were not evident in these analyses.



https://ift.tt/2GFPXgT

Bernard Sachs Lecture of 2016: Timing in Morphogenesis and Genetic Gradients during Normal Development and in Malformations of the Nervous System

Publication date: Available online 30 March 2018
Source:Pediatric Neurology
Author(s): Harvey B. Sarnat
Nervous system development is quadradimensional. Both normal ontogenesis and developmental malformations are explained in the context of the 4^th dimension, timing. Timing of the onset of either the genetic expression of a mutation or an epigenetic event that may be teratogenic is primordial in determining morphogenesis and the forms of malformations with their functional consequences. Multiple genotypes may cause similar phenotypes or a single genotype with different degrees of retained normal genetic expression may result in variable phenotypes. In this treatise, examples are presented of these principles, including both delayed and precocious maturation of processes such as synaptogenesis that may be out of synchrony with other simultaneous processes of neuronal maturation. In postzygotic somatic mosaicism, timing of onset determines not only the character but also the extent of a lesion; focal cortical dysplasia IIb and hemimegalencephaly are the same disease, both sharing activation of the mTOR pathway as the primary mechanism; the difference is timing of onset within the 33 mitotic cycles of the periventricular neuroepithelium. Genetic expression often follows gradients along the 3 axes of the neural tube. Defective gradients often can be identified by their morphological result without knowing the precise mutation. Upregulation in the vertical axis produces hyperplasia or duplication of either dorsal or ventral structures, whereas downregulation yields hypoplasia or fusion in the midline of bilateral structures. Disorders of segmentation or neuromere formation in the neural tube are increasingly recognized as another pathogenesis of cerebral dysgenesis. Our recent investigations show the participation of the U-fibre layer beneath FCD in epileptic networks because of neuronal dispersion with elaborate synaptic plexi and a barrier to deep heterotopia.



https://ift.tt/2uGqvTS

Dynamic semantic cognition: Characterising coherent and controlled conceptual retrieval through time using magnetoencephalography and chronometric transcranial magnetic stimulation

Publication date: Available online 30 March 2018
Source:Cortex
Author(s): Catarina Teige, Giovanna Mollo, Rebecca Millman, Nicola Savill, Jonathan Smallwood, Piers L. Cornelissen, Elizabeth Jefferies
Distinct neural processes are thought to support the retrieval of semantic information that is (i) coherent with strongly-encoded aspects of knowledge, and (ii) non-dominant yet relevant for the current task or context. While the brain regions that support readily coherent and more controlled patterns of semantic retrieval are relatively well-characterised, the temporal dynamics of these processes are not well-understood. This study used magnetoencephalography (MEG) and dual-pulse chronometric transcranial magnetic stimulation (cTMS) in two separate experiments to examine temporal dynamics during the retrieval of strong and weak associations. MEG results revealed a dissociation within left temporal cortex: anterior temporal lobe (ATL) showed greater oscillatory response for strong than weak associations, while posterior middle temporal gyrus (pMTG) showed the reverse pattern. Left inferior frontal gyrus (IFG), a site associated with semantic control and retrieval, showed both patterns at different time points. In the cTMS experiment, stimulation of ATL at ∼150ms disrupted the efficient retrieval of strong associations, indicating a necessary role for ATL in coherent conceptual activations. Stimulation of pMTG at the onset of the second word disrupted the retrieval of weak associations, suggesting this site may maintain information about semantic context from the first word, allowing efficient engagement of semantic control. Together these studies provide converging evidence for a functional dissociation within the temporal lobe, across both tasks and time.



https://ift.tt/2GHTwDn

APOE genotype and cognition in healthy individuals at-risk of Alzheimer’s disease: a review

Publication date: Available online 30 March 2018
Source:Cortex
Author(s): M. Clare O'Donoghue, Susannah E. Murphy, G. Zamboni, A.C. Nobre, Clare E. Mackay
APOE-ε4 is best known as a risk factor for Alzheimer's disease (AD). Consequently, there is considerable research interest in understanding whether APOE-ε4 influences cognition in healthy adults. Despite a substantial literature reporting effects of APOE genotype on cognition, findings are inconsistent. In particular, it is challenging to separate whether cognitive deficits in APOE-ε4 carriers reflect the influence of prodromal dementia pathology ("prodromal hypothesis"), or a direct contribution of APOE genotype to individual differences ("phenotype hypothesis"). Variable methodology across studies further complicates the issue. These challenges have limited what can be learnt about the processes underlying cognitive ageing and dementia by studying the influence of APOE genotype on cognition. In this review, we focus on the two compatible neurobiological mechanisms by which APOE genotype may influence cognition in healthy adults (prodromal and phenotype). We summarise the behavioural evidence for the influence of APOE on cognition in non-demented adults and explore key methodological challenges for disentangling the cognitive effects of different neurobiological mechanisms of APOE. Evidence suggests that at least some APOE-ε4 cognitive deficits are due to early AD pathology, whilst sensitive measures of cognition are beginning to reveal subtle cognitive differences between APOE genotypes in mid-adulthood, prior to the onset of the AD prodromal period. We conclude with recommendations for future research to investigate the cognitive consequences of neurobiological processes affected by APOE and maximise the translational potential of this research.



https://ift.tt/2uDSaVv

Interdigitating dendritic cell sarcoma: Clinicopathologic study of 8 cases with review of the literature

Publication date: Available online 30 March 2018
Source:Annals of Diagnostic Pathology
Author(s): Tian Xue, Xiangnan Jiang, Weige Wang, Xiaoyan Zhou, Xiaoqiu Li
To investigate the clinicopathologic features and differential diagnoses of interdigitating dendritic cell sarcoma (IDCS), the clinical, morphological and immunohistochemical features of eight cases of IDCS were collected and analyzed. Three patients were males and five were females, the mean age and the median age were 56.5 years and 57 years respectively. Clinically, the majority of cases involved lymph nodes. Microscopically, neoplastic cells were spindle or ovoid, forming fascicles or whorls. Every case had active mitosis figures. Immunohistochemically, these neoplastic cells were consistently positive for S100, but negative for CD21 and specific B-cell and T-cell associated antigens. Follow-up results were available in 7 cases, of which 5 cases of localized lesions survived, 2 cases died of organ involvement. Interdigitating dendritic cell sarcoma is an extremely rare neoplasm, with inferior prognosis and without standard treatment regimen. IDCS has similar but unique clinicopathologic features and the differential diagnoses include other histiocytic and dendritic cell neoplasms and malignant melanoma.



https://ift.tt/2H290ju

Differential biotin labelling of the cell envelope proteins in lipopolysaccharidic diderm bacteria: Exploring the proteosurfaceome of Escherichia coli using sulfo-NHS-SS-biotin and sulfo-NHS-PEG4-bismannose-SS-biotin

Publication date: Available online 30 March 2018
Source:Journal of Proteomics
Author(s): Ricardo Monteiro, Ingrid Chafsey, Sabine Leroy, Christophe Chambon, Michel Hébraud, Valérie Livrelli, Mariagrazia Pizza, Alfredo Pezzicoli, Mickaël Desvaux
Surface proteins are the major factor for the interaction between bacteria and its environment, playing an important role in infection, colonisation, virulence and adaptation. However, the study of surface proteins has proven difficult mainly due to their hydrophobicity and/or relatively low abundance compared with cytoplasmic proteins. To overcome these issues new proteomic strategies have been developed, such as cell-surface protein labelling using biotinylation reagents. Sulfo-NHS-SS-biotin is the most commonly used reagent to investigate the proteins expressed at the cell surface of various organisms but its use in lipopolysaccharidic diderm bacteria (archetypical Gram-negative bacteria) remains limited to a handful of species. While generally pass over in silence, some periplasmic proteins, but also some inner membrane lipoproteins, integral membrane proteins and cytoplasmic proteins (cytoproteins) are systematically identified following this approach. To limit cell lysis and diffusion of the sulfo-NHS-SS-biotin through the outer membrane, biotin labelling was tested over short incubation times and proved to be as efficient for 1 min at room temperature. To further limit labelling of protein located below the outer membrane, the use of high-molecular weight sulfo-NHS-PEG4-bismannose-SS-biotin appeared to recover differentially cell-envelope proteins compared to low-molecular weight sulfo-NHS-SS-biotin. Actually, the sulfo-NHS-SS-biotin recovers at a higher extent the proteins completely or partly exposed in the periplasm than sulfo-NHS-PEG4-bismannose-SS-biotin, namely periplasmic and integral membrane proteins as well as inner membrane and outer membrane lipoproteins. These results highlight that protein labelling using biotinylation reagents of different sizes provides a sophisticated and accurate way to differentially explore the cell envelope proteome of lipopolysaccharidic diderm bacteria.SignificanceWhile generally pass over in silence, some periplasmic proteins, inner membrane lipoproteins (IMLs), integral membrane proteins (IMPs) and cytoplasmic proteins (cytoproteins) are systematically identified following cell-surface biotin labelling in lipopolysaccharidic diderm bacteria (archetypal Gram-negative bacteria). The use of biotinylation molecules of different sizes, namely sulfo-NHS-SS-biotin and sulfo-NHS-PEG4-bismannose-SS-biotin, was demonstrated to provide a sophisticated and accurate way to differentially explore the cell envelope proteome of lipopolysaccharidic diderm bacteria.

Graphical abstract

https://ift.tt/2H24kdq

A comparative proteomic characterization and nutritional assessment of naturally- and artificially-cultivated Cordyceps sinensis

Publication date: Available online 30 March 2018
Source:Journal of Proteomics
Author(s): Xu Zhang, Qun Liu, Wei Zhou, Ping Li, Raphael N. Alolga, Zhenming Qian, Wenjia Li, Lian-Wen Qi, Xiaojian Yin
Cordyceps sinensis has gained increasing attention due to its nutritional and medicinal properties. Herein, we employed label-free quantitative mass spectrometry to explore the proteome differences between naturally- and artificially-cultivated C. sinensis. A total of 22,829 peptides with confidence ≥95%, corresponding to 2541 protein groups were identified from the caterpillar bodies/stromata of 12 naturally- and artificially-cultivated samples of C. sinensis. Among them, 341 proteins showed significant differences between the samples of natural and artificial cultivation. These proteins were mainly involved in energy production/conversion, amino acid transport/metabolism, and transcription regulation. The proteomic results were confirmed by the identification of 4 significantly changed metabolites, thus, lysine, threonine, serine, and arginine via untargeted metabolomics. The change tendencies of these metabolites were partly in accordance with changes in abundance of the proteins, which was upstream of their synthetic pathways. In addition, the nutritional value in terms of the levels of nucleosides, nucleotides, and adenosine between the artificially- and naturally-cultivated samples was virtually same. These proteomic data will be useful for understanding the medicinal value of C. sinensis and serve as reference for its artificial cultivation.SignificanceC. sinensis is a precious and valued medicinal product, the current basic proteome dataset would provide useful information to understand its development/infection processes as well as help to artificially cultivate it. This work would also provide basic proteome profile for further study of C. sinensis.

Graphical abstract

https://ift.tt/2pTXDlq

Agerarin inhibits α-MSH–induced TYR gene transcription via STAT3 suppression independent of CREB-MITF pathway

Publication date: Available online 30 March 2018
Source:Journal of Dermatological Science
Author(s): Soon Young Shin, Ha-Na Gil, Ji Hye Choi, Yoongho Lim, Young Han Lee




https://ift.tt/2GZjvE6

Glucocorticoids as an adjunct to oncologic treatment in solid malignancies – not an innocent bystander

Publication date: Available online 31 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Corinne Maurice-Dror, Ruth Perets, Gil Bar-Sela
Glucocorticoids are steroidal hormones which exert their action via genomic and non-genomic mechanisms. In the clinical setting, glucocorticoids are utilized for their anti-inflammatory, anti-allergenic and immunomodulatory effects and for their well-established, pro-apoptotic effects on hematological malignancies. In the treatment of solid tumors, glucocorticoids serve primarily for alleviation of tumor- and treatment-related symptoms and in most cases are not considered to have a direct effect on tumor growth and spread. However, significant pre-clinical data suggest that glucocorticoids have diverse effects on tumor progression, both pro- and anti- tumorigenic. In contrast, the clinical data regarding the pro- and anti-tumorigenic effects of glucocorticoids on solid tumors is scarce, and summarized in this review. The following review presents the suggested glucocorticoids mechanism of action and the effects of glucocorticoids on tumor cells, on the tumor microenvironment and on tumor response to cytotoxic therapy, in the pre-clinical and clinical settings.



https://ift.tt/2J8Lf9L

Prediction models for endometrial cancer for the general population or symptomatic women: a systematic review

Publication date: Available online 31 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Maaike Alblas, Kimberley Velt, Nora Pashayan, Martin Widschwendter, Ewout Steyerberg, Yvonne Vergouwe
ObjectiveTo provide an overview of prediction models for the risk of developing endometrial cancer in women of the general population or for the presence of endometrial cancer in symptomatic women.MethodsWe systematically searched the Embase and Pubmed database until September 2017 for relevant publications. We included studies describing the development, the external validation, or the updating of a multivariable model for predicting endometrial cancer in the general population or symptomatic women.ResultsOut of 2756 references screened, 14 studies were included. We found two prediction models for developing endometrial cancer in the general population (risk models) and one extension. Eight studies described the development of models for symptomatic women (diagnostic models), one comparison of the performance of two diagnostic models and two external validation. Sample size varied from 60 (10 with cancer) to 201,811 (855 with cancer) women. The age of the women was included as a predictor in almost all models. The risk models included epidemiological variables related to the reproductive history of women, hormone use, BMI, and smoking history. The diagnostic models also included clinical predictors, such as endometrial thickness and recurrent bleeding. The concordance statistic (c), assessing the discriminative ability, varied from 0.68 to 0.77 in the risk models and from 0.73 to 0.957 in the diagnostic models. Methodological information was often limited, especially on the handling of missing data, and the selection of predictors. One risk model and four diagnostic models were externally validated.ConclusionsOnly a few models have been developed to predict endometrial cancer in asymptomatic or symptomatic women. The usefulness of most models is unclear considering methodological shortcomings and lack of external validation. Future research should focus on external validation and extension with new predictors or biomarkers, such as genetic and epigenetic markers.



https://ift.tt/2pVERKq

Re-irradiation as salvage treatment in recurrent glioblastoma: a comprehensive literature review to provide practical answers to frequently asked questions

Publication date: Available online 31 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Silvia Scoccianti, Giulio Francolini, Giulio Alberto Carta, Daniela Greto, Beatrice Detti, Gabriele Simontacchi, Luca Visani, Muhammed Baki, Linda Poggesi, Pierluigi Bonomo, Monica Mangoni, Isacco Desideri, Stefania Pallotta, Lorenzo Livi
The primary aim of this review is to provide practical recommendations in terms of fractionation, dose, constraints and selection criteria to be used in the daily clinical routine.Based on the analysis of the literature reviewed, in order to keep the risk of severe side effects <3,5%, patients should be stratified according to the target volume. Thus, patients should be treated with different fractionation and total EQD2 (<12,5 ml: EQD2 < 65 Gy with radiosurgery; >12,5 ml and <35 ml: EQD2 < 50 Gy with hypofractionated stereotactic radiotherapy; >35 m l and <50 ml: EQD2 < 36 Gy with conventionally fractionated radiotherapy).Concurrent approaches with temozolomide or bevacizumab do not seem to improve the outcomes of reirradiation and may lead to a higher risk of toxicity but these findings need to be confirmed in prospective series.



https://ift.tt/2J9wjIG

Sheltered by reeds and settled on sedges: Construction and use of a twenty thousand-year-old hut according to phytolith analysis from Kharaneh IV, Jordan

Publication date: June 2018
Source:Journal of Anthropological Archaeology, Volume 50
Author(s): Monica N. Ramsey, Lisa A. Maher, Danielle A. Macdonald, Dani Nadel, Arlene M. Rosen
This paper employs new phytolith evidence to consider how Early Epipaleolithic people at the site of Kharaneh IV (Azraq Basin, Jordan) used local plant resources to construct their huts, and furnish their indoor space. Forty-five sediment samples from Structure 1 were compared to previously published results (10 sediment samples) from the well-preserved site of Ohalo II (Hut 1) (adjacent to Sea of Galilee, Israel). Our results demonstrate that similar plant resources were employed in both sites' hut constructions, including the heavy use of wetland sedge and reed resources. Interpreting the extensive use of wetland resources in hut construction at Kharaneh IV required the use of new ethnographic analogs focused on wetland-based adaptations, such as Northern Paiute 'tule technology' from the American Great Basin. The phytolith evidence shows that woody and shrubby dicots were employed, likely to construct the hut frame. Phragmites culm may also have been used to frame the structure. While a variety of grasses, wetland reeds, and importantly sedge resources, were used as part of the hut superstructure, perhaps as bundled thatching to cover the frame. In the interior these resources were employed as a loose floor covering or matting to increase the comfort of the living space. Our broader findings emphasize that Early Epipaleolithic hunter-gatherers were increasingly investing in 'place'. Indeed, the construction of these early homes may even have enhanced the ecological productivity and social meaning of the Azraq Landscape.



https://ift.tt/2GZYN73

An audiological evaluation of syndromic and non-syndromic craniosynostosis in pre-school going children

Publication date: June 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 109
Author(s): Liang Chye Goh, Ali Azman, Hufaidah binti Konting Siti, Wee Vien Khoo, Premala a/p Muthukumarasamy, Meow Keong Thong, Zulkiflee Abu Bakar, Anura Michelle Manuel
ObjectiveTo study the audiological outcome and early screening of pre-school going children with craniosynostosis under follow-up at the University of Malaya Medical Center(UMMC), Kuala Lumpur, Malaysia over a 10 year period.MethodsA retrospective descriptive cohort study on the audiological findings detected during the first hearing assessment done on a child with craniosynostosis using otoacoustic emissions, pure tone audiometry or auditory brainstem response examination. The main aim of this study was to evaluate the type and severity of hearing loss when compared between syndromic and non-sydromic craniosynostosis, and other associated contributory factors.ResultsA total of 31 patients with 62 ears consisting of 14 male patients and 17 female patients were evaluated. Twenty two patients (71%) were syndromic and 9 (29%) were non-syndromic craniosynostosis. Amongst the syndromic craniosynostosis, 9 (41%) had Apert syndrome, 7 (32%) had Crouzon syndrome, 5 (23%) had Pfieffer syndrome and 1 (4%) had Shaethre Chotzen syndrome. Patients with syndromic craniosynostosis were more likely to present with all types and severity of hearing loss, including severe to profound sensorineural hearing loss while children with non-syndromic craniosynostosis were likely to present with normal hearing (p < 0.05). In addition, when the first hearing test was done at a later age, a hearing loss including sensorineural hearing loss is more likely to be present in a child with syndromic craniosynostosis (p < 0.05).ConclusionOur study suggested that children who are born with syndromic craniosynostosis were more likely to suffer from a hearing loss, including that of a severe to profound degree compared to children with non-syndromic craniosynostosis. In addition to that, hearing loss is more likely to be detected when the first hearing test is done at a later age, and this can be an irreversible sensorineural hearing loss. We would like to advocate the need for early audiological screening and follow up in children with syndromic craniosynostosis.



https://ift.tt/2JblGFm

Does influenza vaccination during early pregnancy really increase the risk of miscarriage?

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Annette K. Regan, Hannah C. Moore, Sheena G. Sullivan




https://ift.tt/2GYqvRy

Influenza vaccination in early pregnancy

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Cassandra Roeca, Alex J. Polotsky




https://ift.tt/2pQSMBo

Response to three Letters to the Editor regarding: Donahue JG, et al. “Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010–11 and 2011–12”. Vaccine 35 (2017) 5314–5322

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17





https://ift.tt/2H4zYad

The future control of rotavirus disease: Can live oral vaccines alone solve the rotavirus problem?

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Roger I. Glass, Baoming Jiang, Umesh Parashar
Live oral rotavirus (RV) vaccines used worldwide are most effective in reducing diarrheal hospitalizations from RV in high income countries and least effective in low income countries where RV remains a prime cause of death in children. Research has failed to fully explain the reason for this difference of efficacy for RV vaccines, an observation made with other live oral vaccines for polio, cholera and typhoid fever. Use of parenteral vaccines have been successful in overcoming this problem for both polio and typhoid and parenteral RV vaccines are now in development. This approach should be pursued for rotavirus vaccine as well because in low income countries where oral RV vaccines have been introduced and are only partially effective, RV remains the most common cause of diarrhea in children under 5 years. The ultimate control of RV diarrheal will likely require both oral and parenteral vaccines.



https://ift.tt/2E8h0MH

Editorial Board/Aims and Scope

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17





https://ift.tt/2GZbwGY

Immunoinformatics approaches to design a novel multi-epitope subunit vaccine against HIV infection

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Rajan Kumar Pandey, Rupal Ojha, Veeranarayanan Surya Aathmanathan, Muthukalingan Krishnan, Vijay Kumar Prajapati
The end goal of HIV vaccine designing requires novel strategies to elicit a strong humoral and cell-mediated immune response. The emergence of drug resistance and the requirement of next line treatment necessitate the finding of the potential and immunogenic vaccine candidate. This study employed a novel immunoinformatics approach to design multi-epitope subunit vaccine against HIV infection. Here, we designed the subunit vaccine by the combination of CTL, HTL and BCL epitopes along with suitable adjuvant and linkers. Physiochemical characterization of subunit vaccine was assessed to ensure its thermostability, theoretical PI, and amphipathic behavior. In further assessment, subunit vaccine was found to be immunogenic with the capability to generate humoral and cell-mediated immune response. Further, homology modeling and refinement was performed and the refined modeled structure was used for molecular docking with the immune receptor (TLR-3) present on lymphocyte cells. Consequently, molecular dynamics simulation ensured the molecular interaction between TLR-3 and subunit vaccine candidate. Disulfide engineering was performed by placing the cysteine residues in the region of high mobility to enhance the vaccine stability. At last, in silico cloning was performed to warrant the translational efficiency and microbial expression of the designed vaccine.



https://ift.tt/2H047HD

Neutralization effects of antibody elicited by chimeric HBV S antigen viral-like particles presenting HCV neutralization epitopes

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Sanhua Wei, Yingfeng Lei, Jie Yang, Xiaoyan Wang, Fang Shu, Xin Wei, Fang Lin, Bin Li, Ying Cui, Hai Zhang, Sanhua Wei
Hepatitis C virus (HCV) infection is a major public health problem despite effectual direct-acting antivirals (DAAs) therapy. Development of a prophylactic vaccine is essential to block spread of HCV infection. The HBV small surface antigen (HBsAg-S) can self-assemble into virus-like particles (VLPs), has higher immunogenicity and is used as a vaccine against HBV infections. Chimeric HBsAg-S proteins with foreign epitopes allow VLP formation and induce the specific humoral and cellular immune responses against the foreign proteins. In this study, we investigated the immune responses induced by chimeric VLPs with HCV neutralizing epitopes and HBV S antigen in mice. The chimeric HCV-HBV VLPs expressing neutralizing epitopes were prepared and purified. BALB/c mice were immunized with purified chimeric VLPs and the serum neutralizing antibodies were analyzed. We found that these chimeric VLPs induced neutralizing antibodies against HCV in mice. Additionally, the murine serum neutralized infections with HCV pseudoparticles and cell-cultured viruses derived from different heterologous 1a, 1b and 2a genotypes. We also found that immunization with chimeric VLPs induced anti-HBsAg antibodies. This study provides a novel strategy for development of a HCV prophylactic neutralizing epitope vaccine and a HCV-HBV bivalent prophylactic vaccine.



https://ift.tt/2E9L9uT

A phase III, open-label, randomised multicentre study to evaluate the immunogenicity and safety of a booster dose of two different reduced antigen diphtheria-tetanus-acellular pertussis-polio vaccines, when co-administered with measles-mumps-rubella vaccine in 3 and 4-year-old healthy children in the UK

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Robin Marlow, Sherine Kuriyakose, Narcisa Mesaros, Htay Htay Han, Richard Tomlinson, Saul N. Faust, Matthew D. Snape, Andrew J. Pollard, Adam Finn
AimTo evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPVB) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3–4 year old children as compared to dTap-IPVR (Repevax, Sanofi Pasteur), when co-administered with mumps-measles-rubella vaccine (MMRV).MethodsThis phase III, open label, randomised study was conducted in the UK between April 2011 and April 2012. Children due their pre-school dTap-IPV booster vaccination were randomised 2:1 to receive one of two different dTap-IPV vaccines (dTap-IPVB or dTap-IPVR) with blood sample for immunogenicity assessment just prior and one month after vaccination. Immune responses to diphtheria, tetanus and polio antigens were compared between the study vaccines (inferential comparison). In the absence of an accepted pertussis correlate of protection, the immunogenicity of dTap-IPVB vaccine against pertussis was compared with historical pertussis efficacy data (inferential comparison). Safety and reactogenicity of both study vaccines were evaluated.Results387 children were randomised and 385 vaccinated: 255 in the dTap-IPVB group and 130 in the dTap-IPVR group. Prior to vaccination, ≥76.8% of children had anti-diphtheria and ≥65.5% had anti-tetanus titres above the protection threshold; for pertussis, the pre-vaccination seropositivity rate ranged between 18.1 and 70.6%. Both vaccines were immunogenic with 99.2–100% of children achieving titres above the pre-specified seroprotection/seropositivity thresholds. One serious adverse event not considered as causally related to the study vaccination by the study investigator was reported in the dTap-IPVB group.ConclusionNon-inferiority of dTap-IPVB to dTap-IPVR was demonstrated. Both vaccines had a clinically acceptable safety and reactogenicity profile when co-administered with MMRV to children 3–4 years old.Trial registration: NCT01245049 (ClinicalTrials.gov)



https://ift.tt/2GZRV9L

Knowledge, attitudes, and practices regarding hepatitis B vaccination among hospital-based doctors and nurses in China: Results of a multi-site survey

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Yan Liu, Chao Ma, Haimei Jia, Erping Xu, Yong Zhou, Zhujiazi Zhang, Li Lu, Lance Rodewald, Lixin Hao
BackgroundHepatitis B virus (HBV) can cause chronic HBV infection, which may lead to advanced cirrhosis and liver cancer. Healthcare workers (HCWs) are at risk HBV infection as an occupational hazard. Hepatitis B vaccination of HCWs is recommended by WHO, but the status of hepatitis B vaccination among HCWs in China is seldom reported.MethodologyWe conducted a cross-sectional study in 22 hospitals of 3 developed cities in China. We interviewed managers in infectious diseases and occupational health departments, and at least 40 HCWs per hospital.ResultsWe interviewed 929 HCWs; 80.8% were vaccinated against hepatitis B and 96.7% were willing to be vaccinated; 38.2% of HCWs reported having at least one needle stick or sharps injury. Three hospitals provide free hepatitis B vaccination for HCWs; hospitals with a hepatitis B vaccination policy, more HCWs reported being vaccinated (91.7% vs 79.0%, P < 0.001). HCWs in high risk departments (P = 0.011), with more knowledge of hepatitis B vaccine (P < 0.001), and with fewer working years (P = 0.002) were more likely to be vaccinated against HBV. Infectious diseases and occupational health managers had positive attitudes towards hepatitis B vaccination.ConclusionsHepatitis B vaccination was well accepted among HCWs. Hospital provision of free vaccine, greater HCW knowledge of HBV, and working in higher-risk settings were associated with being vaccinated. A national policy of offering hepatitis B vaccine to HCWs should be considered in China. Provision of free hepatitis B vaccine for HBsAb negative HCWs may be acceptable. Education about HBV and hepatitis B vaccine may help promote policy implementation.



https://ift.tt/2pURdSP

Squalene containing solid lipid nanoparticles, a promising adjuvant system for yeast vaccines

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Johannes J. Stelzner, Martina Behrens, Sven-Erik Behrens, Karsten Mäder
Potent adjuvant systems are required for subunit and single antigen based vaccines to provide sufficient immunogenicity. Furthermore, adjuvants can reduce the required number of immunisations and the antigen amount. Squalene nanoemulsions, like MF59® and AddaVax™, are potent, safe and well characterised adjuvant systems and approved for use in humans. Here, we developed squalene containing solid lipid nanoparticles, which can be sterilised by steam sterilisation and stored as freeze-dried power together with a yeast-based vaccine. Detailed size measurements using dynamic and static light scattering were applied, as the immune stimulating effect of squalene emulsions is mainly dependent on the particle size. The size range of AddaVax™ (120–170 nm) was favoured for the developed squalene containing solid lipid nanoparticles. Differential scanning calorimetry (DSC) and H NMR studies were performed to characterise the interactions of the incorporated liquid squalene with the solid hard fat matrix. A homogeneous distribution as liquid domains in the solid glyceride structure was suggested for the liquid squalene. The developed adjuvant was compared with Freund's adjuvant and a commercially available squalene nanoemulsion in a vaccine trial in the mouse model with a yeast-based vaccine directed against the infectious bursal disease virus. All squalene-based adjuvants showed excellent biocompatibility and provided immune stimulating properties comparable to Freund's adjuvant.



https://ift.tt/2H0ukpq

Impact of community-delivered SMS alerts on dog-owner participation during a mass rabies vaccination campaign, Haiti 2017

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Julie M. Cleaton, Ryan M. Wallace, Kelly Crowdis, Andy Gibson, Benjamin Monroe, Fleurinord Ludder, Melissa D. Etheart, Marco Antonio Natal Vigilato, Alasdair King
Haiti has historically vaccinated between 100,000 and 300,000 dogs annually against rabies, however national authorities have not been able to reach and maintain the 70% coverage required to eliminate the canine rabies virus variant. Haiti conducts massive dog vaccination campaigns on an annual basis and utilizes both central point and door-to-door methods. These methods require that dog owners are aware of the dates and locations of the campaign. To improve this awareness among dog owners, 600,000 text messages were sent to phones in two Haitian communes (Gonaives and Saint-Marc) to remind dog owners to attend the campaign. Text messages were delivered on the second day and at the mid-point of the campaign. A post-campaign household survey was conducted to assess dog owner's perception of the text messages and the impact on their participation in the vaccination campaign. Overall, 147 of 160 (91.9%) text-receiving dog owners indicated the text was helpful, and 162 of 187 (86.6%) responding dog owners said they would like to receive text reminders during future rabies vaccination campaigns. In areas hosting one-day central point campaigns, dog owners who received the text were 2.0 (95% CI 1.1, 3.6) times more likely to have participated in the campaign (73.1% attendance among those who received the text vs 36.4% among those who did not). In areas incorporating door-to-door vaccination over multiple days there was no significant difference in participation between dog owners who did and did not receive a text. Text message reminders were well-received and significantly improved campaign attendance, indicating that short message service (SMS) alerts may be a successful strategy in low resource areas with large free roaming dog populations.



https://ift.tt/2pU3eId

The respiratory syncytial virus fusion protein formulated with a polymer-based adjuvant induces multiple signaling pathways in macrophages

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Indranil Sarkar, Ravendra Garg, Sylvia van Drunen Littel-van den Hurk
Respiratory syncytial virus (RSV) causes acute respiratory tract infections in infants, the elderly and immunocompromised individuals. No licensed vaccine is available against RSV. We previously reported that intranasal immunization of rodents and lambs with a RSV vaccine candidate (ΔF/TriAdj) induces protective immunity with a good safety profile. ΔF/TriAdj promoted innate immune responses in respiratory mucosal tissues in vivo, by local chemokine and cytokine production, as well as infiltration and activation of immune cells including macrophages. The macrophage is an important cell type in context of both innate and adaptive immune responses against RSV. Therefore, we characterized the effects of ΔF/TriAdj on a murine macrophage cell line, RAW264.7, and bone marrow-derived macrophages (BMMs). A gene expression study of pattern recognition receptors (PRRs) revealed induction of endosomal and cytosolic receptors in RAW264.7 cells and BMMs by ΔF/TriAdj, but no up-regulation by ΔF in PBS. As a secondary response to the PRR gene expression, induction of several chemokines and pro-inflammatory cytokines, as well as up-regulation of MHC-II and co-stimulatory immune markers, was observed. To further investigate the mechanisms involved in ΔF/TriAdj-mediated secondary responses, we used relevant signal transduction pathway inhibitors. Based on inhibition studies at both transcript and protein levels, JNK, ERK1/2, CaMKII, PI3K and JAK pathways were clearly responsible for ΔF/TriAdj-mediated chemokine and pro-inflammatory cytokine responses, while the p38 and NF-κB pathways appeared to be not or minimally involved. ΔF/TriAdj induced IFN-β, which may participate in the JAK-STAT pathway to further amplify CXCL-10 production, which was strongly up-regulated. Blocking this pathway by a JAK inhibitor almost completely abrogated CXCL-10 production and caused a significant reduction in the cell surface expression of MHC-II and co-stimulatory immune markers. These data demonstrate that ΔF/TriAdj induces multiple signaling pathways in macrophages.



https://ift.tt/2H3EWny

Recombinant NADP-dependent isocitrate dehydrogenase of Edwardsiella tarda induces both Th1 and Th2 type immune responses and evokes protective efficacy against edwardsiellosis

Publication date: 19 April 2018
Source:Vaccine, Volume 36, Issue 17
Author(s): Xiaoqian Tang, Fuguo Liu, Xiuzhen Sheng, Jing Xing, Wenbin Zhan
Edwardsiella tarda has become one of the most severe fish pathogens throughout the world. Thus, studies on the design and production of highly protective vaccines against this pathogen, as well as the mechanisms of vaccine-induced disease resistance are urgently needed. In this study, the NADP-dependent isocitrate dehydrogenase (IDH) of E. tarda was recombinantly expressed and flounder (Paralichthys olivaceus) anti-rIDH serum was prepared. Also, the outer membrane proteins (OMPs) of E. tarda were extracted and analyzed by western blotting. The results showed that flounder anti-rIDH serum could specifically recognize a 44 kDa protein of E. tarda OMPs, which was identified to be the native IDH of E. tarda by mass spectrometric. Consistently, immunogold electron microscopy showed that IDH could be detected on the membrane of E. tarda. Then, the vaccine potential of rIDH was tested in a flounder model, and the results showed that rIDH produced a relative percent survival (RPS) of 73.3%, which was significantly higher than that produced by formalin killed E. tarda cells. Immunological analysis showed that rIDH could induce the proliferation of rIDH-specific sIg+ lymphocytes, which resulted in the production of anti-E. tarda antibodies. Accordingly, serum bactericidal activity assay showed that the serum of rIDH vaccinated fish exhibited the highest bactericidal activity compared with other groups. qRT-PCR analysis showed that rIDH could enhance the expressions of IFN-γ, NKEF, IL-6, MHCIα, CD4-1 and CD8α. Moreover, the bacterial burden was also detected in vaccinated fish after challenge, which showed that the number of E. tarda cells in spleen of rIDH group was significantly lower than other groups. All these results suggested that rIDH is a promising vaccine candidate against E. tarda infection.



https://ift.tt/2E98CN3