An improved procedure for integrated behavioral z-scoring illustrated with modified Hole Board behavior of male inbred laboratory mice

Publication date: Available online 20 September 2017
Source:Journal of Neuroscience Methods
Author(s): M. Maaike Labots, M.C. Marijke Laarakker, D. Dustin Schetters, S.S. Saskia Arndt, H.A. Hein van Lith
BackgroundGuilloux et al. introduced: integrated behavioral z-scoring, a method for behavioral phenotyping of mice. Using this method multiple ethological variables can be combined to show an overall description of a certain behavioral dimension or motivational system. However, a problem may occur when the control group used for the calculation has a standard deviation of zero or when no control group is present to act as a reference group.New MethodIn order to solve these problems, an improved procedure is suggested: taking the pooled data as reference. For this purpose a behavioral study with male mice from three inbred strains was carried out. The integrated behavioral z-scoring methodology was applied, thereby taking five different reference group options. The outcome regarding statistical significance and practical importance was compared.ResultsSignificant effects and effect sizes were influenced by the choice of the reference group. In some cases it was impossible to use a certain population and condition, because one or more behavioral variables in question had a standard deviation of zero. Based on the improved method, male mice from the three inbred strains differed regarding activity and anxiety.Comparison with Existing MethodTaking the method described by Guilloux et al. as basis, the present procedure improved the generalizability to all types of experimental designs in animal behavioral research.ConclusionsTo solve the aforementioned problems and to avoid getting the diagnosis of data manipulation, the pooled data (combining the data from all experimental groups in a study) as reference option is recommended.



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Systematic assessment of clinical outcomes and toxicities of proton radiotherapy for reirradiation

Publication date: Available online 20 September 2017
Source:Radiotherapy and Oncology
Author(s): Vivek Verma, Jean-Claude M. Rwigema, Robert S. Malyapa, William F. Regine, Charles B. Simone
Reirradiation (reRT) for locoregional recurrences poses unique challenges and risks; re-treatment using proton beam radiotherapy (PBT) could prove advantageous. Assessing clinical outcomes and toxicity profiles, this systematic review comprehensively evaluated available evidence regarding PBT reRT. Fourteen original investigations across central nervous system (CNS) (n=6), head/neck (H&N) (n=4), lung (n=2), and gastrointestinal (n=2) malignancies were analyzed. PBT for recurrent uveal melanoma achieved 5-year eye retention of 55%; for chordomas, reRT afforded a 2-year local control and overall survival (OS) of 85% and 80%, respectively. Multiple PBT reRT studies for adult gliomas illustrate no grade ≥3 toxicities. Two pediatric CNS tumor studies demonstrated the safety and efficacy of reRT, with one total grade 3 toxicity and achievement of longer-term OS. PBT for H&N malignancies shows appropriate local/locoregional control and favorable toxicity profiles versus historical photon-based methods, including low (9–10%) rates of feeding tube placement. PBT for recurrent lung cancer can achieve favorable survival with expected toxicities/complications of reRT, especially with concurrent chemotherapy and centrally located recurrences. Lastly, PBT reRT in gastrointestinal malignancies induced very few high-grade complications. Hence, based on the limited existing data, PBT is a notably safe reRT modality for effective salvage of recurrent disease. Institutional experiences must continue to be reported: dosimetric correlations, late toxicities, and advanced PBT techniques.



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Treatment of psoriasis with topical agents: Recommendations from a Tuscany Consensus

Abstract

Psoriasis is a chronic and relapsing inflammatory skin disease, clinically characterized by erythematous and scaly plaques. Treatment approach is mainly driven by disease severity, though several factors should be considered in order to identify the optimal therapeutic choice. Mild psoriasis may be treated with a wide array of topical agents including corticosteroids, vitamin D analogs, keratolytics, and calcipotriol/betamethasone propionate compound. Because guidelines may not provide practical indications regarding the therapeutic approach, the use of topical agents in psoriasis is more individually tailored. In order to homogenize the standard of care, at least in a local setting, we collected the real-life-based recommendations for the use of topical therapies from an expert panel, the Tuscany Consensus Group on Psoriasis, representing all leading centers for psoriasis established in Tuscany. With this document, this consensus group sought to define principles guiding the selection of therapeutic agents with straightforward recommendations derived from a real-life setting.

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Evaluation of Beauveria bassiana infection in the hemolymph serum proteins of the housefly, Musca domestica L. (Diptera: Muscidae)

Abstract

Beauveria bassiana plays a prominent role in biocontrol of houseflies, Musca domestica (L.). Thus, a deeper insight into immune response of M. domestica during B. bassiana infection was warranted to assist the production of more efficient mycoinsecticides. The present study investigates changes in protein profile of M. domestica hemolymph serum post B. bassiana infection using two-dimensional difference gel electrophoresis (2D-DIGE) followed by identification of selected proteins by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The non-infected or control group of flies showed an expression of 54 proteins, while M. domestica infected with B. bassiana expressed a total of 68 hemolymph serum proteins. Thirty three proteins were expressed in both groups of houseflies, whereas 35 proteins were exclusively expressed in infected flies and 21 proteins were exclusively expressed in control flies. Among the 33 proteins which were expressed in both groups of houseflies, 17 proteins showed downregulation, while16 proteins were upregulated in the infected flies compared to the non-infected ones. The results from this study are expected to facilitate better understanding of insect's immune response mechanism.

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An assessment of the potential use of compost filled plastic void forming units to serve as vents on historic landfills and related sites

Abstract

Much of the solid municipal waste generated by society is sent to landfill, where biodegrading processes result in the release of methane, a major contributor to climate change. This work examined the possibility of installing a type of biofilter within paved areas of the landfill site, making use of modified pervious paving, both to allow the escape of ground gas and to avoid contamination of groundwater, using specially designed test models with provision for gas sampling in various chambers. It proposes the incorporation of an active layer within a void forming box with a view to making dual use of the pervious pavement to provide both a drainage feature and a ground gas vent, whilst providing an active layer for the oxidation of methane by microbial action. The methane removal was observed to have been effected by microbial oxidation and as such offers great promise as a method of methane removal to allow for development of landfills.

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Compound-specific isotopic and congener-specific analyses of polychlorinated biphenyl in the heat medium and rice oil of the Yusho incident

Abstract

Compound-specific isotope analysis (CSIA) can be used to examine the source and transformation processes of organic pollutants in the environment. We performed a carbon stable isotope analysis of polychlorinated biphenyl (PCB) congeners in the PCB heat-transfer medium (heat medium) and the original Kanechlor-400 (KC-400, a commercial brand of PCBs) involved in the Yusho incident. The main purpose is to investigate whether isotope fractionation occurred in the rice oil deodorization process that caused the incident. The carbon isotope ratios (δ¹³C values) of the targeted PCB congeners ranged from − 29.39 to − 27.00‰ in the heat medium and from − 28.77 to − 27.05‰ in the original KC-400. No significant differences were found in the δ¹³C values, suggesting carbon isotope fractionation did not occur for the targeted PCB congeners in the heat medium when deodorization of rice oil occurred at temperatures above 200 °C. Furthermore, we also conducted a congener-specific analysis of 64 PCB congeners found in the heat medium and rice oil contaminated by it. The total PCB congener concentrations were 503 mg/g in the heat medium and 81 μg/g in the rice oil. The concentrations of the highly chlorinated congeners were significantly lower in the heat medium than in the original KC-400, and the compositional ratios of the lowly chlorinated congeners were relatively lower in the rice oil than in the heat medium. These results suggest that the PCB congener patterns gradually changed from that of the original KC-400 in the deodorization process and subsequent contamination into the rice oil. Thus, a combination of CSIA and congener-specific analysis is a new approach for investigating the changing PCB congener profiles in samples from the Yusho incident.

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Monitoring harm perceptions of smokeless tobacco products among U.S. adults: Health Information National Trends Survey 2012, 2014, 2015

Publication date: February 2018
Source:Addictive Behaviors, Volume 77
Author(s): Shari P. Feirman, Elisabeth A. Donaldson, Mark Parascandola, Kimberly Snyder, Cindy Tworek
IntroductionChanges to the U.S. smokeless tobacco landscape in recent years include a change to health warnings on packages, the implementation of bans in some stadiums, and the launch of a federal youth prevention campaign. It is unclear whether such changes have impacted consumer beliefs about smokeless tobacco. This study examines relative harm perceptions of smokeless tobacco compared to cigarettes among adults and assesses changes in smokeless tobacco harm perceptions over time.MethodsWe analyzed data from three cycles (2012, 2014, 2015) of the Health Information National Trends Survey (HINTS). Using 2015 data, we assessed bivariate associations between smokeless tobacco harm perceptions and tobacco use, beliefs, information seeking, and demographics. Using 2012, 2014, and 2015 data, we assessed whether smokeless tobacco harm perceptions changed over time within demographic groups using chi-square tests. We then used a weighted multinomial logistic regression to assess the association between smokeless tobacco perceptions and survey year, adjusting for covariates.ResultsWhen asked whether smokeless tobacco products are less harmful than cigarettes, the majority of respondents across cycles said "no." The percent of respondents who selected this response option decreased over time. Findings showed significant differences in relative harm perceptions of smokeless tobacco versus cigarettes for specific demographic subgroups. Among subgroups, these shifts did not occur with a discernible pattern.ConclusionsUnderstanding factors associated with perceptions of smokeless tobacco can inform tobacco control efforts. Additional monitoring of these trends may provide researchers with a deeper understanding of how and why smokeless tobacco harm perceptions change.



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Accesses for alcohol intoxication to the emergency department and the risk of re-hospitalization: An observational retrospective study

Publication date: February 2018
Source:Addictive Behaviors, Volume 77
Author(s): Maurizio Baldassarre, Fabio Caputo, Raimondo Maria Pavarin, Matteo Massimo Bossi, Maria Elena Bonavita, Paolo Caraceni, Alice Grignaschi, Mimosa Balloni, Mario Cavazza, Mauro Bernardi, Marco Domenicali
BackgroundAlcohol use disorders (AUD) are a frequent cause of admission to emergency departments (EDs) for acute alcohol intoxication (AAI). Patients with AUD present a higher risk of readmission to EDs for AAI than the general population, however, the distinction between sporadic AAI and AAI in the context of AUD in the ED setting is difficult.AimsTo analyze the epidemiological characteristics of patients admitted to EDs because of AAI and to identify factors associated with repeated admissions in order to develop a risk stratification system for patients with AUD based on objective data that can be easily applied in an ED setting.MethodsAn observational retrospective study was performed. All patients with diagnosis of AAI at admission in 2014 were enrolled.ResultsFive hundred and sixty-five patients were enrolled, of which 92 (16%) were admitted more than once to the ED. At multivariate analysis, factors associated with readmission were past episodes of alcohol abuse, social discomfort, previous traumas and psychiatric disorders. Basing on this parameter, a risk-score for re-hospitalization was developed. This score has a high predictive power for the risk of readmission to the ED (AROC 0.837, 95%CI 0.808–0.866), moreover, the cumulative probability of readmission within one year, increased in parallel with score value, being highest in patients presenting 3 or more risk factors.ConclusionThe present study demonstrates that several risk factors stratify the risk of re-hospitalization in patients admitted to EDs for AAI, allowing the identification of those presenting more severe conditions and who would likely benefit from multidisciplinary intervention.



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Can attitudes about smoking impact cigarette cravings?

Publication date: January 2018
Source:Addictive Behaviors, Volume 76
Author(s): Lauren Bertin, Samara Lipsky, Joel Erblich
Cigarette cravings, especially those in response to environmental stressors and other smoking-related triggers (e.g., passing by a favorite smoking spot), are important contributors to smoking behavior and relapse. Previous studies have demonstrated significant individual differences in such cravings. This study explores the possibility that attitudes about smoking can influence the experience of cigarette craving. Consistent with classical theories of the links between cognition and motivation, we predicted that smokers who exhibit more favorable attitudes towards smoking would have greater cravings. Daily smokers (n=103, mean age=41.8years, 33% female) were instructed to imagine smoking, stress, and neutral scenarios. Cravings were measured prior to and after each exposure. Participants also completed an abridged version of the Smoking Consequence Questionnaire (SCQ) that had them rate the: 1) desirability and 2) likelihood, for eighteen separate negative smoking consequences (e.g., "The more I smoke, the more I risk my health", "People will think less of me if they see me smoking"). Findings revealed that favorable attitudes about the consequences of smoking, as measured by the SCQ-desirability index, significantly predicted cigarette cravings. Findings suggest that individual attitudes toward smoking may play an important role in better understanding cigarette cravings, which may ultimately help identify targets for more efficient and effective cognitive/attitude-based interventions for smoking cessation.



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Induction of heme oxygenas-1 attenuates NLRP3 inflammasome activation in lipopolysaccharide-induced mastitis in mice

Publication date: November 2017
Source:International Immunopharmacology, Volume 52
Author(s): Hu Xiaoyu, Hongbin Si, Shumin Li, Wenqing Wang, Jian Guo, Yanyi Li, Yongguo Cao, Yunhe Fu, Naisheng Zhang
Mastitis is one of most prevalent production disease in dairy herds worldwide, and is responsible for enormous economic losses. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme, which is involved in the response to oxidative stress and inflammatory response. The purpose of this study was to detect the protective effect of HO-1 on LPS-induced mastitis in mice. BALB/c mice were pretreated with hemin (HO-1 inducer) and zinc protoporphyrin (ZnPP; HO-1 inhibitor) at 2h before LPS stimulation. The results showed that the mammary gland damage, production of inflammatory cytokines IL-1β, and MPO activity in mammary gland tissues were significantly reduced after pretreated with hemin compared with the group of LPS stimulation only. However, ZnPP reversed the effects of hemin. Furthermore, we found that the levels of ROS and NLRP3 inflammasome were increased after LPS stimulation. The increases were inhibited by hemin and the inhibition of hemin on ROS production and NLRP3 inflammasome activation were blocked by ZnPP. In addition, the results showed that hemin reduced the expression of thioredoxin-interacting protein (TXNIP) induced by LPS, and ZnPP attenuated these changes. In conclusion, the results suggested that overproduction of HO-1 may inhibit the activation of NLRP3 inflammasome and the expression of TXNIP. Induction of HO-1 may be served as a promising method against mastitis induced by LPS.

Graphical abstract

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The potent suppressive effect of β-d-mannuronic acid (M2000) on molecular expression of the TLR/NF-kB Signaling Pathway in ankylosing spondylitis patients

Publication date: November 2017
Source:International Immunopharmacology, Volume 52
Author(s): Maryam Roozbehkia, Mahdi Mahmoudi, Somaye Aletaha, Nima Rezaei, Mohammad Javad Fattahi, Fahimeh Jafarnezhad-Ansariha, Anis Barati, Abbas Mirshafiey
Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by the inflammation of sacroiliac joints and axial skeleton. A combination of genetic, environmental and immunological factors are involved in AS's pathogenesis. TLRs are type I transmembrane glycoproteins that play a crucial role in the innate immune responses against invading pathogens. Observational studies have demonstrated a possible association between TLR dysregulation and AS. The β-d-mannuronic acid (M2000), as a novel NSAID with immunosuppressive property, has shown an inhibitory effect on Toll-like receptor (TLR) 2, 4 signaling in HEK293 cells. In the present study, we investigated the gene expression of Myd88, IKB-alpha, NF-kB and MAPK14 (genes of the TLR/NF-kB Signaling Pathway) in AS patients in comparison to healthy subjects and also the effect of β-d-mannuronic acid on disease activity and mRNA expression of these molecules in affected patients. We showed for the first time that the gene expression level of Myd88, IKB-alpha, NF-kB and MAPK14 was higher in AS patients in comparison to healthy subjects. Moreover we confirmed that the β-d-mannuronic acid not just reduced significantly the disease activity of AS individuals compared to placebo, but also it could significantly decrease the expression level of genes associated with TLR/NF-kB Signaling Pathway in treated patients with M2000. These results may provide a new therapeutic approach to attenuate inflammatory responses in AS patients, (Identified; IRCT 2013062213739N1).



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Increased cycles of DC/CIK immunotherapy decreases frequency of Tregs in patients with resected NSCLC

Publication date: November 2017
Source:International Immunopharmacology, Volume 52
Author(s): Haiping Song, Shujuan Liu, Ziyun Zhao, Weihong Sun, Xiaofang Wei, Xuezhen Ma, Peng Zhao, Daiqing Gao
Regulatory T cells (Tregs) suppress antitumor immune responses. Cycles of Dendritic cells (DC) vaccination combined with cytokine-induced killer (CIK) cells (DC/CIK) treatment were significantly related with good prognosis. Therefore, we investigated whether increased cycles of immunotherapy could decrease frequency of Tregs in patients with resected non-small cell lung cancer (NSCLC). Previous study from our laboratory has determined that the optimal cutoff point of the cycle count was 3cycles. We examined the levels of Tregs and the related cytokines by flow cytometric and cytokine analysis in these patients after more than (≥) 3cycles or less than (<) 3cycles of DC/CIK cell treatment. Significant reduction of Tregs frequency, Treg-generated cytokines level and recurrence rate were presented in patients received with ≥3cycles of DC/CIK cell treatment compared with patients with <3cycles of treatment. Interestingly, Tregs frequency and the related cytokines level were similar between patients suffered tumor recurrence and patients without recurrence in both groups. Together, our findings reveal that increased cycle count of DC/CIK cell immunotherapy contribute to decline of Tregs frequency and cancer recurrence rate in patients with resected NSCLC.



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Evaluation of cutaneous rejuvenation associated with the use of ortho-silicic acid stabilized by hydrolyzed marine collagen

Summary

Background

Organic silicon plays an important role in dermal structure by promoting neocollagenesis. Thus, the supplementation of silicon in a highly bioavailable form can be used for skin rejuvenation.

Aims

This study aimed to evaluate skin changes associated with the use of ortho-silicic acid stabilized by hydrolyzed collagen.

Patients/Methods

Patients were randomized to receive 600 mg of ortho-silicic acid stabilized by hydrolyzed collagen (group 1, n = 11) or placebo (group 2, n = 11) to be taken 15 minutes before breakfast for 90 days. Clinical, photographical, and patients' subjective evaluations were conducted.

Results

A total of 22 patients were included. Clinical evaluations demonstrated changes in skin texture, firmness, and hydration statistically superior in group 1. Brightness, firmness, and overall appearance showed trends for a difference favoring group 1 according to patients' subjective evaluations. Objective images showed no statistical differences. No side effects, hypersensitivity, or systemic symptoms were observed in group 1. Treatment satisfaction in group 1 reached 80%.

Conclusions

Ortho-silicic acid stabilized by hydrolyzed collagen in a daily dose of 600 mg showed positive results in skin rejuvenation according to clinical evaluation in firmness, hydration, and skin texture. Further studies with larger and representative samples should be conducted to confirm our results.

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Comparative instrumental evaluation of efficacy and safety between a binary and a ternary system in chemexfoliation

Summary

Objective

To instrumentally evaluate the efficacy and the safety of a new ternary system chemo exfoliating formulation (water-dimethyl isosorbide-acid) vs traditional binary systems (water and acid) where the acid is maintained in both the systems at the same concentration.

Methods

Different peelings (binary system pyruvic acid and trichloroacetic acid—TCA, and ternary system pyruvic acid and TCA) were tested on the volar forearm of 20 volunteers of both sexes between 28 and 50 years old. The outcomes were evaluated at the baseline, 10 minutes, 24 hours, and 1 week after the peeling by means of noninvasive skin diagnosis techniques. In vivo reflectance confocal microscopy was used for stratum corneum evaluation, transepidermal waterloss, and Corneometry for skin barrier and hydration, Laser Doppler velocimetry in association with colorimetry for irritation and erythema analysis.

Results

The instrumental data obtained showed that the efficacy and safety of the new ternary system peel compounds were significantly higher compared with the binary system formulations tested. The new formulation peels improved chemexfoliation and reduced complications such as irritation, redness, and postinflammatory pigmentation compared to the traditional aqueous solutions.

Conclusion

The study showed that ternary system chemexfoliation, using a controlled delivery technology, was able to provide the same clinical effects in term of stratum corneum reduction with a significantly reduced barrier alteration, water loss, and irritation/erythema compared to traditional binary system peels.

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Masthead

Publication date: September–October 2017
Source:Brachytherapy, Volume 16, Issue 5





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Table of Contents

Publication date: September–October 2017
Source:Brachytherapy, Volume 16, Issue 5





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Editorial Board

Publication date: September–October 2017
Source:Brachytherapy, Volume 16, Issue 5





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Cranial nerve non-invasive neuromodulation improves gait and balance in stroke survivors: A pilot randomised controlled trial

Publication date: Available online 20 September 2017
Source:Brain Stimulation
Author(s): Mary P. Galea, L. Eduardo Cofré Lizama, Andisheh Bastani, Maya G. Panisset, Fary Khan




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Short- and long-latency afferent inhibition; uses, mechanisms and influencing factors

Publication date: Available online 20 September 2017
Source:Brain Stimulation
Author(s): Claudia V. Turco, Jenin El-Sayes, Mitchell J. Savoie, Hunter J. Fassett, Mitchell B. Locke, Aimee J. Nelson
Transcranial magnetic stimulation (TMS) is an ideal technique for non-invasively stimulating the brain and assessing intracortical processes. By delivering electrical stimuli to a peripheral nerve prior to a TMS pulse directed to the motor cortex, the excitability and integrity of the sensorimotor system can be probed at short and long time intervals (short latency afferent inhibition, long latency afferent inhibition). The goal of this review is to detail the experimental factors that influence the magnitude and timing of afferent inhibition in the upper limb and these include the intensity of nerve and TMS delivery, and the nerve composition. Second, the neural mechanisms of SAI are discussed highlighting the lack of existing knowledge pertaining to LAI. Third, the usage of SAI and LAI as a tool to probe cognition and sensorimotor function is explored with suggestions for future avenues of research.



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Nanomaterials to microplastics: Swings and roundabouts

Publication date: Available online 19 September 2017
Source:Nano Today
Author(s): J.J. Scott-Fordsmand, J.M. Navas, K. Hund-Rinke, B. Nowack, M.J.B. Amorim
In recent years, the testing of nanomaterials during their use in products has been increasingly emphasized, as this will provide a more realistic risk assessment (RA) compared with RA based on pristine nanomaterials. We show that (i) using such an approach for a "realistic" RA is increasing the complexity of the RA, (ii) several testing-aspects render this approach more challenging than the conventional methods, (iii) interpretation of the results becomes difficult, and (iv) the resulting RA may need to be evaluated carefully as it yields improved understanding of the short-term fate of the individual product, but long-term consequences may be neglected.

Graphical abstract

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Biodiversity change behind wide applications of nanomaterials?

Publication date: Available online 20 September 2017
Source:Nano Today
Author(s): Ming Chen, Xiaosheng Qin, Guangming Zeng
Nanomaterials, like carbon nanotubes, graphene, metal and metal oxide nanoparticles, are increasingly applied in a wide range of areas with numerous benefits to economy and society. Large-scale production and applications of nanomaterials can increase the possibility of exposure to living organisms, pose risks to human health and ecosystems, and potentially lead to biodiversity losses. Previous environmental impact and safety studies that targeted nanomaterials typically focused on their toxicity, fate and behavior; little attention was paid on biodiversity consequences. Evidence for acute biodiversity change derived from nanomaterials is very limited. Several organizations and researchers have started to discern the relationship between biodiversity and nanotechnology. Nevertheless, more efforts are desired to explore the impacts of nanomaterials on biodiversity.

Graphical abstract

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SIRT6 inhibitors with salicylate-like structure show immunosuppressive and chemosensitizing effects

Publication date: Available online 19 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Patrizia Damonte, Giovanna Sociali, Marco Daniele Parenti, Debora Soncini, Inga Bauer, Silvia Boero, Alessia Grozio, Maria von Holtey, Francesco Piacente, Pamela Becherini, Roberta Sanguineti, Annalisa Salis, Gianluca Damonte, Michele Cea, Maximilien Murone, Alessandro Poggi, Alessio Nencioni, Alberto Del Rio, Santina Bruzzone
The NAD⁺-dependent deacetylase SIRT6 is an emerging cancer drug target, whose inhibition sensitizes cancer cells to chemo-radiotherapy and has pro-differentiating effects. Here we report on the identification of novel SIRT6 inhibitors with a salicylate-based structure. The new SIRT6 inhibitors show improved potency and specificity compared to the hit inhibitor identified in an in-silico compound screen. As predicted based on SIRT6 biological roles, the new leads increase histone 3 lysine 9 acetylation and glucose uptake in cultured cells, while blocking TNF-α production and T lymphocyte proliferation. Notably, the new SIRT6 inhibitors effectively sensitize pancreatic cancer cells to gemcitabine. Finally, studies of compound fingerprinting and pharmacokinetics defined the drug-like properties of one of the new SIRT6 inhibitors, potentially allowing for subsequent in vivo proof-of-concept studies. In conclusion, new SIRT6 inhibitors with a salicylate-like structure were identified, which are active in cells and could potentially find applications in disease conditions, including cancer and immune-mediated disorders.

Graphical abstract

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Conjugation of the CRM197-inulin conjugate significantly increases the immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 fusion protein

Publication date: Available online 19 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Shun Hu, Weili Yu, Chunyang Hu, Dong Wei, Lijuan Shen, Tao Hu, Youjin Yi
Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen that causes tuberculosis (TB). Effective vaccination is urgently needed to deal with the serious threaten from TB. Mtb-secreted protein antigens are important virulence determinants of Mtb with poor immunogenicity. Adjuvants and antigen delivery systems are thus highly desired to improve the immunogenicity of protein antigens. Inulin is a biocompatible polysaccharide (PS) adjuvant that can stimulate a strong cellular and humoral immunity. Bacterial capsular PS and haptens have been conjugated with cross-reacting material 197 (CRM197) to improve their immunogenicity. CFP10 and TB10.4 were two Mtb-secreted immunodominant protein antigens. A CFP10-TB10.4 fusion protein (CT) was used as the antigen for covalent conjugation with the CRM197-inulin conjugate (CRM-inu). The resultant conjugate (CT-CRM-inu) elicited high CT-specific IgG titers, stimulated splenocyte proliferation and provoked the secretion of Th1-type and Th2-type cytokines. Conjugation with CRM-inu significantly prolonged the systemic circulation of CT and exposure to the immune system. Moreover, CT-CRM-inu showed no apparent toxicity to cardiac, hepatic and renal functions. Thus, conjugation of CT with CRM-inu provided an effective strategy for development of protein-based vaccines against Mtb infection.

Graphical abstract

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The compound (3- {5- [(2, 5-dimethoxyphenyl) amino]-1,3,4-thiadiazolidin-2-yl}-5,8-methoxy-2H-chromen-2-one) inhibits the prion protein conversion from PrPC to PrPSc with lower IC50 in ScN2a cells

Publication date: Available online 19 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Nataraj S. Pagadala, Trent C. Bjorndahl, Michael Joyce, David S. Wishart, Khajamohiddin Syed, Abdolamir Landi
Prion diseases are fatal neurodegenerative disorders of the central nervous system characterized by the accumulation of a protease resistant form (PrP^Sc) of the cellular prion protein (PrP^C) in the brain. Two types of cellular prion (PrP^C) compounds have been identified that appear to affect prion conversion are known as Effective Binders (EBs) and Accelerators (ACCs). Effective binders shift the balance in favour of PrP^C, whereas Accelerators favour the formation of PrP^Sc. Molecular docking indicates EBs and ACCs both bind to pocket-D of the SHaPrP^C molecule. However, EBs and ACCs may have opposing effects on the stability of the salt bridge between Arg¹⁵⁶ and Glu¹⁹⁶/Glu²⁰⁰. Computational docking data indicate that the hydrophobic benzamide group of the EB, GFP23 and the 1-(3, 3-dimethylcyclohexylidene) piperidinium group of the ACC, GFP22 play an important role in inhibition and conversion from SHaPrP^C to SHaPrP^Sc, respectively. Experimentally, NMR confirmed the amide chemical shift perturbations observed upon the binding of GFP23 to pocket-D of SHaPrP^C. Consistent with its role as an ACC, titration of GFP22 resulted in widespread chemical shift changes and signal intensity loss due to protein unfolding. Virtual screening of a ligand database using the molecular scaffold developed from the set of EBs identified six of our compounds (previously studied using fluorescence quenching) as being among the top 100 best binders. Among them, compounds 5 and 6 were found to be particularly potent in decreasing the accumulation SHaPrP^Sc in ScN2a cells with an IC50 of ∼35 µM and 20 µM.

Graphical abstract

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9-Substituted acridine derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors possessing antioxidant activity for Alzheimer's disease treatment

Publication date: Available online 20 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Galina F. Makhaeva, Sofya V. Lushchekina, Natalia P. Boltneva, Olga G. Serebryakova, Elena V. Rudakova, Alexey A. Ustyugov, Sergey O. Bachurin, Alexander V. Shchepochkin, Oleg N. Chupakhin, Valery N. Charushin, Rudy J. Richardson
We investigated the inhibitory activity of 4 groups of novel acridine derivatives against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE) using the methods of enzyme kinetics and molecular docking. Antioxidant activity of the compounds was determined using the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS^.+) radical decolorization assay as their ability to scavenge free radicals. Analysis of the esterase profiles and antiradical activities of the acridine derivatives showed that 9-aryl(heteroaryl)-N-methyl-9,10-dihydroacridines have a high radical-scavenging activity but low potency as AChE and BChE inhibitors, whereas 9-aryl(heteroaryl)-N-methyl-acridinium tetrafluoroborates effectively inhibit cholinesterases but do not exhibit antiradical activity. In contrast, a group of derivatives of 9-heterocyclic amino-N-methyl-9,10-dihydroacridine has been found that combine effective inhibition of AChE and BChE with rather high radical-scavenging activity. The results of molecular docking well explain the observed features in the efficacy, selectivity, and mechanism of cholinesterase inhibition by the acridine derivatives. Thus, in a series of acridine derivatives we have found compounds possessing dual properties of effective and selective cholinesterase inhibition together with free radical scavenging, which makes promising the use of the acridine scaffold to create multifunctional drugs for the therapy of neurodegenerative diseases.

Graphical abstract

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Synthesis and application of a “plastic antibody” in electrochemical microfluidic platform for oxytocin determination

Publication date: 15 February 2018
Source:Biosensors and Bioelectronics, Volume 100
Author(s): Piyush Sindhu Sharma, Zofia Iskierko, Krzysztof Noworyta, Maciej Cieplak, Pawel Borowicz, Wojciech Lisowski, Francis D'Souza, Wlodzimierz Kutner
By means of molecular imprinting of a conducting polymer, molecular cavities selective for oxytocin nonapeptide, an autism biomarker, were designed. Embedding of the oxytocin template, and then its extracting from the molecularly imprinted polymer (MIP) was confirmed by the XPS analysis. AFM imaging of the MIP film surface indicated changes in mechanical properties of the film after template extraction. The MIP synthetic receptor was deposited by potentiodynamic electropolymerization as a thin film on an Au film electrode in an electrochemical miniaturized microfluidic cell. The use of this cell allowed to shorten analysis time and to decrease the sample volume. The linear dynamic concentration range extended from 0.06 to 1mM with the limit of detection of 60µM (S/N = 3). Advantageously, sensitivity of the diagnostic microfluidic platform devised for oxytocin determination in both synthetic serum samples and in aqueous solutions was similar and, moreover, it was selective to common interferences, such as oxytocin analogs and potential metabolites.



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Electrochemiluminescence resonance energy transfer system between GNRs and Ru(bpy)32+: Application in magnetic aptasensor for β-amyloid

Publication date: 15 February 2018
Source:Biosensors and Bioelectronics, Volume 100
Author(s): Hong Ke, Haifeng Sha, Yinfang Wang, Weiwei Guo, Xin Zhang, Zhiming Wang, Chusen Huang, Nengqin Jia
Electrochemiluminescent (ECL) assay has gradually drawn increasing interest in the biomedical analysis. This paper proposed a new methodology for ultrasensitive and facile detection of Alzheimer's disease marker β-amyloid (Aβ) by fabricating a sandwich-type ECL sensing platform. Herein, electrochemiluminescence resonance energy transfer (ECL-RET) was employed to determine Aβ concentration, which can be attributed to the quenching effect from RET between Ru(bpy)3²⁺ and gold nanorods (GNRs) acting as ECL-RET electron donor and acceptor, respectively. In this protocol, mesoporous carbon nanospheres were adopted to immobilize ECL reactant Ru(bpy)3²⁺ and antibody via nafion to acquire the RET donor nanocomposites (MOCs/nafion/Ru(bpy)3²⁺/antibody), which were tightly interconnected with epoxy group functionalized Fe3O4 nanoparticles. It is of vital importance that GNRs with exquisite rod shape were synthesized and exhibited a typical absorption peak at 650nm to quench ECL signal of Ru(bpy)3²⁺ effectively. In addition, the ECL emission decreased linearly with the logarithm of Aβ concentration in a wide linear range from 1.0 × 10⁻⁵ to 100ng/mL with a detection limit of 4.2 × 10⁻⁶ng/mL. Furthermore, distinctive and desirable properties were verified to declare the promise for being applicable to analyze the Aβ content in real Alzheimer's cerebrospinal fluid samples with satisfactory results.



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Detection of BCG bacteria using a magnetoresistive biosensor: A step towards a fully electronic platform for tuberculosis point-of-care detection

Publication date: 15 February 2018
Source:Biosensors and Bioelectronics, Volume 100
Author(s): Teresa G. Barroso, Rui C. Martins, Elisabete Fernandes, Susana Cardoso, José Rivas, Paulo P. Freitas
Tuberculosis is one of the major public health concerns. This highly contagious disease affects more than 10.4 million people, being a leading cause of morbidity by infection. Tuberculosis is diagnosed at the point-of-care by the Ziehl-Neelsen sputum smear microscopy test. Ziehl-Neelsen is laborious, prone to human error and infection risk, with a limit of detection of 10⁴ cells/mL. In resource-poor nations, a more practical test, with lower detection limit, is paramount. This work uses a magnetoresistive biosensor to detect BCG bacteria for tuberculosis diagnosis. Herein we report: i) nanoparticle assembly method and specificity for tuberculosis detection; ii) demonstration of proportionality between BCG cell concentration and magnetoresistive voltage signal; iii) application of multiplicative signal correction for systematic effects removal; iv) investigation of calibration effectiveness using chemometrics methods; and v) comparison with state-of-the-art point-of-care tuberculosis biosensors.Results present a clear correspondence between voltage signal and cell concentration. Multiplicative signal correction removes baseline shifts within and between biochip sensors, allowing accurate and precise voltage signal between different biochips. The corrected signal was used for multivariate regression models, which significantly decreased the calibration standard error from 0.50 to 0.03log10 (cells/mL). Results show that Ziehl-Neelsen detection limits and below are achievable with the magnetoresistive biochip, when pre-processing and chemometrics are used.



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Tetrahedral DNA probe coupling with hybridization chain reaction for competitive thrombin aptasensor

Publication date: 15 February 2018
Source:Biosensors and Bioelectronics, Volume 100
Author(s): Ying-Xu Chen, Ke-Jing Huang, Liu-Liu He, Yi-Han Wang
A novel competitive aptasensor for thrombin detection is developed by using a tetrahedral DNA (T-DNA) probe and hybridization chain reaction (HCR) signal amplification. Sulfur and nitrogen co-doped reduced graphene oxide (SN-rGO) is firstly prepared by a simple reflux method and used for supporting substrate of biosensor. Then, T-DNA probe is modified on the electrode by Au-S bond and a competition is happened between target thrombin and the complementary DNA (cDNA) of aptamer. The aptamer binding to thrombin forms an aptamer-target conjugate and make the cDNA remained, and subsequently hybridizes with the vertical domain of T-DNA. Finally, the cDNAs trigger HCR, which results in a great current response by the catalysis of horseradish peroxidase to the hydrogen peroxide + hydroquinone system. For thrombin detection, the proposed biosensor shows a wide linearity range of 10^–13–10⁻⁸M and a low detection limit of 11.6fM (S/N = 3), which is hopeful to apply in biotechnology and clinical diagnosis.



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Contents

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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One year on: Test your knowledge from the previous year

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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Editorial Board

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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EJVES vol. 54, issue 4 (October 2017) - Spanish Translated Abstracts

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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Selected Abstracts from the October Issue of the Journal of Vascular Surgery

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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Forthcoming Events

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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Analysis of gene expression of basic fibroblast growth factor (bFGF) following photodynamic therapy in human gingival fibroblasts

Publication date: Available online 19 September 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Roghayeh Mokhtari Asl, Pegah Ghoraeian, Abbas Monzavi, Abbas Bahador
BackgroundPeriodontal diseases are pathological inflammatory conditions of multifactorial etiology that develops in response to periodontopathic bacteria. Recently, photodynamic therapy (PDT) has begun to be incorporated as an adjuvant treatment for periodontal diseases. However, the effect of PDT on tissue regeneration is not yet completely clear. This study aimed to analyze the gene expression of basic fibroblast growth factor (bFGF) following PDT in human gingival fibroblasts (HuGu) cells in vitro.Materials and MethodsHuGu cells were treated in different groups: 1) ICG (Indocyanine green) alone, 2) Diode laser irradiation alone, 3) PDT (combined ICG with diode laser) and 4) Control (untreated cells). The expression of bFGF gene was evaluated by real-time quantitative reverse transcription PCR (qRT-PCR) in different groups.ResultsICG-PDT treatment using 1000–2000μg/mL of ICG at fluency of 31.25J/cm² displayed a significant dose-dependent increase in expression levels of the bFGF (all P<0.05). The expressions of bFGF were upregulated to 4.13-fold following diode laser irradiation alone with a fluency of 31.25J/cm² (P<0.05) while there was no remarkable difference in expression of bFGF following ICG treatment at concentrations of 500–2000μg/mL (all P>0.05).ConclusionOur results suggest PDT is effective in increasing the expression of bFGF gene, an important factor in periodontal tissue regeneration and could indicate periodontal tissue regeneration.



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Sources, composition, and spectroscopiccharacteristics of dissolved organic matter extractedfrom sediments in an anthropogenic-impacted riverin Southeastern China

Abstract

The fluorescence and ultraviolet spectroscopic characteristics of dissolved organic matter extracted from sediments in an anthropogenic-impacted river (Hao River) in Southeastern China were analyzed in the current study. Excitation–emission matrix (EEM) fluorescence combined with parallel factor analysis (PARAFAC) was conducted to analyze the sources and composition of dissolved organic matter (DOM). The average dissolved organic carbon (DOC) concentrations of all samples at depths of 0–10, 10–20, and 20–30 cm were 317, 319, and 319 mg kg⁻¹ dry weight, respectively. Four components were identified from the fluorescence spectra that consisted of three humic-like components (C1, C2, and C3) and one protein-like component (C4). Component C1 was derived from terrestrial plants and soils. Component C2 in the anthropogenic-impacted Hao River was derived from anthropogenic pollution such as wastewater. Component C3 comprised refractory particles derived from terrestrial plants. Component C4 was autochthonous and produced by the aquatic ecosystem. With the exception of site 4, all sites could be assigned to one of two groups. Group 1 consisted of sites 1, 2, 3, and 5, and group 2 consisted of sites 6, 7, and 8. Our result showed that the sediment in group 2 was more anaerobic than in group 1. Consequently, it could be concluded that this river was polluted by both point and non-point pollution. The terrain slopes cause that water flows from the Yangzi River into group 1. The dilution effect in group 1 resulted in less accumulation of DOM in the sediment of group 1 than group 2.

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Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial

Publication date: Available online 19 September 2017
Source:Vaccine
Author(s): Zhaojun Mo, Yi Mo, Mingqiang Li, Junhui Tao, Xu Yang, Jilian Kong, Dingkai Wei, Botao Fu, Xueyan Liao, Jianli Chu, Yuanzheng Qiu, Darcy A. Hille, Micki Nelson, Susan S. Kaplan
BackgroundA randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE).Methods4040 participants aged 6–12weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n=2020) or placebo (n=2020), administered ∼4weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14days after the third dose. All adverse events (AEs) were collected for 30days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385).ResultsVE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related.ConclusionsIn Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.



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Data and product needs for influenza immunization programs in low- and middle-income countries: Rationale and main conclusions of the WHO preferred product characteristics for next-generation influenza vaccines

Publication date: Available online 20 September 2017
Source:Vaccine
Author(s): Kathleen M. Neuzil, Joseph S. Bresee, Fernando de la Hoz, Kari Johansen, Ruth A. Karron, Anand Krishnan, Shabir A. Madhi, Punam Mangtani, David J. Spiro, Justin R. Ortiz
In 2017, WHO convened a working group of global experts to develop the Preferred Product Characteristics (PPC) for Next-Generation Influenza Vaccines. PPCs are intended to encourage innovation in vaccine development. They describe WHO preferences for parameters of vaccines, in particular their indications, target groups, implementation strategies, and clinical data needed for assessment of safety and efficacy. PPCs are shaped by the global unmet public health need in a priority disease area for which WHO encourages vaccine development. These preferences reflect WHO's mandate to promote the development of vaccines with high public health impact and suitability in Low- and Middle-Income Countries (LMIC). The target audience is all entities intending to develop or to achieve widespread adoption of a specific influenza vaccine product in these settings. The working group determined that existing influenza vaccines are not well suited for LMIC use. While many developed country manufactures and research funders prioritize influenza vaccine products for use in adults and the elderly, most LMICs do not have sufficiently strong health systems to deliver vaccines to these groups. Policy makers from LMICs are expected to place higher value on vaccines indicated for prevention of severe illness, however the clinical development of influenza vaccines focuses on demonstrating prevention of any influenza illness. Many influenza vaccine products do not meet WHO standards for programmatic suitability of vaccines, which introduces challenges when vaccines are used in low-resource settings. And finally, current vaccines do not integrate well with routine immunization programs in LMICs, given age of vaccine licensure, arbitrary expiration dates timed for temperate country markets, and the need for year-round immunization in countries with prolonged influenza seasonality. While all interested parties should refer to the full PPC document for details, in this article we highlight data needs for new influenza vaccines to better demonstrate the value proposition in LMICs.



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Molecular evolution of hepatitis B vaccine escape variants in China, during 2000–2016

Publication date: Available online 20 September 2017
Source:Vaccine
Author(s): Jie Wang, Jing Qiu, Yinwei Zhu, Hui Zhou, Lugang Yu, Yi Ding, Lige Zhang, Zhirong Guo, Chen Dong
Hepatitis B vaccine escape variants are the main threat to hepatitis B virus (HBV) infection in vaccination era worldwide. With 215 genotype B HBV and 313 genotype C HBV vaccine escape variants isolated from China during 2000–2016, we reported that genotype B HBV vaccine escape strains diverged in ∼1997 (95% HPD; 1987–2005), while genotype C HBV vaccine escape strains diverged in ∼1976 (95% HPD; 1955–2003). Additionally, the p-distance of genotype C HBV vaccine escape strains was 0.0291±0.0169, which was significantly higher than that in the genotype B HBV (t=131.02, p<0.05). However, genotype B HBV vaccine escape strains evolved more rapidly than genotype C HBV (2.103×10⁻³ vs 1.083×10⁻³ substitutions/site/year). Bayesian skyline plot analysis showed that the populations of genotype C HBV vaccine escape strains fluctuated more than those in genotype B HBV. Four sites (A5T/S, L21S, T/A126S and T/N131I/A) and 13 sites (N3S, T5A, G10Q/R/E, L21S, T47K/A/V, L98V/P, I/S126N/V/T, Q129H/R/L, T131P/I/N/A, G145A/R, L175S/F, L213I/S, V224A/G) were found to be under positive selection in genotype B and C HBV vaccine escape strains, respectively. More importantly, N3S, L21S, T47K, L98V, I/S126T and L213I mutations were detected in 1 (2.5%), 1 (2.5%), 1 (2.5%), 3 (7.5%), 1 (2.5%), 1 (2.5%) genotype C HBV infected Chinese younger with neonatal HBV vaccination, respectively. Therefore, our results should be valuable in further understanding the molecular evolution of HBV and providing new ideas for the elimination of HBV infection.



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Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice

Publication date: Available online 20 September 2017
Source:Vaccine
Author(s): Dev Karan
We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad5-PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic. One of the prime concerns has been to overcome the immunological tolerance and maintenance of long-term effector T cells. In this study, we further characterized the use of the bivalent vaccine (Ad5-PSA+PSCA) in a transgenic mouse model expressing human PSA in the mouse prostate. We demonstrated the expression of PSA analyzed at the mRNA level (by RT-PCR) and protein level (by immunohistochemistry) in the prostate lobes harvested from the PSA-transgenic (PSA-Tg) mice. We established that the administration of the bivalent vaccine in surgifoam to the PSA-Tg mice induces strong PSA-specific effector CD8⁺ T cells as measured by IFN-γ secretion and in vitro cytotoxic T-cell assay. Furthermore, the use of surgifoam with Ad5-PSA+PSCA vaccine allows multiple boosting vaccinations with a significant increase in antigen-specific CD8⁺ T cells. These observations suggest that the formulation of the bivalent prostate cancer vaccine (Ad5-PSA+PSCA) with surgifoam bypasses the neutralizing antibody response, thus allowing multiple boosting. This formulation is also helpful for inducing an antigen-specific immune response in the presence of self-antigen, and maintains long-term effector CD8⁺ T cells.



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mDCF + Avelumab in Resectable Esophago-gastric Adenocarcinoma (EGA)

Conditions:   Gastric Adenocarcinoma;   Esophageal Adenocarcinoma
Intervention:   Drug: mDCF + Avelumab
Sponsor:   McGill University Health Center
Not yet recruiting - verified September 2017

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Therapeutic Effect Of Luteolin Natural Extract Versus Its Nanoparticles On Tongue Squamous Cell Carcinoma Cell Line

Conditions:   Tongue Neoplasms;   Carcinoma
Interventions:   Drug: luteolin;   Drug: nano-luteolin
Sponsor:   Cairo University
Not yet recruiting - verified September 2017

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GR-MD-02 Plus Pembrolizumab in Melanoma, Non-small Cell Lung Cancer, and Squamous Cell Head and Neck Cancer Patients

Conditions:   Melanoma;   Non-Small Cell Lung Cancer;   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: GR-MD-02;   Drug: Pembrolizumab
Sponsors:   Providence Health & Services;   Galectin Therapeutics Inc.
Recruiting - verified September 2017

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Clinical Thyroidology High-Impact Articles

FREE ACCESS through October 3, 2017
Read Now:

Hypothyroid Symptoms in Pregnant Women Fail to Predict Hypothyroid Status
Elizabeth N. Pearce 

Conflicting Occurrence of Thyroid-Stimulating or Blocking Antibodies Is Seen in 4 to 9% of Patients with Autoimmune Thyroid Disease
Tim I. M. Korevaar

A Deiodinase 2 Polymorphism May Lower Serum T3 and Tissue T3 in Levothyroxine-Treated Patients
Jerome M. Hershman 

Is There a Distinct Pattern of Mutations in Benign Adenomatous Nodules?
Stephen W. Spaulding 

 

The post Clinical Thyroidology High-Impact Articles appeared first on American Thyroid Association.

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Differential cortical contribution of syntax and semantics: An fMRI study on two-word phrasal processing

Publication date: Available online 20 September 2017
Source:Cortex
Author(s): Marianne Schell, Emiliano Zaccarella, Angela D. Friederici
Linguistic expressions consist of sequences of words combined together to form phrases and sentences. The neurocognitive process handling word combination is drawing increasing attention among the neuroscientific community, given that the underlying syntactic and semantic mechanisms of such basic combinations—although essential to the generation of more complex structures—still need to be consistently determined. The current experiment was conducted to disentangle the neural networks supporting syntactic and semantic processing at the level of two-word combinations. We manipulated the combinatorial load by using words of different grammatical classes within the phrase, such that determiner-noun combinations (this ship) were used to boost neural activity in syntax-related areas, while adjective-noun combinations (blue ship) were conversely used to measure neural response in semantic-related combinations. By means of functional magnetic resonance imaging (fMRI), we found that syntax-related processing mainly activates the most ventral part of the inferior frontal gyrus, along the frontal operculum (FOP) and anterior insula (aINS). Fine-grained analysis in BA44 confirmed that the most inferior-ventral portion is highly sensitive to syntactic computations driven by function words. Semantic-related processing on the contrary, rather engages the anterior dorsal part of the left inferior frontal gyrus (IFG) and the left angular gyrus (AG) that is two regions which appear to perform different functions within the semantic network. Our findings suggest that syntactic and semantic contribution to phrasal formation can be already differentiated at a very basic level, with each of these two processes comprising non-overlapping areas on the cerebral cortex. Specifically, they confirm the role of the ventral IFG for the construction of syntactically legal linguistic constructions, and the prominence of the more anterior IFG and the AG for conceptual semantics.



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Inside front cover

Publication date: October 2017
Source:Journal of Anxiety Disorders, Volume 51





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Neonatal and Regressive Forms of Autism: Diseases With Similar Symptoms But A Different Etiology

Publication date: Available online 20 September 2017
Source:Medical Hypotheses
Author(s): William E. Barbeau
Autistic Spectrum Disorder (ASD) can be a debilitating, life-long neurocognitive disease. ASD is caused by genetic and epigenetic factors and largely unknown and poorly understood environmental triggers. Signs and symptoms of ASD often appear in the first year of life while the disease strikes other infants who had previously been developing normally at around 2 years of age. Ozonoff and her colleagues recently suggested that there are three different pathways or trajectories for the development of ASD in infants 6 – 24 months of age. I hypothesize that pathway 1 is caused by in utero insult/injury, pathway 2 by obstetric complications at birth, and pathway 3 by environmental triggers of ASD affecting infants 0 – 3 years of age. Faster progress can be made in elucidating the underlying causes of neonatal and regressive forms of ASD if the diseases are investigated separately, instead of being part of the same disorder.



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Potential Role of the Virchow Robin Space in the Pathogenesis of Bacterial Meningitis

Publication date: Available online 19 September 2017
Source:Medical Hypotheses
Author(s): Patrick Chan, Denis J. Meerdink, James A. Uchizono
Meningitis is an infectious disease commonly arising from a bacterial etiology. The rapid progression of morbidity and mortality due to bacterial meningitis requires critical and imminent time-dependent clinical intervention. Although it is unambiguously clear that bacteria must infiltrate the cerebrospinal fluid, the sequence of events in the pathogenesis of bacterial meningitis has not been fully elucidated. Most reviews of the pathogenesis of bacterial meningitis do not specify the anatomical location of bacteria following BBB traversal. We propose an additional hypothesis focusing on the Virchow-Robin space (VRS). The VRS consists of a small, but identifiable perivascular space formed by a sheath of cells derived from the pia mater. The VRS has been described as an immunological space and possibly having a role in several neuropathological diseases. Solute exchange between cerebrospinal fluid and extracellular fluid occurs at the VRS, with subsequent drainage into the subarachnoid space. Because the VRS is continuous with the subpial space, a more direct route to the meninges is facilitated.The involvement of the VRS may have profound implications on the pathogenesis and therapeutic strategies: (1)nasopharyngeal colonization; (2) penetration into the blood stream after crossing the mucosal and epithelial membranes; (3) proliferation in the bloodstream; (4) extravasations through the endothelium of the post-capillary venules to the perivascular VRS; (5) migration from VRS to subpial space; (6) traversal through pia mater, entering the CSF in the subarachnoid space; (7) invasion of the meninges. The implication of the VRS in the pathogenesis of bacterial meningitis would be two-fold. First, the VRS could provide an additional route of entry of bacteria into the brain. Second, the VRS could provide an area for bacterial proliferation, and thereby serve as a bacterial reservoir in relatively close proximity to the meninges.The clinical consequences of this hypothesis are: 1) clinical interpretation of laboratory findings, and 2) effective antibiotic delivery into the VRS. If the role of the VRS is established as part of bacterial meningitis pathogenesis, antibiotic pharmacokinetics and pharmacodynamics in the VRS need to be determined. This may result in developing novel antibiotic delivery and clinical strategies to improve morbidity and mortality



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Anastasis and the ER Stress Response: Solving the Paradox of the Unfolded Protein Response in Cancer

Publication date: Available online 19 September 2017
Source:Medical Hypotheses
Author(s): Rafael Vincent Manalo
In recent years, studies have suggested a novel pathway for cell survival, which faces scientific skepticism and interest due to its unusual concept of cell 'resurrection' – that is, the anastasis of cells that have undergone apoptosis. While biomarkers have been discovered, many of these genes are related to and upregulated in the endoplasmic reticulum (ER) stress response, which also acts to promote cell survival in the presence of perturbations and protein unfolding. The promises of anastasis, if accepted, will greatly impact translational medicine especially in the treatment of cancer, since apoptosis is generally irreversible in the late stages, and chemotherapy is performed to maximize tumor death and minimize off-target effects. As with all new concepts, there is a need to demarcate anastasis from a well-studied survival mechanism – the ER stress response – if the concept is to progress any further. In this article, it is proposed that anastasis and the ER stress response are one and the same mechanism, demarcated only by the presence of persistent stress. Further, anastasis solves the paradox of the unfolded protein response (UPR) in cancer by providing rationale in C/EBP homologous protein (CHOP)-induced tumor survival, such that CHOP-mediated apoptosis initiates genetic alterations in favor of its survival. After which, the cell regenerates through an enhanced ER stress response. Hence, anastatic cell recovery is the ER stress response post-apoptosis.



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A review of prevalence studies of Autism Spectrum Disorder by latitude and solar irradiance impact

Publication date: Available online 19 September 2017
Source:Medical Hypotheses
Author(s): Somayya Syed, Kathleen A. Moore, Evita March
Autism Spectrum Disorder (ASD) is a lifelong disability with no known cause or cure. Among the suggested etiologies, is Cannell's hypothesis of a deficiency in Vitamin D the main natural source of which is Solar Ultraviolet-B (UVB) radiation. The aim in this paper is to build on this hypothesis and explore the relationship of solar irradiance of which UVB is a component, by latitude with the prevalence rates of ASD. Twenty-five reports published between 2011 and 2016 using comparable diagnostic criteria were reviewed. The results suggest a tendency for the prevalence rates of ASD to be lowest in countries near the equator and for this rate to increase as the latitude increases. These findings provide some support not just for the Vitamin D hypothesis, but also for a new proposition that along with UVB radiation, the entire solar radiation spectrum which reaches the earth, may play a role in ASD. While these results are both novel and encouraging in terms of the potential efficacy of exposure to natural sunlight, further research is warranted before results can be considered definitive, and before the implications of the findings can be implemented clinically.



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Skin advanced glycation content reflects vaginal tissue glycation level in relation to pregnancy

Publication date: Available online 19 September 2017
Source:Medical Hypotheses
Author(s): Homayemem Weli, Jason Cooper, Ying Yang
A few studies have revealed that the advanced glycation content of the vaginal wall in pelvic organ prolapse tissues is elevated. This elevation makes advanced glycation a significant association with the disease. Early detection of vaginal wall glycation could therefore be relevant in the prevention and management of pelvic organ prolapse. A vaginal wall biopsy to detect this would be ideal, but is invasive. Therefore the use of a more accessible organ to access, such as skin, would be beneficial. Our previous independent study suggests that conditions such as pregnancy, can induce a change in the vaginal tissues' glycation content. The aim of this study was to assess whether the skin glycation undergoes similar changes as observed in vaginal tissue glycation in the same subjects in order to prove the hypothesis that skin advanced glycation content can predict vaginal tissue glycation. A rat model was used. The vaginal tissues from non-pregnant and E15-E18 pregnant rats and skin tissues from the same rats were taken for the measurement of advanced glycation content. The glycation marker, pentosidine, was quantified by a high performance liquid chromatography. Our results demonstrated that glycation content in vaginal wall tissues from pregnant rats was lower than the tissues from non-pregnant ones, and a strong positive association between skin and vaginal wall pentosidine level was observed. We conclude that skin pentosidine is reflective of vaginal wall pentosidine. Skin glycation may therefore be a potential tool in the prediction and management of pelvic organ prolapse.



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Contextual effects of surprised expressions on the encoding and recognition of emotional target faces: an event-related potential (ERP) study

Publication date: Available online 20 September 2017
Source:Biological Psychology
Author(s): Huiyan Lin, Claudia Schulz, Thomas Straube
Several studies reported that the encoding and recognition of emotional target faces are modulated by negative contextual expressions. However, it is unknown whether other contextual expressions, such as emotionally ambiguous expressions, affect the encoding and recognition of target faces. To this end, electroencephalography (EEG) was recorded during the presentation of angry or happy target faces after a random sequence of surprised or neutral contextual faces that did not differ in normative valence ratings. Subsequently, participants were asked to perform an unexpected old/new recognition task in which target faces were shown in either the encoded or a non-encoded expression. During the encoding phase, event-related potential (ERP) results showed that surprised as compared to neutral contextual faces led to smaller late positive potentials (LPP) for happy but not for angry target faces. Similar effects were also observed in the N170, even though the interaction of context and target expression failed to reach statistical significance. In the later recognition phase, recognition rates were lower for encoded happy faces when they had been encountered in surprised as compared to neutral context, regardless of whether the target face showed the encoded or a non-encoded expression. However, this context effect was not observed for angry-encoded faces. Taken together, the present study indicates that ambiguous contextual expressions, e.g., surprised faces, affect structural and cognitive encoding and later recognition of happy target faces to a larger extent than neutral contextual faces; whereas angry faces are more resistant to context effects.



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Shopping for food with children: A strategy for directing their choices toward novel foods containing vegetables

Publication date: 1 January 2018
Source:Appetite, Volume 120
Author(s): Xavier Allirot, Edurne Maiz, Elena Urdaneta
Involving children in the different steps of meal preparation has been suggested as a strategy for enhancing dietary habits in childhood. It has previously been shown that involving children in cooking can increase their willingness to taste novel foods and direct their food choices towards foods containing vegetables. The objective of the present study was to assess the effect of involving children in food purchasing on food choices, intake, liking and appetite. A between-subject experiment was conducted with 86 children (from 8 to 10 years old). Forty-three children (PURCHASE group) participated in a workshop dedicated to purchasing the necessary ingredients online for the preparation of three unfamiliar foods containing vegetables: apple and beetroot juice, zucchini tortilla sandwich and spinach cookies. Forty-three children (CONTROL group) participated instead in a creativity workshop. Afterwards, all the children were invited to choose, for an afternoon snack, between three familiar vs. unfamiliar foods: orange vs. apple and beetroot juice, potatoes vs. zucchini tortilla sandwich and chocolate vs. spinach cookie. The mean number of unfamiliar foods chosen per child was higher in the PURCHASE (0.70 ± 0.14) vs. CONTROL (0.19 ± 0.07) group (P = 0.003). The liking for 1 of the 3 unfamiliar foods was higher in the PURCHASE group (P < 0.05). We did not find any difference between the two groups in food intake estimation and in the levels of subjective appetite. This study demonstrates that involving children in purchasing food can help in directing their food choices towards unfamiliar foods containing vegetables. It highlights the importance of involving children in the different steps of meal preparation for decreasing food neophobia.



http://ift.tt/2w7eWBd

Reading Faces: From Features to Recognition

Publication date: Available online 19 September 2017
Source:Trends in Cognitive Sciences
Author(s): J. Swaroop Guntupalli, M. Ida Gobbini
Chang and Tsao recently reported that the monkey face patch system encodes facial identity in a space of facial features as opposed to exemplars. Here, we discuss how such coding might contribute to face recognition, emphasizing the critical role of learning and interactions with other brain areas for optimizing the recognition of familiar faces.



http://ift.tt/2jK5Tob

Evidence-based severity assessment: Impact of repeated versus single open-field testing on welfare in C57BL/6J mice

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Carina Bodden, Sophie Siestrup, Rupert Palme, Sylvia Kaiser, Norbert Sachser, S. Helene Richter
According to current guidelines on animal experiments, a prospective assessment of the severity of each procedure is mandatory. However, so far, the classification of procedures into different severity categories mainly relies on theoretic considerations, since it is not entirely clear which of the various procedures compromise the welfare of animals, or, to what extent. Against this background, a systematic empirical investigation of the impact of each procedure, including behavioral testing, seems essential. Therefore, the present study was designed to elucidate the effects of repeated versus single testing on mouse welfare, using one of the most commonly used paradigms for behavioral phenotyping in behavioral neuroscience, the open-field test. In an independent groups design, laboratory mice (Mus musculus f. domestica) experienced either repeated, single, or no open-field testing – procedures that are assigned to different severity categories. Interestingly, testing experiences did not affect fecal corticosterone metabolites, body weights, elevated plus-maze or home cage behavior differentially. Thus, with respect to the assessed endocrinological, physical, and behavioral outcome measures, no signs of compromised welfare could be detected in mice that were tested in the open-field repeatedly, once, or, not at all. These findings challenge current classification guidelines and may, furthermore, stimulate systematic research on the severity of single procedures involving living animals.



http://ift.tt/2xRnUqL

Isolation of 236U and 239,240Pu from seawater samples and its determination by Accelerator Mass Spectrometry

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Mercedes López-Lora, Elena Chamizo, María Villa-Alfageme, Santiago Hurtado-Bermúdez, Núria Casacuberta, Manuel García-León
In this work we present and evaluate a radiochemical procedure optimised for the analysis of ²³⁶U and ^239,240Pu in seawater samples by Accelerator Mass Spectrometry (AMS). The method is based on Fe(OH)3 co-precipitation of actinides and uses TEVA® and UTEVA® extraction chromatography resins in a simplified way for the final U and Pu purification. In order to improve the performance of the method, the radiochemical yields are analysed in 1 to 10L seawater volumes using alpha spectrometry (AS) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Robust 80% plutonium recoveries are obtained; however, it is found that Fe(III) concentration in the precipitation solution and sample volume are the two critical and correlated parameters influencing the initial uranium extraction through Fe(OH)3 co-precipitation. Therefore, we propose an expression that optimises the sample volume and Fe(III) amounts according to both the ²³⁶U and ^239,240Pu concentrations in the samples and the performance parameters of the AMS facility. The method is validated for the current setup of the 1MV AMS system (CNA, Sevilla, Spain), where He gas is used as a stripper, by analysing a set of intercomparison seawater samples, together with the Laboratory of Ion Beam Physics (ETH, Zürich, Switzerland).

Graphical abstract

http://ift.tt/2fbT5C0

Polyaniline-dicationic ionic liquid coated with magnetic nanoparticles composite for magnetic solid phase extraction of polycyclic aromatic hydrocarbons in environmental samples

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Mohamad Shariff Shahriman, Muggundha Raoov Ramachandran, Nur Nadhirah Mohamad Zain, Sharifah Mohamad, Ninie Suhana Abdul Manan, Suhaila Mohd Yaman
In this present study, magnetic nanoparticles (MNPs) nanocomposites modified with polyaniline (PANI) coated newly synthesised dicationic ionic liquid (DICAT) forming MNP-PANI-DICAT were successfully synthesised as new generation material for magnetic solid phase extraction (MSPE). MNP-PANI-DICAT was characterised by FT-IR NMR, CHN, BET, SEM, TEM, and VSM techniques and the results were compared with MNP-PANI and native MNP. This new material was applied as a magnetic adsorbent for the pre-concentration and separation of polycyclic aromatic hydrocarbons (PAHs) due to the π–π interaction between polyaniline shell and dicationic ionic liquid (DICAT) with PAHs compounds. Under the optimal conditions, the proposed method was evaluated and applied for the analysis of PAHs in environmental samples using gas chromatography-mass spectrometry (GC-MS). The validation method showed good linearity (0.005–500µgL⁻¹) with the coefficient of determination (R²) > 0.999. The limits of detection (LOD) and quantification (LOQ) of the developed method (MNP-PANI-DICAT-MSPE) were in the range of 0.0008–0.2086µgL⁻¹ and 0.0024–0.6320µgL⁻¹, respectively. The enrichment factor (EF) of PAHs on MNP-PANI-DICAT-MSPE were in the range of 7.546–29.632. The extraction recoveries of natural water, sludge, and soil samples were ranged from 80.2% to 111.9% with relative standard deviation (RSD) less than 5.6%. The newly synthesised MNP-PANI-DICAT possess good sensitivity, reusability, and fast extraction of PAHs under the MSPE procedure in various environmental samples.

Graphical abstract

http://ift.tt/2fceElD

Quantitative study of zinc and metallothioneins in the human retina and RPE cells by mass spectrometry-based methodologies

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Sara Rodríguez-Menéndez, Beatriz Fernández, Montserrat García, Lydia Álvarez, Maria Luisa Fernández, Alfredo Sanz-Medel, Miguel Coca-Prados, Rosario Pereiro, Héctor González-Iglesias
The retina contains the highest concentration of zinc in the human eye and it is primarily associated with the retinal pigment epithelium (RPE). Metallothioneins (MTs) are the main cytosolic zinc-ion-binding proteins, exerting a tight control in the number of atoms of Zn-bound to the MTs related with their antioxidant and neuroprotective functions. In order to study the Zn-MT system in retina and RPE, we have implemented mass spectrometry (MS)-based technologies: two complementary element detection methodologies (HPLC- and laser ablation (LA)-ICP-MS) have been successfully employed to study metal content in the human eye as well as to perform speciation studies of Zn-MTs. First, Zn-elemental distribution was studied on cryogenic ocular sections by LA-ICP-MS. Quantitative images of Zn along RPE cell layer and the retina were obtained with a laser beam diameter of 25µm, showing a preferential distribution in the RPE. We carried out then the quantitative speciation of Zn, Fe, and Cu in the water-soluble protein fractions of RPE and retina to study their protein binding profile using HPLC-ICP-MS, where Zn is mainly associated to low molecular mass proteins (i.e., MTs). Finally, the effect of addition of different inductors, such as metal (i.e., ⁶⁸ZnSO4), dexamethasone (DEX) and erythropoietin, was investigated in an in vitro cellular model of human RPE cells (HRPEsv), again using HPLC-ICP-MS in combination with stable isotopes and mathematical calculations based on isotope dilution and isotope pattern deconvolution. Exogenous Zn and DEX were found to increase MT proteins synthesis and exerted a stoichiometric transition in MT proteins in HRPEsv cells.

Graphical abstract

http://ift.tt/2yqJako

Immunosurveillance of Malignant Cells with Complex Karyotypes

Publication date: Available online 19 September 2017
Source:Trends in Cell Biology
Author(s): Alejandro López-Soto, Segundo Gonzalez, Carlos López-Larrea, Guido Kroemer
A wide array of cell-intrinsic surveillance mechanisms maintains the homeostasis of dividing cells and the integrity of the genome. Accumulating evidence also supports a role for cell-extrinsic mechanisms. Among them, the immune system, together with cell-autonomous checkpoint processes, eliminates cells that harbor unbalanced karyotypes generated by mitotic defects.



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Qualitative differences in offline improvement of procedural memory by daytime napping and overnight sleep: an fMRI study

Publication date: Available online 20 September 2017
Source:Neuroscience Research
Author(s): Sho K. Sugawara, Takahiko Koike, Hiroaki Kawamichi, Kai Makita, Yuki H. Hamano, Haruka K. Takahashi, Eri Nakagawa, Norihiro Sadato
Daytime napping offers various benefits for healthy adults, including enhancement of motor skill learning. It remains controversial whether napping can provide the same enhancement as overnight sleep, and if so, whether the same neural underpinning is recruited. To investigate this issue, we conducted functional MRI during motor skill learning, before and after a short day-nap, in 13 participants, and compared them with a larger group (N=47) who were tested following regular overnight sleep. Training in a sequential finger-tapping task required participants to press a keyboard in the MRI scanner with their non-dominant left hand as quickly and accurately as possible. The nap group slept for 60minutes in the scanner after the training run, and the previously trained skill was subsequently re-tested. The whole-night sleep group went home after the training, and was tested the next day. Offline improvement of speed was observed in both groups, whereas accuracy was significantly improved only in the whole-night sleep group. Correspondingly, the offline increment in task-related activation was significant in the putamen of the whole-night group. This finding reveals a qualitative difference in the offline improvement effect between daytime napping and overnight sleep.



http://ift.tt/2xnyd4l

Role of the epigenetic factor Sirt7 in neuroinflammation and neurogenesis

Publication date: Available online 20 September 2017
Source:Neuroscience Research
Author(s): Nicolas Burg, Stefan Bittner, Erik Ellwardt
Epigenetic regulators are increasingly recognized as relevant modulators in the immune and nervous system. The class of sirtuins consists of NAD⁺-dependent histone deacetylases that regulate transcription. Sirtuin family member Sirt1 has already been shown to influence the disease course in an animal model of autoimmune neuroinflammation (experimental autoimmune encephalomyelitis (EAE)). A role of Sirt7, a related epigenetic regulator, on immune system regulation has been proposed before, as these mice are more susceptible to develop inflammatory cardiomyopathy. Sirt7^−/− animals showed no differences in clinical score compared to wild-type littermates after EAE induction with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55, although we found subtle immune alterations at different phases of EAE and decreased survival of newly generated neurons in the hippocampus. Our data indicate that Sirt7 has a slight protective impact on both the adaptive immune system and neurogenesis. However, overall this epigenetic factor is not capable of impacting the acute or chronic phase of neuroinflammation.



http://ift.tt/2wGW8Zg

IFC (editorial board)

Publication date: October 2017
Source:Peptides, Volume 96





http://ift.tt/2hiJLwJ

The International Neuropeptide society pages

Publication date: October 2017
Source:Peptides, Volume 96





http://ift.tt/2hfaG06

Gayle & Richard Olson prize pages

Publication date: October 2017
Source:Peptides, Volume 96





http://ift.tt/2hj7Fbt

A Deep Learning Approach to Estimate Chemically-Treated Collagenous Tissue Nonlinear Anisotropic Stress-Strain Responses from Microscopy Images

Publication date: Available online 20 September 2017
Source:Acta Biomaterialia
Author(s): Liang Liang, Minliang Liu, Wei Sun
Biological collagenous tissues comprised of networks of collagen fibers are suitable for a broad spectrum of medical applications owing to their attractive mechanical properties. In this study, we developed a noninvasive approach to estimate collagenous tissue elastic properties directly from microscopy images using Machine Learning (ML) techniques. Glutaraldehyde-treated bovine pericardium (GLBP) tissue, widely used in the fabrication of bioprosthetic heart valves and vascular patches, was chosen to develop a representative application. A Deep Learning model was designed and trained to process second harmonic generation (SHG) images of collagen networks in GLBP tissue samples, and directly predict the tissue elastic mechanical properties. The trained model is capable of identifying the overall tissue stiffness with a classification accuracy of 84%, and predicting the nonlinear anisotropic stress-strain curves with average regression errors of 0.021 and 0.031. Thus, this study demonstrates the feasibility and great potential of using the Deep Learning approach for fast and noninvasive assessment of collagenous tissue elastic properties from microstructural images.Statement of SignificanceIn this study, we developed, to our best knowledge, the first Deep Learning-based approach to estimate the elastic properties of collagenous tissues directly from noninvasive second harmonic generation images. The success of this study holds promise for the use ofMachine Learning techniques to noninvasively and efficiently estimate the mechanical properties of many structure-based biological materials, and italso enables many potential applications such as serving as a quality control tool to select tissue for the manufacturing of medical devices (e.g. bioprosthetic heart valves).

Graphical abstract

http://ift.tt/2yqd5cv

Poly-ADP ribosylation in DNA damage response and cancer therapy

Publication date: Available online 20 September 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): Wei-Hsien Hou, Shih-Hsun Chen, Xiaochun Yu
Poly(ADP-ribosyl)ation (aka PARylation) is a unique protein post-translational modification (PTM) first described over 50 years ago. PARylation regulates a number of biological processes including chromatin remodeling, the DNA damage response (DDR), transcription, apoptosis, and mitosis. The subsequent discovery of poly(ADP-ribose) polymerase-1 (PARP-1) catalyzing DNA-dependent PARylation spearheaded the field of DDR. The expanding knowledge about the poly ADP-ribose (PAR) recognition domains prompted the discovery of novel DDR factors and revealed crosstalk with other protein PTMs including phosphorylation, ubiquitination, methylation and acetylation. In this review, we highlight the current knowledge on PAR-regulated DDR, PAR recognition domain, and PARP inhibition in cancer therapy.



http://ift.tt/2xwvZR0

Quantitative study of zinc and metallothioneins in the human retina and RPE cells by mass spectrometry-based methodologies

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Sara Rodríguez-Menéndez, Beatriz Fernández, Montserrat García, Lydia Álvarez, Maria Luisa Fernández, Alfredo Sanz-Medel, Miguel Coca-Prados, Rosario Pereiro, Héctor González-Iglesias
The retina contains the highest concentration of zinc in the human eye and it is primarily associated with the retinal pigment epithelium (RPE). Metallothioneins (MTs) are the main cytosolic zinc-ion-binding proteins, exerting a tight control in the number of atoms of Zn-bound to the MTs related with their antioxidant and neuroprotective functions. In order to study the Zn-MT system in retina and RPE, we have implemented mass spectrometry (MS)-based technologies: two complementary element detection methodologies (HPLC- and laser ablation (LA)-ICP-MS) have been successfully employed to study metal content in the human eye as well as to perform speciation studies of Zn-MTs. First, Zn-elemental distribution was studied on cryogenic ocular sections by LA-ICP-MS. Quantitative images of Zn along RPE cell layer and the retina were obtained with a laser beam diameter of 25µm, showing a preferential distribution in the RPE. We carried out then the quantitative speciation of Zn, Fe, and Cu in the water-soluble protein fractions of RPE and retina to study their protein binding profile using HPLC-ICP-MS, where Zn is mainly associated to low molecular mass proteins (i.e., MTs). Finally, the effect of addition of different inductors, such as metal (i.e., ⁶⁸ZnSO4), dexamethasone (DEX) and erythropoietin, was investigated in an in vitro cellular model of human RPE cells (HRPEsv), again using HPLC-ICP-MS in combination with stable isotopes and mathematical calculations based on isotope dilution and isotope pattern deconvolution. Exogenous Zn and DEX were found to increase MT proteins synthesis and exerted a stoichiometric transition in MT proteins in HRPEsv cells.

Graphical abstract

http://ift.tt/2yqJako

Chemical-free fabrication of N, P dual-doped honeycomb-like carbon as an efficient electrocatalyst for oxygen reduction

Publication date: 15 January 2018
Source:Journal of Colloid and Interface Science, Volume 510
Author(s): Lianwen Zhu, Jun Wu, Qiao Zhang, Xiangkui Li, Yiming Li, Xuebo Cao
Heteroatom-doped nanoporous carbons are now emerging as alternatives to platinum and its alloys as electrocatalysts to facilitate oxygen reduction reaction in metal-air batteries and fuel cells. However, the synthesis of nanoporous carbons usually involve in complicated procedures and intensive chemicals, which may dramatically raise their manufacture cost that even surpasses that of precious platinum. Herein, we demonstrate the single-step, chemical-free fabrication of N, P dualdoped honeycomb carbon that has hierarchically porous structure and oxygen electrocatalysis activity close to the benchmark Pt/C. This material was fabricated through the direct pyrolysis of popcorn in a static, semi-opened environment. With this strategy, nitrous and phosphoric groups from proteins and phosphates within the popcorn are condensed with graphitic matrix to form NC and PC bonds, and pyrolysis byproducts (such as H2O and CO2) can etch disordered carbon domains to form hierarchical pores and edge carbons. Practical test of this honeycomb carbon as air electrode of a primary Zn-air battery shows an open-circuit potential of 1.44V and peak power density of 36.6mWcm⁻² that is even better than Pt/C. The impact of this work is that it will facilitate the targeted design and cost-saved fabrication of metal-free catalysts for electrocatalytic applications.

Graphical abstract

http://ift.tt/2ypB4s1

Mechanochemical destruction of DDTs with Fe-Zn bimetal in a high-energy planetary ball mill

Publication date: 15 January 2018
Source:Journal of Hazardous Materials, Volume 342
Author(s): Hong Sui, Yuzhou Rong, Jing Song, Dongge Zhang, Haibo Li, Peng Wu, Yangyang Shen, Yujuan Huang
Mechanochemical destruction has been proposed as a promising, non-combustion technology for the disposal of toxic, halogenated, organic pollutants. In the study presented, additives including Fe, Zn, Fe-Zn bimetal, CaO and Fe2O3 were tested for their effectiveness to remove DDTs by MC. The results showed that Fe-Zn bimetal was the most efficient additive, with 98% of DDTs removed after 4h. The Fe-Zn mass ratio was optimized to avoid possible spontaneous combustion of the ground sample during subsample collection. Inorganic water-soluble chloride in the ground sample increased by 91% after 4h of grinding, which indicated dechlorination during destruction of DDTs. In addition, relationships were established between the rate constant and the rotation speed or the charge ratio. Discrete Element Method (DEM) modeling was used to simulate the motion of the grinding ball and calculate both total impact energy and normal impact energy. The latter expressed a stronger, linear correlation with the rate constant. Therefore, normal impact energy is proposed to be the main driving force in the MC destruction of DDTs.



http://ift.tt/2yq366S

A novel bioreactor system for simultaneous mutli-metal leaching from industrial pyrite ash: Effect of agitation and sulphur dosage

Publication date: 15 January 2018
Source:Journal of Hazardous Materials, Volume 342
Author(s): Sandeep Panda, Ata Akcil, Srabani Mishra, Ceren Erust
Simultaneous multi-metal leaching from industrial pyrite ash is reported for the first time using a novel bioreactor system that allows natural diffusion of atmospheric O2 and CO2 along with the required temperature maintenance. The waste containing economically important metals (Cu, Co, Zn & As) was leached using an adapted consortium of meso-acidophilic Fe²⁺ and S oxidising bacteria. The unique property of the sample supported adequate growth and activity of the acidophiles, thereby, driving the (bio) chemical reactions. Oxido-reductive potentials were seen to improve with time and the system's pH lowered as a result of active S oxidation. Increase in sulphur dosage (>1g/L) and agitation speed (>150rpm) did not bear any significant effect on metal dissolution. The consortium was able to leach 94.01% Cu (11.75% dissolution/d), 98.54% Co (12.3% dissolution/d), 75.95% Zn (9.49% dissolution/d) and 60.80% As (7.6% dissolution/d) at 150rpm, 1g/L sulphur, 30°C in 8days.

Graphical abstract

http://ift.tt/2wz1HgV

A novel method for the sequential removal and separation of multiple heavy metals from wastewater

Publication date: 15 January 2018
Source:Journal of Hazardous Materials, Volume 342
Author(s): Li Fang, Liang Li, Zan Qu, Haomiao Xu, Jianfang Xu, Naiqiang Yan
A novel method was developed and applied for the treatment of simulated wastewater containing multiple heavy metals. A sorbent of ZnS nanocrystals (NCs) was synthesized and showed extraordinary performance for the removal of Hg²⁺, Cu²⁺, Pb²⁺ and Cd²⁺. The removal efficiencies of Hg²⁺, Cu²⁺, Pb²⁺ and Cd²⁺ were 99.9%, 99.9%, 90.8% and 66.3%, respectively. Meanwhile, it was determined that solubility product (Ksp) of heavy metal sulfides was closely related to adsorption selectivity of various heavy metals on the sorbent. The removal efficiency of Hg²⁺ was higher than that of Cd²⁺, while the Ksp of HgS was lower than that of CdS. It indicated that preferential adsorption of heavy metals occurred when the Ksp of the heavy metal sulfide was lower. In addition, the differences in the Ksp of heavy metal sulfides allowed for the exchange of heavy metals, indicating the potential application for the sequential removal and separation of heavy metals from wastewater. According to the cumulative adsorption experimental results, multiple heavy metals were sequentially adsorbed and separated from the simulated wastewater in the order of the Ksp of their sulfides. This method holds the promise of sequentially removing and separating multiple heavy metals from wastewater.

Graphical abstract

http://ift.tt/2wz8lUF

Vitamin D and intestinal calcium transport after bariatric surgery

Publication date: October 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 173
Author(s): Anne L. Schafer
Bariatric surgery is a highly effective treatment for obesity, but it may have detrimental effects on the skeleton. Skeletal effects are multifactorial but mediated in part by nutrient malabsorption. While there is increasing interest in non-nutritional mechanisms such as changes in fat-derived and gut-derived hormones, nutritional factors are modifiable and thus represent potential opportunities to prevent and treat skeletal complications. This review begins with a discussion of normal intestinal calcium transport, including recent advances in our understanding of its regulation by vitamin D, and areas of continued uncertainty. Human and animal studies of vitamin D and intestinal calcium transport after bariatric surgery are then summarized. In humans, even with optimized 25-hydroxyvitamin D levels and recommended calcium intake, fractional calcium absorption decreased dramatically after Roux-en-Y gastric bypass (RYGB). In rats, intestinal calcium absorption was lower after RYGB than after sham surgery, despite elevated 1,25-dihyroxyvitamin D levels and intestinal gene expression evidence of vitamin D responsiveness. Such studies have the potential to shed new light on the physiology of vitamin D and intestinal calcium transport. Moreover, understanding the effects of bariatric surgery on these processes may improve the clinical care of bariatric surgery patients.



http://ift.tt/2xock5b

Highlights from the 19th Workshop on Vitamin D in Boston, March 29–31, 2016

Publication date: October 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 173
Author(s): Sylvia Christakos, John H. White, Martin Hewison, JoEllen Welsh, Paul Lips, Roger Bouillon, Marie B. Demay




http://ift.tt/2jNjrPZ

25-hydroxyvitamin D is associated with adiposity and cardiometabolic risk factors in a predominantly vitamin D-deficient and overweight/obese but otherwise healthy cohort

Publication date: October 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 173
Author(s): Aya Mousa, Negar Naderpoor, Maximilian P.J. de Courten, Robert Scragg, Barbora de Courten
Vitamin D deficiency has reached epidemic proportions worldwide and has recently been linked to cardiometabolic risk factors including obesity, insulin resistance, hypertension, dyslipidemia, as well as type 2 diabetes and cardiovascular disease. The objective of this study was to examine the associations between circulating 25-hydrovitamin D (25(OH)D) levels and cardiometabolic risk factors using direct measures of adiposity, glucose intolerance, and insulin resistance, as well as lipids, blood pressure, and plasma markers of inflammation. We measured circulating 25(OH)D, physical activity (International Physical Activity Questionnaire- IPAQ), anthropometry (body mass index (BMI), waist-to-hip ratio (WHR), % body fat (dual energy X-ray absorptiometry)), metabolic parameters (fasting and 2-h plasma glucose levels during oral glucose tolerance test; insulin sensitivity (M, hyperinsulinaemic-euglycaemic clamp), and cardiovascular and inflammatory profiles (blood pressure (BP), pulse pressure (PP), mean arterial pressure (MAP), plasma lipid levels, white blood cell count (WBC), and plasma high-sensitivity C-reactive protein levels (hsCRP)) in 111 healthy, non-diabetic adults (66 males/45 females; age 31.1±9.2years; % body fat 36.0±10.2%). Mean 25(OH)D was 39.8±19.8 nmol/L with no difference between genders (p=0.4). On univariate analysis, 25(OH)D was associated with% body fat (r=−0.27; p=0.005), 2-h glucose (r=−0.21; p=0.03), PP (r=0.26; p=0.006), and insulin sensitivity (r=0.20, p=0.04), but not with age, BMI, WHR, fasting glucose, BP, MAP, lipids, or inflammatory markers (all p>0.05). After adjusting for age and sex, 25(OH)D remained associated with% body fat (β=−0.12%; p=0.003), 2-h glucose (β=−0.13mmol/L; p=0.02), PP (β=0.12mmHg; p=0.009), and insulin sensitivity (β=0.22mg/kg/min; p=0.03), and became associated with fasting glucose (β=−0.04mmol/L; p=0.04) and hsCRP (β=−0.51mg/L; p=0.04). After adjusting for age, sex, and % body fat, 25(OH)D was no longer associated with insulin sensitivity, 2-h glucose, or hsCRP, but remained associated with fasting glucose (β=−0.05mmol/L; p=0.03) and PP (β=0.10mmHg; p=0.03). 25(OH)D remained associated with fasting glucose (β=−0.06mmol/L; p=0.02) after hsCRP and physical activity were added to the model with % body fat, age, and sex. ​These cross-sectional data suggest that associations between vitamin D and cardiometabolic risk among healthy, non-diabetic adults are largely mediated by adiposity. Large-scale intervention and mechanistic studies are needed to further investigate whether vitamin D has an independent role in the prevention and/or management of cardiometabolic risk and disease.



http://ift.tt/2xnLdqZ