In vivo assessment of polydatin, a natural polyphenol compound, on arsenic-induced free radical overproduction, gene expression, and genotoxicity

Abstract

Arsenic (As) is a well-known contaminant of global groundwater. Its exposure causes several hazardous effects on animals and human via oxidative stress. The present study examined the effect of polydatin (PD) on free radical overproduction in rats exposed to As. Thirty-five male rats randomly allocated into five equal groups. To the control group, physiological saline was given orally and to the second group only 100 mg/L As was given by drinking water for 60 days. The other groups were treated with As (100 mg/L) and PD orally at 50, 100, and 200 mg/kg/day, respectively. Treatment with As enhanced malondialdehyde level but decreased glutathione level in blood, liver, kidney, brain, lung, and heart of rats. Also, As decreased superoxide dismutase and catalase activities of erythrocyte, liver, kidney, brain, lung, and heart in rats. Furthermore, As treatment gave rise to increased DNA damage and gene expressions of interleukin 1 beta (IL-1β), nuclear factor kappa beta (NFκB), p53, and tumor necrosis factor-α (TNF-α) in the lung, brain, kidney, and liver. However, treatment of PD ameliorated As-exposed lipid peroxidation, antioxidant enzymes activities, DNA damage, gene expressions, and histopathological changes in tissues. In conclusion, PD has a dose-dependent protective effect on lipid peroxidation and antioxidant defense mechanism in rats against As exposure.

http://ift.tt/2i5IQRo

Heavy metal distribution in Tiaoxi River’s sediment

Abstract

According to current study, seven surface sediments and three sediment cores were collected from three typical areas of Tiaoxi River, which were living area, agricultural area, and industrial area. The water quantity into the Lake Taihu from the Tiaoxi River accounted for almost one third of the total water quantity by all rivers into the Lake Taihu. To study geochemical features and pollution history of heavy metals in three typical areas of Tiaoxi River, total content and chemical fractionations of Cu, Pb, Cd, Cr, Mn, Zn, Fe, As, and Hg were analyzed for surface and core sediments using the speciation extraction procedure, proposed by the Commission of the European Communities Bureau of Reference (BCR), together with grain size and organic carbon measurements. The results showed that the concentration of nine heavy metals and the variation characteristics of Zn, Cu, Fe, Mn, and Cr are different among five cores, which has shown that the river responses to natural and anthropogenic activities were dissimilar in various areas. BCR sequential extraction showed contents of Cr, Fe, and Cu were dominated in the remaining parts. Non-residual fractions for Zn and Mn contained major portions. Based on RAC (risk assessment core), the risk of Mn was high to very high in the three typical areas, and the risk of Zn was medium in the three typical areas.

http://ift.tt/2Azkm9U

Impact of on-site sanitation systems on groundwater sources in a coastal aquifer in Chennai, India

Abstract

On-site sanitation is the most preferred mode of sanitation due to expensive off-site sanitation. The increasing population especially in the peri-urban areas has led to increasing use of on-site sanitation systems in India. However, the habitations in the vicinity of these systems do not have centralised water supply and are dependent on groundwater sources. However, there is concern about leaching of faecal coliforms and nitrate from the septic tanks to the underlying aquifer. The present study is attempted at two sites in the coastal city of Chennai where on-site sanitation is prevailing. The sample locations (16 nos.) are selected in such a way that groundwater sources are situated in the vicinity of on-site sanitation systems. The groundwater sources are the bore wells installed by the private agencies. It is observed that parameters considered key parameters to study the impact of the on-site sanitation systems, namely Na2⁺, Cl⁻, NO₃⁻, faecal coliform and total dissolved solids, exceed the concentration limits recommended by the Bureau of Indian Standards. The piper diagram analysis identifies that the predominant cations and anions are respectively Na⁺, and Cl⁻, SO₄⁻ and HCO₃⁻.The Gibbs plot shows ground water quality is dominated by the evaporation process in both the seasons. The Cl/HCO₃ ratio in many samples confirms the seawater intrusion in the study area. Elevated concentrations of faecal coliforms in all the samples (16 nos.) confirm the significant amount of groundwater pollution from the on-site sanitation systems. It is desired that policy planners and implementation agencies should undertake detailed scientific and hydrogeological studies of the region in order to examine the feasibility of implementing on-site sanitation systems.

http://ift.tt/2i5XlVq

Distinctive accumulation patterns of heavy metals in Sardinella aurita (Clupeidae) and Mugil cephalus (Mugilidae) tissues

Abstract

The present study assessed the impact of metal pollution on two widely consumed types of wild fish Sardinella aurita and Mugil cephalus captured from the Gulf of Gabes (Tunisia) which is currently experiencing acute environmental problems. A study of the Cd, Cu, Zn, and Pb levels present in the studied site and vital in fish tissues (gills, liver, gonad, and muscle) was undertaken. As expected, muscle, liver, and gonad tissues contained the highest concentrations of all metals except for Zn. The metal levels showed a significant variation of accumulation between species with overall effects of the tested tissues. In addition, the results address the significant effects of the species/tissue interaction. Liver sections showed structural alterations consisting mainly of a significant desquamation of the tissue, a fibroblast proliferation, and a lipid droplet accumulation in both species. Additionally, the presence of skeletal abnormalities affecting the vertebral column was observed in the M. cephalus specimens. As a whole, our data provide the first evidence of distinctive metal accumulation patterns in vital fish tissues as well as the interspecific difference that can be correlated with the biological habits of the two selected models, S. aurita and M. cephalus, known respectively as pelagic and benthopelagic species.

http://ift.tt/2AyaJIO

Lying in wait: Limiting factors on a low-density ungulate population and the latent traits that can facilitate escape from them

Publication date: November 2017
Source:Acta Oecologica, Volume 85
Author(s): Kyle Joly, Tim Craig, Matthew D. Cameron, Adrian E. Gall, Mathew S. Sorum
Predation, habitat, hunting, and environmental conditions have all been implicated as regulatory mechanisms in ungulate populations. The low-density equilibrium hypothesis predicts that in low-density populations, predators regulate their prey and that the population will not escape unless predation pressure is eased. We evaluated survival of adult and juvenile moose (Alces alces) in north-central Alaska to determine whether or not the population supported the hypothesis. We instrumented adult male and female moose with radiocollars and used aerial observations to track parturition and subsequent survival of juvenile moose. Generalized linear mixed-effects models were used to assess survival. Adult annual survival rates were high (∼89%), but may be negatively influenced by winter conditions. Migratory status did not affect moose survivorship or productivity. Approximately 60% of the calf crop died before 5 months of age. Productivity was significantly lower in the northern section of the study area where there is less high-quality habitat, suggesting that, even in this low-density population, nutrition could be a limiting factor. It appears that predation on young calves, winter weather, and nutritional constraints may be interacting to limit this population. Latent traits, such as overproduction of calves and migratory behavior, which do not currently enhance fitness, may persist within this population so that individuals with these traits can reap benefits when environmental conditions change.



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Cyclin-dependent kinase 5 regulates MAPK/ERK signaling in the skin of mice

Publication date: Available online 11 November 2017
Source:Acta Histochemica
Author(s): Xuexian Liu, Pengqian Zhang, Kaiyuan Ji, Junzhen Zhang, Shanshan Yang, Bin Du, Shuaipeng Hu, Ruiwen Fan
Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine/threonine kinase that has been shown to play important roles in many tissues except the nervous system. We previously reported that CDK5 showed differential expression in the transcriptome profiles of the skin of alpacas with different hair colors. To understand the functional role of CDK5 in hair color determination, we constructed CDK5-knockdown mice and identified the effect on the mitogen-activated protein kinase (MAPK) pathway in the mouse skin. Quantitative real-time polymerase chain reaction, co-immunoprecipitation, and western blotting were performed to analyze the effects of CDK5-knockdown on the MAPK pathway in mice. The results showed that MAP3K6 was inhibited by phosphorylated CDK5 through its activator CDK7. The decrease in MAP3K6 levels caused down-regulation of MEK1 and ERK expression, leading to the up-regulation of miR-143-3p, which targets MAP3K6 via Dicer. Taken together, our findings indicate that CDK5 functions in regulating the MAPK pathway. Given that MAP3K6 was inhibited in two directions, this mechanism can provide insight into the contributions of the MAPK/ERK pathway to the inhibition of melanin production.



http://ift.tt/2ACqI9l

Extending the Structural View of Class B GPCRs

Publication date: Available online 11 November 2017
Source:Trends in Biochemical Sciences
Author(s): Chris de Graaf, Gaojie Song, Can Cao, Qiang Zhao, Ming-Wei Wang, Beili Wu, Raymond C. Stevens
The secretin-like class B family of G protein-coupled receptors (GPCRs) are key players in hormonal homeostasis. Recent structures of various receptors in complex with a variety of orthosteric and allosteric ligands provide fundamental new insights into the function and mechanism of class B GPCRs, including: (i) ligand-induced changes in the relative orientation of the extracellular and transmembrane receptor domains; (ii) intramolecular interaction networks that stabilize conformational changes to accommodate intracellular G protein binding; and (iii) allosteric modulation of receptor activation. This review provides a comprehensive analysis of the structural, biochemical, and pharmacological data on class B GPCRs for understanding ligand–receptor interaction and modulation mechanisms and assessing the potential implications for drug discovery for the secretin-like GPCR family.



http://ift.tt/2ysbwue

Feel the Way With a Vibrotactile Compass: Does a Navigational Aid Aid Navigation?.

Author: Weisberg, Steven M.; Badgio, Daniel; Chatterjee, Anjan

DOI: 10.1037/xlm0000472

Publication Date: POST AUTHOR CORRECTIONS, 9 November 2017

http://ift.tt/2i4H2rU

Nucleic acid aptamer-based methods for diagnosis of infections

Publication date: 15 April 2018
Source:Biosensors and Bioelectronics, Volume 102
Author(s): Ki Soo Park
Infectious diseases are a serious global problem, which not only take an enormous human toll but also incur tremendous economic losses. In combating infectious diseases, rapid and accurate diagnostic tests are required for pathogen identification at the point of care (POC). In this review, investigations of diagnostic strategies for infectious diseases that are based on aptamers, especially nucleic acid aptamers, oligonucleotides that have high affinities and specificities toward their targets, are described. Owing to their unique features including low cost of production, easy chemical modification, high chemical stability, reproducibility, and low levels of immunogenicity and toxicity, aptamers have been widely utilized as bio-recognition elements (bio-receptors) for the development of infection diagnostic systems. we discuss nucleic acid aptamer-based methods that have been developed for diagnosis of infections using a format that organizes discussion according to the target pathogenic analytes including toxins or proteins, whole cells and nucleic acids. Also included is, a summary of recent advances made in the sensitive detection of pathogenic bacteria utilizing the isothermal nucleic acid amplification method. Lastly, a nucleic acid aptamer-based POC system is described and future directions of studies in this area are discussed.



http://ift.tt/2zuHVnJ

A facile way to fabricate manganese phosphate self-assembled carbon networks as efficient electrochemical catalysts for real-time monitoring of superoxide anions released from HepG2 cells

Publication date: 15 April 2018
Source:Biosensors and Bioelectronics, Volume 102
Author(s): Xuan Cai, Libo Shi, Wenqian Sun, Hongli Zhao, Hong Li, Haiyan He, Minbo Lan
Quantification of superoxide anions (O2^•−) is significant in the monitoring of many serious diseases and the design of enzyme-mimic catalysts plays the main role in the development of non-enzymatic O2^•− sensors. Herein, we proposed a facile self-assembly process to synthesize manganese phosphate modified carbon networks using three kinds of widely-used carbon materials (MWCNTs, NGS and GO) as pillar connectors. Characterizations demonstrate that manganese phosphate is widely dispersed inside and on the surface of carbon networks without visible morphology. Meanwhile, all three kinds of synthesized catalysts were successfully immobilized on the screen-printed carbon electrodes to evaluate the electrochemical performance of fabricated sensors. The results indicate that sensors based on Mnx(PO4)y modified MWCNTs exhibit high sensitivity with an extremely low detection limit of 0.127μM (S/N = 3) and a wide liner range of 0–1.817mM (R² = 0.998). We further employed the recommended sensors in the real-time monitoring of HepG2 cells released O2^•− under the stimulating of Zymosan (20mg/mL). Noticeably, the proposed sensors exhibit not only sensitive response but also stable current steps upon different addition of Zymosan. The calculated concentrations of cell-released O2^•− vary from 6.772 to 24.652pM cell⁻¹ for the Zymosan amount used in this work. The established novel sensors display low background current and signal noises, thus holding unique advantages in the trace analysis of O2^•− in biological samples and in vivo environment.



http://ift.tt/2zQPYf6

Ultrasensitive electrochemical immunosensor for quantitative detection of HBeAg using Au@Pd/MoS2@MWCNTs nanocomposite as enzyme-mimetic labels

Publication date: 15 April 2018
Source:Biosensors and Bioelectronics, Volume 102
Author(s): Zengqiang Gao, Yueyun Li, Xiaobo Zhang, Jinhui Feng, Ling Kong, Ping Wang, Zhiwei Chen, Yunhui Dong, Qin Wei
A sensitive sandwich-type electrochemical immunosensor for the detection of hepatitis B e antigen (HBeAg) was successfully developed based on the gold@palladium nanoparticles (Au@Pd NPs) loaded by molybdenum disulfide functionalized multiwalled carbon nanotubes (Au@Pd/MoS2@MWCNTs). The resultant nanocomposites not only possessed high specific surface area and good biocompatibility, but also exhibited excellent electro-catalytical property. Au NPs functionalized porous graphene oxide (p-GO@Au) were used as sensing platforms and primary antibodies carriers, which can accelerate the electron transfer and improve the load capacity of primary antibodies (Ab1), improving the sensitivity of the immunosensor. Under optimal conditions, the designed immunosensor could detect target HBeAg concentration in the range from 0.1pg/mL to 500pg/mL, with a low detection limit of 26fg/mL (S/N = 3) for HBeAg. Additionally, the designed immunosensor showed excellent specificity, good reproducibility and acceptable stability. The satisfactory results in analysis of human serum samples indicated that it had potential application in clinical monitoring of tumor markers.



http://ift.tt/2zvyynx

A Novel Series of Enoyl Reductase Inhibitors Targeting the ESKAPE Pathogens, Staphylococcus aureus and Acinetobacter baumannii

Publication date: Available online 11 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jieun Kwon, Tina Mistry, Jinhong Ren, Michael E. Johnson, Shahila Mehboob
S. aureus and A. baumannii are among the ESKAPE pathogens that are increasingly difficult to treat due to the rise in the number of drug resistant strains. Novel therapeutics targeting these pathogens are much needed. The bacterial enoyl reductase (FabI) is as potentially significant drug target for developing pathogen-specific antibiotics due to the presence of alternate FabI isoforms in many other bacterial species. We report the identification and development of a novel N-carboxy pyrrolidine scaffold targeting FabI in S. aureus and A. baumannii, two pathogens for which FabI essentiality has been established. This scaffold is unrelated to other known antibiotic families, and FabI is not targeted by any currently approved antibiotic. Our data shows that this scaffold displays promising enzyme inhibitory activity against FabI from both S. aureus and A. baumannii, as well as encouraging antibacterial activity in S. aureus. Compounds also display excellent synergy when combined with colistin and tested against A. baumannii. In this combination the MIC of colistin is reduced by 10 fold. Our first generation compound displays promising enzyme inhibition, targets FabI in S. aureus with a favorable selectivity index (ratio of cytotoxicity to MIC), and has excellent synergy with colistin against A. baumannii, including a multidrug resistant strain.

Graphical abstract

http://ift.tt/2yv8ohf

Editorial Board

Publication date: December 2017
Source:Alexandria Journal of Medicine, Volume 53, Issue 4





http://ift.tt/2Aw0TqL

Microscopy in addition to chemical analyses and ecotoxicological assays for the environmental hazard assessment of coal tar-polluted soils

Abstract

Chemical analysis of soils contaminated with coal tar indicated that most organic compounds, and particularly PAHs, were contained in coarser particles (> 200 μm). Microscopic observations of this fraction, carried out on polished sections, reported the presence of organic particles in addition to mineral particles. Some organic particles had a very low porosity, and their microstructure did not evolve during biotreatment. Alternatively, other organic particles had a large porosity composed of an interconnected pore network that was open to coal tar surface and thus in contact with soil water. Interconnected porosity seemed to increase during biotreatment in relation to a decrease in the amount of organic compounds. The amount of open porosity in contact with soil water was expected to increase the desorption rate of PAHs. Consequently, the environmental hazard could depend on the amount of open porosity in addition to chemical properties of organic particles, such as their concentration in PAHs. Thus, microscopy can be complementary to chemical analysis and ecotoxicological assays to assess the best strategy for remediation but also to follow the advancement of a biotreatment.

http://ift.tt/2yROSQ3

Nuevas perspectivas para la cirugía radioguiada

Publication date: Available online 11 November 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): E. Goñi Gironés




http://ift.tt/2mhbi7s

Cytoprotective effects of glycyrrhetinic acid liposome against cyclophosphamide-induced cystitis through inhibiting inflammatory stress

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Bo Ge, Daping Yang, Xinmou Wu, Jing Zhu, Wu Wei, Bin Yang
This study was designed to investigate the pharmacological efficacy of glycyrrhetinic acid liposome (GAL) against female mice with nonbacterial cystitis induced by cyclophosphamide (CPS). Mice in different groups were subjected to tests for lactate dehydrogenase (LD), cytokine contents (IL-6, TNF-α) in serum, and histological changes in bladder tissue and to immunoassays. As a result, cyclophosphamide-induced cystitis in mice showed an increased LD level in serum, and the contents of cytokines (IL-6, TNF-α) were elevated. Interestingly, GAL-treated mice showed decreased LD and inflammatory cytokines of IL-6 and TNF-α in blood. Inflammatory infiltration and cell death in bladder tissue were reduced by GAL treatments. In addition, intravesical mRNAs of NF-κB and TNF-α were lowered dose-dependently in GAL-treated mice. As shown in cytohistological staining, the number of intravesical caspase-3, PARP-positive cells decreased in GAL-treated mice. Furthermore, a GAL-treated bladder showed down-regulated NF-κB and TNF-α expressions in a dose-dependent manner. In conclusion, our current findings may be the first to provide scientific evidence demonstrating that glycyrrhetinic acid liposomes provide benefits against cyclophosphamide-induced cystitis, which possibly occurs through underlying mechanisms that inhibit cell death and inflammatory stress.



http://ift.tt/2hkIEx1

Malathion-induced spermatozoal oxidative damage and alterations in sperm quality of endangered trout Salmo coruhensis

Abstract

The use of pesticides has been increased along with increasing the farming activities and has caused environmental impacts deleteriously. In particular, non-target organisms including fish can be affected by toxic effects of pesticides. Therefore, the impacts of malathion (MTN) on oxidative stress and sperm quality were investigated in vitro. The MTN concentrations used on this study were 0 (control), 75, 100, and 125 μg/L. Lipid peroxidation (MDA), non-enzymatic (GSH), and enzymatic (SOD, GSH-Px, and CAT) activities in spermatozoa were examined for determination of oxidative stress status. Our findings showed that motility rate and period of sperm cells significantly decreased with exposure to MTN. Biochemical assays revealed that CAT activity and levels of MDA, GSH increased in spermatozoa based on concentration while activity of GSH-Px and SOD decreased. Consequently, spermatozoa were highly sensitive to MTN exposure. MTN has disruptive effects on sperm quality and caused to oxidative stress in spermatozoa.

http://ift.tt/2AwVoZ5

Pattern of relapse and dose received by the recurrent intraprostatic nodule in low- to intermediate-risk prostate cancer treated with single fraction 19 Gy high dose-rate brachytherapy

Publication date: Available online 11 November 2017
Source:Brachytherapy
Author(s): Lucas C. Mendez, Ananth Ravi, Hans Chung, Chia-Lin Tseng, Matt Wronski, Moti Paudel, Merrylee McGuffin, Patrick Cheung, Andrew Loblaw, Gerard Morton
PurposeThe purposes of this study were to investigate the pattern of relapse in patients with low- or intermediate-risk prostate cancer treated with 19-Gy high-dose-rate brachytherapy (HDR-BT) and to calculate the dose received by the area of recurrence.Methods and MaterialsPatients included in this analysis were treated under a Phase II randomized trial that evaluated the role of 19-Gy HDR-BT monotherapy in low- and intermediate-risk prostate cancers. Multiparametric prostate MRI and prostate biopsy were performed in patients with suspicious local recurrence. The site of local relapse was compared with the initial site of disease. The dose received by the site of recurrence was investigated through registration of the posttreatment multiparametric prostate MRI with the HDR-BT treatment plan.ResultsEight of 87 treated patients were found to have local recurrence after 19-Gy HDR-BT. Seven of the eight recurrences were at the site of initial bulk disease. Seven patients were found to have a more aggressive histology in the posttreatment biopsy. The mean volume of prostate that had received 100% of prescription dose was 97%. Mean dose to area of recurrence was 29.1 Gy, whereas dose to 98% and dose to 90% of the recurrence were 21.6 Gy and 23.2 Gy, respectively.ConclusionsThe relapse pattern after a single 19-Gy HDR-BT is predominantly associated with the site of initial disease. This lends some rationale to future strategies of further focused dose escalation to initial site of disease, notwithstanding the fact that the calculated biologically equivalent dose using linear–quadratic assumptions is already very high.



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Comparison of lung tumor motion measured using a model-based 4DCT technique and a commercial protocol

Publication date: Available online 11 November 2017
Source:Practical Radiation Oncology
Author(s): D. O'Connell, N. Shaverdian, A.U. Kishan, D.H. Thomas, T.H. Dou, J.H. Lewis, J.M. Lamb, M. Cao, S. Tenn, P. Lee, D.A. Low
PurposeTo compare lung tumor motion measured with a model-based technique to commercial 4DCT and describe a workflow for using model-based 4DCT as a clinical simulation protocol.Methods20 patients were imaged using a model-based technique and commercial 4DCT. Tumor motion was measured on each commercial 4DCT dataset, and was calculated on model-based datasets for three breathing amplitude percentile intervals: 5th–85th, 5th–95th and 0th–100th. Internal target volumes (ITV) were defined on the 4DCT and 5th to 85th interval datasets and compared using Dice similarity. Images were evaluated for noise and rated by two radiation oncologists for artifacts.ResultsMean differences in tumor motion magnitude between commercial and model-based images were 0.47±3.0mm, 1.63±3.17mm, and 5.16±4.90mm for the 5th–85th, 5th–95th, and 0th–100th amplitude intervals, respectively. Dice coefficients between ITVs defined on commercial and 5th–85th model-based images had a mean value of 0.77±.09. Single standard deviation image noise was 11.6±9.6 HU in the liver and 6.8±4.7 HU in the aorta for the model-based images compared to 57.7±30 and 33.7±15.4 for commercial 4DCT. Mean model error within the ITV regions was 1.71±0.81mm. Model-based images exhibited reduced presence of artifacts at the tumor compared to commercial.ConclusionTumor motion measured with the model-based technique using the 5th to 85th percentile breathing amplitude interval corresponded more closely to commercial 4DCT than the 5th–95th or 0th–100th intervals, which showed greater motion on average. The model-based technique tended to display increased tumor motion when breathing amplitude intervals wider than 5th–85th were used due to the influence of unusually deep inhalations. These results suggest that care must be taken in selecting the appropriate interval during image generation when using model-based 4DCT methods.



http://ift.tt/2AyaRYv

Three-Dimensional Printer-Aided Casting of Soft, Custom Silicone Boluses(Scsbs) for Head and Neck Radiotherapy

Publication date: Available online 11 November 2017
Source:Practical Radiation Oncology
Author(s): Tsuicheng Chiu, Jun Tan, Mathew Brenner, Xuejun Gu, Ming Yang, Kenneth Westover, Tobin Strom, David Sher, Steve Jiang, Bo Zhao
PurposeCustom tissue compensators provide dosimetric advantages for treating superficial or complex anatomy but currently available fabrication technology is expensive or impractical for most clinical operations and yields compensators that are difficult for patients to tolerate. We aimed to develop an inexpensive, clinically feasible workflow for generating patient-specific, soft, custom silicone boluses (SCSBs) for head-and-neck (HN) radiotherapy.MethodsWe developed a method using 3D–printed parts for generating SCSBs for the treatment of head and neck cancers. The clinical workflow for generation of SCSBs was characterized inclusive of patient simulation to treatment in terms of resource time and cost. Dosimetric properties such as percentage depth dose (PDD) and dose profiles were measured for SCSBs using GaF films. Comprehensive measurements were also conducted on a HN phantom. SCSBs were generated and used for electron or photon based radiation treatments of seven head and neck patients with lesions at nose, cheek, eye or ears. In vivo dose measurements with optically simulated luminescence dosimeters (OSLDs) were performed.ResultsTotal design and fabrication time from patient simulation to radiation treatment start required approximately one week, with fabrication constituting 1–2 working days depending on bolus surface area, volume and complexity. CT and dosimetric properties of the soft bolus were similar to water. In vivo dose measurements on seven treated patients confirmed that the dose deposition conformed to planned doses. Material costs were lower than currently available hard plastic boluses generated with 3D printing technology. All treated patients tolerated SCSBs for the duration of therapy.ConclusionsGeneration and use of SCSBs for clinical use is feasible and effective for the treatment of HN cancers.



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A Format for Reviewing a Research Paper

Publication date: Available online 11 November 2017
Source:Practical Radiation Oncology
Author(s): Robert J. Amdur




http://ift.tt/2i7yvEN

A proteometabolomic study of Actinidia deliciosa fruit development

Publication date: Available online 11 November 2017
Source:Journal of Proteomics
Author(s): Anna Maria Salzano, Anatoly Sobolev, Virginia Carbone, Milena Petriccione, Giovanni Renzone, Donatella Capitani, Monica Vitale, Paola Minasi, Maria Silvia Pasquariello, Gianfranco Novi, Nicola Zambrano, Marco Scortichini, Luisa Mannina, Andrea Scaloni

Graphical abstract

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Proteomic approaches to uncover the flooding and drought stress response mechanisms in soybean

Publication date: Available online 11 November 2017
Source:Journal of Proteomics
Author(s): Xin Wang, Setsuko Komatsu
Soybean is the important crop with abundant protein, vegetable oil, and several phytochemicals. With such predominant values, soybean is cultivated with a long history. However, flooding and drought stresses exert deleterious effects on soybean growth. The present review summarizes the morphological changes and affected events in soybean exposed to such extreme-water conditions. Sensitive organ in stressed soybean at different-developmental stages is presented based on protein profiles. Protein quality control and calcium homeostasis in the endoplasmic reticulum are discussed in soybean under both stresses. In addition, the way of calcium homeostasis in mediating protein folding and energy metabolism is addressed. Finally, stress response to flooding and drought is systematically demonstrated. This review concludes the recent findings of plant response to flooding and drought stresses in soybean employed proteomic approaches.Biological significanceSoybean is considered as traditional-health food because of nutritional elements and pharmacological values. Flooding and drought exert deleterious effects to soybean growth. Proteomic approaches have been employed to elucidate stress response in soybean exposed to flooding and drought stresses. In this review, stress response is presented on organ-specific manner in the early-stage plant and soybean seedling exposed to combined stresses. The endoplasmic reticulum (ER) stress is induced by both stresses; and stress-response in the ER is addressed in the root tip of early-stage soybean. Moreover, calcium-response processes in stressed plant are described in the ER and in the cytosol. Additionally, stress-dependent response was discussed in flooded and drought-stressed plant. This review depicts stress response in the sensitive organ of stressed soybean and forms the basis to develop molecular markers related to plant defense under flooding and drought stresses.

Graphical abstract

http://ift.tt/2yS2V87

Application of ESI-HRMS for molybdenum speciation in natural waters: An investigation of molybdate-halide reactions

Publication date: 1 March 2018
Source:Talanta, Volume 179
Author(s): Duc Huy Dang, R. Douglas Evans
High resolution electrospray ionization mass spectrometry (ESI-HRMS) was used to study the speciation of molybdate in interaction with halides (Cl, F, Br). Desolvation during electrospray ionization induced alteration of aqueous species but method optimization successfully suppressed artefact compounds. At low Mo concentrations, chloro(oxo)molybdate and fluoro(oxo)molybdate species were found and in natural samples, MoO3Cl was detected for the first time, to the best of our knowledge. Apparent equilibrium constants for Cl substitution on molybdate were calculated for a range of pH values from 4.5 to 8.5. A minor alteration in speciation during the gas phase (conversion of doubly charged MoO4^2- to HMoO4^-) did not allow investigation of the molybdate acid-base properties; however this could be determined by speciation modeling. This study provides further evidence that ESI-HRMS is a fast and suitable tool to Deceasedassess the speciation of inorganic compounds such as Mo.

Graphical abstract

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Cancer chemoprevention revisited: Cytochrome P450 family 1B1 as a target in the tumor and the microenvironment

Publication date: Available online 11 November 2017
Source:Cancer Treatment Reviews
Author(s): Gabriele D'Uva, Denisa Baci, Adriana Albini, Douglas M. Noonan
Cancer chemoprevention is the use of synthetic, natural or biological agents to prevent or delay the development or progression of malignancies. Intriguingly, many phytochemicals with anti-inflammatory and anti-angiogenic effects, recently proposed as chemoprevention strategies, are inhibitors of Cytochrome P450 family 1B1 (CYP1B1) an enzyme overexpressed in a wide variety of tumors and associated with angiogenesis. In turn, pro-inflammatory cytokines were reported to boost CYP1B1 expression, suggesting a key role of CYP1B1 in a positive loop of inflammatory angiogenesis. Other well-known pro-tumorigenic activities of CYP1B1 rely on metabolic bioactivation of xenobiotics and steroid hormones into their carcinogenic derivatives. In contrast to initial in vitro observations, in vivo studies demonstrated a protecting role against cancer for the other CYP1 family members (CYP1A1 and CYP1A2) suggesting that that the specificity of CYP1 family inhibitors should be carefully taken into account for developing potential chemoprevention strategies. Recent studies also proposed a role of CYP1B1 in multiple cell types found within the tumor microenvironment, including fibroblasts, endothelial and immune cells. Overall, our review of the current literature suggests a positive loop between inflammatory cytokines and CYP1B1, which in turn may play a key role in cancer angiogenesis, acting on both cancer cells and the tumor microenvironment. Strategies aiming at specific CYP1B1 inhibition in multiple cell types may translate into clinical chemoprevention and angioprevention approaches.



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Advances in sarcoma gene mutations and therapeutic targets

Publication date: Available online 11 November 2017
Source:Cancer Treatment Reviews
Author(s): Peng Gao, Nicole A. Seebacher, Francis Hornicek, Zheng Guo, Zhenfeng Duan
Sarcomas are rare and complex malignancies that have been associated with a poor prognostic outcome. Over the last few decades, traditional treatment with surgery and/or chemotherapy has not significantly improved outcomes for most types of sarcomas. In recent years, there have been significant advances in the understanding of specific gene mutations that are important in driving the pathogenesis and progression of sarcomas. Identification of these new gene mutations, using next-generation sequencing and advanced molecular techniques, has revealed a range of potential therapeutic targets. This, in turn, may lead to the development of novel agents targeted to different sarcoma subtypes. In this review, we highlight the advances made in identifying sarcoma gene mutations, including those of p53, RB, PI3K and IDH genes, as well as novel therapeutic strategies aimed at utilizing these mutant genes. In addition, we discuss a number of preclinical studies and ongoing early clinical trials in sarcoma targeting therapies, as well as gene editing technology, which may provide a better choice for sarcoma patient management.



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Characterization of tissue stiffness of the infraspinatus, erector spinae, and gastrocnemius muscle using ultrasound shear wave elastography and superficial mechanical deformation

Publication date: Available online 11 November 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Joseph P. Kelly, Shane L. Koppenhaver, Lori A. Michener, Laurel Proulx, Francis Bisagni, Joshua A. Cleland
The aim of this study was to compare measurement methods of tissue stiffness using ultrasound shear wave elastography (SWE) and superficial mechanical deformation (MyotonPRO) in the infraspinatus, erector spinae, and gastrocnemius muscles. Thirty healthy volunteers were assessed during rest, 40% and 80% maximum voluntary isometric contraction (MVIC). Correlation of the two methods in the three muscle regions was significant (r=0.23-0.71,p<0.05), and strongest in the gastrocnemius. MyotonPRO reliability was excellent (ICC>0.93), and demonstrated ability to discriminate between the three levels of muscle contraction. SWE demonstrated good reliability in the resting condition (ICC>0.88), but lower during the 2 MVIC conditions. The utility of SWE during isometric contraction may be limited due to the inability to discriminate between 40% and 80% MVIC.



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20. Not only the absence but also amplitude reduction of cortical SEPs predict ominous outcome in comatose patients after cardiac arrest

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): R. Carrai, A. Grippo, F. Lolli, M. Spalletti, M. Scarpino, C. Ielapi, G. Lanzo, A. Peris, G. Cianchi, G. Olivo, S. Valente, A. Amantini
In comatose patients after cardiac arrest (CA) bilateral absence of cortical SEPs is a high reliable predictor of poor outcome but it is present in no more than 40%. Low amplitude pathological SEPs were found in 28.9% of subjects but only few papers analysed the prognostic significance of this pattern.To evaluated prognostic value of N20-P25 amplitude of SEPs, recorded at 6–12h after CA.Retrospectively, we analysed comatose patients after CA admitted to our hospital. SEPs were recorded at 6–12hs after CA. We determined the lowest SEP amplitude in a subject that recovery consciousness We evaluated the accuracy of SEP amplitude in predicting the "no consciousness recovery" by ROC curves. Outcome was evaluated at 6months by GOS.One-hundred and eighteen patients were analysed. None of subjects with N20-P25 amplitude less than 1.2μV recovered consciousness. The area under the ROC curves was 0.96 for "no consciousness recovery". SEP amplitude threshold determined by ROC analysis was 1.21μV. For this SEP amplitude threshold, we found a sensibility: 85.9% and specificity: 100.0%.Not only the absence but also the amplitude reduction (less than 1.2μV) of N20-P25 is associated with no consciousness recovery with very high predictive value.



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Cerebellar transcranial direct current stimulation improves adaptive postural control

Publication date: January 2018
Source:Clinical Neurophysiology, Volume 129, Issue 1
Author(s): Peter Poortvliet, Billie Hsieh, Andrew Cresswell, Jacky Au, Marcus Meinzer
ObjectiveRehabilitation interventions contribute to recovery of impaired postural control, but it remains a priority to optimize their effectiveness. A promising strategy may involve transcranial direct current stimulation (tDCS) of brain areas involved in fine-tuning of motor adaptation. This study explored the effects of cerebellar tDCS (ctDCS) on postural recovery from disturbance by Achilles tendon vibration.MethodsTwenty-eight healthy volunteers participated in this sham-ctDCS controlled study. Standing blindfolded on a force platform, four trials were completed: 60 s quiet standing followed by 20 min active (anodal-tDCS, 1 mA, 20 min, N = 14) or sham-ctDCS (40 s, N = 14) tDCS; three quiet standing trials with 15 s of Achilles tendon vibration and 25 s of postural recovery. Postural steadiness was quantified as displacement, standard deviation and path derived from the center of pressure (COP).ResultsBaseline demographics and quiet standing postural steadiness, and backwards displacement during vibration were comparable between groups. However, active-tDCS significantly improved postural steadiness during vibration and reduced forward displacement and variability in COP derivatives during recovery.ConclusionsWe demonstrate that ctDCS results in short-term improvement of postural adaptation in healthy individuals.SignificanceFuture studies need to investigate if multisession ctDCS combined with training or rehabilitation interventions can induce prolonged improvement of postural balance.



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12. New Telemedicine protocol and patented remote-EEG system from Terni S. Maria Hospital Neurophysiology Division: Experimental assessment and pathway towards large scale service

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): G. Stipa, F. Gabbrielli, D. Frondizi, C. Colosimo, S. Caproni, C. Fanelli, D. Gobbi, L. Giorgi, A. Mancini, M. Domiziani, R. Pasqui, S. Carletti
Terni S. Maria Hospital Neurophysiology Division successfully performed experimental trial for innovative Telemedicine service, using patented remote-EEG system.The Neurophysiologist can be connected from everywhere to the hospital information system through virtual private network and remote device. EEG-passive electrode device is effectively controlled by different direct Remote Desktop freeware softwares. EEG-diagnosis is possible at distance avoiding file exchanges and fulfilling privacy and safety criteria. The connection shares the graphic interface from EEG device desktop to the remote Neurophysiologist, who can also directly control EEG device functions. From 2009 to 2017 a total of 261 EEGs (standard and continuous monitoring) were examined. In the first 6years, specialists operated on EEG device at distance but they sent medical reports by telefax, while from 2016 to 2017 they used report files with digital signature.Two hospital deliberations (n. 875 dated 2008/12/29 and n. 198 dated 2015/03/18) validated the procedure for clinical use, even if into the research protocol. These trial-evidences as well the new regulations on Telemedicine (Intesa Stato-Regioni n. 123/CSR 2016/7/7; EU Directive 2011/24; EU Regulation 2016/679) pave the way for large scale usage of this protocol.The Group of study on Telemedicine in Neurophysiology founded by SINC and Digital-SIT works on this purpose.



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Editorial Board

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12





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Contents

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12





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8. Neurophysiological comparison among tonic, high frequency and burst spinal cord simulation: Novel insights into spinal and brain mechanisms of action

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): T. Bocci, G. De Carolis, D. Barloscio, L. Parenti, M. Valeriani, F. Sartucci
Spinal cord Stimulation (SCS) is an effective option for neuropathic pain treatment. New technological developments, as high-frequency (HF) and Theta Burst Stimulation (TBS), have shown promising results, although putative mechanisms of action are still debated.Twenty-five patients with lower back pain were enrolled and underwent LF, HF and TBS. LEPs were recorded by using a Nd:YAG laser: amplitudes and latencies of the main two components (N1, N2/P2) were compared among different experimental conditions. Similarly, changes in Resting Motor Threshold (RMT), cortical Silent Period (cSP), Short Intracortical Inhibition (SICI) and Intracortical Facilitation (ICF) were evaluated.TBS dampened LEP amplitudes compared with LF (N1: p=0.016; N2/P2: p=0.02) and HF stimulation (p=0.015; p=0.031); while RMT and SICI did not change among experimental conditions, TBS significantly prolonged cSP duration compared with baseline (p=0.002), LF (p=0.048) and HF-SCS (p=0.016); both HF (p=0.004) and TBS (p=0.0039) increased ICF.TBS modulates the sensory-discriminative and the affective-emotional dimension of pain through distinct mechanisms, thus involving intracortical GABAergic and Glutamatergic networks. These results have implications for therapy and for the choice of the stimulation protocol.



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Ultrasound in polyneuropathies – Is size or structure all that matters?

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): A. Kerasnoudis, K. Pitarokoilli, M.-S. Yoon




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First virtual special issue (VSI) in Clinical Neurophysiology: A novel way of enhancing accessibility and visibility of published research

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): Ulf Ziemann




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2. Pain catastrophizing and features of cortical response to painful stimuli in fibromyalgia

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): K. Ricci, E. Vecchio, M. Delussi, A. Montemurno, E. Gentile, M. de Tommaso
Gamma Band Oscillations (GBO) after laser stimuli are currently considered a correlate of subjective pain perception. Habituation of laser evoked potentials (LEPs) is reduced in patients with central amplification of pain stimuli.To correlate LEPs habituation and GBO induced by laser stimulation with subjective pain rating and pain catastrophizing in patients with Fibromyalgia (FM) and controls.We recorded LEPs in 30 FM patients and 15 healthy controls by stimulating the dorsum of the right hand. At the end of each series, the perceived pain was rated on a visual pain analogue scale (VAS). All subjects were submitted to the Pain Catastrophizing Scale – Italian version (PCS-I).The FM patients showed reduced LEPs habituation and increased laser-related GBO. Both patterns correlated with the PCS-I, but not with subjective pain rating.LEPs habituation and GBO may be the expression of cortical mechanisms of nociceptive stimuli processing and exaggerated attentional orientation toward pain experiences.



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6. Trigeminal neuralgia typical and atypical. A disease or two?

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): C.M. Leone, G. Di Stefano, G. Cruccu, A. Truini
Trigeminal Neuralgia (TN) is a clinical condition characterized by a sudden, usually unilateral, brief, stabbing, recurrent pain with a distribution consistent with one or more divisions of the fifth cranial nerve. In the classical form, the genesis of paroxysmal pain has been attributed to areas of focal demyelination due to vascular compression on the nerve. The 20–50% of patients with TN have an atypical form characterized by the presence of constant pain, often described as burning continuous or sub-continuous, as well as paroxysmal pain.We hypothesize an axonal damage underlying the constant pain component.We enrolled 55 patients with typical (n=36) and atypical (n=19) TN according to the criteria of the 3rd edition of the International Classification of Headache Disorders (ICHD-3). Each patient underwent magnetic resonance imaging (MRI), laser evoked potentials (LEPs) and trigeminal reflexes.The comparison between the duration of disease between the two groups showed no significant differences. We found a greater asymmetry of amplitude (healthy side vs affected side) of N2-P2 component from thermal stimulation in the group with atypical TN (p<0.047).The atypical form has an axonal damage and is not a time-bound phenomenon. The involvement of C-fibers could be the mechanism behind continuous pain.



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10. Neurophysiological prognosis in comatose patients after cardiac arrest: The Italian Multicentric Study (ProNeCA)

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): A. Grippo, R. Carrai, D. Audenino, C. Callegarin, M.G. Celani, M. Lombardi, A. Marrelli, O. Mecarelli, C. Minardi, F. Minicucci, L. Motti, L. Politini, F. Valzania, E. Vitelli, M. Scarpino, M. Spalletti, G. Lanzo, C. Cossu, A. Peris, S. Amantini
To evaluate the prognostic value of EEG and SEPs association in post-anoxic comatose patients at different recording time from cardiac arrest (CA) with a prospectic multicentre study.Twelve hospitals participated to the study. EEG and SEPs were recorded within 12, 24, and at 72hs after CA. EEG was classified into "non-continuous" and "continuous". SEPs were dichotomized into "bilaterally absent" (BA) and "present". Neurologic outcome was evaluated at 6months by Cerebral Performance Category.Among the 392 patients admitted after CA in the 11 hospitals 298 where enrolled. Within 12h (120 patients) after CA, continuous EEG predicted good outcome and BA SEPs predicted poor outcome. Continuous EEG and BA-SEPs were never found in the same patient. At 48–72h after CA (142 patients) both grade 2 EEG and BA-SEPs predicted poor outcome.The combination of EEG/SEP findings allows prediction of good and poor outcome (within 12h after CA) and of poor outcome (after 48–72h). Recording of EEG and SEPs in the same patients allows always an increase in the number of cases correctly classified, and an increase of the reliability of prognostication in a single patient due to concordance of patterns.



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14. Cerebellar direct current stimulation modulates hand blink reflex: Implications for defensive behavior in humans

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): T. Bocci, R. Ferrucci, D. Barloscio, L. Parenti, F. Cortese, A. Priori, F. Sartucci
The cerebellum is involved in a wide number of integrative functions. We evaluated the role of cerebellum in peripersonal defensive behavior, as assessed by the so-called hand blink reflex (HBR).Twenty subjects underwent to cerebellar (sham, anodal, cathodal) and motor cortex (anodal or cathodal) tDCS (20′, 2mA). For the recording of HBR, electrical stimuli were delivered using a surface bipolar electrode placed on the median nerve at the wrist and EMG activity recorded from the orbicularis oculi muscle bilaterally. HBR was assessed in four different conditions: "hand far", "hand near" (eyes open), "side hand" and "hand patched" (eyes closed).While sham and cathodal cerebellar stimulation had no significant effect, anodal tcDCS dramatically dampened the magnitude of the HBR, as measured by the area under the curve (AUC), in the hand-patched and side hand conditions only, for ipsilateral (p<0.0001; p=0.0008) as well as contralateral recordings (p=0.46; p=0.66). tDCS applied over the motor area did not affect HBR.Our results support a role of the cerebellum in the defensive responses within the peripersonal space surrounding the face and suggesting a cerebellar involvement in visual-independent learning of defensive behavior.



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18. Intraoperative monitoring in calcified giant thoracic disc herniations in anterior thoracic approach surgery

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): C. Minardi, F. Cultrera, M. Bocchino, G. Pugliese, G. Fedeli, R. Donati
Giant herniated thoracic disc (GHTD) is a surgical challenge with high rate of complication. This was a retrospective study of all patients with calcified GHTD operated between July 2012 and February 2017 with intraoperative neurophysiological monitoring (IOM).The study included 10 patients (9 females and 1 male).IOM study comprised: transcranial electric motor evoked potentials (MEP) and somatosensory evoked potentials (SEP) from all limbs in supine position and after lateral position.IOM MEP at the end of surgery were reduced in 4 recovered in 1, stable in 5 patients and disappeared at left lower limb in 1 patient.IOM SEP were stable in 6 patients, reduced in amplitude in 2, disappeared in 1 and in 1 case SEP at lower limbs were absent from preoperative study.The neurological outcome was stable in 9 and transitory worsened in 1 patient, who lost MEP in lower left limb.The surgical strategy was modified according to IOM findings in 4 cases leading to a partial disc excision, one where IOM MEP disappeared and 3 where MEP decreased without recovering.IOM is usefull in this combined surgery (thoracic surgery and neurosurgery) and can help to remove safely GHDT without new permanent neurological deficits.



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22. New frontiers in neurophysiological instrumental diagnostics in the neonatal intensive care unit: “Smart-EEG”

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): I. Capuano, S. Gabbanini, M. Bastianelli, C. Cossu, I. Roma, S. Lori
The neurophysiological instrumental diagnostics is gaining increasingly an undisputed value, revealing an indispensable practice for both diagnostic and prognostic purposes.Many novelties in medicine have introduced an innovative model of Electronic Health, called E-Health.The purpose of this study is to verify that a new modular device, the BluNet®, is a device able to maximize patient comfort and to operate in a way effective but minimally invasive.The study was conducted on a sample of 10 neonates (5F), with gestational ages between the 27+6 and 41weeks, and the recordings were done simultaneously with two devices: NeMus® (gold standard) and BluNet.We made a visual comparison with the reading software, we extracted and compared the frequency of polygraphic channels (ECG and abdominal breathing) and we made two Bland-Altman-Plots. We also conducted a spectral analysis of the traces.The signals' studies showed that there aren't substantial differences between the signals acquired through the two different methods.BluNet, thanks to its innovative features, is a valid tool for electroencephalographic evaluation and the prospects for future use are manifold: screening for early differential diagnosis, initial evaluation for possible hospitalization, ability to get tests at home.



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1. Laser evoked potential in clinical practice: The diagnostic field in small fiber neuropathy

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): G. Devigili, S. Rinaldo, C. Lettieri, R. Eleopra
Small fiber neuropathy (SFN) is frequently encountered in clinical practice. Due to the small nerve fiber characteristics, the diagnosis requires the use of not conventional tests like skin biopsy, Quantitative sensory testing (QST) and Laser Evoked Potentials (LEPs). The aim of this study was to evaluate the diagnostic value of A-delta LEPs in clinical practice in a large cohort of patients with diagnosis of "definite" SFN.We screened 296 patients evaluated in our institution with confirmed diagnosis of sensory neuropathy. We collected 140 patients with pure SFN and 79 patients with mixed fiber neuropathy (MFN). All underwent clinical evaluation, sensory, painful thermal and mechanical detection thresholds, and quantification of somatic intraepidermal nerve fibers (IENF) by skin biopsy to define the diagnosis. Then, all SFN and MFN patients underwent LEPs. The sensitivity and specificity were calculated compared with our normative data on 67 healthy age-matched subjects. A-delta LEPs at dorsal foot showed 76% sensitivity and 80% specificity in SFN diagnosis, and, if performed bilaterally, the sensitivity and specificity increased (81% and 84%). We did not find any correlation between LEPs and entity of skin denervation, but we found good concordance with warm, heat pain thresholds and pinprick perception.



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3. Immunofluorescence characterization of skin nerve misfolded α-synuclein in different synucleinopathies: A confocal study

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): V. Donadio, A. Incensi, O. El-Agnaf, G. Rizzo, N. Vaikath, C. Scaglione, S. Capellari, M. Stanzani Maserati, R. Pantieri, R. Liguori
Intraneural misfolded α-synuclein (syn) characterized different synucleinopathies such as pure autonomic failure (PAF), idiopathic Parkinson disease (IPD) and dementia with Lewy Bodies (DLB). The aim of this study is to characterize by immunofluorescence the skin intraneural α-synuclein (syn) deposits in PAF, IPD and DLB to ascertain conformation-specific differences which may justify a different clinical phenotype.We identified a total of 21 skin intraneural abnormal syn deposits in PAF (3 patients), 22 in IPD (8 patients) and 40 in DLB (7 patients). Ten healthy subjects were used controls. Skin biopsy was performed on proximal (C7 paravertebral) and distal (thigh and leg) sites. To characterize abnormal syn deposits we used primary antibodies against native α-synuclein (NAC) and against C-terminal α-synuclein epitopes involved in post-translational modifications such as phosphorylation at serine 129 (pS129) and tyrosine 125 (pY125), nitrate α-synuclein at tyr125-133 (nY125-133) and advanced glycation end products (AGEs). Furthermore, the mature amyloid α-synuclein fibrils were characterized by using a non-commercial antibody (Syn-F) and ubiquitin deposits were identified by a specific antibody (UBI).Antibody raised against pS129 disclosed abnormal skin nerves syn deposits in all patients and never in the control group. Abnormal pS129 syn deposits were often (80–90% of all analysed deposits) stained by the antibody recognizing a fibril conformation, seldom (around 40%) by native antibodies and very occasionally by antibodies against nY125-133. Furthermore, abnormal syn deposits were not stained by antibodies against pY125, AGEs and UBI. The immunofluorescence characterization of abnormal syn deposits showed similar findings in IPD, PAF and DLB although in these latter abnormal deposits were quantitatively higher than in IPD.Phosphorylation at serine 129 was the most sensitive and specific epitope to identify skin nerves abnormal syn deposits for the in vivo diagnosis of synucleinopathies; (2) skin syn neuritis showed no relevant immunofluorescence differences in PAF, IPD and DLB suggesting a similar conformation among different clinical phenotypes.



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A look inside the nerve – Morphology of nerve fascicles in healthy controls and patients with polyneuropathy

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): Alexander Grimm, Natalie Winter, Tim W. Rattay, Florian Härtig, Nele M. Dammeier, Eva Auffenberg, Marilin Koch, Hubertus Axer
ObjectivePolyneuropathies are increasingly analyzed by ultrasound. Summarizing, diffuse enlargement is typical in Charcot-Marie Tooth type 1 (CMT1a), regional enlargement occurs in inflammatory neuropathies. However, a distinction of subtypes is still challenging. Therefore, this study focused on fascicle size and pattern in controls and distinct neuropathies.MethodsCross-sectional area (CSA) of the median, ulnar and peroneal nerve (MN, UN, PN) was measured at predefined landmarks in 50 healthy controls, 15 CMT1a and 13 MMN patients. Additionally, largest fascicle size and number of visible fascicles was obtained at the mid-upper arm cross-section of the MN and UN and in the popliteal fossa cross-section of the PN.ResultsCut-off normal values for fascicle size in the MN, UN and PN were defined (<4.8mm², <2.8mm² and <3.5mm²). In CMT1a CSA and fascicle values are significantly enlarged in all nerves, while in MMN CSA and fascicles are regionally enlarged with predominance in the upper arm nerves. The ratio of enlarged fascicles and all fascicles was significantly increased in CMT1a (>50%) in all nerves (p<0.0001), representing diffuse fascicle enlargement, and moderately increased in MMN (>20%), representing differential fascicle enlargement (enlarged and normal fascicles at the same location) sparing the peroneal nerve (regional fascicle enlargement). Based on these findings distinct fascicle patterns were defined.ConclusionNormal values for fascicle size could be evaluated; while CMT1a features diffuse fascicle enlargement, MMN shows regional and differential predominance with enlarged fascicles as single pathology.SignificancePattern analysis of fascicles might facilitate distinction of several otherwise similar neuropathies.



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5. Vocal cord paralysis in children: A new neurophysiological approach for diagnosis and functional prognosis

Publication date: December 2017
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): P. Lanteri, S. Martelli, F. Bollati, L. Pisciotta, M. Tumulo, R. D'Agostino
To establish the possibility to use the methodology of recording corticobulbar motor evoked potentials (CoMEPs) from cricothyroid muscles (CTHY) and vocal cord elicited by transcranial electrical stimulation (TES), as diagnostic tool for predicting function recovery in children with vocal fold immobility (VFI).We included six children (mean age: 4.7years; range: 2–9years) with diagnosis of cord immobility that underwent video-fibro-endoscopy procedure. Under general anaesthesia, we used TES by stimulation over C3/Cz or C4/Cz to elicit CoMEPs. To record CoMEPs from vocal muscles we used two hook wire electrodes (76 micron diameter) passing through a 27-gauge needle endotracheally placed in the vocal muscles after intubation.Recording of CoMEPs in the vocal muscles after TES was successfully performed bilaterally in 4 patients and monolaterally in two patients. TES over the right or left hemisphere elicited responses bilaterally. The mean onset latency for the vocal muscles was 16.4±3ms. The possibility to record CoMEP from vocal muscle was a positive prognostic feature for clinical improvement.This method shows the ability to evaluate the functional integrity of corticobulbar pathways in a reliable manner and adds an additional tool in the diagnosis and prognosis of VFI.



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Influence of lighting color temperature on effort-related cardiac response

Publication date: Available online 11 November 2017
Source:Biological Psychology
Author(s): Ruta Lasauskaite, Christian Cajochen
Higher color temperature refers to a higher proportion of blue spectral components of light, that are known to be associated with higher alertness state in humans. Based on motivational intensity theory (Brehm & Self, 1989), here we predicted that this lighting-induced alertness state should inform about the readiness to perform and this way influence subjective task demand and thus mental effort. To test this, study participants spent 15min under one of four lighting color temperature conditions and then performed a cognitive task. As predicted, effort-related cardiac response, as indexed by a shortened cardiac pre-ejection period, decreased with increasing color temperature of light, as indicated by a significant single planned linear contrast. These results demonstrate that spectral properties of light can influence mental effort mobilization.



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Commentary on “Popliteal Artery Aneurysms in Women”

Publication date: Available online 11 November 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): John D. Kakisis, George Geroulakos




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Thyroid evaluation of children and adolescents with Williams syndrome in Zhejiang Province

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Relation between circulating oxidized-LDL and metabolic syndrome in children with obesity: the role of hypertriglyceridemic waist phenotype

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Marine-Lenhart syndrome in two adolescents, including one with thyroid cancer: a case series and review of the literature

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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High aldosterone and cortisol levels in salt wasting congenital adrenal hyperplasia: a clinical conundrum

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Etiologies of short stature in a pediatric endocrine clinic in Southern Thailand

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Diabetic ketoacidosis, hyperuricemia, and encephalopathy intractable to regular-dose insulin

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Dynamic transcriptional control of macrophage miRNA signature via inflammation responsive enhancers revealed using a combination of next generation sequencing-based approaches

Publication date: Available online 11 November 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Zsolt Czimmerer, Attila Horvath, Bence Daniel, Gergely Nagy, Ixchelt Cuaranta-Monroy, Mate Kiss, Zsuzsanna Kolostyak, Szilard Poliska, Laszlo Steiner, Nikolas Giannakis, Tamas Varga, Laszlo Nagy
MicroRNAs are important components of the post-transcriptional fine-tuning of macrophage gene expression in physiological and pathological conditions. However, the mechanistic underpinnings and the cis-acting genomic factors of how macrophage polarizing signals induce miRNA expression changes are not well characterized. Therefore, we systematically evaluated the transcriptional basis underlying the inflammation-mediated regulation of macrophage microRNome using the combination of different next generation sequencing datasets. We investigated the LPS-induced expression changes at mature miRNA and pri-miRNA levels in mouse macrophages utilizing a small RNA-seq method and publicly available GRO-seq dataset, respectively. Next, we identified an enhancer set associated with LPS-responsive pri-miRNAs based on publicly available H3K4 mono-methylation-specific ChIP-seq and GRO-seq datasets. This enhancer set was further characterized by the combination of publicly available ChIP and ATAC-seq datasets. Finally, direct interactions between the miR-155-coding genomic region and its distal regulatory elements were identified using a 3C–seq approach. Our analysis revealed 15 robustly LPS-regulated miRNAs at the transcriptional level. In addition, we found that these miRNA genes are associated with an inflammation-responsive enhancer network. Based on NFκB-p65 and JunB transcription factor binding, we showed two distinct enhancer subsets associated with LPS-activated miRNAs that possess distinct epigenetic characteristics and LPS-responsiveness. Finally, our 3C–seq analysis revealed the LPS-induced extensive reorganization of the pri-miR-155-associated functional chromatin domain as well as chromatin loop formation between LPS-responsive enhancers and the promoter region. Our genomic approach successfully combines various genome-wide datasets and allows the identification of the putative regulatory elements controlling miRNA expression in classically activated macrophages.



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Rpb5 modulates the RNA polymerase II transition from initiation to elongation by influencing Spt5 association and backtracking

Publication date: Available online 11 November 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Verónica Martínez-Fernández, Ana Isabel Garrido-Godino, María Carmen Mirón-García, Victoria Begley, Antonio Fernández-Pévida, Jesús de la Cruz, Sebastián Chávez, Francisco Navarro
Rpb5 is a subunit shared by the three eukaryotic RNA polymerases although its role in transcription remains unclear. It has been proposed that it makes contact with the promoter DNA and to participate in the co-ordination of the opening/closing of the RNA polymerase II DNA cleft. Here, we report the specific role of Rpb5 in the function of the yeast RNA polymerase II. The rpb5-P151T mutation specifically impairs transcription elongation by RNA polymerase II but does not influence the functions of RNA polymerases I or III. The comparison of RNA polymerase II ChIP and run-on signals indicates a higher tendency to backtrack by this mutant, in agreement with its lower elongation rate and its genetic interactions with dst1Δ mutant. This phenotype is particularly striking shortly after transcription initiation and is linked to differences in the phosphorylation state of the RNA polymerase II and reduced recruitment of Spt5 to transcribe chromatin, thus influencing its anti-backtracking activity. All together, our results reveal an important role of Rpb5 in the transition from initiation to elongation mediated by the RNA polymerase II, by modulating the Spt5 association, and the backtracking activity of the enzyme.



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Title Page/Sections Editors

Publication date: December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1860, Issue 12





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Spontaneous eye blink rate: An index of dopaminergic component of sustained attention and fatigue

Publication date: Available online 11 November 2017
Source:International Journal of Psychophysiology
Author(s): Antonio Maffei, Alessandro Angrilli
Blink rate is a behavioral index highly correlated with frontostriatal dopaminergic activity. The present research was aimed at studying the modulation of spontaneous blink rate in function of the increasing attentional load induced by the Mackworth Clock Test. Since blinking interferes with sensory processing, we expected a decreasing blink rate with increasing attentional demand. Three tasks of 7-min each and different difficulties were administered: the Mackworth had a red dot moving in a circle with intervals varying from 500ms, 350ms to 200ms, corresponding to increasing task difficulty. Participant had to detect the rare jumps of one position by the red dot (targets). The blink rate was recorded from thirty-three female students starting from vertical oculogram recording of the right eye. The time course of blink rate across the 7-min task was also analyzed to test the hypothesis that fatigue arises also during brief tasks depending on the difficulty level. Results showed that the Hard task (200ms dot intervals) was associated with greater percentage of missed targets, faster response times and smaller blink rates with respect to the Medium and Easy ones. Analysis of the time course within the task revealed an increase of blink rate, indexing larger fatigue, starting in the 4th minute, independent from the difficulty level. In addition, trial-by-trial analysis showed that under strong attentional demand dopamine-related blink activity was inhibited throughout the whole task. Results point to the use of blink rate as an ecological index of dopaminergic component of attentional load and fatigue and revealed how human attentiondrops after relatively brief intervals of about 4min.



http://ift.tt/2jiNIGv

Short body length phenotype is compensated by the upregulation of nidogen family members in a deleterious nid1a mutation of zebrafish

Publication date: Available online 11 November 2017
Source:Journal of Genetics and Genomics
Author(s): Peipei Zhu, Zhipeng Ma, Liwei Guo, Wei Zhang, Qinghe Zhang, Ting Zhao, Kunpeng Jiang, Jinrong Peng, Jun Chen




http://ift.tt/2yswGIs

Ataxin-10 is involved in Golgi membrane dynamics

Publication date: Available online 11 November 2017
Source:Journal of Genetics and Genomics
Author(s): Jie Tian, Yingxin Shi, Shanshan Nai, Qizhi Geng, Leiliang Zhang, Gonghong Wei, Xingzhi Xu, Jing Li




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Stress relaxing hyaluronic acid-collagen hydrogels promote cell spreading, fiber remodeling, and focal adhesion formation in 3D cell culture

Publication date: February 2018
Source:Biomaterials, Volume 154
Author(s): Junzhe Lou, Ryan Stowers, Sungmin Nam, Yan Xia, Ovijit Chaudhuri
The physical and architectural cues of the extracellular matrix (ECM) play a critical role in regulating important cellular functions such as spreading, migration, proliferation, and differentiation. Natural ECM is a complex viscoelastic scaffold composed of various distinct components that are often organized into a fibrillar microstructure. Hydrogels are frequently used as synthetic ECMs for 3D cell culture, but are typically elastic, due to covalent crosslinking, and non-fibrillar. Recent work has revealed the importance of stress relaxation in viscoelastic hydrogels in regulating biological processes such as spreading and differentiation, but these studies all utilize synthetic ECM hydrogels that are non-fibrillar. Key mechanotransduction events, such as focal adhesion formation, have only been observed in fibrillar networks in 3D culture to date. Here we present an interpenetrating network (IPN) hydrogel system based on HA crosslinked with dynamic covalent bonds and collagen I that captures the viscoelasticity and fibrillarity of ECM in tissues. The IPN hydrogels exhibit two distinct processes in stress relaxation, one from collagen and the other from HA crosslinking dynamics. Stress relaxation in the IPN hydrogels can be tuned by modulating HA crosslinker affinity, molecular weight of the HA, or HA concentration. Faster relaxation in the IPN hydrogels promotes cell spreading, fiber remodeling, and focal adhesion (FA) formation – behaviors often inhibited in other hydrogel-based materials in 3D culture. This study presents a new, broadly adaptable materials platform for mimicking key ECM features of viscoelasticity and fibrillarity in hydrogels for 3D cell culture and sheds light on how these mechanical and structural cues regulate cell behavior.



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In situ label-free monitoring of human adipose-derived mesenchymal stem cell differentiation into multiple lineages

Publication date: February 2018
Source:Biomaterials, Volume 154
Author(s): Intan Rosalina Suhito, Yoojoong Han, Junhong Min, Hyungbin Son, Tae-Hyung Kim
Precise characterizations of stem cell differentiation into specific lineages, especially in non-destructive and non-invasive manner, are extremely important for generating patient-specific cells without mass loss of differentiated cells. Here, we report a new method capable of in situ label-free quantification of stem cell differentiation into multiple lineages, even at a single cell level. The human adipose-derived mesenchymal stem cells (hADMSCs) were first differentiated into two different types of cells (osteoblasts and adipocytes) and these differentiated cells were then intensively analyzed by micro-Raman spectroscopy. Interestingly, the Raman peaks assigned to lipid droplets and hydroxyapatite were found to be highly specific to the adipocyte (fat cell) and osteoblast (bone cell) and were thus found to be useful for generating label-free single cell Raman images in combination with CH3 (2935 cm⁻¹) peaks for visualizing cell shape. Remarkably, based on these Raman images, we found that the osteogenesis of hADMSCs could be determined and quantified after 9 days of differentiation, which is a week earlier than with the typical alizarin red staining method. In the case of adipogenesis, the increase of lipid droplets in the cytoplasm at the single cell level could be clearly visualized and detected during the entire period of adipogenesis, which is impossible using any other currently available methods such as Oil Red O and immunostaining. Hence, the new method reported in this study is highly promising as an analytical tool for precise in-situ monitoring of stem cell differentiation, and could facilitate the use of stem cell-based materials for the regenerative therapies.



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Evolution of the hygiene hypothesis into biota alteration theory: What are the paradigms and where are the clinical applications?

Publication date: Available online 10 November 2017
Source:Microbes and Infection
Author(s): Chantal Villeneuve, Henry H. Kou, Henrik Eckermann, Antara Palkar, Lauren G. Anderson, Erin A. McKenney, R Randal Bollinger, William Parker
For thousands of years, changes in human cultures have altered the biota associated with the human body, and those alterations have strongly influenced human health. The hygiene hypothesis has evolved over the past 30 years into a nuanced biota alteration theory, but modern medical priorities and regulatory policies have resulted in tragic underutilization of the acquired knowledge.



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Immunomodulation of dual specificity phosphatase 4 during visceral leishmaniasis

Publication date: Available online 10 November 2017
Source:Microbes and Infection
Author(s): Shabina Parveen, Atish Roy Chowdhury, Junaid Jibran Jawed, Suchandra Bhattacharyya Majumdar, Bhaskar Saha, Subrata Majumdar
DUSP4, an inducible protein has a substrate specificity toward ERK1/2, a component of MAP kinase which is enhanced during Leishmania infection. The DUSP4^-/- mice show increased susceptibility towards the infection caused by Toxoplasma gondii and Leishmania mexicana. These observations emphatically established the fact that unlike DUSP1, DUSP4 has host protective role. In our study, it has been Leishmania donovani, the causative agent of visceral leishmaniasis (VL) significantly reduced the expression of DUSP4 during infection. In order to find out the host protective role of DUSP4 in macrophages during VL, we silenced DUSP4 prior to infection and the parasite number within macrophage was counted. Under DUSP4 knock-down condition, phosphorylation of p38 MAPK and generation of pro-inflammatory response like IL-12, TNF-α, and iNOS was decreased significantly. Silencing DUSP4 promoted the phosphorylation of ERK1/2 and the generation of anti-inflammatory response like- IL-10, TGF-β with increased Arginase-1 and Cox-2 activity. Glycyrrhizic Acid (GA), an immunomodulator, already known to suppress L. donovani infection, found to up-regulate DUSP4 expression during L. donovani infection. On the other hand, GA failed to increase Th1 cytokine production and decrease Th2 response during DUSP4 knock-down condition suggesting the key role of DUSP4 while providing protection during L. donovani infection.



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Natural stable isotopic compositions of mercury in aerosols and wet precipitations around a coal-fired power plant in Xiamen, southeast China

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Shuyuan Huang, Lumin Sun, Tingjin Zhou, Dongxing Yuan, Bing Du, Xiuwu Sun
In this study, samples of 18 wet precipitations (WPs) and 38 aerosols were collected around a coal-fired power plant (CFPP) located in Xiamen, southeast China, which was equipped with a seawater flue gas desulfurization system. Total particulate mercury (TPM) in aerosol samples, and total mercury (WP-TM), dissolved mercury (WP-DM) and particulate mercury (WP-PM) in WP samples were analyzed for the natural isotopic compositions of mercury. For the first time, both mass dependent fractionation (MDF) and mass independent fractionation of odd (odd-MIF) and even (even-MIF) isotopes of WP-DM and WP-PM were reported and discussed. Both WP-TM and TPM displayed negative MDF and slightly positive even-MIF. Negative odd-MIF was observed in TPM and WP-PM, whereas positive odd-MIF was observed in WP-TM and WP-DM. It was found that the mercury budget in WP-PM samples was mainly controlled by atmospheric particles. Potential sources of mercury in samples were identified via analysis of mercury isotopic signatures and meteorological data with the NOAA HYSPLIT model. The results showed that TPM and WP-PM in solid samples were homologous and the isotopic compositions of WP-TM depended on those of WP-DM. The ratios of Δ¹⁹⁹Hg/Δ²⁰¹Hg resulting from photochemical reactions and positive Δ²⁰⁰Hg values (from -0.06‰ to 0.27‰) in all samples indicated that the mercury coming from local emission of the CFPP together with long-distance transportation were the two main contributing sources.



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DIDEM - An integrated model for comparative health damage costs calculation of air pollution

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Marco Ravina, Deborah Panepinto, Maria Chiara Zanetti
Air pollution represents a continuous hazard to human health. Administration, companies and population need efficient indicators of the possible effects given by a change in decision, strategy or habit. The monetary quantification of health effects of air pollution through the definition of external costs is increasingly recognized as a useful indicator to support decision and information at all levels. The development of modelling tools for the calculation of external costs can provide support to analysts in the development of consistent and comparable assessments. In this paper, the DIATI Dispersion and Externalities Model (DIDEM) is presented. The DIDEM model calculates the delta-external costs of air pollution comparing two alternative emission scenarios. This tool integrates CALPUFF's advanced dispersion modelling with the latest WHO recommendations on concentration-response functions. The model is based on the impact pathway method. It was designed to work with a fine spatial resolution and a local or national geographic scope. The modular structure allows users to input their own data sets. The DIDEM model was tested on a real case study, represented by a comparative analysis of the district heating system in Turin, Italy. Additional advantages and drawbacks of the tool are discussed in the paper. A comparison with other existing models worldwide is reported.

Graphical abstract

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Evaluating commercial marine emissions and their role in air quality policy using observations and the CMAQ model

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Allison M. Ring, Timothy P. Canty, Daniel C. Anderson, Timothy P. Vinciguerra, Hao He, Daniel L. Goldberg, Sheryl H. Ehrman, Russell R. Dickerson, Ross J. Salawitch
We investigate the representation of emissions from the largest (Class 3) commercial marine vessels (c3 Marine) within the Community Multiscale Air Quality (CMAQ) model. In present emissions inventories developed by the United States Environmental Protection Agency (EPA), c3 Marine emissions are divided into off-shore and near-shore files. Off-shore c3 Marine emissions are vertically distributed within the atmospheric column, reflecting stack-height and plume rise. Near-shore c3 Marine emissions, located close to the US shoreline, are erroneously assumed to occur only at the surface. We adjust the near-shore c3 Marine emissions inventory by vertically distributing these emissions to be consistent with the off-shore c3 Marine inventory. Additionally, we remove near-shore c3 Marine emissions that overlap with off-shore c3 Marine emissions within the EPA files.The CMAQ model generally overestimates surface ozone (O3) compared to Air Quality System (AQS) site observations, with the largest discrepancies occurring near coastal waterways. We compare modeled O3 from two CMAQ simulations for June, July, and August (JJA) 2011 to surface O3 observations from AQS sites to examine the efficacy of the c3 Marine emissions improvements. Model results at AQS sites show average maximum 8-hr surface O3 decreases up to ∼6.5 ppb along the Chesapeake Bay, and increases ∼3–4 ppb around Long Island Sound, when the adjusted c3 Marine emissions are used.Along with the c3 Marine emissions adjustments, we reduce on-road mobile NOX emissions by 50%, motivated by work from Anderson et al. 2014, and reduce the lifetime of the alkyl nitrate species group from ∼10 days to ∼1 day based on work by Canty et al. 2015, to develop the "c3 Science" model scenario. Simulations with these adjustments further improve model representation of the atmosphere. We calculate the ratio of column formaldehyde (HCHO) and tropospheric column nitrogen dioxide (NO2) using observations from the Ozone Monitoring Instrument and CMAQ model output to investigate the photochemical O3 production regime (VOC or NOX-limited) of the observed and modeled atmosphere. Compared to the baseline, the c3 Science model scenario more closely simulates the HCHO/NO2 ratio calculated from OMI data.Model simulations for JJA 2018 using the c3 Science scenario show a reduction of surface O3 by as much as ∼13 ppb for areas around the Chesapeake Bay and ∼2–3 ppb at locations in NY and CT downwind of New York City. These reductions are larger in 2018 than in 2011 due to a change in the photochemical O3 production regime in the Long Island Sound region and the projected decline of other (non-c3 Marine) sources of O3 precursors, highlighting the importance of proper representation of c3 Marine emissions in future modeling scenarios.



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Observation-based trends in ambient ozone in the Czech Republic over the past two decades

Publication date: January 2018
Source:Atmospheric Environment, Volume 172
Author(s): Iva Hůnová, Vít Bäumelt
We present the trends in ambient ozone concentrations based on high quality data measured continuously at 26 long-term monitoring sites (9 urban, 17 rural including 10 mountain stations) in the Czech Republic in 1994–2015. We considered annual and summer medians, the 10^th and 98^th percentiles, maximum daily 8-h running mean concentrations and exposure index AOT40F. For all indicators taken into account except for the 10^th percentile, our results showed a similar pattern with significant decreasing trends for about one half of the examined sites. We obtained similar results for all types of sites. The most pronounced decrease in O3 concentrations was recorded at mountain sites. Namely, at the Šerlich mountain site, with an overall decrease per year in annual median by 0.43 ppb, summer median by 1.17 ppb, maximal daily 8-h average by 0.45 ppb, the 10^th percentile by 0.62 ppb. The peak concentrations indicated by the 98^th percentile and AOT40F decreased most at urban site České Budějovice by 0.75 ppb and 0.84 ppb h per year, respectively. For sites exhibiting significant decreasing trends, an overall decrease per year in annual median was 0.22 ppb, in summer median 0.41 ppb, in the 10^th percentile 0.23 ppb, in the 98^th percentile 0.53 ppb, and in AOT40F 0.51 ppb h. A significant increasing trend was detected only in the 10^th percentile at just three sites, with the highest increase of 0.19 ppb per year recorded at the rural site Sněžník. Moreover, a consistent decrease in limit value exceedances was detected, with by far the highest violation recorded in the meteorologically exceptional year of 2003.Out of the 26 sites under review, seven have not recorded a significant decreasing trend in O3 in any of the considered statistics. The lack of trends in O3 at these seven sites is likely associated with changing time patterns in local NO and NO2 emissions: in particular, with the increasing ratio in NO2/NOx. There is an obvious geographical pattern in recorded O3 trends: most of the sites with no trend detected are situated in the North-western region of the CR with numerous energy-producing large emission sources, partly denitrified recently. Our results clearly indicated that, for O3 decrease, the ratio between individual NO and NO2 forms is critical, and that a simultaneous significant decrease in both NO and NO2 concentrations is not a sufficient prerequisite. Apart from changes in car fleet in urban areas or near motorways, this factor might be of particular relevance in formerly highly polluted areas, where emissions from large power plants recently substantially decreased.



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Impact of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) on cancer treatment outcomes: An overview about well-established and recently emerging clinical data.

Publication date: Available online 11 November 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Yassine Lalami, Jean Klastersky
Despite the overwhelming evidence for the role of granulocyte colony stimulating factors (G-CSF) in managing febrile neutropenia (FN) risk, chemotherapy-induced neutropenia (CIN) and/or FN still remain the most common reasons for reducing relative dose intensity (RDI) and/or delaying chemotherapy schedule. The need to maintain RDI to ensure optimal clinical outcomes is one of the key rationales for utilizing G-CSF. There is a high incidence of reduced RDI in both curative and palliative settings, and this observation is especially evidenced in retrospective analyses. Reduced RDI leads to significantly decreased survival outcomes and quality of life in various malignancies at various clinical settings and stages.Beyond its role as a surrogate prognostic marker, high-grade CIN may have an unexpected predictive role in clinical practice, as illustrated by several data relating CIN occurrence with favorable survival outcomes; this may be due to the fact that body surface area (BSA) – based calculation of dose may not fully account for the pharmacokinetics (PK) of cytotoxic drugs and the fact that there may be variability in drug metabolism between patients treated with same chemotherapy regimens.



http://ift.tt/2AvwYyU

Improvement of in-situ gamma spectrometry methods by Monte-Carlo simulations

Publication date: Available online 10 November 2017
Source:Journal of Environmental Radioactivity
Author(s): Dusan Mrdja, Kristina Bikit, Sofija Forkapic, Istvan Bikit, Jaroslav Slivka, Jan Hansman
Performing in-situ measurements of gamma radiation originating from soil requires adequate detection efficiency curves, which can be obtained by Monte-Carlo simulations. In simulations, soil density of 1.046 g/cm³ was used, with the following elemental composition of soil in which gamma radiation was generated: O - 47%, Si −35%, Al - 8%, Fe - 3.9%, C - 2.1%, Ca - 1.4%, K - 1.3%, N - 0.6%, Mg - 0.6%, N - 0.1%. Soil matrix was represented by cylindrical volume of 1.5 m diameter and 0.5m thickness, while germanium detector was placed at 1 m height above the soil. The simulated gamma spectrum, originated from K-40, as well as from members of Th-232 chain, and daughters of Ra-226, was obtained. Homogeneous distribution of various radionuclides (Ra-226, Th-232, K-40) in soil matrix is considered in this work. Gamma spectra obtained in simulations were analyzed, and together with simulated detection efficiency data they provide comparison with real experimental measurements and practical application of results derived by Monte-Carlo simulations. As a result of this work, the corresponding detection efficiency curve for HPGe detector was obtained, which can be applied for in-situ measurements of radionuclide concentration in soil, assuming uniform radionuclide distribution.In order to validate our simulation results regarding detection efficiency, we performed in-situ measurements of soil radioactivity and compared the obtained activity concentrations with laboratory measurements. We found a good agreement, within activity concentration uncertainty, between in-situ measurement results and average values of activity concentrations obtained by laboratory measurements.



http://ift.tt/2zuHIkb

TERT promoter hypermethylation is associated with metastatic disease in abdominal paraganglioma

Abstract

Telomere maintenance, a hallmark of cancer for cell immortalization, is commonly achieved by telomerase activation through induction of the telomerase reverse transcriptase (TERT) gene. Pheochromocytomas (PCC) and abdominal paragangliomas (PGL) (together PPGL) are endocrine tumours for which TERT promoter mutations and telomerase activation have been previously reported [1]. Only 10-15% of PPGL metastasize, however in the absence of metastases, the identification of malignant disease is a diagnostic dilemma. Over 30% of PPGL exhibit a constitutional mutation in one of 14 susceptibility genes, and additionally, recurrent somatic mutations occur frequently [2]. Mutations in VHL, SDHx and EPAS1 define the Cluster 1 mRNA expression profile with pseudo-hypoxic effects, and mutations in HRAS, MAX, NF1, RET and TMEM127 define Cluster 2 with activation of kinase-signaling pathways [2].

This article is protected by copyright. All rights reserved.

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Efficacy of subcutaneous injection of platelet-rich plasma in alopecia: A clinical and histological pilot study on a rat model with a six-month long-term follow-up experience

Summary

Purpose

To assess the potential of platelet-rich plasma (PRP) subcutaneous injection of to treat alopecia and to evaluate local toxicity.

Materials-Methods

Twelve Hairless rats were used. At D0, we performed systematic clinical examination and divided the rat back into four quadrants (Q). We initiated subcutaneous injection using either PRP in PRPQ+, platelet-poor plasma (PPP) in PPPQ+, physiological serum (PS) in PSQ+, or no treatment (Q4). At D7, D14, D21, and D28 but also second month (M2), M3, M4, M5, rats had exactly the same injection procedure. Follow-up with PRP efficacy and toxicity at D28 and M6 using clinical and histological evaluation was performed.

Results

Hair density was significantly improved at D28 and at M6 for PRPQ+ vs PSQ+ (respectively, P = .0156 and P = .0313), PPPQ+ (respectively, P = .042 and P = .046). Significant histological improvement was observed between D28 and M6, for PRPQ+ vs PPPQ+ and PSQ+ for vessels (respectively, P = .0160 and P = .021), collagen (respectively, P = .0036 and P = .032), and epithelium (respectively, P = .0138 and P = .022) with no local toxicity.

Conclusion

Our study suggests that subcutaneous PRP injections using controlled concentration of platelets and leukocytes improve hair growth.

http://ift.tt/2AAMTwT

Filling the periorbital hollows with hyaluronic acid gel: Long-term review of outcomes and complications

Summary

Introduction

Hyaluronic acid gel has been used for rejuvenation of the periorbital tissues since 2004. The in-office, nonsurgical procedural nature has resulted in the growing popularity of the use of fillers. The periorbital region poses unique challenges to the cosmetic surgeon. Malar edema, blue-gray dyschromia, and contour irregularities are well reported short-term complications. We present a long-term follow-up review of complications associated with periocular injection of hyaluronic acid gel fillers.

Methods

Retrospective review of 147 patients with at least a 5-year follow-up period since the first injection. Five senior masked reviewers were asked to grade photographs of patients in comparison with preinjection photographs. Grading was based on a reference photographic key looking specifically at the presence and severity of malar edema, blue-gray dyschromia, and contour irregularity.

Results

Malar edema (11%), blue-gray dyschromia (31.3%), and contour irregularities (30.5%) continue to be problems in longer term follow-up of patients. The vast majority (90%) of these complications were mild and required no intervention. There is no statistically significant difference in the mean volumes injected by severity grading of each measured complication.

Conclusion

Hyaluronic acid gel fillers of the periorbital region are well tolerated in our long-term follow-up experience. The vast majority of cases of malar edema, blue-gray dyschromia, and contour irregularities are mild and do not require intervention. Conservative treatment and tailored treatment approaches, in terms of volume and frequency of injections, may decrease the tendency of these adverse effects to occur.

http://ift.tt/2yrEeuY

Microparticules membranaires et maladies respiratoires

Publication date: Available online 11 November 2017
Source:Revue des Maladies Respiratoires
Author(s): B. Renaud-Picard, J. Toussaint, A. Leclercq, J. Reeb, L. Kessler, F. Toti, R. Kessler
Les microparticules (MP) sont des fragments de membrane plasmiques émis par les cellules après stimulation physiologique ou lors d'un stress comme l'inflammation ou les infections. Leur production est corrélée au taux d'apoptose cellulaire. Toutes les cellules peuvent produire des MP, mais elles sont principalement émises par les plaquettes, les cellules endothéliales et les leucocytes. Elles sont porteuses de nombreuses molécules bio-actives, caractéristiques de la cellule parentale qui leur confèrent des capacités de biomarqueurs et de bio-effecteurs. Les MP sont présentes dans la circulation sanguine, mais aussi les tissus et divers fluides biologiques. Le taux de MP circulantes peut varier au cours de multiples pathologies. Elles ont été le sujet de nombreuses études dans le domaine des maladies cardiovasculaires et de l'oncologie. Au niveau pulmonaire, elles sont présentes dans le sang et dans le compartiment aérien. Elles semblent jouer un rôle dans l'homéostasie pulmonaire à l'état physiologique mais également dans l'expression de diverses pathologies. Dans cette revue de la littérature, nous nous sommes intéressés aux variations quantitatives et qualitatives des MP ainsi qu'à leur impact potentiel au cours des pathologies des voies aériennes telles que la bronchopneumopathie chronique obstructive (BPCO), l'asthme, la fibrose pulmonaire et l'hypertension pulmonaire.Microparticles (MP) are plasmic membrane fragments released from cells after physiological stimulation or stress conditions like inflammation or infection. Their production is correlated to the rate of cell apoptosis. All types of cells can produce MP but they are produced mainly by platelets, endothelial cells, and leukocytes. They carry many bio-active molecules on their surface, specific to the parental cell, giving them the ability to be biomarkers and bio-effectors. MP are present in circulating blood, tissues and many biological fluids. Circulating MP levels can change during the course of many diseases. They have been the subject of many studies in the fields of cardiovascular disease and oncology. In the lungs, they are present in circulating blood and in the airways. They seem to have a role in pulmonary homeostasis in physiological situations and also in the expression of several disease processes. In this review of the literature, we were interested in the quantitative and qualitative variations in MP and their impact in airway diseases like chronic obstructive pulmonary disease (COPD) and asthma, pulmonary fibrosis and pulmonary hypertension.



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Morphométrie du tissu pulmonaire : de la méthode manuelle à l’automatisation à haut débit

Publication date: Available online 11 November 2017
Source:Revue des Maladies Respiratoires
Author(s): C. Sallon, D. Soulet, Y. Tremblay
Les recherches de Weibel ont démontré que toute altération de la structure pulmonaire a des effets sur la fonction. Cette démonstration a nécessité une analyse quantitative des structures pulmonaires nommée morphométrie, possible grâce à la stéréologie, un ensemble de méthodes basées sur des principes de géométrie et de statistiques. Ses travaux ont permis de mieux comprendre l'harmonie morphologique du poumon, indispensable à son bon fonctionnement. Un déséquilibre conduit à des physiopathologies telles que la bronchopneumopathie chronique obstructive ou maladies pulmonaires obstructives chroniques (appellation nord-américaine) chez l'adulte et la dysplasie bronchopulmonaire chez le nourrisson. C'est en étudiant ce déséquilibre que de nouvelles approches thérapeutiques peuvent être élaborées. Ces avancées ne sont réalisables que grâce à des méthodes d'analyses morphométriques de plus en plus précises et pointues, en particulier grâce à l'automatisation à haut débit de ces méthodes. Cette revue fait un comparatif entre une méthode automatisée que nous avons développée dans le laboratoire et les méthodes semi-manuelles d'analyses morphométriques. L'automatisation des mesures morphométriques est un atout fondamental dans l'étude de la physiopathologie pulmonaire car c'est une assurance de robustesse, de reproductibilité et de rapidité. Cet outil va ainsi contribuer significativement à l'accélération de la course au développement de nouveaux médicaments.Weibel's research has shown that any alteration of the pulmonary structure has effects on function. This demonstration required a quantitative analysis of lung structures called morphometry. This is possible thanks to stereology, a set of methods based on principles of geometry and statistics. His work has helped to better understand the morphological harmony of the lung, which is essential for its proper functioning. An imbalance leads to pathophysiology such as chronic obstructive pulmonary disease in adults and bronchopulmonary dysplasia in neonates. It is by studying this imbalance that new therapeutic approaches can be developed. These advances are achievable only through morphometric analytical methods, which are increasingly precise and focused, in particular thanks to the high-throughput automation of these methods. This review makes a comparison between an automated method that we developed in the laboratory and semi-manual methods of morphometric analyzes. The automation of morphometric measurements is a fundamental asset in the study of pulmonary pathophysiology because it is an assurance of robustness, reproducibility and speed. This tool will thus contribute significantly to the acceleration of the race for the development of new drugs.



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