Πέμπτη 12 Οκτωβρίου 2017
Overexpression of microRNA-495 improves the intestinal mucosal barrier function by targeting STAT3 via inhibition of the JAK/STAT3 signaling pathway in a mouse model of ulcerative colitis
Publication date: Available online 12 October 2017
Source:Pathology - Research and Practice
Author(s): Xian-Qun Chu, Jing Wang, Guang-Xiang Chen, Guan-Qi Zhang, De-Yong Zhang, Yong-Yan Cai
We aim to investigate the role of microRNA-495 (miR-495) in the intestinal mucosal barrier by indirectly targeting signal transducer and activator of transcription 3 (STAT3) through the Janus kinase-signal transducer and activator of transcription (JAK)/STAT3 signaling pathway in a mouse model of ulcerative colitis (UC). BALB/c mice were selected for establishing a mice model of UC, and intestinal tissues of normal and UC mice were collected. ELISA was conducted for detecting levels of TNF-α, IL-6, IFN-γ and IL-10. The levels of SOD, MPO, MDA and NO were tested in the intestinal tissues. Dual luciferase reporter gene assay was applied to determine whether miR-495 directly targets STAT3. Cells were cultured, transfected and assigned into: normal group, blank group, NC group, miR-495 mimic group, miR-495 inhibitor group, siRNA-STAT3 group and miR-495 inhibitor+siRNA-STAT3 group. MTT was used for testing cell proliferation, flow cytometry for cell cycle and apoptosis. Northern blotting and Western blotting were performed to detect miR-495 expression and expressions of STAT3, JAK and Claudin-1. Results show that the UC group had higher expression levels of TNF-α, IL-6, IFN-γ, MPO, MDA, NO, STAT3 and JAK and lower expression levels of IL-10, SOD, miR-495 and Claudin-1, compared to the normal group. Dual luciferase reporter gene assay confirmed that STAT3 was the target gene of miR-495. The miR-495 mimic and siRNA-STAT3 groups had higher expressions of Claudin-1, higher cell proliferation and increased amount of cells in S phase, but lower expressions of STAT3 and JAK, decreased amount of cells in G0/G1 phase and cell apoptotic rate compared with the blank, NC groups. We also found that the miR-495 inhibitor+siRNA-STAT3 group had reduced miR-495 expression. No significant differences were found in mRNA and protein expressions of STAT3, JAK and Claudin-1, cell proliferation, apoptosis and cycle amongst the miR-495 inhibitor+siRNA-STAT3 groups. Our study provides evidence that miR-495 improves the intestinal mucosal barrier function by targeting STAT3 through inhibiting the JAK/STAT3 signaling pathway in UC mice.
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A systematic review of land use regression models for volatile organic compounds
Publication date: December 2017
Source:Atmospheric Environment, Volume 171
Author(s): Heresh Amini, Masud Yunesian, Vahid Hosseini, Christian Schindler, Sarah B. Henderson, Nino Künzli
Various aspects of land use regression (LUR) models for volatile organic compounds (VOCs) were systematically reviewed. Sixteen studies were identified published between 2002 and 2017. Of these, six were conducted in Canada, five in the USA, two in Spain, and one each in Germany, Italy, and Iran. They were developed for 14 different individual VOCs or groupings: benzene; toluene; ethylbenzene; m-xylene; p-xylene; (m/p)-xylene; o-xylene; total BTEX; 1,3-butadiene; formaldehyde; n-hexane; total hydro carbons; styrene; and acrolein. The models were based on measurements ranging from 22 sites in El Paso (USA) to 179 sites in Tehran (Iran). Only four studies in Rome (Italy), Sabadell (Spain), Tehran, and Windsor (Canada) met the Cocheo's criterion of having at least one passive sampler per 3.4 km2 of study area. The range of R2 values across all models was from 0.26 for 1,3-butadiene in Dallas (USA) to 0.93 for benzene in El Paso. The average R2 values among two or more studies of the same VOCs were as follows: benzene (0.70); toluene (0.60); ethylbenzene (0.66); (m/p)-xylene (0.65); o-xylene (0.61); total BTEX (0.66); 1,3-butadiene (0.46); and formaldehyde (0.56). The common spatial predictors of studied VOC concentrations were dominated by traffic-related variables, but they also included proximity to ports in the USA, number of chimneys in Canada, altitude in Spain, northern latitudes in Italy, and proximity to sewage treatment plants and to gas filling stores in Iran. For the traffic-related variables, the review suggests that large buffers, up to 5,000 m, should be considered in large cities. Although most studies reported logical directions of association for predictors, some reported inconsistent results. Some studies included log-transformed predictors while others divided one variable by another. Only six studies provided the p-values of predictors. Future work may incorporate chemistry-transport models, satellite observations, meteorological variables, particularly temperature, consider specific sources of aromatic vs aliphatic compounds, or may develop hybrid models. Currently, only one national model has been developed for Canada, and there are no global LUR models for VOCs. Overall, studies from outside North America and Europe are critically needed to describe the wide range of exposures experienced by different populations.
Graphical abstract
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Effects of submicron ammonium sulfate particles on the growth and yield of komatsuna (Brassica rapa L. var. perviridis)
Source:Atmospheric Environment, Volume 169
Author(s): Akira Motai, Satoshi Nakaba, I. Wuled Lenggoro, Makoto Watanabe, Yoshiharu Wada, Takeshi Izuta
The aim of this study was to determine the effects of submicron ammonium sulfate (AS) particles on komatsuna (Brassica rapa L. cv. Hakkei) plants. First, we optimized a leaf-washing method to measure the amount of AS particles deposited on the leaf surface of the plants. Then, we used this method to determine the retention time of particles deposited on the leaf surface of the plants. We also investigated the effects of AS particles on the growth and yield of the plants. Almost all the AS particles deposited on the leaf surface were removed within 1 min washing time with ultrapure water, and ion leaching from the leaf was relatively slow but continuous during the leaf-washing procedure. On the basis of these results, we determined that 1 min was a suitable washing time to remove most of the AS particles while minimizing the influence of ion leaching from the leaf. The amount of particulate SO42− deposited on the leaf surface decreased over time, probably because AS particles deposited on the leaf surface deliquesced, allowing ions such as SO42− in the deliquescence solution to be absorbed into the leaf. The plants were grown and exposed to AS particles for 16 days in naturally lit phytotrons. The daily mean increase in the concentration of SO42− in PM2.5 by the exposure to AS particles was 22.5 μg m−3 in the phytotrons. The growth and yield of the plants were significantly reduced by the exposure to AS particles. The exposure to AS particles did not affect the leaf concentrations of nitrogen and chlorophyll, but significantly reduced stomatal conductance. Therefore, stomatal closure is one of the reasons for the AS particle-induced reductions in the growth and yield of komatsuna plants.
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Editorial board
Source:Atmospheric Environment, Volume 169
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Impacts of ozone air pollution and temperature extremes on crop yields: Spatial variability, adaptation and implications for future food security
Publication date: November 2017
Source:Atmospheric Environment, Volume 169
Author(s): Amos P.K. Tai, Maria Val Martin
Ozone air pollution and climate change pose major threats to global crop production, with ramifications for future food security. Previous studies of ozone and warming impacts on crops typically do not account for the strong ozone-temperature correlation when interpreting crop-ozone or crop-temperature relationships, or the spatial variability of crop-to-ozone sensitivity arising from varietal and environmental differences, leading to potential biases in their estimated crop losses. Here we develop an empirical model, called the partial derivative-linear regression (PDLR) model, to estimate the spatial variations in the sensitivities of wheat, maize and soybean yields to ozone exposures and temperature extremes in the US and Europe using a composite of multidecadal datasets, fully correcting for ozone-temperature covariation. We find generally larger and more spatially varying sensitivities of all three crops to ozone exposures than are implied by experimentally derived concentration-response functions used in most previous studies. Stronger ozone tolerance is found in regions with high ozone levels and high consumptive crop water use, reflecting the existence of spatial adaptation and effect of water constraints. The spatially varying sensitivities to temperature extremes also indicate stronger heat tolerance in crops grown in warmer regions. The spatial adaptation of crops to ozone and temperature we find can serve as a surrogate for future adaptation. Using the PDLR-derived sensitivities and 2000–2050 ozone and temperature projections by the Community Earth System Model, we estimate that future warming and unmitigated ozone pollution can combine to cause an average decline in US wheat, maize and soybean production by 13%, 43% and 28%, respectively, and a smaller decline for European crops. Aggressive ozone regulation is shown to offset such decline to various extents, especially for wheat. Our findings demonstrate the importance of considering ozone regulation as well as ozone and climate change adaptation (e.g., selecting heat- and ozone-tolerant cultivars, irrigation) as possible strategies to enhance future food security in response to imminent environmental threats.
Graphical abstract
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Temporal multiscaling characteristics of particulate matter PM10 and ground-level ozone O3 concentrations in Caribbean region
Publication date: November 2017
Source:Atmospheric Environment, Volume 169
Author(s): Thomas Plocoste, Rudy Calif, Sandra Jacoby-Koaly
A good knowledge of the intermittency of atmospheric pollutants is crucial for air pollution management. We consider here particulate matter PM10 and ground-level ozone O3 time series in Guadeloupe archipelago which experiments a tropical and humid climate in the Caribbean zone. The aim of this paper is to study their scaling statistics in the framework of fully developed turbulence and Kolmogorov's theory. Firstly, we estimate their Fourier power spectra and consider their scaling properties in the physical space. The power spectra computed follows a power law behavior for both considered pollutants. Thereafter we study the scaling behavior of PM10 and O3 time series. Contrary to numerous studies where the multifractal detrended fluctuation analysis is frequently applied, here, the classical structure function analysis is used to extract the scaling exponent or multifractal spectrum ζ(q); this function provides a full characterization of a process at all intensities and all scales. The obtained results show that PM10 and O3 possess intermittent and multifractal properties. The singularity spectrum MS(α) also confirms both pollutants multifractal features. The originality of this work comes from a statistical modeling performed on ζ(q) and MS(α) by a lognormal model to compute the intermittency parameter μ. By contrast with PM10 which mainly depends on puffs of Saharan dust (synoptic-scale), O3 is more intermittent due to variability of its local precursors. The results presented in this paper can help to better understand the mechanisms governing the dynamics of PM10 and O3 in Caribbean islands context.
Graphical abstract
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Characterization of atmospheric black carbon and co-pollutants in urban and rural areas of Spain
Source:Atmospheric Environment, Volume 169
Author(s): M. Becerril-Valle, E. Coz, A.S.H. Prévôt, G. Močnik, S.N. Pandis, A.M. Sánchez de la Campa, A. Alastuey, E. Díaz, R.M. Pérez, B. Artíñano
A one-year black carbon (BC) experimental study was performed at three different locations (urban traffic, urban background, rural) in Spain with different equivalent BC (eBC) source characteristics by means of multi-wavelength Aethalometers. The Aethalometer model was used for the source apportionment study, based on the difference in absorption spectral dependence of emissions from biomass burning (bb) and fossil fuel (ff) combustion. Most studies use a single bb and ff absorption Ångström exponent (AAE) pair (AAEbb and AAEff), however in this work we use a range of AAE values associated with fossil fuel and biomass burning based on the available measurements, which represents more properly all conditions. A sensitivity analysis of the source specific AAE was carried out to determine the most appropriate AAE values, being site dependent and seasonally variable. Here we present a methodology for the determination of the ranges of AAEbb and AAEff by evaluating the correlations between the source apportionment of eBC using the Aethalometer model with four biomass burning tracers measured at the rural site. The best combination was AAEbb = [1.63–1.74] and AAEff = [0.97–1.12]. Mean eBC values (±SD) obtained during the period of study were 3.70 ± 3.73 μg m−3 at the traffic urban site, 2.33 ± 2.96 μg m−3 at the urban background location, and 2.61 ± 5.04 μg m−3 in the rural area. High contributions of eBC to the PM10 mass were found (values up to 21% in winter), but with high eBC/PM10 variability. The hourly mean eBCff and eBCbb concentrations varied from 0 to 51 μg m−3 and from 0 to 50 μg m−3 at the three sites, respectively, exhibiting distinct seasonal and daily patterns. The fossil fuel combustion was the dominant eBC source at the urban sites, while biomass burning dominated during the cold season (88% of eBCbb) in the rural area. Daily PM2.5 and PM10 samples were collected using high-volume air samplers and analyzed for OC and EC. Analysis of biomass burning tracers and organic (OC) and elemental (EC) carbon in the rural area indicate that biomass combustion is the main source, while OC and EC indicate a lower influence of this source at the urban site.
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Observations of biomass burning tracers in PM2.5 at two megacities in North China during 2014 APEC summit
Source:Atmospheric Environment, Volume 169
Author(s): Zhisheng Zhang, Jian Gao, Leiming Zhang, Han Wang, Jun Tao, Xionghui Qiu, Fahe Chai, Yang Li, Shulan Wang
To evaluate the effectiveness of biomass burning control measures on PM2.5 reduction, day- and nighttime PM2.5 samples were collected at two urban sites in North China, one in Beijing (BJ) and the other in Shijiazhuang (SJZ), during the 2014 Asia-Pacific Economic Cooperation (APEC) summit. Typical biomass burning aerosol tracers including levoglucosan (LG), Mannosan (MN), and water-soluble potassium (K+), together with other water-soluble ions and carbonaceous species were determined. The levels of biomass burning tracers dropped dramatically during the APEC period when open biomass burning activities were well controlled in North China, yet they increased sharply to even higher levels during the post-APEC period. Distinct linear regression relationships between LG and MN were found with lower LG/MN ratios from periods with much reduced open biomass burning activities. This was likely resulted from the reduced open crop residues burning and increased residential wood burning emissions, as was also supported by the simultaneous decrease in K+/LG ratio. The positive matrix factorization and air quality model simulation analyses suggested that PM2.5 concentration produced from biomass burning sources was reduced by 22% at BJ and 46% at SJZ during the APEC period compared to pre-APEC period, although they increased to higher levels after APEC mainly due to increased residential biomass burning emissions in winter heating season. Biomass burning was also found to be the most important contributor to carbonaceous species that might cause significant light extinction in this region. This study not only suggested implementing biomass burning controls measures were helpful to reduce PM2.5 in North China, but also pointed out both open crop residues burning and indoor biomass burning activities could make substantial contributions to PM2.5 and its major components in urban areas in North China.
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Paula Moynihan: 'We really need to look at a holistic, systemic approach'
Jonathan Lewney, Associate Editor for the BDJ Portfolio, interviews Professor Paula Moynihan. Paula is Professor of Nutrition & Oral Health at Newcastle University School of Dental Sciences, Director of Newcastle University Centre for Oral Health Research, and Director of the World Health Organisation Collaborating Centre for Nutrition and Oral Health. In December 2016, Paula was elected Vice-President of the International Association of Dental Research (IADR), which means she will become IADR President in 2019.
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Perspectives: 'Patients with 40-60/day habits are now few and far between'
What impact has the smoking ban had on dental patients, ten years down the line? asks Kate Quinlan.
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Alternative sugars: Honey
Elaine Gardner, British Dietetic Association (BDA) Spokesperson, discusses the sugar content in honey and provides related oral health advice.
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Oestrogen receptor β (ERβ) regulates osteogenic differentiation of human dental pulp cells
Publication date: Available online 12 October 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Aishah Alhodhodi, Hanaa Alkharobi, Matthew Humphries, Hasanain Alkhafaji, Reem El-Gendy, Georg Feichtinger, Valerie Speirs, James Beattie
Estradiol (E2) has many important actions in the tissues of the oral cavity. Disruption of E2 metabolism or alterations in systemic E2 concentrations have been associated with compromised periodontal health. In many instances such changes occur secondarily to the well characterised effects of E2 on bone physiology −especially maintenance of bone mineral density (BMD). Despite these important epidemiological findings, little is known about the mechanism of action of E2 in oral tissues or the expression and function of oestrogen receptor (ER) isoforms in these tissues. We have isolated human dental pulp cells (hDPCs), which are able to differentiate towards an osteogenic lineage under appropriate culture conditions. We show that hDPCs express ERα, ERβ1, ERβ2 and the cell membrane associated G protein-coupled ER (GPR30). Following osteogenic differentiation of hDPCs, ERβ1 and ERβ2 were up regulated approximately 50-fold while ERα and GPR30 were down regulated, but to a much lesser degree (approximately 2-fold). ERβ was characterised as a 59kDa protein following Western blot analysis with validated antibodies and ERβ was detected in both nuclear and cytoplasmic cell compartments following immunofluorescence (IF) and immunohistochemical (IHC) analysis of cultured cells. Furthermore isoform specific antibodies detected both ERβ1 and ERβ2 in DPC cultures and in situ analysis of ERβ expression in decalcified tooth/pulp sections identified the odontoblast layer of pulp cells juxtaposed to the tooth enamel as strongly reactive for both ERβ isoforms. Finally the use of isoform specific agonists identified ERβ as the main receptor responsible for the pro-osteogenic effect of oestrogenic hormones in this tissue. Our data suggest that oestrogens stimulated osteogenic differentiation in hDPCs and that this action is mediated principally through the ERβ isoform. These findings may have important consequences for the investigation and treatment of oral and periodontal pathologies which are associated with imbalances in oestrogen concentrations and action.
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Vitamin D deficiency is associated with poor breast cancer prognostic features in postmenopausal women
Publication date: Available online 12 October 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Benedito de Sousa Almeida-Filho, Heloisa De Luca Vespoli, Eduardo Carvalho Pessoa, Murilo Machado, Jorge Nahas-Neto, Eliana Aguiar Petri Nahas
This study aimed to evaluate the association between pretreatment vitamin D (VD) deficiency with breast cancer prognostic features in Brazilian postmenopausal women. An analytical cross sectional study was conducted with 192 women, aged 45-75 years, attended at University Hospital. Women with recent diagnosis of breast cancer, in amenorrhea >12months and age ≥45 years, without medication use or clinical conditions that interfere with VD values were included. Clinical and anthropometric data were collected. Serum level of 25 hydroxyvitamin D [25(OH)D] was measured in all patients until 20days after breast cancer diagnosis, and was classified as normal (≥30ng/mL), insufficiency (20–29ng/mL) and deficiency (<20ng/mL).Data on breast cancer (histopathological type, grade, tumor stage, lymph node status), hormone status (estrogen receptor, ER, progesterone receptor, PR), human epidermal growth factor receptor type 2 (HER2) and epithelial proliferative activity (Ki-67) were collected. For statistical analysis, the t-student test, the Gamma Distribution (asymmetric variables), the chi-square test and the logistic regression (OR-odds ratio) were used. The median 25(OH)D level was 25.8ng/ml (range 12.0-59.2ng/ml). Sufficient vitamin D levels were detected in 65 patients (33.9%), whereas insufficient levels in 92 patients (47.9%), and deficient levels in 35 patients (18.2%). Participants with insufficient and deficient 25(OH)D levels had a higher proportion of tumors with a high grade and locally advanced and metastatic disease, more positive lymph node, a lower proportion of ER, PR positives tumors and higher Ki-67(p <0.05). Patients with normal vitamin D had a higher frequency of luminal A (47.7%) and luminal B (32.2%) tumors when compared to patients with vitamin D insufficiency or deficiency. Furthermore, all cases of triple negative were detected in women with low VD levels. Multivariate analysis, after adjusting for age, time since menopause and BMI, showed that insufficient and deficient level of vitamin D were significantly associated with negative estrogen receptor (OR 3.77 CI 95% 1.76-8.09 and OR 3.99 CI 95% 1.83-8.68), high Ki-67 (OR 2.50, CI 95% 1.35-4.63, and OR 2.62, CI 95% 1.40-4.98), and positive axillary lymph node status (OR 1.59, CI 95% 1.03-2.33, and OR 1.58, CI 95% 1.02-2.92) respectively. In Brazilian postmenopausal women with breast cancer, there was an association between vitamin D insufficiency or deficiency and tumors with worse prognostic features. Low vitamin D levels were shown to be a risk factor for ER negative tumors, with positive axilla and a higher rate of cell proliferation.
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Structure-function relationships for the selective inhibition of human 3β-hydroxysteroid dehydrogenase type 1 by a novel androgen analog
Publication date: Available online 12 October 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Jenny H. Pham, Catherine M. Will, Vance L. Mack, Matthew Halbert, Edward Alexander Conner, Kevin M. Bucholtz, James L. Thomas
3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1) is selectively expressed in human placenta, mammary glands and breast tumors in women. Human 3β-HSD2 is selectively expressed in adrenal glands and ovaries. Based on AutoDock 3 and 4 results, we have exploited key differences in the amino acid sequences of 3β-HSD1 (Ser194, Arg195) and 3β-HSD2 (Gly194, Pro195) by designing a selective inhibitor of 3β-HSD1. 2,16-Dicyano-4,5-epoxy-androstane-3,17-dione (16-cyano-17-keto-trilostane or DiCN-AND) was synthesized in a 4-step procedure from androstenedione. In purified 3β-HSD inhibition studies, DiCN-AND competitively inhibited 3β- HSD1 with Ki=4.7μM and noncompetitively inhibited 3β-HSD2 with a 6.5-fold higher Ki=30.7μM. We previously reported similar isoenzyme-specific inhibition profiles for trilostane. Based on our docking results, we created, expressed and purified the chimeric S194G-1 mutant of 3β-HSD1. Trilostane inhibited S194G-1 (Ki=0.67μM) with a noncompetitive mode compared to its 6.7-fold higher affinity, competitive inhibition of 3β-HSD1 (Ki=0.10μM). DiCN-AND inhibited S194G-1 with a 6.3-fold higher Ki (29.5μM) than measured for 3β-HSD1 (Ki=4.7μM) but with the same competitive mode for both enzyme species. Since DiCN-AND noncompetitively inhibits 3β-HSD2, which has the Gly194 and Pro195 of 3β-HSD2 in place of the Ser194 and Arg195 in 3β-HSD1, this suggests that Arg195 alone in 3β-HSD1 or S194G-1 is required to bind DiCN-AND in the substrate binding site (competitive inhibition). However, both Ser194 and Arg195 are required to bind trilostane in the 3β-HSD1 substrate site based on its noncompetitive inhibition of S194G-1 and 3β-HSD2. In support of this hypothesis, DiCN-AND inhibited our chimeric R195P-1 mutant noncompetitively with a Ki=41.3μM (similar to the 3β-HSD2 inhibition profile). Since DiCN-AND competitively inhibited S194G-1 that still contains R195 but noncompetitively inhibited R195P-1 that still contains S194, our data provides strong evidence that the Arg195 being mutated to Pro195 (as present in 3β-HSD2) shifts the inhibition mode from competitive to noncompetitive in 3β-HSD1. This supports the key role of Arg195 in 3β-HSD1 for the high affinity, competitive binding of the trilostane analogs. Our new structure/function information for the design of targeted 3β-HSD1 inhibitors may lead to important new treatments for the prevention of spontaneous premature birth.
Graphical abstract
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Comparison of the composition of bile acids in bile of patients with adenocarcinoma of the pancreas and benign disease
Publication date: Available online 12 October 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): David O. Rees, Peter J. Crick, Gareth J. Jenkins, Yuqin Wang, William J. Griffiths, Tim H. Brown, Bilal Al-Sarireh
Bile acids have been implicated in the development of gastrointestinal malignancies. Both the specific nature of individual bile acids and their concentration appear key factors in the carcinogenic potency of bile. Using liquid chromatography mass spectrometry (LC-MS) we performed quantitative profiling of bile extracted directly from the common bile duct in 30 patients (15 patients with pancreatic cancer and 15 patients with benign disease). Separation and detection of bile acids was performed using a 1.7μm particle size reversed-phase C18 LC column at a flow rate of 200μL/min with negative electrospray ionization MS. A significant difference (p=0.018) was seen in the concentration of unconjugated cholic acid in the malignant group (0.643mmol/L) compared to the benign group (0.022mmol/L), with an overall significant difference (p=0.04) seen in the level of total unconjugated bile acids in the malignant group (1.816mmol/L) compared to the benign group (0.069mmol/L). This finding may offer the possibility of both understanding the biology of cancer development in the pancreas, as well as offering a potential diagnostic avenue to explore. However, a larger study is necessary to confirm the alterations in bile acid profiles reported here and explore factors such as diet and microbial populations on the bile acid profiles of these patient groups.
Graphical abstract
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Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair
Source:Progress in Neurobiology
Author(s): Wei Cai, Tuo Yang, Huan Liu, Lijuan Han, Kai Zhang, Xiaoming Hu, Xuejing Zhang, Ke-Jie Yin, Yanqin Gao, Michael V.L. Bennett, Rehana K. Leak, Jun Chen
Peroxisome proliferator-activated receptor γ (PPARγ) is a widely expressed ligand-modulated transcription factor that governs the expression of genes involved in inflammation, redox equilibrium, trophic factor production, insulin sensitivity, and the metabolism of lipids and glucose. Synthetic PPARγ agonists (e.g. thiazolidinediones) are used to treat Type II diabetes and have the potential to limit the risk of developing brain injury by mitigating the influence of comorbidities. If brain injury develops, PPARγ serves as a master gatekeeper of cytoprotective stress responses, improving the chances of survival and recovery of homeostatic equilibrium. In the acute injury phase, PPARγ directly restricts tissue damage by inhibiting the NFκB pathway to mitigate inflammation and stimulating the Nrf2/ARE axis to neutralize oxidative stress. During the chronic phase of acute brain injuries, PPARγ activation in injured cells culminates in the repair of gray and white matter, preservation of the blood-brain barrier, reconstruction of the neurovascular unit, resolution of inflammation, and long-term functional recovery. Thus, PPARγ lies at the apex of cell fate decisions and exerts profound effects on the chronic progression of acute injury conditions. Here, we review the therapeutic potential of PPARγ in stroke and brain trauma and highlight the novel role of PPARγ in long-term tissue repair. We describe its structure and function and identify the genes that it targets. PPARγ regulation of inflammation, metabolism, cell fate (proliferation/differentiation/maturation/survival), and many other processes also has relevance to other neurological diseases. Therefore, PPARγ is an attractive target for therapies against a number of progressive neurological disorders.
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Biallelic mutations in SZT2 cause a discernible clinical entity with epilepsy, developmental delay, macrocephaly and a dysmorphic corpus callosum
Source:Brain and Development
Author(s): Yuji Nakamura, Yasuko Togawa, Yusuke Okuno, Hideki Muramatsu, Kazuhiko Nakabayashi, Yoko Kuroki, Daisuke Ieda, Ikumi Hori, Yutaka Negishi, Takao Togawa, Ayako Hattori, Seiji Kojima, Shinji Saitoh
Mutations in SZT2 were first reported in 2013 as a cause of early-onset epileptic encephalopathy. Because only five reports have been published to date, the clinical features associated with SZT2 remain unclear. We herein report an additional patient with biallelic mutations in SZT2. The proband, a four-year-old girl, showed developmental delay and seizures from two years of age. Her seizures were not intractable and readily controlled by valproate. She showed mildly dysmorphic facies with macrocephaly, high forehead, and hypertelorism, and also had pectus carinatum. An EEG showed epileptic discharges which rarely occurred. A brain MRI revealed a short and thick corpus callosum. Whole-exome sequencing detected compound heterozygous biallelic mutations (c.8596dup (p.Tyr2866Leufs∗42) and c.2930-17_2930-3delinsCTCGTG) in SZT2, both of which were novel and predicted to be truncating. This case suggested a broad phenotypic spectrum arises from SZT2 mutations, forming a continuum from epileptic encephalopathy and severe developmental delay to mild intellectual disability without epilepsy. The characteristic thick and short corpus callosum observed in 7/8 cases with epilepsy, including the proband, but not in three non-syndromic cases, appears to be specific, and thus useful for indicating the possibility of SZT2 mutations. This feature has the potential to make loss of SZT2 a clinically discernible disorder despite a wide clinical spectrum.
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Can fine-scale post-pollination variation of fig volatile compounds explain some steps of the temporal succession of fig wasps associated with Ficus racemosa?
Source:Acta Oecologica
Author(s): Magali Proffit, Jean-Marie Bessière, Bertrand Schatz, Martine Hossaert-McKey
Volatile organic compounds (VOCs) emitted by flowers play an essential role in mediating the attraction of pollinators. However, they also attract other species exploiting resources associated with flowers. For instance, VOCs emitted by figs play a major role in encounters between Ficus spp., their mutualistic pollinating wasps, and all the members of the community of non-pollinating fig wasps (NPFWs) that exploit the mutualistic interaction. Because pollinators might be in limited supply for a tree bearing many inflorescences, the plant might maximize its individual reproductive success by reducing the attractiveness of inflorescences once they are pollinated, so that pollinators orient only towards the tree's unpollinated figs. Changes in VOCs emission that bring this about could represent an important cue for NPFWs that exploit particular stages of fig development. In this study, by monitoring precisely the presence of fig-associated wasps on figs of F. racemosa, a common widespread fig species, we demonstrated that 4–5 days and 15 days following pollination represent two critical transitional steps in the succession of different wasp species. Then, focusing on the first one of these transitional steps, by investigating the composition of fig VOCs at receptivity and from 1 to 5 days following pollination, we detected progressive quantitative and qualitative variation of floral scent following pollination. These changes are significant at 5 days following pollination. The qualitative changes are mainly due to an increase in the relative proportions of two monoterpenes (α-pinene and limonene). These variations of the floral VOCs following pollination could explain why pollinating wasps stop visiting figs very shortly after the first pollinators enter receptive figs. They also possibly explain the succession of non-pollinating wasps on the figs following pollination.
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Heart valve scaffold fabrication: Bioinspired control of macro-scale morphology, mechanics and micro-structure
Source:Biomaterials, Volume 150
Author(s): Antonio D'Amore, Samuel K. Luketich, Giuseppe M. Raffa, Salim Olia, Giorgio Menallo, Antonino Mazzola, Flavio D'Accardi, Tamir Grunberg, Xinzhu Gu, Michele Pilato, Marina V. Kameneva, Vinay Badhwar, William R. Wagner
Valvular heart disease is currently treated with mechanical valves, which benefit from longevity, but are burdened by chronic anticoagulation therapy, or with bioprosthetic valves, which have reduced thromboembolic risk, but limited durability. Tissue engineered heart valves have been proposed to resolve these issues by implanting a scaffold that is replaced by endogenous growth, leaving autologous, functional leaflets that would putatively eliminate the need for anticoagulation and avoid calcification. Despite the diversity in fabrication strategies and encouraging results in large animal models, control over engineered valve structure-function remains at best partial. This study aimed to overcome these limitations by introducing double component deposition (DCD), an electrodeposition technique that employs multi-phase electrodes to dictate valve macro and microstructure and resultant function. Results in this report demonstrate the capacity of the DCD method to simultaneously control scaffold macro-scale morphology, mechanics and microstructure while producing fully assembled stent-less multi-leaflet valves composed of microscopic fibers. DCD engineered valve characterization included: leaflet thickness, biaxial properties, bending properties, and quantitative structural analysis of multi-photon and scanning electron micrographs. Quasi-static ex-vivo valve coaptation testing and dynamic organ level functional assessment in a pressure pulse duplicating device demonstrated appropriate acute valve functionality.
http://ift.tt/2z4qupR
Successful transdermal allergen delivery and allergen-specific immunotherapy using biodegradable microneedle patches
Publication date: January 2018
Source:Biomaterials, Volume 150
Author(s): Ji Hye Kim, Jung U. Shin, Seo Hyeong Kim, Ji Yeon Noh, Hye Ran Kim, Jungsoo Lee, Howard Chu, Kyoung Yong Jeong, Kyung Hee Park, Jung Dong Kim, Hong Kee Kim, Do Hyeon Jeong, Tai-Soon Yong, Jung-Won Park, Kwang Hoon Lee
Allergen-specific immunotherapy (SIT) is an effective treatment modality for allergic diseases such as atopic dermatitis (AD). However, frequent visits over a 3-year period as well as looming adverse events tend to discourage patient compliance. Therefore, a more convenient, effective, and safe method of SIT is needed.For several decades, use of microneedles has been promoted as an efficient and precise transdermal drug delivery method. In this study, we developed Dermatophagoides farinae (D. farinae) extract (DfE)-loaded microneedle patches, and evaluated their safety and efficacy as a novel SIT method. After 4 weeks of patch application, efficient allergen delivery and successful induction of immune response to DfE were demonstrated in mice, with no apparent adverse events. AD-induced NC/Nga mice received microneedle immunotherapy (MNIT) (10 μg), subcutaneous immunotherapy (SCIT) (10 μg), SCIT (100 μg), or placebo. Both MNIT (10 μg) and SCIT (100 μg) treatments improved clinical and histologic manifestations of AD skin lesions, altered immunoglobulin production, dampened Th2 cellular response, and boosted Treg infiltrates, without significant side effects; whereas SCIT (10 μg) or placebo subsets failed to show any effects. Based on the favorable safety and efficacy profiles demonstrated in mice by MNIT in the current study, we believe that MNIT may serve as a new SIT modality.
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Photodynamic Therapy Associated with a Blue Dye Papain-Based Gel and Evaluation of Its Degradation of Type I Collagen Fibers
Photomedicine and Laser Surgery , Vol. 0, No. 0.
http://ift.tt/2kLTdgT
Evaluation of the Effect of Phototherapy in Patients with Mandibular Fracture on Mandibular Dynamics, Pain, Edema, and Bite Force: A Pilot Study
Photomedicine and Laser Surgery , Vol. 0, No. 0.
http://ift.tt/2xBklW1
Fate of triclocarban in agricultural soils after biosolid applications
Abstract
Triclocarban [N-(4-chlorophenyl)-N-(3,4-dichlorophenyl) urea] (TCC) is an antimicrobial agent utilized in a variety of consumer products. It is commonly released into domestic wastewaters and upon treatment, it is known to accumulate in biosolids. This study examines the occurrence of TCC in biosolids and its long-term fate in biosolid-treated soils. TCC levels in the biosolids from a large waste water treatment plant (WWTP) over 2 years showed little variability at 18,800 ± 700 ng g−1 dry wt. (mean ± SEM). Surface soil samples (top 10 cm) were collected from 26 commercial farms located in northern VA, US that had received biosolid applications from the WWTP. Samples were grouped as farms receiving no biosolids, farms with a single biosolid application, and those receiving multiple biosolid applications from 1992 to 2006. Our results illustrate that TCC soil residues remained years after biosolid application. The two most important parameters controlling TCC topsoil concentrations were the biosolid application rate and the period since the last application. No TCC removal was observed in farms where the time since biosolid application was between 7 and 9 months. TCC concentration analyzed 7 and 8 years after biosolid applications were 45.8 ± 6.1 and 72.4 ± 15.3 ng g−1 dry wt., respectively, showing its persistence in soils and build-up upon multiple biosolid applications. A soil TCC half-life of 287.5 ± 45.5 days was estimated.
http://ift.tt/2gAzign
Effectiveness of Low-Intensity Laser Therapy on Tissue Repair Following Saphenectomy in Patients Who Underwent Coronary Artery Bypass Graft: A Randomized, Double-Blind Study
Photomedicine and Laser Surgery , Vol. 0, No. 0.
http://ift.tt/2kMClXC
Manual Operated Ultraviolet Surface Decontamination for Healthcare Environments
Photomedicine and Laser Surgery , Vol. 0, No. 0.
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Optimization of non-thermal plasma efficiency in the simultaneous elimination of benzene, toluene, ethyl-benzene, and xylene from polluted airstreams using response surface methodology
Abstract
Treatment with a non-thermal plasma (NTP) is a new and effective technology applied recently for conversion of gases for air pollution control. This research was initiated to optimize the efficient application of the NTP process in benzene, toluene, ethyl-benzene, and xylene (BTEX) removal. The effects of four variables including temperature, initial BTEX concentration, voltage, and flow rate on the BTEX elimination efficiency were investigated using response surface methodology (RSM). The constructed model was evaluated by analysis of variance (ANOVA). The model goodness-of-fit and statistical significance was assessed using determination coefficients (R 2 and R 2adj) and the F-test. The results revealed that the R 2 proportion was greater than 0.96 for BTEX removal efficiency. The statistical analysis demonstrated that the BTEX removal efficiency was significantly correlated with the temperature, BTEX concentration, voltage, and flow rate. Voltage was the most influential variable affecting the dependent variable as it exerted a significant effect (p < 0.0001) on the response variable. According to the achieved results, NTP can be applied as a progressive, cost-effective, and practical process for treatment of airstreams polluted with BTEX in conditions of low residence time and high concentrations of pollutants.
http://ift.tt/2i6gjOp
Photobiomodulation for Achilles Tendinopathy
Photomedicine and Laser Surgery , Vol. 0, No. 0.
http://ift.tt/2kLmUyF
Different Protocols of Photobiomodulation Therapy of Hyposalivation
Photomedicine and Laser Surgery , Vol. 0, No. 0.
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Laser Biophotomodulation in Patients with Neurosensory Disturbance of the Inferior Alveolar Nerve After Sagittal Split Ramus Osteotomy: A 2-Year Follow-Up Study
Photomedicine and Laser Surgery , Vol. 0, No. 0.
http://ift.tt/2kMc0IW
A Study on the Macroscopic Morphometry of the Lesion Area on Diabetic Ulcers in Humans Treated with Photodynamic Therapy Using Two Methods of Measurement
Photomedicine and Laser Surgery , Vol. 0, No. 0.
http://ift.tt/2xDcN5e
A dual-type responsive electrochemical immunosensor for quantitative detection of PCSK9 based on n-C60-PdPt/N-GNRs and Pt-poly (methylene blue) nanocomposites
Source:Biosensors and Bioelectronics, Volume 101
Author(s): Yan Li, Junlin He, Jun Chen, Yazhen Niu, Yilin Zhao, Yuchan Zhang, Chao Yu
In this study, a dual-type responsive electrochemical immunosensor was developed for the quantitative detection of proprotein convertase subtilisin/kexin type 9 (PCSK9), a potential biomarker of cardiovascular disease in serum. N-doped graphene nanoribbons (N-GNRs) with good conductivity were used as the sensing matrix modifying the glassy carbon electrode. Palladium platinum alloy (PdPt) nanoparticles with high catalytic performance toward the reduction of hydrogen peroxide (H2O2) were reduced onto amino-functionalized fullerene (n-C60-PdPt) and significantly amplified the electrochemical signal recorded by the amperometric i-t curve. Furthermore, staphylococcus protein A (SPA) with antibody orientation function was introduced to improve the immunoreaction efficiency. Accordingly, a label-free immunosensor was fabricated based on n-C60-PdPt/N-GNRs for the quick detection of PCSK9. Meanwhile, to realize ultrasensitive detection of PCSK9, Pt-poly (methylene blue) (Pt-PMB) nanocomposites synthesized by a one-pot method for the first time were used as a novel signal label, which exhibited uniform morphology as well as good conductivity and produced an electrochemical signal recorded by differential pulse voltammetry (DPV). Herein, a novel sandwich-type immunosensor was designed using n-C60-PdPt/N-GNRs as the sensing matrix and Pt-PMB as the signal label for sensitive detection of PCSK9. Under optimal conditions, the label-free immunosensor showed a linear range of 10pgmL−1 to 100ngmL −1 with a detection limit of 3.33pgmL−1 (S/N=3), and the sandwich-type immunosensor exhibited a linear range of 100 fg mL−1 to 100ngmL −1 with a detection limit of 0.033pgmL−1 (S/N=3) for PCSK9 detection, indicating its potential application in clinical bioassay analysis.
http://ift.tt/2yInOlV
Multiple signal-amplification via Ag and TiO2 decorated 3D nitrogen doped graphene hydrogel for fabricating sensitive label-free photoelectrochemical thrombin aptasensor
Source:Biosensors and Bioelectronics, Volume 101
Author(s): Nan Hao, Rong Hua, Saibo Chen, Ying Zhang, Zhou Zhou, Jing Qian, Qian Liu, Kun Wang
In this study, Ag/TiO2/3D nitrogen doped graphene hydrogel (3DNGH) was prepared for the first time and the photocurrent intensity of this material was greatly enhanced, which was attributed to the multiple enhancements accomplished in one step. The porous structure of 3DNGH could provide an exceptionally large accessible surface area, which was beneficial for the anchoring of Ag and TiO2 nanoparticles. The introduction of nitrogen doped graphene and metal nanoparticles was capable to facilitate the charge separation efficiency and accelerate the transfer rate of the photogenerated electron-hole pairs. Then the photoelectrochemical performance was further amplified by the localized surface plasmon resonance of Ag nanoparticles. On the basis of excellent PEC properties of Ag/TiO2/3DNGH, a sensitive label-free PEC sensor has been established for the determination of thrombin successfully. This proposed PEC biosensor exhibited good PEC performances with a wide linear in the range from 0.01p.M. to 10p.M. as well as a relative low detection limit of 3 fM (S/N = 3), indicating that Ag/TiO2/3DNGH would serve as a promising photoactive material in the applications of PEC biosensors.
http://ift.tt/2hEMQHu
Electrochemically mediated in situ growth of electroactive polymers for highly sensitive detection of double-stranded DNA without sequence-preference
Source:Biosensors and Bioelectronics, Volume 101
Author(s): Qiong Hu, Qiangwei Wang, Jinming Kong, Lianzhi Li, Xueji Zhang
The ability to directly detect double-stranded DNA (dsDNA) without sequence-preference continues to be a major challenge. Herein, we report an electrochemical method for the direct, highly sensitive detection of dsDNA based on the strand replacement of dsDNA by peptide nucleic acid (PNA) and the in situ growth of electroactive polymers through the surface-initiated electrochemically mediated atom transfer radical polymerization (SI-eATRP). Thiolated PNA molecules are firstly self-assembled onto gold electrode surface for the specific recognition of target dsDNA (dsDNA-T), which in turn leads to the formation of a high density of PNA/DNA heteroduplexes on the electrode surface for the subsequent attachment of ATRP initiators via the phosphate-Zr4+-carboxylate chemistry. By applying a negative potential to the electrode, the air-stable CuII deactivators can be reduced into the CuI activators so as to trigger the surface-initiated polymerization for the in situ growth of electroactive polymers. Due to the strand replacement of dsDNA by PNA, dsDNA can be directly detected without sequence-preference. Besides, the growth of polymers enables the modification of numerous electroactive probes, thereby greatly improving the electrochemical signal. Under optimal conditions, a good linearity between the electrochemical signal and the logarithm of dsDNA-T concentration over the range from 1.0 fM to 1.0nM, with a detection limit of 0.47 fM, can be obtained. Results indicate that it is highly selective, and holds high anti-interference capability in the presence of human serum samples. Therefore, this method offers great promises in providing a universal and efficient solution for the direct detection of dsDNA.
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Nuclear Magnetic Resonance-Assisted Metabolic Analysis of Plasma for Mild Gestational Diabetes Mellitus Patients
Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.
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iASPP Is an Antioxidative Factor and Drives Cancer Growth and Drug Resistance by Competing with Nrf2 for Keap1 Binding
Publication date: Available online 12 October 2017
Source:Cancer Cell
Author(s): Wenjie Ge, Kunming Zhao, Xingwen Wang, Huayi Li, Miao Yu, Mengmeng He, Xuting Xue, Yifu Zhu, Cheng Zhang, Yiwei Cheng, Shijian Jiang, Ying Hu
Reactive oxygen species (ROS) have emerged as important signaling molecules that play crucial roles in carcinogenesis and cytotoxic responses. Nrf2 is the master regulator of ROS balance. Thus, uncovering mechanisms of Nrf2 regulation is important for the development of alternative treatment strategies for cancers. Here, we demonstrate that iASPP, a known p53 inhibitor, lowers ROS independently of p53. Mechanistically, iASPP competes with Nrf2 for Keap1 binding via a DLT motif, leading to decreased Nrf2 ubiquitination and increased Nrf2 accumulation, nuclear translocation, and antioxidative transactivation. This iASPP-Keap1-Nrf2 axis promotes cancer growth and drug resistance both in vitro and in vivo. Thus, iASPP is an antioxidative factor and represents a promising target to improve cancer treatment, regardless of p53 status.
Graphical abstract
Teaser
Ge et al. show that iASPP, a known p53 inhibitor, functions independently of p53 to compete with Keap1 for Nrf2 binding, leading to decreased Nrf2 ubiquitination and increased Nrf2 accumulation and antioxidative transactivation. The iASPP-Keap1-Nrf2 axis promotes cancer growth and drug resistance.http://ift.tt/2zjP7ji
Low-intensity LED therapy ( λ 640 ± 20 nm) on saphenectomy healing in patients who underwent coronary artery bypass graft: a randomized, double-blind study
Abstract
Myocardial revascularization surgery (CABG) is the most appropriate treatment for coronary artery disease. Currently, the great challenge is to reduce postoperative complications, such as wound infections, dehiscence, pain, and patients' quality of life. The saphenectomy is the target of complications in 10% of cases, which can cause greater morbidity, time, and cost of hospitalization. Studies show that low-intensity laser or light-emitted diode (LED) therapy promotes positive biomodulation of the tissue repair process, culminating in a lower incidence of dehiscence, pain reduction, and improvement in quality of life. The objective of the present study was to evaluate clinically the saphenous tissue repair after LED therapy. Forty subjects of both genders who underwent CABG with extracorporeal circulation were randomly divided into two groups: the placebo (PG) and experimental (EG). The experimental group underwent low-intensity LED therapy (λ 640 ± 20 nm, 6 J/cm2) on saphenectomy. The tissue repair was analyzed by digital photogrammetry on the first and fifth postoperative day. The border closure was blindly evaluated by three researchers. The hematoma and hyperemia area was quantitatively analyzed using ImageJ© software. The results showed that in the experimental group, there were less bleeding points and no dehiscence in saphenectomy, as compared to the placebo group. There was also a smaller area of hematoma and hyperemia in the experimental group (p < 0.0009). These data lead to the conclusion that the type of phototherapy protocol employed can assist in tissue repair.
http://ift.tt/2wRDMFC
Analysis of choroidal thickness in ocular hypertensive patients using enhanced depth imaging optical coherence tomography
Abstract
This study aimed to compare choroidal thickness between subjects with ocular hypertension (OHT) and normal individuals and explore factors affecting choroidal thickness. This study included 60 untreated newly diagnosed OHT eyes and 60 normal eyes. Choroidal thickness obtained from Cirrus HD-OCT was measured at different locations in the macular and peripapillary regions and compared between the two groups before and after adjusting for potential confounding variables. Regression analysis was performed to figure out factors influencing choroidal thickness. The macular choroidal thickness did not vary significantly between OHT patients and normal controls regardless of locations (all P > 0.05). The average peripapillary choroidal thickness was 167 ± 53 μm in OHT eyes and 185 ± 63 μm in the normal eyes; no significant differences were identified (P = 0.107). Only one of the locations in the temporal area in the OHT group demonstrated significantly thinner peripapillary choroidal thickness as compared to the normal group (P = 0.033). Age was the only significant factor affecting choroidal thickness on multivariate analysis regardless of locations (all P < 0.001). Choroidal thickness of the macular and peripapillary regions in OHT patients is not decreased significantly except one location in the temporal area of the optic disc when comparing with the normal subjects. Anatomic peripapillary choroidal thickness measurements with SD-OCT might be one more tool to track changes in OHT patients.
http://ift.tt/2yh13lX
Publisher's Note: Rho differentially regulates the Hippo pathway by modulating the interaction between Amot and Nf2 in the blastocyst. Development doi: 10.1242/dev.157917 [PUBLISHER'S NOTE]
Xianle Shi, Zixi Yin, Bin Ling, Lingling Wang, Chang Liu, Xianhui Ruan, Weiyu Zhang, and Lingyi Chen
http://ift.tt/2zlUbE2
http://ift.tt/2zlUbE2
Establishment of a chronic activity-based anorexia rat model
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Linda Frintrop, Stefanie Trinh, Johanna Liesbrock, Lisa Paulukat, Martien J. Kas, Rene Tolba, Kerstin Konrad, Beate Herpertz-Dahlmann, Cordian Beyer, Jochen Seitz
BackgroundAnorexia nervosa (AN) is often a chronic eating disorder characterised by body image disturbance and low body weight often associated with starvation-induced amenorrhoea and excessive exercise. Activity-based anorexia (ABA) is an animal model representing many somatic aspects of this psychiatric illness. We systematically manipulated the extent and length of starvation and animal age to find the optimal parameters to study chronic starvation.New methodsWistar rats had 24h/day running wheel access and received 40% of their baseline food intake until a 20% or 25% weight reduction was reached (acute starvation). This body weight was then maintained for two weeks (chronic starvation). The rats of different ages of 4 or 8 weeks were used to represent early and late adolescent animals, respectively. The complete absence of a menstrual cycle was defined as the primary outcome parameter.ResultsAcute starvation caused a disruption of the oestrous cycle in 58% of the animals. During chronic starvation, a complete loss of the oestrous cycle could be found. Furthermore, 4-week-old rats exhibited higher levels of hyperactivity and amenorrhoea than 8-week-old animals. A 20% starvation level led to 90% loss of cycle, while a 25% starvation level triggered complete loss.Comparison with existing methodsMost current ABA models focus on acute starvation, while most patients are chronically ill.ConclusionsThe optimal parameters to achieve complete amenorrhoea included early adolescence, chronic starvation and 25% weight loss. The new ABA model allows studying the effects of chronic AN on underlying behavioural, hormonal and brain pathobiology.
http://ift.tt/2z4x7IO
Stimuli to differentiate the neural response at successive stages of visual processing using the VEP from human visual cortex
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Valentine L. Marcar, Lutz Jäncke
BackgroundClarifying the enigmatic relationship between stimulus property, neural response and the evoked potential is essential if non-invasive functional imaging is to make a meaningful contribution to the understanding of how maturational or degenerative processes influence brain activity. Visual cortex has proven a favourite target to elucidate this relationship. However, to date most studies involving the visual system have yielded inconsistent results or have been strongly criticised.New methodWe developed a set of three visual stimuli, two of which either had the same low- or high spatial frequency characteristic. Adult volunteers viewed these as pattern reversing stimuli while the scalp electric potential was recorded using a 10-10 array of electrodes.ResultsEstablished processing mechanisms of the primate visual system enabled us to link the amplitude of the N75 and P100 to the size of the neural population processing the temporal luminance contrast, and the amplitude of the N135 and P240 to the size of the neural processing the spatial luminance contrast in our stimuli. Calculating the distribution of current source density enabled us to identify the neural source of each VEP component.ConclusionsDemonstrating a direct relationship between the temporal- and spatial luminance contrast properties of our stimuli and the size of the neural population involved provides a better understanding of the nature of the relationship between stimulus property, neural response and the VEP. It also shows that EEG can contribute in a significant manner to the study of the influence of maturational or degenerative processes on brain activity.
http://ift.tt/2zkhe1N
Pediatric Auditory Brainstem Implantation: Surgical, Electrophysiologic, and Behavioral Outcomes.
Objectives: The objectives of this study were to demonstrate the safety of auditory brainstem implant (ABI) surgery and document the subsequent development of auditory and spoken language skills in children without neurofibromatosis type II (NFII). Design: A prospective, single-subject observational study of ABI in children without NFII was undertaken at the University of North Carolina at Chapel Hill. Five children were enrolled under an investigational device exemption sponsored by the investigators. Over 3 years, patient demographics, medical/surgical findings, complications, device mapping, electrophysiologic measures, audiologic outcomes, and speech and language measures were collected. Results: Five children without NFII have received ABIs to date without permanent medical sequelae, although 2 children required treatment after surgery for temporary complications. All children wear their device daily, and the benefits of sound awareness have developed slowly. Intra-and postoperative electrophysiologic measures augmented surgical placement and device programming. The slow development of audition skills precipitated limited changes in speech production but had little impact on growth in spoken language. Conclusions: ABI surgery is safe in young children without NFII. Benefits from device use develop slowly and include sound awareness and the use of pattern and timing aspects of sound. These skills may augment progress in speech production but progress in language development is dependent upon visual communication. Further monitoring of this cohort is needed to better delineate the benefits of this intervention in this patient population. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2xCn7pa
http://ift.tt/2xCn7pa
A dose-escalation study of bi-daily once weekly oral docetaxel either as ModraDoc001 or ModraDoc006 combined with ritonavir
Source:European Journal of Cancer, Volume 86
Author(s): Vincent A. de Weger, Frederik E. Stuurman, Jeroen J.M.A. Hendrikx, Johannes J. Moes, Emilia Sawicki, Alwin D.R. Huitema, Bastiaan Nuijen, Bas Thijssen, Hilde Rosing, Marianne Keessen, Marja Mergui-Roelvink, Jos H. Beijnen, Jan H.M. Schellens, Serena Marchetti
IntroductionTwo solid dispersions of docetaxel (denoted ModraDoc001 capsule and ModraDoc006 tablet (both 10 mg)) were co-administered with 100 mg ritonavir (/r) and investigated in a bi-daily once weekly (BIDW) schedule. Safety, maximum tolerated dose (MTD), pharmacokinetics (PK) and preliminary activity were explored.MethodsAdult patients with metastatic solid tumours were included in two dose-escalation arms. PK sampling was performed during the first week and the second or third week. Safety was evaluated using US National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0. Antitumour activity was assessed every 6 weeks according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0.ResultsModraDoc001 capsule/r and ModraDoc006 tablet/r were administered to 17 and 28 patients, respectively. The most common adverse events were nausea, vomiting, diarrhoea and fatigue, mostly of grade 1–2 severity. Grade 3/4 neutropenia/neutropenic fever was observed in 2 patients (4%). The MTD was determined as 20/20 mg ModraDoc001/r and 30/20 mg ModraDoc006/r (morning/afternoon dose) once weekly. The mean area under the plasma concentration–time curve (AUC0–48) ± standard deviation at the MTD for ModraDoc001/r and ModraDoc006/r were 686 ± 388 ng/ml*h and 1126 ± 382 ng/ml*h, respectively. Five partial responses were reported as best response to treatment.ConclusionOral administration of BIDW ModraDoc001/r or ModraDoc006/r is feasible. The once weekly 30/20 mg ModraDoc006 tablet/r dose-level was selected for future clinical development. Antitumour activity is promising.
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A concealed giant peritonsillolith masquerading as oropharyngeal tumor
Publication date: Available online 12 October 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Boon Chye Gan, Irfan Mohamad, Norhafiza Mat Lazim
http://ift.tt/2z3vLhB
Democrats’ Bill Requires Sleep Apnea Testing For Engineers
NEWARK, N.J. – Democratic lawmakers from New York and New Jersey are introducing legislation Thursday to force federal transportation officials to implement a rule to test train engineers for sleep apnea.
Minority Leader Chuck Schumer of New York and New Jersey U.S. Sen. Cory Booker announced the legislation a week after the National Transportation Safety Board said that the engineers involved in crashes in Hoboken and Brooklyn were suffering from undiagnosed sleep apnea.
To read the full article, click here.
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Radio-guided minimally invasive parathyroidectomy: A descriptive report of the experience from tertiary center
Indian Journal of Nuclear Medicine 2017 32(4):383-383
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Primitive neuroectodermal tumor of nasal cavity on 18F-Fluorodeoxyglucose positron emission tomography-computed tomography
Indian Journal of Nuclear Medicine 2017 32(4):363-364
Primitive neuroectodermal tumor is a malignant small round cell tumor of presumed neural crest origin, usually affecting the bony structures of the nasal cavity and its clinical and radiological features may be confused with those of infection and malignancy. I report a case with primitive neuroectodermal tumor of the nasal cavity showing increased tracer uptake on 18F-fluorodeoxyglucose positron emission tomography-computed tomography mimicking an another primary malignancy in a 17-year-old boy.
http://ift.tt/2yjOQyn
In-house preparation and quality control of Tc99m TRODAT 1 for diagnostic single-photon emission computed tomography/computed tomography imaging in parkinson's disease
Indian Journal of Nuclear Medicine 2017 32(4):266-270
Purpose of Study: Loss of dopamine neurons in the brain is a characteristic feature of Parkinson's disease (PD). TRODAT-1 is a tropane derivative that binds to dopamine transporter (DAT) receptors. It can be used for noninvasive in vivo imaging of DAT receptors leading to the early detection of PD. The present study aims to optimize the in-house radiolabeling of TRODAT-1 with Tc-99 m in hospital radiopharmacy set up along with performing single-photon emission computed tomography/computed tomography imaging in patients with PD. Materials and Methods: Radiolabeling was performed through transchelation method. For optimization studies, varied amount of glucoheptonate (GHA) and stannous chloride was incubated with Tc-99 m for 10 min at room temperature. TRODAT-1 was added to the reaction mixture followed by incubation at 95°C for various time intervals. Phosphate buffer saline was added to maintain the pH of the final product. After performing the quality checks, whole-body imaging was performed to check the biodistribution in 4 patients at 1 h postinjection of 20–25 mCi (740–925 MBq) of Tc-99 m-TRODAT-1. Regional brain imaging was performed at 3–4 h. Clinical evaluation was done in control (n = 5) and in patients with PD (n = 5). Results: Radiolabeling yield of 100% was achieved by incubating TRODAT-1 with Tc-99 m GHA. All the quality control indicated the suitability of radiopharmaceutical for the intravenous administration. Good uptake of Tc-99 m TRODAT-1 was observed in the striatum of normal patients. However, decreased uptake was seen in patients with PD. Conclusion: Tc-99 m TRODAT-1 is a potential radiopharmaceutical for the diagnosis and staging PD which can be radiolabeled in-house with good yield leading to its easy availability.
http://ift.tt/2ygME9n
Prevalence of subclinical peripheral vascular disease in obese Egyptian patients
Indian Journal of Nuclear Medicine 2017 32(4):271-278
Objective: To detect subclinical peripheral vascular disease in obese Egyptian patients and establish relations between obesity, metabolic risk factors, and PVD. Methods: This was a prospective case-control study including 100 obese patients (BMI >30) (G1). In addition, 100 age and sex matched non-obese healthy subjects as a control group (G2). Both groups were subjected to duplex ultrasound, Radionuclide muscle scan. Angiography was done for 17 patients. Results: The image pattern of 99mTc-MIBI muscles uptake was studied and perfusion reserve (PR%) was calculated in (G1) and (G2). Comparison between the two groups showed statistically significant difference (P < 0.001) as regarding laboratory findings. Patients were categorized according to PR% into +ve for ischemia (mean PR% was 28.4 ± 20.3) and -ve for ischemia (mean PR% was 65.0 ± 11.4). Among (G1) 64 patients positive for ischemia by both PR% and Doppler, 36 patients were negative by Doppler and 22 of them were positive for ischemia by PR%. Angiography was done for 17 of them and proved ischemia in all of them. Conclusion: The Tc-99m sestamibi muscle scan can be used as a screening and diagnostic tool of preclinical atherosclerosis in obese patients.
http://ift.tt/2yi6z7R
Nested stromal-epithelial tumor of liver with recurrent extrahepatic metastasis: Role of fluorodeoxyglucose positron emission tomography/computed tomography
Indian Journal of Nuclear Medicine 2017 32(4):372-373
Nested stromal-epithelial tumor (NSET) is a very rare nonhepatocytic and nonbiliary primary tumor of the liver. An 8-year-old boy was incidentally detected with hepatic lesions, involving both lobes of the liver for which he later underwent orthotopic liver transplant. The hepatic lesions were confirmed to be NSET following histopathological examination of explant liver specimen. He later developed recurrence with multiple metastatic lesions, including multi-station nodal and right talar bone involvement. We here present the case highlighting the importance of 18F-fludeoxyglucose positron emission tomography/computed tomography in the management of this rare tumor, in particular for monitoring disease progression and/or recurrence.
http://ift.tt/2ylbxm1
Calculating gamma camera uniformity parameters: Beyond the vendor-specific protocol
Indian Journal of Nuclear Medicine 2017 32(4):279-282
Objectives: The aim of this study was to develop and verify a personal computer-based software tool for calculating uniformity indices of gamma camera. Materials and Methods: The program was developed in MATLAB R2013b under Microsoft Windows operating system. Noise-less digital phantoms with known uniformity parameters were used to verify the accuracy of the program. Two hundred and forty-four Co-57 flood source images were acquired on Symbia T6 and Discovery nuclear medicine/computed tomography 670. The uniformity indices of these images were determined with their respective vendor's software and also by the tool developed. Bland–Altman plots were used for measuring the agreements between the developed program and the vendor's program for the calculation of uniformity indices. Results: The tool for calculating uniformity indices was found to be accurate. Uniformity indices measured with the tool revealed a very good correlation with vendor's software based on Bland–Altman analysis, as almost all measurements were within the ±2 standard deviation range. Conclusion: The software tool for calculation of uniformity indices is accurate, and the uniformity indices calculated by it are in agreement with uniformity indices calculated by the vendor's software.
http://ift.tt/2ygEbD6
Clinically occult rectal carcinoma identified in a case of Streptococcus bovis Endocarditis on fluorodeoxyglucose positron emission tomography/computed tomography: A case report and review of literature
Indian Journal of Nuclear Medicine 2017 32(4):345-347
Numerous studies over past four decades have implicated a strong association of Streptoccus bovis infection with colorectal carcinomas. Strong is this association that a screening colonoscopy for identifying malignancy is considered mandatory in patients whose blood/fecal cultures show growth of this particular pathogen. Here, we report an interesting case of a 61-year-old female patient who presented with pyrexia of unknown origin for 3 weeks. Positron emission tomography/computed tomography, in addition to helping diagnose mitral valve endocarditis, also identified a clinically occult T2N0 rectal carcinoma.
http://ift.tt/2ykFR06
Investigating the role of global histogram equalization technique for 99mTechnetium-Methylene diphosphonate bone scan image enhancement
Indian Journal of Nuclear Medicine 2017 32(4):283-288
Purpose of the Study: 99mTechnetium-methylene diphosphonate (99mTc-MDP) bone scan images have limited number of counts per pixel, and hence, they have inferior image quality compared to X-rays. Theoretically, global histogram equalization (GHE) technique can improve the contrast of a given image though practical benefits of doing so have only limited acceptance. In this study, we have investigated the effect of GHE technique for 99mTc-MDP-bone scan images. Materials and Methods: A set of 89 low contrast 99mTc-MDP whole-body bone scan images were included in this study. These images were acquired with parallel hole collimation on Symbia E gamma camera. The images were then processed with histogram equalization technique. The image quality of input and processed images were reviewed by two nuclear medicine physicians on a 5-point scale where score of 1 is for very poor and 5 is for the best image quality. A statistical test was applied to find the significance of difference between the mean scores assigned to input and processed images. Results: This technique improves the contrast of the images; however, oversaturation was noticed in the processed images. Student's t-test was applied, and a statistically significant difference in the input and processed image quality was found at P < 0.001 (with α = 0.05). However, further improvement in image quality is needed as per requirements of nuclear medicine physicians. Conclusion: GHE techniques can be used on low contrast bone scan images. In some of the cases, a histogram equalization technique in combination with some other postprocessing technique is useful.
http://ift.tt/2yhsw70
Abnormal fluorodeoxyglucose uptake in lung without structural abnormality on computed tomography
Indian Journal of Nuclear Medicine 2017 32(4):359-360
Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is a useful proven imaging modality in the management of many types of cancers. It is being used at various stages of treatment of cancer. Knowledge regarding the physiological biodistribution and false-positive findings should be kept in mind for correct interpretation. Pulmonary FDG uptake can be due to different causes such as infection, inflammation, and metastases which are invariably associated with structural abnormality on CT. In rare circumstances, there can be a focus of FDG uptake in the lung with no corresponding structural abnormality which might be due to an inflammatory vascular microthrombus or due to iatrogenic microembolism caused during the injection of radiotracer. It is important to be aware of this as it can cause difficulty in interpreting the scan and can lead to false-positive findings. It also highlights the importance of hybrid imaging in the form of PET-CT as there is a definite possibility of misinterpreting this as a site of metastasis in a known carcinoma patient if there was no corresponding CT image.
http://ift.tt/2ykzjhK
In vitro protective effect of rutin and quercetin against radiation-induced genetic damage in human lymphocytes
Indian Journal of Nuclear Medicine 2017 32(4):289-295
Purpose of the Study: Rutin (RUT) and quercetin (QRT) which are dietary compounds were investigated for their ability to protect against ionizing radiation (IR)-induced genotoxicity in human lymphocytes. Materials and Methods: The radiation antagonistic potential of RUT and QRT was assessed by alkaline comet and cytokinesis-block micronucleus (CBMN) assay. Results: Treatment of lymphocytes with RUT and QRT (25 μg/ml) prior exposure to 2 Gy gamma radiation resulted in a significant reduction of frequency of micronuclei as compared to the control set of cells evaluated by CBMN assay. Similarly, treatment of lymphocytes with RUT and QRT before radiation exposure showed significant decrease in the DNA damage as assessed by comet parameters, such as percent tail DNA and olive tail moment. Conclusion: The study demonstrates the protective effect of RUT and QRT against IR-induced DNA damage in human lymphocytes, which may be partly attributed to scavenging of IR-induced free radicals and also by the inhibition of IR-induced oxidative stress.
http://ift.tt/2yi6wsH
Bone scan in evaluation of bone viability in severe frostbite of the hand
Indian Journal of Nuclear Medicine 2017 32(4):367-368
A 39-year-old male presented to the emergency department (ED) with frostbite to the fingers of both hands. In the ED, he received warm baths, acetylsalicylic acid, clopidogrel, and heparin. A three-phase bone scintigraphy with technetium-99m-methylene diphosphonate revealed absent radiotracer uptake in distal phalanges of both hands. The patient received acetylsalicylic acid, clopidogrel and wound care for the next 5 days and made an excellent recovery with satisfactory wound healing in both hands. Early rapid rewarming and reperfusion can improve the prognosis significantly and therefore bone scan done within first 1–2 days may give spurious results.
http://ift.tt/2xBSOim
Conjugation of antibodies with radiogold nanoparticles, as an effector targeting agents in radiobioconjugate cancer therapy: Optimized labeling and biodistribution results
Indian Journal of Nuclear Medicine 2017 32(4):296-303
Purpose of the Study: Drug accessibility to the tumor cells is an important area of concern with an anticipation of increasing the efficacy of the drug to be delivered to a specific site. The biogenesis of gold nanoparticles using plant-mediated phytochemical extracts and their possible linkage to cancer antibodies with an aim at delivering the conjugate specifically to the tumor-associated antigen is the basic objective of the research. Materials and Methodology: Radiolabeling of antibodies with gold nanoparticles was carried out by a protocol, and the labeling extent of antibodies was compared with that of a radiogold solution to ordinary particulate size (AuNO-Ab). The amount of radiolabeling was estimated by subjecting the reaction mixtures to thin layer chromatography (ITLC-Silica-gel) in different solvent mediums, both by visual inspection of images of the Siemens Orbitor Gamma Camera ZLC-7500 and also by in vitro counting of the radioactive counts in different quarters of the chromatographic strips. Biodistribution relating to the deposition of injected dose in nontargeting sites (reticuloendothelial system [RES]-localization) was studied and efforts were made for reducing the same. Results: Much improved gold incorporation was confirmed at various molar ratios of gold to immunoglobulin (antibody) using nanogold solution (>85%). The RES uptake in the liver, spleen etc., was observed as a problem and the prior administration of unlabeled nonspecific gammaglobulin (before the actual radiolabeled product) was identified as the suitable blocking agent for this purpose. Conclusion: The study signifies the potential for PEGylated gold nanoparticles of a precise size range, suitable to use as a delivery vehicle for targeting small biomolecules (antibody etc.) to the tumor site. The stability of this labeled immunoconjugate and other toxicity effects under physiological conditions needs further evaluation. If successful, this could be a role model for attaining high tumor/nontumor ratio.
http://ift.tt/2ykCw1b
Fluorodeoxyglucose positron emission tomography–computed tomography in disseminated cryptococcosis
Indian Journal of Nuclear Medicine 2017 32(4):377-379
Disseminated cryptococcosis without pulmonary involvement is a very rare phenomenon. Patterns of organ involvement in cryptococcosis resemble various other infective conditions as well as malignant conditions on fluorodeoxyglucose positron emission tomography–computed tomography. We present a case of a 43-year-old male patient who had disseminated cryptococcosis. The rarity of the case being noninvolvement of lungs and meninges and resembling more like lymphoma due to the diffuse involvement of the lymph nodes on both sides of the diaphragm.
http://ift.tt/2xC3bCW
Disease- and treatment-related complication on F-18-Fluorodeoxyglucose positron emission tomography/computed tomography in oncology practice: A pictorial review
Indian Journal of Nuclear Medicine 2017 32(4):304-315
F-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is routinely performed in oncology patients for various indications including staging, restaging, recurrence detection, and treatment response evaluation. Many disease- and treatment-related complications can be incidentally detected on PET/CT, which may be due to the complication of radiotherapy, chemotherapy, intervention, or primary tumor itself. Some of these complications could be life threatening and need urgent intervention. Therefore, these incidental findings should be recognized on PET/CT and immediately informed to the treating physicians if required urgent intervention.
http://ift.tt/2ykkAUj
Clinical pearls: Etiologies of superscan appearance on Fluorine-18-Fludeoxyglucose positron emission tomography-computed tomography
Indian Journal of Nuclear Medicine 2017 32(4):259-265
The term "superscan" usually refers to a characteristic pattern on skeletal scintigraphy consisting of symmetrically intense and diffuse radiotracer uptake in the skeleton with absent or diminished visualization of the genitourinary system and soft tissues. Superscans and superscan-like appearances have also been described on fluorine-18-fludeoxyglucose positron emission tomography-computed tomography (18-F-FDG PET/CT). We review reported cases of 18-F-FDG PET/CT superscans and propose criteria for differentiating pathologic superscans from physiologic causes. Knowledge of the 18-F-FDG PET/CT superscan, its reported pathologic causes, its benign imitators, and its clinical implications is important to the nuclear medicine physician or radiologist specializing in the interpretation of nuclear studies to avoid several diagnostic pitfalls.
http://ift.tt/2xCeKdr
Single coronary artery demonstrating slightly decreased 13NH3Stress flows in its distal flow territories
Indian Journal of Nuclear Medicine 2017 32(4):348-350
A 54-year-old male patient was referred for computed tomography angiography to rule out cardiovascular disease. The examination revealed a single coronary artery originating from the right sinus of Valsalva, extending to the normal left circumflex artery and left anterior descending artery domains. The computed tomography showed only mild coronary sclerosis. The myocardial stress flow on the subsequently performed 13NH3myocardial perfusion positron emission tomography demonstrated a relative stress flow reduction in the distal segments along the monocoronary. In the presented patient without significant coronary disease and a benign course of the monocoronary, the relative inability to increase blood flow during stress in the distal segments of the artery is a remarkable finding.
http://ift.tt/2ykCYfw
Non-Hodgkin's lymphoma with pelvic skeletal muscle involvement presenting as low back ache: An uncommon presentation of a rather common malignancy
Indian Journal of Nuclear Medicine 2017 32(4):355-358
Lymphoma with skeletal muscle involvement is a rare clinical presentation. They may occur as primary skeletal muscle lymphoma, contiguous spread from bones or by metastatic spread. We present a rare case of non-Hodgkin's lymphoma with pelvic skeletal muscle involvement presenting as low back ache. Lymphoma as the first differential diagnosis in this case was clinched after an 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and confirmed as diffuse large B-cell lymphoma on histopathology. We seek to present an uncommon manifestation of lymphoma and highlight the role of 18F-FDG PET CT in the diagnosis, staging, and management of lymphoma.
http://ift.tt/2ykAyh8
Convergent Transcriptional Programs Regulate cAMP Levels in C. elegans GABAergic Motor Neurons
Publication date: Available online 12 October 2017
Source:Developmental Cell
Author(s): Bin Yu, Xiaolin Wang, Shuai Wei, Tao Fu, Emmanuel Enoch Dzakah, Ahmed Waqas, Walter W. Walthall, Ge Shan
Both transcriptional regulation and signaling pathways play crucial roles in neuronal differentiation and plasticity. Caenorhabditis elegans possesses 19 GABAergic motor neurons (MNs) called D MNs, which are divided into two subgroups: DD and VD. DD, but not VD, MNs reverse their cellular polarity in a developmental process called respecification. UNC-30 and UNC-55 are two critical transcription factors in D MNs. By using chromatin immunoprecipitation with CRISPR/Cas9 knockin of GFP fusion, we uncovered the global targets of UNC-30 and UNC-55. UNC-30 and UNC-55 are largely converged to regulate over 1,300 noncoding and coding genes, and genes in multiple biological processes, including cAMP metabolism, are co-regulated. Increase in cAMP levels may serve as a timing signal for respecification, whereas UNC-55 regulates genes such as pde-4 to keep the cAMP levels low in VD. Other genes modulating DD respecification such as lin-14, irx-1, and oig-1 are also found to affect cAMP levels.
Graphical abstract
Teaser
Yu et al. demonstrate that UNC-30 and UNC-55 converge to target ∼1,300 genes using ChIP-seq on endogenously tagged proteins. Multiple processes, including cAMP metabolism, are co-regulated. Increase in cAMP may regulate the timing of DD respecification, whereas UNC-55 keeps cAMP low in VD via regulation of targets such as pde-4.http://ift.tt/2hEhWiB
Binding of PLD2-Generated Phosphatidic Acid to KIF5B Promotes MT1-MMP Surface Trafficking and Lung Metastasis of Mouse Breast Cancer Cells
Publication date: Available online 12 October 2017
Source:Developmental Cell
Author(s): Ziqing Wang, Feng Zhang, Jingquan He, Ping Wu, Li Wei Rachel Tay, Ming Cai, Weiqi Nian, Yuanyuan Weng, Li Qin, Jeffrey T. Chang, Laura B. McIntire, Gilbert Di Paolo, Jianming Xu, Junmin Peng, Guangwei Du
Little is known about the cellular events promoting metastasis. We show that knockout of phospholipase D2 (PLD2), which generates the signaling lipid phosphatidic acid (PA), inhibits lung metastases in the mammary tumor virus (MMTV)-Neu transgenic mouse breast cancer model. PLD2 promotes local invasion through the regulation of the plasma membrane targeting of MT1-MMP and its associated invadopodia. A liposome pull-down screen identifies KIF5B, the heavy chain of the motor protein kinesin-1, as a new PA-binding protein. In vitro assays reveal that PA specifically and directly binds to the C terminus of KIF5B. The binding between PLD2-generated PA and KIF5B is required for the vesicular association of KIF5B, surface localization of MT1-MMP, invadopodia, and invasion in cancer cells. Taken together, these results identify a role of PLD2-generated PA in the regulation of kinesin-1 motor functions and breast cancer metastasis and suggest PLD2 as a potential therapeutic target for metastatic breast cancer.
Graphical abstract
Teaser
The cellular events that regulate cancer metastasis are poorly understood. Wang et al. demonstrate that PLD2, through generating the signaling lipid phosphatidic acid (PA), promotes breast cancer lung metastasis. Direct PA binding to the motor protein KIF5B controls MT1-MMP plasma membrane trafficking, invadopodia formation, and local invasion.http://ift.tt/2hEGDez
An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate
Publication date: Available online 12 October 2017
Source:Developmental Cell
Author(s): Vanessa Barone, Moritz Lang, S.F. Gabriel Krens, Saurabh J. Pradhan, Shayan Shamipour, Keisuke Sako, Mateusz Sikora, Călin C. Guet, Carl-Philipp Heisenberg
Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo.
Graphical abstract
Teaser
Barone et al. find a positive feedback loop between cell-cell contact duration and Nodal signaling that determines whether mesendoderm progenitors become mesoderm or endoderm. These findings highlight how the crosstalk between cell behavior and signaling affects the regulatory networks determining cell-fate decision.http://ift.tt/2hE2N0G
2017 ATA Annual Alliance for Patient Education Public Health Forum
2017 ATA Annual Alliance for Patient Education Public Health Forum – Saturday, October 21, 2017
October 11, 2017– The public is invited to attend a free public health forum focused on thyroid disease, in which leading physicians will be present to discuss and answer questions about different types of thyroid disorders and symptoms. The informational forum is free and open to the public. Walk-in attendance is welcome although reservations are encouraged. The public forum is sponsored and organized by the American Thyroid Association (ATA) and will take place Saturday, October 21, 2017, 2:00-4:00pm at the The Fairmont Empress, Victoria, BC, Canada. Endocrinologists and Thyroid Patient Support Groups will be available to meet with thyroid patients during the forum.
Who Should Attend?
Anyone who has or cares for someone with an overactive or underactive thyroid, thyroiditis, a thyroid nodule, thyroid cancer, or a family history of thyroid problems or related disorders, including rheumatoid arthritis, juvenile diabetes, pernicious anemia, or prematurely gray hair (starting before age 30).
Do you have questions or concerns about thyroid disease? Have you experienced any of the following symptoms and wonder if they might be related to a thyroid disorder: low energy, memory loss, fatigue, depression, rapid heartbeat, restlessness, infertility, weight or hair changes, or a lump in your neck?
Anyone with questions, symptoms, or concerns about a thyroid problem should join ATA physician experts at the free public form on Saturday, October 21st. Free educational materials will be available.
Do I Need to Register?
Reservations are requested. To register or for more information, please e-mail: thyroid@thyroid.org
(Please indicate in your message the thyroid condition you are most concerned about.)
Walk-ins welcome! Please come if you have questions, symptoms, or concerns about a thyroid problem. More information about thyroid disease and thyroid cancer is available at www.thyroid.org. Join Friends of the ATA and receive news of the latest thyroid research.
Flyer for Printing and Posting (PDF File 136 KB)
The post 2017 ATA Annual Alliance for Patient Education Public Health Forum appeared first on American Thyroid Association.
http://ift.tt/2z3yx6u
2017 ATA Annual Alliance for Patient Education Public Health Forum
2017 ATA Annual Alliance for Patient Education Public Health Forum – Saturday, October 21, 2017
October 11, 2017– The public is invited to attend a free public health forum focused on thyroid disease, in which leading physicians will be present to discuss and answer questions about different types of thyroid disorders and symptoms. The informational forum is free and open to the public. Walk-in attendance is welcome although reservations are encouraged. The public forum is sponsored and organized by the American Thyroid Association (ATA) and will take place Saturday, October 21, 2017, 2:00-4:00pm at the The Fairmont Empress, Victoria, BC, Canada. Endocrinologists and Thyroid Patient Support Groups will be available to meet with thyroid patients during the forum.
Who Should Attend?
Anyone who has or cares for someone with an overactive or underactive thyroid, thyroiditis, a thyroid nodule, thyroid cancer, or a family history of thyroid problems or related disorders, including rheumatoid arthritis, juvenile diabetes, pernicious anemia, or prematurely gray hair (starting before age 30).
Do you have questions or concerns about thyroid disease? Have you experienced any of the following symptoms and wonder if they might be related to a thyroid disorder: low energy, memory loss, fatigue, depression, rapid heartbeat, restlessness, infertility, weight or hair changes, or a lump in your neck?
Anyone with questions, symptoms, or concerns about a thyroid problem should join ATA physician experts at the free public form on Saturday, October 21st. Free educational materials will be available.
Do I Need to Register?
Reservations are requested. To register or for more information, please e-mail: thyroid@thyroid.org
(Please indicate in your message the thyroid condition you are most concerned about.)
Walk-ins welcome! Please come if you have questions, symptoms, or concerns about a thyroid problem. More information about thyroid disease and thyroid cancer is available at www.thyroid.org. Join Friends of the ATA and receive news of the latest thyroid research.
Flyer for Printing and Posting (PDF File 136 KB)
The post 2017 ATA Annual Alliance for Patient Education Public Health Forum appeared first on American Thyroid Association.
http://ift.tt/2z3yx6u
Xenohormesis in early life: new avenues of research to explore anti-aging strategies through the maternal diet.
Source:Medical Hypotheses
Author(s): Philippe de Medina
Aging is a progressive internal physiological deterioration of the organism, leading to the occurrence of age-related lethal diseases. It has become a major societal challenge to understand the processes that drive aging and to develop rational pharmacological agents and dietary approaches to fight against age-related deterioration and diseases. Interestingly, several lines of evidence highlight an influence of the developmental period on the risk of age-related diseases later in life. This field is known as the developmental origins of health and disease. Following this logic, studying the modification of maternal diet during early life may provide innovative new anti-aging approaches. Nutritional and psychological stresses during gestation are associated with poorer offspring health conditions in late life, and must be avoided during pregnancy. Besides these recommendations, very little has been published about the possible use of maternal diet to program offspring for healthy aging and an extended lifespan. Such health benefits may be provided by different foreign molecules, and particularly the phytochemicals produced by stressed plants, or xenohormetins. The xenohormesis hypothesis proposes that xenohormetins are signals of environmental change and trigger a beneficial adaptive response in individuals who consume them. No studies to date have investigated whether the consumption of stressed plants during pregnancy and lactation could provide chemical cues that impact early life programming and thus influence the future health and lifespan of offspring. Investigating the effect of xenohormesis in early life will involve adding edible plants exposed to different stressors (i.e. UV light, heat, ozone, etc.) to maternal diet and the exposure of offspring to this xenohormetin-enriched maternal diet at different periods of their prenatal life. The hypothesis proposed in this article is a potential tool to decipher the possible impact of xenohormesis during early life, and paving the way toward an innovative maternal diet that ensures the healthy aging of the progeny.
http://ift.tt/2xBLZ09
Transcutaneous Neuromuscular Electrical Stimulation may be Beneficial in he Treatment of Premature Ejaculation
Source:Medical Hypotheses
Author(s): Ilan Gruenwald, Ege Can Serefoglu, Tal Gollan, Shmuel Springer, Gideon Meiry, Appel Boaz, Shechter Arik
Premature ejaculation (PE) is a very common and disturbing sexual dysfunction in men, associated with detrimental psychological, physical and social effects. Approximately 20-30% of sexually active men suffer from PE [1–3]. Although this dysfunction has been widely investigated, its pathophysiology still remains unclear. Today, there is only one oral compound, which has been specifically developed for the pharmaceutical treatment of PE, Dapoxetine. Although it has been approved by the European Medical Agency (EMEA), Dapoxetine has not been approved by the U.S. Food and Drug Administration (FDA), due to its controversial efficacy and safety [4,5]. Therefore, the treatment of PE continues to be a major area of medical research.
http://ift.tt/2xBM0kY
Characteristics of 2.5 MV beam and imaging dose to patients
Source:Radiotherapy and Oncology
Author(s): George X. Ding, Peter Munro
PurposeThis work provides the beam characteristics and evaluates the imaging dose to patients for a 2.5 MV portal imaging beam.Method and materialsThe Monte Carlo technique has been used to simulate the 2.5 MV imaging beam. Beam characteristics have been analyzed including the energy spectra and the fluence distributions as a function of position away from the beam central axis. The accuracy of a simulated beam was validated through comparisons between the Monte Carlo calculated and measured dose distributions in a water phantom. The simulated 2.5 MV beam was also used to obtain the absorbed-dose beam quality conversion factor, kQ, for absorbed dose calibration. The simulated beams were then used to evaluate the imaging dose to patients compared with that from a conventional therapeutic 6 MV beam.ResultsThe mean energies of photons and electrons in the 2.5 MV beam are 0.48 MeV and 0.37 MeV respectively. The photon fluence decreases at 20 cm away from the central axis by only up to 30% for this flattening-filter free beam. The values of %dd curves at depth = 10 cm are 53% and 63% for 10 × 10 cm2 and 40 × 40 cm2 fields respectively. Portal imaging doses (D50 of the DVHs) to the eyes, heart and bladder from representative pairs of 2.5 MV (or 6 MV) setup images are 1.8 cGy (3.5 cGy), 1.1 cGy (2.5 cGy) and 1.0 cGy (2.4 cGy) for head, thorax and pelvis image acquisitions respectively.ConclusionWe provide dosimetric data, as well as estimates of organ imaging doses, for this 2.5 MV beam. When clinical default imaging protocols are used, the imaging dose from the 2.5 MV beam is about 50% of that from a 6 MV beam. The information can be used to select image procedures and to estimate organ dose from imaging procedures.
http://ift.tt/2hDWo5M
Multi-criterial patient positioning based on dose recalculation on scatter-corrected CBCT images
Source:Radiotherapy and Oncology
Author(s): Jan Hofmaier, Jonas Haehnle, Christopher Kurz, Guillaume Landry, Cornelius Maihoefer, Lars Schüttrumpf, Philipp Süss, Katrin Teichert, Matthias Söhn, Nadine Spahr, Christoph Brachmann, Florian Weiler, Christian Thieke, Karl-Heinz Küfer, Claus Belka, Katia Parodi, Florian Kamp
Background and purposeOur aim was to evaluate the feasibility and potential advantages of dose guided patient positioning based on dose recalculation on scatter corrected cone beam computed tomography (CBCT) image data.Material and methodsA scatter correction approach has been employed to enable dose calculations on CBCT images. A recently proposed tool for interactive multicriterial dose-guided patient positioning which uses interpolation between pre-calculated sample doses has been utilized. The workflow was retrospectively evaluated for two head and neck patients with a total of 39 CBCTs. Dose–volume histogram (DVH) parameters were compared to rigid image registration based isocenter corrections (clinical scenario).ResultsThe accuracy of the dose interpolation was found sufficient, facilitating the implementation of dose guided patient positioning. Compared to the clinical scenario, the mean dose to the parotid glands could be improved for 2 out of 5 fractions for the first patient while other parameters were preserved. For the second patient, the mean coverage over all fractions of the high dose PTV could be improved by 4%. For this patient, coverage improvements had to be traded against organ at risk (OAR) doses within their clinical tolerance limits.ConclusionsDose guided patient positioning using in-room CBCT data is feasible and offers increased control over target coverage and doses to OARs.
http://ift.tt/2hDWmea
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