Implicit and Explicit Measurements of Affective Responses to Food Odors

One of the main functions of olfaction is to activate approach/avoidance behavior, toward or away from people, foods, or other odor sources. These behaviors are partly automated and therefore poorly accessible via introspection. Explicit tests need therefore be complemented by implicit tests to provide additional insights into the underlying processes of these behaviors. Affective responses to seven food odors plus one control nonodor were assessed in 28 female participants (18–30 years) using explicit tests [pleasantness, intensity, and non-verbal emotional ratings (PrEmo)] as well as implicit tests that reflect dynamic expressive emotional reactions (facial expressions) as well as behavioral-preparation responses (autonomic nervous system responses: heart rate, skin conductance, and skin temperature). Explicit tests showed significant differences in pleasantness (P < 0.05), and all PrEmo emotions (P < 0.05) except shame. Explicit emotional responses were summarized by valence (explaining 83% of the responses variance) and arousal (14%) as principal components. Early implicit facial and ANS responses (after 1s) seem to reflect the odors' arousal, whereas later ANS responses (after 3–4s) reflected the odors' valence. The results suggest that explicit measures primarily reflect the odors' valence, as result of from relatively long (conscious) processing, which may be less relevant for odor acceptance in the real world where fast and automated processes based on arousal may play a larger role.

http://ift.tt/2cZ4Dcd

Olfactory Performance Can Be Influenced by the Presentation Order, Background Noise, and Positive Concurrent Feedback

Sniffin' Sticks have become a popular procedure to measure overall olfactory functionality with 3 subtest: phenyl ethyl alcohol threshold test (T), discrimination (D), and identification (I). However, several procedural components specified by the original paper have not been tested nor has the impact of deviations been measured. The aim of the present work was to measure olfactory performance under modified testing procedures. First, the reverse order of subtests (IDT) was compared with more standard practices (TDI). Next, the possible impact of background noise and positive concurrent feedback were assessed. A total of 120 individuals participated in the study where the 3 conditional experiments, each involving 40 participants, were completed. Testing procedures that reversed the presentation order of subtests (I->D->T) scored a significantly lower overall TDI score than standard testing order with the threshold subtest being the most influenced. Additionally, nonverbal background noise lowered overall olfactory performance while concurrent feedback modulated threshold performance. These results emphasize the importance of testing parameters where olfactory perception and tasks may be modulated by adaptation and attentional distraction, respectively. This study helped furthermore to demonstrate that the investigated 3 deviations from the standard procedure revealed a significant impact on the performance outcome in olfactory assessment using the Sniffin' Sticks.

http://ift.tt/2d8etpz

Editorial Board

http://ift.tt/2cZ4q91

Perceived Odor-Taste Congruence Influences Intensity and Pleasantness Differently

The role of congruence in cross-modal interactions has received little attention. In most experiments involving cross-modal pairs, congruence is conceived of as a binary process according to which cross-modal pairs are categorized as perceptually and/or semantically matching or mismatching. The present study investigated whether odor–taste congruence can be perceived gradually and whether congruence impacts other facets of subjective experience, that is, intensity, pleasantness, and familiarity. To address these questions, we presented food odorants (chicken, orange, and 3 mixtures of the 2) and tastants (savory–salty and sour–sweet) in pairs varying in congruence. Participants were to report the perceived congruence of the pairs along with intensity, pleasantness, and familiarity. We found that participants could perceive distinct congruence levels, thereby favoring a multilevel account of congruence perception. In addition, familiarity and pleasantness followed the same pattern as the congruence while intensity was highest for the most congruent and the most incongruent pairs whereas intensities of the intermediary-congruent pairs were reduced. Principal component analysis revealed that pleasantness and familiarity form one dimension of the phenomenological experience of odor–taste pairs that was orthogonal to intensity. The results bear implications for the understanding the behavioral underpinnings of perseverance of habitual food choices.

http://ift.tt/2d8eRUZ

Subscriptions

http://ift.tt/2cZ4yW9

Copy Number Variation in TAS2R Bitter Taste Receptor Genes: Structure, Origin, and Population Genetics

Bitter taste receptor genes (TAS2Rs) harbor extensive diversity, which is broadly distributed across human populations and strongly associated with taste response phenotypes. The majority of TAS2R variation is composed of single-nucleotide polymorphisms. However, 2 closely positioned loci at 12p13, TAS2R43 and -45, harbor high-frequency deletion () alleles in which genomic segments are absent, resulting in copy number variation (CNV). To resolve their chromosomal structure and organization, we generated maps using long-range contig alignments and local sequencing across the TAS2R43–45 region. These revealed that the deletion alleles (43 and 45) are 37.8 and 32.2kb in length, respectively and span the complete coding region of each gene (~1kb) along with extensive up- and downstream flanking sequence, producing separate CNVs at the 2 loci. Comparisons with a chimpanzee genome, which contained intact homologs of TAS2R43, -45, and nearby TAS2Rs, indicated that the deletions evolved recently, through unequal recombination in a cluster of closely related loci. Population genetic analyses in 946 subjects from 52 worldwide populations revealed that copy number ranged from 0 to 2 at both TAS2R43 and TAS2R45, with 43 and 45 occurring at high global frequencies (0.33 and 0.18). Estimated recombination rates between the loci were low ( = 2.7x10^–4; r = 6.6x10^–9) and linkage disequilibrium was high (D' = 1.0), consistent with their adjacent genomic positioning and recent origin. Geographic variation pointed to an African origin for the deletions. However, no signatures of natural selection were found in population structure or integrated haplotype scores spanning the region, suggesting that patterns of diversity at TAS2R43 and -45 are primarily due to genetic drift.

http://ift.tt/2d8eqdn

Table of Contents

http://ift.tt/2cZ5ARY

Elevated Cytosolic Cl- Concentrations in Dendritic Knobs of Mouse Vomeronasal Sensory Neurons

In rodents, the vomeronasal system controls social and sexual behavior. However, several mechanistic aspects of sensory signaling in the vomeronasal organ remain unclear. Here, we investigate the biophysical basis of a recently proposed vomeronasal signal transduction component—a Ca²⁺-activated Cl^– current. As the physiological role of such a current is a direct function of the Cl^– equilibrium potential, we determined the intracellular Cl^– concentration in dendritic knobs of vomeronasal neurons. Quantitative fluorescence lifetime imaging of a Cl^–-sensitive dye at the apical surface of the intact vomeronasal neuroepithelium revealed increased cytosolic Cl^– levels in dendritic knobs, a substantially lower Cl^– concentration in vomeronasal sustentacular cells, and an apparent Cl^– gradient in vomeronasal neurons along their dendritic apicobasal axis. Together, our data provide a biophysical basis for sensory signal amplification in vomeronasal neuron microvilli by opening Ca²⁺-activated Cl^– channels.

http://ift.tt/2d8fRsf

Characteristics of PM2.5 concentrations across Beijing during 2013–2015

Publication date: November 2016
Source:Atmospheric Environment, Volume 145
Author(s): Stuart Batterman, Lizhong Xu, Feng Chen, Fang Chen, Xuefen Zhong
High concentrations of particulate matter (PM2.5) and frequent air pollution episodes in Beijing have attracted widespread attention. This paper utilizes data from the new air pollution network in China to examine the current spatial and temporal variability of PM2.5 at 12 monitoring sites in Beijing over a recent 2-year period (April 2013 to March 2015). The long term (2-year) average concentration was 83 μg m⁻³, well above Chinese and international standards. Across the region, annual average concentrations varied by 20 μg m⁻³ (25% of the average level), with lower levels in suburban areas compared to periurban and urban areas, which had similar concentrations. The spatial variation in PM2.5 concentrations was associated with several land use and economic variables, including the fraction of vegetated land and building construction activity, which together explained 71% of the spatial variation. Daily air quality was characterized as "polluted" (above 75 μg m⁻³) on 36–47% of days, depending on site. There were 77 pollution episodes during the study period (defined as two or more consecutive days with Beijing-wide 24-hour average concentrations over 75 μg m⁻³), and 2 to 5 episodes occurred each month, including summer months. The longest episode lasted 9 days and daily concentrations exceeded 450 μg m⁻³. Daily PM2.5 levels were autocorrelated (rlag1 = 0.516) and associated with many meteorological variables, including barometric pressure, relative humidity, hours of sunshine, surface and ambient temperature, precipitation and scavenging coefficient, and wind direction. Parsimonious models with meteorological and autoregressive terms explained over 60% of the variation in daily PM2.5 levels. The first autoregressive term and hours of sunshine were the most important variables in these models, however, the latter variable is PM2.5-dependent and thus not an explanatory variable. The present study can serve as a baseline to compare the improved air quality in Beijing expected in future years.



http://ift.tt/2cQ9IDn

Articles Highlighted

http://ift.tt/2cZ4DsG

Size distribution of particle-phase sugar and nitrophenol tracers during severe urban haze episodes in Shanghai

Publication date: November 2016
Source:Atmospheric Environment, Volume 145
Author(s): Xiang Li, Li Jiang, Le Phuoc Hoa, Yan Lyu, Tingting Xu, Xin Yang, Yoshiteru Iinuma, Jianmin Chen, Hartmut Herrmann
In this study, measurements of size-resolved sugar and nitrophenol concentrations and their distributions during Shanghai haze episodes were performed. The primary goal was to track their possible source categories and investigate the contribution of biological and biomass burning aerosols to urban haze events through regional transport. The results showed that levoglucosan had the highest concentration (40–852 ng m⁻³) followed by 4-nitrophenol (151–768 ng m⁻³), sucrose (38–380 ng m⁻³), 4-nitrocatechol (22–154 ng m⁻³), and mannitol (5–160 ng m⁻³). Size distributions exhibited over 90% of levoglucosan and 4-nitrocatechol to the total accumulated in the fine-particle size fraction (<2.1 μm), particularly in heavier haze periods. The back trajectories further supported the fact that levoglucosan was linked to biomass-burning particles, with higher values of associated with air masses passing from biomass burning areas (fire spots) before reaching Shanghai. Other primary saccharide and nitrophenol species showed an unusually large peak in the coarse-mode size fraction (>2.1 μm), which can be correlated with emissions from local sources (biological emission). Principal component analysis (PCA) and positive matrix factorization (PMF) revealed four probable sources (biomass burning: 28%, airborne pollen: 25%, fungal spores: 24%, and combustion emission: 23%) responsible for urban haze events. Taken together, these findings provide useful insight into size-resolved source apportionment analysis via molecular markers for urban haze pollution events in Shanghai.



http://ift.tt/2dgyvyo

Relationship of Phenylthiocarbamide (PTC) Taster Status to Olfactory and Gustatory Function in Patients with Chemosensory Disturbances

Poor sensitivity to the bitter taste of phenylthiocarbamide (PTC) and related substances has been associated with a number of diseases. We determined, in patients with chemosensory dysfunction from multiple etiologies, whether PTC "tasters" (n = 511) exhibit less smell and taste dysfunction than their non-PTC-tasting counterparts (n = 432) on a comprehensive battery of olfactory and gustatory tests. The proportion of tasters (54%) in our study population was much lower than that calculated from 11 North American population studies (76.5%; P < 0.0001). This taster/nontaster ratio was maintained across a range of etiologic categories. More women (60.7%) than men (45.5%) were PTC tasters (P < 0.0001). Although PTC tasting status was unrelated to scores on the olfactory tests (which included tests of odor identification, detection threshold, and odor memory/discrimination), tasters significantly outperformed nontasters on suprathreshold identification and intensity taste tests employing both bitter (caffeine) and nonbitter (sucrose, citric acid, sodium chloride) tasting stimuli. Regardless of PTC taster status, women outperformed men on the taste tests. Our findings suggest the possibility that the T2R38 gene may protect against significant olfactory dysfunction, but once such dysfunction becomes manifest at a level where professional help is sought, such protection is not evident. However, other hypotheses for this phenomenon are possible. This study demonstrates that patients with chemosensory disturbances who are PTC tasters outperform their non-PTC taster counterparts in both identifying and perceiving the intensity of a range of suprathreshold tastants, including ones that do not taste bitter.

http://ift.tt/2d8fP3j

Source apportionment advances using polar plots of bivariate correlation and regression statistics

Publication date: November 2016
Source:Atmospheric Environment, Volume 145
Author(s): Stuart K. Grange, Alastair C. Lewis, David C. Carslaw
This paper outlines the development of enhanced bivariate polar plots that allow the concentrations of two pollutants to be compared using pair-wise statistics for exploring the sources of atmospheric pollutants. The new method combines bivariate polar plots, which provide source characteristic information, with pair-wise statistics that provide information on how two pollutants are related to one another. The pair-wise statistics implemented include weighted Pearson correlation and slope from two linear regression methods. The development uses a Gaussian kernel to locally weight the statistical calculations on a wind speed-direction surface together with variable-scaling. Example applications of the enhanced polar plots are presented by using routine air quality data for two monitoring sites in London, United Kingdom for a single year (2013). The London examples demonstrate that the combination of bivariate polar plots, correlation, and regression techniques can offer considerable insight into air pollution source characteristics, which would be missed if only scatter plots and mean polar plots were used for analysis. Specifically, using correlation and slopes as pair-wise statistics, long-range transport processes were isolated and black carbon (BC) contributions to PM2.5 for a kerbside monitoring location were quantified. Wider applications and future advancements are also discussed.



http://ift.tt/2cQ9D2p

Olfactory Performance in a Large Sample of Early-Blind and Late-Blind Individuals

Previous examinations of olfactory sensitivity in blind people have produced contradictory findings. Thus, whether visual impairment is associated with increased olfactory abilities is unclear. In the present investigation, I aimed to resolve the existing questions via a relatively large-scale study comprising early-blind (N = 43), and late-blind (N = 41) and sighted (N = 84) individuals matched in terms of gender and age. To compare the results with those of previous studies, I combined data from a free odor identification test, extensive psychophysical testing (Sniffin' Sticks test), and self-assessed olfactory performance. The analyses revealed no significant effects of sight on olfactory threshold, odor discrimination, cued identification, or free identification scores; neither was the performance of the early-blind and late-blind participants significantly different. Additionally, the self-assessed olfactory abilities of the blind people were no different than those of the sighted people. These results suggest that sensory compensation in visually impaired is not pronounced with regards to olfactory abilities as measured by standardized smell tests.

http://ift.tt/2cZ5h9x

Cover

http://ift.tt/2d8fsWw

Managing Scalp Psoriasis: An Evidence-Based Review

Abstract

Background

Scalp psoriasis is commonly the initial presentation of psoriasis, and almost 80 % of patients with psoriasis will eventually experience it.

Objective

Although several systematic reviews and guidelines exist, an up-to-date evidence-based review including more recent progress on the use of biologics and new oral small molecules was timely.

Methods

Of the 475 studies initially retrieved from PubMed and the 845 from Embase (up to May 2016), this review includes 27 clinical trials, four papers reporting pooled analyses of other clinical trials, ten open-label trials, one case series, and two case reports after excluding non-English literature.

Results

To our knowledge, few randomized controlled trials (RCTs) are conducted specifically in scalp psoriasis. Topical corticosteroids provide good effects and are usually recommended as first-line treatment. Calcipotriol–betamethasone dipropionate is well tolerated and more effective than either of its individual components. Localized phototherapy is better than generalized phototherapy on hair-bearing areas. Methotrexate, cyclosporine, fumaric acid esters, and acitretin are well-recognized agents in the treatment of psoriasis, but we found no published RCTs evaluating these agents specifically in scalp psoriasis. Biologics and new small-molecule agents show excellent effects on scalp psoriasis, but the high cost of these treatments mean they may be limited to use in extensive scalp psoriasis.

Conclusions

More controlled studies are needed for an evidence-based approach to scalp psoriasis.

http://ift.tt/2daoFlV

Total thyroidectomy: a clue to understanding the metabolic changes induced by subclinical hyperthyroidism?

Abstract

Objective

The effects of endogenous subclinical hyperthyroidism (eSCH) on heart and bone have been well documented. There are only limited data available regarding the impact of eSCH on weight regulation and lipid metabolism. Our aim was to evaluate the changes in body weight and metabolic parameters after total thyroidectomy in patients with preoperative eSCH compared with preoperative euthyroid patients (EUT).

Design

A retrospective study of 505 patients who underwent total thyroidectomy for benign multinodular goiter in an academic hospital in Brussels (Belgium) was performed.

Patients measurements

Two hundred and twenty-five patients were included (eSCH group: n=74; EUT group: n=151). The mean follow-up time was 26.1 ± 0.8 months and was similar in both groups.

Results

Absolute BMI gain was significantly greater in the eSCH group than in the EUT group (1.11 ± 0.17 vs. 0.33 ± 0.13 kg/m²; p=0.003). A significant increase in LDL cholesterol was observed in the eSCH group (16.1 ± 3.8 mg/dl; p<0.001) but not in the EUT group (0.0 ± 3.0 mg/dl; p=0.88). In a multivariate model, preoperative TSH levels were the main factor significantly associated with increases in BMI or LDL cholesterol. Postoperative median TSH levels and L-thyroxine substitution were similar in both groups.

Conclusion

After total thyroidectomy, increases in weight and serum cholesterol were observed in the eSCH group. Given that postoperative TSH levels were similar in the two groups, these observations are probably due to the correction of eSCH, suggesting a direct effect of eSCH on body weight regulation and lipid metabolism.

This article is protected by copyright. All rights reserved.

http://ift.tt/2diREmh

Endocannabinoid receptor blockade increases vascular endothelial growth factor and inflammatory markers in obese women with polycystic ovary syndrome

Abstract

Context

Animal studies suggest that cannabinoid receptor-1 (CB-1) blockade reduces inflammation and neovascularization by decreasing vascular endothelial growth factor (VEGF) levels associated with a reduction in inflammatory markers, thereby potentially reducing cardiovascular risk.

Objective

To determine the impact of CB1 antagonism by rimonabant on VEGF and inflammatory markers in obese PCOS women.

Design

Randomised, open-labelled parallel study.

Setting

Endocrinology outpatient clinic in a referral centre.

Subjects

Twenty patients with PCOS and biochemical hyperandrogenaemia with a body mass index of ≥ 30kg/m² were recruited. Patients were randomised to 1.5g daily of metformin or 20mg daily of rimonabant.

Main Outcome Measures

Post hoc review to detect VEGF and pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 before and after 12 weeks treatment.

Results

After 12 weeks of rimonabant there was a significant increase in VEGF (99.2±17.6 vs 116.2±15.8pg/ml, p<0.01) and IL-8 (7.4±11.0 vs 18.1±13.2pg/ml, p<0.05) but not after metformin (VEGF p=0.7; IL-8 p=0.9). There was no significant difference in the pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 following either treatment.

Conclusion

This study suggests that rimonabant CB-I blockade paradoxically raised VEGF and the cytokine IL-8 in obese women with PCOS that may have offset the potential benefit associated with weight loss.

This article is protected by copyright. All rights reserved.

http://ift.tt/2d1pwBP

Long-term results of cabergoline therapy for macroprolactinomas and analyses of factors associated with remission after withdrawal

Abstract

Objective

Withdrawal of cabergoline is generally challenging, especially in patients with large or invasive macroprolactinomas. Therefore, we aimed to assess long-term results of cabergoline therapy for macroprolactinomas and remission achievement results after withdrawal in patients with macroprolactinomas. We also investigated clinical characteristics and factors related to remission after withdrawal.

Methods

This was an institutional review board approved retrospective analysis. We studied 46 macroprolactinoma patients who had taken cabergoline during the period from 2003 through 2013. Administration of cabergoline was maintained for 5 years before withdrawal in all cases.

Results

Median follow-up after the initiation of cabergoline therapy was 54.3 (range 5.3 to 137.2) months. Recurrences of hyperprolactinemia were observed in 3 of 11 (27%) post-withdrawal patients at a median time of 3.0 (range; 2.9-11.2) months, indicating that a high percentage (73%) maintained remission for at least 12 months after cabergoline cessation. Factors significantly associated with remission were analyzed in 21 patients receiving long-term cabergoline administration. On multivariate analysis, absence of cavernous sinus invasion on pretreatment MRI (≥3/4 tumor encasement of the intracavernous internal carotid artery) (HR; 21.94, 95% CI; 2.06-1071.0, p=0.006), initial PRL <132.7 ng/ml (HR; 8.28, 95% CI; 1.24-199.6, p=0.03), and nadir PRL <1.9 ng/ml during cabergoline therapy (HR; 5.14, 95% CI; 1.10-39.02, p=0.04) showed statistically significant correlations with remission after withdrawal.

Conclusions

Cabergoline therapy can achieve a high percentage (73% in this series) of remission maintenance for at least 12 months after cessation of a 5-year course of therapy, even in patients with macroprolactinomas. Absence of cavernous sinus invasion, serum PRL level lower than 132.7 ng/ml before cabergoline therapy, or nadir serum PRL below 1.9 ng/ml were related to more frequent remission after withdrawal of cabergoline in patients receiving this medication for 5 years.

This article is protected by copyright. All rights reserved.

http://ift.tt/2diT0xu

Increased glucose-stimulated FGF21 response to oral glucose in obese non-diabetic subjects after Roux-en-Y Gastric Bypass

Abstract

Objective

The positive metabolic outcome of Roux-en-Y Gastric Bypass (RYGB) surgery may involve Fibroblast Growth Factor 21 (FGF21), both in the fasting state and postprandially. We measured the fasting levels of FGF21 before and after bariatric surgery as well as the postprandial FGF21 responses after a glucose load and after a mixed meal.

Design

Observational intervention trial.

Patients and measurements

Eight obese, non-diabetics patients underwent RYGB. Plasma FGF21 was measured both before and after surgery on three different days during oral glucose loads (25 g or 50 g glucose) or a mixed meal. Blood samples were taken right before the meal and at 15 min intervals until 90 min and at 150 min and 210 min relative to the start of the meal.

Results

Overall, fasting plasma FGF21 did not change significantly before and after surgery (262±71 vs 411±119 pg/ml), but for three subjects fasting plasma FGF21 increased significantly after surgery. Furthermore, FGF21 levels increased significantly at t=90 and t=150 min in response to 50 g glucose, but not after a mixed meal.

Conclusions

In conclusion, the observed increase in postprandial plasma FGF21 in response to glucose and the lack of FGF21 response to a mixed meal may have important implications for the physiologic role of FGF21. The increase in postprandial FGF21 in response to glucose in the early post-operative period may contribute to the metabolic improvements observed after gastric bypass.

This article is protected by copyright. All rights reserved.

http://ift.tt/2d1pQRb

Variability in Response to Quadripulse Stimulation of the Motor Cortex

Publication date: Available online 21 September 2016
Source:Brain Stimulation
Author(s): Koichiro Nakamura, Stefan Jun Groiss, Masashi Hamada, Hiroyuki Enomoto, Suguru Kadowaki, Mitsunari Abe, Takenobu Murakami, Winnugroho Wiratman, Fangyu Chang, Shunsuke Kobayashi, Ritsuko Hanajima, Yasuo Terao, Yoshikazu Ugawa
BackgroundResponses to plasticity-inducing brain stimulation protocols are highly variable. However, no data are available concerning the variability of responses to quadripulse stimulation (QPS).ObjectiveWe assessed the QPS parameters of motor cortical plasticity induction in a systematic manner, and later investigated the variability of QPS using optimal parameters.MethodsFirst, two different interburst intervals (IBI) with the same total number of pulses were compared. Next we investigated three different IBIs with a different total number of pulses but with same duration of intervention. We also compared the after-effects of monophasic and biphasic QPS. Finally, variability of QPS was tested in 35 healthy subjects. Twenty motor evoked potentials (MEPs) were measured every 5 to 10 min for up to one hour after intervention.ResultsQPS at an IBI of 5 s produced MEPs changes that are dependent on the interstimulus interval of the four magnetic pulses, consistent with previous reports. Unexpectedly, QPS at an IBI of 2.5 s did not induce any plasticity, even with the same total number of pulses, that is, 1,440. QPS at an IBI of 7.5 s produced a variable response but was likely to be comparable to conventional QPS. Biphasic QPS had shorter lasting after-effects compared with monophasic QPS. Finally, the after-effects of QPS were relatively consistent across subjects: more than 80% of subjects responded as expected in the excitatory QPS at an IBI of 5 s.ConclusionsThe IBI, total duration of the procedure and pulse waveform strongly affected the magnitude or duration of the plasticity induced by QPS. In this cohort, 80% of subjects responded to excitatory QPS as expected.



http://ift.tt/2clFS5w

Monocyte subsets in blood correlate with obesity related response of macrophages to biomaterials in vitro

Publication date: December 2016
Source:Biomaterials, Volume 109
Author(s): G.S.A. Boersema, L. Utomo, Y. Bayon, N. Kops, E. van der Harst, J.F. Lange, Y.M. Bastiaansen-Jenniskens
Macrophages play a key role in the foreign body response. In this study it was investigated whether obesity affects the acute response of macrophages to biomaterials in vitro and whether this response is associated with biomarkers in blood. CD14 ⁺ monocytes were isolated from blood from obese and age and gender matched lean persons. Monocyte subsets were determined based on CD14 and CD16 on their surface. C-reactive protein (CRP) was measured in peripheral blood. The response of monocyte-derived macrophages to polypropylene (PP), polylactic acid (PLA), polyethylene terephthalate (PET) monofilament, and PET-multifilament (mPET) in culture was based on cytokine production. More IL-6 (for PET), less CCL18 (all materials) and IL-1ra (for PLA) was produced by macrophages from obese patients than lean subjects. Body mass index, serum CRP and to a lesser extend percentages of monocyte subtypes correlated with IL-6, TNFα, CCL18, and IL-1ra production. Taken together, monocyte-derived macrophages of obese patients respond more pro-inflammatory and less anti-inflammatory to biomaterials than macrophages from lean subjects, depending on the material. These results are a step towards personalized medicine for the development of a model or even a blood test to decide which biomaterial might be suitable for each patient.



http://ift.tt/2d1o5Ud

Probabilistic tractography using Lasso bootstrap

Publication date: January 2017
Source:Medical Image Analysis, Volume 35
Author(s): Chuyang Ye, Jerry L. Prince
Diffusion magnetic resonance imaging (dMRI) can be used for noninvasive imaging of white matter tracts. Using fiber tracking, which propagates fiber streamlines according to fiber orientations (FOs) computed from dMRI, white matter tracts can be reconstructed for investigation of brain diseases and the brain connectome. Because of image noise, probabilistic tractography has been proposed to characterize uncertainties in FO estimation. Bootstrap provides a nonparametric approach to the estimation of FO uncertainties and residual bootstrap has been used for developing probabilistic tractography. However, recently developed models have incorporated sparsity regularization to reduce the required number of gradient directions to resolve crossing FOs, and the residual bootstrap used in previous methods is not applicable to these models. In this work, we propose a probabilistic tractography algorithm named Lasso bootstrap tractography (LBT) for the models that incorporate sparsity. Using a fixed tensor basis and a sparsity assumption, diffusion signals are modeled using a Lasso formulation. With the residuals from the Lasso model, a distribution of diffusion signals is obtained according to a modified Lasso bootstrap strategy. FOs are then estimated from the synthesized diffusion signals by an algorithm that improves FO estimation by enforcing spatial consistency of FOs. Finally, streamlining fiber tracking is performed with the computed FOs. The LBT algorithm was evaluated on simulated and real dMRI data both qualitatively and quantitatively. Results demonstrate that LBT outperforms state-of-the-art algorithms.

Graphical abstract

http://ift.tt/2d1eOeQ

The genetics of the bitter taste receptor T2R38 in upper airway innate immunity and implications for chronic rhinosinusitis

Objective

Chronic rhinosinusitis (CRS) refractory to therapeutic intervention may involve a particularly resistant infection known as a bacterial biofilm. Critical to biofilm formation is the microbial process of quorum sensing whereby microbes secrete factors that regulate the expression of microbial genes involved in biofilm formation, persistence, and virulence. Here, we review recent work demonstrating that the bitter taste receptor T2R38, expressed on the apical surface of the sinonasal epithelium, serves a sentinel role in eavesdropping on microbial quorum-sensing communications and regulates localized innate biocidal defenses. Furthermore, studies investigating whether cilia are necessary for T2R38 expression and function in the upper airway are presented.

Methods

Primary human sinonasal air–liquid interface cultures were used to elucidate cellular pathways responsive to quorum-sensing molecules, whereas clinical studies investigated the contribution of T2R38 polymorphisms to recalcitrant chronic rhinosinusitis.

Results

T2R38 is stimulated by acyl-homoserine lactones, gram-negative quorum-sensing molecules, and subsequently activates nitric oxide-dependent innate immune responses. The formation of mature cilia is necessary for T2R38 expression and function, and polymorphisms that underlie T2R38 functionality appear to be involved in susceptibility to upper respiratory infection and recalcitrant CRS.

Conclusion

Taste receptors are emerging as critical components of early-phase respiratory innate immunity, detecting molecules used by microbes to communicate and stimulating localized host defenses. Genetic polymorphisms are very common within the taste receptors, and recent linkage studies have demonstrated associations of taste receptor genetics with CRS. Lastly, ciliogenesis, which is often impacted in CRS, is critical for the functional expression of T2R38.

Level of Evidence

N/A. Laryngoscope, 2016

http://ift.tt/2d7TEuh

Expression of Concern: “Prevention of Nausea and Vomiting After Middle Ear Surgery: Granisetron Versus Ramosetron,” “Prevention of Vomiting After Tonsillectomy in Children: Granisetron Versus Ramosetron,” and “Granisetron, Droperidol, and Metoclopramide for Preventing Postoperative Nausea and Vomiting After Thyroidectomy” by Dr Yoshitaka Fujii

http://ift.tt/2cJn72g

Bioactive forms of vitamin D selectively stimulate the skin analog of the hypothalamus-pituitary-adrenal axis in human epidermal keratinocytes

Publication date: 5 December 2016
Source:Molecular and Cellular Endocrinology, Volume 437
Author(s): Justyna M. Wierzbicka, Michał A. Żmijewski, Anna Piotrowska, Boguslaw Nedoszytko, Magdalena Lange, Robert C. Tuckey, Andrzej T. Slominski
Ultraviolet radiation B stimulates both the production of vitamin D3 in the skin and the activation of the skin analog of the hypothalamic-pituitary-adrenal axis (HPA) as well as the central HPA. Since the role of vitamin D3 in the regulation of the HPA is largely unknown, we investigated the impact of 1,25(OH)2D3 and its noncalcemic analogs, 20(OH)D3 and 21(OH)pD, on the expression of the local HPA in human epidermal keratinocytes. The noncalcemic analogs showed similar efficacy to 1,25(OH)2D3 in stimulating the expression of neuropeptides, CRF, urocortins and POMC, and their receptors, CRFR1, CRFR2, MC1R, MC2R, MC3R and MC4R. Interestingly, unlike other secosteroids, the activity of 21(OH)pD did not correlate with induction of differentiation, suggesting a separate but overlapping mechanism of action. Thus, biologically active forms of vitamin D can regulate different elements of the local equivalent of the HPA with implications for the systemic HPA.



http://ift.tt/2d7RpXU

Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe: An Innovative Therapies for Children with Cancer study

Publication date: November 2016
Source:European Journal of Cancer, Volume 67
Author(s): Fernando Carceller, Francisco J. Bautista, Irene Jiménez, Raquel Hladun-Álvaro, Cécile Giraud, Luca Bergamaschi, Madhumita Dandapani, Isabelle Aerts, François Doz, Didier Frappaz, Michela Casanova, Bruce Morland, Darren R. Hargrave, Lynley V. Marshall, Gilles Vassal, Andrew D.J. Pearson, Birgit Geoerger, Lucas Moreno
ObjectivesDose-finding trials are fundamental to develop novel drugs for children and adolescents with advanced cancer. It is crucial to maximise individual benefit, whilst ensuring adequate assessment of key study end-points. We assessed prognostic factors of survival in paediatric phase I trials, including two predictive scores validated in adult oncology: the Royal Marsden Hospital (RMH) and the MD Anderson Cancer Center (MDACC) scores.MethodsData of patients with solid tumours aged <18 years at enrolment in their first dose-finding trial between 2000 and 2014 at eight centres of the Innovative Therapies for Children with Cancer European consortium were collected. Survival distributions were compared using log-rank test and Cox regression analyses.ResultsOverall, 248 patients were evaluated: median age, 11.2 years (range 1.0–17.9); 46% had central nervous system (CNS) tumours and 54% extra-CNS tumours. Complete responses were observed in 2.1%, partial responses in 7.2% and stable disease in 25.9%. Median overall survival (OS) was 6.3 months (95% confidence interval, 5.2–7.4). Lansky/Karnofsky ≤80%, no school/work attendance, elevated creatinine and RMH score ≥1 correlated with worse OS in the multivariate analysis. The RMH and MDACC scores correlated with OS in adolescents (12–17 years), p = 0.002, but not in children (2–11 years).ConclusionsPerformance status of 90–100% and school/work attendance at enrolment are strong indicators of longer OS in paediatric phase I trials. Adult predictive scores correlate with survival in adolescents. These findings provide a useful orientation about potential prognosis and could lead in the future to more paediatric-adapted eligibility criteria in early-phase trials.



http://ift.tt/2d7Q9UP

The risk of pre-eclampsia according to high thyroid function in pregnancy differs by hCG concentration

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cPHJDJ

Relationships Between Urinary Phthalate Metabolite and Bisphenol A Concentrations and Vitamin D Levels in U.S. Adults: National Health and Nutrition Examination Survey (NHANES), 2005–2010

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2dga83X

Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cPH0SP

Treatment with recombinant human insulin-like growth factor-I improves growth in patients with PAPP-A2 deficiency

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2dgawzo

Aldosterone producing adenoma with a somatic KCNJ5 mutation revealing APC dependent Familial Adenomatous Polyposis

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cPHfxk

Intraoperative Real-Time Localization of Normal Parathyroid Glands with Autofluorescence Imaging

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2dgaqYy

Body fat mass is associated with ratio of steroid metabolites reflecting 17,20-lyase activity in prepubertal girls

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cPHsRf

Thyroid Function and Cancer Risk: The Rotterdam Study

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2dg9pQo

Cord blood adipokines and lipids and adolescent non-alcoholic fatty liver disease

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cPGMeB

Liver and muscle contribute differently to the plasma acylcarnitine pool during fasting and exercise in humans

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2dg9K5w

Erratum to: Expression of messenger molecules and receptors in rat and human sphenopalatine ganglion indicating therapeutic targets

http://ift.tt/2cJbZT2

Medial Femoral Condyle Flap

No abstract available

http://ift.tt/2d3L4AL

The association between parental attributions of misbehavior and parenting practices in caregivers raising children with prenatal alcohol exposure: A mixed-methods study

Publication date: December 2016
Source:Research in Developmental Disabilities, Volume 59
Author(s): Christie L.M. Petrenko, Mary E. Pandolfino, Rachael Roddenbery
Background and aimsLimited research has focused on parenting practices used by caregivers raising children with fetal alcohol spectrum disorders (FASD). The current study hypothesized that parental attributions of children's misbehavior would relate to the parenting strategies caregivers utilize with children with FASD. This study also aimed to develop a coding scheme to allow quantification of these treatment-relevant constructs in future intervention trials.MethodsThirty-one caregivers of children with FASD (age 4–8) were interviewed with the Parenting Practices Interview (PPI), a study-developed qualitative interview. Quantitative measures of FASD knowledge, parenting sense of competence and stress, and child behavior problems were included. Mixed-method analyses assessed the relationship between parental attributions of misbehavior and parenting practices.ResultsCaregivers who attributed their child's misbehavior to underlying neurodevelopmental disabilities were more likely to use antecedent strategies and feel more confident in managing their child's behavior. Parents who attributed their child's misbehavior to willful disobedience were more likely to rely on consequence strategies and feel more ineffective.ConclusionsResults are consistent with theoretical models for FASD parent training interventions. Assessment of theorized mechanisms of change in intervention trials is needed; the development of the PPI and quantitative coding system will facilitate this type of research.

Graphical abstract

http://ift.tt/2d7IO7u

Multidirectional lip-closing force in adult females after short-term lip training

Summary

The purpose of this study was to investigate the multidirectional lip-closing force in adult females before and after short-term lip training. Sixty-six Japanese females participated in this study. The subjects performed lip training that involved maintaining 200 or 400 g of bottled water in the oral vestibule. The signals of directional lip-closing force were investigated in eight directions before training and 5 and 7 days after the lip training. The differences in the closing force between pre- and post-training were then analysed statistically. The lip-closing force increased in the following order: pre-training, 5 days post-training and 7 days post-training in every direction (P < 0·05). The patterns of the increase in the lip-closing force in the upper, lower, right and left directions as a result of the repetitions were similar. No significant differences were noted between the training effects with loads of 200 and 400 g. Our findings demonstrated that the lip-closing force was influenced by the short-term lip training.

http://ift.tt/2d7Gv4b

Giant Cell Tumor of Midface: A Rare Aggressive Entity With an Easy Solution That Even Caters for Recurrence.

No abstract available

http://ift.tt/2cYDt5o

Concha Bullosa and Ethmoid Structures Pneumatization: The Effect of Altitude and Other Variables.

The effect of altitude on the paranasal sinus pneumatization is not well understood. This study aims to evaluate the effect of altitude on the surface area and type of the concha bullosa (CB) as well as the number of aerated ethmoid structures, and to study the correlation between CB, age, gender, and Lund-Mackay score (LMS). Sixty-five randomly collected paranasal sinus computed tomography scans of adult patients with sinonasal symptoms who had CB were reviewed for the type and surface area of CB, ethmoid structures pnumatization including crista galli, nasal septum, superior turbinate, and uncinate process, as well as the LMS. The mean age of patients was 35 +/- 9.64 years, with 29 females (41.7%) and 36 males (58.3%). The average LMS, altitude, and number of aerated ethmoid structures were 6 +/- 4, 580 +/- 325 m, and 4 +/- 1.4, respectively. The average CB surface area in females was 163 mm2 compared to 109 mm2 in men; this difference was statistically significant. Furthermore, females had significantly higher prevalence of bulbous and extensive CB. There was no significant correlation between altitude and the presence of ethmoid structures pneumatization. We concluded that altitude is not an important factor in ethmoid structures aeration. Our results indicate that female patients have larger CB and number of pneumatized ethmoid structures than males. We found a significant correlation between the surface area of CB and the number of aerated ethmoid structures, which indicates possible common etiology. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2cCe9yr

Aphthous Ulcer of the Vocal Cord Leading to Hoarseness.

Acute or chronic laryngitis, laryngeal trauma, vocal cord paralysis, cysts of the vocal cord, and benign or malignant tumors of the vocal folds are frequent causes of hoarseness. It is important to identify the cause of hoarseness to rule out potential malignancies. In this case report, we describe a patient with a bilateral aphthous ulcer in the vocal cords who was admitted with hoarseness and had been previously diagnosed with Behcet disease. Behcet disease is characterized by mucosal aphthous lesions, which are found primarily in oral and genital regions. To the best of our knowledge, this is the first instance of a patient with bilateral aphthous ulcer in the vocal cords. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2cYCNwN

Characteristics of Posed Smiles for Class III Female Patients Before and After Osteotomy Using Principal Component Analysis.

The purpose of this study was to clarify characteristics of posed smiles for Class III female patients before and after orthognathic surgery. Just before retrusion surgery and the removal of fixation plates, 2 sets of posed smiles were recorded for 7 Class III female patients. As normal controls, 7 healthy female volunteers were also recorded. Using our video-based motion analyzing system, range images and 5 x 5 virtual grids projected onto the lips were recorded for all patients while making a posed smile. The gravity for each area in the lips was calculated from the intersections of the virtual grids. Principal component analysis was applied to the normalized virtual grids, that is, a homologous model of lip shape, for all frames of the posed smiles. While the sample size was too small to generalize from these results, we found that the upper vermilion shifted posteriorly and laterally in posed smiles for Class III female patients after retrusion surgery as compared with the preoperative posed smiles. In addition, the characteristic lip movements during postoperative posed smiles for Class III female patients did not resemble those of the normal controls. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2cCdKfj

Evaluation of Repairing Facial Depression Deformities Secondary to Lupus Erythematosus Panniculitis With Autologous Fat Grafting.

Background: A facial depression deformity secondary to lupus erythematosus panniculitis results from fat necrosis, which seriously alters the patients' appearance and thus affects their psychological health. Few studies have discussed the repair of depression deformities. The authors repaired depression deformities due to atrophic lesions by using autologous fat grafting to obtain volumetric restoration of the facial skin, and the authors report our outcomes. Methods: In this series, 30 depression deformities in 18 patients were repaired. The authors suctioned fat grafts from the abdomen and centrifuged them at 500xg for 2 minutes. After discarding the upper oil and bottom liquid, the middle fat was injected into the depressed areas (ie, the cheek, temple, and zygoma) by using multiplane and multitunnel injections. The patients, plastic surgeons on staff, and laypersons evaluated the cosmetic outcome of each patient. Results: No infection, subcutaneous nodules or cysts, cutaneous necrosis, blood vessel embolism, or other complications were found in any patient. Five patients had 1 injection, 5 had 2 injections, and 8 had 3 injections. All depression deformities improved. Regarding the cosmetic outcome, 33.3% of patients, 27.8% of laypersons, and 38.9% of doctors were satisfied with the results; 44.4% of patients, 55.6% of laypersons, and 50.0% of doctors were mostly satisfied. Conclusion: Autologous fat grafting can be a good choice for repairing facial depression deformities in patients with lupus erythematosus panniculitis, although 1 or more subsequent injections may be required to maintain the improved outcome. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2cYDbvc

Useful Method for Intraoperative Monitoring of Facial Nerve in a Scarred Bed.

Facial nerve is the main cranial nerve for the innervation of facial expression muscles. Main trunk of facial nerve passes approximately 1 to 2 cm deep to tragal pointer. In some patients, where a patient has multiple operations, fibrosis due to previous operations may change the natural anatomy and direction of the branches of facial nerve. A 22-year-old male patient had 2 operations for mandibular reconstruction after gunshot wound. During the second operation, there was a possible injury to the marginal mandibular nerve and a nerve stimulator was used intraoperatively to monitor the nerve at the tragal pointer because the excitability of the distal segments remains intact for 24 to 48 hours after nerve injuries. Thus, using a nerve stimulator at the operational site may lead to false-positive muscle movements in case of injuries. Using the nerve stimulator to stimulate the main trunk at the tragal point may help to distinguish the presence of possible injuries. A reliable method for intraoperative facial nerve monitoring in a scarred operational site was introduced in this letter. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2cCcOYo

Ophthalmologic Outcomes Following Fronto-Orbital Advancement for Unicoronal Craniosynostosis.

Unicoronal craniosynostosis predisposes to ophthalmologic abnormalities such as strabismus, astigmatism, and amblyopia. The authors explored the ophthalmologic outcomes following fronto-orbital advancement (FOA). A systematic search of PubMed, Embase, and the Cochrane Library was conducted. Included studies reported postoperative rates of strabismus, astigmatism, and/or amblyopia. Two independent reviewers performed screening and extracted data including preoperative rates, laterality and severity of findings, need for ocular surgery, and timing of FOA. Methodologic quality was assessed using the Methodologic Index for Non-Randomized Studies scale and American Society of Plastic Surgeons Evidence Rating Scale for Therapeutic Studies. A total of 231 abstracts were screened. Sixteen articles were eligible for qualitative synthesis including 13 case series and 3 retrospective comparative studies. Nine studies contained both preoperative and postoperative data, but for strabismus only. Postoperative prevalence of strabismus was 19% to 100%. Rates increased in 4 studies and decreased in 3. Incidences of new and resolved cases of strabismus were 0% to 60% and 0% to 33%, respectively. Twenty-five percent to 100% of patients required strabismus surgery. Postoperative rates of astigmatism were 15% to 92%. Fourteen percent to 41% had clinically significant anisometropia, predisposing to amblyopia. The postoperative prevalence of amblyopia was 3% to 56%. In summary, FOA does not appear to reduce rates of strabismus, astigmatism, or amblyopia. In addition, surgery carries the risk of iatrogenic strabismus. Earlier intervention and endoscopic techniques may reduce prevalence and severity, but additional research is required. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2cYCpyt

Evaluation of Three Different Osteosynthesis Methods for Mandibular Angle Fractures: Vertical Load Test.

The aim of this study was to evaluate the mechanical behavior of different rigid fixation methods in mandible angle fractures. Three different plates were tested: one 4-hole grid miniplate, one 8-hole curved grid miniplate, and one 4-hole straight miniplate. For the loading tests, 30 polyurethane hemimandibles sectioned at the angle area to simulate a simple angle fracture were used: 10 hemimandibles for each group. The mechanical evaluation revealed that the straight plate positioned at the tension zone presented the best results in supporting vertical loading in the predefined displacement moments of 1, 3, and 5 mm. Regarding the grid plates, there was no statistically significant difference between the smaller and the larger plate. According to this sample, the straight plate positioned in the tension zone presented better results than the other 2 different grid plates positioned at the neutral zone. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2cCdXzi

Usefulness of Microfat Grafting in Patients With Repaired Cleft Lip.

In many patients, the volume of the upper lip is deficient after cleft lip repair operation. However, there is no well-established procedure to correct this volume deficiency. In the present study, the authors attempted to increase the overall three-dimensional volume of the upper lip in repaired cleft lip patients with upper lip volume deficiency through autogenous microfat grafting. Thirty patients with upper lip volume deficiency after cleft lip repair underwent fat grafting in the upper lip from November 2007 to March 2015. Among these patients, postoperative outcome was evaluated in 15 patients using 2 methods for the evaluation. One method involved measuring the change in the shape of lips using pre- and postoperative photographs, and the other involved investigating the levels of satisfaction with the surgical results by distributing a scoring questionnaire to patients, doctors, and the general public. The ratio of upper lip protrusion relative to the lower lip increased by 46.71% on average after operation, and the sum of the vermilion heights increased by 31.68% on average. In the survey of satisfaction levels, patients, plastic surgeons, and the general public gave mean scores of 3.80, 3.91, and 4.03, respectively. When volume deficiency of the upper lip is present in repaired cleft lip patients, correction using autogenous microfat grafting is believed to be effective. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2cYD6rh

To what extent is alcohol consumption associated with breast cancer recurrence and second primary breast cancer?: A systematic review

Publication date: Available online 20 September 2016
Source:Cancer Treatment Reviews
Author(s): Phanthira Simapivapan, Anna Boltong, Allison Hodge
BackgroundThe association between alcohol intake and breast cancer recurrence or development of second primary breast cancer in the survivor population is unclear. The aim of this systematic review was to evaluate the existing evidence to assess the extent to which alcohol consumption is associated with breast cancer recurrence and second primary breast cancer.MethodsSix databases (Cochrane Library, EMBASE, MEDLINE, PubMed, Scopus and Web of Science) were searched using the following search phrase: (breast cancer OR breast adenocarcinoma OR breast neoplasm OR breast tumor) AND (alcohol^∗ OR alcohol intake OR alcohol consumption OR ethanol) AND (recurrence OR second primary). A narrative synthesis was conducted on studies meeting the inclusion criteria.ResultsAfter screening, 16 studies met the inclusion criteria, of which 11 assessed breast cancer recurrence and 5 assessed second primary breast cancer. Considerable clinical and methodological heterogeneity was observed between studies. Approximately half of the included studies observed a modest, but significant, association between alcohol consumption and increased risk of breast cancer recurrence or development of a second primary breast cancer, with some studies observing associations from as little as six grams of alcohol intake per day. Two studies suggest this association was stronger in postmenopausal women.ConclusionThere is some evidence that alcohol consumption increases the risk of breast cancer recurrence, particularly in postmenopausal women. The association between alcohol and development of a second primary breast cancer is less clear. Inconsistencies in methodology and results across studies complicate attempts to develop a cohesive interpretation of findings.



http://ift.tt/2d8qkbk

Mechanism of drug resistance in relation to site of metastasis: Meta-analyses of randomized controlled trials in advanced breast cancer according to anticancer strategy

Publication date: Available online 20 September 2016
Source:Cancer Treatment Reviews
Author(s): Saroj Niraula, Alberto Ocana
BackgroundBreast cancer is heterogeneous at different levels: biologic subtypes, intratumoral areas, and sites of metastases. Randomized controlled trials (RCTs) classify metastatic sites as visceral or non-visceral, but this has little influence in treatment decisions, particularly in the absence of clinical urgency. Indeed, it is unclear if response to treatments differs among sites of metastases.Patients and MethodsRCTs investigating 3 different anticancer strategies in metastatic breast cancer were identified: (1) new hormonal therapy, (2) new targeted therapies in hormone receptor positive tumours (everolimus or palbociclib), and (3) new anti-HER2 therapies. RCTs reporting hazard ratios (HR) for Progression Free Survival (PFS) and Overall Survival (OS) for sub-groups based on sites of metastases were weighted using generic inverse variance approach, and pooled in meta-analyses using Revman 5.3. Subgroup difference was tested with Chi² statistics.ResultsEleven RCTs (6,701 pts.) qualified. There was a significant difference in PFS between women with visceral versus non-visceral metastases when two endocrine strategies were compared, with benefits limited to women with visceral metastases [Pooled HR 0.85; 95% CI, 0.77-0.95 versus 1.02(0.88-1.18) for non-visceral; p(difference)=0.05]. However, combination of an endocrine therapy and a targeted therapy was associated with better PFS compared to endocrine therapy alone for both groups [HR 0.51(0.43-0.60) versus 0.45(0.36-0.56) for non-visceral; p(difference)=0. 36]. Novel HER-2 targeted therapies were associated with significantly better PFS and OS only in visceral metastases [HR 0.59 (0.52-0.66) versus 0.71(0.44-1.13) for non-visceral, p(difference)=0.45, for PFS; and 0.64 (0.56-0.73) versus 0.82 (0.57=1.19) for non-visceral, p(difference)=0.20, for OS].ConclusionCombination of targeted agents and endocrine therapy results in concordant, superior PFS suggesting targetable endocrine resistance across metastatic sites. Discordant responses with endocrine strategy alone support use of targeted therapy, rather than change in endocrine agent at disease progression. HER2 targeted therapies may be less effective in areas of poor vascularization.



http://ift.tt/2cAyK6r

The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Publication date: December 2016
Source:Neurobiology of Aging, Volume 48
Author(s): Claire Lancaster, Naji Tabet, Jennifer Rusted
Possession of an Apolipoprotein E (APOE) e4 allele is an established risk factor for Alzheimer's disease, whereas the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. Sixty-six volunteers, aged 45–55 years, completed 3 tasks that provided complementary measures of attentional control: prospective memory, sustained attention, and inhibition. Performance was compared between e2 carriers, e4 carriers, and e3 homozygotes (the population norm). Carriers of the e4 allele showed subtle disadvantages, compared with the e3 group, in accuracy of Stroop task and prospective memory performance. Contrary to expectations, e2 carriers showed performance disadvantages in sustained attention. The finding of detrimental effects in attentional control for both e4 and e2 complicates the current model that proposes opposing effects of these variants on later-life cognition. Future research is needed to understand how cognitive differences develop with increasing age, and the physiological mechanisms that underpin these changes.



http://ift.tt/2cQXgjv

Varied incidence of immediate adverse reactions to low-osmolar non-ionic iodide radiocontrast media used in computed tomography

Abstract

Background

Low-osmolar nonionic radiocontrast media (RCMs) are commonly used throughout hospitals. However, the incidence of immediate adverse drug reactions (ADRs) to various low-osmolar nonionic RCMs is not well studied. We compared the incidence of immediate ADRs among different low-osmolar nonionic RCMs used in computed tomography (CT).

Methods

Severance Hospital has collected data for adverse reactions occurring in-hospital using an internally developed system. Using this data, we reviewed 1969 immediate ADRs from 286,087 RCM-contrasted CT examinations of 142,099 patients and compared the immediate ADRs of iobitridol, iohexol, iopamidol, and iopromide. We analyzed the incidence of immediate ADRs to different RCMs, as well as the effect of single or multiple CT examinations per day.

Results

Iopromide showed the highest incidence of immediate ADRs (1.03%) and was followed by iopamidol (0.67%), iohexol (0.64%), and iobitridol (0.34%). In cases of anaphylaxis, iopromide also showed the highest incidence (0.041%), followed by iopamidol (0.023%), iohexol (0.018%), and iobitridol (0.012%). Risk of immediate ADR due to multiple CT examinations (1.19%) was significantly higher than the risk due to a single CT examination (0.63%). Risk of anaphylaxis was also higher for multiple CT examinations (0.052%) than for a single CT examination (0.020%).

Conclusions

The incidence of immediate ADRs varied according to the low-osmolar nonionic RCM used. Iopromide-induced immediate ADRs were more frequent, while iobitridol was associated with fewer immediate ADRs than other RCMs. Multiple CT examinations per day resulted in a higher incidence of immediate ADRs and anaphylaxis than a single CT examination. Clinicians should consider these risk differences of immediate ADRs when prescribing contrasted CT examinations.

This article is protected by copyright. All rights reserved.

http://ift.tt/2cmkAtF

Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodeling in asthma

Abstract

Background

Allergic asthma is characterized by inflammation and airway remodeling. Airway remodeling with excessive deposition of extracellular matrix (ECM) and larger smooth muscle mass are correlated with increased airway responsiveness and asthma severity. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodeling. However, the role of calpain in airway smooth muscle remodeling remains unknown.

Objective

To investigate the role of calpain in asthmatic airway remodeling as well as the underling mechanism.

Methods

The mouse asthma model was made by ovalbumin sensitization and challenge. Calpain conditional knockout mice were studied in the model. Airway smooth muscle cells (ASMCs) were isolated from smooth muscle bundles in airway of rats. Cytokines IL-4, IL-5, TNF-α and TGF-β1, and serum from asthmatic patients were selected to treated ASMCs. Collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs were analyzed.

Results

Inhibition of calpain using calpain knockout mice attenuated airway smooth muscle remodeling in mouse asthma models. Cytokines IL-4, IL-5, TNF-α and TGF-β1, and serum from asthmatic patients increased collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs, which were blocked by the calpain inhibitor MDL28170. Moreover, MDL28170 reduced cytokine-induced increases in Rictor protein which is the most important component of mammalian target of rapamycin complex 2 (mTORC2). Blockage of the mTORC2 signal pathway prevented cytokine-induced phosphorylation of Akt, collagen-I synthesis and cell proliferation of ASMCs, and attenuated airway smooth muscle remodeling in mouse asthma models.

Conclusions

Our results indicate that calpain mediates cytokine-induced collagen-I synthesis and proliferation of ASMCs via the mTORC2/Akt signaling pathway, thereby regulating airway smooth muscle remodeling in asthma.

This article is protected by copyright. All rights reserved.

http://ift.tt/2cjWV8h

In silico, in vitro and case-control analyses as an effective combination for analyzing BRCA1 and BRCA2 unclassified variants in a population-based sample

Publication date: Available online 20 September 2016
Source:Cancer Genetics
Author(s): Marta Rodríguez-Balada, Bàrbara Roig, Lourdes Martorell, Mireia Melé, Mònica Salvat, Elisabet Vilella, Joan Borràs, Josep Gumà
Ascertaining the clinical consequences of BRCA1 and BRCA2 variants of uncertain significance (VUS) is currently indispensable for providing effective genetic counseling and preventive actions for families with hereditary breast and ovarian cancer (HBOC). To this end, we conducted a combination of in silico prediction and cDNA splicing analyses of 13 BRCA1 and 10 BRCA2 VUS identified in our cohort as well as a case-control analysis in a population-based sample of 10 recurrent VUS. We observed consistent results between the in silico predictions and sequencing analyses for all analyzed VUS. An abnormal cDNA pattern was observed for variants c.212+1G>A and c.5278-1G>A in BRCA1 and c.516+2T>A and c.8168A>G in BRCA2 according to in silico splicing prediction.. A case-control study of VUS confirmed the polymorphisms of the c.67+62A>G, c.7008-62A>G and c.8851G>A BRCA2 variants previously published. c.4068G>A in the BRCA2 gene can also be considered a polymorphism due to its occurrence at a frequency greater than 1% in our population.Our study shows that employing population-based analysis and a combination of several in silico methods yields highly accurate information, resulting in a reliable tool for selecting variants for cDNA sequencing analysis in routine cancer genetic counseling units.



http://ift.tt/2d1YZHr

Novel Insights into PML-Dependent Oncosuppression

Publication date: Available online 20 September 2016
Source:Trends in Cell Biology
Author(s): Lorenzo Galluzzi
At odds with its nuclear counterpart, extranuclear promyelocytic leukemia constitutively inhibits autophagy, hence limiting cancer progression. These data raise the interesting possibility that some tumor suppressors have become specialized to operate at multiple subcellular compartments for counteracting different aspects of the oncogenic process.



http://ift.tt/2d5qoo3

N-cadherin regulates beta-catenin signal and its misexpression perturbs commissural axon projection in the developing chicken spinal cord

Abstract

N-cadherin is a calcium-sensitive cell adhesion molecule that plays an important role in the formation of the neural circuit and the development of the nervous system. In the present study, we investigated the function of N-cadherin in cell–cell connection in vitro with HEK293T cells, and in commissural axon projections in the developing chicken spinal cord using in ovo electroporation. Cell–cell connections increased with N-cadherin overexpression in HEK293T cells, while cell contacts disappeared after co-transfection with an N-cadherin-shRNA plasmid. The knockdown of N-cadherin caused the accumulation of β-catenin in the nucleus, supporting the notion that N-cadherin regulates β-catenin signaling in vitro. Furthermore, N-cadherin misexpression perturbed commissural axon projections in the spinal cord. The overexpression of N-cadherin reduced the number of axons that projected alongside the contralateral margin of the floor plate, and formed intermediate longitudinal commissural axons. In contrast, the knockdown of N-cadherin perturbed commissural axon projections significantly, affecting the projections alongside the contralateral margin of the floor plate, but did not affect intermediate longitudinal commissural axons. Taken together, these findings suggest that N-cadherin regulates commissural axon projections in the developing chicken spinal cord.

http://ift.tt/2d5o14q

Receding Gums: Treatment Options and Causes

Gingival recession is when the gum tissue covering the root of the tooth is pushed back. Learn about its causes and forms of treatment with this article.

http://ift.tt/2crs9NP

Human tolerogenic dendritic cells generated with protein kinase C inhibitor are optimal for functional regulatory T cell induction – A comparative study

Publication date: Available online 19 September 2016
Source:Clinical Immunology
Author(s): Endy Adnan, Takuya Matsumoto, Jun Ishizaki, Sachiko Onishi, Koichiro Suemori, Masaki Yasukawa, Hitoshi Hasegawa
Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3 (Vit D3), rapamycin (Rapa), interleukin (IL)-10, transforming growth factor (TGF)-β, and a combination of peroxisome proliferator-activated receptor γ agonist and retinoic acid. All tDCs had a semi-mature DC phenotype. PKCI-, TGF-β-, and Rapa-tDCs showed CCR7 expression and migration to CCL19, but other tDCs showed little or none. PKCI- and IL-10-tDCs induced functional regulatory T cells more strongly than other tDCs. The tolerogenic properties of all tDCs were stable against proinflammatory stimuli. Furthermore, PKCI-tDCs were generated from patients with rheumatoid arthritis and primary Sjögren's syndrome. Therefore, PKCI-tDCs showed the characteristics best suited for tolerance-inducing therapy.



http://ift.tt/2cQN9uY

Long-term Outcomes of Superficial Esophageal Squamous Cell Carcinoma

Condition:   Esophageal Neoplasms
Intervention:  
Sponsors:   Shanghai Zhongshan Hospital;   The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School;   Tongji Hospital;   The affiliated Hospital of Shihezi University
Not yet recruiting - verified September 2016

http://ift.tt/2cOAeve

Endostar Combined With Concurrent Chemoradiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma

Condition:   Nasopharyngeal Carcinoma
Interventions:   Drug: Endostar;   Drug: DDP
Sponsor:   First Affiliated Hospital of Guangxi Medical University
Not yet recruiting - verified September 2016

http://ift.tt/2d1RKiR

Ontario-wide Cancer TArgeted Nucleic Acid Evaluation

Conditions:   Breast Cancer;   Lung Cancer;   Colorectal Cancer;   Melanoma;   Gynecological Cancer;   Genitourinary Cancer;   Pancreatobiliary Cancer;   Gastrointestinal Cancer;   Head and Neck Cancer;   Rare Cancer;   Unknown Primary Cancer
Intervention:  
Sponsors:   University Health Network, Toronto;   Princess Margaret Hospital, Canada
Recruiting - verified September 2016

http://ift.tt/2cOAmuE

Potentiation of Cisplatin-based Chemotherapy by Digoxin in Advanced Unresectable Head and Neck Cancer Patients

Condition:   Head and Neck Cancer
Intervention:   Drug: Digoxin
Sponsors:   Assistance Publique - Hôpitaux de Paris;   Cancer Research and Personalized Medicine (Carpem);   Laboratoire d'excellence en immuno-oncologie (Labex)
Not yet recruiting - verified June 2016

http://ift.tt/2d1RoZD

Synthesis and Structure–Activity Relationships of 1-Benzylindane Derivatives as Selective Agonists for Estrogen Receptor Beta

Publication date: Available online 20 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Shigeru Yonekubo, Nobuhiko Fushimi, Takashi Miyagi, Osamu Nakanishi, Kenji Katsuno, Motoyasu Ozawa, Chiaki Handa, Noritaka Furuya, Hideyuki Muranaka
The estrogen receptor beta (ERβ) selective agonist is considered a promising candidate for the treatment of estrogen deficiency symptoms in ERβ-expressing tissues, without the risk of breast cancer, and multiple classes of compounds have been reported as ERβ selective agonists. Among them, 6-6 bicyclic ring-containing structures (e.g., isoflavone phytoestrogens) are regarded as one of the cyclized analogues of isobutestrol 5b, and suggest that other cyclized scaffolds comprising 5-6 bicyclic rings could also act as selective ERβ ligands.In this study, we evaluated the selective ERβ agonistic activity of 1-(4-hydroxybenzyl)indan-5-ol 7a and studied structure–activity relationship (SAR) of its derivatives. Some functional groups improved the properties of 7a; introduction of a nitrile group on the indane-1-position resulted in higher selectivity for ERβ (12a), and further substitution with a fluoro or a methyl group to the pendant phenyl ring was also preferable (12b, d, and e). Subsequent chiral resolution of 12a identified that R-12a has a superior profile over S-12a. This is comparable to diarylpropionitrile (DPN) 5c, one of the promising selective ERβ agonists and indicates that this indane-based scaffold has the potential to provide better ERβ agonistic probes.

Graphical abstract

http://ift.tt/2d5j6AJ

Synthesis and antimicrobial activity of small cationic amphipathic aminobenzamide marine natural product mimics and evaluation of relevance against clinical isolates including ESBL-CARBA multi-resistant bacteria

Publication date: Available online 20 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Elizaveta M. Igumnova, Ekaterina Mishchenko, Tor Haug, Hans-Matti Blencke, Johanna U. Ericson Sollid, Elizabeth G. Aarag Fredheim, Silje Lauksund, Klara Stensvåg, Morten B. Strøm
A library of small aminobenzamide derivatives was synthesised to explore a cationic amphipathic motif found in marine natural antimicrobials. The most potent compound E23 displayed minimal inhibitory concentrations (MICs) of 0.5 – 2 μg/ml against several Gram-positive bacterial strains, including methicillin resistant Staphylococcus epidermidis (MRSE).E23 was also potent against 275 clinical isolates including Staphylococcus aureus, Enterococcus spp., Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, as well as methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci (VRE), and ESBL-CARBA multi-resistant Gram-negative bacteria. The study demonstrates how structural motifs found in marine natural antimicrobials can be a valuable source for making novel antimicrobial lead-compounds.

Graphical abstract

http://ift.tt/2d5j5wF

Tyrosyl-DNA phosphodiesterase inhibitors: Progress and potential

Publication date: Available online 20 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Sergey S. Laev, Nariman F. Salakhutdinov, Olga I. Lavrik
DNA topoisomerases are essential during transcription and replication. The therapeutic mechanism of action of topoisomerase inhibitors is enzyme poisoning rather than catalytic inhibition. Tyrosyl-DNA phosphodiesterases 1 or 2 were found as DNA repair enzymes hydrolyzing the covalent bond between the tyrosyl residue of topoisomerases I or II and the 3'- or 5'-phosphate groups in DNA, respectively. Tyrosyl-DNA phosphodiesterase 1 is a key enzyme in DNA repair machinery and a promising target for antitumor and neurodegenerative therapy. Inhibitors of tyrosyl-DNA phosphodiesterase 1 could act synergistically with topoisomerase I inhibitors and thereby potentiate the effects of topoisomerase I poisons. Tyrosyl-DNA phosphodiesterase 2 is an enzyme that specifically repairs DNA damages induced by topoisomerase II poisons and causes resistance to these drugs. Selective inhibition of tyrosyl-DNA phosphodiesterase 2 may be a novel approach to overcome intrinsic or acquired resistance to topoisomerase II-targeted drug therapy. Thus, agents that inhibit tyrosyl-DNA phosphodiesterases 1 and 2 have many applications in biochemical and physiological research and they have the potential to become anticancer and antiviral drugs. The structures, mechanism of action and therapeutic rationale of tyrosyl-DNA phosphodiesterase inhibitors and their development for combinations with topoisomerase inhibitors and DNA damaging agents are discussed.

Graphical abstract

http://ift.tt/2d5j3Vg

A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities

Publication date: Available online 19 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Chelliah Bharkavi, Sundaravel Vivek Kumar, Mohamed Ashraf Ali, Hasnah Osman, Shanmugam Muthusubramanian, Subbu Perumal
A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07 μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 < 1.56 μM) and 6l (IC50 = 2.87 μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16 μmol/L respectively.

Graphical abstract

http://ift.tt/2d5kvHi

Response of wine grape growth, development and the transfer of copper, lead, and cadmium in soil-fruit system to sludge compost amendment

Abstract

Sludge is an organic waste after domestic sewage being treated and contains phytonutrients and organic matter. In this study, recycling of sludge compost (SC) and its compound fertilizer (SCF) to wine grape resulted in improvement in vegetative growth, reproductive development of wine grape, and potential wine quality of grape fruit. The amounts of Cu, Pb, and Cd in grape fruit were significantly higher in response to sludge amendment than in the control, but were all below the permissible limits for agricultural product. The contents of Cu and Pb in sludge-amended soil decreased with increasing soil depth, but Cd content increased with soil depth. Ongoing monitoring of on mobility of Cd downward is proposed with sludge recycling to wine grape soil.

http://ift.tt/2cWdZFq

A modified biotrickling filter for nitrification-denitrification in the treatment of an ammonia-contaminated air stream

Abstract

A conventional biotrickling filter for airborne ammonia nitrification has been modified, by converting the liquid sump into a biological denitrifying reactor. The biotrickling filter achieves an average ammonia removal efficiency of 92.4 %, with an empty bed retention time (EBRT) equal to 36 s and an average ammonia concentration of 54.7 mg Nm⁻³ in the raw air stream. The denitrification reactor converts ammonia into inert gas N₂, in addition to other important advantages connected to the alkaline character of the biochemical pathway of the denitrifying bacteria. Firstly, the trickling water crossing the denitrification reactor underwent a notable pH increase from 7.3 to 8.0 which prevented the acidic inhibition of the nitrifying bacteria due to the buildup of nitric and nitrous acids. Secondly, the pH increase created the ideal conditions for the autotrophic nitrifying bacteria. The tests proved that an ammonia removal efficiency of above 90 % can be achieved with an EBRT greater than 30 s and a volumetric load lower than 200 g NH₃ m⁻³ day⁻¹. The results of the biofilm observation by using a scanning confocal laser microscope are reported together with the identification of degrading bacteria genera in the biotrickling filter. The efficiency of the plant and its excellent operational stability highlight the effectiveness of the synergistic action between the denitrification reactor and the biotrickling filter in removing airborne ammonia.

http://ift.tt/2d59Ufp

Effects of salinity on simultaneous reduction of perchlorate and nitrate in a methane-based membrane biofilm reactor

Abstract

This study builds upon prior work showing that methane (CH₄) could be utilized as the sole electron donor and carbon source in a membrane biofilm reactor (MBfR) for complete perchlorate (ClO₄⁻) and nitrate (NO₃⁻) removal. Here, we further investigated the effects of salinity on the simultaneous removal of the two contaminants in the reactor. By testing ClO₄⁻ and NO₃⁻ at different salinities, we found that the reactor performance was very sensitive to salinity. While 0.2 % salinity did not significantly affect the hydrogen-based MBfR for ClO₄⁻ and NO₃⁻ removals, 1 % salinity completely inhibited ClO₄⁻ reduction and significantly lowered NO₃⁻ reduction in the CH₄-based MBfR. In salinity-free conditions, NO₃⁻ and ClO₄⁻ removal fluxes were 0.171 g N/m²-day and 0.091 g/m²-day, respectively, but NO₃⁻ removal fluxes dropped to 0.0085 g N/m²-day and ClO₄⁻ reduction was completely inhibited when the medium changed to 1 % salinity. Scanning electron microscopy (SEM) showed that the salinity dramatically changed the microbial morphology, which led to the development of wire-like cell structures. Quantitative real-time PCR (qPCR) indicated that the total number of microorganisms and abundances of functional genes significantly declined in the presence of NaCl. The relative abundances of Methylomonas (methanogens) decreased from 31.3 to 5.9 % and Denitratisoma (denitrifiers) decreased from 10.6 to 4.4 % when 1 % salinity was introduced.

http://ift.tt/2cWbXFp

Theoretical and experimental study of the mechanisms of phosphate removal in the system containing Fe(III)-ions

Abstract

A process-oriented investigation of phosphate removal by ferric salt was carried out in this study. The kinetics of amorphous ferric phosphate (FePO₄(s)) formation has been investigated over the pH range of 6.0–8.0 using sulfosalicylic acid as a competitive ligand. The FePO₄(s) formation rate constants varied in a narrow range over the pH range examined in this study. And the maximum of (0.90 ± 0.11) × 10⁴ L mol⁻¹ s⁻¹ was obtained at pH 7.5 and the minimum value of (0.05 ± 0.01) × 10⁴ L mol⁻¹ s⁻¹ was obtained at pH 6.0. These values are two orders of magnitude lower than the rate constants for Fe(III) hydrolysis-precipitation, and hence, the extent of FePO₄(s) formation when ferric ions are added to aqueous solution is extremely low. Subsequently, the characteristics of the amorphous ferric oxide (AFO) with different ages were investigated, and it was found that the BET surface area, the average pore width, and the charge capacitance were various for different AFO with various ages. Phosphate adsorption by AFO was significantly affected by AFO aging and the manner of adding Fe(III), which was successfully described by a diffuse layer model. By using surface sites concentration obtained, the kinetics constant of AFO aging could be calculated by a functional equation at a certain pH and time.

Graphic abstract

Description of the precipitation and aging processes for the phosphate removal by Fe(III)-ions

http://ift.tt/2cOoBUN

Phosphorus partitioning in sediments from a tropical reservoir during a strong period of drought

Abstract

Monitoring phosphorus (P) concentration in water and sediments in the Castanhão reservoir, under intensive aquaculture, in Northeastern Brazil showed internal process to dominate P cycling following a reduction of reservoir volume due to an extended drought period. A strong negative correlation between soluble reactive phosphorus in surface waters (SRPs) with the reservoir volume results from diminishing dilution capacity; bottom water SRP showed no significant correlation with volume and imply SRP remobilization to surface layers. Total suspended solids (TSS) showed a significant correlation with chlorophyll-a, suggesting change primary productivity following SRP enrichment of surface waters and living cells dominating the TSS. As a result, eutrophication, as established by a trophic state index, was triggered in the reservoir probably enforced by intensive fish farming effluents, whose nutrients accumulated in bottom waters and which became available due to breaking of the thermocline. Since low rainfall periods are typical of the semiarid region and tend to be more frequent and stronger due to climate change, multiple use of reservoirs in NE Brazil should be reevaluated.

http://ift.tt/2cOo5Gk

Flexible Fiber Optic Carbon-Dioxide Laser Assisted Stapedotomy in Otosclerosis

Objective. The aim of this study is to analyze the hearing and vestibular outcome of patients with otosclerosis who have been operated on by fiber optic flexible CO2 laser. Study Design. A preliminary and retrospective study was conducted in 30 patients with otosclerosis. Results. Comparative analysis of average air conduction thresholds ( dB versus  dB) and air-bone gaps ( dB versus  dB) before and after the surgery were statistically significant (

http://ift.tt/2dgjHTf

Immunosuppressive effect of ASP2408, a novel CD86-selective variant of CTLA4-Ig, in rats and cynomolgus monkeys

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Shinsuke Oshima, Yasutomo Fujii, Erik E. Karrer, Fujiko Takamura, Steven J. Chapin, Margaret Neighbors, Sridhar Viswanathan, Bruce H. Devens, Yasuyuki Higashi, Hidekazu Mizuhara
The CTLA4-Ig fusion proteins abatacept and belatacept inhibit CD28-mediated T cell activation by binding CD80 (B7-1) and CD86 (B7-2) costimulatory ligands and are clinically proven immunosuppressants used for rheumatoid arthritis and renal transplantation, respectively. Abatacept and belatacept preferentially bind CD80, yet CD86 has been implicated as the dominant ligand for CD28-mediated costimulation of T cells. We investigated the immunosuppressive effects of ASP2408, a novel CTLA4-Ig with CD86 selectivity and high potency created by directed evolution methods. Here we evaluated the effect of ASP2408 in vitro using cynomolgus monkey and rat T cell proliferation assays and in vivo using cynomolgus monkey tetanus toxoid (TTx) immunization and a rat rheumatoid arthritis model. ASP2408 was 290-fold and 21-fold more potent in suppressing in vitro monkey T cell proliferation than abatacept and belatacept, respectively. ASP2408 inhibited anti-TTx immunological reactions in cynomolgus monkey at a 10-fold lower dose level than belatacept, through complete CD86 and partial CD80 receptor occupancies, and also suppressed inflammation in the rat collagen-induced arthritis model. Overall, improved immunosuppressive potency of ASP2408 relative to abatacept and belatacept correlated well with improved CD86 binding affinity. These results may support the advantage of preferential enhancement of CD86 binding affinity to inhibit T cell-mediated immune response and improved dosing convenience in humans relative to abatacept or belatacept.



http://ift.tt/2cEssVl

CONDYDAV : étude observationnelle multicentrique des patients présentant des condylomes dans les dispensaires antivénériens en France

Publication date: Available online 19 September 2016
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J. Chanal, S. Fouéré, F. Yassir-Oria, N. Spenatto, F. Bouscarat, E. Picot, P. Martinet, C. Vernay-Vaisse, F. Pelletier, C. Courtieu, V. Baclet, C. Bernier, D. Aymar-Moulene, F. Dupuis-Fourdan, A. Passeron, C. Bara-Passot, A.-L. Pinault, L. Misery, M. Janier, N. Dupin
IntroductionLes condylomes sont un des premiers motifs de consultation dans les centres de maladies sexuellement transmissibles (MST). Depuis 2007, la vaccination contre les papillomavirus humains (PVH) est autorisée en France. L'objectif de notre étude était de déterminer la prévalence des condylomes et le profil clinique et épidémiologique des patients avec condylomes consultant dans des centres de MST.Patients et méthodesÉtude observationnelle prospective multicentrique, non interventionnelle, analysant les données épidémiologiques et cliniques des patients porteurs de condylomes ainsi que les traitements utilisés dans 15 centres de MST entre le 1^er janvier et le 31 mars 2012.RésultatsOnt été inclus 372 hommes et 111 femmes ; l'âge moyen était de 31,2ans. Les femmes étaient plus jeunes que les hommes (respectivement 28,9 et 31,7ans, p<0,05). Quatre cent quatorze patients étaient hétérosexuels et 66 étaient des hommes ayant des rapports sexuels avec des hommes (HSH). Chez les hommes, 230 avaient une atteinte du pénis isolée et 46 une atteinte de l'anus isolée. En tout, 76 avaient une atteinte de l'anus, dont 26 étaient HSH. Chez les femmes, 76 avaient une atteinte de la vulve isolée et 22 une co-infection de la vulve et de l'anus. L'atteinte anale était significativement plus fréquente chez les HSH et les femmes que chez les hommes hétérosexuels (p<0,0001 et p=0,004, respectivement). Trois femmes avaient été vaccinées : deux par Gardasil^® et une par Cervarix^®. Le traitement de première intention était la cryothérapie dans les deux groupes.ConclusionUn examen complet, notamment anal, doit être effectué chez les femmes et chez les HSH. Une globalisation de la vaccination anti-HPV devrait permettre une réduction des infections et l'implantation d'une stratégie globale de contrôle de la maladie.BackgroundSince 2007 in France, human papilloma virus (HPV) vaccination has been licensed for use as a vaccine against HPV 6, 11, 16 and 18. The impact on the epidemiology of external genital warts (EGWs) in a large population remains unclear.ObjectivesTo determine epidemiologic and clinical features of patients presenting EGWs in France in the era of HPV vaccination.Patients and methodsIn this prospective, observational study, we analyzed clinical features and treatments between January 1st, 2012 and March 31, 2012 for patients consulting for EGWs at 15 STI clinics throughout France.ResultsA total of 372 men and 111 women were included; mean age 31.2 years. The women were younger than the men (31.7 and 28.9 years respectively P<0.05). Among the patients, 416 (85.7%) were heterosexual, 13 bisexual and 54 (11.2%) homosexual, including one female. Males reported more sexual partners in the last 12 months (more than 3 partners in 32.6% versus 11.9%, P<0.01). Among the men, 230 had involvement of the penis alone and 46 had involvement of the anus alone. Seventy-six patients had EGWs of the anus, and of these 26 were MSM. In females, 76 had an infection of the vulva alone and 22 co-infection of the vulva and anus. MSM and females were at higher risk than heterosexual males for anal involvement (P<0.0001 and P=0.004, respectively). Three women had been vaccinated: two with Gardasil^® and one with Cervarix^®. Cryotherapy was the preferred treatment.ConclusionWith the advent of HPV vaccination, a global strategy for the prevention and treatment of EGW should be implemented.



http://ift.tt/2d7Y6gS

Nævus comédonien : mutations somatiques de NEK9

Publication date: Available online 19 September 2016
Source:Annales de Dermatologie et de Vénéréologie
Author(s): O. Dereure




http://ift.tt/2cA9jC0

Apport de la microscopie confocale par réflectance dans le diagnostic d’érucisme oculocutané ou réaction aux poils de chenilles processionnaires

Publication date: Available online 19 September 2016
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-L. Perrot, R. Julienne, M. Kaspi, B. Labeille, D. Grivet, A. Vercherin, F. Cambazard, E. Cinotti




http://ift.tt/2d7YUT5

Low-intensity laser (660 nm) on sternotomy healing in patients who underwent coronary artery bypass graft: a randomized, double-blind study

Abstract

The aim of this study was to analyze the healing effects of low-level laser therapy (LLLT) on the longitudinal sternotomy incisions of patients who underwent coronary artery bypass graft (CABG). The volunteers were randomized into three groups of equal size (n = 30): control, placebo, and laser (λ = 660 nm and spatial average energy fluency [SAEF] = 1.06 J/cm²). The patients in the laser group underwent irradiation on postoperative days 2, 4, 6, and 8, and their sternotomy incisions were photographed immediately after the surgery and 8 days later for analysis. Three researchers who were blinded to the patient treatment groups analyzed the incision photographs to assess hyperemia and wound closure on the day of hospital discharge (eighth postoperative day). The sternotomy incisions in the LLLT group demonstrated less hyperemia, incisional bleeding, and dehiscence (p ≤ 0.005).

http://ift.tt/2d1xeil

Effect of low-level laser therapy on angiogenesis and matrix metalloproteinase-2 immunoexpression in wound repair

Abstract

Low-level laser therapy (LLLT) induces anti-inflammatory and angiogenic activities in wound healing. However, the mechanism of action and optimal parameters require further clarification. In this study, we investigated the effects of LLLT on wound healing matrix metalloproteinase (MMP)-2 immunoexpression and angiogenic processes. Twenty female Wistar rats were randomly divided into four groups (n = 5) according to the treatments as follows. CG7 and CG14 were control groups at days 7 and 14, respectively, which received physiological saline (0.9 % NaCl daily). LG7 and LG14 were laser therapy groups at days 7 and 14, respectively, which received two (LG7) or four (LG14) LLLT applications (40 mW; 660 nm; 4 J/cm²). A dorsal skin sample in the wound area (measuring 2 cm²) was removed after the experimental period, and then the animals were euthanized. The specimens were processed for qualitative and quantitative histological analyses and measurement of MMP-2 expression in the dermis and epidermis. A persistent crust and moderate number of inflammatory cells were found in CG7 and CG14 groups. In the LG14 group, wounds demonstrated complete re-epithelization at the remodeling phase. Angiogenesis and MMP-2 expression were higher in LLLT-treated groups, particularly the LG14 group, which correlated according to the Spearman correlation test. LLLT improves wound healing by enhancing neocollagenesis, increasing the amount of new vessels formed in the tissue (neoangiogenesis), and modulating MMP-2 expression. Epidermal overexpression of MMP-2 was correlated to angiogenic processes.

http://ift.tt/2cOcZRL

High Prevalence of Back Pain and Axial Spondyloarthropathy in Patients with Hidradenitis Suppurativa

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease, causing fistulating sinuses in the intertriginous skin of axillary, genitofemoral and perianal sites. Objective: As other chronic inflammatory diseases, e.g. psoriasis, are frequently associated with spondyloarthropathies (SpA), the goal of this study was to quantify the prevalence of back pain and SpA in HS patients. Methods: A prospective questionnaire survey in 100 HS patients and a retrospective evaluation of pelvic magnetic resonance imaging (MRI) scans in 46 HS patients were conducted. Results: 71% of HS patients were suffering from back pain. There was no difference between age at onset of HS, disease duration, body mass index (BMI), or disease severity between HS patients with and without back pain. Evaluating pelvic MRI scans, 32.6% of HS patients showed signs of chronic SpA and 39.1% signs of active SpA. Again, no significant differences between patients with/without SpA were found regarding age at time of MRI, age at onset of HS, disease duration, smoking habits, and BMI. Furthermore, there was no correlation between these parameters and the degree of SpA. Limitations: Only patients with moderate/severe HS (Hurley stage II and III) in genitofemoral/perianal sites were analysed via MRI scans. Conclusion: Back pain and SpA are very common among patients with moderate/severe HS. Neither medical history nor clinical parameters provide hints for the presence of SpA.
Dermatology

http://ift.tt/2cMV3sC

PTPN2-deficiency exacerbates T follicular helper cell and B cell responses and promotes the development of autoimmunity

Publication date: Available online 19 September 2016
Source:Journal of Autoimmunity
Author(s): Florian Wiede, Faruk Sacirbegovic, Yew Ann Leong, Di Yu, Tony Tiganis
Non-coding single nucleotide polymorphisms that repress PTPN2 expression have been linked with the development of type 1 diabetes, rheumatoid arthritis and Crohn's disease. PTPN2 attenuates CD8⁺ T cell responses to self and prevents overt autoreactivity in the context of T cell homeostasis and antigen cross-presentation. The role of PTPN2 in other immune subsets in the development of autoimmunity remains unclear. Here we show that the inducible deletion of PTPN2 in hematopoietic compartment of adult non-autoimmune prone mice results in systemic inflammation and autoimmunity. PTPN2-deficient mice had increased inflammatory monocytes, B cells and effector T cells in lymphoid and non-lymphoid tissues and exhibited symptoms of dermatitis, glomerulonephritis, pancreatitis and overt liver disease. Autoimmunity was characterised by the formation of germinal centers in the spleen and associated with markedly increased germinal center B cells and T follicular helper (Tfh) cells and circulating anti-nuclear antibodies, inflammatory cytokines and immunoglobulins. CD8⁺ T cell proliferative responses were enhanced, and interleukin-21-induced STAT-3 signalling in Tfh cells and B cells was increased and accompanied by enhanced B cell proliferation ex vivo. These results indicate that deficiencies in PTPN2 across multiple immune lineages, including naive T cells, Tfh cells and B cells, contribute to the development of autoimmunity.



http://ift.tt/2cVUXiD

The role of dopamine in positive and negative prediction error utilization during incidental learning – insights from Positron Emission Tomography, Parkinson’s disease and Huntington’s disease

Publication date: Available online 19 September 2016
Source:Cortex
Author(s): David Mathar, Leonora Wilkinson, Anna Holl, Jane Neumann, Lorenz Deserno, Arno Villringer, Marjan Jahanshahi, Annette Horstmann
Incidental learning of appropriate stimulus-response associations is crucial for optimal functioning within our complex environment. Positive and negative prediction errors (PEs) serve as neural teaching signals within distinct ('direct'/'indirect') dopaminergic pathways to update associations and optimize subsequent behavior. Using a computational reinforcement-learning model, we assessed learning from positive and negative PEs on a probabilistic task (Weather Prediction Task, [WPT]) in three populations that allow different inferences on the role of dopamine (DA) signals: (1) Healthy volunteers that repeatedly underwent [11C]raclopride Positron Emission Tomography, allowing for assessment of striatal DA release during learning, (2) Parkinson's disease (PD) patients tested both on and off L-DOPA medication, (3) early Huntington's disease (HD) patients, a disease that is associated with hyper-activation of the 'direct' pathway. Our results show that learning from positive and negative feedback on the WPT is intimately linked to different aspects of dopaminergic transmission. In healthy individuals, the difference in [11C]raclopride binding potential (BP) as a measure for striatal DA release was linearly associated with the positive learning rate. Further, asymmetry between baseline DA tone in the left and right ventral striatum was negatively associated with learning from positive PEs. Female patients with early HD exhibited exaggerated learning rates from positive feedback. In contrast, dopaminergic tone predicted learning from negative feedback, as indicated by an inverted-u-shaped association observed with baseline [11C]raclopride BP in healthy controls and the difference between PD patients' learning rate on and off dopaminergic medication. Thus, the ability to learn from positive and negative feedback is a sensitive marker for the integrity of dopaminergic signal transmission in the 'direct' and 'indirect' dopaminergic pathways. The present data are interesting beyond clinical context in that imbalances of dopaminergic signaling have not only been observed for neurological and psychiatric conditions but also been proposed for obesity and adolescence.



http://ift.tt/2clTd2N