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Τετάρτη 21 Σεπτεμβρίου 2016
Scholar : These new articles for Civil Engineering and Environmental Systems are available online
Scholar : These new articles for Archives of Agronomy and Soil Science are available online
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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.
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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.
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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
Scholar : These new articles for Research in Drama Education: The Journal of Applied Theatre and Performance are available online
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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
Scholar : Communication Law and Policy, Volume 21, Issue 4, Autumn 2016 is now available online on Taylor & Francis Online
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Monocyte subsets in blood correlate with obesity related response of macrophages to biomaterials in vitro
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
Scholar : These new articles for Bulletin of Spanish Studies are available online
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Scholar : These new articles for Aging & Mental Health are available online
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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
Bioactive forms of vitamin D selectively stimulate the skin analog of the hypothalamus-pituitary-adrenal axis in human epidermal keratinocytes
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
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
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
Τρίτη 20 Σεπτεμβρίου 2016
To what extent is alcohol consumption associated with breast cancer recurrence and second primary breast cancer?: A systematic review
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
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
In silico, in vitro and case-control analyses as an effective combination for analyzing BRCA1 and BRCA2 unclassified variants in a population-based sample
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
Scholar : These new articles for The American Journal of Family Therapy are available online
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Novel Insights into PML-Dependent Oncosuppression
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
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
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
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
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
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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
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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
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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
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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
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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
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
Scholar : These new articles for International Journal of Heritage Studies are available online
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Scholar : These new articles for Behavioral Sciences of Terrorism and Political Aggression are available online
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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
Scholar : These new articles for African Security Review are available online
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Ειδοποίηση Μελετητή:[ ωτα ] [HTML] Gender, identity and material: Film screening C Brand - 2017 ftypM4V *M4V M4A mp42isom*a┌moovlmvhd...
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
