Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Δευτέρα 26 Φεβρουαρίου 2018

Correction to: Behaviour and risk assessment of fluopyram and its metabolite in cucumber ( Cucumis sativus ) fruit and in soil

Abstract

Unfortunately, the original publication of this paper contains a mistake. The correct name of the 3rd Author is Sunny H. Patel. The original article has been corrected.



http://ift.tt/2oBCsUn

18 F-Fluorocholine PET/CT as a second line nuclear imaging technique before surgery for primary hyperparathyroidism



http://ift.tt/2sXsPVL

Low baseline and subsequent higher aortic abdominal aneurysm FDG uptake are associated with poor sac shrinkage post endovascular repair

Abstract

Purpose

The growth phases of medically treated abdominal aortic aneurysms (AAA) are frequently associated with an 18F–fluorodesoxyglucose positron emission tomography (FDG-PET) pattern involving low baseline and subsequent higher FDG uptake. However, the FDG-PET patterns associated with the endovascular aneurysm repair (EVAR) of larger AAA are presently unknown. This study aimed to investigate the relationship between serial AAA FDG uptake measurements, obtained before EVAR and 1 and 6 months post-intervention and subsequent sac shrinkage at 6 months, a well-recognized indicator of successful repair.

Methods

Thirty-three AAA patients referred for EVAR (maximal diameter: 55.4 ± 6.0 mm, total volume: 205.7 ± 63.0 mL) underwent FDG-PET/computed tomography (CT) before EVAR and at 1 and 6 months thereafter, with the monitoring of AAA volume and of a maximal standardized FDG uptake [SUVmax] averaged between the axial slices encompassing the AAA.

Results

Sac shrinkage was highly variable and could be stratified into three terciles: a first tercile in which shrinkage was absent or very limited (0–29 mL) and a third tercile with pronounced shrinkage (56–165 mL). SUVmax values were relatively low at baseline in the 1st tercile (SUVmax: 1.69 ± 0.33), but markedly increased at 6 months (2.42 ± 0.69, p = 0.02 vs. baseline). These SUV max values were by contrast much higher at baseline in the 3rd tercile (SUVmax: 2.53 ± 0.83 p = 0.009 vs. 1st tercile) and stable at 6 months (2.49 ± 0.80), while intermediate results were documented in the 2nd tercile. Lastly, the amount of sac shrinkage, expressed in absolute values or in percentages of baseline AAA volumes, was positively correlated with baseline SUVmax (p = 0.001 for both).

Conclusion

A low pre-EVAR FDG uptake and increased AAA FDG uptake at 6 months are associated with reduced sac shrinkage. This sequential FDG-PET pattern is similar to that already shown to accompany growth phases of medically treated AAA.



http://ift.tt/2Cp9roz

Val M. Runge. Imaging of Cerebrovascular Disease. A Practical Guide



http://ift.tt/2sYRI3g

[68Ga]Pentixafor-PET/MRI for the detection of Chemokine receptor 4 expression in atherosclerotic plaques

Abstract

Purpose

The expression of chemokine receptor type 4 (CXCR4) was found co-localized with macrophages on the atherosclerotic vessel wall and participated in the initial emigration of leukocytes. Gallium-68 [68Ga]Pentixafor has recently been introduced for the imaging of atherosclerosis by targeting CXCR4. We sought to evaluate human atherosclerotic lesions using [68Ga]Pentixafor PET/MRI.

Methods

Thirty-eight oncology patients underwent [68Ga]Pentixafor PET/MR imaging at baseline. Maximum standardized uptake values (SUVmax) were derived from hot lesions in seven arterial segments and target-to-blood ratios (TBR) were calculated. ANOVA post-hoc and paired t test were performed for statistical comparison, Spearman's correlation coefficient between uptake ratios and cardiovascular risk factors were assessed. The reproducibility of [68Ga]Pentixafor PET/MRI was assessed in seven patients with a follow-up exanimation by Pearson's regression and Bland–Altman plots analysis.

Results

Thirty-four of 38 patients showed 611 focal [68Ga]Pentixafor uptake that followed the contours of the large arteries. Both prevalence and mean TBRmax were highest in the descending aorta. There were significantly higher TBR values found in men (1.9 ± 0.3) as compared to women (1.7 ± 0.2; p < 0.05). Patients with mean TBRmax > 1.7 showed a significantly higher incidence of diabetes, hypertension hypercholesterolemia and history of cardiovascular disease than patients with mean TBRmax ≤ 1.7. [68Ga]Pentixafor uptake showed a good reproducibility (r = 0.6, p < 0.01), and there was no difference between the mean TBRmax values of plaque lesions (TBRbaseline1.8 ± 0.3 vs TBRfollow-up1.8 ± 0.3) (p = 0.9).

Conclusion

Patients with high arterial uptake showed increased incidence of cardiovascular risk factors, suggesting a potential role of [68Ga]Pentixafor in characterization of atherosclerosis.



http://ift.tt/2F9XUKD

Correction to: Diagnostic and prognostic value of baseline FDG PET/CT skeletal textural features in diffuse large B cell lymphoma

Abstract

The formulae for Dice and Jaccard indices used to assess volumes concordance should read as follows:



http://ift.tt/2sZRHvJ

11 C–MET PET/MRI for detection of recurrent glioma

Abstract

Introduction

Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid 11C–MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma.

Methods

Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid 11C–MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid 11C–MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis.

Results

Hybrid 11C–MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for 11C–MET PET (96.77% and 73.68%), and for hybrid 11C–MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid 11C–MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C–MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing 11C–MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733).

Conclusion

This feasibility study showed that hybrid PET/MRI might strengthen RANO classification by adding metabolic information to conventional MRI information. Future studies should evaluate the clinical utility of the combined use of 11C–MET PET/MRI in larger patient cohorts.



http://ift.tt/2Co65C0

FDG PET-CT as a powerful tool for diagnosing and monitoring treatment outcomes of relapsing polychondritis



http://ift.tt/2sW0Rtn

Prediction of functional recovery after primary PCI using the estimate of myocardial salvage in gated SPECT early after acute myocardial infarction

Abstract

Purpose

Primary percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) aims to achieve myocardial salvage (MS). Because the reference method for measuring MS requires myocardial perfusion imaging (MPI) after tracer injection before PCI, alternative approaches have been proposed, but none has gained wide acceptance. Gated SPECT MPI can assess infarct size (IS), but can also show myocardial stunning. Thus, we compared functional and perfusion abnormalities early after AMI to estimate MS, and to predict left ventricular ejection fraction (LVEF) recovery at follow-up.

Methods

We studied 120 patients with AMI. Gated SPECT MPI was performed early (before hospital discharge) and at 6 months after AMI to measure IS, MS and functional outcome. MS was defined as the difference between the number of segments with abnormal thickening (i.e. the stunned area or area at risk) and the number of segments with abnormal perfusion (i.e. the final IS), expressed as a percentage of the total number of segments in the AHA model. LVEF was calculated using quantitative gated SPECT.

Results

The area at risk was 40 ± 25%, IS was 17.3 ± 16% and MS was 22 ± 19%. Early LVEF was 46.6 ± 11.6% and late LVEF was 51.4 ± 11.6%, with 54 patients showing at least an increase in LVEF of more than 5 units. ROC analysis showed that MS was able to predict LVEF recovery with an area under the curve (AUC) of 0.79 (p < 0.0001), and using a cut off >23% detected LVEF recovery with 74% sensitivity and 71% specificity. Conversely, IS was associated with an AUC 0.53 (not significant).

Conclusion

MS assessed by a single early gated SPECT MPI study can accurately predict LVEF evolution after primary PCI for AMI.



http://ift.tt/2CpjCta

Chun K. Kim and Katherine A. Zukotynski (editors): SPECT and SPECT/CT: a clinical guide



http://ift.tt/2t2KStC

Correction to: Dosimetry in clinical radionuclide therapy: the devil is in the detail

Abstract

The above article which was published in Volume 44/ Issue 12 has incorrect page numbers. Instead of 1-3, it should have been 2137-2139.



http://ift.tt/2Cp3VlF

Anaplastic thyroid carcinoma on 68 Ga-PSMA PET/CT: opening new frontiers



http://ift.tt/2t26CWe

Preclinical evaluation of an 18 F-trifluoroborate methionine derivative for glioma imaging

Abstract

Purpose

11C–methionine (MET) is one of the most commonly used amino acid tracers for PET imaging of brain tumors. In this study, we report an 18F-labeled boron-derived methionine analogue, denoted as 18F-B-MET, as a potential substitute of 11C–MET for glioma PET imaging.

Methods

19F-B-MET was synthesized from readily available chemicals according to our previous publication. For kit development, 19F-B-MET was aliquoted in quantities of 10 nmol for on-demand one-step labeling. The 18F-labeling was performed by 18F-19F isotope exchange, and quality control was performed by both HPLC and radio-TLC. Uptake of the tracer was determined in GL26, C6 and U87 tumor cells. PET imaging and the biodistribution assay were performed on mice bearing subcutaneous or orthotopic C6 and U87 tumor xenografts.

Results

Starting with 740–1110 MBq 18F-fluoride, >370 MBq of 18F-B-MET was obtained in 25 min (n = 5) with >99% purity and high specific activity (>37 GBq/μmol). 18F-B-MET demonstrated excellent in vitro stability with <1% decomposition after incubation with plasma for 2 h. In vitro cell uptake assay showed that 18F-B-MET accumulated in tumor cells in a time dependent manner and could be competitively inhibited by natural methionine and other L-type transporter transported amino acids. In vivo biodistribution and imaging studies showed high tumor accumulation (2.99 ± 0.23 %ID/g, n = 6) compared with low uptake of brain (0.262 ± 0.05 %ID/g, n = 6) at 60 min after injection in a subcutaneous C6 tumor model. Orthotropic C6 and U87 tumors were clearly visualized with high tumor to brain ratios at 60 min post-injection, corroborating with tumor L-type amino acid transporter 1 (LAT-1) expression levels.

Conclusion

18F-B-MET was radiolabeled with high yield in a one-step labeling process, showed excellent pharmacokinetic properties in vivo, with high tumor-to-brain contrast.



http://ift.tt/2F7TB2o

Isam Alobid and Paolo Castelnuovo (editors): Nasoseptal Perforations: Endoscopic Repair Techniques



http://ift.tt/2t26bLA

Comparison of 18 F–FDG PET/MRI and MRI alone for whole-body staging and potential impact on therapeutic management of women with suspected recurrent pelvic cancer: a follow-up study

Abstract

Purpose

To evaluate the diagnostic performance of 18F–FDG PET/MRI for whole-body staging and potential changes in therapeutic management of women with suspected recurrent pelvic cancer in comparison with MRI alone.

Methods

Seventy-one consecutive women (54 ± 13 years, range: 25–80 years) with suspected recurrence of cervical (32), ovarian (26), endometrial (7), vulvar (4), and vaginal (2) cancer underwent PET/MRI including a diagnostic contrast-enhanced MRI protocol. PET/MRI and MRI datasets were separately evaluated regarding lesion count, localization, categorization (benign/malignant), and diagnostic confidence (3-point scale; 1–3) by two physicians. The reference standard was based on histopathology results and follow-up imaging. Diagnostic accuracy and proportions of malignant and benign lesions rated correctly were retrospectively compared using McNemar's chi2 test. Differences in diagnostic confidence were assessed by Wilcoxon test.

Results

Fifty-five patients showed cancer recurrence. PET/MRI correctly identified more patients with cancer recurrence than MRI alone (100% vs. 83.6%, p < 0.01). In contrast to PET/MRI, MRI alone missed 4/15 patients with pelvic recurrence and miscategorized 8/40 patients with distant metastases as having local recurrence only. Based on the reference standard, 241 lesions were detected in the study cohort (181 malignant, 60 benign). While PET/MRI provided correct identification of 181/181 (100%) malignant lesions, MRI alone correctly identified 135/181 (74.6%) malignant lesions, which was significantly less compared to PET/MRI (p < 0.001). PET/MRI offered superior diagnostic accuracy (99.2% vs. 79.3%, p < 0.001) and diagnostic confidence in the categorization of malignant lesions compared with MRI alone (2.7 ± 0.5 vs. 2.4 ± 0.7, p < 0.001).

Conclusion

PET/MRI demonstrates excellent diagnostic performance and outperforms MRI alone for whole-body staging of women with suspected recurrent pelvic cancer, indicating potential changes in therapy management based on evaluation of local recurrence and distant metastatic spread.



http://ift.tt/2F3XVzR

Up-front PET/CT changes treatment intent in patients with head and neck squamous cell carcinoma

Abstract

Purpose

In patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), we wanted to examine the differences in overall treatment decisions, i.e. curative versus palliative treatment intent, reached by a multidisciplinary team conference (MDTC) based on 18F–fluoro-deoxy-glucose-positron emission tomography/computed tomography (PET/CT) or chest X-ray + MRI of the head and neck (CXR/MRI).

Patients and methods

This was a prospective blinded cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were invited to participate. All included patients underwent CXR/MRI and PET/CT before diagnostic biopsy. An ordinary MDTC using all available imaging was conducted as per standard practice. After at least 3 months (to eliminate recall bias in the team), the first project MDTC was conducted, based on either CXR/MRI or PET/CT, and the tumor board drew conclusions regarding treatment. After an additional 3 months, a second project MDTC was conducted using the complementary imaging modality.

Results

A total of 307 patients were included. Based on CXR/MRI, 303 patients (99%) were recommended for curative treatment and only four patients (1%) for palliative treatment. Based on PET/CT, the MDTC concluded that 278 (91%) patients were suitable for curative treatment and 29 (9%) patients for palliative treatment. The absolute difference of 8% was statistically significant (95% CI: 4.8%–11.5%, p < 0.001).

Conclusions

A PET/CT-based imaging strategy significantly changed the decisions regarding treatment intent made by a MDTC for patients diagnosed with HNSCC, when compared with the standard imaging strategy of CXR/MRI.



http://ift.tt/2sZDfE5

Impact of initial myocardial perfusion imaging versus invasive coronary angiography on outcomes in coronary artery disease: a nationwide cohort study

Abstract

Purpose

In patients with stable coronary artery disease (CAD), two main options exist to guide management: initial invasive coronary angiography (CAG), or selective CAG after risk stratification using myocardial perfusion imaging (MPI). This study compared clinical outcomes between these two strategies in a large, real-world population.

Methods

The initial cohort comprised 1,000,000 randomly selected patients who had been entered in the National Health Insurance Research Database of Taiwan between 2000 and 2011. Patients with acute coronary syndromes, prior myocardial infarction (MI) or coronary revascularization, and prior treadmill testing or stress echocardiography were excluded. The remaining patients with suspected or known CAD were divided into those in whom initial CAG had been performed and those in whom initial MPI had been performed, and were followed until the end of 2011 for all-cause mortality, MI, and revascularization. A Cox proportional hazards model was used to estimate the risk of events after adjusting for covariates.

Results

The MPI and CAG groups each comprised 4,495 patients after frequency matching, with a similar Charlson comorbidity index (CCI). The MPI group had a significantly and dramatically lower incidence of revascularization (729 vs. 2,380, p < 0.001), MI (268 vs. 1,044, p < 0.001), and all-cause mortality (522 vs. 784, p < 0.001) than the CAG group. Multivariable analysis adjusting for age, gender, CCI, and comorbidities showed that in the MPI group fewer patients had revascularization (HR 0.24, 95% CI 0.22–0.26) and MI (HR 0.23, 95% CI 0.20–0.26), and the rate of all-cause mortality was lower (HR 0.58, 95% CI 0.52–0.64).

Conclusions

In patients with suspected stable CAD, compared with initial invasive CAG, a selective strategy guided by MPI was associated with lower rates of revascularization and MI and improved survival.



http://ift.tt/2ConmLc

Combined evaluation of regional coronary artery calcium and myocardial perfusion by 82 Rb PET/CT in the identification of obstructive coronary artery disease

Abstract

Purpose

Cardiac imaging with PET/CT allows measurement of coronary artery calcium (CAC), myocardial perfusion and coronary vascular function. We investigated whether the combined assessment of regional CAC score, ischemic total perfusion deficit (ITPD) and quantitative coronary vascular function would further improve the diagnostic accuracy of PET/CT in predicting obstructive coronary artery disease (CAD).

Methods

We analyzed 113 patients with suspected CAD referred to 82Rb PET/CT myocardial perfusion imaging with available coronary angiographic data. Obstructive CAD was defined as ≥75% stenosis. The receiver operating characteristic area under curve (AUC) was applied to evaluate the ability of CAC score, ITPD, hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) to identify CAD.

Results

Vessels with obstructive CAD (71 vessels) had higher ITPD (4.6 ± 6.2 vs. 0.6 ± 1.3) and lower hyperemic MBF (1.01 ± 0.5 vs. 1.75 ± 0.6 ml/min/g) and CFR (1.56 ± 0.6 vs. 2.38 ± 0.7; all p < 0.001) than those without. In prediction of per-vessel CAD, the AUCs for the models including CAC/ITPD/hyperemic MBF (0.869) and CAC/ITPD/CFR (0.875) were higher (both p < 0.01) than for the model including CAC/ITPD (0.790). Compared with CAC/ITPD, continuous net reclassification improvement was 0.69 (95% bootstrap confidence interval, CI, 0.365–1.088) for the CAC/ITPD/hyperemic MBF model and 0.99 (95% bootstrap CI 0.64–1.26) for the CAC/ITPD/CFR model.

Conclusion

Hyperemic MBF and CFR provide incremental information about the presence of CAD over CAC score and perfusion imaging parameters. The combined use of CAC, myocardial perfusion imaging and quantitative coronary vascular function in may help predict more accurately the presence of obstructive CAD.



http://ift.tt/2sUUnuU

F18-choline PET/CT guided surgery in primary hyperparathyroidism when ultrasound and MIBI SPECT/CT are negative or inconclusive: the APACH1 study

Abstract

Purpose

To evaluate the sensitivity of F18-choline (FCH) PET/CT for parathyroid adenoma detection prior to surgery in patients with primary hyperparathyroidism and negative or inconclusive cervical ultrasound and Tc99m-sestaMIBI SPECT/CT.

Methods

We conducted a prospective bicentric study (NCT02432599). All patients underwent FCH PET/CT. The result was scored positive, inconclusive or negative. The number of uptakes and their sites were recorded. The FCH PET/CT result guided the surgical procedure (minimally invasive parathyroidectomy, bilateral cervical exploration, or other in case of multiple or ectopic foci). FCH PET/CT results were compared to the surgical and pathological findings and the follow-up.

Results

Twenty-five patients were included. Mean calcium and PTH levels prior to surgery were 2.76 ± 0.17 mmol/l and 94.8 ± 37.4 ng/l. Nineteen (76%) FCH PET/CTs were scored positive, 3 (12%) inconclusive and 3 (12%) negative, showing 21 cases of uniglandular disease, including 1 ectopic localization and 1 case of multiglandular (3 foci) disease. Mean lesion size was 13.1 ± 8.6 mm. Twenty-four patients underwent surgery. FCH PET/CT guided surgery in 22 (88%) patients, allowing for 17 minimally invasive parathyroidectomies, 1 bilateral cervical exploration for multifocality and 4 other surgical procedures. Two patients with negative FCH-PET/CT underwent bilateral cervical exploration. When dichotomizing the FCH PET/CT results, thereby classifying the inconclusive FCH PET/CT results as positive, the per lesion and per patient sensitivities were 91.3% (95%CI: 72.0–98.9) and 90.5% (95%CI: 69.6–98.8) and the corresponding positive predictive values were 87.5% (95%CI: 67.6–97.3) and 86.4% (95%CI: 65.1–97.1), respectively.

Twenty-one (88%) patients were considered cured after surgery. Their mean calcium level after surgery was 2.36 ± 0.17 mmol/l.

Conclusions

Preoperative FCH PET/CT has a high sensitivity and positive predictive value for parathyroid adenoma detection in patients with primary hyperparathyroidism and negative or inconclusive conventional imaging results. Bilateral cervical exploration could be avoided in the majority (75%) of patients.



http://ift.tt/2CqBFPq

Effect of CRP value on 18 F–FDG PET vascular positivity in Takayasu arteritis: a systematic review and per-patient based meta-analysis

Abstract

Purpose

The aim of this study was to quantify the association between the CRP value and 18F–FDG PET vascular positivity in Takayasu arteritis (TAK) through a structured dedicated systematic review and meta-analysis.

Methods

From January 2000 to December 2016, the PubMed/MEDLINE database was searched for articles specifically dealing with the assessment of vascular inflammation using 18F–FDG PET and CRP biomarkers in TAK. Inclusion criteria for the qualitative analysis were (1) 18F–FDG PET used to assess the disease activity, (2) The use of the ACR criteria for the diagnosis of TAK, (3) No case mixed vasculitis (i.e., no giant cell arteritis), and (4) CRP concentration and clinical disease activity available. For the meta-analysis, PET-positive and PET-negative subgroups with the corresponding CRP concentrations were generated based on per patient data. The standard mean difference, which represents the effect of the CRP concentrations on the 18F–FDG PET vascular uptake, was computed for all studies, and then the results were pooled together.

Results

Among the 33 initial citations, nine complete articles including 210 patients fulfilled the inclusion criteria. Five studies found a significant correlation between the 18F–FDG PET and CRP concentration, one provided a trend towards association and three did not find any association between the two biomarkers. Six studies found a significant association between 18F–FDG PET and clinical disease activity, one found a trend towards association and the last two studies did not evaluate this correlation. The meta-analysis (121 patients) provided the following results: Standard Mean Deviation = 0.54 [0.15;0.92]; Chi2 = 3.35; I2 = 0%; Test for overall effect: Z = 2.70 (P = 0.007).

Conclusion

The CRP concentration only moderately reflects the 18F–FDG PET vascular positivity in TAK, suggesting dissociated information. Standardized longitudinal prospective studies are necessary to assess the value of 18F–FDG PET as an independent biomarker for subtle vascular wall inflammation detection.



http://ift.tt/2sWKDA9

Multi-centre phase IV trial to investigate the immunogenicity of a new liquid formulation of recombinant human growth hormone in adults with growth hormone deficiency

Abstract

Purpose

To investigate whether a new liquid formulation of recombinant human growth hormone (r-hGH) induces the production of binding antibodies (BAbs) in adults with congenital or adult-onset growth hormone deficiency (GHD).

Methods

Men or women aged 19–65 years with adult growth hormone deficiency who were r-hGH-naïve or had stopped treatment ≥ 1 month before screening were treated with between 0.15 and 0.30 mg/day r-hGH liquid formulation for 39 weeks. The primary endpoint was the proportion of patients who developed BAbs at any time. Secondary endpoints were the proportion of patients with BAbs who became positive for neutralising antibodies, the effects on biomarkers of r-hGH exposure, safety, and adherence to treatment downloaded from the easypod™ connect software.

Results

Seventy-eight patients (61.5% men) with mean age 44.5 years (range 21–65) started and 68 (87.2%) completed the 39-week treatment period. 82.1% were treatment naïve; all were negative for BAbs to r-hGH at baseline. The median (interquartile range) duration of treatment [273 (267.0–277.0) days] was consistent with patients receiving the required doses, and mean treatment adherence measured using easypod™ connect was 89.3%. The proportion of patients who developed BAbs was 0% (95% confidence interval 0–4.68%) and biomarker profiles were consistent with exposure to r-hGH. 92.3% of patients reported ≥ 1 adverse event during treatment. Most events were mild or moderate and no new safety concerns were detected.

Conclusions

The low immunogenicity profile of the liquid formulation was consistent with that for the freeze-dried formulation, and no new safety concerns were reported.



http://ift.tt/2ot1t4Y

Quinoline derivative containing monomeric and polymeric metal carboxylates: Synthesis, crystal structure and gas adsorption study over a 2D layered framework

Publication date: 15 June 2018
Source:Journal of Molecular Structure, Volume 1162
Author(s): Saikat Gayen, Debraj Saha, Subratanath Koner
A new supramolecular metal-carboxylate framework [Co(mqc)2]n (1), and another monomeric compound [Zn (mqc)2(H2O)] (2) (mqcH = 4-methoxy 2-quinolinecarboxylic acid) have been synthesized solvothermally and characterized by single crystal X-ray diffraction, elemental analysis, IR spectra, UV–vis spectra, powdered X-ray diffraction (PXRD) and thermogravimetric analysis. Compound 1 is a 2D coordination polymer, extended to a 3D porous supramolecular network having void space in between 2D layers. Compound 1 exhibits gas uptake capacity of N2, H2, CO2 and CH4 like small gas molecules in which moderately high uptake of H2 and CO2 takes place among the 2D MOFs. While the Zn variety, compound 2 features a one-dimensional chain like structure through strong intermolecular hydrogen-bonding.

Graphical abstract

image


http://ift.tt/2otkTXA

Raman spectroscopic analysis on Li, N and (Li,N) implanted ZnO

Publication date: 15 June 2018
Source:Materials Science in Semiconductor Processing, Volume 80
Author(s): Apu Mondal, S. Pal, A. Sarkar, T.S. Bhattacharya, Avishek Das, N. Gogurla, S.K. Ray, Pravin Kumar, D. Kanjilal, K.D. Devi, A. Singha, S. Chattopadhyay, D. Jana
Doping lithium (Li) and/or nitrogen (N) in ZnO and activation of shallow acceptors thereby have drawn specific scientific interest for the last few years. A comprehensive study employing Raman spectroscopy is being reported here on N and Li implantation effects in ZnO. Strong presence of 275 cm−1 Raman mode after N and (Li,N) implantation confirms its relation with doped nitrogen in ZnO. Weak presence of 510 cm−1 mode in the high fluence implanted ZnO indicates its origin with interstitial defects. No extra Raman mode has been identified in Li implanted samples. Raman mode with anomalously large intensity is found at 1562 cm−1 after (Li,N) co-implantation (highest fluence). Implantation causes huge increase of Raman modes ~ 540, 555 and 579 cm−1, with the last two bearing clear co-relations with interstitial Zn and O vacancy, respectively. To identify shallow acceptors due to dopant-defect complex, low temperature photoluminescence (PL) has been monitored but only donor related excitonic features are visible in the near band edge (NBE) emission. However, indications in favour of deep acceptors states are noted, particularly when Li is present in the sample. The deep acceptor level may be at~ 300 meV above the valence band consistent with previous results.



http://ift.tt/2oAbQ6t

Diversity of Cortico-descending Projections: Histological and Diffusion MRI Characterization in the Monkey

Abstract
The axonal composition of cortical projections originating in premotor, supplementary motor (SMA), primary motor (a4), somatosensory and parietal areas and descending towards the brain stem and spinal cord was characterized in the monkey with histological tract tracing, electron microscopy (EM) and diffusion MRI (dMRI). These 3 approaches provided complementary information. Histology provided accurate assessment of axonal diameters and size of synaptic boutons. dMRI revealed the topography of the projections (tractography), notably in the internal capsule. From measurements of axon diameters axonal conduction velocities were computed. Each area communicates with different diameter axons and this generates a hierarchy of conduction delays in this order: a4 (the shortest), SMA, premotor (F7), parietal, somatosensory, premotor F4 (the longest). We provide new interpretations for i) the well-known different anatomical and electrophysiological estimates of conduction velocity; ii) why conduction delays are probably an essential component of the cortical motor command; and iii) how histological and dMRI tractography can be integrated.

http://ift.tt/2EZXtzm

The Temporal Dynamics of Brain Plasticity in Aging

Abstract
Cognitive training has been suggested as a possible remediation of decline in brain structure with older age. However, it is unknown whether training effects are transient or enduring, as no studies have examined training-induced plasticity relative to decline in older adults across extended periods with multiple intervention phases. We investigated the temporal dynamics of brain plasticity across periods on and off memory training, hypothesizing that (1) a decline in white matter (WM) microstructure would be observed across the duration of the study and (2) that periods of memory training would moderate the WM microstructural decline. In total, 107 older adults followed a 40-week program, including 2 training periods separated by periods with no intervention. The general decline in WM microstructure observed across the duration of the study was moderated following the training periods, demonstrating that cognitive training may mitigate age-related brain deterioration. The training-related improvements were estimated to subside over time, indicating that continuous training may be a premise for the enduring attenuation of neural decline. Memory improvements were largely maintained after the initial training period, and may thus not rely on continuous training to the same degree as WM microstructure.

http://ift.tt/2FxykNj

Sfrp1 Modulates Cell-signaling Events Underlying Telencephalic Patterning, Growth and Differentiation

Abstract
The mammalian dorsal telencephalic neuroepithelium develops—from medial to lateral—into the choroid plaque, cortical hem, hippocampal primordium and isocortex under the influence of Bmp, Wnt and Notch signaling. Correct telencephalic development requires a tight coordination of the extent/duration of these signals, but the identification of possible molecular coordinators is still limited. Here, we postulated that Secreted Frizzled Related Protein 1 (Sfrp1), a multifunctional regulator of Bmp, Wnt and Notch signaling strongly expressed during early telencephalic development, may represent 1 of such molecules. We report that in E10.5–E12.5 Sfrp1/ embryos, the hem and hippocampal domains are reduced in size whereas the prospective neocortex is medially extended. These changes are associated with a significant reduction of the medio-lateral telencephalic expression of Axin2, a read-out of Wnt/βcatenin signaling activation. Furthermore, in the absence of Sfrp1, Notch signaling is increased, cortical progenitor cell cycle is shorter, with expanded progenitor pools and enhanced generation of early-born neurons. Hence, in postnatal Sfrp1/ animals the anterior hippocampus is reduced and the neocortex is shorter in the antero-posterior and medio-lateral axis but is thicker. We propose that, by controlling Wnt and Notch signaling in opposite directions, Sfrp1 promotes hippocampal patterning and balances medio-lateral and antero-posterior cortex expansion.

http://ift.tt/2F0IULy

Gap Junctions Interconnect Different Subtypes of Parvalbumin-Positive Interneurons in Barrels and Septa with Connectivity Unique to Each Subtype

Abstract
Parvalbumin (PV)-positive interneurons form dendritic gap junctions with one another, but the connectivity among gap junction-coupled dendrites remains uninvestigated in most neocortical areas. We visualized gap junctions in layer 4 of the mouse barrel cortex and examined their structural details. PV neurons were divided into 4 types based on the location of soma and dendrites within or outside barrels. Type 1 neurons that had soma and all dendrites inside a barrel, considered most specific to single vibrissa-derived signals, unexpectedly formed gap junctions only with other types but never with each other. Type 2 neurons inside a barrel elongated dendrites outward, forming gap junctions within a column that contained the home barrel. Type 3 neurons located outside barrels established connections with all types including Type 4 neurons that were confined inside the inter-barrel septa. The majority (33/38, 86.8%) of dendritic gap junctions were within 75 μm from at least 1 of 2 paired somata. All types received vesicular glutamate transporter 2-positive axon terminals preferentially on somata and proximal dendrites, indicating the involvement of all types in thalamocortical feedforward regulation in which proximal gap junctions may also participate. These structural organizations provide a new morphological basis for regulatory mechanisms in barrel cortex.

http://ift.tt/2FxyiVH

Controlled release of chlorhexidine from a HEMA-UDMA resin using a magnetic field

Publication date: Available online 26 February 2018
Source:Dental Materials
Author(s): Dong Luo, Saroash Shahid, Samiul Md. Hasan, Robert Whiley, Gleb B. Sukhorukov, Michael J. Cattell
ObjectivesTo functionalize novel chlorhexidine (CHX) particles with iron oxide (Fe3O4) nanoparticles and control their release kinetics in a dental resin using an external magnetic field.MethodsFe3O4 nanoparticles were synthesized and incorporated into spherical CHX particles and the powder was freeze dried. Resin disc specimens were produced using a UDMA-HEMA resin mixed with freeze dried spherical Fe3O4-CHX particles (5wt.%), which were placed into a Teflon mould (10mm diameter×1mm depth) and covered with a Mylar strip. A MACS magnet was left in contact for 0min (Group 1), 5min (Group 2) or 10min (Group 3) and the resin discs subsequently light cured (Bluedent LED pen, Bulgaria) for 60s per side. The resin discs were immersed in deionized water at various time points up to 650h. UV–Vis absorbance was used to determine the CHX content. CHX released for each time point was determined. The functionalized CHX particles and resin discs were characterized using TEM, TGA, EDX and SEM.ResultsFe3O4 nanoparticles (20nm) incorporated into the spherical CHX particles led to a mean (SD) particle size reduction from 17.15 (1.99)μm to 10.39 (2.61)μm. The presence of Fe3O4 nanoparticles in the spherical CHX particles was confirmed with SEM, EDX, and TGA. SEM of Group 1 resin discs (no magnetic exposure) showed functionalized CHX spheres were homogeneously distributed within the resin discs. For resin discs which had magnetic exposure (5 or 10min) the particles started to cluster nearer the surface (Group 2: 43.7%, Group 3: 57.3%), to a depth of 94μm. UV–Vis absorbance revealed Group 1 resin discs had a cumulative CHX release of 4.4% compared to 5.9% for Group 2 and 7.4% for Group 3 resin discs, which had magnetic exposure (5, 10min).SignificanceFe3O4 nanoparticle functionalized CHX spheres demonstrated a magnetic field responsive property. A magnetic field responsive release of CHX may be useful in clinical situations where the drug can be directed to give a tailored release at the site of infection.



http://ift.tt/2EYZqMg

Primary synovial sarcoma (SS) of larynx: An unusual site

Publication date: Available online 26 February 2018
Source:Oral Oncology
Author(s): Irappa Madabhavi, Vishalkumar Bhardawa, Mitul Modi, Apurva Patel, Malay Sarkar
Soft tissue sarcomas (STSs) are heterogeneous disorders comprises myriad subtypes originated from mesenchymal stem cells. Synovial sarcomas (SSs) are belligerent malignant tumours included in this group affecting extremities of patients' age ranging between 15 and 35 years. SS taking place in head and neck region is rare event and primary laryngeal involvement is even rarer happening. There are 20 odd published cases documented in world literature so far. Here we are presenting primary laryngeal SS occurred in 31 year old male patient initially mimicking laryngeal carcinoma as patient was chronic smoker and classic symptom of hoarseness of voice.



http://ift.tt/2GMEbOm

Editorial Board/Aims & Scope

Publication date: March 2018
Source:Oral Oncology, Volume 78





http://ift.tt/2HQlGdg

New research directions for areca nut/betel quid and oral submucous fibrosis for holistic prevention and treatment

Publication date: March 2018
Source:Oral Oncology, Volume 78
Author(s): Sachin C. Sarode, Prashanth Panta, Gargi S. Sarode, Amol R. Gadbail, Shailesh M. Gondivkar, Shankargouda Patil




http://ift.tt/2GM5XKF

RETRACTED: Systemic therapy in the management of metastatic or advanced salivary gland cancers

Publication date: March 2018
Source:Oral Oncology, Volume 78
Author(s): Aymen Lagha, Nesrine Chraiet, Mouna Ayadi, Sarra Krimi, Bassem Allani, Hela Rifi, Henda Raies, Amel Mezlini




http://ift.tt/2HO6nle

Airborne gamma-ray spectra processing: Extracting photopeaks

S0265931X.gif

Publication date: July 2018
Source:Journal of Environmental Radioactivity, Volume 187
Author(s): Eugene Druker
The acquisition of information from the airborne gamma-ray spectra is based on the ability to evaluate photopeak areas in regular spectra from natural and other sources. In airborne gamma-ray spectrometry, extraction of photopeaks of radionuclides from regular one-second spectra is a complex problem. In the region of higher energies, difficulties are associated with low signal level, i.e. low count rates, whereas at lower energies difficulties are associated with high noises due to a high signal level. In this article, a new procedure is proposed for processing the measured spectra up to and including the extraction of evident photopeaks. The procedure consists of reducing the noise in the energy channels along the flight lines, transforming the spectra into the spectra of equal resolution, removing the background from each spectrum, sharpening the details, and transforming the spectra back to the original energy scale. The resulting spectra are better suited for examining and using the photopeaks. No assumptions are required regarding the number, locations, and magnitudes of photopeaks. The procedure does not generate negative photopeaks. The resolution of the spectrometer is used for the purpose. The proposed methodology, apparently, will contribute also to study environmental problems, soil characterization, and other near-surface geophysical methods.



http://ift.tt/2EZTa7a

Non Inferiority Trial of Standard RT Versus Hypofractionated Split Course in Elderly Vulnerable Patients With HNSCC

Condition:   Head and Neck Squamous Cell Carcinoma
Interventions:   Radiation: Standard RT;   Radiation: Hypofractionated RT
Sponsors:   Groupe Oncologie Radiotherapie Tete et Cou;   Gustave Roussy, Cancer Campus, Grand Paris
Recruiting

http://ift.tt/2CoCIPZ

Non Inferiority Trial of Standard RT Versus Hypofractionated Split Course in Elderly Vulnerable Patients With HNSCC

Condition:   Head and Neck Squamous Cell Carcinoma
Interventions:   Radiation: Standard RT;   Radiation: Hypofractionated RT
Sponsors:   Groupe Oncologie Radiotherapie Tete et Cou;   Gustave Roussy, Cancer Campus, Grand Paris
Recruiting

http://ift.tt/2CoCIPZ

Multi-Channel Multi-Scale Fully Convolutional Network for 3D Perivascular Spaces Segmentation in 7T MR Images

Publication date: Available online 27 February 2018
Source:Medical Image Analysis
Author(s): Chunfeng Lian, Jun Zhang, Mingxia Liu, Xiaopeng Zong, Sheng-Che Hung, Weili Lin, Dinggang Shen
Accurate segmentation of perivascular spaces (PVSs) is an important step for quantitative study of PVS morphology. However, since PVSs are the thin tubular structures with relatively low contrast and also the number of PVSs is often large, it is challenging and time-consuming for manual delineation of PVSs. Although several automatic/semi-automatic methods, especially the traditional learning-based approaches, have been proposed for segmentation of 3D PVSs, their performance often depends on the hand-crafted image features, as well as sophisticated preprocessing operations prior to segmentation (e.g., specially defined regions-of-interest (ROIs)). In this paper, a novel fully convolutional neural network (FCN) with no requirement of any specified hand-crafted features and ROIs is proposed for efficient segmentation of PVSs. Particularly, the original T2-weighted 7T magnetic resonance (MR) images are first filtered via a non-local Haar-transform-based line singularity representation method to enhance the thin tubular structures. Both the original and enhanced MR images are used as multi-channel inputs to complementarily provide detailed image information and enhanced tubular structural information for the localization of PVSs. Multi-scale features are then automatically learned to characterize the spatial associations between PVSs and adjacent brain tissues. Finally, the produced PVS probability maps are recursively loaded into the network as an additional channel of inputs to provide the auxiliary contextual information for further refining the segmentation results. The proposed multi-channel multi-scale FCN has been evaluated on the 7T brain MR images scanned from 20 subjects. The experimental results show its superior performance compared with several state-of-the-art methods.

Graphical abstract

image


http://ift.tt/2oyttEz

Enhancing denitrification with waste sludge carbon source: the substrate metabolism process and mechanisms

Abstract

Using waste sludge internal carbon source for nitrogen removal in wastewater has drawn much attention, due to its economic advantages and sludge reduction. In this study, the performance of enhanced denitrification with waste sludge thermal hydrolysate and fermentation liquid as carbon sources at different SCOD/N (soluble chemical oxygen demand/NO3--N) was investigated. The optimum SCOD/N was 8 for sludge thermal hydrolysate and 7 for fermentation liquid, with NO3--N removal efficiency of 92.3 and 98.9%, respectively, and no NO2--N accumulation. To further understand the fate of sludge carbon source during denitrification, the changes of SCOD, proteins, carbohydrates, and volatile fatty acids (VFAs) were analyzed, and three-dimensional fluorescence excitation-emission matrix (EEM) spectroscopy with fluorescence regional integration (FRI) analysis was introduced. The utilization of SCOD was consistent with NO3--N reduction, and the utilization efficiency of different organic matter was as follows: VFAs > proteins > carbohydrates. The soluble organic-like materials (region IV) were the most readily utilized organic matter according to three-dimensional fluorescence EEM spectroscopy. Regarding denitrification mechanisms, the denitrification rate (VDN), denitrification potential (PDN), heterotroph anoxic yield (YH), and the most readily biodegradable COD (SS) were also investigated.



http://ift.tt/2CMgSla

Fluorinated waste and firefighting activities: biodegradation of hydrocarbons from petrochemical refinery soil co-contaminated with halogenated foams

Abstract

Perfluorinated compounds, including fluorotelomers, are important constituents of firefighting foams to extinguish fuel fires in the petrochemical industry, airports, and at fire-training sites. In this study, we monitored the biodegradation process in a co-contamination scenario with monoaromatic hydrocarbons commonly found in fuels (benzene, toluene) and fluorotelomers. The CO2 production rates were evaluated by a factorial design taking into account the effect of seasonality at in situ natural attenuation processes. Headspace analysis by gas chromatography with a thermal conductivity detector (GC-TCD) was applied to detect CO2 production, whereas monoaromatics were analyzed by gas chromatography coupled to mass spectrometry (GC–MS). According to our results, seasonality had a detectable effect during summer, yielding different CO2 production rates. Higher temperatures increased CO2 production rate, while higher concentrations of fluorotelomer inhibited the biodegradation process. On average, benzene and toluene were depleted 17.5 days earlier in control assays without fluorotelomers. Toluene removal efficiency was also notably higher than benzene. The noticeable decrease in degradation rates of monoaromatics was caused by perfluorinated compounds that are possibly linked to metabolic inhibition mechanisms. Fluorotelomer diminished catabolism in all of our batch cultures. In addition to this, an alternative production of by-products could be detected. Thus, we propose that transient components of the benzene and toluene degradation may be differentially formed, causing the benzene, toluene, and perfluorinated co-contaminations to go through switched metabolic stages under the presence of fluoride in a contamination scenario.



http://ift.tt/2EVDXIb

Polycyclic aromatic hydrocarbons in a bakery indoor air: trends, dynamics, and dispersion

Abstract

Indoor air pollution assessment in work environments remains challenging due to a combination of logistic reasons and availability of costly instrumentation for data acquisition and post-processing. Existing literature focuses on energy production environments, hospitals, and less so on food production spaces. Studies on indoor air quality in bakeries are scarce or even absent. Motivated by this, the present study investigates indoor air quality in a bakery located in Bari province in South Italy, using a combination of approaches including analytical chemistry analyses and computational fluid dynamics to reconstruct the air ventilation in response to air temperature gradients within the working environment. PM2.5 indoor samplings were collected every 6 h from 7 to 19 April 2013 in the proximity of two bakery ovens powered by gas and wood, respectively. For each sampling day, 4 PM2.5 samples were collected: from 3:00 to 9:00 h (first), from 9:00 to 13:30 h (second), from 14:00 to 21:00 h (third), and from 21:00 to 3:00 h (fourth). In total, 40 samples were collected. On each sample, several polycyclic aromatic hydrocarbons (PAHs) were determined such as benzo[a]anthracene (228), benzo[b]fluoranthene (252), benzo[k]fluoranthene (252), benzo[a]pyrene (252), benzo[g,h,i]perylene (276), indeno[1,2,3-cd]pyrene (276), and dibenzo[a,h]anthracene (278), the main compounds of 16 priority US Environmental Protection Agency (US-EPA) PAHs in particulate phase. The PAH mean concentrations showed higher values during the first (from 3:00 to 9:00 h) and fourth (from 21:00 to 3:00 h) sampling intervals than the other two with benzo[a]pyrene mean values exceeding the Italian law limit of 1 ng/m3. Taking into account benzo[a]pyrene mean concentration for the first interval and the first plus the second one, which are the hours with the largest working activity, we have estimated that the baker and co-workers are exposed to a cancer risk of 4.3 × 10−7 and 5.8 × 10−7, respectively (these values are lower than US-EPA recommended guideline of 10−6). Our study was complemented by numerical analyses using state-of-the-art computational fluid dynamics to reconstruct at high resolution air movement from the various working places, i.e., the bakery and the selling area which were connected via a door. The numerical simulations were possible given that surface temperature using infrared thermography as well as air temperature was continuously recorded throughout the sampling acquisition. The use of this approach allowed us to estimate the transport and diffusion of benzo[a]pyrene from one area to the other thus complementing the point sampling information. Computational fluid dynamic simulation results confirm the presence of benzo[a]pyrene in the laboratory as obtained from the measurements and suggests its presence in the sales' area of the bakery with concentrations similar those found in the laboratory.



http://ift.tt/2CMgJ16

Second Annual Go Red for Women Issue.

Author: Reimold, Sharon C. MD; Hill, Joseph A. MD, PhD
Page: 761-762


http://ift.tt/2BQHXXw

Redressing the Red Dress: Rethinking the Campaign.

Author: Zwas, Donna R. MD, MPH
Page: 763-765


http://ift.tt/2EVkYxn

Poorly Understood Maternal Risks of Pregnancy in Women With Heart Disease.

Author: Florio, Karen DO; Daming, Tara Banaszek MD; Grodzinsky, Anna MD, MSc
Page: 766-768


http://ift.tt/2BUM05r

Who Resembles a Scientific Leader-Jack or Jill?: How Implicit Bias Could Influence Research Grant Funding.

Author: Kolehmainen, Christine MD, MS; Carnes, Molly MD, MS
Page: 769-770


http://ift.tt/2oypsQv

Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization: Results From the STICH Trial (Surgical Treatment for Ischemic Heart Failure).

Author: Pina, Ileana L. MD, MPH; Zheng, Qi MD, MHS; She, Lilin PhD; Szwed, Hanna MD; Lang, Irene M. MD; Farsky, Pedro S. MD; Castelvecchio, Serenella MD; Biernat, Jolanta MD; Paraforos, Alexandros MD; Kosevic, Dragana MD; Favaloro, Liliana E. MD; Nicolau, Jose C. MD, PhD; Varadarajan, Padmini MD; Velazquez, Eric J. MD; Pai, Ramdas G. MD; Cyrille, Nicole MD; Lee, Kerry L. PhD; Desvigne-Nickens, Patrice MD; On behalf of the STICH Trial Investigators
Page: 771-780


http://ift.tt/2BSLEfy

Sex Differences in the Presentation and Perception of Symptoms Among Young Patients With Myocardial Infarction: Evidence from the VIRGO Study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients).

Author: Lichtman, Judith H. PhD; Leifheit, Erica C. PhD; Safdar, Basmah MD; Bao, Haikun PhD; Krumholz, Harlan M. MD; Lorenze, Nancy P. DNSc; Daneshvar, Mitra MD; Spertus, John A. MD; D'Onofrio, Gail MD
Page: 781-790


http://ift.tt/2EWndAI

Sauce for the Goose Versus Sauce for the Gander: Should Men and Women Play the Same Game But With Different Rules?.

Author: Wenger, Nanette K. MD
Page: 791-793


http://ift.tt/2BTqf5V

Mental Stress-Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction: Sex Differences and Mechanisms.

Author: Vaccarino, Viola MD, PhD; Sullivan, Samaah PhD; Hammadah, Muhammad MD; Wilmot, Kobina MD; Al Mheid, Ibhar MD; Ramadan, Ronnie MD; Elon, Lisa MS, MPH; Pimple, Pratik M. MBBS, MPH; Garcia, Ernest V. PhD; Nye, Jonathon PhD; Shah, Amit J. MD, MSCR; Alkhoder, Ayman MD; Levantsevych, Oleksiy MD; Gay, Hawkins MD; Obideen, Malik MD; Huang, Minxuan MPH; Lewis, Tene T. PhD; Bremner, J. Douglas MD; Quyyumi, Arshed A. MD; Raggi, Paolo MD
Page: 794-805


http://ift.tt/2osIOXc

Pregnancy Outcomes in Women With Rheumatic Mitral Valve Disease: Results From the Registry of Pregnancy and Cardiac Disease.

Author: van Hagen, Iris M. MD, PhD; Thorne, Sara A. MD; Taha, Nasser MD; Youssef, Ghada MD; Elnagar, Amro MD; Gabriel, Harald MD; ElRakshy, Yahia MD; Iung, Bernard MD; Johnson, Mark R. MD, PhD; Hall, Roger MD; Roos-Hesselink, Jolien W. MD, PhD; On behalf of the ROPAC Investigators and EORP Team
Page: 806-816


http://ift.tt/2BSJ215

Rheumatic Heart Disease in Pregnancy: Global Challenges and Clear Opportunities.

Author: French, Katharine A. MD; Poppas, Athena MD
Page: 817-819


http://ift.tt/2osQHf2

Genetics, Lifestyle, and Low-Density Lipoprotein Cholesterol in Young and Apparently Healthy Women.

Author: Balder, Jan-Willem BSc ,,*; Rimbert, Antoine PhD ,*; Zhang, Xiang MSc; Viel, Martijn BSc; Kanninga, Roan BSc; van Dijk, Freerk BSc; Lansberg, Peter MD, PhD; Sinke, Richard PhD; Kuivenhoven, Jan Albert PhD
Page: 820-831


http://ift.tt/2BSQ0TJ

Female Sex Is a Risk Modifier Rather Than a Risk Factor for Stroke in Atrial Fibrillation: Should We Use a CHA2DS2-VA Score Rather Than CHA2DS2-VASc?.

Author: Nielsen, Peter Bronnum MSc, PhD; Skjoth, Flemming MSc, PhD; Overvad, Thure Filskov MD, PhD; Larsen, Torben Bjerregaard MD, PhD; Lip, Gregory Y. H. MD
Page: 832-840


http://ift.tt/2ETfTps

Metabolic Predictors of Incident Coronary Heart Disease in Women.

Author: Paynter, Nina P. PhD; Balasubramanian, Raji ScD; Giulianini, Franco PhD; Wang, Dong D. MD, DSc; Tinker, Lesley F. PhD; Gopal, Shuba PhD; Deik, Amy A. BA; Bullock, Kevin MS; Pierce, Kerry A. MLA; Scott, Justin BS; Martinez-Gonzalez, Miguel A. MD, PhD, MPH; Estruch, Ramon MD, PhD; Manson, JoAnn E. MD, DrPH; Cook, Nancy R. ScD; Albert, Christine M. MD, MPH; Clish, Clary B. PhD; Rexrode, Kathryn M. MD, MPH
Page: 841-853


http://ift.tt/2BPLdCJ

Gender/Sex as a Social Determinant of Cardiovascular Risk.

Author: O'Neil, Adrienne PhD; Scovelle, Anna J. BPsych (Hons); Milner, Allison J. PhD; Kavanagh, Anne PhD
Page: 854-864


http://ift.tt/2osvsdm

Association of Spontaneous Preterm Delivery and Future Maternal Cardiovascular Disease.

Author: Minissian, Margo B. PhD; Kilpatrick, Sarah MD, PhD; Eastwood, Jo-Ann PhD; Robbins, Wendie A. PhD; Accortt, Eynav E. PhD; Wei, Janet MD; Shufelt, Chrisandra L. MD, MS; Doering, Lynn V. PhD; Merz, C. Noel Bairey MD
Page: 865-871


http://ift.tt/2BSLvZy

Women Not Receiving Optimal Preventive Medications.

Author: Kuehn, Bridget M. MSJ
Page: 872-873


http://ift.tt/2osIXK6

Myocardial Scar Is Prevalent and Associated With Subclinical Myocardial Dysfunction in Women With Suspected Ischemia But No Obstructive Coronary Artery Disease: From the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Study.

Author: Wei, Janet MD; Bakir, May MD; Darounian, Navid MD; Li, Quanlin MS; Landes, Sofy MD; Mehta, Puja K. MD; Shufelt, Chrisandra L. MD; Handberg, Eileen M. PhD; Kelsey, Sheryl F. MD; Sopko, George MD; Pepine, Carl J. MD; Petersen, John W. MD; Berman, Daniel S. MD; Thomson, Louise E.J. MBChB; Bairey Merz, C. Noel MD
Page: 874-876


http://ift.tt/2BR5c3Y

Prevalence of Subclinical Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography in 45- to 55-Year-Old Women With a History of Preeclampsia.

Author: Zoet, Gerbrand A. MD, PhD; Benschop, Laura MD; Boersma, Eric MD, PhD; Budde, Ricardo P.J. MD, PhD; Fauser, Bart C.J.M. MD, PhD; van der Graaf, Yolanda MD, PhD; de Groot, Christianne J.M. MD, PhD; Maas, Angela H.E.M. MD, PhD; Roeters van Lennep, Jeanine E. MD, PhD; Steegers, Eric A.P. MD, PhD; Visseren, Frank L. MD, PhD; van Rijn, Bas B. MD, PhD; Velthuis, Birgitta K. MD, PhD; Franx, Arie MD, PhD; on behalf of the CREW Consortium; Appelman, Yolande E.; Baart, Sara J.; Brouwers, Laura; Cannegieter, Suzanne C.; Dam, Veerle; Eijkemans, M.C.J.; Ferrari, Michel D.; Gunning, Marlise N.; Hoek, Annemieke; Koffijberg, Erik; Koster, M.P.H.; Kruit, Mark; Lagerwij, Giske R.; Lambalk, C.B.; Laven, Joop S.; Linstra, Katie; van der Lugt, Aad; Maassen van den Brink, Antoinette; Meun, Cindy; Middeldorp, Saskia; Moons, Karel G.M.; Roos-Hesselink, Jolien W.; Scheres, Luuk J.J.; Steegers-Theunissen, Regine P.M.; Terwindt, Gisela M.; Wermer, Marieke J.H.
Page: 877-879


http://ift.tt/2EVlmf8

Long-Term Analysis of Sex Differences in Prestigious Authorships in Cardiovascular Research Supported by the National Institutes of Health.

Author: Lerchenmuller, Carolin MD ,,*; Lerchenmueller, Marc J. PhD, MPH ,*; Sorenson, Olav PhD ,*
Page: 880-882


http://ift.tt/2BSLvsw

Cardiovascular Disease and Breast Cancer: Where These Entities Intersect: A Scientific Statement From the American Heart Association.

Author: Mehta, Laxmi S. MD, FAHA, Chair; Watson, Karol E. MD, PhD, FAHA, Vice Chair; Barac, Ana MD, PhD; Beckie, Theresa M. PhD, FAHA; Bittner, Vera MD, MSPH, FAHA; Cruz-Flores, Salvador MD, MPH, FAHA; Dent, Susan MD; Kondapalli, Lavanya MD; Ky, Bonnie MD, MSCE; Okwuosa, Tochukwu DO; Pina, Ileana L. MD, MPH, FAHA; Volgman, Annabelle Santos MD, FAHA; On behalf of the American Heart Association Cardiovascular Disease in Women and Special Populations Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research
Page: e30-e66


http://ift.tt/2ERlT1I

Osteotomies and autografted artificial dermal substitute over bone marrow in a bone-deep burn in an elder patient: An alternative to amputation

Abstract

In this report, we describe the case of an elder patient who suffered a third-degree fire burn with extensive bone affection and exposure of both tibias. The usual treatment strategy for this type of case would have been amputation, or the performance of a multiple free flap surgery. Notwithstanding taking into account the age and the functional objectives for this patient, the multiple free flap option was disregarded. Therefore, we performed an original limb salvage procedure which consisted in bilateral anterior tibial cortex osteotomies and direct grafting over bone marrow, applying skin grafts over a monolayer artificial dermal substitute (Integra®), covered by a negative pressure therapy device. The wound was successfully and early covered, preventing the patient from the long hospital stay and derived complications that other coverage strategies would have carried.

Level of Evidence: Level V, therapeutic study.



http://ift.tt/2t1enfg

Management of nipple-areola complex ischemia after breast reduction: A systematic literature review and algorithm proposal

Abstract

Background

Rare and dreaded, necrosis of the nipple-areola complex (NAC) is one of the major complications of breast reduction surgery. Our objective was to establish a management algorithm summarizing the different possible treatments reported in the literature.

Methods

The data extracted from the articles selected for this literature review covered surgical techniques, frequency of NAC necrosis, type of necrosis, and management proposed for women who have had this surgery for macromastia.

Results

In the 54 articles finally selected, the mean frequency of NAC necrosis was 5.1%. The risk factors for necrosis were the weight of the tissue resected, smoking, obesity, the surgical technique used, and stretch marks. The treatments proposed were listed according to four categories of issues: patient-specific susceptibility, type of breast, surgical technique, and its technical performance.

Conclusions

No consensus exists about the management of NAC necrosis, which remains a complication feared by surgeons. We propose a management algorithm that simplifies the therapeutic indications.

Level of Evidence: Not ratable



http://ift.tt/2Cp9hgQ

Near-infrared fluorescence image-guidance in plastic surgery: A systematic review

Abstract

Background

Near-infrared fluorescence (NIRF) imaging technique, after administration of contrast agents with fluorescent characteristics in the near-infrared (700–900 nm) range, is considered to possess great potential for the future of plastic surgery, given its capacity for perioperative, real-time anatomical guidance and identification. This study aimed to provide a comprehensive literature review concerning current and potential future applications of NIRF imaging in plastic surgery, thereby guiding future research.

Methods

A systematic literature search was performed in databases of Cochrane Library CENTRAL, MEDLINE, and EMBASE (last search Oct 2017) regarding NIRF imaging in plastic surgery. Identified articles were screened and checked for eligibility by two authors independently.

Results

Forty-eight selected studies included 1166 animal/human subjects in total. NIRF imaging was described for a variety of (pre)clinical applications in plastic surgery. Thirty-two articles used NIRF angiography, i.e., vascular imaging after intravenous dye administration. Ten articles reported on NIRF lymphography after subcutaneous dye administration. Although currently most applied, general protocols for dosage and timing of dye administration for NIRF angiography and lymphography are still lacking. Three articles applied NIRF to detect nerve injury, and another three studies described other novel applications in plastic surgery.

Conclusions

Future standard implementation of novel intraoperative optical techniques, such as NIRF imaging, could significantly contribute to perioperative anatomy guidance and facilitate critical decision-making in plastic surgical procedures. Further investigation (i.e., large multicenter randomized controlled trials) is mandatory to establish the true value of this innovative surgical imaging technique in standard clinical practice and to aid in forming consensus on protocols for general use.

Level of Evidence: Not ratable



http://ift.tt/2sXaWX7

The presence of tumor extrachomosomal circular DNA (ecDNA) as a component of liquid biopsy in blood

S03069877.gif

Publication date: Available online 26 February 2018
Source:Medical Hypotheses
Author(s): Fatemeh Khatami, Bagher Larijani, Seyed Mohammad Tavangar
In molecular biology covalently closed circular DNAsare able to passthrough double layer of eukaryotic cellular membrane. Very recently the presence of circular extra chromosomal DNA (ecDNA) has been shown which are different in seventeen different types of cancers. In fact, ecDNA are the tricky way of oncogenes to increase their copy number. We hypothesis the presence of ecDNA in the blood of cancer patients as a subpopulation of liquid biopsy. On the occasion of their presence in blood they will be very beneficial to cover the small amount of cell frees DNA (cfDNA). Isolation and characterization of ecDNA will be possible by a sensitive method entitled Circle-Seq. The origin of tumor more than its prognosis and diagnosis will be possible in the easiest way by using ecDNA.



http://ift.tt/2EZFxVy

Role of Apolipoprotein E in the tangled mystery of pain

S03069877.gif

Publication date: Available online 26 February 2018
Source:Medical Hypotheses
Author(s): Harjot Dhillon, Sargun Singh
Pain is one of the common and debilitating manifestations associated with the majority of diseased conditions, making it a serious health concern worldwide. While trying to decipher the cryptic mechanism of pain in hope to provide better gene-based therapeutics, researchers have concluded pain to be of multigenic origin.Apolipoprotein E is a protein coded by APOE gene containing 4 exons, located on chromosome 19q13.2. It is among the key regulators of various crucial body functions such as lipid transport, apoptosis, vitamin k pathway, and cognition, hence, it is highly suspected to play a pivotal role in the nociception process. However, very few studies have tried and succeeded to find a direct involvement of APOE in pain processing.The current article attempts to throw light on some of the major clinical research findings strengthens the hypothesis stating that Apolipoprotein E has a deeply embedded association with the pain regulating pathways, through several underlying physiological, biochemical and neurological processes, that in turn, decide the fate of pain in a complex manner.



http://ift.tt/2FywLPa

Seminal cell-free DNA molecular profile as a tool to discover novel diagnostic and prognostic prostate cancer biomarkers.

alertIcon.gif

Publication date: Available online 26 February 2018
Source:Medical Hypotheses
Author(s): G. Ponti, M. Maccaferri, M. Manfredini, M. Cotugno, G. Pellacani, A. Conti, S. Micali, M. Mandrioli, A. Tomasi




http://ift.tt/2EZdtBH

Optimise the microbial flora with milk and yoghurt to prevent disease.

S03069877.gif

Publication date: Available online 26 February 2018
Source:Medical Hypotheses
Author(s): James A Morris
Pathogenic bacteria, which are temporary or permanent members of our microbial flora, cause or contribute to a wide range of human disease at all ages. Conditions include Alzheimer's disease, atherosclerosis, diabetes mellitus, obesity, cancer, autoimmunity and psychosis, amongst others. The mechanism of damage is inflammation which can be chronic or acute. An optimal microbial flora includes a wide range of pathogenic bacteria in low dose. This allows specific immunity to be developed and maintained with minimal inflammatory damage. Human milk has evolved to deliver an optimal microbial flora to the infant. Cow's milk has the potential, following appropriate fortification, to maintain an optimal human microbial flora throughout life. Yoghurt is a fermented milk product in which bacteria normally present in milk convert sugars to lactic acid. The acid suppresses the growth of pathogens in the oral cavity, oropharynx and oesophagus. Thus yoghurt can restore an optimal flora in these regions in the short term. Since bacteria are transported between epithelial surfaces, yoghurt will also optimise the flora elsewhere. The judicious use of milk and yogurt could prevent a high proportion of human disease.



http://ift.tt/2FAG7tN

Up-regulated MiR-27-3p promotes the G1-S phase transition by targeting inhibitor of growth family member 5 in osteosarcoma

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Pei Ye, Xueping Ke, Xuehui Zang, Hui Sun, Zhixing Dong, Jun Lin, Lihui Wang, Wenzhou Liu, Guiqiang Miao, Yongtao Tan, Weilai Tong, Haichang Xiao, Lihua Gao
ObjectiveMicroRNAs (miRNAs) play an essential role in regulating malignant progression of tumour cells by inhibiting translation or stability of messenger RNA. However, the expression pattern and regulatory mechanism of miR-27-3p in osteosarcoma remains unclear.MethodsWe examined the expression of miR-27-3p in 5 osteosarcoma cell lines compared with that in 2 normal osteocyte cell lines. Osteosarcoma cells U-2OS and MG-63 were transduced to up-regulate or down-regulate the expression of miR-27-3p. The 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide, or MTT, assay, colony formation assays, BrdUrd labelling, immunofluorescence, anchorage-independent growth ability assay and flow cytometry analysis were used to test the effect of miR-27-3p. Luciferase assays were added to verify the direct relationship between miR-27-3p and the predicted target gene inhibitor of growth family member 5 (ING5).ResultsThe expression of miR-27-3p was significantly increased in examined osteosarcoma cell lines compared with that in normal osteocyte cell lines. Up-regulation of miR-27-3p significantly accelerated osteosarcoma cell growth via promoting G1-S transition. In addition, the opposite result was observed in miR-27-3p-down-regulated cells. Up-regulation of ING5 significantly attenuated the miR-27-3p-induced proliferation in osteosarcoma cells.ConclusionsThese data suggested that miR-27-3p could promote the G1-S phase transition that leads to proliferation by down-regulating the expression of ING5 in osteosarcoma.

Graphical abstract

image


http://ift.tt/2t0SjRS

Abiraterone acetate in the treatment of prostate cancer

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Abhimanyu Thakur, Aishwarya Roy, Arijit Ghosh, Mohit Chhabra, Sugato Banerjee




http://ift.tt/2Cqk61W

Polysaccharide isolated from Aloe vera gel suppresses ovalbumin-induced food allergy through inhibition of Th2 immunity in mice

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Dajeong Lee, Hyuk Soon Kim, Eunju Shin, Seon-Gil Do, Chong-Kil Lee, Young Mi Kim, Min Bum Lee, Keun Young Min, Jimo Koo, Su Jeong Kim, Seung Taek Nam, Hyun Woo Kim, Young Hwan Park, Wahn Soo Choi
An allergic reaction occurs when the immune system overreacts to harmless substance called allergen that gains access to the body. Food allergy is a hypersensitive immune reaction to food proteins and the number of patients with food allergy has recently increased. Aloe Vera is used for wellness and medicinal purposes. In particular, Aloe vera has been reported to enhance immunity. However, the effect of Aloe vera on food allergy is not yet known. In this study, we investigated the effects of processed Aloe vera gel (PAG) containing low molecular weight Aloe polysaccharide (AP) on ovalbumin (OVA)-induced food allergy in mice. Allergic symptoms, rectal temperature, and diarrhea were measured in OVA-induced food allergy mice. Other allergic parameters were also analyzed by RT-PCR, ELISA, flow cytometry, and other biochemical methods. As the results, PAG suppressed the decrease of body temperature, diarrhea, and allergic symptoms in OVA-induced food allergy mice. PAG also reduced serum concentrations of type 2 helper T cell (Th2) cytokines (Interleukin-(IL)-4, IL-5, and IL-13) as well as histamine, mast cell protease-1 (MCP-1), and immunoglobulin (Ig)E. PAG blocked the degranulation of mast cells and infiltration of eosinophils in intestine. Furthermore, PAG suppressed the population of Th2 cells in spleen and mesenteric lymph nodes. PAG also increased the production of IL-10 and population of type 1 regulatory T (Tr1) cells in mice with food allergy. Taken together, our findings suggest that PAG suppressed Th2 immune responses through, at least partially, stimulating the secretion of IL-10 in food allergy mice.

Graphical abstract

image


http://ift.tt/2sVIRPP

Prevention of doxorubicin (DOX)-induced genotoxicity and cardiotoxicity: Effect of plant derived small molecule indole-3-carbinol (I3C) on oxidative stress and inflammation

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Subhadip Hajra, Arup Ranjan Patra, Abhishek Basu, Sudin Bhattacharya
Doxorubicin (DOX) is an anthracycline group of antibiotic available for the treatment of broad spectrum of human cancers. However, patient receiving DOX-therapy, myelosuppression and genotoxicity which may lead to secondary malignancy and dose dependent cardiotoxicity is an imperative adverse effect. Mechanisms behind the DOX-induced toxicities are increased level of oxidative damage, inflammation and apoptosis. Therefore, in search of a potential chemoprotectant, naturally occurring glucosinolate breakdown product Indole-3-Carbinol (I3C) was evaluated against DOX-induced toxicities in Swiss albino mice. DOX was administered (5 mg/kg b.w., i.p.) and I3C was administered (20 mg/kg b.w., p.o.) in concomitant and 15 days pretreatment schedule. Results of the present study showed that I3C appreciably mitigated DOX-induced chromosomal aberrations, micronuclei formation, DNA damage and apoptosis in bone marrow niche. Histopathological observations revealed that DOX-intoxication resulted in massive structural and functional impairment of heart and bone marrow niche. However, oral administration of I3C significantly attenuated DOX-induced oxidative stress in the cardiac tissues as evident from decreased levels of ROS/RNS and lipid peroxidation, and by increased level of glutathione (reduced) and the activity of phase-II antioxidant enzymes. Additionally, administration of I3C significantly (P < 0.05) stimulated Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of cytoprotective proteins heme oxygenase 1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO1) and GSTπ in bone marrow and cardiac tissues. In connection with that, I3C significantly attenuated DOX-induced inflammation by downregulation of pro-inflammatory mediators, viz., NF-kβ(p50), iNOS, COX-2 and IL-6 expression. Moreover, I3C attenuate DOX-induced apoptosis by up-regulation of Bcl2 and down-regulation of Bax and caspase-3 expression in bone marrow cells. Thus, this study suggests that I3C has promising chemoprotective efficacy against DOX-induced toxicities and indicates its future use as an adjuvant in chemotherapy.



http://ift.tt/2F8yIny

MiR-133a/133b inhibits Treg differentiation in IgA nephropathy through targeting FOXP3

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Ling-Wei Jin, Han-Yang Ye, Xiao-Yan Xu, Yu Zheng, Yan Chen
ObjectiveThe aim of this study was to investigate the effect of miR-133a and miR-133b on regulatory T cell (Treg) differentiation in IgA nephropathy (IgAN) through targeting forkhead box P3 (FOXP3).MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from IgAN patients (n = 20) and healthy controls (n = 20). Percentage of Tregs defined as CD4 + CD25 + FOXP3 + T cells were determined by flow cytometry. The mRNA expression levels of miR-133a, miR-133b and FOXP3 were measured by real-time PCR. FOXP3 protein level was analyzed by western blotting.ResultsTregs percentage in PBMCs of IgAN patients was significantly lower than that of healthy controls, whereas the expression levels of miR-133a and miR-133b in IgAN patients were dramatically higher than that in the control group. Treg percentage was negatively correlated with miR-133a and miR-133b expressions. Meanwhile, miR-133a and miR-133b modulated FOXP3 expression by detecting of its gene 3′-untranslated region. MiR-133a or miR-133b overexpression significantly decreased the % Tregs (CD4 + CD25 + FOXP3+) of the total CD4 + T cells while miR-133a or miR-133b knockdown led to an opposite effect. Moreover, FOXP3 levels in IgAN patients was significantly lower than that in the control group and was negatively correlated with miR-133a and miR-133b expression.ConclusionMiR-133a and miR-133b inhibited Treg differentiation in IgA nephropathy through targeting FOXP3.



http://ift.tt/2sXTK3r

Commentary on the paper: “efficacy of a novel strategy for poststernotomy deep sternal infection after thoracic aorta replacement using a prosthetic graft”

Deep sternal wound infections and especially sternal osteomyelitis and mediastinitis in post cardiac surgery still remains a plastic surgical challenge because the reconstructive procedure is extremely intertwined with human physiology. This is in part due to the typically existing multiple co-morbidities in patients afflicted with this complication in addition to the thoracic defect. Since in most cases the thoracic vessels on either one or both sides have been harvested for cardiac revascularization there is the problem of a diminished local peristernal microcirculation 1 .

http://ift.tt/2sZLYGs

PD-L1, B7-H3, and PD-1 expression in immunocompetent vs. immunosuppressed patients with cutaneous squamous cell carcinoma

Abstract

Background

To characterize the expression of co-signaling molecules PD-L1, PD-1, and B7-H3 in cutaneous squamous cell carcinoma (cSCC) by immune status.

Methods

We retrospectively analyzed 66 cases of cSCC treated with surgical resection from 2012 to 2015. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (Tum-PD-L1%), B7-H3 (Tum-B7-H3%), density of peri and intratumoral CD8 T cells (CD8 density), proportion of CD8 T cells expressing PD-1 (CD8-PD-1%) and of tumor-infiltrating immune cells (TII) expressing PD-L1 (TII-PD-L1%).

Results

Of 66 cases, 42 were immunocompetent, 24 immunosuppressed (13 organ transplant, 8 HIV+, 3 other). Defining positive expression at > 5%, 26% of tumors were positive for PD-L1, 85% for B7-H3, 80% had CD8 T cells that expressed PD-1 and 55% had TII that expressed PD-L1. Tum-B7-H3% was significantly higher (median 60 vs. 28%, p = 0.025) in immunocompetent vs. immunosuppressed patients, including when factoring in cause of immunosuppression. No significant difference in Tum-PD-L1%, TII-PD-L1%, CD8 density, or CD8-PD-1% was observed. Tumors from HIV+ patients lacked PD-L1 expression, and had lower B7-H3% (median 2.5 vs. 60%, p = 0.007), and higher CD8 density (median 75% vs. 40%, p = 0.04) compared to immunocompetent patients. Higher tumor grade (Rs = 0.34, p = 0.006) and LVI (Rs = 0.61, p < 0.001) were both associated with higher Tum-PD-L1%.

Conclusion

cSCC showed expression of PD-L1 on tumor in 26% of cases, and high tumor B7-H3 expression (85%) and PD-1 expression on CD8 TILs (80%). Tumor B7-H3 expression was significantly higher in immunocompetent vs. immunosuppressed patients, largely driven by very low expression in HIV+ patients.



http://ift.tt/2F7Yet7

Editors, contents and cover information

Publication date: March 2018
Source:Trends in Biochemical Sciences, Volume 43, Issue 3





http://ift.tt/2EYx8l2

Risk of thromboembolic events in patients treated with thalidomide for cutaneous lupus erythematosus: a multicenter-retrospective study



http://ift.tt/2F5nal5

Air pollution from industrial waste gas emissions is associated with cancer incidences in Shanghai, China

Abstract

Outdoor air pollution may be associated with cancer risk at different sites. This study sought to investigate outdoor air pollution from waste gas emission effects on multiple cancer incidences in a retrospective population-based study in Shanghai, China. Trends in cancer incidence for males and females and trends in waste gas emissions for the total waste gas, industrial waste gas, other waste gas, SO2, and soot were investigated between 1983 and 2010 in Shanghai, China. Regression models after adjusting for confounding variables were constructed to estimate associations between waste gas emissions and multiple cancer incidences in the whole group and stratified by sex, Engel coefficient, life expectancy, and number of doctors per 10,000 populations to further explore whether changes of waste gas emissions were associated with multiple cancer incidences. More than 550,000 new cancer patients were enrolled and reviewed. Upward trends in multiple cancer incidences for males and females and in waste gas emissions were observed from 1983 to 2010 in Shanghai, China. Waste gas emissions came mainly from industrial waste gas. Waste gas emissions was significantly positively associated with cancer incidence of salivary gland, small intestine, colorectal, anus, gallbladder, thoracic organs, connective and soft tissue, prostate, kidney, bladder, thyroid, non-Hodgkin's lymphoma, lymphatic leukemia, myeloid leukemia, and other unspecified sites (all p < 0.05). Negative association between waste gas emissions and the esophagus cancer incidence was observed (p < 0.05). The results of the whole group were basically consistent with the results of the stratified analysis. The results from this retrospective population-based study suggest ambient air pollution from waste gas emissions was associated with multiple cancer incidences.



http://ift.tt/2F5nK2i

Fate of perfluorooctanoic acid (PFOA) in sewage sludge during microwave-assisted persulfate oxidation treatment

Abstract

The fate of perfluorooctanoic acid (PFOA) has been investigated for an emerging sludge treatment technique using microwave heating-assisted persulfate (PS) oxidation. The effect of heating temperature (20, 50, and 70 °C) and PS dose (PS1: 0.01; PS2: 0.1; PS3: 0.2 g/g wet sludge) was studied in sludge spiked with PFOA at an environmentally relevant concentration (200 ng/g wet weight). Control degradation experiments using spiked sludge without PS addition and background sludge (no PFOA spike) with PS addition were also conducted at each temperature. Sludge samples were analyzed for eight perfluorocarboxylic acids (PFCAs) (C4 – C11) using LC-MS/MS. At 20 °C (PS2 dose), minimal (~ 5%) removal of the spiked PFOA was observed after 72 h, suggesting the need for elevated treatment temperature. For the same PS dose (0.1 g /g sludge), treatment at 50 and 70 °C showed a decrease in PFOA concentration with increasing temperature, with ~ 28 and ~ 42% removal following 4 h of treatment. No significant increase in degradation was observed for the highest dose (PS3) after 2 h, possibly indicating self-scavenging of PS at high dosage. Due to the low initial spiking concentration of PFOA and low extraction recovery, all shorter-chain PFCAs (< C8), the degradation products of PFOA, were below quantification limits in all sludge samples.



http://ift.tt/2CNsPHy

Atopic dermatitis is an important comorbidity in severe asthma

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease characterized by pruritus and rash. Severe asthma is another heterogeneous chronic inflammatory disease comprising diverse phenotypic subgroups1. With biologic therapies reflected in the Global Initiative for Asthma 2017 guidelines, it is imperative that all available pertinent information including biomarkers are utilized in selecting the optimal biologic therapy. Recently the term "eosinophilic" asthma has been in vogue due to the availability of anti-IL-5 monoclonal antibody class of medications, mepolizumab, benralizumab, and reslizumab2.

http://ift.tt/2t2mbgU

Treatment of hypereosinophilic syndrome and eosinophilic dermatitis with reslizumab

Hypereosinophilic syndrome (HES) is a rare disease defined by organ damage directly attributable to hypereosinophilia that is either primary (neoplastic), secondary (reactive) or idiopathic. The mainstay of therapy in idiopathic HES centers around systemic steroids, and cytoreduction with hydroxyurea and interferon-alfa in steroid refractory cases. We describe the successful treatment of recalcitrant, idiopathic cutaneous HES with reslizumab, a humanized interleukin-5 blocker.

http://ift.tt/2F7owM7

Bronchiectasis in severe asthma: clinical features and outcomes

Bronchiectasis are increasingly identified in subjects with severe asthma and could contribute to disease severity.

http://ift.tt/2sUgMIy

Carnosine protects pancreatic beta cells and islets against oxidative stress damage

Publication date: Available online 26 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Vitale Miceli, Mariangela Pampalone, Giovanna Frazziano, Giuseppe Grasso, Enrico Rizzarelli, Camillo Ricordi, Anna Casu, Gioacchin Iannolo, Pier Giulio Conaldi
Islet transplantation is a valid therapeutic option for type 1 diabetes treatment. However, in this procedure one of the major problems is the oxidative stress produced during pancreatic islet isolation. The aim of our study was to evaluate potential protective effects of L-carnosine and its isomer D-carnosine against oxidative stress. We evaluated the carnosine effect on cell growth, cell death, insulin production, and the main markers of oxidative stress in rat and murine stressed beta cell lines as well as in human pancreatic islets. Both isomers clearly inhibited hydrogen peroxide induced cytotoxicity, with a decrease in intracellular reactive oxygen and nitrogen species, prevented hydrogen peroxide induced apoptosis/necrosis, nitrite production, and reduced glucose-induced insulin secretion. In addition, NF-κB expression/translocation and nitrated protein induced in stressed cells was significantly reduced. Furthermore, both isomers improved survival and function, and decreased reactive oxygen and nitrogen species, and nitrite and nitrotyrosine production in human islets cultured for 1, 3, and 7 days. These results seem to indicate that both L and D-carnosine have a significant cytoprotective effect by reducing oxidative stress in beta cell lines and human islets, suggesting their potential use to improve islet survival during the islet transplantation procedure.

Graphical abstract

image


http://ift.tt/2EWY1G9

Effects of repeated potassium iodide administration on genes involved in synthesis and secretion of thyroid hormone in adult male rat

S03037207.gif

Publication date: Available online 26 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Dalila Lebsir, Line Manens, Stephane Grison, Philippe Lestaevel, Teni Ebrahimian, David Suhard, Guillaume Phan, Isabelle Dublineau, Karine Tack, Marc Benderitter, Annick Pech, Jean-Rene Jourdain, Maâmar Souidi
BackgroundA single dose of potassium iodide (KI) is recommended to reduce the risk of thyroid cancer during nuclear accidents. However in case of prolonged radioiodine exposure, more than one dose of KI may be necessary. This work aims to evaluate the potential toxic effect of repeated administration of KI.MethodsAdult Wistar rats received an optimal dose of KI 1 mg/kg over a period of 1, 4 or 8 days.Resultshormonal status (TSH, FT4) of treated rats was unaffected. Contrariwise, a sequential Wolff-Chaikoff effect was observed, resulting in a prompt decrease of NIS and MCT8 mRNA expression (−58% and −26% respectively), followed by a delayed decrease of TPO mRNA expression (−33%) in conjunction with a stimulation of PDS mRNA expression (+62%).Conclusionwe show for the first time that repeated administration of KI at 1 mg/kg/24h doesn't cause modification of thyroid hormones level, but leads to a reversible modification of the expression of genes involved in the synthesis and secretion of thyroid hormones.



http://ift.tt/2FxYDTC

Pyrolysis of wastewater sludge and composted organic fines from municipal solid waste: laboratory reactor characterisation and product distribution

Abstract

Sludge from municipal wastewater treatment plants and organic fines from mechanical sorting of municipal solid waste (MSW) are two common widespread waste streams that are becoming increasingly difficult to utilise. Changing perceptions of risk in food production has limited the appeal of sludge use on agricultural land, and outlets via landfilling are diminishing rapidly. These factors have led to interest in thermal conversion technologies whose aim is to recover energy and nutrients from waste while reducing health and environmental risks associated with material re-use. Pyrolysis yields three output products: solid char, liquid oils and gas. Their relative distribution depends on process parameters which can be somewhat optimised depending on the end use of product. The potential of pyrolysis for the conversion of wastewater sludge (SS) and organic fines of MSW (OF) to a combustion gas and a carbon-rich char has been investigated. Pyrolysis of SS and OF was done using a laboratory fixed-bed reactor. Herein, the physical characterisation of the reactor is described, and results on pyrolysis yields are presented. Feedstock and chars have been characterised using standard laboratory methods, and the composition of pyrolysis gases was analysed using micro gas chromatography. Product distribution (char/liquid/gas) from the pyrolysis of sewage sludge and composted MSW fines at 700°C for 10 min were 45/26/29 and 53/14/33%, respectively. The combustible fractions of pyrolysis gases range from 36 to 54% for SS feedstock and 62 to 72% from OF. The corresponding lower heating value range of sampled gases were 11.8–19.1 and 18.2–21.0 MJ m−3, respectively.



http://ift.tt/2ETGBOt

Ascorbic acid protects male rat brain from oral potassium dichromate-induced oxdative DNA damage and apoptotic changes: the expression patterns of caspase-3, P 53, Bax, and Bcl-2 genes

Abstract

Our study designed to study the potential of potassium dichromate (K2Cr2O7) oral exposure to induce damage in male rat brain and to compare the possible protective role of vitamin C (VC) either pre and/or concurrent supply against (K2Cr2O7) induced changes. Thirty male rats were divided into five groups. First control group received distilled water (C), second received 120 mg/kg b.wt (VC), third received 25 mg/kg b.wt K2Cr2O7 (Cr), fourth group received VC together with K2Cr2O7 by the same former doses (VC + Cr), and the fifth group received the same oral doses of VC 2 weeks prior to and along with K2Cr2O7 for 6 weeks (VC + Cr pro/co treated). The obtained results revealed that K2Cr2O7 induced a significant decrease in cholinergic activity, glutathione reductase GR activity, reduced glutathione content GSH and ATP levels. Furthermore, K2Cr2O7 induced a significant increase in oxidative DNA damage indicated by 8-hydroxy 2′-deoxyguanosine (8OH2′dG) and formation of apoptotic DNA ladders, significant increase in malondialdehyde (MDA), protein carbonyl, and lactate dehydrogenase enzyme. Increased mRNA expression of pro-apoptotic genes, including caspase-3, p53, and Bax, unlike Bcl-2 expression, was decreased. K2Cr2O7 increased caspase-3 and decreased Bcl-2 immuno-labeling. VC supply noticeably ameliorates K2Cr2O7-induced changes which were more significantly in VC pro and concurrent supplement rather than VC concurrent supply only. Finally, it is concluded that K2Cr2O7 oral administration induced oxidative apoptotic changes in rat brain and confirms the usefulness of VC pre and concurrent supply for the amelioration of K2Cr2O7-induced events more significantly than VC concurrent supply only.



http://ift.tt/2BSpud6

A Fat Lot of Good for Wound Healing

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4
Author(s): Alessandra Maria Casano, Michael Sixt
The insect's fat body combines metabolic and immunological functions. In this issue of Developmental Cell, Franz et al. (2018) show that in Drosophila, cells of the fat body are not static, but can actively "swim" toward sites of epithelial injury, where they physically clog the wound and locally secrete antimicrobial peptides.

Teaser

The insect's fat body combines metabolic and immunological functions. In this issue of Developmental Cell, Franz et al. (2018) show that in Drosophila, cells of the fat body are not static, but can actively "swim" toward sites of epithelial injury, where they physically clog the wound and locally secrete antimicrobial peptides.


http://ift.tt/2F8exWQ

Organizing Complex Tissue Architecture by Pushing and Pulling Cell Contacts

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4
Author(s): Yixie Zhang, Tony J.C. Harris
Changes to cell shape and interaction drive animal tissue morphogenesis. Reporting now in Developmental Cell, Del Signore et al. (2018) describe active lengthening of cell-cell contacts by Arp2/3-based actin networks. Through cycles of contact lengthening and shortening, the developing Drosophila eye passes through various multicellular configurations to achieve its complex architecture.

Teaser

Changes to cell shape and interaction drive animal tissue morphogenesis. Reporting now in Developmental Cell, Del Signore et al. (2018) describe active lengthening of cell-cell contacts by Arp2/3-based actin networks. Through cycles of contact lengthening and shortening, the developing Drosophila eye passes through various multicellular configurations to achieve its complex architecture.


http://ift.tt/2sZD0ZF

Ultraviolet Rays Light Up Transcriptional Networks Regulating Plant Growth

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4
Author(s): Eirini Kaiserli
Light and hormones tightly regulate plant growth and development by both synergistic and antagonistic actions. In the current issue of Developmental Cell, Liang et al. (2018) uncover how the UV-B photoreceptor UVR8 mediates inhibition of plant growth via direct interactions with key transcriptional regulators of brassinosteroid signaling.

Teaser

Light and hormones tightly regulate plant growth and development by both synergistic and antagonistic actions. In the current issue of Developmental Cell, Liang et al. (2018) uncover how the UV-B photoreceptor UVR8 mediates inhibition of plant growth via direct interactions with key transcriptional regulators of brassinosteroid signaling.


http://ift.tt/2CmP6jl

Dynamic Encoding in the Notch Pathway

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4
Author(s): Sean G. Megason
A small number of signaling pathways are used ubiquitously throughout development. How can enough information be carried through such a small number of channels? Reporting in Cell, Nandagopal et al. (2018) reveal how different Notch ligands can regulate different targets through the same receptor using differences in signaling dynamics.

Teaser

A small number of signaling pathways are used ubiquitously throughout development. How can enough information be carried through such a small number of channels? Reporting in Cell, Nandagopal et al. (2018) reveal how different Notch ligands can regulate different targets through the same receptor using differences in signaling dynamics.


http://ift.tt/2t0Pws5

Ben Barres (1954–2017)

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4
Author(s): Marc Tessier-Lavigne




http://ift.tt/2F4tABb

A Role for Ploidy in Heart Regeneration

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4
Author(s): Zachary A. Kadow, James F. Martin
There is mounting circumstantial evidence that ploidy, a cell's relative DNA content, is in part responsible for the differential cardiac regenerative capacity observed between regenerative and non-regenerative organisms. In this issue of Developmental Cell, González-Rosa et al. (2018) provide direct evidence that polyploid cardiomyocytes have reduced proliferative and regenerative potential.

Teaser

There is mounting circumstantial evidence that ploidy, a cell's relative DNA content, is in part responsible for the differential cardiac regenerative capacity observed between regenerative and non-regenerative organisms. In this issue of Developmental Cell, González-Rosa et al. (2018) provide direct evidence that polyploid cardiomyocytes have reduced proliferative and regenerative potential.


http://ift.tt/2sXva2F

A Tribute to Ben Barres: Remembrances from Barres Lab Members

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4





http://ift.tt/2F5xLwl

Cellular Stress Associated with Aneuploidy

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4
Author(s): Jin Zhu, Hung-Ji Tsai, Molly R. Gordon, Rong Li
Aneuploidy, chromosome stoichiometry that deviates from exact multiples of the haploid compliment of an organism, exists in eukaryotic microbes, several normal human tissues, and the majority of solid tumors. Here, we review the current understanding about the cellular stress states that may result from aneuploidy. The topics of aneuploidy-induced proteotoxic, metabolic, replication, and mitotic stress are assessed in the context of the gene dosage imbalance observed in aneuploid cells. We also highlight emerging findings related to the downstream effects of aneuploidy-induced cellular stress on the immune surveillance against aneuploid cells.

Teaser

Aneuploidy refers to chromosome stoichiometry deviating from exact multiples of the haploid compliment of an organism. Zhu et al. review our current understanding of the cellular stress states that may result from aneuploidy, including proteotoxic, metabolic, replication, and mitotic stress. They also discuss immune surveillance against aneuploid cells.


http://ift.tt/2sYjtJg

Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4
Author(s): Juan Manuel González-Rosa, Michka Sharpe, Dorothy Field, Mark H. Soonpaa, Loren J. Field, Caroline E. Burns, C. Geoffrey Burns
Correlative evidence suggests that polyploidization of heart muscle, which occurs naturally in post-natal mammals, creates a barrier to heart regeneration. Here, we move beyond a correlation by demonstrating that experimental polyploidization of zebrafish cardiomyocytes is sufficient to suppress their proliferative potential during regeneration. Initially, we determined that zebrafish myocardium becomes susceptible to polyploidization upon transient cytokinesis inhibition mediated by dominant-negative Ect2. Using a transgenic strategy, we generated adult animals containing mosaic hearts composed of differentially labeled diploid and polyploid-enriched cardiomyocyte populations. Diploid cardiomyocytes outcompeted their polyploid neighbors in producing regenerated heart muscle. Moreover, hearts composed of equivalent proportions of diploid and polyploid cardiomyocytes failed to regenerate altogether, demonstrating that a critical percentage of diploid cardiomyocytes is required to achieve heart regeneration. Our data identify cardiomyocyte polyploidization as a barrier to heart regeneration and suggest that mobilizing rare diploid cardiomyocytes in the human heart will improve its regenerative capacity.

Graphical abstract

image

Teaser

It remains unclear why certain non-mammalian species efficiently regenerate their hearts while mammals fail in this endeavor. González-Rosa et al. demonstrate that simply increasing the DNA content of the highly regenerative zebrafish myocardium, to more closely resemble that in mammals, is sufficient to dampen cardiomyocyte proliferative capacity and organ regeneration.


http://ift.tt/2Cny6K2

The Polyploid State Plays a Tumor-Suppressive Role in the Liver

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4
Author(s): Shuyuan Zhang, Kejin Zhou, Xin Luo, Lin Li, Ho-Chou Tu, Alfica Sehgal, Liem H. Nguyen, Yu Zhang, Purva Gopal, Branden D. Tarlow, Daniel J. Siegwart, Hao Zhu
Most cells in the liver are polyploid, but the functional role of polyploidy is unknown. Polyploidization occurs through cytokinesis failure and endoreduplication around the time of weaning. To interrogate polyploidy while avoiding irreversible manipulations of essential cell-cycle genes, we developed orthogonal mouse models to transiently and potently alter liver ploidy. Premature weaning, as well as knockdown of E2f8 or Anln, allowed us to toggle between diploid and polyploid states. While there was no detectable impact of ploidy alterations on liver function, metabolism, or regeneration, mice with more polyploid hepatocytes suppressed tumorigenesis and mice with more diploid hepatocytes accelerated tumorigenesis in mutagen- and high-fat-induced models. Mechanistically, the diploid state was more susceptible to Cas9-mediated tumor-suppressor loss but was similarly susceptible to MYC oncogene activation, indicating that polyploidy differentially protected the liver from distinct genomic aberrations. This suggests that polyploidy evolved in part to prevent malignant outcomes of liver injury.

Graphical abstract

image

Teaser

Most liver cells are polyploid, but the functional role of wholesale genome duplications is unknown. To interrogate liver polyploidy function without irreversible manipulations of cell-cycle genes, Zhang et al. developed models to transiently alter ploidy, finding that polyploidy reduces tumor development by buffering against tumor-suppressor loss of heterozygosity.


http://ift.tt/2EVR4Vv

Fat Body Cells Are Motile and Actively Migrate to Wounds to Drive Repair and Prevent Infection

Publication date: 26 February 2018
Source:Developmental Cell, Volume 44, Issue 4
Author(s): Anna Franz, Will Wood, Paul Martin
Adipocytes have many functions in various tissues beyond energy storage, including regulating metabolism, growth, and immunity. However, little is known about their role in wound healing. Here we use live imaging of fat body cells, the equivalent of vertebrate adipocytes in Drosophila, to investigate their potential behaviors and functions following skin wounding. We find that pupal fat body cells are not immotile, as previously presumed, but actively migrate to wounds using an unusual adhesion-independent, actomyosin-driven, peristaltic mode of motility. Once at the wound, fat body cells collaborate with hemocytes, Drosophila macrophages, to clear the wound of cell debris; they also tightly seal the epithelial wound gap and locally release antimicrobial peptides to fight wound infection. Thus, fat body cells are motile cells, enabling them to migrate to wounds to undertake several local functions needed to drive wound repair and prevent infections.

Teaser

Adipocytes and their fly equivalent, fat body cells, have been considered immotile, but Franz et al. now show the latter can actively migrate to wounds using a peristaltic-like "swimming" motility. Once there, they multitask to clear wound cell debris, plug the epithelial gap, and upregulate AMPs to prevent infection.


http://ift.tt/2FAdRaH

Αρχειοθήκη ιστολογίου