Inflammatory chemokines and their receptors in human visceral leishmaniasis: Gene expression profile in peripheral blood, splenic cellular sources and their impact on trafficking of inflammatory cells

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Neetu Singh, Shyam Sundar
Chemokines play an important role in determining cellular composition at inflammatory sites, and as such, influence disease outcome. In this study, we investigated the expression profile and splenic cellular source of various inflammatory chemokines and their receptors in human visceral leishmaniasis (VL). The expression of chemokines or their receptors was measured at the gene and protein level by employing real time qPCR and a cytometric bead array assay, respectively. In addition, the cellular source of chemokines and their receptors in the spleen was identified employing gene expression analyses in sequentially selected cell subsets. We identified elevated expression of CXCL10, CXCL9, CXCL8, and decreased CCL2 from VL patients. Further, we found reduced expression of the chemokine receptors CXCR1, CXCR2, CXCR3 and CCR2, but increased expression of CCR7 on VL PBMC, compared to endemic healthy controls. Additionally, splenic monocytes were found to be the major source of CXCL10, CXCL9 and CCR2, whereas T cells were the main source of CXCR3 and CCR7. We also report a strong association between plasma IFN-γ and CXCL-10, CXCL-9 levels. Enhanced parasite burden positively correlates with increased expression of CXCL10, CXCL9, IFN-γ and IL-10. Overall our result indicates that VL patients have an elevated inflammatory chemokine milieu which correlated with disease severity. However, expression of their chemokine receptors was significantly impaired, which may have contributed to reduced frequencies of blood monocytes and neutrophils in peripheral blood. In contrast, enhanced expression of CCR7 was associated with increased numbers of activated T cells in circulation. These findings highlight the importance of chemokines for recruitment of various cell populations in VL, and the knowledge gained may help in global understandings of the complex interaction between chemokines and pathological processes, and therefore will contribute towards the design of novel chemokine based immunological therapies against VL.

Graphical abstract

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Hereditary C1 inhibitor deficiency is associated with high spontaneous amidase activity

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Delphine Charignon, Arije Ghannam, Denise Ponard, Christian Drouet
BackgroundAngioedema diagnosis classically targets the complement system (via C1 inhibitor (C1Inh) function and antigenic C4 level) and contact phase activation (via amidase activity). Bradykinin is responsible for angioedema attacks and is produced from contact phase activation secondary to failed C1Inh control.ObjectiveWe aimed to compare the diagnostic performances of spontaneous amidase activity and antigenic C4 level in C1Inh hereditary angioedema (C1Inh-HAE) patients.MethodsSamples from 185 C1Inh-HAE patients (81 men, 104 women; confirmed by SERPING1 gene mutations) and from 99 blood donors (50 men, 49 women) were tested for C1Inh function, antigenic C4 level and spontaneous amidase activity.ResultsIn the C1Inh-HAE group, antigenic C4 level was decreased (n=135) and amidase activity was increased (n=181). Receiver operating characteristic analyses showed higher diagnostic performance values for the spontaneous amidase assay compared to those of antigenic C4.ConclusionThe spontaneous amidase activity assay should replace antigenic C4 level testing and should be tested alongside the C1Inh function for both AE screening and follow up of HAE patients.



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International Recommendations for Electrocardiographic Interpretation in Athletes

Abstract

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural, or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly over the last decade; pushed by a growing body of scientific data that both tests proposed criteria sets and establishes new evidence to guide refinements. On February 26-27, 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington, to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD.

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Reply: Heart Rate Reduction and Cardiovascular Outcome in Hypertension

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Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention

AbstractBackground

Ezetimibe improves cardiovascular (CV) outcomes in patients stabilized after acute coronary syndrome (ACS) when added to statin therapy. After ACS, patients vary considerably in their risk for recurrent CV events.

Objectives

This study tested the hypothesis that atherothrombotic risk stratification may be useful to identify post-ACS patients who have the greatest potential for benefit from the addition of ezetimibe to statin therapy.

Methods

The TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention (TRS 2°P) is a simple 9-point risk stratification tool, previously developed in a large population with atherothrombosis to predict CV death, myocardial infarction (MI), and ischemic stroke (CV death/MI/ischemic cerebrovascular accident [iCVA]). The current study applied this tool prospectively to 17,717 post-ACS patients randomized either to ezetimibe and simvastatin or to placebo and simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Treatment efficacy was assessed by baseline risk for CV death/MI/iCVA, the IMPROVE-IT composite endpoints (CE), and individual component endpoints at 7 years.

Results

All 9 clinical variables in the TRS 2°P were independent risk indicators for CV death/MI/iCVA (p < 0.001). The integer-based scheme showed a strong graded relationship with the rate of CV death/MI/iCVA, the trial CE, and the individual components (p trend <0.0001 for each). High-risk patients (n = 4,393; 25%), defined by ≥3 risk indicators, had a 6.3% (95% confidence interval: 2.9% to 9.7%) absolute risk reduction in CV death/MI/iCVA at 7 years with ezetimibe/simvastatin, thus translating to a number-needed-to-treat of 16. Intermediate-risk patients (2 risk indicators; n = 5,292; 30%) had a 2.2% (95% confidence interval: –0.3% to 4.6%) absolute risk reduction. Low-risk patients (0 to 1 risk indicators; n = 8,032; 45%) did not appear to derive benefit from the addition of ezetimibe (p interaction = 0.010). Similar findings were observed for the IMPROVE-IT primary CE.

Conclusions

Atherothrombotic risk stratification using the TRS 2°P identifies high-risk patients who derive greatest benefit from the addition of ezetimibe to statin therapy for secondary prevention after ACS. (Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878)

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Effect of Linagliptin on Arterial 18F-Fluorodeoxyglucose Positron Emission Tomography Uptake: A Randomized Controlled Trial (RELEASE)

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Who Should Receive Ezetimibe?

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Editor-in-Chiefs Top Picks From 2016: Part Two

Each week, I record audio summaries for every article in JACC, as well as an issue summary. While this process has been incredibly time-consuming, I have become quite familiar with every paper that we publish. Thus, I personally select papers (both original investigations and review articles) from 15 distinct specialties each year for your review. In addition to my personal choices, I have included manuscripts that have been the most accessed or downloaded on our websites, as well as those selected by the JACC Editorial Board members. In order to present the full breadth of this important research in a consumable fashion, we will present these manuscripts in this issue of JACC.

Part One included the sections: Basic & Translational Research, Cardiac Failure, Cardiomyopathies/Myocardial & Pericardial Diseases, Congenital Heart Disease, Coronary Disease & Interventions, and CVD Prevention & Health Promotion.

Part Two includes the sections: CV Medicine & Society, Hypertension, Imaging, Metabolic & Lipid Disorders, Rhythm Disorders, Valvular Heart Disease, and Vascular Medicine (1–84).

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Coronary Artery Bypass Grafting With and Without Manipulation of the Ascending Aorta: A Network Meta-Analysis

AbstractBackground

Coronary artery bypass grafting (CABG) remains the standard of treatment for 3-vessel and left main coronary disease, but is associated with an increased risk of post-operative stroke compared to percutaneous coronary intervention. It has been suggested that CABG techniques that eliminate cardiopulmonary bypass and reduce aortic manipulation may reduce the incidence of post-operative stroke.

Objectives

A network meta-analysis was performed to compare post-operative outcomes between all CABG techniques, including anaortic off-pump CABG (anOPCABG), off-pump with the clampless Heartstring device (OPCABG-HS), off-pump with a partial clamp (OPCABG-PC), and traditional on-pump CABG with aortic cross-clamping.

Methods

A systematic search of 6 electronic databases was performed to identify all publications reporting the outcomes of the included operations. Studies reporting the primary endpoint, 30-day post-operative stroke rate, were included in a Bayesian network meta-analysis.

Results

There were 13 included studies with 37,720 patients. At baseline, anOPCABG patients had higher previous stroke than did the OPCABG-PC (7.4% vs. 6.5%; p = 0.02) and CABG (7.4% vs. 3.2%; p = 0.001) patients. AnOPCABG was the most effective treatment for decreasing the risk of post-operative stroke (–78% vs. CABG, 95% confidence interval [CI]: 0.14 to 0.33; –66% vs. OPCABG-PC, 95% CI: 0.22 to 0.52; –52% vs. OPCABG-HS, 95% CI: 0.27 to 0.86), mortality (–50% vs. CABG, 95% CI: 0.35 to 0.70; –40% vs. OPCABG-HS, 95% CI: 0.38 to 0.94), renal failure (–53% vs. CABG, 95% CI: 0.31 to 0.68), bleeding complications (–48% vs. OPCABG-HS, 95% CI: 0.31 to 0.87; –36% vs. CABG, 95% CI: 0.42 to 0.95), atrial fibrillation (–34% vs. OPCABG-HS, 95% CI: 0.49 to 0.89; –29% vs. CABG, 95% CI: 0.55 to 0.87; –20% vs. OPCABG-PC, 95% CI: 0.68 to 0.97), and shortening the length of intensive care unit stay (–13.3 h; 95% CI: –19.32 to –7.26; p < 0.0001).

Conclusions

Avoidance of aortic manipulation in anOPCABG may decrease the risk of post-operative stroke, especially in patients with higher stroke risk. In addition, the elimination of cardiopulmonary bypass may reduce the risk of short-term mortality, renal failure, atrial fibrillation, bleeding, and length of intensive care unit stay.

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JACC: Basic to Translational Science: Adding the Arc of Discovery to the JACC Family

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Off-Pump CABG Surgery "No-Touch" Technique to Reduce Adverse Neurological Outcomes

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Reply: Poor Sensitivity and Specificity of Electrocardiographic Estimation of Myocardial Mass

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Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial

AbstractBackground

Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers.

Objectives

The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers.

Methods

A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days.

Results

Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or posaconazole combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days; 93.3% and 88.9% and 60 days; 90%, and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all were superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%) versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (6 patients) and were observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole.

Conclusions

Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole [POS] in the Treatment of Asymptomatic Chronic Chagas Disease [P05267] [STOP CHAGAS]: NCT01377480)

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JACC Instructions for Authors

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A New Epoch in Antitrypanosomal Treatment for Chagas Disease

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A Test in Context: Myocardial Strain Measured by Speckle-Tracking Echocardiography

Abstract

Strain-based imaging techniques (and specifically speckle-tracking echocardiography) have been shown to have clinical utility in a variety of settings. This technique is being embraced and increasingly adopted in many echocardiography laboratories worldwide. This review appraised speckle-tracking echocardiography in a clinical context by providing a critical evaluation of the prognostic and diagnostic insights that this technology can provide. In particular, we discuss the use of speckle-tracking strain in selected areas, such as undifferentiated left ventricular hypertrophy, cardio-oncology, aortic stenosis, and ischemic heart disease. The potential utility of regional and chamber strains (namely segmental left ventricular strain, left atrial strain, and right ventricular strain) are also discussed. Future directions for this technology are explored. Before its clinical application, it is particularly important that physicians be cognizant of the technical challenges and inherent limitations of strain data, which are also addressed here.

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Catheter-Based Renal Denervation Exacerbates Blood Pressure Fall During Hemorrhage

AbstractBackground

Clinical trials applying catheter-based radiofrequency renal denervation (RDN) demonstrated a favorable safety profile with minimal acute or procedural adverse events. Whether ablation of renal nerves adversely affects compensatory responses to hemodynamic challenge has not been extensively investigated.

Objectives

The aim of this study was to examine the effect of RDN on mean arterial pressure, renal function, and the reflex response to hemorrhage in sheep with normotension (control) or with hypertensive chronic kidney disease (CKD).

Methods

Sheep underwent RDN (control-RDN, n = 8; CKD-RDN, n = 7) or sham procedures (control-intact, n = 6; CKD-intact, n = 7). Response to hemorrhage (20% loss of blood volume), including plasma renin activity, was assessed at 2 and 5 months post-procedure.

Results

RDN caused a complete reversal of hypertension and improved renal function in CKD-RDN sheep (p < 0.0001 for 2 and 5 months vs. pre-RDN). In response to hemorrhage, mean arterial pressure fell in all groups, with the fall being greater in the RDN than the intact group (2-month fall in mean arterial pressure: control-intact, –10 ± 1 mm Hg; control-RDN, –15 ± 1 mm Hg; p < 0.05; CKD-intact, –11 ± 3 mm Hg; CKD-RDN, –19 ± 9 mm Hg; p < 0.001). Hemorrhage increased heart rate and plasma renin activity in intact sheep, but these responses were significantly attenuated in control-RDN and CKD-RDN animals. Responses to hemorrhage were remarkably similar at 2 and 5 months post-RDN, which suggests that nerve function had not returned within this time frame.

Conclusions

In hypertensive CKD sheep, RDN reduced blood pressure and improved basal renal function but markedly compromised compensatory hemodynamic responses to hemorrhage. Therefore, the capacity to respond to a physiological challenge to body fluid homeostasis may be compromised following RDN.

http://ift.tt/2l0O2p9

ACC/AHA Special Report: Clinical Practice Guideline Implementation Strategies: A Summary of Systematic Reviews by the NHLBI Implementation Science Work Group: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

AbstractBackground

In 2008, the National Heart, Lung, and Blood Institute convened an Implementation Science Work Group to assess evidence-based strategies for effectively implementing clinical practice guidelines. This was part of a larger effort to update existing clinical practice guidelines on cholesterol, blood pressure, and overweight/obesity.

Objectives

Review evidence from the published implementation science literature and identify effective or promising strategies to enhance the adoption and implementation of clinical practice guidelines.

Methods

This systematic review was conducted on 4 critical questions, each focusing on the adoption and effectiveness of 4 intervention strategies: (1) reminders, (2) educational outreach visits, (3) audit and feedback, and (4) provider incentives. A scoping review of the Rx for Change database of systematic reviews was used to identify promising guideline implementation interventions aimed at providers. Inclusion and exclusion criteria were developed a priori for each question, and the published literature was initially searched up to 2012, and then updated with a supplemental search to 2015. Two independent reviewers screened the returned citations to identify relevant reviews and rated the quality of each included review.

Results

Audit and feedback and educational outreach visits were generally effective in improving both process of care (15 of 21 reviews and 12 of 13 reviews, respectively) and clinical outcomes (7 of 12 reviews and 3 of 5 reviews, respectively). Provider incentives showed mixed effectiveness for improving both process of care (3 of 4 reviews) and clinical outcomes (3 reviews equally distributed between generally effective, mixed, and generally ineffective). Reminders showed mixed effectiveness for improving process of care outcomes (27 reviews with 11 mixed and 3 generally ineffective results) and were generally ineffective for clinical outcomes (18 reviews with 6 mixed and 9 generally ineffective results). Educational outreach visits (2 of 2 reviews), reminders (3 of 4 reviews), and provider incentives (1 of 1 review) were generally effective for cost reduction. Educational outreach visits (1 of 1 review) and provider incentives (1 of 1 review) were also generally effective for cost-effectiveness outcomes. Barriers to clinician adoption or adherence to guidelines included time constraints (8 reviews/overviews); limited staffing resources (2 overviews); timing (5 reviews/overviews); clinician skepticism (5 reviews/overviews); clinician knowledge of guidelines (4 reviews/overviews); and higher age of the clinician (1 overview). Facilitating factors included guideline characteristics such as format, resources, and end-user involvement (6 reviews/overviews); involving stakeholders (5 reviews/overviews); leadership support (5 reviews/overviews); scope of implementation (5 reviews/overviews); organizational culture such as multidisciplinary teams and low-baseline adherence (9 reviews/overviews); and electronic guidelines systems (3 reviews).

Conclusion

The strategies of audit and feedback and educational outreach visits were generally effective in improving both process of care and clinical outcomes. Reminders and provider incentives showed mixed effectiveness, or were generally ineffective. No general conclusion could be reached about cost effectiveness, because of limitations in the evidence. Important gaps exist in the evidence on effectiveness of implementation interventions, especially regarding clinical outcomes, cost effectiveness and contextual issues affecting successful implementation.

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Are Important Components of Kidney Function Lost With Renal Denervation?

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Successful Percutaneous Coronary Intervention Improves Cardiopulmonary Exercise Capacity in Patients With Chronic Total Occlusions

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Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against {beta}1-Adrenergic Receptors

AbstractBackground

Among various cardiac autoantibodies (AAbs), those recognizing the β₁-adrenergic receptor (β₁AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption.

Objectives

The goal of this study was to investigate the role of β₁AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy.

Methods

Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-β₁AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months.

Results

Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β₁AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β₁AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint.

Conclusions

IgG3-β₁AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.

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Poor Sensitivity and Specificity of Electrocardiographic Estimation of Myocardial Mass

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Bacterial colonization of the peri-implant sulcus in dentate patients: a prospective observational study

Abstract

Objectives

The aim of the present study was to compare the composition of the periodontal microflora at baseline (T0) with the submucosal microflora at least 1 year after implant placement (T1) in periodontally healthy patients.

Material and methods

For all 169 consecutive patients that visited our clinic during 1 year, we determined their periodontal parameters, implant mucosal index, and presence of implant calculus. At T0, self-reported smoking status was recorded and subgingival and submucosal biofilm samples were obtained and analyzed for the presence and numbers of selected periodontal pathogens. All measurements were repeated at T1.

Results

One hundred twenty patients completed the study. Periodontal parameters were stable or had improved at T1. The total bacterial load was lower at implant sites (P < 0.05). The prevalence of Porphyromonas gingivalis was low at baseline, but at T1, detection rate and numbers were higher at implant sites compared to dentate sites. At T1, the frequency of detection of P. gingivalis (P = 0.01), Parvimonas micra (P = 0.018), and Fusobacterium nucleatum (P = 0.035) was higher in smoking patients (n = 23) than in non-smokers (n = 97).

Conclusions

Colonization of the submucosal peri-implant area is similar to the composition of subgingival microbiota. Smoking has a measurable effect on the colonization of implant-associated biofilms and may select for P. gingivalis, P. micra, and F. nucleatum.

Clinical relevance

The colonization of implants by well-known periodontal pathogens is very similar to that in normal dentition, also in a healthy cohort. Smoking status was related with the prevalence of periodontal pathogens where smokers harbored more often periodontal pathogens such as P. gingivalis, P. micra, and F. nucleatum.

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Three-year clinical evaluation of class II posterior composite restorations placed with different techniques and flowable composite linings in endodontically treated teeth

Abstract

Objective

The objective of this study is to evaluate the clinical performance of direct resin composite restorations placed with different techniques (incremental or bulk) and different flowable linings (conventional or bulk-fill) in endodontically treated teeth.

Materials and methods

Forty-seven pair class II (mesio-occlusal or disto-occlusal) composite restorations were placed in 37 patients. In all cavities, Adper Single Bond 2 was used. In one of the cavities of each pair, a conventional flowable composite, Aelite Flo, was applied in approximately 2 mm thick, and the remaining cavity was restored incrementally with GrandioSO. In the second cavity, a bulk-fill flowable composite, x-tra base, was applied in approximately 4 mm thick in bulk increments and the remaining 2-mm occlusal part of the cavity was restored with GrandioSO. All cavities were restored with open-sandwich technique by the same operator. At baseline and after 6-month, 1-, 2-, and 3-year follow-up visits, restorations were evaluated by modified USPHS criteria.

Results

At 3-year recall, 33 restorations with Aelite Flo lining and 33 with x-tra base lining were available. Two restorations from each group (6.0 %) were scored as Bravo in terms of surface texture. One restoration's color match from x-tra base group scored as Bravo (3.0 %). All other evaluated criteria were scored as Alfa (100 %) for all restorations. No statistically significant difference between the two groups was found in all evaluated criteria during 3-year period (p > 0.05).

Conclusion

Bulk-filling technique showed clinically acceptable performance comparable to the incremental technique.

Clinical relevance

Restorations placed with bulk-filling technique with x-tra base lining and incremental technique with a conventional flowable lining showed highly clinical performance over 3-year period.

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Knowledge, opinions and practices of French general practitioners in the assessment of caries risk: results of a national survey

Abstract

Objectives

The objective of this study was to describe the knowledge, opinions and practices of French general dental practitioners with respect to caries risk assessment (CRA) through the use of a national questionnaire survey.

Materials and methods

A postal questionnaire survey was applied to a simple random sample of dentists (n = 2000) in France. Descriptive and logistic regression analyses were performed.

Results

The response rate was 34.7 %. Of the respondents, 38.4 % reported that CRA was not part of their routine practice. Among those who claimed to use CRA only 4.5 % did so using a specific evaluation form. Responses showed that there is great variation among respondents with respect to the importance given to different factors to be considered for the development of a treatment plan in adults. Moreover, 32.3 % of respondents reported no regular scheduling of preventive care based on the caries risk of their patients. Nearly 12 % of respondents admitted they did not know exactly what minimal intervention in caries management involved. The results also showed that socio-demographic characteristics of the practitioner influence the use of CRA and other practice patterns.

Conclusions

CRA has not widely entered clinical practice in France.

Clinical relevance: This study, the first of its nature in France, shows the need to develop the use of CRA in daily dental practice in France.

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Small bowel protection in IMRT for rectal cancer

Abstract

Background

This treatment planning study analyzes dose coverage and dose to organs at risk (OAR) in intensity-modulated radiotherapy (IMRT) of rectal cancer and compares prone vs. supine positioning as well as the effect of dose optimization for the small bowel (SB) by additional dose constraints in the inverse planning process.

Patients and methods

Based on the CT datasets of ten male patients in both prone and supine position, a total of four different IMRT plans were created for each patient. OAR were defined as the SB, bladder, and femoral heads. In half of the plans, two additional SB cost functions were used in the inverse planning process.

Results

There was a statistically significant dose reduction for the SB in prone position of up to 41% in the high and intermediate dose region, compared with the supine position. Furthermore, the femoral heads showed a significant dose reduction in prone position in the low dose region. Regarding the additional active SB constraints, the dose in the high dose region of the SB was significantly reduced by up to 14% with the additional cost functions. There were no significant differences in the dose distribution of the planning target volume (PTV) and the bladder.

Conclusion

Prone positioning can significantly reduce dose to the SB in IMRT for rectal cancer and therefore should not only be used in 3D conformal radiotherapy but also in IMRT of rectal cancer. Further protection of the SB can be achieved by additional dose constraints in inverse planning without jeopardizing the homogeneity of the PTV.

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The clinical value and biological function of PTTG1 in colorectal cancer

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Qinggui Ren, Bingwei Jin
Pituitary tumor transforming gene-1 (PTTG1) has been suggested to serve as an oncogene in several types of human tumors, but little is known about the biological function of PTTG1 in colorectal cancer. PTTG1 mRNA and protein expressions in colorectal cancer tissues and cell lines were measured by qRT-PCR, western blot or immunohistochemistry. The association between PTTG1 protein expression and clinicopathological features was analyzed. The function of PTTG1 on colorectal cancer cell proliferation and metastasis were explored through MTT, colony formation, migration and invasion assays. In our results, PTTG1 mRNA and protein expressions were increased in colorectal cancer tissues and cell lines compared with normal colonic tissues and colon epithelial cell line. PTTG1 overexpression positively associated with clinical stage, T classification, N classification, M classification and differentiation. The univariate and multivariate analyses suggested PTTG1 overexpression was an independent poor prognostic factor for colorectal cancer patients. The in vitro experiments showed knocking down PTTG1 inhibited colorectal cancer growth and metastasis. In conclusion, PTTG1 is an independent prognostic factor and acts as an oncogene in colorectal cancer.



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Synergism and mechanism of Astragaloside IV combined with Ginsenoside Rg1 against autophagic injury of PC12 cells induced by oxygen glucose deprivation/reoxygenation

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Xiao-Ping Huang, Huang Ding, Xiao-Qian Yang, Jing-Xian Li, Biao Tang, Xiao-Dan Liu, Ying-Hong Tang, Chang-Qing Deng
The aim of this study was to explore the effect by which the combination of Astragaloside IV (AST IV) and Ginsenoside Rg1 (Rg1) resisted autophagic injury in PC12 cells induced by oxygen glucose deprivation/reoxygenation (OGD/R). We studied the nature of the interaction between AST IV and Rg1 that inhibited autophagy through the Isobologram method, and investigated the synergistic mechanism via the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways. Our results showed that, based on the 50% inhibiting concentration (IC50), AST IV combined with Rg1 at a 1:1 ratio resulted in a synergistic effect, whereas the combination of the two had an antagonistic effect on autophagy at ratios of 1:2 and 2:1. Meanwhile, AST IV and Rg1 alone increased cell survival and decreased lactate dehydrogenase (LDH) leakage induced by OGD/R, reduced autophagosomes and the LC3 II positive patch, down-regulated the LC3 II/LC3 I ratio and up-regulated the p62 protein; the 1:1 combination enhanced these effects. Mechanistic study showed that Rg1 and the 1:1 combination increased the phosphorylation of PI3K I, Akt and mTOR; the effects of the combination were greater than those of the drugs alone. AST IV and the 1:1 combination suppressed the expression of PI3K III and Becline-1, and the combination elevated Bcl-2 protein expression; the effects of the combination were better than those of the drugs alone. These results suggest that after 2 h-OGD followed by reoxygenation for 24h, PC12 cells suffer excessive autophagy and damage, which are blocked by AST IV or Rg1; moreover, the combination of AST IV and Rg1 at a 1:1 ratio of their IC50 concentrations has a synergistic inhibition on autophagic injury. The synergistic mechanism may be associated with the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways.



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Antiprotozoal, antimycobacterial, and anti-inflammatory evaluation of Cnidoscolus chayamansa (Mc Vaugh) extract and the isolated compounds

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Mariana Z. Pérez-González, Gabriel A. Gutiérrez-Rebolledo, Lilián Yépez-Mulia, Irma S. Rojas-Tomé, Julieta Luna-Herrera, María A. Jiménez-Arellanes
Cnidoscolus chayamansa is a medicinal and edible plant known as Chaya, is commonly used as an anti-inflammatory, antiprotozoal, antibacterial agent and as a remedy for respiratory illness, gastrointestinal disorders, and vaginal infections related with the inflammation process. In this paper, we describe the plant's phytochemical analysis and biological activities (antimycobacterial, antibacterial, antiprotozoal, and anti-inflammatory properties) of the CHCl3:MeOH (1:1) leaves extract and isolated compounds, as well as the acute and sub-acute toxic effects.Chemical identification of isolated compounds was performed by ¹H- and ¹³C NMR spectra data. In vitro antibacterial and antimycobacterial activities were determined by disc diffusion and MABA assays, respectively; antiprotozoal test by means of the sub-culture test. Topical and systemic anti-inflammatory effects were tested by TPA and carrageenan assay on BALB/c mice.Moretenol, moretenyl acetate, kaempferol-3,7-dimethyl ether, and 5-hydroxy-7-3′,4′-trimethoxyflavanone were the main compounds isolated. The CHCl3:MeOH extract showed antiprotozoal (IC50≤65.29μg/mL), antimycobacterial (MIC≤50μg/mL), and anti-inflammatory activities (ED50=1.66mg/ear and 467.73mg/kg), but was inactive against the bacterial strains tested. The LD50 for extract was >2g/kg. In the sub-acute toxicity test, the extract was administered at 1g/kg for 28days and did not cause lethality or any alteration in hematological and biochemical parameters; in addition, liver, kidney, and spleen histological analysis exhibited no structural changes. Moretenol and moretenyl acetate showed MIC=25μg/mL against Mycobacterium tuberculosis H37Rv and against four monoresistant strains of M. tuberculosis H37Rv. Both compounds exhibited moderate activity against Entamoeba histolytica and Giardia lamblia (IC50≤71.70μg/mL). Kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3′,4′-trimethoxy-flavanone were more active than the extract against E. histolytica and G. lamblia, showing IC50 ≤27.43μg/mL. As topical anti-inflammatory agents, moretenol and kaempferol-3,7-dimethyl ether were the most active compounds inhibiting the edema in 30.52 and 26.67%, respectively.Moretenol and moretenyl acetate showed significant antimycobacterial and antiprotozoal activities; in addition, important antiprotozoal effect was detected with kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3′,4′-trimethoxyflavanone. The extract and the terpenoids possess good anti-inflammatory activity. The extract did not produce lethality or adverse effects in acute and sub-acute tests.



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Combination of Sitagliptin and Silymarin ameliorates liver fibrosis induced by carbon tetrachloride in rats

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Samia Salem Sokar, Magda El-Sayed El-Sayad, Mai El-Sayed Ghoneim, Abdelhadi Mohamed Shebl
Liver fibrosis is a common pathological condition that occurs in most conditions associated with chronic liver injury. Silymarin is a herbal product widely used for its hepatoprotective effect. Sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4-I), is clinically used as an oral antidiabetic agent. This study was designed to investigate the effects of Sitagliptin, Silymarin, and their combination on established liver fibrosis in carbon tetrachloride (CCl4) rat model. Male albino rats received intraperitoneal injections of CCl4 three times a week for 7 weeks, as well as daily oral treatments of Sitagliptin (100mg/kg) or Silymarin (100mg/kg) or their combination during the 7 weeks of intoxication. Hepatic fibrotic changes were evaluated by measuring hepatic enzymes (ALT, AST, ALP, and GGT) and markers of fibrosis (transforming growth factor β1 (TGF-β1), tissue 4-hydroxyproline level, histopathological score), oxidative stress (MDA, GSH, and NOx levels), inflammation (interleukin-6) as well as markers of HSCs activation (α-smooth muscle actin (α-SMA) expression). The injected rats with CCl4 for 7 weeks resulted in a marked elevation of hepatic fibrotic changes and reduction of GSH level, while the combination therapy showed a significant decrease in the former one and a significant increase in the later. In conclusion, this study shows that the combination therapy is more beneficial than monotherapy in ameliorating liver fibrosis in rats. Our findings suggest that Sitagliptin alone or in combination with Silymarin may introduce a new strategy for treating liver fibrosis in humans.



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Lawsone suppresses azoxymethane mediated colon cancer in rats and reduces proliferation of DLD-1 cells via NF-κB pathway

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Shi-Bin Wang, Zhenzhou Tao, Ping Li
Lawsone (LS) a colored napthoquinone compound obtained from the plant Lawsonia inermis L. (Lythraceae) is known for its usefulness of being a precursor for synthesis of some anticancer compounds. Literatures support potent anticancer activity of napthoquinone derivatives in human colon cancer, present study evaluates the effect and mechanism of LS on chemical induced colon cancerous rats and human colon cancer DLD-1 cells, the study was supported by endoscopy, histological and immunohistochemistry analysis. KAD rats were subjected to colon cancer mediated by Azoxymethane (AOM) injections followed Dextran sodium sulfate (DSS) orally in drinking water. After endoscopic confirmation the rats were given LS (200mg/ml) orally for 8 weeks. Presence of aberrant foci, types of tumors and the proliferative effect on tumor lesions was studied by macroscopic, histological and immunohistochemical analysis. To establish the mechanism, human colon DLD-1 cancer cells were exposed to LS and its effect on proliferation were studied. LS reduced aberrant crypt without affecting tumor pathology. Histological study of colon suggested decrease in numbers of adenomas and lesions. Immunohistochemistry confirmed the antiproliferative activity in adenocarcinomas without affecting the cells of normal colon mucosa. Results on human DLD-1 cells showed LS delayed progression of cell cycle by decreasing expression of cyclin B1 as well as cdk1 by inactivating NF-κB without inducing apoptosis. The study concluded role of LS in suppressing cell proliferation of colon tumors. The suppressive activity on DLD-1 cells was not by apoptosis but by decreased NF-κB activity resulting in suppression of expression levels of cyclin B1 and cdk1.



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Isolation of a new resorcinolic lipid from Mangifera zeylanica Hook.f. bark and its cytotoxic and apoptotic potential

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Meran Keshawa Ediriweera, Kamani Hemamala Tennekoon, Sameera Ranganath Samarakoon, Achyut Adhikari, Ira Thabrew, E. Dilip de Silva
Mangifera zeylanica is a plant endemic to Sri Lanka and its bark has been used in traditional medicine to treat some cancers. This study was aimed to isolate potentially cytotoxic compound/s from the hexane extract of the bark of M. zeylanica by bio-activity guided fractionation. The structure of the isolated compound (1) was elucidated using ¹H, ¹³C NMR and mass spectrometric techniques. Compound 1 was identified as a new resorcinolic lipid (5-((8Z, 11Z, 14Z)-hexatriaconta-8, 11, 14-trienyl) benzene-1,3-diol). Apoptotic potential of the isolated compound was determined only in MCF-7 (estrogen receptor positive) breast cancer cells to which it was more cytotoxic than to normal mammary epithelial cells. Oxidative stress markers [reactive oxygen species (ROS), glutathione levels (GSH) and glutathione-S-transferase (GSH)] were also determined in MCF-7 cells treated with compound 1. Treatment with compound 1 led to an increase in caspase 7 activity, morphological features of apoptosis and DNA fragmentation in MCF-7 cells. Furthermore, it also led to an increase in ROS and GST levels while depleting GSH levels. Results of this study suggest that isolated new resorcinolic lipid can induce apoptosis in MCF-7 cells, possibly via oxidative stress mechanism.

Graphical abstract

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A novel approach towards design, synthesis and evaluation of some Schiff base analogues of 2-aminopyridine and 2-aminobezothiazole against hepatocellular carcinoma

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Shinu Chacko, Subir Samanta
Hepatocellular carcinoma is the most common primary malignancy of the liver with poor prognosis. In this study novel, Schiff's bases of 2-aminopyridine (SSSC-26 to 31) and 2-aminobenzothiazole (SSSC-32 to 37) were designed, synthesised and evaluated for antioxidant potential using DPPH method, and anti-hepatocellular carcinoma property using diethylnitrosamine (DEN) induced hepatocellular carcinoma rat model. The in-silico pharmacokinetic, rule of five and toxicity studies reveals that all the leads have an excellent intrinsic quality and sufficient structural features necessary for an oral activity. Molecular docking studies of all compounds into the ligand binding pocket of checkpoint kinase1 and vascular endothelial growth factor receptor-2 was also performed using Schrodinger software suite v8.5, and which have shown good Glide scores. Further compounds were synthesised based on the docking score and ADMET profile. The 1,1-diphenyl­2-picrylhydrazil (DPPH) scavenging study was carried out, and results showed that SSSC-29 (IC50-63.60) and SSSC-33 (IC50-60.32) were having good anti-oxidant potential in comparison with ascorbic acid (IC50-55.27). SSSC-33 further evaluated for anti-cancer potential against diethylnitrosamine (200mg/kg bw) induced hepatocellular carcinoma in rats. The biochemical, histopathological and morphological data showed that SSSC-33 can reverse the changes occurred in the cancerous liver significantly. All these findings suggested that SSSC-33-((benzo[d]thiazol-2-ylimino) methyl)phenol) could be a potential compound in combating the oxidative damage of hepatic cells occurred due to the development of hepatocellular carcinoma induced by a chemical carcinogen, DEN.



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HPLC-DAD-QTOF-MS profiling of phenolics from leaf extracts of two Tunisian fig cultivars: Potential as a functional food

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Olfa Belguith-Hadriche, Sonda Ammar, María del Mar Contreras, Hamadi Fetoui, Antonio Segura-Carretero, Abdelfattah El Feki, Mohamed Bouaziz
The phenolic constituents of the aqueous-ethanolic extract of two Tunisian Ficus carica leaves cultivars and their hypoglycaemic, hypolipidaemic and antioxidative activities in alloxan-induced diabetic rats were investigated. Our results demonstrated that the treatment with the leaves extracts of F. carica improved lipid profile and reduced blood glucose level as well as thiobarbituric acid-reactive substances content. The antioxidant enzymes activity in the liver and heart tissues of diabetic rats was increased after the treatment. These antihyperglycaemic, antihyperlipidaemic and antioxidant effects of both leaf extracts could be associated with their in vitro scavenging ability and their phenolic composition. The HPLC-DAD-QTOF-MS analysis of both extracts revealed the presence of dihydroxybenzoic acid, dipentoside, rutin, psoralen, methoxypsoralen and oxypeudacin hydrate as relatively the most abundant compounds. These results showed indicated the capacity of the leaves extracts of F. carica to ameliorate hyperglycaemia, hyperlipidaemia and antioxidant status in diabetic rats.

Graphical abstract

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Physico-chemical characterization and antibacterial activity of inclusion complexes of Hyptis martiusii Benth essential oil in β-cyclodextrin

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Tatianny A. Andrade, Thiago S. Freitas, Francielly O. Araújo, Paula P. Menezes, Grace Anne A. Dória, Alessandra S. Rabelo, Lucindo J. Quintans-Júnior, Márcio R.V. Santos, Daniel P. Bezerra, Mairim R. Serafini, Irwin Rose A. Menezes, Paula Santos Nunes, Adriano A.S. Araújo, Maria S. Costa, Fábia F. Campina, Antonia T.L. Santos, Ana R.P. Silva, Henrique D.M. Coutinho
Cyclodextrins (CDs) have been used as important pharmaceutical excipients for improve the physicochemical properties of the drugs of low solubility as the essential oil of Hyptis martiusii. This oil is important therapeutically, but the low solubility and bioavailability compromises your use. Therein, the aim of this study was to obtain and to characterize physico-chemically the samples obtained by physical mixture (PM), paste complexation (PC) and slurry complexation (SC) of the essential oil Hyptis martiusii (EOHM) in β-CD, and to compare the antibacterial and modulatory-antibiotic activity of products obtained and oil free. The physicochemical characterization was performed by differential scanning calorimetry (DSC), thermogravimetry/derivative thermogravimetry (TG/DTG), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Karl Fischer titration. Additionally, the antibacterial tests were performed by microdilution technique. Thus, it was observed that the PM method showed low complexing capacity, unlike PC and SC in which it was observed the formation of inclusion complexes. In addition, the second stage of the TG/DTG curves showed that SC was the best method inclusion with mass loss of 6.9% over the PC that was 6.0%. The XRD results corroborate with the results above suggesting the formation of new solid phase and the SEM photomicrographs showed the porous surface of the samples PC and SC. The essential oil alone demonstrated an antibacterial and modulatory effect against the S. aureus and the Gram negative strain, respectively. However, the β-CD and the inclusion complex did not demonstrate any biological activity in the performed antibacterial assays.



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Editorial Board

Publication date: March 2017
Source:Dental Materials, Volume 33, Issue 3





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Selective adsorption and recycle of Cu 2+ from aqueous solution by modified sugarcane bagasse under dynamic condition

Abstract

Tetraethylenepentamine modified sugarcane bagasse was prepared and applied to test its feasibility in removing and recovering Cu²⁺ from wastewater under dynamic condition. Results showed that the Cu²⁺ could be selectively absorbed from wastewater by the modified SCB fixed bed column. To understand the adsorption mechanism, Cd²⁺ had been selected as the model interfering ion to investigate how co-ions influence the adsorption of Cu²⁺ on the sorbent. It was observed that the adsorption capacity of the sorbent for Cu²⁺ (0.26 mmol g⁻¹) was significantly higher than that of Cd²⁺ (0.03 mmol g⁻¹), even when the Cd²⁺ initial concentration was 100 times higher than that of Cu²⁺ in the binary system. This finding indicated that the presence of Cd²⁺ in the solution exerted negligible influence on the adsorption of Cu²⁺ on the modified SCB. The selectivity of the modified sorbent was further confirmed in the Cu/Cd/Mg/Pb/K quinary system. Further analysis to dynamic adsorption experiment illustrated that, due to the presence of amine groups, the modified SCB showed strong coordination ability to Cu²⁺, which allowed the other adsorbed ions (e.g., Cd²⁺) desorbed. This high adsorption selectivity toward Cu²⁺ suggested that this prepared sorbent would be a promising candidate for removing and recovering Cu²⁺ from wastewater.

http://ift.tt/2lzx98k

Removal of DDE by exploiting the alcoho-phobic interactions

Abstract

DDE (1,1-bis-(4-chlorophenyl)-2,2-dichloroethene), which is a commonly used pesticides in agriculture, has harmful effects on human health. Therefore, the removal of this substance from the drinking water and the soil is essential. Since DDT (1,1″-(2,2,2-Trichloroethane-1,1-diyl) bis(4-chlorobenzene)) is derivation of DDE, the presence of DDT can be monitored by the detection of DDE present in the environment. Herein, we report on the development of aspartic acid-incorporated poly(2-hydroxyethyl methacrylate-L-aspartic acid) [poly(HEMA-MAsp)] cryogel for the removal of DDE from aqueous solutions for the first time in the literature. The synthesized cryogels were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), an N₂ adsorption method, elemental analysis, and swelling test. The separation experiments were carried out via a batch system to get the optimum adsorption conditions including pH, interaction time, initial DDE concentration, and temperature. The desorption and the reusability results revealed that there was no significant decrease in the DDE adsorption capacity of the cryogels after five adsorption-desorption cycles. The maximum DDE adsorption capacity of poly(HEMA-MAsp) cryogels was found to be 31.51 mg DDE/g polymer for 50 mg DDE/L solution.

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Human exposure to perfluoroalkyl substances near a fluorochemical industrial park in China

Abstract

Severe perfluoroalkyl substance (PFAS) contaminations have been observed in both surface water and groundwater in the vicinity of Fuxin, China, over the past years, attributing to the fast-growing fluorochemical industries locally. However, little is known about the overall daily intake of PFAS contaminations by Fuxin residents recently. In the present study, ten target PFAS analytes in the blood serum samples collected from 100 non-occupationally exposed healthy residents in Fuxin, with an average age of 47.6 years, together with 14 drinking water samples obtained from the public water system (PWS) of Fuxin were analyzed via high-performance liquid chromotography–tandem mass spectrometry (HPLC–MS/MS). As the dominant PFAS contaminant, the serum concentrations of perfluorooctanoic acid (PFOA) in Fuxin residents ranged between <0.05 and 160 ng/mL, with a median concentration of 9.4 ng/mL, which was higher than those reported previously for Fuxin and other areas worldwide. In drinking water samples, PFOA had a median value of 8.5 ng/L, ranging from 7.7 to 8.8 ng/L. Based upon the simplified one-compartment pharmacokinetic model, the total daily intake of PFOA for individuals residing in Fuxin ranged from 0.30 to 1.76 ng/kg bw/day, with a median of 0.79 ng/kg bw/day; furthermore, daily consumption of drinking water from the PWS in Fuxin appeared to contribute 35% of overall PFOA burden in local residents, which was approximately 3-fold higher compared to that estimated for Fuxin residents in 2009.

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Editorial Board

Publication date: February 2017
Source:Radiotherapy and Oncology, Volume 122, Issue 2





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Contents

Publication date: February 2017
Source:Radiotherapy and Oncology, Volume 122, Issue 2





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Texture analysis of parotid gland as a predictive factor of radiation induced xerostomia: A subset analysis

Publication date: February 2017
Source:Radiotherapy and Oncology, Volume 122, Issue 2
Author(s): Valerio Nardone, Paolo Tini, Christophe Nioche, Michelangelo Biondi, Lucio Sebaste, Maria Antonietta Mazzei, Fabrizio Banci Buonamici, Luigi Pirtoli




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Important ESTRO dates

Publication date: February 2017
Source:Radiotherapy and Oncology, Volume 122, Issue 2





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Effect of Chinese herbal medicine on stroke patients with type 2 diabetes

Publication date: 22 March 2017
Source:Journal of Ethnopharmacology, Volume 200
Author(s): Fuu-Jen Tsai, Tsung-Jung Ho, Chi-Fung Cheng, Xiang Liu, Hsinyi Tsang, Ting-Hsu Lin, Chiu-Chu Liao, Shao-Mei Huang, Ju-Pi Li, Cheng-Wen Lin, Jaung-Geng Lin, Jung-Chun Lin, Chih-Chien Lin, Wen-Miin Liang, Ying-Ju Lin
Ethnopharmacological relevanceComplications of type 2 diabetes (T2D) include stroke, which is a cerebrovascular disturbance characterized by reduced blood flow in the brain, leading to death or physical disability. Chinese herbal medicine (CHM) has been widely used in ancient China for the treatment of diabetes and stroke by supplementing Qi and activating blood circulation.Aim of the studyThis study aimed to investigate the frequencies and patterns of CHM treatment for stroke patients with T2D and the outcomes of long-term use in Taiwan.Materials and methodsWe identified 3079 stroke patients (ICD-9-CM: 430–438) with T2D. We allocated 618 stroke patients, matched for age, gender, and T2D-to-stroke duration, to both CHM and non-CHM groups. Chi-square test, conditional multivariable logistic regression, Kaplan-Meier method, and the log-rank test were used in this study.ResultsThe CHM group was characterized by more cases of chronic obstructive pulmonary disease, ulcer disease, hyperlipidemia, tobacco use, and higher income. The cumulative survival probability was higher in the CHM group (P<0.001, log rank test); after adjusting for comorbidities, income, and urbanization level, this group also exhibited a lower mortality hazard ratio (0.37, 95% confidence interval [0.25–0.55]). Shu-Jing-Huo-Xue-Tang, Xue-Fu-Zhu-Yu-Tang, and Du-Huo-Ji-Sheng-Tang; and Dan-Shen, Niu-Xi, and Yan-Hu-Suo represented the top three formulas and herbs, respectively.ConclusionThe use of CHM as adjunctive therapy may improve the overall survival (OS) of stroke patients with T2D. The list of the comprehensive herbal medicines that they used might be useful in future large-scale, randomized clinical investigations of agent effectiveness, safety, and potential interactions with conventional treatments in stroke patients with T2D.

Graphical abstract

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Protective effect of HwangRyunHaeDok-Tang water extract against chronic obstructive pulmonary disease induced by cigarette smoke and lipopolysaccharide in a mouse model

Publication date: 22 March 2017
Source:Journal of Ethnopharmacology, Volume 200
Author(s): Na-Rae Shin, Je-Won Ko, Sung-Hyeuk Park, Young-Kwon Cho, Sei-Ryang Oh, Kyung-Seob Ahn, Jung-Min Ryu, Jong-Choon Kim, Chang-Seob Seo, In-Sik Shin
Ethnopharmacological relevanceHwangryunhaedok-tang is an oriental herbal formula treated to cure inflammation and gastric disorders in China, Japan, and Korea. We explored the protective effects of Hwangryunhaedok-tang water extract (HRWE) against airway pathophysiological changes caused by cigarette smoke (CS) and lipopolysaccharide (LPS) in a mouse.Materials and methodsWe performed quantitative analyses of five marker components, namely geniposide, baicalin, coptisine, plamatine, and berberine, using high-performance liquid chromatography. Animals were received CS exposure (1h per day) for 7 days. LPS was administered intranasally on day 4. Mice were received HRWE at dose of 100 or 200mg/kg for 1h before CS exposure.ResultsTreatment with HRWE significantly suppressed the increased inflammatory cell count induced by CS and LPS exposure. In addition, reduction in IL-6, TNF-α and IL-1β in broncho-alveolar lavage fluid (BALF) was observed after HRWE treatment. HRWE not only decreased inflammatory cell infiltration in lung, but also decreased the expression of iNOS, NF-κB and matrix metallopeptidase (MMP)-9 in lung tissues.ConclusionThis study showed that HRWE can attenuate respiratory inflammation caused by CS and LPS exposure. Therefore, HRWE has potential for treating airway inflammatory disease.

Graphical abstract

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Intestinal transport and absorption of bioactive phenolic compounds from a chemically characterized aqueous extract of Athrixia phylicoides

Publication date: 22 March 2017
Source:Journal of Ethnopharmacology, Volume 200
Author(s): Sandra L. Bowles, Yonela Ntamo, Christiaan J. Malherbe, Abidemi M.P. Kappo, Johan Louw, Christo J.F. Muller
Ethnopharmacological relevanceAthrixia phylicoides, popularly known as "bush tea", is an indigenous aromatic shrub found in mountainous and grassland areas of the northern and eastern parts of southern Africa. The plant is traditionally used for the treatment of several ailments, including coughing, treating infected wounds, treating boils and sore throat, hypertension and heart disease. Potential anti-diabetic effects have also been demonstrated in vitro.Aim of the studyTo investigate the intestinal transport of prominent phenolic constituents, across a fully differentiated Caco-2 monolayer, using a characterized aqueous extract of A. phylicoides, previously shown to have bioactivity.Materials and methodsHPLC-DAD and LC/MS analyses were used to identify the major phenolic compounds within the extract. Intestinal transport of the phenolic compounds was assessed using a differentiated Caco-2 monolayer model in order to predict bioavailability and identify metabolite formation. Rate of transport, efflux and percentage cross-over were calculated for the respective phenolic compounds.ResultsNine prominent compounds, present in the aqueous extract of A. phylicoides, were identified. Of these, three phenolic acids (protocatechuic acid, caffeic acid and para-coumaric acid), crossed the Caco-2 cell monolayer in significant amounts, with Papp values of 4.52, 4.35 (×10⁻⁶cm/s) and 2.38 (×10⁻⁵cm/s), respectively. para-Coumaric acid was shown to have the highest predicted bioavailability.ConclusionsPara-Coumaric acid, identified for the first time in A. phylicoides, was shown to have the highest predicted bioavailability suggesting that it could play a major role in the bioactivity of A. phylicoides.

Graphical abstract

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Elucidation of the possible mechanism of analgesic actions of butanol leaf fraction of Olax subscorpioidea Oliv

Publication date: 6 March 2017
Source:Journal of Ethnopharmacology, Volume 199
Author(s): Saidi Odoma, Abdulkadir Umar Zezi, Nuhu Mohammed Danjuma, Abubakar Ahmed, Muhammed Garba Magaji
Ethnopharmacological relevancePreparations of Olax subscorpioidea have been used traditionally for the management of pains, inflammatory diseases, yellow fever, cancer and rheumatism. Previously, the analgesic activity of its leaf extract have been reported. Furthermore, an analgesic assay guided fractionation showed that the butanol soluble fraction is the most active. However, the mechanism of this activity remains to be elucidated. This present study investigated the possible pharmacological mechanisms involved in the analgesic activity of the butanol leaf fraction of Olax subscorpioidea (BFOS) using the acetic acid induced writhing test in mice.Materials and methodsAnimals were orally administered distilled water (10ml/kg), BFOS (1,000mg/kg) and morphine (10mg/kg) 60minutes before i.p administration of acetic acid and the resulting writhing were counted for 10minutes. To establish the possible mechanism(s) of action of BFOS, separate group of animals were pretreated with naloxone (2mg/kg, i.p), prazosin (1mg/kg, i.p), yohimbine (1mg/kg, i.p), propranolol (20mg/kg, i.p), metergoline (2mg/kg, i.p), glibenclamide (5mg/kg, i.p) and l-arginine (50mg/kg, i.p) 15minutes before BFOS.ResultsBFOS and morphine showed marked analgesic activities (p<0.001); the pretreatment of animals with naloxone, metergoline and l-arginine significantly (p<0.05 and p<0.001) reduced the analgesic activity of BFOS; however, pretreatment with prazosin, yohimbine, propranolol and glinbenclamide showed no effect on its analgesic activity.ConclusionResults obtained in this study suggest the involvement of opioidergic, serotonergic and nitric oxide-l-arginine pathways in the analgesic effect of butanol leaf fraction of Olax subscorpioidea.

Graphical abstract

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A highly derived pliopithecoid from the Late Miocene of Haritalyangar, India

Publication date: April 2017
Source:Journal of Human Evolution, Volume 105
Author(s): Anek R. Sankhyan, Jay Kelley, Terry Harrison
The Late Miocene sequence at Haritalyangar, Himachal Pradesh, India, has produced abundant remains of the hominid Sivapithecus and the sivaladapids Sivaladapis and Indraloris. Also recovered from these sediments is an isolated and worn upper molar that was made the holotype of Krishnapithecus krishnaii and assigned to the Pliopithecoidea. However, the heavy wear and absence of definitive pliopithecoid features on the tooth rendered the assignment to this superfamily unconvincing. Here, we describe two lower molars from Haritalyangar that bear unmistakable pliopithecoid features and that are plausibly assignable to the same species as the type specimen of K. krishnaii. They convincingly demonstrate for the first time the presence of the Pliopithecoidea in South Asia. The new molars also reveal that K. krishnaii was perhaps the largest known pliopithecoid and that it possessed highly derived postcanine dental morphology. Because of its highly derived nature, it is difficult to determine its relationships within Pliopithecoidea, but a sister taxon relationship with either the Dionysopithecidae or Pliopithecinae is equally plausible; it is only distantly related to the Crouzeliinae. It is sufficiently distinct, however, from all other pliopithecoids to warrant placement in a separate family.



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The Interplay of Axonal Energy Homeostasis and Mitochondrial Trafficking and Anchoring

Publication date: Available online 20 February 2017
Source:Trends in Cell Biology
Author(s): Zu-Hang Sheng
Mitochondria are key cellular power plants essential for neuronal growth, survival, function, and regeneration after injury. Given their unique morphological features, neurons face exceptional challenges in maintaining energy homeostasis at distal synapses and growth cones where energy is in high demand. Efficient regulation of mitochondrial trafficking and anchoring is critical for neurons to meet altered energy requirements. Mitochondrial dysfunction and impaired transport have been implicated in several major neurological disorders. Thus, research into energy-mediated regulation of mitochondrial recruitment and redistribution is an important emerging frontier. In this review, I discuss new insights into the mechanisms regulating mitochondrial trafficking and anchoring, and provide an updated overview of how mitochondrial motility maintains energy homeostasis in axons, thus contributing to neuronal growth, regeneration, and synaptic function.



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Computer-aided Detection Fidelity of Pulmonary Nodules in Chest Radiograph

Nikolaos Dellios, Ulf Teichgraeber, Robert Chelaru, Ansgar Malich, Ismini E Papageorgiou

Journal of Clinical Imaging Science 2017 7(1):8-8

Aim: The most ubiquitous chest diagnostic method is the chest radiograph. A common radiographic finding, quite often incidental, is the nodular pulmonary lesion. The detection of small lesions out of complex parenchymal structure is a daily clinical challenge. In this study, we investigate the efficacy of the computer-aided detection (CAD) software package SoftView™ 2.4A for bone suppression and OnGuard™ 5.2 (Riverain Technologies, Miamisburg, OH, USA) for automated detection of pulmonary nodules in chest radiographs. Subjects and Methods: We retrospectively evaluated a dataset of 100 posteroanterior chest radiographs with pulmonary nodular lesions ranging from 5 to 85 mm. All nodules were confirmed with a consecutive computed tomography scan and histologically classified as 75% malignant. The number of detected lesions by observation in unprocessed images was compared to the number and dignity of CAD-detected lesions in bone-suppressed images (BSIs). Results: SoftView™ BSI does not affect the objective lesion-to-background contrast. OnGuard™ has a stand-alone sensitivity of 62% and specificity of 58% for nodular lesion detection in chest radiographs. The false positive rate is 0.88/image and the false negative (FN) rate is 0.35/image. From the true positive lesions, 20% were proven benign and 80% were malignant. FN lesions were 47% benign and 53% malignant. Conclusion: We conclude that CAD does not qualify for a stand-alone standard of diagnosis. The use of CAD accompanied with a critical radiological assessment of the software suggested pattern appears more realistic. Accordingly, it is essential to focus on studies assessing the quality-time-cost profile of real-time (as opposed to retrospective) CAD implementation in clinical diagnostics.

http://ift.tt/2m42b5Y

Erratum: SYNTAX Score in Patients with High Computed Tomography Coronary Calcium Score

Journal of Clinical Imaging Science 2017 7(1):10-10



http://ift.tt/2m0D1IE

Asymptomatic Urolithiasis Complicated by Nephrocutaneous Fistula

Marion Hamard, Gaël Amzalag, Christoph D Becker, Pierre-Alexandre Poletti

Journal of Clinical Imaging Science 2017 7(1):9-9

Asymptomatic spontaneous nephrocutaneous fistula is a rare and severe complication of chronic urolithiasis. We report a case of 56-year-old woman with a nephrocutaneous fistula (NFC) which developed from a superinfected urinoma following calyceal rupture due to an obstructing calculus in the left ureter. The patient was clinically asymptomatic and came to the emergency department for a painless left flank fluctuating mass. This urinoma was superinfected, with a delayed development of renal abscesses and perirenal phlegmon found on contrast-enhanced uro-computed tomography (CT), responsible for left renal vein thrombophlebitis and left psoas abscess.. Thereafter, a 99 mTc dimercaptosuccinic acid (DMSA) scintigraphy revealed a nonfunctional left kidney, leading to the decision of left nephrectomy. Chronic urolithiasis complications are rare and only few cases are reported in medical literature. A systematic medical approach helped selecting the best imaging modality to help diagnosis and treatment. Indeed, uro-CT scan and renal scintigraphy with 99 mTc-DMSA are the most sensitive imaging modalities to investigate morphological and functional urinary tract consequences of NFC, secondary to chronic urolithiasis.

http://ift.tt/2m450DR

Gastropleural Fistula with Aortic Intramural Involvement

Akshya Gupta, Abhishek Chaturvedi, Patrick Fultz, Susan Hobbs

Journal of Clinical Imaging Science 2017 7(1):7-7

Gastropleural fistula is a relatively rare complication that can be seen as a result of traumatic, nontraumatic, benign, and neoplastic etiologies. Most commonly, these are found in patients with diaphragmatic herniation or prior thoracic surgery. Aortoenteric fistulas are rare communications typically between the abdominal aorta and bowel. We present a rare case of an 88-year-old male who developed a gastropleural fistula with erosions into the wall of the descending thoracic aorta. Computed tomography (CT) is a leading modality in evaluation of suspected gastropleural or aortoenteric fistulas given the quick scan time and widespread availability. Prompt diagnosis is essential and requires an understanding of appropriate CT protocols and CT imaging appearance.

http://ift.tt/2m0DJFH

Different Sonographic Faces of Ectopic Pregnancy

Charu Chanana, Nishant Gupta, Itisha Bansal, Kusum Hooda, Pranav Sharma, Mohit Gupta, Darshan Gandhi, Yogesh Kumar

Journal of Clinical Imaging Science 2017 7(1):6-6

Vaginal bleeding in the first trimester has wide differential diagnoses, the most common being a normal early intrauterine pregnancy, with other potential causes including spontaneous abortion and ectopic pregnancy. The incidence of ectopic pregnancy is approximately 2% of all reported pregnancies and is one of the leading causes of maternal mortality worldwide. Clinical signs and symptoms of ectopic pregnancy are often nonspecific. History of pelvic pain with bleeding and positive β-human chorionic gonadotropin should raise the possibility of ectopic pregnancy. Knowledge of the different locations of ectopic pregnancy is of utmost importance, in which ultrasound imaging plays a crucial role. This pictorial essay depicts sonographic findings and essential pitfalls in diagnosing ectopic pregnancy.

http://ift.tt/2m49RFj

Evaluating the Pre-Positioning Frame for Robotic Acoustic Neuroma Removal Surgery

Condition:   Acoustic Neuroma
Intervention:   Other: Testing of Pre-Positioning Frame
Sponsors:   Vanderbilt University Medical Center;   National Institute on Deafness and Other Communication Disorders (NIDCD)
Not yet recruiting - verified February 2017

http://ift.tt/2ldOPpv

A Study of the Addition of Pembrolizumab to Postoperative Radiotherapy in Resected High Risk Cutaneous Squamous Cell Cancer of the Head and Neck

Condition:   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: Pembrolizumab;   Radiation: IMRT 60-66Gy
Sponsor:   Case Comprehensive Cancer Center
Not yet recruiting - verified February 2017

http://ift.tt/2meH689

Ultrasound-guided Percutaneous Microwave Ablation for Benign Thyroid Nodules

Condition:   Thyroid Nodule
Intervention:   Device: Microwave Ablation
Sponsors:   Wenjun Wu;   First Affiliated Hospital of Wenzhou Medical Univeristy
Not yet recruiting - verified February 2017

http://ift.tt/2ldNf6U

A Phase 1/2 Safety Study of Intratumorally Dosed INT230-6

Conditions:   Melanoma;   Head and Neck Cancer;   Lymphoma;   Breast Cancer;   Pancreatic Cancer;   Liver Cancer;   Colon Cancer;   Lung Cancer;   Glioblastoma
Interventions:   Drug: INT230-6;   Biological: anti-PD-1;   Biological: anti-PD-1 antibody
Sponsors:   Intensity Therapeutics, Inc.;   University of Southern California;   University Health Network, Toronto
Recruiting - verified February 2017

http://ift.tt/2meJ6gE

PDL and Fractional Photothermolysis for Postsurgical Scars

Condition:   Scar
Interventions:   Device: PDL (Pulsed Dye Laser);   Device: Fractional Photothermolysis Laser
Sponsor:   Northwestern University
Not yet recruiting - verified February 2017

http://ift.tt/2ldXdoD

Prospective Study Evaluating the Feasibility of Fiducial Markers Placement for Patients With Esophageal or Rectal Cancer

Conditions:   Esophageal Neoplasm;   Rectal Neoplasms
Intervention:   Device: fiducial markers placement
Sponsors:   Société Française d'Endoscopie Digestive;   Cook
Recruiting - verified February 2017

http://ift.tt/2meGkrJ

Trial of Image-Guided Cochlear Implant Programming Versus Standard of Care

Condition:   Cochlear Implant
Interventions:   Other: Standard of Care;   Other: Image-Guided Cochlear Implant Programming
Sponsors:   Vanderbilt University Medical Center;   National Institute on Deafness and Other Communication Disorders (NIDCD)
Recruiting - verified February 2017

http://ift.tt/2ldSPWJ

Interventional Endoscopy Database for Pancreatico-biliary, Gastrointestinal and Esophageal Disorders

Conditions:   Ampullary Cancer;   Duodenal Cancer;   Bile Duct Cancer;   Bile Duct Disorders;   Gallstones;   Obstructive Jaundice;   Pancreatic Disorders (Noncancerous);   Colorectal Cancer;   Esophageal Cancer;   Barrett's Esophagus;   Gastric Malignancies;   Pancreatic Cancer;   Pediatric Gastroenterology;   Cholangiocarcinoma;   Pancreatic Pseudocysts;   Acute and Chronic Pancreatitis;   Recurrent Pancreatitis;   Cholangitis;   Bile Leak;   Biliary Strictures;   Pancreatic Divisum;   Biliary and Pancreatic Stones;   Choledocholithiasis
Intervention:   Procedure: Interventional Endoscopy
Sponsor:   Weill Medical College of Cornell University
Recruiting - verified February 2017

http://ift.tt/2meJ7kQ

Cover Image, Volume 86, Issue 3

The image is based on the Original article, "Altered Spontaneous Brain Activity in Cushing's disease: A Resting-State Functional MRI Study," by QING-FANG SUN et al., 10.1111/cen.13277.

http://ift.tt/2m0hShG

Discoloured saggy skin in a 57-year-old woman

http://ift.tt/2lmvrET

Bullous pemphigoid arising in a patient with acquired perforating dermatosis

Summary

A middle-aged Japanese man who had been on haemodialysis treatment for diabetic nephropathy developed multiple itchy papules and nodules, which were histopathologically diagnosed as acquired perforating dermatosis. Two years later he developed oral lesions and subsequently numerous erosive plaques with necrotic crusts on the trunk and extremities. Histopathology of a papule showed a parakeratotic plug intermingled with basophilic, necrotic debris and collagen bundles, along with penetration of collagen bundles across the epidermis and subepidermal blister. Immunoblotting studies revealed IgG autoantibodies in the patient's serum, which reacted with the C-terminal and the NC16a domains of bullous pemphigoid (BP)180, indicating presence of BP. We searched the literature and found no other cases of an autoimmune blistering disease occurring in association with a perforating disorder. Possible injury to the basement membrane zone induced during the process of transepidermal elimination might be involved in the pathogenesis of the pemphigoid disease.

http://ift.tt/2kE08Z5

Superficial granulomatous pyoderma with eye and lung involvement in a patient with multiple sclerosis

http://ift.tt/2lmFdap

Compliance with national guidelines on isotretinoin: where are we 2 years since the last audit? Results of the National Isotretinoin Re-Audit 2014

Summary

Background

In 2010, the British Association of Dermatologists (BAD) published clinical guidelines for the safe introduction and continued use of isotretinoin in patients with acne in the UK. The BAD provides UK dermatologists with a facility for national audit, and it undertook an audit on compliance with these guidelines in 2012.

Aim

To determine current clinical practices relating to use of isotretinoin among dermatologists in the UK (including geographical variations) as measured against BAD standards, and to ascertain any improvement since the 2012 audit.

Methods

The 2012 isotretinoin audit proforma was used, with additional questions on clinical setting, complaints and litigation. A web-based survey tool was used for data entry and submission, with email invitation to working, UK-based BAD members (n = 1226) in December 2013 and weekly reminders during the 8.5-week data collection period. Responders were requested to enter data for the three most recent consecutive patients (including one male and one female patient) who had completed treatment within the previous 6 months.

Results

In total, 338 (27.6%) respondents provided data on 1013 patients. Serum lipids were checked in 93.4% of patients and documentation of mental health and/or mood state was recorded in 82.1%. Regarding the Pregnancy Prevention Programme (PPP), 91.6% of female patients of childbearing potential had signed the PPP information form, while 93.3% who had followed the PPP had taken pregnancy tests both before and during treatment, and 54.7% had taken a pregnancy test 5 weeks post-treatment.

Conclusion

Overall, there is currently good compliance with standards. Certain aspects of care that are less frequently preformed, such as pregnancy testing post-treatment, are highlighted.

http://ift.tt/2kE6vfc

Clearer labelling of ingredients in medicines is required

http://ift.tt/2lmw9C5

Recurrent penile squamous cell carcinoma in an elderly circumcised man

http://ift.tt/2kE1bbv

Diagnostic accuracy of reflectance confocal microscopy using VivaScope for detecting and monitoring skin lesions: a systematic review

Summary

Background

Skin cancer is one of the most common cancers in the UK. Patients with suspicious skin lesions are assessed clinically with/without dermoscopy, and lesions still considered suspicious are then surgically removed or have the diagnosis confirmed by a punch biopsy.

Aim

To evaluate the diagnostic accuracy of the in vivo VivaScope^© reflective confocal microscopy (RCM) system, a noninvasive technology designed to provide a more accurate presurgical diagnosis, leading to fewer biopsies of benign lesions, or to provide greater accuracy for lesion margins.

Methods

MEDLINE, EMBASE and the Cochrane Library were searched to identify studies evaluating dermoscopy plus RCM, or RCM alone, with histopathology as the reference test. Clinical experts were also contacted for information on unpublished studies.

Results

Eleven studies met the inclusion criteria but were too heterogeneous to be combined by meta-analysis. Results indicated that VivaScope subsequent to dermoscopy may improve diagnostic accuracy of malignant melanomas compared with dermoscopy. For margin delineation, the data suggest that mapping using VivaScope 1500 for lentigo maligna (LM) and LM melanoma may improve accuracy in terms of complete excision of lesions compared with dermoscopically determined margins. For basal cell carcinoma, the limited data show high diagnostic accuracy with both VivaScope 1500 and VivaScope 3000. Evidence on the effectiveness of VivaScope in diagnosing cutaneous squamous cell carcinomas was very limited.

Conclusion

The use of VivaScope 1500 following dermoscopy may improve patient care and management of suspicious skin lesions, although the generalizability of these results to the UK population remains unclear.

http://ift.tt/2lmzlxR

Quantitative light-induced fluorescence images and digital photographs - Reproducibility of manually marked demineralisations

Abstract

Objective

Hard tooth tissue demineralisation is an undesirable side effect of orthodontic treatment with fixed appliances. Whereas both clinically and in digital photographs (DP), demineralisations appear as white spot lesions, WSLs appear as dark areas when quantitative light-induced fluorescence (QLF) imaging is used. This study aims at comparing the reproducibility of the detection of decalcified tooth areas in DP and QLF.

Materials and methods

DP and QLF pairs were acquired from 139 teeth of 32 patients after braces removal. Three raters manually marked the decalcified area on both DP and QLF images. The markings were repeated after 2 weeks. A ground truth was estimated for each tooth and modality using the simultaneous truth and performance level estimation (STAPLE) algorithm. The Dice coefficients (DC) of each rater marking to the ground truth were calculated for all teeth and modalities to quantify the spatial agreement. A three-way repeated measures analysis of variance (ANOVA) was used to compare the means of the DCs for both modalities ( \( p\; < \;0.05 \) ). Intra-observer and intercycle variabilities were assessed comparing the means across the raters and the cycles for both modalities.

Results

ANOVA revealed a statistical significant difference between the modalities [ \( F (1, 138)\; = \; 62.89 \) , \( p \; < \; 0.001 \) ]. The standard deviation of the DC for the photographs are lower than those for the QLF images. Intra-observer and intercycle differences are rather small as compared to the intermodality differences.

Conclusions

The results indicate a higher spatial reproducibility in identifying a decalcified area on a tooth surface using visual inspection of DP rather than QLF images.

http://ift.tt/2lyIO7e

Retrospective 25-year follow-up of treatment outcomes in angle Class III patients

Abstract

Objectives

To assess early versus late treatment of Class III syndrome for skeletal and dental differences.

Methods

Thirty-eight Class III patients treated with a chincup were retrospectively analyzed. Baseline data were obtained by reviewing pretreatment (T0) anamnestic records, cephalograms, and casts. The cases were assigned to an early or a late treatment group based on age at T0 (up to 9 years or older than 9 years but before the pubertal growth spurt). Both groups were further compared based on posttreatment data (T1) and long-term follow-up data collected approximately 25 years after treatment (T2).

Results

Early treatment was successful in 74% and late treatment in 67% of cases. More failures were noted among male patients. The late treatment group was characterized post therapeutically by significantly more pronounced skeletal parameters of jaw size relative to normal Class I values; in addition, a greater skeletal discrepancy between maxilla and mandible, higher values for mandibular length, Cond-Pog, ramus height, overjet, anterior posterior dysplasia indicator (APDI), lower anterior face height, and gonial angle were measured at T1. The angle between the AB line and mandibular plane was found to be larger at T0, T1, and T2, as well as more pronounced camouflage positions of the lower anterior teeth at T0. The early treatment group was found to exhibit greater amounts of negative overjet at T0 but more effective correction at T1.

Conclusions

Early treatment of Class III syndrome resulted in greater skeletal changes with less dental compensation.

http://ift.tt/2kZchnK

Quantitative light-induced fluorescence images and digital photographs - Reproducibility of manually marked demineralisations

Abstract

Objective

Hard tooth tissue demineralisation is an undesirable side effect of orthodontic treatment with fixed appliances. Whereas both clinically and in digital photographs (DP), demineralisations appear as white spot lesions, WSLs appear as dark areas when quantitative light-induced fluorescence (QLF) imaging is used. This study aims at comparing the reproducibility of the detection of decalcified tooth areas in DP and QLF.

Materials and methods

DP and QLF pairs were acquired from 139 teeth of 32 patients after braces removal. Three raters manually marked the decalcified area on both DP and QLF images. The markings were repeated after 2 weeks. A ground truth was estimated for each tooth and modality using the simultaneous truth and performance level estimation (STAPLE) algorithm. The Dice coefficients (DC) of each rater marking to the ground truth were calculated for all teeth and modalities to quantify the spatial agreement. A three-way repeated measures analysis of variance (ANOVA) was used to compare the means of the DCs for both modalities ( \( p\; < \;0.05 \) ). Intra-observer and intercycle variabilities were assessed comparing the means across the raters and the cycles for both modalities.

Results

ANOVA revealed a statistical significant difference between the modalities [ \( F (1, 138)\; = \; 62.89 \) , \( p \; < \; 0.001 \) ]. The standard deviation of the DC for the photographs are lower than those for the QLF images. Intra-observer and intercycle differences are rather small as compared to the intermodality differences.

Conclusions

The results indicate a higher spatial reproducibility in identifying a decalcified area on a tooth surface using visual inspection of DP rather than QLF images.

http://ift.tt/2lyIO7e

Retrospective 25-year follow-up of treatment outcomes in angle Class III patients

Abstract

Objectives

To assess early versus late treatment of Class III syndrome for skeletal and dental differences.

Methods

Thirty-eight Class III patients treated with a chincup were retrospectively analyzed. Baseline data were obtained by reviewing pretreatment (T0) anamnestic records, cephalograms, and casts. The cases were assigned to an early or a late treatment group based on age at T0 (up to 9 years or older than 9 years but before the pubertal growth spurt). Both groups were further compared based on posttreatment data (T1) and long-term follow-up data collected approximately 25 years after treatment (T2).

Results

Early treatment was successful in 74% and late treatment in 67% of cases. More failures were noted among male patients. The late treatment group was characterized post therapeutically by significantly more pronounced skeletal parameters of jaw size relative to normal Class I values; in addition, a greater skeletal discrepancy between maxilla and mandible, higher values for mandibular length, Cond-Pog, ramus height, overjet, anterior posterior dysplasia indicator (APDI), lower anterior face height, and gonial angle were measured at T1. The angle between the AB line and mandibular plane was found to be larger at T0, T1, and T2, as well as more pronounced camouflage positions of the lower anterior teeth at T0. The early treatment group was found to exhibit greater amounts of negative overjet at T0 but more effective correction at T1.

Conclusions

Early treatment of Class III syndrome resulted in greater skeletal changes with less dental compensation.

http://ift.tt/2kZchnK

The C1q complement family of synaptic organizers: not just complementary

Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Michisuke Yuzaki
Molecules that regulate formation, differentiation, and maintenance of synapses are called synaptic organizers. Recently, various 'C1q family' proteins have been shown to be released from neurons, and serve as a new class of synaptic organizers. Cbln1 and C1ql1 proteins regulate the formation and maintenance of parallel fiber-Purkinje cell and climbing fiber-Purkinje cell synapses, respectively, in the cerebellum. Cbln1 also modulates the function of postsynaptic delta2 glutamate receptors to regulate synaptic plasticity. C1ql2 and C1ql3, released from mossy fibers, determine the synaptic localization of postsynaptic kainate receptors in the hippocampus. C1ql3 also regulates the formation of synapses between the basolateral amygdala and the prefrontal cortex. These findings indicate the diverse functions of C1q family proteins in various brain regions.

Graphical abstract

http://ift.tt/2lyq5bQ

Epilepsy and synaptic proteins

Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Yuko Fukata, Masaki Fukata
Throughout history, epilepsy affects about 1–2% of the population worldwide. Epilepsy can be caused by traumatic brain injury, exposure to certain toxins and drugs, and mutations of genes that often encode synaptic proteins. In addition to conventional linkage and association studies, the recent trio exome sequencing in epilepsy and proteomic analysis in autoimmune synaptopathies have accelerated identification of novel epilepsy-related proteins, most of which play critical roles in synaptic transmission. Furthermore, super-resolution microscopy analysis has revealed subsynaptic nanoscale distribution of presynaptic and postsynaptic proteins and suggests a precise trans-synaptic alignment of neurotransmitter release to receptors. Such identification and characterization of epilepsy-related synaptic proteins have been promoting the development of anti-epileptic drugs and the understanding of mechanisms of synaptic transmission.



http://ift.tt/2lyEogE

Hippocampal NR3C1 DNA methylation can mediate part of preconception paternal stress effects in rat offspring

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Somayeh Niknazar, Arezo Nahavandi, Ali Asghar Peyvandi, Hassan Peyvandi, Navid Ahmady Roozbahany, Hojjat-Allah Abbaszadeh
Many studies have been shown that maternal stress during pregnancy and in early life period influences offspring in the behavioral and molecular aspects in human and animal models. Recent research has indicated that the environmental condition of males before conception has effects on next generations. We evaluated whether preconception paternal stress (PPS) could influence on hippocampal glucocorticoid receptor gene (GR), (NR3C1) expression, corticosterone response and behavioral outcomes of their offspring. For this purpose, adult male rats were subjected to daily 10min session of forced swimming for 21 consecutive days. Then, two parental breeding groups were formed: stressed father (SF) and non-stressed father (NSF) or control group. 30-day-old pups were tested for anxiety-like behavior by using the elevated plus maze (EPM). Serum corticosterone level was also measured by ELISA. Hippocampal NR3C1 DNA methylation, gene and protein expression were respectively assayed by methylation sensitive restriction enzymes (Real Time PCR), Reverse Transcriptase PCR (RT-PCR) and Western-blotting in all groups. More anxiety-related behavior, serum corticosterone concentration, DNA methylation levels of NR3C1 and lower expression of this gene were significantly observed in paternally stressed pups compared to control pups. As well, molecular changes were more pronounced in male pups compared to female pups. Our results revealed that paternal stress prior to conception has a negative effect on molecular, hormonal and behavioral outcomes in their offspring.



http://ift.tt/2lypjvH

Think twice, it’s all right: Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Johannes Björkstrand, Thomas Agren, Fredrik Åhs, Andreas Frick, Elna-Marie Larsson, Olof Hjorth, Tomas Furmark, Mats Fredrikson
Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10min than the 6h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10min than the 6h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance.



http://ift.tt/2kZ4xC8

Sex differences in interval timing and attention to time in C57Bl/6J mice

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Mona Buhusi, Mitchell J. Bartlett, Catalin V. Buhusi
Interval timing is crucial for decision-making and motor control and is impaired in many neuropsychiatric disorders. Previous studies examined timing in various strains or genetically-altered mice, but not in parallel in male and female mice in the same experimental setting. We investigated timing and attention to time in male and female C57Bl/6J mice, when presented with gaps in the timed stimulus, novel auditory distracters presented during the un-interrupted timed stimulus, and gap+distracter combinations. No sex differences were found in regard to timing accuracy and precision. However, presentation of the gap+distracter combination over-reset timing in males but had a much smaller effect in females. The over-reset strategy was reported previously with emotional distracters (e.g., previously paired with footshock) but not with neutral distracters. These results reveal sex differences in attentional gating/switching or working memory for time.



http://ift.tt/2lynyhK

Detecting RNA modifications in the epitranscriptome: predict and validate

Nature Reviews Genetics. doi:10.1038/nrg.2016.169

Authors: Mark Helm & Yuri Motorin

http://ift.tt/2mdkBAw

Sinigrin inhibits production of inflammatory mediators by suppressing NF-κB/MAPK pathways or NLRP3 inflammasome activation in macrophages

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Hee-Weon Lee, Chung Gi Lee, Dong-Kwon Rhee, Sung Hee Um, Sukneung Pyo
Sinigrin (2-propenyl glucosinolate) is found mainly in broccoli, brussels sprouts, and black mustard seeds. Recently, sinigrin has received attention for its role in disease prevention and health. This study investigated the effect of sinigrin on macrophage function, including the activity of Nod-like receptor protein 3 (NLRP3) inflammasome. In a concentration-dependent manner, sinigrin inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production and the expression of COX-2 and prostaglandin E2 (PGE2) in RAW 264.7 cells. In addition, sinigrin significantly suppressed the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 via suppression of MAPK phosphorylation and nuclear factor-kappa B (NF-κB) activity. Treatment with sinigrin decreased IL-1β and IL-18 production and concurrently suppressed NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 expression in LPS/ATP-stimulated cells, suggesting that the blocking of NLRP3 inflammasome activation prevented the production of both cytokines. Collectively, these results suggest that sinigrin has immunomodulatory effects by suppressing the production of inflammatory mediators, possibly by inhibiting the NF-κB/MAPK pathways or NLRP3 inflammasome activation. Our findings also provide evidence that the pharmacological modulation of sinigrin could have an anti-inflammatory effect.



http://ift.tt/2lBHzEG

Do Mammalian Cells Really Need to Export and Import Heme?

Publication date: Available online 20 February 2017
Source:Trends in Biochemical Sciences
Author(s): Prem Ponka, Alex D. Sheftel, Ann M. English, D. Scott Bohle, Daniel Garcia-Santos
Heme is a cofactor that is essential to almost all forms of life. The production of heme is a balancing act between the generation of the requisite levels of the end-product and protection of the cell and/or organism against any toxic substrates, intermediates and, in this case, end-product. In this review, we provide an overview of our understanding of the formation and regulation of this metallocofactor and discuss new research on the cell biology of heme homeostasis, with a focus on putative transmembrane transporters now proposed to be important regulators of heme distribution. The main text is complemented by a discussion dedicated to the intricate chemistry and biochemistry of heme, which is often overlooked when new pathways of heme transport are conceived.



http://ift.tt/2lcuccU

Detecting RNA modifications in the epitranscriptome: predict and validate

Although it has been known for decades that RNA is subjected to numerous covalent modifications, there has been a recent surge in interest driven by sequencing-based transcriptome-wide detection methods and the realization that RNA modifications have important roles in diverse biological processes. This Review describes the range of detection strategies for RNA modifications, their particular strengths and limitations, and how responsible and complementary application of these techniques will be required to ensure the quality and interpretability of the rapidly accumulating data sets.

http://ift.tt/2m2TOr9

Multi-resolution multi-object statistical shape models based on the locality assumption

Publication date: Available online 17 February 2017
Source:Medical Image Analysis
Author(s): Matthias Wilms, Heinz Handels, Jan Ehrhardt
Statistical shape models learned from a population of previously observed training shapes are nowadays widely used in medical image analysis to aid segmentation or classification. However, providing an appropriate and representative training population of preferably manual segmentations is typically either very labor-intensive or even impossible. Therefore, statistical shape models in practice frequently suffer from the high-dimension-low-sample-size (HDLSS) problem resulting in models with insufficient expressiveness.In this paper, a novel approach for learning representative multi-resolution multi-object statistical shape models from a small number of training samples that adequately model the variability of each individual object as well as their interrelations is presented. The method is based on the assumption of locality, which means that local shape variations have limited effects in distant areas and, therefore, can be modeled independently. This locality assumption is integrated into the standard statistical shape modeling framework by manipulating the sample covariance matrix (non-zero covariances between distant landmarks are set to zero). To allow for multi-object modeling, a method for computing distances between points located on different object shapes is proposed. Furthermore, different levels of locality are introduced by deriving a multi-resolution scheme, which is equipped with a method to combine variability information modeled at different levels into a single shape model. This combined representation of global and local variability in a single shape model allows the use of the classical active shape model strategy for model-based image segmentation.An extensive evaluation based on a public data base of 247 chest radiographs is performed to show the modeling and segmentation capabilities of the proposed approach in single- and multi-object HDLSS scenarios. The new approach is not only compared to the classical shape modeling method but also to three state-of-the-art shape modeling approaches specifically designed to cope with the HDLSS problem. The results show that the new approach significantly outperforms all other approaches in terms of generalization ability and model-based segmentation accuracy.

Graphical abstract

http://ift.tt/2l8sJV6

Visfatin correlates with hot flashes in postmenopausal women with metabolic syndrome: effects of genistein

Abstract

During menopause, an increased prevalence of metabolic syndrome (MetS) and central obesity seems to increase hot flashes (HFs). Visfatin is an inflammatory adipokine secreted by visceral fat. We investigated visfatin levels and its relationship with hot flash number and BMI, in postmenopausal women with MetS. We also evaluated the effect of genistein, an isoflavone effective in reducing HFs, on visfatin levels and HFs after 1 year of treatment. This was a randomized, double-blind, placebo-controlled trial. Postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein (n = 60), daily for 1 year. As main outcome measures, hot flashes number and circulating visfatin levels were evaluated. Visfatin significantly correlated with BMI and HFs number in women with MetS at basal. After 6 and 12 months, our results indicate a strong correlation and a significant effect of genistein in reducing both HFs and visfatin in women with MetS. The present study suggests that visfatin plays a role in the vasomotor symptoms, at least in postmenopausal women with metabolic syndrome. Genistein may reduce HFs decreasing the circulating levels of this inflammatory adipokine.

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