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Πέμπτη, 22 Φεβρουαρίου 2018

Revenue Increase following 2017 Multiple Procedures Payment Reduction Modification: Differential Impact on Neuroradiology--Report from an Academic Medical Center [PRACTICE PERSPECTIVES]

BACKGROUND AND PURPOSE:

The Centers for Medicare and Medicaid Services imposed a 25% professional component multiple procedure payment reduction for the professional component of advanced diagnostic imaging modalities in January 2012. In 2017, the Centers for Medicare and Medicaid Services rolled back the multiple procedure payment reduction to 5% for subsequent imaging. To evaluate the effect of this change, we analyzed 5 months of Centers for Medicare and Medicaid Services procedures at Johns Hopkins Medical Institution.

MATERIALS AND METHODS:

We analyzed the procedure codes and reimbursement rate for studies performed between January 1 and May 31, 2017. Patients with Medicare insurance who had multiple diagnostic procedures in a day were selected. Per the Centers for Medicare and Medicaid Services guidelines, procedures with the highest price were considered fully reimbursed and subsequent studies were marked for differences between 25% (2013–2016) and 5% reduction (2017).

RESULTS:

We included 8787 patients with 22,236 procedures (mean, 2.53 studies/day). CT, MR imaging, and ultrasound scans composed 75.9%, 21.5%, and 2.6% of all studies, with 61.2%, 54.9%, and 85.4% of the procedures of each technique subject to multiple procedure payment reduction, respectively. The projected reimbursement for these studies was $1,666,437, which translated to a $179,782 (12.1%) increase in revenue comparing 25%-versus-5% multiple procedure payment reduction rates for 5 months: $128,542 for CT, $47,802 for MR imaging, and $3439 for ultrasound. The annual overall prorated increase in revenue would be $431,476. The impact was maximal for neuroradiology.

CONCLUSIONS:

With the recent favorable adjustment in multiple procedure payment reduction regulations, CT-heavy subspecialties like neuroradiology benefit the most with revenue increases. Different practice settings might experience revenue increases to a different extent, depending on the procedure and payer mix.



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HARMless: Transient Cortical and Sulcal Hyperintensity on Gadolinium-Enhanced FLAIR after Elective Endovascular Coiling of Intracranial Aneurysms [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR has been increasingly recognized after iodinated contrast medium exposure during angiographic procedures. The goal of this study was to assess the relationship of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR against various variables in patients following elective endovascular treatment of intracranial aneurysms.

MATERIALS AND METHODS:

We performed a retrospective review of 58 patients with 62 MR imaging studies performed within 72 hours following endovascular treatment of intracranial aneurysms. Patient demographics, aneurysm location, and vascular territory distribution of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR were documented. Analysis of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR with iodinated contrast medium volume, procedural duration, number of angiographic runs, and DWI lesions was performed.

RESULTS:

Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR was found in 32/62 (51.61%) post-endovascular treatment MR imaging studies, with complete resolution of findings in all patients on the available follow-up studies (27/27). Angiographic iodinated contrast medium injection and arterial anatomy matched the vascular distribution of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR. No significant association was found between cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR with iodinated contrast medium volume (P = .56 value) and the presence of DWI lesions (P = .68). However, a significant association was found with procedural time (P = .001) and the number of angiographic runs (P = .019). No adverse clinical outcomes were documented.

CONCLUSIONS:

Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR is a transient observation in the arterial territory exposed to iodinated contrast medium during endovascular treatment of intracranial aneurysms. Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR is significantly associated with procedural time, and the frequency of angiographic runs suggesting a potential technical influence on the breakdown of the BBB, but no reported adverse clinical outcome or association with both iodinated contrast medium volume and DWI lesions was found. Recognition of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR as a benign incidental finding is vital to avoid unnecessary investigation.



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Quantification of Intracranial Aneurysm Volume Pulsation with 7T MRI [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Aneurysm volume pulsation is a potential predictor of intracranial aneurysm rupture. We evaluated whether 7T MR imaging can quantify aneurysm volume pulsation.

MATERIALS AND METHODS:

In Stage I of the study, 10 unruptured aneurysms in 9 patients were studied using a high-resolution (0.6-mm, isotropic) 3D gradient-echo sequence with cardiac gating. Semiautomatic segmentation was used to measure aneurysm volume (in cubic millimeters) per cardiac phase. Aneurysm pulsation was defined as the relative increase in volume between the phase with the smallest volume and the phase with the largest volume. The accuracy and precision of the measured volume pulsations were addressed by digital phantom simulations and a repeat image analysis. In Stage II, the imaging protocol was optimized and 9 patients with 9 aneurysms were studied with and without administration of a contrast agent.

RESULTS:

The mean aneurysm pulsation in Stage I was 8% ± 7% (range, 2%–27%), with a mean volume change of 15 ± 14 mm3 (range, 3–51 mm3). The mean difference in volume change for the repeat image analysis was 2 ± 6 mm3. The artifactual volume pulsations measured with the digital phantom simulations were of the same magnitude as the volume pulsations observed in the patient data, even after protocol optimization in Stage II.

CONCLUSIONS:

Volume pulsation quantification with the current imaging protocol on 7T MR imaging is not accurate due to multiple imaging artifacts. Future studies should always include aneurysm-specific accuracy analysis.



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An Automated Statistical Technique for Counting Distinct Multiple Sclerosis Lesions [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions.

MATERIALS AND METHODS:

MR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites.

RESULTS:

The proposed count and the criterion standard count were highly correlated (r = 0.97, P < .001) and not significantly different (t59 = –.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated (t58 = –2.73, P < .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale (r = 0.35, P < .01) than lesion load (r = 0.10, P = .44) or lesion count (r = –.12, P = .36) alone.

CONCLUSIONS:

This study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone.



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Sonographic Development of the Pericallosal Vascularization in the First and Early Second Trimester of Pregnancy [PEDIATRICS]

BACKGROUND AND PURPOSE:

Anomalies of the corpus callosum are rare. Routine scanning in midtrimester of the pregnancy often fails to identify defective development. The purpose of the study was to identify the pericallosal artery and all its main branching arteries during early gestation from the first trimester onward, to measure the length of the pericallosal artery during its development, and to establish a normal vascular map for each week of development.

MATERIALS AND METHODS:

We performed a single-center prospective, longitudinal clinical study in 15 patients between 11 and 22 weeks of gestation. The origin and course of the different blood vessels were identified.

RESULTS:

There was a linear association among gestational age, the biparietal diameter, and the length of the pericallosal artery. The curvature of the developing pericallosal artery increases linearly with the gestational age and biparietal diameter, and 4 variations of branching of the callosomarginal artery were observed.

CONCLUSIONS:

The pericallosal artery and its branches can be identified and measured from 11 weeks on, and the pericallosal artery takes its characteristic course. A defective course or an abnormal biometry of the pericallosal artery could be an early sonographic marker of abnormal development of the corpus callosum.



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Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Inhomogeneous magnetization transfer is a new endogenous MR imaging contrast mechanism that has demonstrated high specificity for myelin. Here, we tested the hypothesis that inhomogeneous magnetization transfer is sensitive to pathology in a population of patients with relapsing-remitting MS in a way that both differs from and complements conventional magnetization transfer.

MATERIALS AND METHODS:

Twenty-five patients with relapsing-remitting MS and 20 healthy volunteers were enrolled in a prospective MR imaging research study, whose protocol included anatomic imaging, standard magnetization transfer, and inhomogeneous magnetization transfer imaging. Magnetization transfer and inhomogeneous magnetization transfer ratios measured in normal-appearing brain tissue and in MS lesions of patients were compared with values measured in control subjects. The potential association of inhomogeneous magnetization transfer ratio variations with the clinical scores (Expanded Disability Status Scale) of patients was further evaluated.

RESULTS:

The magnetization transfer ratio and inhomogeneous magnetization transfer ratio measured in the thalami and frontal, occipital, and temporal WM of patients with MS were lower compared with those of controls (P < .05). The mean inhomogeneous magnetization transfer ratio measured in lesions was lower than that in normal-appearing WM (P < .05). Significant (P < .05) negative correlations were found between the clinical scores and inhomogeneous magnetization transfer ratio measured in normal-appearing WM structures. Weaker nonsignificant correlation trends were found for the magnetization transfer ratio.

CONCLUSIONS:

The sensitivity of the inhomogeneous magnetization transfer technique for MS was highlighted by the reduction in the inhomogeneous magnetization transfer ratio in MS lesions and in normal-appearing WM of patients compared with controls. Stronger correlations with the Expanded Disability Status Scale score were obtained with the inhomogeneous magnetization transfer ratio compared with the standard magnetization transfer ratio, which may be explained by the higher specificity of inhomogeneous magnetization transfer for myelin.



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Brain Injury Lesion Imaging Using Preconditioned Quantitative Susceptibility Mapping without Skull Stripping [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Identifying cerebral microhemorrhage burden can aid in the diagnosis and management of traumatic brain injury, stroke, hypertension, and cerebral amyloid angiopathy. MR imaging susceptibility-based methods are more sensitive than CT for detecting cerebral microhemorrhage, but methods other than quantitative susceptibility mapping provide results that vary with field strength and TE, require additional phase maps to distinguish blood from calcification, and depict cerebral microhemorrhages as bloom artifacts. Quantitative susceptibility mapping provides universal quantification of tissue magnetic property without these constraints but traditionally requires a mask generated by skull-stripping, which can pose challenges at tissue interphases. We evaluated the preconditioned quantitative susceptibility mapping MR imaging method, which does not require skull-stripping, for improved depiction of brain parenchyma and pathology.

MATERIALS AND METHODS:

Fifty-six subjects underwent brain MR imaging with a 3D multiecho gradient recalled echo acquisition. Mask-based quantitative susceptibility mapping images were created using a commonly used mask-based quantitative susceptibility mapping method, and preconditioned quantitative susceptibility images were made using precondition-based total field inversion. All images were reviewed by a neuroradiologist and a radiology resident.

RESULTS:

Ten subjects (18%), all with traumatic brain injury, demonstrated blood products on 3D gradient recalled echo imaging. All lesions were visible on preconditioned quantitative susceptibility mapping, while 6 were not visible on mask-based quantitative susceptibility mapping. Thirty-one subjects (55%) demonstrated brain parenchyma and/or lesions that were visible on preconditioned quantitative susceptibility mapping but not on mask-based quantitative susceptibility mapping. Six subjects (11%) demonstrated pons artifacts on preconditioned quantitative susceptibility mapping and mask-based quantitative susceptibility mapping; they were worse on preconditioned quantitative susceptibility mapping.

CONCLUSIONS:

Preconditioned quantitative susceptibility mapping MR imaging can bring the benefits of quantitative susceptibility mapping imaging to clinical practice without the limitations of mask-based quantitative susceptibility mapping, especially for evaluating cerebral microhemorrhage–associated pathologies, such as traumatic brain injury.



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Intraoperative Conebeam CT for Assessment of Intracochlear Positioning of Electrode Arrays in Adult Recipients of Cochlear Implants [HEAD & NECK]

BACKGROUND AND PURPOSE:

Intraoperative conebeam CT has been introduced into the operating room and provides quick radiologic feedback. This study aimed to investigate its utility in the assessment of the positioning of the electrode array after cochlear implantation.

MATERIALS AND METHODS:

This was a retrospective study of 51 patients (65 ears) with intraoperative imaging by conebeam CT (O-arm) after cochlear implantation between 2013 and 2017. Correct placement into the cochlea was immediately identified. Positioning assessments were later analyzed with OsiriX software.

RESULTS:

Intraoperative imaging was quickly performed in all cases. No misplacement into the vestibule or semicircular canals was found. A foldover of the implanted array was identified in 1 patient. Secondary analysis by 2 raters showed excellent agreement on insertion depth angle (intraclass correlation = 0.96, P < .001) and length of insertion of the electrode array (intraclass correlation coefficient = 0.93, P = .04) measurements. The evaluation of the number of extracochlear electrodes was identical between the 2 raters in 78% of cases (Cohen = 0.55, P < .001). The scalar position was inconsistent between raters. When we compared O-arm and high-resolution CT images in 14 cases, the agreement was excellent for insertion depth angle (intraclass correlation coefficient = 0.97, P < .001) and insertion length (intraclass correlation coefficient = 0.98, P < .001), good for the number of extracochlear electrodes (Cohen = 0.63, P = .01), but moderate for the scalar position (Cohen = 0.59, P = .02).

CONCLUSIONS:

Intraoperative conebeam CT using the O-arm is a safe, rapid, easy, and reliable procedure to immediately identify a misplacement or foldover of an electrode array. The insertion depth angle, insertion length, and number of electrodes inserted can be accurately assessed.



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Esophagus toxicity after stereotactic and hypofractionated radiotherapy for central lung tumors: Normal tissue complication probability modeling

To correlate esophagus toxicity and dose-volume histogram (DVH) parameters in order to assess risks, and derive a Normal Tissue Complication Probability (NTCP) model.

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Do radiation oncology outreach clinics affect the use of radiotherapy?

The scope and effect of radiation oncology (RO) outreach activities within centralized radiotherapy (RT) systems is poorly defined. The purpose of this study was to describe the outreach activities of Ontario's regional cancer centres, and to explore the relationship between radiation oncology (RO) outreach clinics and rates of radiotherapy (RT) utilization at hospitals without RT on site (HWOS-RT).

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Association of Mucoid Degeneration of the Anterior Cruciate Ligament at MR Imaging with Medial Tibiofemoral Osteoarthritis Progression at Radiography: Data from the Osteoarthritis Initiative.

Association of Mucoid Degeneration of the Anterior Cruciate Ligament at MR Imaging with Medial Tibiofemoral Osteoarthritis Progression at Radiography: Data from the Osteoarthritis Initiative.

Radiology. 2018 Feb 21;:171565

Authors: Kwee RM, Hafezi-Nejad N, Roemer FW, Zikria BA, Hunter DJ, Guermazi A, Demehri S

Abstract
Purpose To determine whether anterior cruciate ligament (ACL) mucoid degeneration in participants with or at risk for osteoarthritis is associated with longitudinal risk of radiographic progression of medial tibiofemoral compartment joint space loss (JSL). Materials and Methods Baseline demographic, clinical, radiographic, and Magnetic Resonance (MR) Imaging Osteoarthritis Knee Score (MOAKS) data were evaluated in 600 participants from the Osteoarthritis Initiative database. Two blinded musculoskeletal radiologists independently evaluated baseline MR images for ACL mucoid degeneration. Multiple logistic regression was used to investigate the association between ACL mucoid degeneration at MR imaging and JSL progression at radiography, defined as a minimum joint space width decrease greater than 0.7 mm (48 months; cutoff according to mean and standard deviation of 1-year minimum joint space width changes in 90 knees of reference group). Stratified analysis was performed based on baseline cartilage surface damage. Results Knees with ACL mucoid degeneration showed a greater proportion of JSL progression compared with knees with a normal ACL (64% vs 47%; P = .004). After adjustment for all demographic, clinical, radiographic, and MOAKS variables, ACL mucoid degeneration was not statistically significantly associated with JSL progression in the entire cohort (adjusted odds ratio, 1.66; 95% confidence interval: 1.00, 2.77; P = .051). In subgroup analysis, ACL mucoid degeneration was statistically significantly associated with JSL progression in participants with less baseline cartilage surface damage (maximum cartilage surface loss of ≤75% in all subregions [P = .015] and ≤4 of involved subregions with cartilage surface loss [P = .028]). Conclusion ACL mucoid degeneration in participants with or at risk for osteoarthritis is associated with progression of medial tibiofemoral compartment JSL in knees with less baseline cartilage surface area damage. © RSNA, 2018 Online supplemental material is available for this article.

PMID: 29465334 [PubMed - as supplied by publisher]



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US Fine-Needle Aspiration Biopsy for Thyroid Malignancy: Diagnostic Performance of Seven Society Guidelines Applied to 2000 Thyroid Nodules.

US Fine-Needle Aspiration Biopsy for Thyroid Malignancy: Diagnostic Performance of Seven Society Guidelines Applied to 2000 Thyroid Nodules.

Radiology. 2018 Feb 21;:171074

Authors: Ha EJ, Na DG, Baek JH, Sung JY, Kim JH, Kang SY

Abstract
Purpose To compare the diagnostic performance of ultrasonography (US)-based fine-needle aspiration biopsy (FNAB) criteria from seven international societies in the detection of thyroid malignancy. Materials and Methods This study included a total of 2000 consecutive thyroid nodules (≥1 cm) in 1802 patients with final diagnoses from January 2010 to May 2011. US features of the thyroid nodules were retrospectively reviewed and were classified according to the categories defined by the seven international society guidelines. The diagnostic performance of US-based FNAB criteria in the detection of thyroid malignancy and unnecessary FNAB rates were calculated and compared by using a generalized estimating equation method. Results Of the 2000 thyroid nodules, 1546 (78.3%) were benign and 454 (22.7%) were malignant, with papillary carcinoma comprising 85.5% of all malignancies. The Korean Thyroid Association/Korean Society of Thyroid Radiology (KTA/KSThR) (94.5%), National Comprehensive Cancer Network (NCCN) (92.5%), and American Thyroid Association (ATA) (89.6%) guidelines were more sensitive than those of the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME) (80.4%), American College of Radiology (ACR) (74.7%), French Society of Endocrinology (FSE) (72.7%), and Society of Radiology in Ultrasound (SRU) (70.9%) (P < .001), while the latter guidelines had higher specificity (P < .001). The rate of unnecessary FNAB was lowest with the ACR guidelines (25.3%), followed by the FSE (29.1%), AACE/ACE/AME (32.5%), SRU (45.2%), ATA (51.7%), NCCN (54.0%), and KTA/KSThR (56.9%) guidelines. Conclusion Because the diagnostic performance of US-based FNAB criteria varies according to the individual international society guidelines, clinicians should be aware of the strengths and weaknesses of US-based FNAB criteria in the management of thyroid nodules. © RSNA, 2018 Online supplemental material is available for this article.

PMID: 29465333 [PubMed - as supplied by publisher]



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Cardiac-gated intravoxel incoherent motion diffusion-weighted magnetic resonance imaging for the investigation of intracranial cerebrospinal fluid dynamics in the lateral ventricle: a feasibility study

Abstract

Purpose

Intravoxel incoherent motion (IVIM) in diffusion-weighted magnetic resonance imaging (DW-MRI) attributes the signal attenuation to the molecular diffusion and to a faster pseudo-diffusion. Purpose of the study was to demonstrate the feasibility of IVIM for the investigation of intracranial cerebrospinal fluid (CSF) dynamics.

Methods

Cardiac-gated DW-MRI images with fifteen b-values (0–1300s/mm2) along three orthogonal directions (mediolateral (ML), anteroposterior (AP), and craniocaudal (CC)) were acquired during maximum systole and diastole in 10 healthy volunteers (6 males, mean age 36 ± 15 years). A pixel-wise bi-exponential fitting with an iterative nonparametric algorithm was carried out to calculate the following parameters: diffusion coefficient (D), fast diffusion coefficient (D*), and fraction of fast diffusion (f). Region of interest measurements were performed in both lateral ventricles. Comparison of IVIM parameters was performed among two cardiac cycle acquisitions and among the diffusion-encoding directions using a paired Student's t test.

Results

f significantly (p < 0.05) depended on the diffusion-encoding direction and on the cardiac cycle (diastole AP 0.30 ± 0.13, ML 0.22 ± 0.12, CC 0.26 ± 0.17; systole AP 0.45 ± 0.17, ML 0.34 ± 0.15, CC 0.40 ± 0.21). Neither a cardiac cycle nor a direction dependency was found among mean D values (which is in line with the expected intraventricular isotropic diffusion) and D* values (p > 0.05 each).

Conclusion

The fraction of fast diffusion from IVIM is feasible to detect a direction-dependent and cardiac-dependent pulsatile CSF flow within the lateral ventricles allowing for quantitative monitoring of CSF dynamics. This technique might provide opportunities to further investigate the pathophysiology of various neurological disorders involving altered CSF dynamics.



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Chronic painful oral ulcers in a heart transplant recipient

Publication date: Available online 21 February 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Manoela S. Pereira, Vivian P. Wagner, Maria Cristina Munerato, Nadine O. Clausell, Livia A. Goldraich, Marco Antonio T. Martins, Manoela D. Martins, Vinicius C. Carrard




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The impact of chemotherapeutic treatment on the oral microbiota of cancer patients: A systematic review

Publication date: Available online 21 February 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Kelly Rocio Vargas Villafuerte, Cristhiam de Jesus Hernandez Martinez, Felipe Torres Dantas, Helio Humberto Angotti Carrara, Francisco José Candido dos Reis, Daniela Bazan Palioto
ObjectiveChemotherapy is a type of systemic treatment that inhibitsneoplastic cells (cancer), producing immunosuppression, and may lead to changes in the oral mucosa and, consequently, in the oral microbiota. The aim of this systematic review was to analyze, in the scientific literature, evidence of the impact of chemotherapy on the oral microbiota.MethodsThe authors conducted a search in the electronic databases PubMed/MEDLINE, Scientific Electronic Library Online (SciELO), LILACS, ScienceDirect, Web of Science, and Cochrane Library for studies that discuss the change of oral microbiota in cancer patients during chemotherapy. Articles published in English were included until July 2017. The quality of the study was assessed using the Ottawa-Newcastle scale.ResultsOf 5252 papers potentially relevant to this review, 17 studies were included in this study. Of these studies, 16 studies used culture techniques and one of them used genetic sequencing. The most frequently observed bacteria were aerobic gram-negative (Klebsiella spp, E. coli, Enterobacter, Pseudomonas spp), anaerobic gram-negative (Veillonella spp, Capnocytophaga), and gram-positive bacteria (Streptococcus spp, Staphylococcus spp).ConclusionsPatients with cancer during chemotherapy present a more complex oral microbiota under favorable conditions for their development during immunosuppression, and these may be responsible for different serious local or systemic pathologies.



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Orofacial granulomatosis: an unsuccessful response to weekly azithromycin pulse therapy

Publication date: Available online 21 February 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Philip A. Atkin, Melanie L. Simms
Treatment of orofacial granulomatosis (OFG) is difficult and unpredictable, and currently there is not a treatment with guaranteed success. Macrolides have been suggested to give dramatic improvements in idiopathic OFG; however, this was not our experience. Following on from remarkable findings with weekly azithromycin pulse therapy reported in JAMA Dermatology, 2015, we treated 5 male patients with idiopathic OFG with the same regimen. Case 1 had a slight improvement but stopped treatment after 5 weeks due to gastrointestinal upset. Cases 2 and 3 had an initial improvement; however, symptoms returned once treatment had ceased. Case 3 received a second course of azithromycin with no improvement. Cases 4 and 5 did not have any improvement at all.We concluded that weekly azithromycin pulse therapy was not a successful treatment for idiopathic OFG. It may provide some short-term improvement in symptoms but does not dramatically resolve symptoms.



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Exploring the relationship between local food environments and obesity in UK, Ireland, Australia and New Zealand: a systematic review protocol

Introduction

Obesity is a global pandemic that affects all socioeconomic strata, however, the highest figures have been observed in the most disadvantaged social groups. Evidence from the USA and Canada showed that specific urban settings encourage obesogenic behaviour in the population living and/or working there. We aim to examine the evidence on the association between local food environments and obesity in the UK, Ireland, Australia and New Zealand.

Methods

Six databases from 1990 to 2017 will be searched: MEDLINE (Ovid), Embase (Ovid), Scopus, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Applied Social Sciences Index and Abstracts (ASSIA) and Web of Science. Grey literature will also be sought by searching Opengrey Europe, The Grey Literature Report and relevant government websites. Additional studies will be retrieved from the reference lists of the selected articles. It will include cohort, longitudinal, case study and cross-sectional studies that have assessed the relationship between local food environments and obesity in the UK, Ireland, Australia and New Zealand regardless of sex, age and ethnicity of the population. Two researchers will independently select the studies and extract the data. Data items will incorporate: author names, title, study design, year of study, year exposure data collected, country, city, urban/rural, age range, study exclusions, special characteristics of study populations, aims, working definitions of food environments and food outlets, exposure and methods of data collection, outcomes and key findings. A narrative synthesis and a summary of the results will be produced separately for children and adults, according to the type of food exposure–outcome. All the selected studies will be assessed using The Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.

Ethics and dissemination

This study will be based on published literature, and therefore ethical approval has not been sought. Our findings will be presented at relevant national and international scientific conferences and published in a peer-reviewed journal.



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Comparison of new-generation drug-eluting stents versus drug-coated balloon for in-stent restenosis: a meta-analysis of randomised controlled trials

Objective

The study sought to compare angiographic and clinical outcomes of new-generation drug-eluting stents (DES) versus drug-coated balloon (DCB) in patients with coronary in-stent restenosis (ISR).

Design

Meta-analysis using data from randomised trial found by searches on PubMed, the Cochrane Library, ClinicalTrials.gov and websites of major cardiovascular congresses.

Setting

Only randomised trials comparing DES with DCB were included.

Participants

Patients with ISR in the included trials.

Interventions

New-generation DES versus DCB.

Outcomes

The angiographic and clinical outcomes including cardiac death, all-cause death, myocardial infarction, target lesion revascularisation (TLR), target vessel revascularisation (TVR), major adverse cardiac events (MACE) and stent thrombosis were investigated.

Results

Five trials including 913 patients were eligible and included. Pooled analysis in angiographic results identified that new-generation DES were associated with higher acute luminal gain (–0.31 mm, 95% CI –0.42 to –0.20, P<0.001) and lower per cent diameter stenosis (risk ratio (RR): 0.28, 95% CI 0.02 to 0.55, P=0.04). DES significantly reduced the risk of TLR (RR: 1.96, 95% CI 1.17 to 3.28, P=0.01) compared with DCB; however, there was no statistical differences for MACE (RR: 1.21, 95% CI 0.67 to 2.17, P=0.53), myocardial infarction (RR: 1.16, 95% CI 0.55 to 2.48, P=0.69) and cardiac death (RR: 1.80, 95% CI 0.60 to 5.39, P=0.29).

Conclusions

Interventions with new-generation DES appear to be associated with significant reduction in per cent diameter stenosis and TLR at short-term follow-up, but had similar MACE, myocardial infarction and cardiac death for patients with coronary ISR compared with DCB. Appropriately powered studies with longer term follow-up are warranted to confirm these findings.



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Cost-effectiveness of mechanical thrombectomy within 6 hours of acute ischaemic stroke in China

Objectives

Endovascular mechanical thrombectomy is an effective but expensive therapy for acute ischaemic stroke with proximal anterior circulation occlusion. This study aimed to determine the cost-effectiveness of mechanical thrombectomy in China, which is the largest developing country.

Design

A combination of decision tree and Markov model was developed. Outcome and cost data were derived from the published literature and claims database. The efficacy data were derived from the meta-analyses of nine trials. One-way and probabilistic sensitivity analyses were performed in order to assess the uncertainty of the results.

Setting

Hospitals in China.

Participants

The patients with acute ischaemic stroke caused by proximal anterior circulation occlusion within 6 hours.

Interventions

Mechanical thrombectomy within 6 hours with intravenous tissue plasminogen activator (tPA) treatment within 4.5 hours versus intravenous tPA treatment alone.

Outcome measures

The benefit conferred by the treatment was assessed by estimating the cost per quality-adjusted life-year (QALY) gained in the long term (30 years).

Results

The addition of mechanical thrombectomy to intravenous tPA treatment compared with standard treatment alone yielded a lifetime gain of 0.794 QALYs at an additional cost of CNY 50 000 (US$7700), resulting in a cost of CNY 63 010 (US$9690) per QALY gained. The probabilistic sensitivity analysis indicated that mechanical thrombectomy was cost-effective in 99.9% of the simulation runs at a willingness-to-pay threshold of CNY 125 700 (US$19 300) per QALY.

Conclusions

Mechanical thrombectomy for acute ischaemic stroke caused by proximal anterior circulation occlusion within 6 hours was cost-effective in China. The data may be used as a reference with regard to medical resources allocation for stroke treatment in low-income and middle-income countries as well as in the remote areas in the developed countries.



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Comparison of a newly established emotional stimulus approach to a classical assessment-driven approach in BLS training: a randomised controlled trial

Objective

The study objective was to implement two strategies (short emotional stimulus vs announced practical assessment) in the teaching of resuscitation skills in order to evaluate whether one led to superior outcomes.

Setting

This study is an educational intervention provided in one German academic university hospital.

Participants

First-yearmedical students (n=271) during the first3 weeks of their studies.

Interventions

Participants were randomly assigned to one of two groups following a sequence of random numbers: the emotional stimulus group (EG) and the assessment group (AG). In the EG, the intervention included watching an emotionally stimulating video prior to the Basic Life Support (BLS) course. In the AG, a practical assessment of the BLS algorithm was announced and tested within a 2 min simulated cardiac arrest scenario. After the baseline testing, a standardised BLS course was provided. Evaluation points were defined 1 week and 6 months after.

Primary outcome measures

Compression depth (CD) and compression rate (CR) were recorded as the primary endpoints for BLS quality.

Results

Within the study, 137 participants were allocated to the EG and 134 to the AG. 104 participants from EG and 120 from AG were analysed1 week after the intervention, where they reached comparable chest-compression performance without significant differences (CR P=0.49; CD P=0.28). The chest-compression performance improved significantly for the EG (P<0.01) and the AG (P<0.01) while adhering to the current resuscitation guidelines criteria for CD and CR.

Conclusions

There was no statistical difference between both groups’ practical chest-compression-performance. Nevertheless, the 2 min video sequence used in the EG with its low production effort and costs, compared with the expensive assessment approach, provides broad opportunities for applicability in BLS training.



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A prospective cohort study to investigate parental stress and child health in low-income Chinese families: protocol paper

Introduction

Chronic stress has adverse effects on health. Adults and children from low-income families are subject to multiple sources of stress. Existing literature about economic hardship mostly focuses on either adults or children but not both. Moreover, there is limited knowledge on the relationship between parental generalised stress and child health problems. This study aims to explore the bidirectional relationship between parental stress and child health in Chinese low-income families and to identify other modifiable factors influencing this relationship.

Methods and analysis

This prospective cohort study will sample 254 low-income parent–child pairs and follow them up for 24 months with assessments at three time points (baseline, 12 and 24 months) on parental stress, health-related quality of life (HRQOL) and child health and behaviour using both subjective measures and objective physiological parameters. This study will collect data using standardised measures on HRQOL and behaviours of children as well as on HRQOL, mental health and stress levels of parents along with physiological tests of allostatic load and telomere length. The mediating or moderating effect of family harmony, parenting style and neighbourhood conditions will also be assessed. Data will be analysed using latent growth modelling and cross-lagged path analysis modelling to examine the bidirectional effect of parental stress and child health over time. Mediation and moderation analysis will also be conducted to examine the mechanism by which the variables relate.

Ethics and dissemination

This study was approved by the institutional review board of the University of Hong Kong—the Hospital Authority Hong Kong West Cluster, reference no: UW 16-415. The study findings will be disseminated through peer-reviewed publications and international conferences.

Trial registration number

NCT03185273; Pre-results.



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Protocol for a longitudinal twin birth cohort study to unravel the complex interplay between early-life environmental and genetic risk factors in health and disease: the Chongqing Longitudinal Twin Study (LoTiS)

Introduction

Non-communicable diseases (NCD) now represent the major burden of adverse health in most countries. It is clear that much of the risk of such conditions begins very early in life, potentially in utero. Given their complex aetiology, an understanding of the origins of NCD requires an in-depth analysis of the interplay between genetic variation and environment, preferably over time. For decades, twin studies have played a key role in understanding such traits. Their strength lies in the ability to disentangle genetic and environmental factors that contribute to a phenotype. This is done by comparing genetically identical monozygotic (MZ) with dizygotic twins, who share on average 50% of genetic variation, or by comparing MZ twins within a pair. This study aims to determine the relative contributions of genes and environment to early-onset intermediate phenotypes related to later adult onset disease (such as growth and neurodevelopment) and to identify specific biomarkers and time points for emergence of phenotypes from infancy, largely independent of underlying genetic factors.

Methods/design

The Chongqing Longitudinal Twin Study (LoTiS) will recruit 300 women pregnant with twins, enriched for MZ pregnancies, with follow-up to 3 years of age. Data collection will be undertaken at key time points in gestation (x3), at delivery and postnatally (x9). Maternal and infant biospecimens including blood, urine, hair, nails and buccal swabs along with measures such as fetal scans and body measurements will be collected. Additional information from questionnaires and medical records includes pregnancy, diet, sociodemographics, maternal stress, and infant growth and neurodevelopment.

Ethics and dissemination

This study has been approved by the Ethics Committee of Chongqing Medical University (record no: 201530) and has been registered with the Chinese Clinical Trial Registry (registry no: ChiCTR-OOC-16008203). Results of the recruitment and all subsequent analyses will be submitted for publication in peer-reviewed journals.

Trial registration number

ChiCTR-OOC-16008203; Results.



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Density and location of CD3+ and CD8+ tumor-infiltrating lymphocytes correlate with prognosis of oral squamous cell carcinoma

Abstract

Background

Tumor-infiltrating lymphocytes (TILs) are regarded as adaptive immune response of the host to cancer cells and valuable prognostic factors. Here, we sought to characterize the densities and locations of CD3+ and CD8+ TILs in primary oral squamous cell carcinoma (OSCC) samples and assess their clinicopathological and prognostic significance.

Methods

A total number of 169 OSCC samples from two independent patient cohorts (Nanjing cohort, 93 cases; Wuxi cohort, 76 cases) were retrospectively collected. The numbers of CD3+ and CD8+ TILs at tumor center (CT) and invasive margin (IM) of OSCC were identified by immunohistochemistry and calculated. The optimal cutoff values for CD3+ and CD8+ TILs to stratify patients were determined by X-tile software in Nanjing cohort and further utilized in Wuxi cohort. The associations between CD3+/CD8+ TILs and clinicopathological parameters or patient survival were assessed. The prognostic values of CD3+/ CD8+ TILs were evaluated by Cox regression analyses.

Results

CD3+ and CD8+ TILs were identified at both CT and IM and enriched at IM. High density of CD3+ TILs at IM (CD3 IM) was significantly associated with increased overall and disease-specific survival (P<0.05). High density of CD8+ TILs at CT (CD8 CT) was significantly associated with increased overall but not disease-specific survival. Moreover, CD3 IM and CD8 CT were identified as independent prognostic factors for patient survival.

Conclusions

Our findings provide further evidence to support the prognostic values of CD3+ and CD8+ TILs for OSCC, suggesting that TILs subsets might be viable biomarkers and therapeutic targets with translational significance.

This article is protected by copyright. All rights reserved.



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Comment on the article “TFM classification and Staging of oral submucous fibrosis: A new proposal”

Abstract

The article tilted - TFM classification and Staging of oral submucous fibrosis: A new proposal, authored by Arakeri et al was an interesting read. The authors have reviewed the current grading and staging schemes for oral submucous fibrosis (OSMF) and evaluated the clinicopathological classification system proposed by Khanna and Andrade for agreement and correlation I congratulate the authors for proposing a very comprehensive, treatment-oriented classification and staging system for OSMF.

This article is protected by copyright. All rights reserved.



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Cooling of the oral mucosa to prevent adverse effects of chemotherapeutic agents - an in vitro study

Abstract

Background

The cytotoxic effect of chemotherapeutic agents to the oral mucosa, as a side-effect of cancer treatment, is a major problem. Cooling the oral mucosa using ice chips in conjunction with chemotherapy is known to reduce the severity of oral mucositis. However, although the use of ice chips is of clinical value, this method of cooling has inherent problems including discomfort for the patient, non-uniformity and fluctuations in cooling temperature throughout the oral cavity. Furthermore, despite being used clinically, it is not known what reduction in temperature is required to prevent oral mucositis. The aim of the present study was therefore to determine in vitro if the cytotoxic effect of 5-Fluorouracil (5-FU) on the oral mucosa could be reduced by lowering the temperature during chemotherapeutic treatment.

Methods

Tissue engineered oral mucosal (TEOM) models were incubated at 20, 25, 30, or 35 °C for 30 minutes followed by exposure to a clinically relevant concentration of 5-FU (162 μg/ml) for two hours and compared to untreated models (35°C). Cell viability and inflammatory cytokine production (IL-6 and TNF-α) were measured using PrestoBlue® and ELISA, respectively.

Results

TEOM models incubated at 20°C showed an increased cell viability and had a reduced IL-6 and TNF-α production compared to models treated with 5-FU incubated at 35°C.

Conclusion

This study demonstrates a reduced cytotoxic effect to the TEOM by reducing the temperature of the tissue during chemotherapy treatment and suggests that decreasing the temperature to 20°C could have clinical advantages.

This article is protected by copyright. All rights reserved.



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Human serum alters cell culture behavior and improves spheroid formation in comparison to fetal bovine serum

Publication date: Available online 21 February 2018
Source:Experimental Cell Research
Author(s): Julia I. Heger, Karolin Froehlich, Jana Pastuschek, Astrid Schmidt, Christin Baer, Ralf Mrowka, Claudia Backsch, Ekkehard Schleußner, Udo R. Markert, André Schmidt
BackgroundThe use of fetal bovine serum (FBS) as growth supplement for human cell and tissue culture is widely spread in basic research as well as in clinical approaches, although several limitations must be considered, such as unstable composition and availability, biosafety and ethical aspects. Regarding interspecies differences, xenogeneic growth factors may evoke incompatibilities and non-desired interactions with human cells resulting in imprecise outcome of human-relevant data.MethodsIn this study the functionality of human serum (HS) has been investigated in comparison to FBS by assessing proliferation, migration and invasion of the human cervical cancer cell lines SiHa and HeLa. The effects of both sera on spheroid formation were analyzed microscopically.ResultsBoth, FBS and HS, stimulate cell proliferation and migration similarly, whereas HS significantly enhanced cell invasion. The spheroid formation assay revealed remarkable differences between both sera, especially for SiHa cells. While in FBS supplemented medium cells only formed loose aggregates, HS induced regularly shaped spheroids under all tested conditions.ConclusionWe were able to demonstrate that HS and FBS differently influence behavior of cells in culture which may have an impact on experimental results, especially in 3D cultures.



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CD 18-mediated adhesion is required for the induction of a proinflammatory phenotype in lung epithelial cells by mononuclear cell-derived extracellular vesicles

Publication date: Available online 21 February 2018
Source:Experimental Cell Research
Author(s): Tommaso Neri, Valentina Scalise, Ilaria Passalacqua, Ilaria Giusti, Stefania Lombardi, Cristina Balia, Delfo D’Alessandro, Stefano Berrettini, Roberto Pedrinelli, Pierluigi Paggiaro, Vincenza Dolo, Alessandro Celi
Extracellular vesicles are submicron vesicles that upregulate the synthesis of proinflammatory mediators by lung epithelial cells.We investigated whether these structures adhere to lung epithelial cells, and whether adhesion is a prerequisite for their proinflammatory activity.Extracellular vesicles were generated by stimulation of normal human mononuclear cells with the calcium ionophore A23187, and labelled with carboxyfluorescein diacetate succinimidyl ester. Adhesion of vesicles to monolayers of immortalized bronchial epithelial (16HBE) and alveolar (A549) cells was analysed by fluorescence microscopy. The role of candidate adhesion receptors was evaluated with inhibitory monoclonal antibodies and soluble peptides. The synthesis of proinflammatory mediators was assessed by ELISA.Transmission electron microscopy confirmed the generation of closed vesicles with an approximate size range between 50 and 600nm. Adhesion of extracellular vesicles to epithelial cells was upregulated upon stimulation of the latter with tumour necrosis factor-α. Adhesion was blocked by an anti-CD18 antibody, by peptides containing the sequence RGD and, to a lesser extent, by an antibody to ICAM-1. The same molecules also blocked the upregulation of the synthesis of interleukin-8 and monocyte chemotactic protein-1 induced by extracellular vesicles.CD18-mediated adhesion of extracellular vesicles is a prerequisite for their proinflammatory activity.



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Novel Proteins that Regulate Cell Extension Formation in Fibroblasts

Publication date: Available online 21 February 2018
Source:Experimental Cell Research
Author(s): A. Yuda, W.S. Lee, P. Petrovic, C.A. McCulloch
Cell extensions are critical structures that enable matrix remodeling in wound healing and cancer invasion but the regulation of their formation is not well-defined. We searched for new proteins that mediated cell extension formation over collagen by tandem mass tagged mass spectrometry analysis of purified extensions in 3T3 fibroblasts. Unexpectedly, importin-5, ENH isoform 1b (PDLIM5) and 26S protease regulatory subunit 6B (PSMC4) were more abundant (>10-fold) in membrane-penetrating cell extensions than cell bodies, which was confirmed by immunostaining and immunoblotting and also observed in human gingival fibroblasts. After siRNA knockdown of these proteins and plating cells on grid-supported floating collagen gels for 6 h, formation of cell extensions and collagen remodeling were examined. Knockdown of importin-5 reduced collagen compaction (1.9-fold), pericellular collagen degradation (~ 1.8-fold) and number of cell extensions (~ 69%). Knockdown of PSMC4 reduced collagen compaction (~ 1.5-fold), pericellular collagen degradation (~ 1.7-fold) and number of cell extensions (~ 42%). Knockdown of PDLIM5 reduced collagen compaction (~ 1.6-fold) and number of cell extensions (~ 21%). Inhibition of the TGF-β RI kinase, Smad3 or ROCK-II signaling pathways reduced the abundance of PDLIM5 in cell extensions but PSMC4 and importin-5 were reduced only by Smad3 or ROCK-II inhibitors.We conclude that these novel proteins are required for cell extension formation and their recruitment into extensions involves the Smad3 and ROCK signaling pathways.



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Almost every antidepressant headline you’ll read today is wrong

A review of the evidence on antidepressants has been hailed as the final word on these drugs, but questions remain for people with less severe depression

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Work the crowd: How ordinary people can predict the future

Want to know if a dictator will be deposed? Or shares will crash? Intelligence agencies and firms are realising groups of everyday people can foresee what will happen

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First speakers announced for New Scientist Live 2018

Join us for  thought-provoking talks, groundbreaking discoveries and interactive experiences at New Scientist Live in London this September

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Cycling in later life makes you less likely to have a bad fall

Riding a bike into your older years means stronger legs, better balance and a lower risk of falls that injure and kill millions of elderly people

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Almost every antidepressant headline you’ll read today is wrong

A review of the evidence on antidepressants has been hailed as the final word on these drugs, but questions remain for people with less severe depression

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Work the crowd: How ordinary people can predict the future

Want to know if a dictator will be deposed? Or shares will crash? Intelligence agencies and firms are realising groups of everyday people can foresee what will happen

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First speakers announced for New Scientist Live 2018

Join us for  thought-provoking talks, groundbreaking discoveries and interactive experiences at New Scientist Live in London this September

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Cycling in later life makes you less likely to have a bad fall

Riding a bike into your older years means stronger legs, better balance and a lower risk of falls that injure and kill millions of elderly people

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Editorial Board

Publication date: March 2018
Source:Journal of Fluency Disorders, Volume 55





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Exogenously Triggered Response Inhibition in Developmental Stuttering

Publication date: Available online 21 February 2018
Source:Journal of Fluency Disorders
Author(s): Kurt Eggers, Luc F. De Nil, Bea R.H. Van den Bergh
PurposeThe purpose of the present study was to examine relations between children’s exogenously triggered response inhibition and stuttering.MethodParticipants were 18 children who stutter (CWS; mean age = 9;01 years) and 18 children who not stutter (CWNS; mean age = 9;01 years). Participants were matched on age (± 3 months) and gender. Response inhibition was assessed by a stop signal task (Verbruggen, Logan, & Stevens, 2008).ResultsResults suggest that CWS, compared to CWNS, perform comparable to CWNS in a task where response control is externally triggered.ConclusionsOur findings seem to indicate that previous questionnaire-based findings (Eggers, De Nil, & Van den Bergh, 2010) of a decreased efficiency of response inhibition cannot be generalized to all types of response inhibition.



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Doctors developing apps to try to modernise the NHS

A new breed of doctor is stalking UK hospitals and clinics—young, tech savvy, and frustrated with clunky NHS processes, these “doctorpreneurs” are setting up technology companies in a bid to make the...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=qnqqBojXyR8:bw3KqyfGQ10:V_sGLiP recent?d=qj6IDK7rITs recent?i=qnqqBojXyR8:bw3KqyfGQ10:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=qnqqBojXyR8:bw3KqyfGQ10:F7zBnMy recent?i=qnqqBojXyR8:bw3KqyfGQ10:-BTjWOF


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A luciferase immunoprecipitation assay for the detection of proinsulin/insulin autoantibodies

Publication date: Available online 21 February 2018
Source:Clinical Biochemistry
Author(s): Yun Ling, Pengjun Jiang, Nan Li, Qianhua Yan, Xin Wang
AimLuciferase immunoprecipitation (LIPS) assays show good sensitivity and specificity in testing islet specific autoantibodies for diagnosis of type 1 diabetes (T1D). However, there are currently no LIPS assays available for detecting proinsulin/insulin autoantibody (IAA) previously. We here developed a LIPS assay to measure IAA using nano luciferase (NanoLuc)-proinsulin fusion protein.MethodsThe NanoLuc-proinsulin fusion protein expression plasmid was constructed and transfected to COS1 cells. Expression and binding specificity to IAA of the fusion protein were validated. A LIPS assay using the NL-proinsulin fusion protein was developed and compared to radioimmunoassay (RIPA) in testing sera from 50 healthy controls and 34 T1D patients.ResultsThe fusion protein was correctly expressed in transfected COS1 cells. Both NANOLUC activity and proinsulin were detected in the medium of transfected COS1 cells. Fusion protein bound to monoclonal anti insulin antibody and sera from T1D patients or NOD mice, these bindings were inhibited by recombinant human insulin. The LIPS assay using the fusion protein showed sensitivity of 47.1% and specificity of 98.0%. Further analysis supported correlation between the IAA indexes of all the T1D samples detected by LIPS assay and radioimmunoassay (RIPA, R2 = 0.6132, p < 0.0001).ConclusionsThe NanoLuc-proinsulin fusion protein based LIPS has the potential to detect IAA for diagnosis of T1D.



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What will the impact be of the EU general data protection regulation on scientific research?… https://t.co/xMLk2XreeN

What will the impact be of the EU general data protection regulation on scientific research?… https://t.co/xMLk2XreeN

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Learn how to educate your patients to recognise signs and symptoms of potential infection during neutropenia:… https://t.co/B4BI5sL0ek

Learn how to educate your patients to recognise signs and symptoms of potential infection during neutropenia:… https://t.co/B4BI5sL0ek

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New trial results identify five mutations linked to #pancreatic cancer @NatureComms @HopkinsMedicine … https://t.co/R3nTrgnZ7F

New trial results identify five mutations linked to #pancreatic cancer @NatureComms @HopkinsMedicinehttps://t.co/R3nTrgnZ7F

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Origanum vulgare mediated green synthesis of biocompatible gold nanoparticles simultaneously possessing plasmonic, antioxidant and antimicrobial properties



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Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo–in vivo evaluation study



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A little key to oxalate formation in oil paints: protective patina or chemical reactor?

GA?id=C7PP00307B

Photochem. Photobiol. Sci., 2018, Advance Article
DOI: 10.1039/C7PP00307B, Communication
V. Otero, M. Vilarigues, L. Carlyle, M. Cotte, W. De Nolf, M. J. Melo
A novel degradation mechanism for 19th c. chrome yellow oil paints is proposed based on the oil photodegradation induced and calcium oxalate formation. It was proved by synchrotron radiation using artificially aged pigment reconstructions.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry


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Publication trends of Allergy, Pediatric Allergy and Immunology, and Clinical and Translational Allergy journals: a MeSH term-based bibliometric analysis

We performed a MeSH term-based bibliometric analysis aiming to assess the publication trends of EAACI journals, namely Allergy, Pediatric Allergy and Immunology (PAI) (from 1990 to 2015) and Clinical and Trans...

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Mesalazine-induced myocarditis: a case report

Myocarditis is a rare complication of therapy with mesalazine, a drug widely prescribed in the treatment of inflammatory bowel disease.

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China’s “new” silk road

The “new” silk road—the belt and road initiative (BRI)—is China’s grand idea for the 21st century, promising to transform international development assistance for health. Named after the ancient...
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Hospitals in England see deficits grow as wage bills rise and earning capacity falls

NHS hospitals in England are facing ballooning deficits as they struggle to maintain quality of care for growing numbers of patients, show the latest quarterly statistics from NHS Improvement.1 At...
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Prof Pier Guiseppe Pelicci spoke at ecancer's Milan Summit on Precision Medicine 2018 about the challenges of perso… https://t.co/vusLZkMajO

Prof Pier Guiseppe Pelicci spoke at ecancer's Milan Summit on Precision Medicine 2018 about the challenges of perso… https://t.co/vusLZkMajO

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What Can Immunologists Learn from Systems Approaches?

Publication date: Available online 21 February 2018
Source:Trends in Immunology





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Pushing the frontiers of cardiovascular biology

The Council for Basic Cardiovascular Science (CBCS), founded in 2004 with the mission to foster and support basic research in cardiovascular biology within the European Society of Cardiology (ESC), brought together ESC working groups and societies outside the ESC that shared a common interest in various aspects of cardiovascular biology and medicine. To pursue this aim CBCS with the continuous and generous support of the ESC since then has started a host of initiatives (https://www.escardio.org/Councils/Council-on-Basic-Cardiovascular-Science-(CBCS)). CBCS launched a biennial Summer School in Cardiovascular Biology and provides travel grants for young researchers to attend the annual ESC congress. In addition, CBCS offers the ESC Basic Research Fellowship to successful and promising young scientists in cardiovascular research designed to allow them to spend one year in a European research laboratory. Other initiatives of the CBCS to support young researchers and to acknowledge their achievements in their field of endeavour are the ESC First Contact Initiative Grant and the Outstanding Achievement Award.

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The Secret of the Kissing Cousins: an ER-mitochondrial tethering protein regulates Ca2+ crosstalk in mammalian neurons



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Bariatric surgery helps to reduce blood pressure - insights from GATEWAY trial

Jesper Bäckdahl is a resident in Endocrinology and PhD student under the supervision of Mikael Rydén. Dr Bäckdahl holds a master degree in Public Health from the London School of Hygiene and Tropical Medicine. His research revolves around adipose tissue and its link to arterial stiffness and hypertension.

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Dr Jyoti Patel, ESC Scientist of Tomorrow, interviews Dr Eva Van Rooij



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The nerve of the spleen! Causing hypertension by placental growth factor



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Electrical coupling between cardiomyocytes and fibroblasts: experimental testing of a challenging and important concept

This editorial refers to ‘Electrical coupling between ventricular myocytes and myofibroblasts in the infarcted mouse heart’ by M. Rubart et al., pp. 389–400.

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Deoxycorticosterone acetate-salt hypertension activates placental growth factor in the spleen to couple sympathetic drive and immune system activation

Abstract
Aims
Chronic increase of mineralocorticoids obtained by administration of deoxycorticosterone acetate (DOCA) results in salt-dependent hypertension in animals. Despite the lack of a generalized sympathoexcitation, DOCA-salt hypertension has been also associated to overdrive of peripheral nervous system in organs typically targeted by blood pressure (BP), as kidneys and vasculature. Aim of this study was to explore whether DOCA-salt recruits immune system by overactivating sympathetic nervous system in lymphoid organs and whether this is relevant for hypertension.
Methods and results
To evaluate the role of the neurosplenic sympathetic drive in DOCA-salt hypertension, we challenged splenectomized mice or mice with left coeliac ganglionectomy with DOCA-salt, observing that they were both unable to increase BP. Then, we evaluated by immunofluorescence and ELISA levels of the placental growth factor (PlGF) upon DOCA-salt challenge, which significantly increased the growth factor expression, but only in the presence of an intact neurosplenic sympathetic drive. When PlGF KO mice were subjected to DOCA-salt, they were significantly protected from the increased BP observed in WT mice under same experimental conditions. In addition, absence of PlGF hampered DOCA-salt mediated T cells co-stimulation and their consequent deployment towards kidneys where they infiltrated tissue and provoked end-organ damage.
Conclusion
Overall, our study demonstrates that DOCA-salt requires an intact sympathetic drive to the spleen for priming of immunity and consequent BP increase. The coupling of nervous system and immune cells activation in the splenic marginal zone is established through a sympathetic-mediated PlGF release, suggesting that this pathway could be a valid therapeutic target for hypertension.

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Cardiovascular protection by Nox4

This editorial refers to ‘Both cardiomyocyte and endothelial cell Nox4 mediate protection against hemodynamic overload-induced remodelling’ by M. Zhang et al., pp. 401–408.

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Exploring immune checkpoints as potential therapeutic targets in atherosclerosis

Abstract
In the past decades, the inflammatory nature of atherosclerosis has been well-recognized and despite the development of therapeutic strategies targeted at its classical risk factors such as dyslipidemia and hypertension, atherosclerosis remains a major cause of morbidity and mortality. Additional strategies targeting the chronic inflammatory pathways underlying the development of atherosclerosis are therefore required. Interactions between different immune cells result in the secretion of inflammatory mediators, such as cytokines and chemokines, and fuel atherogenesis. Immune checkpoint proteins have a critical role in facilitating immune cell interactions and play an essential role in the development of atherosclerosis. Although the therapeutic potential of these molecules is well-recognized in clinical oncology, the use of immune checkpoint modulators in atherosclerosis is still limited to experimental models. Here, we review recent insights on the role of immune checkpoint proteins in atherosclerosis. Additionally, we explore the therapeutic potential and challenges of immune checkpoint modulating strategies in cardiovascular medicine and we discuss novel therapeutic approaches to target these proteins in atherosclerosis.

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LUMA in cardiac development and function

This editorial refers to ‘Luma is not essential for murine cardiac development and function' by M.J. Stroud et al., pp. 378–388.

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Mitochondrial targeted peptides preserve mitochondrial organization and decrease reversible myocardial changes in early swine metabolic syndrome

Abstract
Aims
The mechanisms responsible for cardiac damage in the early stages of metabolic syndrome (MetS) remain unknown. Mitochondria are intimately associated with cellular myofibrils, with the cytoskeleton functioning as a linkage coordinator, and closely associated to the calcium release sites of the sarcoplasmic reticulum (SR). We hypothesized that early MetS is characterized by mitochondria-related myocardial damage, associated with altered cytoskeletal–mitochondria–SR interaction.
Methods and results
Domestic pigs were studied after 16 weeks of diet-induced MetS, MetS treated for the last 4 weeks with the mitochondrial-targeted peptide elamipretide (ELAM; 0.1 mg/kg SC q.d), or Lean controls (n = 6/group). Cardiac remodeling and function were assessed by fast comuted tomography. Myocardial mitochondrial structure, SR–mitochondria interaction, calcium handling, cytoskeletal proteins, oxidative stress, and apoptosis were studied ex-vivo. MetS pigs developed hyperlipidemia, hypertension, and insulin resistance, yet cardiac function was preserved. MetS-induced mitochondrial disorganization, decreased (C18:2)4 cardiolipin, disrupted ATP/ADP balance, and decreased cytochrome-c oxidase (COX)-IV activity. MetS also increased mitochondrial hydrogen peroxide (H2O2) production, decreased nicotinamide adenine dinucleotide phosphate (NADPH)/NADP and GSH/GSSG, and decreased myocardial desmin and β2 tubulin immunoreactivity, and impaired SR–mitochondrial interaction and mitochondrial calcium handling, eliciting myocardial oxidative stress and apoptosis. ELAM improved mitochondrial organization and cardiolipin species profile, restored ATP/ADP ratio and COX-IV activity, decreased H202 production, and improved generation of NADPH and GSH. ELAM also improved cytoskeletal–mitochondria–SR interaction and mitochondrial calcium handling, attenuating oxidative stress, and apoptosis.
Conclusions
Disorganization of cardiomyocyte cytoskeletal-mitochondria-SR network is associated with cardiac reversible changes in early MetS, preceding overt cardiac dysfunction. These findings may introduce novel therapeutic targets for blunting cardiac damage in early MetS.

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An autofluorescence-based method for the isolation of highly purified ventricular cardiomyocytes

Abstract
Aims
The aim of our study was to set up a simple and reliable isolation method of living ventricular cardiomyocytes (vCMs) for molecular and biological studies.
Methods and results
A standard technique for the retrograde perfusion of an enzymatic solution was used to isolate cardiac cells from adult mouse heart. Fluorescence-activated cell sorting (FACS) on adult murine cardiac ventricle cells was performed, comparing the intrinsic autofluorescence in the FITC channel and the forward scatter (FSC) parameter in order to isolate highly fluorescent cells. The expression of cell-specific mRNAs was assessed with real-time PCR in cells sorted on the basis of their FITC and FSC characteristics. We identified two distinct subpopulations of cells harvested after retrograde perfusion of wild-type heart: FITChigh/FSCdim and FITCdim/FSChigh. Immunophenotyping and mRNA analysis (qPCR and RNA sequencing) revealed that only FITChigh/FSCdim cells were highly enriched in CM markers. Genes with high expression in endothelial cells and fibroblasts were enriched in the FITCdim/FSChigh subpopulation. With the use of tdTomatofl/fl-α-myosin heavy chain MerCreMer+/−mouse heart, we found that tdTomato-positive vCMs were present in the FITChigh/FSCdim region but were only rare in the FITCdim/FSChigh fraction.
Conclusion
We have developed a simple and reliable method for the isolation of highly purified vCMs from the adult murine myocardium, avoiding fixation and permeabilization steps. These isolated vCMs can be used in particular for detailed molecular studies, avoiding contamination with other myocardial cell types.

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Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine

Abstract
Aims
Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesized that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality.
Methods and results
Withdrawal of dietary creatine in AGAT-/- mice provided an estimate of myocardial creatine efflux of ∼2.7%/day; however, in vivo cardiac function was maintained despite low levels of myocardial creatine. Using AGAT-/- mice naïve to dietary creatine we confirmed absence of phosphocreatine in the heart, but crucially, ATP levels were unchanged. Potential compensatory adaptations were absent, AMPK was not activated and respiration in isolated mitochondria was normal. AGAT-/- mice had rescuable changes in body water and organ weights suggesting a role for creatine as a compatible osmolyte. Creatine-naïve AGAT-/- mice had haemodynamic impairment with low LV systolic pressure and reduced inotropy, lusitropy, and contractile reserve. Creatine supplementation only corrected systolic pressure despite normalization of myocardial creatine. AGAT-/- mice had low plasma HA and supplementation completely rescued all other haemodynamic parameters. Contractile dysfunction in AGAT-/- was confirmed in Langendorff perfused hearts and in creatine-replete isolated cardiomyocytes, indicating that HA is necessary for normal cardiac function.
Conclusions
Our findings argue against low myocardial creatine per se as a major contributor to cardiac dysfunction. Conversely, we show that HA deficiency can impair cardiac function, which may explain why low HA is an independent risk factor for multiple cardiovascular diseases.

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Cbx3 inhibits vascular smooth muscle cell proliferation, migration, and neointima formation

Abstract
Aims
To investigate the role of chromobox protein homolog 3 (Cbx3) in vascular smooth muscle cell (VSMC) proliferation, migration, and neointima formation following vascular injury.
Methods and results
Overexpression of Cbx3 led to a significant increase in VSMC contractile gene expression and VSMC apoptosis as well as a dramatic decrease in collagen gene expression, VSMC proliferation, and migration. Meanwhile, the opposite was observed following inhibition of endogenous Cbx3. Luciferase activity assays revealed that Notch signalling, but neither β-catenin nor NF-κB signalling, is regulated by Cbx3 in VSMCs, and among the four Notch receptors, Notch3 is selectively down-regulated by Cbx3 through a transcriptional repression mechanism. Notch3 gene activation recapitulates the effects of Cbx3 knockdown on VSMC proliferation and migration. Consequently, the inhibitory effects of Cbx3 over-expression on VSMC proliferation and migration were reversed by Notch3 gene reactivation. In a model of vascular damage by carotid wire injury, we observed that Cbx3 expression was dramatically down-regulated in the injured arteries. Local ectopic over-expression of Cbx3 in the injured arteries significantly inhibited Notch3 expression, thereby reducing VSMCs proliferation and causing an overall decrease in neointima formation. Additionally, injury-induced neointimal SMC hyperplasia was significantly reduced by aortic inhibition of Notch3. Importantly, a decreased expression level of Cbx3, but an increased expression level of Notch3, was observed in human femoral arteries with atherosclerotic lesions.
Conclusion
Cbx3 modulates VSMC contractile and collagen gene expression, as well as VSMC proliferation, migration, and apoptosis via a Notch3 pathway, and plays an important role in controlling injury-induced neointima formation.

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CCR2 expression on circulating monocytes is associated with arterial wall inflammation assessed by 18F-FDG PET/CT in patients at risk for cardiovascular disease

Abstract
Aims
Circulating monocytes infiltrate the plaque and differentiate into macrophages, contributing to an inflammatory environment which is associated with higher risk of cardiovascular events. Although the pivotal role of circulating monocytes in plaque inflammation has been firmly established, the search continues to identify specific monocyte subsets that may be especially atherogenic. Therefore, we evaluated the relation between monocyte phenotype, particularly surface receptor expression, and arterial wall inflammation in patients at increased cardiovascular risk.
Methods and results
We performed a multivariate linear regression analysis in 79 patients at increased cardiovascular risk who had both an 18F-fluorodeoxyglucose positron emission tomography/computed tomography to assess arterial wall inflammation and extensive monocyte characterization (using flow cytometry). We found that CCR2, a monocyte chemokine receptor essential for transmigration, significantly correlates with arterial wall inflammation. This relationship was independent of traditional cardiovascular risk factors and statin use (β = 0.429, P = 0.015). We found no relation between arterial wall inflammation and monocyte count or monocyte subsets, namely CD14+CD16−, CD14+CD16+, CD14+CD16 ++, CCR5+, CD18+, CD11b+, or CD11c+ monocytes.
Conclusion
Monocyte CCR2 expression is associated with arterial wall inflammation in patients at increased cardiovascular risk. Our data warrant further studies to assess if inhibition of CCR2 may attenuate atherosclerotic plaque inflammation.

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Both cardiomyocyte and endothelial cell Nox4 mediate protection against hemodynamic overload-induced remodelling

Abstract
Aims
NADPH oxidase-4 (Nox4) is an important reactive oxygen species (ROS) source that is upregulated in the haemodynamically overloaded heart. Our previous studies using global Nox4 knockout (Nox4KO) mice demonstrated a protective role of Nox4 during chronic abdominal aortic banding, involving a paracrine enhancement of myocardial capillary density. However, other authors who studied cardiac-specific Nox4KO mice reported detrimental effects of Nox4 in response to transverse aortic constriction (TAC). It has been speculated that these divergent results are due to cell-specific actions of Nox4 (i.e. cardiomyocyte Nox4 detrimental but endothelial Nox4 beneficial) and/or differences in the model of pressure overload (i.e. abdominal banding vs. TAC). This study aimed to (i) investigate whether the effects of Nox4 on pressure overload-induced cardiac remodelling vary according to the pressure overload model and (ii) compare the roles of cardiomyocyte vs. endothelial cell Nox4.
Methods and results
Global Nox4KO mice subjected to TAC developed worse cardiac remodelling and contractile dysfunction than wild-type littermates, consistent with our previous results with abdominal aortic banding. Next, we generated inducible cardiomyocyte-specific Nox4 KO mice (Cardio-Nox4KO) and endothelial-specific Nox4 KO mice (Endo-Nox4KO) and studied their responses to pressure overload. Both Cardio-Nox4KO and Endo-Nox4KO developed worse pressure overload-induced cardiac remodelling and dysfunction than wild-type littermates, associated with significant decrease in protein levels of HIF1α and VEGF and impairment of myocardial capillarization.
Conclusions
Cardiomyocyte as well as endothelial cell Nox4 contributes to protection against chronic hemodynamic overload-induced cardiac remodelling, at least in part through common effects on myocardial capillary density.

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Therapeutic strategies utilizing SDF-1α in ischaemic cardiomyopathy

Abstract
Heart failure is rapidly increasing in prevalence and will redraw the global landscape for cardiovascular health. Alleviating and repairing cardiac injury associated with myocardial infarction (MI) is key to improving this burden. Homing signals mobilize and recruit stem cells to the ischaemic myocardium where they exert beneficial paracrine effects. The chemoattractant cytokine SDF-1α and its associated receptor CXCR4 are upregulated after MI and appear to be important in this context. Activation of CXCR4 promotes both cardiomyocyte survival and stem cell migration towards the infarcted myocardium. These effects have beneficial effects on infarct size, and left ventricular remodelling and function. However, the timing of endogenous SDF-1α release and CXCR4 upregulation may not be optimal. Furthermore, current ELISA-based assays cannot distinguish between active SDF-1α, and SDF-1α inactivated by dipeptidyl peptidase 4 (DPP4). Current therapeutic approaches aim to recruit the SDF-1α-CXCR4 pathway or prolong SDF-1α life-time by preventing its cleavage by DPP4. This review assesses the evidence supporting these approaches and proposes SDF-1α as an important confounder in recent studies of DPP4 inhibitors.

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Luma is not essential for murine cardiac development and function

Abstract
Aims
Luma is a recently discovered, evolutionarily conserved protein expressed in mammalian heart, which is associated with the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex. The LINC complex structurally integrates the nucleus and the cytoplasm and plays a critical role in mechanotransduction across the nuclear envelope. Mutations in several LINC components in both humans and mice result in various cardiomyopathies, implying they play essential, non-redundant roles. A single amino acid substitution of serine 358 to leucine (S358L) in Luma is the unequivocal cause of a distinct form of arrhythmogenic cardiomyopathy. However, the role of Luma in heart has remained obscure. In addition, it also remains to be determined how the S358L mutation in Luma leads to cardiomyopathy.
Methods and results
To determine the role of Luma in the heart, we first determined the expression pattern of Luma in mouse heart. Luma was sporadically expressed in cardiomyocytes throughout the heart, but was highly and uniformly expressed in cardiac fibroblasts and vascular smooth muscle cells. We also generated germline null Luma mice and discovered that germline null mutants were viable and exhibited normal cardiac function. Luma null mice also responded normally to pressure overload induced by transverse aortic constriction. In addition, localization and expression of other LINC complex components in both cardiac myocytes and fibroblasts was unaffected by global loss of Luma. Furthermore, we also generated and characterized Luma S358L knock-in mice, which displayed normal cardiac function and morphology.
Conclusion
Our data suggest that Luma is dispensable for murine cardiac development and function and that the Luma S358L mutation alone may not cause cardiomyopathy in mice.

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Minimum alcohol pricing in Wales would cut deaths and hospital admissions, study finds

Introducing a 50p (€0.56; $0.69) minimum unit price for alcohol in Wales would reduce deaths and hospital admissions related to alcohol, as well as crimes and work absences associated with drinking,...
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Population attributable fraction

Much statistical analysis seeks to identify associations between exposures and outcomes. The population attributable fraction (PAF) is an epidemiologic measure widely used to assess the public health...
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