Plasma-induced High-efficient Synthesis of Boron Doped Reduced Graphene Oxide for Supercapacitors

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC04052G, Communication

Shaobo Li, Zhaofeng Wang, Hanmei Jiang, Limei Zhang, Jingzheng Ren, Ming Tao Zheng, Lichun Dong, Luyi Sun
In this work, we presented a novel route to synthesize boron doped reduced graphene oxide (rGO) by using the dielectric barrier discharge (DBD) plasma technology under ambient conditions. The doping...
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Exploration of K2Ti8O17 as the Anode Materials for Potassium-ion Batteries

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC05102B, Communication

Jin Han, Mao-Wen Xu, Yu-Bin Niu, guannan Li, Min-Qiang Wang, Yan Zhang, Min Jia, Changming Li
Novel K2Ti8O17 is successfully fabricated via a facile hydrothermal method combined with a subsequent annealing treatment and further evaluated as anode material for potassium-ion batteries for the first time. This...
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Does Quantitative Research in Child Maltreatment Tell the Whole Story? The Need for Mixed-Methods Approaches to Explore the Effects of Maltreatment in Infancy

Background and Aims. Research on child maltreatment has largely overlooked the under-five age group and focuses primarily on quantitative measurement. This mixed-methods study of maltreated children () entering care (age 6–60 months) combines a quantitative focus on the associations between care journey characteristics and mental health outcomes with a qualitative exploration of maltreatment in four different families. Methods. Care journey data was obtained from social care records; mental health and attachment assessments were carried out following entry to care; qualitative data comprised semistructured interviews with professionals, foster carers, and parents. Results. Significant associations were found between suspected sexual abuse and increased DAI inhibited attachment symptoms () and between reported domestic violence and decreased DAI inhibited () and disinhibited () attachment symptoms. Qualitative results: two themes demonstrate the complexity of assessing maltreatment: (1) overlapping maltreatment factors occur in most cases and (2) maltreatment effects may be particularly challenging to isolate. Conclusions. Qualitative exploration has underscored the complexity of assessing maltreatment, indicating why expected associations were not found in this study and posing questions for the quantitative measurement of maltreatment in general. We therefore suggest a new categorisation of maltreatment and call for the complimentary research lenses of further mixed-methods approaches.

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Predictive value of T2 relative signal intensity for response to somatostatin analogs in newly diagnosed acromegaly

Abstract

Introduction

The difficulty of predicting the efficacy of somatostatin analogs (SSA) is not fully resolved. Here, we quantitatively evaluated the predictive value of relative signal intensity (rSI) on T1- and T2-weighted magnetic resonance imaging (MRI) for the short-term efficacy (3 months) of SSA therapy in patients with active acromegaly and assessed the correlation between MRI rSI and expression of somatostatin receptors (SSTR).

Methods

This was a retrospective review of prospectively recorded data. Ninety-two newly diagnosed patients (37 males and 55 females) with active acromegaly were recruited. All patients were treated with pre-surgical SSA, followed by reassessment and transspenoidal surgery. rSI values were generated by calculating the ratio of SI in the tumor to the SI of normal frontal white matter. The Youden indices were calculated to determine the optimal cutoff of rSI to determine the efficacy of SSA. The correlation between rSI and expression of SSTR2/5 was analyzed by the Spearman rank correlation coefficient.

Results

T2 rSI was strongly correlated with biochemical sensitivity to SSA. The cutoff value of T2 rSI to distinguish biochemical sensitivity was 1.205, with a positive predictive value (PPV) of 81.5 % and a negative predictive value (NPV) of 77.3 %. No correlation was found between MRI and tumor size sensitivity. Moreover, T2 rSI was negatively correlated with the expression of SSTR5.

Conclusion

T2 rSI correlates with the expression of SSTR5 and quantitatively predicts the biochemical efficacy of SSA in acromegaly.

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Spontaneous dissections of the anterior cerebral artery: a meta-analysis of the literature and three recent cases

Abstract

Introduction

Spontaneous dissections of intracranial arteries are rare, but important causes of stroke, especially in younger patients. Dissections of the anterior cerebral artery (ACA) have been reported only very rarely in the European and North American populations but might be more prevalent than previously thought.

Methods

This paper describes the presenting pattern of the disease, the clinical and imaging findings, as well as endovascular therapeutical options with respect to a meta-analysis of cases reported in the literature. Additionally, own observations in three recent representative cases are discussed.

Results

Overall, 80 cases from recent literature were included to the meta-analysis. The median age was 51 (35–82) years. Ischemia alone was described in 58 cases (73 %), subarachnoid hemorrhage (SAH) in 8 cases (10 %), and a combination of both in 14 cases (17 %). Radiological diagnosis including use of thin-layered 3T-MRI vessel wall imaging with black blood technique was verified by double lumen, by a string sign or string and pearl sign, or by a vessel wall hematoma in 23 (32 %), 62 (89 %), and 14 (20 %) cases, respectively. Interventional or surgical treatment was performed in 7 cases. A good clinical recovery was achieved in 77 % of cases.

Conclusion

Dissections of the ACA mostly cause ischemia, but can cause SAH or a combination of both in a relatively young population. Detailed neuroradiological diagnosis including 3T-MRI vessel wall imaging is required as a double lumen, isolated stenosis due to vessel wall hematoma, or the secondary development of a pseudoaneurysm might occur. Interventional therapy is the primary therapy for these vascular complications.

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Spinal dual-energy computed tomography: improved visualisation of spinal tumorous growth with a noise-optimised advanced monoenergetic post-processing algorithm

Abstract

Introduction

The aim of this study was to evaluate the effect of advanced monoenergetic post-processing (MEI+) on the visualisation of spinal growth in contrast-enhanced dual-energy CT (DE-CT).

Methods

Twenty-six oncologic patients (age, 61 ± 17 years) with spinal tumorous growth were included. Patients underwent contrast-enhanced dual-energy CT on a third-generation dual-source CT scanner. Image acquisition was in dual-energy mode (100/Sn150kV), and scans were initiated 90 s after contrast agent administration. Virtual monoenergertic images (MEI+) were reconstructed at four different kiloelectron volts (keV) levels (40, 60, 80, 100) and compared to the standard blended portal venous computed tomography (CT_pv). Image quality was assessed qualitatively (conspicuity, delineation, sharpness, noise, confidence; two independent readers; 5-point Likert scale; 5 = excellent) and quantitatively by calculating signal-to-noise (SNR) and contrast-to-noise-ratios (CNR). For a subgroup of 10 patients with MR imaging within 4 months of the DE-CT, we compared the monoenergetic images to the MRIs qualitatively.

Results

Highest contrast of spinal growth was observed in MEI+ at 40 keV, with significant differences to CT_pv and all other keV reconstructions (60, 80, 100; p < 0.01). Highest conspicuity, delineation and sharpness were observed in MEI+ at 40 keV, with significant differences to CT_pv (p < 0.001). Similarly, MEI+ at 40 keV yielded highest diagnostic confidence (4.6 ± 0.6), also with significant differences to CT_pv (3.45 ± 0.9, p < 0.001) and to high keV reconstructions (80, 100; p ≤ 0.001). Similarly, CNR calculations revealed highest scores for MEI+ at 40 keV followed by 60 keV and CT_pv, with significant differences to high keV MEI+ reconstructions. Qualitative analysis scores peaked for MR images followed by the MEI+ 40-keV reconstructions.

Conclusion

MEI+ at low keV levels can significantly improve image quality and delineation of spinal growth in patients with portal-venous phase CT scans due to increased CNR and limited image noise.

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Optic radiations evaluation in patients affected by high-grade gliomas: a side-by-side constrained spherical deconvolution and diffusion tensor imaging study

Abstract

Introduction

The need to improve surgical efficacy in patients affected by high-grade gliomas has led to development of advanced pre-surgical MRI-based techniques such as tractography. This study investigates pre-surgical planning of optic radiations (ORs) in patients affected by occipito-temporo-parietal high-grade gliomas, by means of constrained spherical deconvolution (CSD) and diffusion tensor imaging (DTI) tractography.

Methods

Twelve patients with occipito-temporo-parietal high-grade gliomas were recruited and analyzed using a 3 T MRI scanner. Diffusion-weighted imaging (DWI) was conducted with 64 gradient diffusion directions. OR alterations were assessed qualitatively and quantitatively to evaluate the effectiveness of CSD- and DTI-based pre-surgical planning.

Results

CSD-based tractography provided better qualitative evaluation of affected white matter tracts when compared to DTI; by thresholding tractographic probabilistic maps coming from all reconstructions, we detected, at the highest cutoff level, OR involvement in 75 % of patients (vs 41.67 % of patients with probabilistic DTI). Quantitative analysis of diffusion parameters revealed a statistically significant decrease in fractional anisotropy (FA) in the affected side following CSD-based reconstructions; on the contrary, DTI-based reconstructions did not show any significant quantitative alteration.

Conclusion

Our results showed improvement in pre-surgical planning of high-grade gliomas involving ORs with use of CSD-based tractography. This technique provided more useful information regarding the white matter spatial relationship with brain neoplasm and its involvement in the glioma, when compared to DTI. Using CSD model for OR evaluation may optimize safe surgical resection margins, helping to reduce risk of post-operative visual deficits.

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Validation of the finding of hypertrophy of the clava in infantile neuroaxonal dystrophy/ PLA2G6 by biometric analysis

Abstract

Introduction

Infantile neuroaxonal dystrophy (INAD), an autosomal recessive neurodegenerative disorder due to PLA2G6 mutation, is classified both as a PLA2G6-associated neurodegeneration (PLAN) disorder and as one of the neurodegeneration with brain iron accumulation (NBIA) disorders. Age of onset and clinical presentation in INAD is variable. Typically described imaging features of cerebellar atrophy, cerebellar cortex bright FLAIR signal, and globus pallidus iron deposition are variable or late findings. We characterize clinical and neuroimaging phenotypes in nine children with confirmed PLA2G6 mutations and show a useful imaging feature, clava hypertrophy, which may aid in earlier identification of patients. Measurements of the clava confirm actual enlargement, rather than apparent enlargement due to volume loss of the other brain stem structures.

Methods

A retrospective clinical and MRI review was performed. Brain stem measurements were performed and compared with age-matched controls.

Results

We identified nine patients, all with novel PLA2G6 gene mutations. MRI, available in eight, showed clava hypertrophy, regardless of age or the absence of other more typically described neuroimaging findings. Brain autopsy in our cohort confirmed prominent spheroid bodies in the clava nuclei.

Conclusion

Clava hypertrophy is an important early imaging feature which may aid in indentification of children who would benefit from specific testing for PLA2G6 mutations.

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Firefighter/EMT - City of Albany

ALBANY, CITY OF 333 BROADALBIN SW ALBANY, OREGON 97321 Updated: July 25, 2016 Classification: Firefighter/EMT The City of Albany is creating a hiring list for upcoming future openings. Applications will be reviewed when a sufficient number of applications have been received. The recruitment will stay open until a hiring pool has been established. All candidates must take FireTEAM and have a valid NTN ...

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High-Resolution Inductively Coupled Plasma Optical Emission Spectrometry for 234U/238Pu Age Dating of Plutonium Materials and Comparison to Sector Field Inductively Coupled Plasma Mass Spectrometry

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b02472

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Measuring Connectivity in the Primary Visual Pathway in Human Albinism Using Diffusion Tensor Imaging and Tractography

This manuscript describes deterministic and probabilistic algorithms for white matter (WM) reconstruction, used to examine differences in optic radiation (OR) connectivity between albinism and controls. Although probabilistic tractography follows the true course of nerve fibers more closely, deterministic tractography was run to compare the reliability and reproducibility of both techniques.

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Ultrasensitive sliver nanorods array SERS sensor for mercury ions

Publication date: 15 January 2017
Source:Biosensors and Bioelectronics, Volume 87
Author(s): Chunyuan Song, Boyue Yang, Yu Zhu, Yanjun Yang, Lianhui Wang
With years of outrageous mercury emissions, there is an urgent need to develop convenient and sensitive methods for detecting mercury ions in response to increasingly serious mercury pollution in water. In the present work, a portable, ultrasensitive SERS sensor is proposed and utilized for detecting trace mercury ions in water. The SERS sensor is prepared on an excellent sliver nanorods array SERS substrate by immobilizing T-component oligonucleotide probes labeled with dye on the 3′-end and –SH on the 5′-end. The SERS sensor responses to the specific chemical bonding between thymine and mercury ions, which causes the previous flexible single strand of oligonucleotide probe changing into rigid and upright double chain structure. Such change in the structure drives the dyes far away from the excellent SERS substrate and results in a SERS signal attenuation of the dye. Therefore, by monitoring the decay of SERS signal of the dye, mercury ions in water can be detected qualitatively and quantitatively. The experimental results indicate that the proposed optimal SERS sensor owns a linear response with wide detecting range from 1pM to 1μM, and a detection limit of 0.16pM is obtained. In addition, the SERS sensor demonstrates good specificity for Hg²⁺, which can accurately identify trace mercury ions from a mixture of ten kinds of other ions. The SERS sensor has been further executed to analyze the trace mercury ions in tap water and lake water respectively, and good recovery rates are obtained for sensing both kinds of water. With its high selectivity and good portability, the ultrasensitive SERS sensor is expected to be a promising candidate for discriminating mercury ions in the fields of environmental monitoring and food safety.



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A novel fluorescent DNA sensor for ultrasensitive detection of Helicobacter pylori

Publication date: 15 January 2017
Source:Biosensors and Bioelectronics, Volume 87
Author(s): Ziping Liu, Xingguang Su
In this work, a novel fluorescent DNA sensor for ultrasensitive detection of Helicobacter pylori (H. pylori) DNA was developed. This strategy took advantage of DNA hybridization between single-stranded DNA (ssDNA, which had been designed as an aptamer specific for H. pylori DNA) and the complementary target H. pylori DNA, and the feature that ssDNA bound to graphene oxide (GO) with significantly higher affinity than double-stranded DNA (dsDNA). ssDNA were firstly covalent conjugated with CuInS2 quantum dots (QDs) by reaction between the carboxy group of QDs and amino group modified ssDNA, forming ssDNA-QDs genosensor. In the absence of the complementary target H. pylori DNA, GO could adsorb ssDNA-QDs DNA sensor and efficiently quench the fluorescence of ssDNA-QDs. While the complementary target H. pylori DNA was introduced, the ssDNA-QDs preferentially bound with the H. pylori DNA. The formation of dsDNA would alter the conformation of ssDNA and disturb the interaction between ssDNA and GO. Thus, the dsDNA-QDs/GO system exhibited a stronger fluorescence emission than that of the ssDNA-QDs/GO system. Under the optimized conditions, a linear correlation was established between the fluorescence intensity ratio I/I0 and the concentration of H. pylori DNA in the range of 1.25–875pmolL⁻¹ with a detection limit of 0.46pmolL⁻¹. The proposed method was applied to the determination of H. pylori DNA sequence in milk samples with satisfactory results.



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A two-photon fluorescent probe for exogenous and endogenous superoxide anion imaging in vitro and in vivo

Publication date: 15 January 2017
Source:Biosensors and Bioelectronics, Volume 87
Author(s): Run-Qing Li, Zhi-Qiang Mao, Lei Rong, Nian Wu, Qi Lei, Jing-Yi Zhu, Lin Zhuang, Xian-Zheng Zhang, Zhi-Hong Liu
Herein, we report a novel quinoline derivative-based two-photon fluorescent probe 6-(dimethylamino)quinoline-2-benzothiazoline (HQ), which is capable of tracking superoxide anion in organisms with specific "turn-on" fluorescence response based on extension of π-conjugations and moderate ICT process. The probe exhibited favorable photophysical properties, a broad linear range and high photostability. It can specifically detect superoxide anion with a significant fluorescence enhancement and great linearity from 0 to 500μM in PBS buffer. Furthermore, HQ shows low cytotoxicity and excellent photostability toward living cells and organisms, which was able to monitor endogenous superoxide anion fluxes in living cells and in vivo. For the first time, endogenous superoxide anion in lung inflammation was visualized successfully by using HQ through two-photon microscopy, and the probe HQ shows great potential for fast in-situ detecting of inflammatory response in live organisms.



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Enhancing biosensor properties of conducting polymers via copolymerization: Synthesis of EDOT-substituted bis(2-pyridylimino)isoindolato-palladium complex and electrochemical sensing of glucose by its copolymerized film

Publication date: 15 January 2017
Source:Biosensors and Bioelectronics, Volume 87
Author(s): Tuğçe Yazıcı Tekbaşoğlu, Tugba Soganci, Metin Ak, Atıf Koca, M. Kasım Şener
1,3-Bis(2-pyridylimino)isoindoline derivative bearing 3,4-ethylenedioxythiophene (EDOT-BPI) and its palladium complex (EDOT-PdBPI) were synthesized and characterized by FT-IR, ¹H NMR, ¹³C NMR, UV–Vis spectroscopies and via mass spectrometric analysis. Polymerization of EDOT-PdBPI and copolymerization with 4-amino-N-(2,5-di(thiophene-2-yl)-1H-pyrrol-1-yl)benzamide (HKCN) were carried out by an electrochemical method. In addition, P(EDOT-PdBPI-co-HKCN) modified graphite rod electrode was improved for amperometric glucose sensor based on glucose oxidase (GOx). In this novel biosensor matrix, amino groups in HKCN were used for the enzyme immobilization. On the other hand, EDOT-PdBPI used to mediate the bioelectrocatalytic reaction. Amperometric detection was carried out following oxygen consumption at −0.7V vs. the Ag reference electrode in phosphate buffer (50mM, pH 6.0). The novel biosensor showed a linear amperometric response for glucose within a concentration range of 0.25mM to 2.5mM (LOD: 0.176mM). Amperometric signals at 1mM of glucose were 17.9μA under anaerobic conditions. Amperometric response of the P(EDOT-PdBPI-co-HKCN)/GOx electrode decreased only by 13% within eight weeks. The P(EDOT-PdBPI-co-HKCN)/GOx electrode showed good selectivity in the presence of ethanol and phenol. This result shows that, modification of the proposed biosensor by copolymerization of amine functionalized monomer, which is indispensable to the enzyme immobilization, with palladium complex bearing monomer, which is mediate the bioelectrocatalytic reaction, have provided to give perfect response to different glucose concentrations.

Graphical abstract

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Real-time and in situ enzyme inhibition assay for the flux of hydrogen sulfide based on 3D interwoven AuPd-reduced graphene oxide network

Publication date: 15 January 2017
Source:Biosensors and Bioelectronics, Volume 87
Author(s): Hongmei Yang, Yan Zhang, Li Li, Guoqiang Sun, Lina Zhang, Shenguang Ge, Jinghua Yu
A highly sensitive enzyme inhibition analytical platform was established firstly based on paper-supported 3D interwoven AuPd-reduced graphene oxide (rGO) network (NW) for real-time and in situ analysis of H2S released from cancer cells. The novel paper working electrode (PWE) with large electric conductivity, effective surface area and unusual biocompatibility, was fabricated via controllably assembling rGO and AuPd alloy nanoparticles onto the surface of cellulose fibers and into the macropores of paper, which was employed as affinity matrix for horseradish peroxidase (HRP) loading and cells capture. It was the superior performances of AuPd-rGO-NW-PWE that made the loaded HRP exhibit excellent electrocatalytic behavior to H2O2, bring the rapid enhancement of current response. After releasing H2S, the current response would be obviously decreased due to the efficient inhibition effect of H2S on HRP activity. The inhibition degree of HRP was directly proportional to the amount of H2S, and so, the flux of H2S released from cells could be recorded availably. Thus, this proposed enzyme inhibition cyto-sensor could be applied for efficient recording of the release of H2S, which had potential utility to cellular biology and pathophysiology.



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Comparing neurostimulation technologies in refractory focal-onset epilepsy

For patients with pharmacoresistant focal epilepsy in whom surgical resection of the epileptogenic focus fails or was not feasible in the first place, there were few therapeutic options. Increasingly, neurostimulation provides an alternative treatment strategy for these patients. Vagal nerve stimulation (VNS) is well established. Deep brain stimulation (DBS) and cortical responsive stimulation (CRS) are newer neurostimulation therapies with recently published long-term efficacy and safety data. In this literature review, we introduce these therapies to a non-specialist audience. Furthermore, we compare and contrast long-term (5-year) outcomes of newer neurostimulation techniques with the more established VNS. A search to identify all studies reporting long-term efficacy (>5 years) of VNS, CRS and DBS in patients with refractory focal/partial epilepsy was conducted using PubMed and Cochrane databases. The outcomes compared were responder rate, percentage seizure frequency reduction, seizure freedom, adverse events, neuropsychological outcome and quality of life. We identified 1 study for DBS, 1 study for CRS and 4 studies for VNS. All neurostimulation technologies showed long-term efficacy, with progressively better seizure control over time. Sustained improvement in quality of life measures was demonstrated in all modalities. Intracranial neurostimulation had a greater side effect profile compared with extracranial stimulation, though all forms of stimulation are safe. Methodological differences between the studies mean that direct comparisons are not straightforward. We have synthesised the findings of this review into a pragmatic decision tree, to guide the further management of the individual patient with pharmacoresistant focal-onset epilepsy.

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Early work-related physical exposures and low back pain in midlife: the Cardiovascular Risk in Young Finns Study

Objective

To examine whether heavy physical workload in young adulthood increases the risk of local and radiating low back pain (LBP) in midlife.

Methods

Longitudinal nationally representative Young Finns Study data among women (n=414) and men (n=324), aged 18–24 years in 1986 (baseline), were used. Physical heaviness of work was reported at baseline and follow-up (2007), and local and radiating LBP at follow-up. Covariates were age, smoking and body mass index. Logistic regression was used to examine the associations between physical heaviness of work and LBP. Additionally, the mediating effect of back pain at baseline was examined (the Sobel test).

Results

After adjustment for the covariates, and as compared with sedentary/light physical workload, heavy physical workload was associated with radiating LBP among women (OR 4.09, 95% CI 1.62 to 10.31) and men (OR 2.01, 95% CI 1.06 to 3.82). Among men, early back pain mediated the association (p value from the Sobel test=0.006). Among women, early exposure to physically heavy work showed the most consistent associations, while early and late exposures were associated with radiating and local LBP among men. Persistently heavy physical work was associated with radiating LBP among women and men.

Conclusions

Physically heavy work at a young age can have a long-lasting effect on the risk of LBP, radiating LBP in particular. These results highlight the need to consider early and persistent exposures to prevent the adverse consequences of physical workload for the low back.

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Mustard gas exposure and mortality among retired workers at a poisonous gas factory in Japan: a 57-year follow-up cohort study

Objectives

Mustard gas (MG) has been the most widely used chemical warfare agent in the past century. However, few but conflicting data exist on the effects of MG exposure on long-term mortality. We investigated MG-related mortality in retired workers at a poisonous gas factory.

Methods

We assessed mortality rates among 2392 male and 1226 female workers, whose vital status could be determined through 31 December 2009, at a poisonous gas factory operating from 1929 to 1945 in Okuno-jima, Japan. The analysis employed standardised mortality ratios (SMRs) calculated using national and prefectural references and a Cox proportional hazard regression model. Applying the Kaplan-Meier method, we compared cumulative death rates in the study cohort stratified by an 'Okuno-jima MG Index' which represented the product of HRs derived for job category and length of service.

Results

Among male workers, we found significant excesses in mortality from upper respiratory tract cancer (SMR 3.06), liver cancer (1.67), lung cancer (2.01) and chronic bronchitis/emphysema (4.84) compared with the national population, as well as stomach cancer (1.20) versus the Hiroshima Prefecture population. When stratified into 3 subgroups by the Okuno-jima MG Index, those with a higher Okuno-jima MG Index had significantly higher cumulative rates of death from respiratory cancer and chronic bronchitis/emphysema.

Conclusions

MG exposure significantly increases the long-term risk of death from respiratory cancer and chronic bronchitis/emphysema. The Okuno-jima MG Index may be a useful indicator for estimating cumulative MG exposure.

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The Immune System in Tissue Environments Regaining Homeostasis after Injury: Is “Inflammation” Always Inflammation?

Inflammation is a response to infections or tissue injuries. Inflammation was once defined by clinical signs, later by the presence of leukocytes, and nowadays by expression of "proinflammatory" cytokines and chemokines. But leukocytes and cytokines often have rather anti-inflammatory, proregenerative, and homeostatic effects. Is there a need to redefine "inflammation"? In this review, we discuss the functions of "inflammatory" mediators/regulators of the innate immune system that determine tissue environments to fulfill the need of the tissue while regaining homeostasis after injury.

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Surgical management of petrous apex cholesterol granulomas by an infralabyrinthine approach: Our experience with fourteen cases

Abstract

Cholesterol granulomas represent 40% of benign lesions developed within the petrous apex.¹ Most of them are asymptomatic and do not require any treatment.² When they involve adjacent structures such as the inner ear, the internal auditory meatus, the cranial nerves, or when they are painful, surgical management is required although this is challenging because of the position of the lesion, and the high rate of recurrence.

This article is protected by copyright. All rights reserved.

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A Copper Catalyzed Azidation and Peroxidation of [small beta]-Napthols via Oxidative Dearomatization Strategy

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC04894C, Communication

Jayaraman Dhineshkumar, Prasanjit Samaddar, Kandikere Ramaiah Prabhu
Dearomatizative azidation and peroxidation of [small beta]-naphthols have been explored using copper bromide as a catalyst. These reactions lead to highly valuable naphthalenone derivatives such as quaternary azide derivatives and quaternary...
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An Exploration of the Reactivity of Singlet Oxygen with Biomolecular Constituents

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC05392K, Communication

barbara marchetti, Tolga Karsili
The thermal reaction between biomolecules and singlet oxygen (1O2) is important for rendering the genetic material within toxic cells inactive. Here we present results from state-of-the-art multi-reference computational methods that...
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Etiological associations and outcome predictors of acute electroencephalography in childhood encephalitis

Publication date: October 2016
Source:Clinical Neurophysiology, Volume 127, Issue 10
Author(s): Shekeeb S. Mohammad, Samantha M. Soe, Sekhar C. Pillai, Margherita Nosadini, Elizabeth H. Barnes, Deepak Gill, Russell C. Dale
ObjectivesTo examine EEG features in a retrospective 13-year cohort of children with encephalitis.Methods354 EEGs from 119 patients during their admission were rated blind using a proforma with demonstrated inter-rater reliability (mean k=0.78). Patients belonged to 12 etiological groups that could be grouped into infectious and infection-associated (n=47), immune-mediated (n=36) and unknown (n=33). EEG features were analyzed between groups and for risk of abnormal Liverpool Outcome Score and drug resistant epilepsy (DRE) at last follow up.Results86% children had an abnormal first EEG and 89% had at least one abnormal EEG. 55% had an abnormal outcome, and 13% had DRE after median follow-up of 7.3years (2.0–15.8years). Reactive background on first EEGs (9/11, p=0.04) and extreme spindles (4/11, p<0.001) distinguished patients with anti-N-Methyl-d-Aspartate Receptor encephalitis. Non-reactive EEG background (48% first EEGs) predicted abnormal outcome (OR 3.8, p<0.001). A shifting focal seizure pattern, seen in FIRES (4/5), anti-voltage gated potassium channel (2/3), Mycoplasma (1/10), other viral (1/10) and other unknown (1/28) encephalitis, was most predictive of DRE after multivariable analysis (OR 11.9, p<0.001).ConclusionsNon-reactive EEG background and the presence of shifting focal seizures resembling migrating partial seizures of infancy are predictors of abnormal outcome and DRE respectively in childhood encephalitis.SignificanceEEG is a sensitive but non-discriminatory marker of childhood encephalitis. We highlight the EEG features that predict abnormal outcome and DRE.



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Improving value-add work and satisfaction in medical residents training: a resident-led quality improvement project employing the lean method to improve hospital supply usage

Purpose

Our hospital has a Housestaff Quality Council that fosters education and mentorship of medical residents for quality improvement methodologies. Medical residents on our council identified non-standardised storage rooms as a source of medical resident inefficiency and dissatisfaction. To improve value-add work, medical residents implemented and evaluated a quality improvement project of storage room supplies using the lean method.

Methods

Using 5S principle and lean methodology, we designed and implemented a standardised supply cart with physician specific supplies. Between April 2014 and April 2015, 40 random observations (20 residents and 20 nurses) both before and after the standardised supply cart implementation were made. The duration time to locate an item was measured in seconds. The paths taken to locate items were drawn as spaghetti diagrams. Nurses served as our control group given that their supplies were not moved in the implementation. Fifty residents were surveyed to assess their satisfaction.

Results

Implementation of the standardised supply cart reduced the time for residents to locate an item per visit from 50.8 to 30.2 s in one unit (p<0.05) and 127 to 28.3 s in the second unit (p<0.05). Mean time savings per day per resident were 5 min. The spaghetti diagrams indicated that finding supplies became more efficient after the intervention for residents. After the intervention, 92% of residents reported finding supplies more rapidly and 86% reported less frustration with finding supplies.

Conclusions

Residents applied the 5S principles and lean methodology to identify and solve a problem that created inefficiency and dissatisfaction.

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Long-term anticoagulation with rivaroxaban for preventing recurrent VTE: A benefit–risk analysis of EINSTEIN EXTENSION

Background

Short-term anticoagulant treatment for acute deep-vein thrombosis (DVT) or pulmonary embolism (PE) effectively reduces the risk of recurrent disease during the first 6 to 12 months of therapy. Continued anticoagulation is often not instituted because of the perception among physicians that the risk of major bleeding will outweigh the risk of new venous thrombotic episodes.

Methods

Benefit-risk analysis using the randomized EINSTEIN-EXTENSION trial, which compared continued rivaroxaban versus placebo in 1197 patients with symptomatic DVT or PE who had completed 6-12 months of anticoagulation and in whom physicians had equipoise with respect to the need for continued anticoagulation. One-year Kaplan-Meier rates and rate differences of recurrent venous thromboembolism (VTE) and major bleeding were calculated. Benefits and risks were assessed using rate differences scaled to a population size of 10000 patients treated for 1 year.

Results

Recurrent VTE occurred in 8 (3.0%) rivaroxaban recipients and 42 (9.6%) placebo patients. In a population of 10000 patients treated for 1 year, rivaroxaban treatment would have resulted in 665 (95% CI 246-1084) fewer recurrent VTEs than placebo (number needed to treat=15). Major bleeding occurred in 4 (0.7%) and 0 patients, respectively. Rivaroxaban treatment would have resulted in 68 (95% CI 2-134) more major bleeding events than placebo (number needed to harm=147). Kaplan–Meier analysis showed early recurrent VTE reduction with rivaroxaban that continued to improve throughout treatment; major bleeding increased gradually, plateauing at ±100 days.

Conclusions

A clinically important benefit and a favorable benefit–risk profile of continued rivaroxaban anticoagulation was observed.

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Ageless beauty

Volumetric rejuvenation of the face with fillers has gained popularity as being the least invasive intervention whose adverse effects are mostly minor, short-lived and self-limited.1 However, this is not always the case.

An 83-year-old woman who had a longstanding history of diabetes, hypertension and myocardial infarction was admitted after fainting. Her vital signs, initial examination, laboratory tests and ECG were unremarkable. However, head CT yielded a surprising incidental and asymptomatic finding (figure 1). She was discharged 1 day later with a diagnosis of syncope due to orthostatic hypotension due to diabetic autonomic neuropathy.

Cheek augmentation is usually done either by surgical placement of solid implants (commonly silicone) or much more often by injections using hyaluronic acid—currently, the most widely used filler; or autologous fat; collagen; calcium hydroxylapatite; etc. The goal is to achieve aesthetic enhancement by adding volume to areas that had recessed with age.

Head CT is very...

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Pulmonary rehabilitation as a mechanism to reduce hospitalizations for acute exacerbations of chronic obstructive pulmonary disease: A systematic review and meta-analysis

Background

Acute exacerbations of COPD (AECOPD) have a significant impact on healthcare utilization, including physician visits and hospitalizations. Previous studies and reviews have shown that pulmonary rehabilitation has many benefits but the effect on hospitalizations for AECOPD is inconclusive.

Methods

A literature search was carried out to find studies that might help determine, using a meta-analysis, the impact of pulmonary rehabilitation on AECOPD, defined as unscheduled or emergency hospitalizations and emergency room (ER) visits. Cohort studies and randomised controlled trials (RCTs) reporting hospitalizations for AECOPD as an outcome were included. Meta-analyses compared hospitalization rates between eligible pulmonary rehabilitation recipients and non-recipients, before and after rehabilitation.

Results

18 studies were included in the meta-analysis. Results from ten RCTs showed that the control groups had a higher overall rate of hospitalizations than the pulmonary rehabilitation groups (0.97 hospitalizations/patient-year, 95% Confidence Intervals (CIs) 0.67, 1.40; 0.62 hospitalizations/patient-year, 95% CI 0.33, 1.16 respectively). Five studies compared admission numbers in the 12 months before and after rehabilitation, finding a significantly higher admission rate before compared to after (1.24 hospitalizations/patient-year, 95% CIs 0.66, 2.34; 0.47 hospitalizations/patient-year, 95% CIs 0.28, 0.79 respectively). The pooled result of three cohort studies found the reference group had a lower admission rate compared to the pulmonary rehabilitation group (0.18 hospitalizations/patient-year, 95% CI 0.11, 0.32 for reference group versus 0.28 hospitalizations/patient-year, 95% CI 0.25, 0.32 for pulmonary rehabilitation).

Conclusions

Although results from RCTs suggested that pulmonary rehabilitation reduces subsequent admissions, pooled results from the cohort studies did not, likely reflecting the heterogeneous nature of individuals included in observational research and the varying standard of pulmonary rehabilitation programmes.

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The bimodal P300 oddball component is decreased in patients with an adjustment disorder: An event-related potentials study

Publication date: October 2016
Source:Clinical Neurophysiology, Volume 127, Issue 10
Author(s): Hendrik Kajosch, Bernd Gallhofer, Philippe Corten, Léon From, Paul Verbanck, Salvatore Campanella
ObjectiveWe found previously that use of a bimodal oddball design with synchronized pairs of audio-visual stimuli increased the sensitivity of the P300 wave to detect subclinical anxiety–depression in otherwise healthy subjects. Here, we wished to determine whether these P300 modulations would also be encountered when a clinical population comprised of patients with an adjustment disorder (AJD) was compared to healthy controls.MethodTwo groups, each comprised of twenty-five participants (AJD patients, and controls; N=50) had to detect deviant stimuli among frequent stimuli in an oddball task by clicking on a button. Separate blocks involving audio (A), visual (V) or bimodal congruent (AV) stimuli were used and compared.ResultsP300 amplitudes of the control group were higher than those displayed by AJD patients, but only in the bimodal AV oddball task, while unimodal (visual or auditory) oddball tasks did not reveal any significant differences.ConclusionsThe increased sensitivity of the bimodal P300 that we observed previously in subclinical anxiety–depression was also observed in AJD patients.SignificanceThe impaired "bimodal congruence effect" in AJD suggests that these patients have altered integrative processes, which has potential implications for cognitive therapy.



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Cultivation strategies for growth of uncultivated bacteria

Publication date: Available online 11 August 2016
Source:Journal of Oral Biosciences
Author(s): Sonia R. Vartoukian
BackgroundThe majority of environmental bacteria and around a third of oral bacteria remain uncultivated. Furthermore, several bacterial phyla have no cultivable members and are recognised only by detection of their DNA by molecular methods. Possible explanations for the resistance of certain bacteria to cultivation in purity in vitro include: unmet fastidious growth requirements; inhibition by environmental conditions or chemical factors produced by neighbouring bacteria in mixed cultures; or conversely, dependence on interactions with other bacteria in the natural environment, without which they cannot survive in isolation. Auxotrophic bacteria, with small genomes lacking in the necessary genetic material to encode for essential nutrients, frequently rely on close symbiotic relationships with other bacteria for survival, and may therefore be recalcitrant to cultivation in purity.HighlightSince in-vitro culture is essential for the comprehensive characterisation of bacteria, particularly with regard to virulence and antimicrobial resistance, the cultivation of uncultivated organisms has been a primary focus of several research laboratories. Many targeted and open-ended strategies have been devised and successfully used. Examples include: the targeted detection of specific bacteria in mixed plate cultures using colony hybridisation; growth in simulated natural environments or in co-culture with 'helper' strains; and modified media preparation techniques or development of customised media eg. supplementation of media with potential growth-stimulatory factors such as siderophores.ConclusionDespite significant advances in recent years in methodologies for the cultivation of previously uncultivated bacteria, a substantial proportion remain to be cultured and efforts to devise high-throughput strategies should be a high priority.



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Chemoprevention of basal cell carcinoma: reply from authors

Abstract

The review started from the question whether early detection of BCC in the general (asymptomatic) population could lead to any benefit in terms of outcome and cost. In other words, should early detection efforts for skin cancer (secondary prevention) also include BCC? Review of available literature suggests that early detection and adequate treatment of BCC of the face could increase cost-effectiveness.

Although these results could also pertain to patients who have had already a history of BCC, their setting is different since they may already be in a follow-up programme (tertiary prevention).

This article is protected by copyright. All rights reserved.

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Novel Bioceramic-Reinforced Hydrogel for Alveolar Bone Regeneration

Publication date: Available online 10 August 2016
Source:Acta Biomaterialia
Author(s): Giorgio Iviglia, Clara Cassinelli, Elisa Torre, Francesco Baino, Marco Morra, Chiara Vitale-Brovarone
The osseointegration of dental implants and their consequent long-term success is guaranteed by the presence, in the extraction site, of healthy and sufficient alveolar bone. Bone deficiencies may be the result of extraction traumas, periodontal disease and infection. In these cases, placement of titanium implants is contraindicated until a vertical bone augmentation is obtained. This goal is achieved using bone graft materials, which should simulate extracellular matrix (ECM), in order to promote osteoblast proliferation and fill the void, maintaining the space without collapsing until the new bone is formed. In this work, we design, develop and characterize a novel, moldable chitosan-pectin hydrogel reinforced by biphasic calcium phosphate particles with size in the range of 100-300 μm. The polysaccharide nature of the hydrogel mimics the ECM of natural bone, and the ceramic particles promote high osteoblast proliferation, assessed by Scanning Electron Microscopy analysis. Swelling properties allow significant adsorption of water solution (up to 200% of solution content) so that the bone defect space can be filled by the material in an in vivo scenario. The incorporation of ceramic particles makes the material stable at different pH and increases the compressive elastic modulus, toughness and ultimate tensile strength. Furthermore, cell studies with SAOS-2 human osteoblastic cell line show high cell proliferation and adhesion already after 72 h, and the presence of ceramic particles increases the expression of Alkaline Phosphatase activity after 1 week. These results suggest a great potential of the developed moldable biomaterials for the regeneration of the alveolar bone.Statement of SignificanceThe positive fate of a surgical procedure involving the insertion of a titanium screw still depends on the quality and quantity of alveolar bone which is present in the extraction site. Available materials are basically hard scaffold materials with un-predictable behavior in different condition and difficult shaping properties. In this work we developed a novel pectin-chitosan hydrogel reinforced with ceramic particles. Polysaccharides simulates the Extracellular Matrix of natural bone and the extensive in vitro cells culture study allow to assess that the incorporation of the ceramic particles promote a pro-osteogenic response. Shape control, easy adaption of the extraction site, predictable behavior in different environment condition, swelling properties and an anti-inflammatory response are the significant characteristics of the developed biomaterial.

Graphical abstract

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In vitro colonization of stratified bioactive scaffolds by pre-osteoblast cells

Publication date: Available online 10 August 2016
Source:Acta Biomaterialia
Author(s): N. Gómez-Cerezo, S. Sánchez-Salcedo, I. Izquierdo-Barba, D. Arcos, M. Vallet-Regí
Mesoporous bioactive glass-polycaprolactone (MBG-PCL) scaffolds have been prepared by robocasting, a layer by layer rapid prototyping method, by stacking of individual strati. Each stratus was independently analyzed during the cell culture tests with MC3T3-E1 preosteblast-like cells. The presence of MBG stimulates the colonization of the scaffolds by increasing the cell proliferation and differentiation. MBG-PCL composites not only enhanced pre-osteoblast functions but also allowed cell movement along its surface, reaching the upper stratus faster than in pure PCL scaffolds. The cells behavior on each individual stratus revealed that the scaffolds colonization depends on the chemical stimuli supplied by the MBG dissolution and surface changes associated to the apatite-like formation during the bioactive process. Finally, scanning electron and fluorescence microscopy revealed that the kinetic of cell migration strongly depends on the architectural features of the scaffolds, in such a way that layers interconnections are used as migration routes to reach the farther scaffolds locations from the initial cells source.Statement of SignificanceThis manuscript provides new insights on cell behavior in bioceramic/polymer macroporous scaffolds prepared by rapid prototyping methods. The experiments proposed in this work have allowed the evaluation of cell behavior within the different levels of the scaffolds, i.e. from the initials source of cells towards the farther scaffold locations. We could demonstrate that the in vitro cell colonization is encouraged by the presence of a highly bioactive mesoporous glass (MBG). This bioceramic enhances the cell migration towards upper strati through the dissolution of chemical signals and the changes occurred on the scaffolds surface during the bioactive process. In addition the MBG promotes preosteblastic proliferation and differentiation respect to scaffolds made of pure polycaprolactone. Finally, this study reveals the significance of the architectural design to accelerate the cell colonization. These experiments put light on the factors that should be taken into account to accelerate the regeneration processes under in vivo conditions

Graphical abstract

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Novel bioactive materials developed by SBF evaluation: Surface-modified Ti metal and its alloys

Publication date: Available online 10 August 2016
Source:Acta Biomaterialia
Author(s): Tadashi Kokubo, Seiji Yamaguchi
Until the discovery of the bone-bonding activity of Bioglass by Hench et al. in the early 1970s, it had not been demonstrated that a synthetic material could bond to living bone without eliciting a foreign body reaction. Since then, various kinds of materials based on calcium phosphate, such as sintered hydroxyapatite and β -tricalcium phosphate have also been shown to bond to living bone. Until the discovery of the bone-bonding activity of Ti metal formed with a sodium titanate surface layer by the present authors in 1996, it had not been shown that a metallic material could bond to living bone. Since then, various kinds of surface-modified Ti metal and its alloys have been found to bond to living bone. Until the discovery of the osteoinduction of porous hydroxyapatite by Yamasaki in 1990, it was unknown whether a synthetic material could induce bone formation even in muscle tissue. Since then, various kinds of porous calcium phosphate ceramics have been shown to induce osteoinduction. Until the discovery of osteoinduction induced by a porous Ti metal formed with a titanium oxide surface layer by Fujibayashi et al. in 2004, it had been unclear whether porous metals would be able to induce osteoinduction.These novel bioactive materials have been developed by systematic research into the apatite formation that occurs on surface-modified Ti metal and its related materials in an acellular simulated body fluid (SBF) having ion concentrations almost equal to those of human blood plasma.Some of the novel bioactive materials based on Ti metal are already in clinical use or clinical trials, such as artificial hip joints and spinal fusion devices.In the present paper, we review how these novel bioactive materials based on Ti metal have been developed based on an evaluation of apatite formation in SBF. Without the SBF evaluation, these novel bioactive materials would most likely never have been developed.Statement of significanceOn the basis of systematic study of apatite formation on a material in a simulated body fluid, various kinds of novel bioactive materials possessing not only bone-bonding activity and but also various other functions such as bone growth promotion, antibacterial activity and osteoinduction have been developed. Some of them are already successfully applied to clinical applications or trials for artificial hip joints and spinal fusion devices. It is shown in the present paper how these novel bioactive materials have been developed.

Graphical abstract

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Microneedle-based Minimally-Invasive Measurement of Puncture Resistance and Fracture Toughness of Sclera

Publication date: Available online 10 August 2016
Source:Acta Biomaterialia
Author(s): Seung Hyun Park, Kang Ju Lee, JiYong Lee, Jae Hyoung Yoon, Dong Hyun Jo, Jeong Hun Kim, Keonwook Kang, WonHyoung Ryu
The sclera provides the structural support of the eye and protects the intraocular contents. Since it covers a large portion of the eye surface and has relatively high permeability for most drugs, the sclera has been used as a major pathway for drug administration. Recently, microneedle (MN) technology has shown the possibility of highly local and minimally-invasive drug delivery to the eye by MN insertion through the sclera or the suprachoroidal space. Although ocular MN needs to be inserted through the sclera, there has been no systematic study to understand the mechanical properties of the sclera, which are important to design ocular MNs. In this study, we investigated a MN-based method to measure the puncture resistance and fracture toughness of the sclera. To reflect the conditions of MN insertion into the sclera, force-displacement curves obtained from MN-insertion tests were used to estimate the puncture resistance and fracture toughness of sclera tissue. To understand the effect of the insertion conditions, dependency of the mechanical properties on insertion speeds, pre-strain of the sclera, and MN sizes was analyzed and discussed.Statement of SignificanceMeasurement of mechanical property of soft biological tissue is challenging due to variations between tissue samples or lack of well-defined measurement techniques. Although non-invasive measurement techniques such as nano/micro indentation were employed to locally measure the elastic modulus of soft biological materials, mechanical properties such as puncture resistance or fracture toughness, which requires "invasive" measurement and is important for the application of "microneedles or hypodermic needles", has not been well studied. In this work, we report minimally-invasive measurement of puncture resistance and fracture toughness of sclera using a double MN insertion method. Parametric studies showed that use of MN proved to be advantageous because of minimally-invasive insertion into tissue as well as higher sensitivity to sub-tissue architecture during the measurement.

Graphical abstract

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Outcomes After Endoscopic Airway Surgery for Laryngotracheal Stenosis

This case series describes changes in acoustic and aerodynamic measures and in voice- and dyspnea-related quality of life in adults with laryngotracheal stenosis after endoscopic airway surgery.

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Endoluminal Spray Cryotherapy for Benign Tracheal Stenosis

This case series describes outcomes of spray cryotherapy for patients with benign tracheal stenosis due to granulomatosis with polyangiitis, prior tracheotomy, and idiopathic stricture.

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Timing of Care With vs Without CT Evaluation of Peritonsillar Abscess

This cohort study describes differences in timing of care in children with peritonsillar abscess evaluated with vs without computed tomographic imaging..

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S-Nitrosylation of Endogenous Protein Tyrosine Phosphatases in Endothelial Insulin Signaling

Publication date: Available online 10 August 2016
Source:Free Radical Biology and Medicine
Author(s): Ming-Fo Hsu, Kuan-Ting Pan, Fan-Yu Chang, Kay-Hooi Khoo, Henning Urlaub, Ching-Feng Cheng, Geen-Dong Chang, Fawaz G. Haj, Tzu-Ching meng
Nitric oxide (NO) exerts its biological function through S-nitrosylation of cellular proteins. Due to the labile nature of this modification under physiological condition, identification of S-nitrosylated residue in enzymes involved in signaling regulation remains technically challenging. The present study investigated whether intrinsic NO produced in endothelium-derived MS-1 cells response to insulin stimulation might target endogenous protein tyrosine phosphatases (PTPs). For this, we have developed an approach using a synthetic reagent that introduces a phenylacetamidyl moiety on S-nitrosylated Cys, followed by detection with anti-phenylacetamidyl Cys (PAC) antibody. Coupling with sequential blocking of free thiols with multiple iodoacetyl-based Cys-reactive chemicals, we employed this PAC-switch method to show that endogenous SHP-2 and PTP1B were S-nitrosylated in MS-1 cells exposed to insulin. The mass spectrometry detected a phenylacetamidyl moiety specifically present on the active-site Cys463 of SHP-2. Focusing on the regulatory role of PTP1B, we showed S-nitrosylation to be the principal Cys reversible redox modification in endothelial insulin signaling. The PAC-switch method in an imaging format illustrated that a pool of S-nitrosylated PTP1B was colocalized with activated insulin receptor to the cell periphery, and that such event was endothelial NO synthase (eNOS)-dependent. Moreover, ectopic expression of the C215S mutant of PTP1B that mimics the active-site Cys215 S-nitrosylated form restored insulin responsiveness in eNOS-ablated cells, which was otherwise insensitive to insulin stimulation. This work not only introduces a new method that explores the role of physiological NO in regulating signal transduction, but also highlights a positive NO effect on promoting insulin responsiveness through S-nitrosylation of PTP1B's active-site Cys215.

Graphical abstract

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Benchmarking of protein carbonylation analysis in Caenorhabditis elegans: specific considerations and general advice

Publication date: Available online 10 August 2016
Source:Free Radical Biology and Medicine
Author(s): S. Pyr dit Ruys, J.-M. Bonzom, S. Frelon
Oxidative stress has been extensively studied due to its correlation with cellular disorders and aging. In proteins, one biomarker of oxidative stress is the presence of carbonyl groups, such as aldehyde and ketone, in specific amino acid side chains such as lysine, proline, arginine and threonine, so-called protein carbonylation (PC). PC study is now a growing field in general and medical science since PC accumulation is associated with various pathologies and disorders.At present, enzyme-linked immunosorbent assays (ELISA) seem to be the most robust method of quantifying the presence of carbonyl groups in proteins, despite having some recognised caveats. In parallel, gel-based approaches present cross-comparison difficulties, along with other technical problems. As generic PC analyses still suffer from poor homogeneity, leading to cross-data analysis difficulties and poor results overlap, the need for harmonisation in the field of carbonyl detection is now widely accepted. This study aims to highlight some of the technical challenges in proteomic gel-based multiplexing experiments when dealing with PC in difficult samples like those from Caenorhabditis elegans, from protein extraction to carbonyl detection.We demonstrate that some critical technical parameters, such as labelling time, probe concentration, and total and carbonylated protein recovery rates, should be re-addressed in a sample-specific way. We also defined a procedure to cost-effectively adapt CyDye™-hydrazide-based protocols to specific samples, especially when the experimental interest is focused on studying differences between stimulating conditions with a maximised signal-to-noise ratio. Moreover, we have improved an already-existing powerful solubilisation buffer, making it potentially useful for hard-to-solubilise protein pellets. Lastly, the depicted methodology exemplifies a simple way of normalising carbonyl-related signal to total protein in SDS-PAGE multiplexing experiments. Within that scope, we also proposed a simple way to quantify carbonyl groups by on-gel spotting diluted dye-containing labelling buffer. Proof of the robustness of the procedure was also highlighted by the high linear correlation between the level of carbonyls and the ultraviolet exposure duration of whole worms (R²= 0.993).Altogether, these results will help to standardise existing protocols in the growing field of proteomic carbonylation studies.

Graphical abstract

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Nrf2 promotes reparative angiogenesis through regulation of NADPH oxidase-2 in oxygen-induced retinopathy

Publication date: Available online 10 August 2016
Source:Free Radical Biology and Medicine
Author(s): Yanhong Wei, Junsong Gong, Zhenhua Xu, Elia J. Duh
Revascularization of ischemic tissue is a highly desirable outcome in multiple diseases, including cardiovascular diseases and ischemic retinopathies. Oxidative stress and inflammation are both known to play a role in suppressing reparative angiogenesis in ischemic disease models including oxygen-induced retinopathy (OIR), but the regulatory molecules governing these pathophysiologic processes in retinal ischemia are largely unknown. Nrf2 is a major stress-response transcription factor that has been implicated in regulating ischemic angiogenesis in the retina and other tissue beds. Using Nrf2-deficient mice, we investigated the effects of Nrf2 in regulating revascularization and modulating the retinal tissue milieu during ischemia. Strikingly, Nrf2's beneficial effect on reparative angiogenesis only became manifested in the later phase of ischemia in OIR, from postnatal day 14 (P14) to P17. This was temporally associated with a reduction in both oxidative stress and inflammatory mediators in wild-type compared to Nrf2^-/- mice. Nrf2^-/- retinas exhibited an increase in VEGF but also induction of anti-angiogenic Dll4-Notch signaling. NADPH oxidase (NOX), and especially NOX2, is a major pathogenic molecule and a particularly important contributor to oxidative stress in multiple retinal disease processes. Nrf2^-/- mice exhibited a significant exacerbation of NOX2 induction in OIR that manifested in the later phases of ischemia. Pharmacologic inhibition of NADPH oxidase abrogated the adverse effect of Nrf2 deficiency on reparative angiogenesis. Taken together, this suggests that Nrf2 is an important regulator of the retinal milieu during tissue ischemia, and that the Nrf2/NOX2 balance may play a critical role in determining the fate of ischemic revascularization.

Graphical abstract

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Short Pulsed Electric Fields for Prevention of Burn Scars

Appearance of treated and untreated wound healing 6 months after burn injury. Images from representative rats from all treatment groups are shown (n=3 animals per experimental condition). Yellow lines indicate the measured surface area of burn scars.

Although the proliferation of collagen-producing cells following burn injury is the body's natural response to trauma, the excessive collagen production leads to the formation of permanent, painful scars.  Burn scars secondary to collagen cell proliferation cause intense and ongoing physical and psychological suffering to burn patients who survive the initial destruction of skin and tissue.  A recent publication in the Journal of Investigative Dermatology by a team of researchers at Tel Aviv and Harvard Universities details a novel non-invasive technology that mitigates the proliferation of the collagen-producing cells that contribute to scarring. Using short, pulsed electric fields, the researchers showed that debilitating burn scars, which develop due to the overproduction of collagen, can be prevented.

The technique, termed partial irreversible electroporation (pIRE), utilizes non-thermal, high-voltage, microsecond-pulsed electric fields to cause partial destruction to collagen-producing cells in the wound bed.  The technique was tested in a pre-clinical model of burn injury by providing five therapeutic sessions over a period of six months.  The scars were then imaged, with treated scars demonstrating a 58% decrease in scar area versus untreated scars.

The results are exciting given that current methods for alleviating the lifelong suffering associated with hypertrophic burn scars, such as silicone sheets, surgical excision, compression dressings, electron-beam irradiation, and laser therapy, provide only moderate improvements.

Manuscript: Preventing Scars after Injury with Partial Irreversible Electroporation

This post Short Pulsed Electric Fields for Prevention of Burn Scars appeared first on Medgadget.

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GFP chromophore derivative suppresses ultraviolet A-induced JNK-signaling and apoptosis in keratinocytes, and adverse effects in zebrafish embryos

Abstract

Solar ultraviolet (UV) light has been recognized as the important environmental hazard and contributes to diverse skin damage such as cell death, photoaging and even carcinogenesis. Revelation of harmful responses attributed to UVA radiation has promoted the development of photoprotective agents against UVA-induced skin damage. In the present study, we tried to evaluate the potential protective effects of a synthetic green fluorescent protein (GFP) chromophore derivative, 4-chlorobenzyldene-1, 2-dimethylimidazolinone (Cl-BDI, called TC-22) on UVA- and UVB- induced stress responses in skin. The HaCaT keratinocytes were used to evaluate the cellular effects. Zebrafish (Danio rerio), which is regarded as a useful and cost-effective alternative to some mammalian models, was applied as the in vivo animal model. In HaCaT keratinocytes, TC-22 was able to obviously decrease UVA-induced cell death. Dissection of the UVA-induced signaling pathways revealed that TC-22 could suppress activation of JNK and caspase 3, but not of ERK and p38. Reduction of UVA-induced cleavage of caspase 3 and sub-G1 phase accumulation by pretreatment of TC-22 was also observed. In zebrafish, we showed that UVA irradiation could decrease the survival and hatching rate, suppress heart beats of embryos, and enhance the pigmentation of larvae. Pretreatment of TC-22 could significantly reverse UVA-induced suppression in hatching of eggs and heart beating of embryos, and also lowered the UVA-induced pigmentation in zebrafish. Collectively, we demonstrate that TC-22, a GFP chromophore derivative, can ameliorate the UVA-induced stress responses in both epidermal keratinocytes and zebrafish, suggesting the potential use of TC-22 in photoprotection in the future.

This article is protected by copyright. All rights reserved.

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Is early inflammation good or bad? Linking early immune changes to hypertrophic scarring

Abstract

The mechanisms regulating hypertrophic scar (HTS) formation are multifactorial and complex. Early inflammation following dermal injury is believed to be a critical and essential event in the progression of normal wound healing and repair. It is generally accepted that acute inflammatory responses are necessary for normal wound repair, while chronic or excessive inflammation may lead to pathological scarring and fibrosis. A new study published in Experimental Dermatology revisited this topic and demonstrated that reduced and/or delayed early immunological responses were actually associated with HTS formation (1).

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The role of RNase 7 in innate cutaneous defense against Pseudomonas aeruginosa

Abstract

The ribonuclease RNase 7 is a major skin-derived human antimicrobial protein expressed in keratinocytes. Here we show that the gram-negative pathogen Pseudomonas aeruginosa secretes factor(s) that induced RNase 7 gene and protein expression in human primary keratinocytes. The metalloprotease inhibitor marimastat, the epidermal growth factor receptor (EGFR) inhibitor AG1478 and the EGFR blocking antibody cetuximab significantly attenuated this induction indicating an important role of the EGFR for the P. aeruginosa-mediated RNase 7 induction. In line with this, siRNA-mediated downregulation of ADAM17, a metalloprotease known to proteolytically mediate the release of soluble EGFR ligands, decreased the P. aeruginosa-mediated RNase 7 induction in keratinocytes. The impact of the EGFR was also demonstrated in a human 3D skin equivalent where blockade of the EGFR diminished induction of RNase 7 by P. aeruginosa. Blockade of toll-like receptor 5 (TLR5), a pattern recognition receptor (PRR) known to be activated by P. aeruginosa, only moderately reduced the P. aeruginosa-mediated RNase 7 induction in keratinocytes. The functional relevance of RNase 7 to participate in cutaneous defense against P. aeruginosa was demonstrated by antibodies that neutralized the antimicrobial activity of RNase 7. These antibodies significantly inhibited the capacity of human stratum corneum skin extracts to control growth of P. aeruginosa. Taken together, our results indicate that P. aeruginosa induces the expression of RNase 7 in keratinocytes in an EGFR-dependent manner. Enhanced release of RNase 7 contributes to control cutaneous growth of P. aeruginosa.

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Tissue fibrosis: a pathomechanistically unresolved challenge and scary clinical problem

Abstract

Fibrosis is defined as the replacement of healthy tissue by an excessive deposition of extracellular matrix, leading gradually to the disturbance and finally to loss of the original tissue architecture and function. Scarring and tissue fibrosis represent major unresolved medical problems resulting in increased morbidity and mortality (1). The initial tissue damage can result from multiple acute or chronic stimuli, including autoimmune reactions, infections, or mechanical injury (s1). Detailed mechanisms how tissue injury leads to tissue fibrosis and how fibrosis can be therapeutically perturbed or reversed are still poorly understood (s2; s3). A thorough investigation of the underlying molecular and cellular components is required to improve therapeutic options for the often devastating pro-fibrotic health conditions.

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MicroRNA Let-7b inhibits keratinocyte migration in cutaneous wound healing by targeting IGF2BP2

Abstract

Wound healing is a complex process involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family let-7b, have been expressed in mammalian skin but its exact role in keratinocyte migration is still not in knowledge. Here we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2BP2. Overexpression of let-7b led to reduced HaCaT cell migration while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. By using bioinformatics prediction software and a reporter gene assay, we found that IGF2BP2 was a target of let-7b, which contributes to keratinocyte migration. Introduction of an expression vector of IGF2BP2 also rescued let-7b-induced migration deficiency, confirms that IGF2BP2 is an important target for let-7b regulation. Our findings suggest that let-7b significantly delayed the re-epithelialization possibly due to reduction of keratinocyte migration and restraints IGF2BP2 during skin wound healing.

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In vivo enzymatic modulation of IgG antibodies prevents immune complex-dependent skin injury

Abstract

IgG antibodies are potent inducers of proinflammatory responses by cross-linking Fc receptors on innate immune effector cells resulting in tissue injury. The recently discovered enzymes endoglycosidase S (EndoS) and IgG-degrading enzyme (IdeS) of Streptococcus pyogenes are able to modulate the interaction between IgG antibodies and the Fc receptors, by hydrolysis of the glycan associated with the heavy chain of the IgG molecule (EndoS), or cleavage in the hinge region of the heavy IgG chain (IdeS). In this work, we investigated their ability to inhibit damage mediated by skin-bound antibodies in vivo in two different experimental models, the Arthus reaction, and epidermolysis bullosa acquisita, an autoimmune blistering skin disease associated with autoantibodies against type VII collagen. We demonstrate that both enzymes efficiently interfere with IgG-mediated proinflammatory processes, offering a great asset to specifically target pathological IgG antibodies in the skin and holding great promise for future applications in human therapy.

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Microbial elements as the initial triggers in the pathogenesis of polymorphic light eruption?

Abstract

As early as 1942, Epstein suggested a photoallergic concept for photodermatoses [s1]. Since then much progress has been made in understanding the pathophysiology of photodermatoses and their most common form, polymorphic light eruption (PLE) (1) (s2-s13). However, specific photoantigens that initiate PLE have not yet been identified. We hypothesize that PLE may be initiated by elements resulting from UV-induced damage to microbial communities of the skin, leading to a cascade of events eventually resulting in the skin rash of the disease.

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Composition of elastin like polypeptide–collagen composite scaffold influences in vitro osteogenic activity of human adipose derived stem cells

Publication date: Available online 11 August 2016
Source:Dental Materials
Author(s): Bhuvaneswari Gurumurthy, Patrick C. Bierdeman, Amol V. Janorkar
ObjectiveCollagen-based scaffolds for guided bone regeneration (GBR) are continuously improved to overcome the mechanical weaknesses of collagen. We have previously demonstrated superior mechanical characteristics of the elastin-like polypeptide (ELP) reinforced collagen composites. The objectives of this research were to evaluate the efficacy of ELP-collagen composites to culture human adipose-derived stem cells (hASCs) and allow them to undergo osteogenic differentiation. We hypothesized that hASCs would show a superior osteogenic differentiation in stiffer ELP-collagen composites compared to the neat collagen hydrogels.MethodsComposite specimens were made by varying ELP (0–18mg/mL) and collagen (2–6mg/mL) in a 3:1 ratio. Tensile strength, elastic modulus, and toughness were determined by uniaxial tensile testing. hASCs cultured within the composites were characterized by biochemical assays to measure cell viability, protein content, and osteogenic differentiation (alkaline phosphatase activity, osteocalcin, and Alizarin red staining). Scanning electron microscopy and energy dispersive spectroscopy were used for morphological characterization of composites.ResultsAll composites were suitable for hASCs culture with viable cells over the 22-day culture period. The ELP-collagen composite with 18mg/mL of ELP and 6mg/mL of collagen had greater tensile strength and elastic modulus combined with higher osteogenic activity in terms of differentiation and subsequent mineralization over a period of 3 weeks compared to other compositions. The extra-cellular matrix deposits composed of calcium and phosphorous were specifically seen in the 18:6mg/mL ELP-collagen composite.SignificanceThe success of the 18:6mg/mL ELP-collagen composite to achieve long-term, 3-dimensional culture and osteogenic differentiation indicates its potential as a GBR scaffold.



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