Head and Neck Diseases by Alexandros G.Sfakianakis: 09/07/17

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare inflammatory condition describing the combination of skin, bone, and joint manifestations that has a heterogeneous presentation. We report a case of severe SAPHO syndrome in association with hidradenitis suppurativa and pyoderma gangrenosum in a 27-year-old male. The patient had an initial migratory arthritis affecting the knees, ankles, metacarpophalangeal joints, proximal interphalangeal joints, wrists, shoulder, and lower back, which progressed to a persistent arthritis and swelling at the sternum, shoulders, wrists, hands, feet, and lower back. Radiographic changes were consistent with the diagnosis of SAPHO syndrome. Serum proinflammatory cytokine levels were significantly elevated and improved substantially after 3 months of therapy. Rationale for therapy in this patient was the observation that tumor necrosis alpha antagonists have been successfully used in SAPHO syndrome, and since arthropathy was so prominent in our patient, we elected to use adalimumab combined with methotrexate.

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Teriflunomide-induced psoriasiform changes of fingernails: a new example of paradoxical side effect?

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Evaluation of the relation between lipid coat, transepidermal water loss, and skin pH

Abstract

Objective

The epidermis is an epidermal barrier which accumulates lipid substances and participates in skin moisturizing. An evaluation of the epidermal barrier efficiency can be made, among others, by the measurement of the following values: the lipid coat, the transepidermal water loss (TEWL) index, and pH.

Materials

The study involved 50 Caucasian, healthy women aged 19–35 years (mean 20.56).

Methods

Measurements were made using Courage & Khazaka Multi Probe Adapter MPA 580: Tewameter TM 300, pH-Meter PH 905, Sebumeter SM 815. The areas of measurements included forehead, nose, left cheek, right cheek, chin, and thigh.

Results

In the T-zone, the lipid coat was in the range between 0 and 270 μg/cm² (mean 128 μg/cm²), TEWL between 1 and 55 g/m²/h (mean 11.1 g/m²/h), and pH 4.0–5.6 (mean 5.39). Lower values of the lipid coat up to 100 μg/cm² were accompanied by TEWL greater than 30 g/m²/h and less acidic pH of 5.6–9.0. In the U-zone the range of lipid coat was up to 200 μg/cm² (mean 65.2 μg/cm²), the skin pH remained 4.0–5.6 (mean 5.47), and TEWL was in the range between 1 and 20 g/m²/h (mean 8.7 g/m²/h). Lower values of the lipid coat up to 100 μg/cm² were accompanied by TEWL between 1 and 20 g/m²/h and less acidic pH of 5.6–9.0. High values of the lipid coat between 180 and 200 μg/cm² were connected with TEWL of 1–15 g/m²/h. On the skin of the thigh, we observed a very thin lipid coat – 35 μg/cm² (mean 5.6 μg/cm²), pH (mean 5.37), and TEWL (mean 8.5 g/m²/h) were considered by us to be within regular limits.

Conclusions

In the T-zone, a thinner lipid coat resulted in relatively high TEWL and pH levels changing toward alkaline. In the U-zone, thinner lipid coat was accompanied by lower TEWL and pH changing toward alkaline. We also observed that lower values of lipid coat up to 100 μg/cm² were associated with higher pH values ranging toward the basic character pH 5.6–9.0).

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Large-Scale Quantitative Proteomics Identifies the Ubiquitin Ligase Nedd4-1 as an Essential Regulator of Liver Regeneration

Publication date: Available online 7 September 2017
Source:Developmental Cell
Author(s): Marc Bachofner, Tobias Speicher, Roman L. Bogorad, Sukalp Muzumdar, Carina P. Derrer, Fabrizio Hürlimann, Friederike Böhm, Paolo Nanni, Tobias Kockmann, Ekaterina Kachaylo, Michael Meyer, Susagna Padrissa-Altés, Rolf Graf, Daniel G. Anderson, Victor Koteliansky, Ulrich auf dem Keller, Sabine Werner
The liver is the only organ in mammals that fully regenerates even after major injury. To identify orchestrators of this regenerative response, we performed quantitative large-scale proteomics analysis of cytoplasmic and nuclear fractions from normal versus regenerating mouse liver. Proteins of the ubiquitin-proteasome pathway were rapidly upregulated after two-third hepatectomy, with the ubiquitin ligase Nedd4-1 being a top hit. In vivo knockdown of Nedd4-1 in hepatocytes through nanoparticle-mediated delivery of small interfering RNA caused severe liver damage and inhibition of cell proliferation after hepatectomy, resulting in liver failure. Mechanistically, we demonstrate that Nedd4-1 is required for efficient internalization of major growth factor receptors involved in liver regeneration and their downstream mitogenic signaling. These results highlight the power of large-scale proteomics to identify key players in liver regeneration and the importance of posttranslational regulation of growth factor signaling in this process. Finally, they identify an essential function of Nedd4-1 in tissue repair.

Teaser

Using large-scale quantitative proteomics, Bachofner, Speicher et al. identified the ubiquitin ligase Nedd4-1 as an essential regulator of liver regeneration. Nedd4-1 deficiency attenuated growth factor receptor internalization and signaling, demonstrating a crucial role of posttranslational modification of growth factor signaling in liver regeneration.

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Alternative Progenitor Cells Compensate to Rebuild the Coronary Vasculature in Elabela- and Apj-Deficient Hearts

Publication date: Available online 7 September 2017
Source:Developmental Cell
Author(s): Bikram Sharma, Lena Ho, Gretchen Hazel Ford, Heidi I. Chen, Andrew B. Goldstone, Y. Joseph Woo, Thomas Quertermous, Bruno Reversade, Kristy Red-Horse
Organogenesis during embryonic development occurs through the differentiation of progenitor cells. This process is extraordinarily accurate, but the mechanisms ensuring high fidelity are poorly understood. Coronary vessels of the mouse heart derive from at least two progenitor pools, the sinus venosus and endocardium. We find that the ELABELA (ELA)-APJ signaling axis is only required for sinus venosus-derived progenitors. Because they do not depend on ELA-APJ, endocardial progenitors are able to expand and compensate for faulty sinus venosus development in Apj mutants, leading to normal adult heart function. An upregulation of endocardial SOX17 accompanied compensation in Apj mutants, which was also seen in Ccbe1 knockouts, indicating that the endocardium is activated in multiple cases where sinus venosus angiogenesis is stunted. Our data demonstrate that by diversifying their responsivity to growth cues, distinct coronary progenitor pools are able to compensate for each other during coronary development, thereby providing robustness to organ development.

Graphical abstract

Teaser

Coronary blood vessels of the heart are formed from two progenitor sources: the sinus venosus (SV) and the endocardium. Sharma et al. show that ELA-APJ is only required for growth from the SV and that endocardial-derived CVs can compensate for loss of SV-derived vessels to restore heart function, ensuring developmental robustness.

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FPGA implementation of real-time SENSE reconstruction using pre-scan and Emaps sensitivities

Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Muhammad Faisal Siddiqui, Ahmed Wasif Reza, Abubakr Shafique, Hammad Omer, Jeevan Kanesan
Sensitivity Encoding (SENSE) is a widely used technique in Parallel Magnetic Resonance Imaging (MRI) to reduce scan time. Reconfigurable hardware based architecture for SENSE can potentially provide image reconstruction with much less computation time. Application specific hardware platform for SENSE may dramatically increase the power efficiency of the system and can decrease the execution time to obtain MR images. A new implementation of SENSE on Field Programmable Gate Array (FPGA) is presented in this study, which provides real-time SENSE reconstruction right on the receiver coil data acquisition system with no need to transfer the raw data to the MRI server, thereby minimizing the transmission noise and memory usage. The proposed SENSE architecture can reconstruct MR images using receiver coil sensitivity maps obtained using pre-scan and eigenvector (E-maps) methods. The results show that the proposed system consumes remarkably less computation time for SENSE reconstruction, i.e., 0.164ms @ 200MHz, while maintaining the quality of the reconstructed images with good mean SNR (29+ dB), less RMSE (<5×10⁻²) and comparable artefact power (<9×10⁻⁴) to conventional SENSE reconstruction. A comparison of the center line profiles of the reconstructed and reference images also indicates a good quality of the reconstructed images. Furthermore, the results indicate that the proposed architectural design can prove to be a significant tool for SENSE reconstruction in modern MRI scanners and its low power consumption feature can be remarkable for portable MRI scanners.

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Static and dynamic liver stiffness: An ex vivo porcine liver study using MR elastography

Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Chun Yang, Meng Yin, Kevin J. Glaser, Xiangyang Zhu, Kai Xu, Richard L. Ehman, Jun Chen
Magnetic resonance elastography (MRE) is an MRI-based noninvasive technique for quantitatively assessing tissue stiffness. The hypothesis of this study is that stiffness increases with portal pressure. We further hypothesized that the rate of stiffness change with pressure would be larger in liver tissue treated to simulate the stiffening effects of fibrosis. In agreement with our hypothesis, the formalin-treated livers were stiffer than the untreated livers, and in both groups the liver stiffness increased with portal venous pressure. The rate of stiffness change with portal pressure was significantly greater after formalin treatment. In this study, we have developed an ex vivo liver model incorporating portal venous pressure variations and observed significant changes in liver stiffness due to portal pressure. This model could be useful for understanding and investigating the changes in the static and dynamic components of liver stiffness.

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MRI protocol optimization for quantitative DCE-MRI of the spine

Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Cristina Lavini, Gem Kramer, Indra Pieters-den Bos, Otto Hoekstra, J. Tim Marcus
PurposeIn this study we systematically investigated different Dynamic Contrast Enhancement (DCE)-MRI protocols in the spine, with the goal of finding an optimal protocol that provides data suitable for quantitative pharmacokinetic modelling (PKM).Materials and methodsIn 13 patients referred for MRI of the spine, DCE-MRI of the spine was performed with 2D and 3D MRI protocols on a 3T Philips Ingenuity MR system. A standard bolus of contrast agent (Dotarem - 0.2ml/kg body weight) was injected intravenously at a speed of 3ml/s. Different techniques for acceleration and motion compensation were tested: parallel imaging, partial-Fourier imaging and flow compensation. The quality of the DCE MRI images was scored on the basis of SNR, motion artefacts due to flow and respiration, signal enhancement, quality of the T1 map and of the arterial input function, and quality of pharmacokinetic model fitting to the extended Tofts model.ResultsSagittal 3D sequences are to be preferred for PKM of the spine. Acceleration techniques were unsuccessful due to increased flow or motion artefacts. Motion compensating gradients failed to improve the DCE scans due to the longer echo time and the T2* decay which becomes more dominant and leads to signal loss, especially in the aorta. The quality scoring revealed that the best method was a conventional 3D gradient–echo acquisition without any acceleration or motion compensation technique. The priority in the choice of sequence parameters should be given to reducing echo time and keeping the dynamic temporal resolution below 5s. Increasing the number of acquisition, when possible, helps towards reducing flow artefacts. In our setting we achieved this with a sagittal 3D slab with 5 slices with a thickness of 4.5mm and two acquisitions.ConclusionThe proposed DCE protocol, encompassing the spine and the descending aorta, produces a realistic arterial input function and dynamic data suitable for PKM.

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The development and optimisation of 3D black-blood R2* mapping of the carotid artery wall

Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Jianmin Yuan, Martin J. Graves, Andrew J. Patterson, Andrew N. Priest, Pascal P.R. Ruetten, Ammara Usman, Jonathan H. Gillard
PurposeTo develop and optimise a 3D black-blood R2* mapping sequence for imaging the carotid artery wall, using optimal blood suppression and k-space view ordering.MethodsTwo different blood suppression preparation methods were used; Delay Alternating with Nutation for Tailored Excitation (DANTE) and improved Motion Sensitive Driven Equilibrium (iMSDE) were each combined with a three-dimensional (3D) multi-echo Fast Spoiled GRadient echo (ME-FSPGR) readout. Three different k-space view-order designs: Radial Fan-beam Encoding Ordering (RFEO), Distance-Determined Encoding Ordering (DDEO) and Centric Phase Encoding Order (CPEO) were investigated. The sequences were evaluated through Bloch simulation and in a cohort of twenty volunteers. The vessel wall Signal-to-Noise Ratio (SNR), Contrast-to-Noise Ratio (CNR) and R2*, and the sternocleidomastoid muscle R2* were measured and compared. Different numbers of acquisitions-per-shot (APS) were evaluated to further optimise the effectiveness of blood suppression.ResultsAll sequences resulted in comparable R2* measurements to a conventional, i.e. non-blood suppressed sequence in the sternocleidomastoid muscle of the volunteers. Both Bloch simulations and volunteer data showed that DANTE has a higher signal intensity and results in a higher image SNR than iMSDE. Blood suppression efficiency was not significantly different when using different k-space view orders. Smaller APS achieved better blood suppression.ConclusionThe use of blood-suppression preparation methods does not affect the measurement of R2*. DANTE prepared ME-FSPGR sequence with a small number of acquisitions-per-shot can provide high quality black-blood R2* measurements of the carotid vessel wall.

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COnstrained Data Extrapolation (CODE): A new approach for high definition vascular imaging from low resolution data

Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Yang Song, Ehsan Hamtaei, Sean K. Sethi, Guang Yang, Haibin Xie, E. Mark Haacke
PurposeTo introduce a new approach to reconstruct high definition vascular images using COnstrained Data Extrapolation (CODE) and evaluate its capability in estimating vessel area and stenosis.Materials and methodsCODE is based on the constraint that the full width half maximum of a vessel can be accurately estimated and, since it represents the best estimate for the width of the object, higher k-space data can be generated from this information. To demonstrate the potential of extracting high definition vessel edges using low resolution data, both simulated and human data were analyzed to better visualize the vessels and to quantify both area and stenosis measurements. The results from CODE using one-fourth of the fully sampled k-space data were compared with a compressed sensing (CS) reconstruction approach using the same total amount of data but spread out between the center of k-space and the outer portions of the original k-space to accelerate data acquisition by a factor of four.ResultsFor a sufficiently high signal-to-noise ratio (SNR) such as 16 (8), we found that objects as small as 3 voxels in the 25% under-sampled data (6 voxels when zero-filled) could be used for CODE and CS and provide an estimate of area with an error <5% (10%). For estimating up to a 70% stenosis with an SNR of 4, CODE was found to be more robust to noise than CS having a smaller variance albeit a larger bias. Reconstruction times were >200 (30) times faster for CODE compared to CS in the simulated (human) data.ConclusionCODE was capable of producing sharp sub-voxel edges and accurately estimating stenosis to within 5% for clinically relevant studies of vessels with a width of at least 3pixels in the low resolution images.

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Reduced distortion artifact whole brain CBF mapping using blip-reversed non-segmented 3D echo planar imaging with pseudo-continuous arterial spin labeling

Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Neville D. Gai, Yi Yu Chou, Dzung Pham, John A. Butman
PurposeTo implement and evaluate interleaved blip-up, blip-down, non-segmented 3D echo planar imaging (EPI) with pseudo-continuous arterial spin labeling (pCASL) and post-processing for reduced susceptibility artifact cerebral blood flow (CBF) maps.Materials and methods3D EPI non-segmented acquisition with a pCASL labeling sequence was modified to include alternating k-space coverage along phase encoding direction (referred to as "blip-reversed") for alternating dynamic acquisitions of control and label pairs. Eight volunteers were imaged on a 3T scanner. Images were corrected for distortion using spatial shifting transformation of the underlying field map. CBF maps were calculated and compared with maps obtained without blip reversal using matching gray matter (GM) images from a high resolution 3D scan. Additional benefit of using the correction for alternating blip-up and blip-down acquisitions was assessed by comparing to corrected blip-up only and corrected blip-down only CBF maps. Matched Student t-test of overlapping voxels for the eight volunteers was done to ascertain statistical improvement in distortion.ResultsMean CBF value in GM for the eight volunteers from distortion corrected CBF maps was 50.8±9.9ml/min/100 gm tissue. Corrected CBF maps had 6.3% and 4.1% more voxels in GM when compared with uncorrected blip up (BU) and blip down (BD) images, respectively. Student t-test showed significant reduction in distortion when compared with blip-up images and blip-down images (p<0.001). When compared with corrected BU and corrected BD only CBF maps, BU and BD corrected maps had 2.3% and 1% more voxels (p=0.006 and 0.04, respectively).ConclusionPseudo-continuous arterial spin labeling with non-segmented 3D EPI acquisition using alternating blip-reversed k-space traversal and distortion correction provided significantly better matching GM CBF maps. In addition, employing alternating blip-reversed acquisitions during pCASL acquisition resulted in statistically significant improvement over corrected blip-up and blip-down CBF maps.

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Neonatal skin care: what should we do? A four-week follow-up randomized controlled trial at Zagazig University Hospitals

Abstract

Introduction

Taking care of newborn skin is necessary to avoid skin infections. The normal daily exposure to external factors affects the skin negatively. Skin hygiene and proper skin cleansing as well as protection of the infant skin barrier are essential to maintain barrier function and overall infant health.

Aim

The aim of this work is to assess the neonatal skin care effectiveness in promotion of normal skin development and protection of the optimal skin function by avoiding the different neonatal skin disorders which cause skin infection.

Conclusion

In conclusion, proper care and good hygiene of the normal mature neonatal skin are essential to maintain skin barrier function and overall health. This is achieved by optimizing epidermal barrier integrity that includes:

bathing and using emollient;
preventing and managing infections and skin injury;
minimizing transepidermal water loss (TEWL);
minimizing heat loss and percutaneous absorption of toxins.

Baby bath products as well as baby wipes are safe to use and do not appear to affect an infant's skin barrier integrity. It is therefore sensible to use cleansers that have been specially designed for baby's skin, which are pH neutral and very mild to avoid irritant dermatitis and allergic dermatitis.

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A photoconverter gel-assisted blue light therapy for the treatment of rosacea

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Triple cancers concurrently detected in a case of antitranscriptional intermediary factor-1γ antibody-positive dermatomyositis

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Histopathology of Urticaria

Opinion statement

Purpose of review

Urticaria is a common skin manifestation with many different causes. It is characterized by local or generalized edematous erythema with itching and increased blood flow and vascular permeability. Individual urticaria lesions typically last less than 24 h (usually less than 12 h), but new lesions may appear and resolve sporadically. Since the diagnosis is usually made based on the history and clinical appearance of the lesions, skin biopsy is not necessarily performed, but it is recommended for evaluating patients with refractory eruptions or suspicion of other diseases exhibiting urticaria-like lesions. The histopathological features of urticaria are dermal edema and perivascular and interstitial inflammatory cell infiltration, and there is only minimal change in the epidermis. Cellular infiltrates are composed of lymphocytes, neutrophils, and eosinophils.

Recent findings

In our 64 patients with urticaria, severe edema was found in 48 cases (75%) with mixed cellular infiltration in 45 (70%), lymphocytic infiltration in 17 (27%), and neutrophilic infiltration in 2 cases (3%). Perivascular infiltration was found in 35 cases (55%), and the others were classified into the perivascular and interstitial infiltration type. Subcutaneous cellular infiltration has been shown to be associated with poor treatment response.

Summary

In this review, we summarize the histopathological findings of urticaria and its differential diagnosis. Evaluation of the histopathological features may provide further insight into the mechanism of urticaria and potentially provide valuable information to develop more effective treatments.

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Toxicity, uptake, and accumulation of nano and bulk cerium oxide particles in Artemia salina

Abstract

Although the toxicological impact of metal oxide nanoparticles has been studied for the last few decades on aquatic organisms, the exact mechanism of action is still unclear. The fate, behavior, and biological activity of nanoparticles are dependent on physicochemical factors like size, shape, surface area, and stability in the medium. This study deals with the effect of nano and bulk CeO₂ particles on marine microcrustacean, Artemia salina. The primary size was found to be 15 ± 3.5 and 582 ± 50 nm for nano and bulk CeO₂ (TEM), respectively. The colloidal stability and sedimentation assays showed rapid aggregation of bulk particles in seawater. Both the sizes of CeO₂ particles inhibited the hatching rate of brine shrimp cyst. Nano CeO₂ was found to be more toxic to A. salina (48 h LC₅₀ 38.0 mg/L) when compared to bulk CeO₂ (48 h LC₅₀ 92.2 mg/L). Nano CeO₂-treated A. salina showed higher oxidative stress (ROS) than those treated with the bulk form. The reduction in the antioxidant activity indicated an increase in oxidative stress in the cells. Higher acetylcholinesterase activity (AChE) was observed upon exposure to nano and bulk CeO₂ particles. The uptake and accumulation of CeO₂ particles were increased with respect to the concentration and particle size. Thus, the above results revealed that nano CeO₂ was more lethal to A. salina as compared to bulk particles.

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EGFR T790M mutation testing of non-small cell lung cancer tissue and blood samples artificially spiked with circulating cell-free tumor DNA: results of a round robin trial

Abstract

The European Commision (EC) recently approved osimertinib for the treatment of adult patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) harboring EGFR T790M mutations. Besides tissue-based testing, blood samples containing cell-free circulating tumor DNA (ctDNA) can be used to interrogate T790M status. Herein, we describe the conditions and results of a round robin trial (RRT) for T790M mutation testing in NSCLC tissue specimens and peripheral blood samples spiked with cell line DNA mimicking tumor-derived ctDNA. The underlying objectives of this two-staged external quality assessment (EQA) approach were (a) to evaluate the accuracy of T790M mutations testing across multiple centers and (b) to investigate if a liquid biopsy-based testing for T790M mutations in spiked blood samples is feasible in routine diagnostic. Based on a successfully completed internal phase I RRT, an open RRT for EGFR T790M mutation testing in tumor tissue and blood samples was initiated. In total, 48 pathology centers participated in the EQA. Of these, 47 (97.9%) centers submitted their analyses within the pre-defined time frame and 44 (tissue), respectively, 40 (plasma) successfully passed the test. The overall success rates in the RRT phase II were 91.7% (tissue) and 83.3% (blood), respectively. Thirty-eight out of 48 participants (79.2%) successfully passed both parts of the RRT. The RRT for blood-based EGFR testing initiated in Germany is, to the best of our knowledge, the first of his kind in Europe. In summary, our results demonstrate that blood-based genotyping for EGFR resistance mutations can be successfully integrated in routine molecular diagnostics complementing the array of molecular methods already available at pathology centers in Germany.

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Histiocytoid cardiomyopathy and ventricular noncompaction presenting as sudden death in an adult male

Publication date: Available online 7 September 2017
Source:Pathology - Research and Practice
Author(s): J. Fernando Val-Bernal, Marta Mayorga, Clara Ortega, Emma Linares
Histiocytoid/oncocytic cardiomyopathy (HCM) is a rare, distinctive arrhythmogenic disorder that presents as arrhythmia or sudden death in infants and children. Ventricular noncompaction (VNC) is a rare cardiomyopathy characterized by a thickened endocardial layer of noncompacted myocardium and a thin epicardial layer of compacted myocardium. Only six cases of the association of both cardiomyopathies have been reported previously in the literature. All these cases were in children. To the best of our knowledge, a case of HCM has not been described in the adult. We report the case of a 45-year-old man with an increased heart weight and involvement of both ventricles by HCM and VNC cardiomyopathy. Besides, multiple foci of myocardial disorganization were detected. He died suddenly while hiking. The association of both processes HCM and VNC was an unexpected finding at autopsy. The death was linked to functional abnormalities of the cardiac histiocytoid cells, and it was favored by a state of abnormal development of the heart.

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Upregulation of uc.189 in patients with esophageal squamous cell carcinoma and its clinicopathologic value

Publication date: Available online 7 September 2017
Source:Pathology - Research and Practice
Author(s): Yan Guo, Chenghai Wang, Xin Miao, Siyu Chen, Yu Qian, Guoli Li, Ying Jiang
Ultraconserved elements (UCEs) encoding noncoding RNAs serve as important regulators in cancer biology. Until now, the role of the UCE uc.189 in human cancers remains undefined and the clinical significance of uc.189 in esophageal cancers remains unknown. This study was to identify the prognostic value of uc.189 expression in esophageal squamous cell carcinomas (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of uc.189 in matched cancerous tissues and adjacent noncancerous tissues from 152 patients with ESCC. The correlation of uc.189 with clinicopathological features and prognosis were also analyzed. The expression of uc.189 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (122/152, 80.3%, p<0.01), and the high level of uc.189 expression was significantly correlated with invasion of the tumor (p=0.009), advanced clinical stage (p=0.000), lymph node metastasis (p=0.000), and poor prognosis. High expression of uc.189 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.

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AEG-1 mRNA expression in non-small cell lung cancer is associated with increased tumor angiogenesis

Publication date: Available online 7 September 2017
Source:Pathology - Research and Practice
Author(s): Zhihong Ma, Yingrong Chen, Shunli Dong, Xuting Xu, Jin Liu, Pengtao Song, Caihua Yu, Licheng Dai
Astrocyte-elevated gene-1 (AEG-1) is implicated in the oncogenesis and angiogenesis of various types of human malignant disease. However, the angiogenesis roles of AEG-1 in non-small cell lung cancer (NSCLC) remain to be further elucidated. In the present study, the expression level of AEG-1 mRNA in seven human lung cell lines and 89 paired tissue samples (tumor tissues (TTs) and pair-matched normal adjacent tissues (PMNATs)) from NSCLC patients was detected by real-time PCR. Staining of vascular endothelial growth factor (VEGF) and intratumoral microvessel density (iMVD, labeled by CD105) were assessed by immunohistochemistry. Furthermore, cell migration and invasion were evaluated by wound healing assay and transwell assays. AEG-1 mRNA level was significantly higher in human lung cancer cells and TTs than that in human normal bronchial epithelial cell line 16HBE and PMNATs, respectively (P<0.001). Higher AEG-1 mRNA level in patients with NSCLC was correlated with clinical stages (P=0.028), differentiation (P=0.042), and lymph node metastasis (P=0.004). Moreover, Upregulated AEG-1 mRNA expression level was associated with higher tumor angiogenesis, reflected by the increase of VEGF expression and iMVD counting (P=0.021, P<0.001). However, 95D cell line transfected with AEG-1 siRNA oligos (siAEG-1) exhibited no significant decrease of cell invasion or migration capacities when compared with the control cells (P>0.05).These results suggested that AEG-1 may play important roles at the transcription level in malignant transformation and tumor angiogenesis in NSCLC, and anti-AEG-1 mRNA expression may be a novel potential strategy for anti-angiogenic therapy of NSCLC.

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Relationship between swallowing function and breathing/phonation

Clarification of the association between the swallowing function and respiratory and phonatory functions.

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Natural course of tonsillectomy pain: A prospective patient cohort study

The aim of this study was to determine the natural course of pain after tonsillectomy.

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Knowledge of food protein–induced enterocolitis syndrome among general pediatricians

Food protein–induced enterocolitis syndrome (FPIES) is a potentially severe, non–IgE-mediated food hypersensitivity. Typically, FPIES presents in infancy, either acutely with profuse emesis, dehydration, and lethargy 1 to 4 hours after intermittent ingestions; or insidiously with frequent, watery diarrhea, intermittent emesis, and failure to thrive with chronic ingestions.1 Common eliciting foods include cow's milk and soy proteins; solids (rice, oat, fish, poultry, fish, and shellfish) are also culprits.

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Lymphoproliferative responses to dendritic cell presentation of sensitizing allergens in atopic children with multiple allergies

Peripheral blood mononuclear cells (PBMCs) proliferate inconsistently, rendering current lymphoproliferation assays unreliable in diagnosis.

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Genetically modified products and food allergy

The effect of genetically modified (GM) products on human health is a timely and important topic. This month's CME Review does an excellent job providing background on this technology, outlining potential health concerns as they relate to food allergy, and summarizing evidence on this topic.1 The article addresses 2 issues that practicing physicians face. First is the increasing disconnect between scientific evidence and popularized fixed health care beliefs and concerns. The second is the many questions we face for which evidence is lacking.

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Information for Readers

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The national cost of asthma among school-aged children in the United States

Recent research has quantified the national health care resource use (HCRU) and health care expenditure (HCE) burden associated with adult asthma; however, estimates specific to school-aged children are more than 2 decades old.

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Instructions for Authors

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Editorial Board

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The allergenicity of genetically modified foods from genetically engineered crops

During the past 2 decades, the diagnosis of food allergy has increased in industrialized countries. Immunoglobulin E (IgE) food allergies affect an estimated 4% to 8% of the American population.1,2 The reason for this increase remains unclear, but food allergy has become an increasingly difficult challenge for patients and their physicians to manage. Repeated exposures lead to significant morbidity, life-threatening anaphylaxis, and substantial health care costs. Because proteins are the primary precipitant of many allergic reactions, some members of the public have become concerned that the proteins produced in genetically modified (GM) crops will lead to an increase in allergic reactions in people who consume those crops.

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An unusual cause of fever in a patient with common variable immunodeficiency

The patient is a 22-year-old man with a history of common variable immunodeficiency (CVID) associated with a heterozygous mutation in TNFRSF13B (TACI), granulomatous lymphocytic interstitial lung disease (GLILD), massive splenomegaly, immune thrombocytopenia, and autoimmune hemolytic anemia. He presented with a 5-day history of fever with temperatures up to 38.9°C, malaise, sinus congestion, intermittent headaches, and loose stools. He had no cough, dyspnea, vomiting, abdominal pain, joint pain, or rash.

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Penicillin skin testing

Although approximately 10% of the population carries a label of penicillin allergy, the vast majority of these individuals turn out to be tolerant of penicillins. The rate of positive penicillin skin test reactions in patients with a history of penicillin allergy seems to have been decreasing in the past 2 decades.1,2 For example, Jost et al1 reported a skin test positive rate of 6% from 1993 through 2003 compared with 27% from 1979 through 1992 in consecutive pediatric patients using the same full set of penicillin skin test reagents.

http://ift.tt/2xTd3th

Author's response

We would like to thank authors for their comments on our article,1 which are both valid and valuable to consider. We agree that the estimated odds ratios are biased away from the null hypothesis given the sparse data. We also agree that the use of the word independently is incorrect in the abstract. The odds ratios reported in the abstract and in table 4 are univariate odds ratios. The term independently associated should be reserved for results from a multivariable analysis in which we have adjusted for the other variables in the model.

http://ift.tt/2ePUSjl

Unusual presentation of combined immunodeficiency in a child with homozygous DOCK8 mutation

Autosomal recessive hyper-IgE syndrome with combined immunodeficiency was first described in patients and linked to a mutation in the gene encoding the dedicator of cytokinesis 8 (DOCK8) in 2009.1,2 The DOCK8 gene is located on chromosome 9 and encodes for a protein that functions as a guanine nucleotide exchange factor, which interacts with the Rho family of GTPases.3 The activated Rho-GTPases are vital to cytoskeletal development, cell growth, migration, and adhesion. DOCK8 plays a critical role in immunologic synapse formation, linking the T-cell receptor to the actin cytoskeleton, thereby leading to T-cell activation and proliferation and T-, B-, and natural killer cell survival.

http://ift.tt/2xTdaFd

http://ift.tt/2eQnHMX

Predictors of granulomatous lymphocytic interstitial lung disease in common variable immunodeficiency: Methodological issues

We read with great interest the article by Hartono et al1 that was published in the Annals of Allergy, Asthma & Immunology in May 2017. They intended to determine a set of clinical and/or laboratory parameters associated with granulomatous lymphocytic interstitial lung disease (GLILD). Based on univariable analysis, they stated that splenomegaly was independently associated with GLILD (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.9–74.5). Although the study was useful and very interesting, some methodologic issues need to be considered.

http://ift.tt/2xTuPN8

Single recombinant and purified major allergens and peptides

To review the current knowledge regarding recombinant and purified allergens and allergen-derived peptides.

http://ift.tt/2eQvyd5

Sensitization profiles to peanut allergens across the United States

Measurement of IgE antibody to peanut components can aid in the prediction of allergic responses the food.

http://ift.tt/2xTur18

Allergic sensitization and objective measures of sleep in urban school-aged children with asthma

Allergic sensitization is associated with increased child asthma morbidity and decreased pulmonary function. Nocturnal symptoms and/or awakenings typically are measured by self-report from diary data, whereas objective assessments of sleep in child asthma studies are lacking.

http://ift.tt/2eQJpjP

Evaluating proteins for potential allergenicity using bioinformatic approaches

Ever since the introduction of a tougher tomato1 and, more recently, the discovery of a "DNA nanosurgery" system based on CRISPR-CAS,2 we are inexorably headed to a new world where genetically modified (GM) animals will consume GM plants, both of which will be labeled GM foods. These in turn will be (futuristically) consumed by GM humans. It is natural for allergists to wonder whether this could increase the incidence of allergy as we strive to primum non nocere and apply bioinformatics approaches to assess this at the bedside.

http://ift.tt/2xTY7eC

Knowledge of food protein–induced enterocolitis syndrome among general pediatricians

Lymphoproliferative responses to dendritic cell presentation of sensitizing allergens in atopic children with multiple allergies

Peripheral blood mononuclear cells (PBMCs) proliferate inconsistently, rendering current lymphoproliferation assays unreliable in diagnosis.

http://ift.tt/2xSWy0o

Genetically modified products and food allergy

Information for Readers

http://ift.tt/2xTx9Ug

The national cost of asthma among school-aged children in the United States

Instructions for Authors

http://ift.tt/2xTPP6v

Editorial Board

http://ift.tt/2eQx7Yt

The allergenicity of genetically modified foods from genetically engineered crops

An unusual cause of fever in a patient with common variable immunodeficiency

Penicillin skin testing

Author's response

Unusual presentation of combined immunodeficiency in a child with homozygous DOCK8 mutation

http://ift.tt/2eQnHMX

Predictors of granulomatous lymphocytic interstitial lung disease in common variable immunodeficiency: Methodological issues

Single recombinant and purified major allergens and peptides

To review the current knowledge regarding recombinant and purified allergens and allergen-derived peptides.

http://ift.tt/2eQvyd5

Sensitization profiles to peanut allergens across the United States

Measurement of IgE antibody to peanut components can aid in the prediction of allergic responses the food.

http://ift.tt/2xTur18

Allergic sensitization and objective measures of sleep in urban school-aged children with asthma

Evaluating proteins for potential allergenicity using bioinformatic approaches

Relationship between swallowing function and breathing/phonation

Clarification of the association between the swallowing function and respiratory and phonatory functions.

http://ift.tt/2wMJYiR

Natural course of tonsillectomy pain: A prospective patient cohort study

The aim of this study was to determine the natural course of pain after tonsillectomy.

http://ift.tt/2xfJ7KD

Comparison of Localized and Systemic Otitis Media With ANCA-associated Vasculitis.

Objective: To investigate differences in immune activity based on the presence of multiple organ involvement in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and whether hearing outcomes are different between patients with AAV localized to the ear and patients with systemic AAV. Study Design: Retrospective case review. Setting: University hospital. Patients: Twenty patients with otitis media with AAV (OMAAV) who met the criteria proposed by the OMAAV study group in Japan. Main Outcome Measure(s): Serum levels of C-reactive protein, ANCA titer, soluble interleukin-2 receptor levels, and hearing outcome. Results: Thirteen patients had disease involvement of organs other than the ear (systemic OMAAV group); involvement was localized to the ear in seven patients (localized OMAAV group). Serum levels of C-reactive protein, ANCA titer, and soluble interleukin-2 receptor were not significantly different between the groups. Hearing levels at diagnosis and in remission were significantly worse in the localized OMAAV group compared with the systemic OMAAV group. Hearing gain was not significantly different between groups. Conclusion: It is suggested that immune activity in patients with AAV localized to the ear is equivalent to activity in patients with systemic AAV. Therefore, we may need treatment for OMAAV equal in intensity to that for systemic AAV. As the hearing level at diagnosis was worse in patients with AAV localized to the ear than in patients with systemic AAV, earlier diagnosis may be needed to improve hearing outcome. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

http://ift.tt/2xfAKPp

Assessing Readability and Reliability of Online Patient Information Regarding Vestibular Schwannoma.

Hypothesis: The aim of this study is to objectively assess the quality and readability of websites related to vestibular schwannomas. Background: Patients are increasingly seeking information on confirmed or suspected diagnoses through the Internet. Clinicians are often concerned regarding the accuracy, quality, and readability of web-based sites. Methods: Online information relating to vestibular schwannoma was searched using the three most popular search engines. The terms "acoustic neuroma" and "vestibular schwannoma" were used. The top 50 results from each site were assessed for readability using the Flesch-Kincaid Grade Level, Flesch Reading Ease Score, and the Gunning-Fog Index. Quality of website information was scored using the DISCERN tool. Results: Of 300 search results analyzed, 58 separate appropriate websites were identified. The mean readability score using Flesch-Kincaid Grade Level was 10.27 (95% confidence interval [CI] 9.84-10.70). The mean Flesch Reading Ease Score was 48.75 (95% CI 46.57-50.92). The Gunning-Fog Index was 13.40 (95% CI 12.92-13.89). These scores equate to someone finishing secondary school/first year university student. DISCERN scores were highly variable but consistently demonstrated great variability in quality of information. Conclusion: Online patient information on vestibular schwannoma is highly variable in quality. Although there are a wide range of different websites easily available to patients on their condition and its treatment options, the information is written at a difficult level which may exceed the understanding level of many patients as it is written at a higher than average level of expected reading ability. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

http://ift.tt/2gM16xO

Comparison of an Electromagnetic Middle Ear Implant and Hearing Aid Word Recognition Performance to Word Recognition Performance Obtained Under Earphones.

Objective: To report the results of patients with the Maxum middle ear implant (MEI) and compare word recognition scores (WRS) and speech perception gap (SP Gap) of Maxum versus optimally fit hearing aids (HA). Study Design: Case series with chart review. Setting: Single, private otology clinic. Patients: Eleven ears, in nine adult patients (two women; average age 62.7 yr). Interventions: Twelve consecutive ears with moderate to severe (SNHL) underwent implantation of the Maxum system. One patient was not included due to inadequate preoperative testing. Main Outcome Measures: Primary outcome measures included word recognition score (WRS) and SP Gap (maximum word understanding [PB max] - WRSaided) improvement compared with HAs. Results: The average Maxum WRS was 64.7% (range, 28-94%), a 41.6% improvement (range, 10-66%) over HAs (p

http://ift.tt/2xfNLIJ

The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues

Publication date: Available online 7 September 2017
Source:Cell Reports
Author(s): Ajithkumar Vasanthakumar, Yang Liao, Peggy Teh, Maria F. Pascutti, Anna E. Oja, Alexandra L. Garnham, Renee Gloury, Jessica C. Tempany, Tom Sidwell, Eloy Cuadrado, Paul Tuijnenburg, Taco W. Kuijpers, Najoua Lalaoui, Lisa A. Mielke, Vanessa L. Bryant, Philip D. Hodgkin, John Silke, Gordon K. Smyth, Martijn A. Nolte, Wei Shi, Axel Kallies
After exiting the thymus, Foxp3⁺ regulatory T (Treg) cells undergo further differentiation in the periphery, resulting in the generation of mature, fully suppressive effector (e)Treg cells in a process dependent on TCR signaling and the transcription factor IRF4. Here, we show that tumor necrosis factor receptor superfamily (TNFRSF) signaling plays a crucial role in the development and maintenance of eTreg cells. TNFRSF signaling activated the NF-κB transcription factor RelA, which was required to maintain eTreg cells in lymphoid and non-lymphoid tissues, including RORγt⁺ Treg cells in the small intestine. In response to TNFRSF signaling, RelA regulated basic cellular processes, including cell survival and proliferation, but was dispensable for IRF4 expression or DNA binding, indicating that both pathways operated independently. Importantly, mutations in the RelA binding partner NF-κB1 compromised eTreg cells in humans, suggesting that the TNFRSF-NF-κB axis was required in a non-redundant manner to maintain eTreg cells in mice and humans.

Graphical abstract

Teaser

Effector regulatory T (eTreg) cells are potent repressors of immune pathology in lymphoid and non-lymphoid tissues. Vasanthakumar et al. have identified a signaling nexus, composed of TNFRSF and NF-κB/RelA, which operates independently of TCR-induced transcription factor IRF4 and is required for the differentiation and maintenance of eTreg cells.

http://ift.tt/2wN3ko7

Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis

Chamith Y Fonseka | Deepak A Rao | Soumya Raychaudhuri

http://ift.tt/2f7Gvnx

Novel mechanisms in immune tolerance to allergens during natural allergen exposure and allergen-specific immunotherapy

Willem van de Veen | Oliver F Wirz | Anna Globinska | Mübeccel Akdis

http://ift.tt/2f7Cj7l

Development of 1,3,4-oxadiazole thione based novel anticancer agents: Design, synthesis and in-vitro studies

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Nalini Yadav, Parveen Kumar, Aruna Chhikara, Madhu Chopra
A series of new 1,3,4-oxadiazole-2(3H)-thione analogues (3a to 3o) have been designed, synthesized and evaluated for their anticancer activity. Four different cancerous cell lines viz. HeLa (cervical), U-87 (glioblastoma), Panc (pancreatic) and MCF-7 (breast) were used to assess the potency of the synthesized compounds as anticancer agents. Among them 3i and 3j showed promising cytotoxicity against HeLa cell line. Further, 3i and 3j successfully inhibited cell cycle progression and displayed cell death in HeLa cells via apoptosis as visualized by Annexin V APC and DNA fragmentation assay. 3i and 3j induced caspase-3 activation, PARP cleavage, increase in expression of proapoptotic protein Bax and decrease in the expression of antiapoptotic protein Bcl-2. Also, 3i and 3j induced overexpression of p21 and decreased expression of cyclin B1 indicating the arrest of cells in G2-M phase of the cell cycle. Therefore, new lead compounds are being suggested having anticancer activity through cell cycle inhibition and apoptosis.

Graphical abstract

http://ift.tt/2wdSq9a

Cardioprotective effect of Malva sylvestris L. in myocardial ischemic/reprefused rats

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Hanheng Zuo, Yinping Li, Yinghua Cui, Yi An
PurposeThe present investigation evaluated the cardioprotective effect of Malva sylvestris L. (MS) on myocardial ischemic/reperfusion (MI/R) in rats.MethodsAll animals were divided into four groups: the sham operated group, ischemia/reperfusion group (MI/R), and the MS (250 and 500mg/kg) treated groups, who received MS 250 and 500mg/kg intragastrically for 15 consecutive days, respectively. At the end of the protocol, concentrations of aspartate transaminase (AST), creatine kinase-MB fraction (CK-MB) and lactate dehydrogenase (LDH) were estimated in serum and the concentrations of other parameters, such as C-reactive protein, macrophage inflammatory protein 1 alpha (MIP-1α), and nitric oxide (NO) were also estimated in the blood. Tissue homogenate concentrations of inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interlukin-1β (IL-1β), IL-10 and IL-6 as well as oxidative stress parameters, such as lipid peroxidation, catalase, and superoxide dismutase were estimated in MI/R rats.ResultSignificant decreases (p<0.01) in AST, LDH, and CK-MB levels were observed in the MS-treated group compared with those in the MI/R group. C-reactive protein and MIP-1α levels decreased in the MS-treated group compared with those in the MI/R group. Plasma NO level was significantly enhanced in the MS-treated group than in the MI/R group. Moreover, treatment with MS significantly reduced TNF-α, IL-1β, and IL-6 levels and increased IL-10 levels in the MS group compared with the MI/R group. Treatment with MS also attenuated the altered oxidative stress parameters in MI/R rats.ConclusionThe present results indicate the cardioprotective effects of MS of reducing oxidative stress and the inflammatory response in MI/R rats.

http://ift.tt/2wddnkB

N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2′-deoxycytidine as a potential boron delivery agent with respect to glioblastoma

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Łukasz Uram, Joanna Nizioł, Piotr Maj, Justyna Sobich, Wojciech Rode, Tomasz Ruman
Glioblastoma multiforme (GBM) is a central nervous system tumor of grade IV, according to the WHO classification, extremely resistant to all currently used forms of therapy, including resection, radiotherapy, chemotherapy or combined therapy. Therefore, more effective treatment strategies of this tumor are needed, with boron neutron capture therapy (BNCT) being a potential solution, provided a proper cancer cells-targeted 10B delivery agent is found. In search of such an agent, toxicity and capacity to target DNA of a boronated derivative of 2′-deoxycytidine, N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2′-deoxycytidine (1), was tested against human tumor vs. normal cells. The present in vitro results revealed 1 to show low toxicity for human U-118 MG glioma cells (in the mM range) and even by 3–4 – fold lower against normal human fibroblasts. In accord, induction of apoptosis dependent on caspase-3 and caspase-7 was detected at high (>20mM) concentration of 1. Although demonstrated to be susceptible to phosphorylation by human deoxycytidine kinase and to undergo incorporation in cellular DNA, the boron analogue did not disturb cell proliferation when applied at non-toxic concentrations and showed low toxicity to a model metazoan organism, Caenorhabditis elegans. Thus, N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2′-deoxycytidine appears a promising candidate for a 10B delivery agent to be used in BNCT, with C. elegans indicated as a good model for in vivo studies.

Graphical abstract

http://ift.tt/2wMxfP9

Prophetic medicine as potential functional food elements in the intervention of cancer: A review

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Bassem Y. Sheikh, Md. Moklesur Rahman Sarker, Muhamad Noor Alfarizal Kamarudin, Amin Ismail
Amounting scientific evidences have revealed the antitumor, antimetastatic, antiangiogenic, antiproliferative, chemopreventive and neo-adjuvant efficacy of Prophetic Medicine in various in vitro, in vivo and clinical cancer models. Prophetic Medicine includes plants, dietary materials or spices that were used as remedy recipes and nutrition by the great Prophet Mohammed (peace be upon him) to treat various ailments. Prophetic medicine is the total authentic Hadith narrated by the Prophet (PBUH) in relation to medicine, whether Qur'anic verses or honourable Prophetic Hadith. The ability of functional foods from Prophetic Medicine to modulate various signalling pathways and multidrug resistance conferring proteins with low side-effects exemplify their great potential as neo-adjuvants and/or chemotherapeutics. The present review aims to provide the collective in vitro, in vivo, clinical and epidemiology information of Prophetic Medicines, and their bioactive constituents and molecular mechanisms as potential functional foods for the management of cancer.

Graphical abstract

http://ift.tt/2wM48LH

Perillyl alcohol protects human renal tubular epithelial cells from hypoxia/reoxygenation injury via inhibition of ROS, endoplasmic reticulum stress and activation of PI3K/Akt/eNOS pathway

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Yixiao Xu, Wantie Wang, Keke Jin, Qifan Zhu, Hongzhou Lin, Minye Xie, Dexuan Wang
Ischemia/reperfusion (I/R) injury plays an essential role in renal transplantation, and represents a crucial risk factor for allograft dysfunction and acute renal failure. Modulation of oxidative stress is an effective therapeutic strategy for I/R injury. Perillyl alcohol (POH), a dietary monoterpene with antioxidant activity is found in a variety of plants. The study was carried out to investigate whether treatment of POH could reduce hypoxia/reoxygenation (H/R)-induced injury. H/R induced significant injury in HK-2 cells. H/R caused an increase in ROS level, apoptosis and ER stress. Meanwhile H/R also inhibited the cell viability and PI3K/Akt/eNOS signaling pathway. Pretreatment with POH prior to H/R improved cell viability, reduce ROS level, ER stress and apoptosis. Moreover, POH could also activate the PI3K/Akt/eNOS pathway. Therefore, POH may possess protective effects in H/R-induced cellular damage.

http://ift.tt/2wLI5EL

An increased expression of long non-coding RNA PANDAR promotes cell proliferation and inhibits cell apoptosis in pancreatic ductal adenocarcinoma

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Yuehong Jiang, Enhang Feng, Lifang Sun, Wei Jin, Yuhong You, Yue Yao, Yi Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies worldwide. Emerging evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) act as imperative roles in tumorigenesis and progression. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) is a novel lncRNA that contributes to the development of various cancers. However, its clinical significance and potential effects on PDAC remains unknown. In the present study, qRT-PCR was performed to explore the expression levels of PANDAR in PDAC tissues and corresponding non-tumor tissues, the correlation between PANDAR expression and clinicopathological characteristics was also analyzed. The functional roles of lncRNA PANDAR in PDAC cells were evaluated both in vitro and in vivo. The results indicated that PANDAR was aberrantly overexpressed in PDAC tissues and cell lines, and this overexpression was closely associated with tumor stage and vascular invasion in PDAC patients. Besides, silencing of PANDAR exerted tumor suppressive effect via reducing cell proliferation, colony-forming ability, inducing cell cycle G0/G1 arrest and apoptosis in PANC1 and Capan-2 cells. Further in vivo study confirmed the oncogenesis role of PANDAR in PDAC cells. Overall, our findings may help to develop a potential therapeutic target for the patients with PDAC.

http://ift.tt/2wcUmP8

Glycyrrhizic acid: A promising carrier material for anticancer therapy

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Xitong Su, Lei Wu, Mingming Hu, Wenxiang Dong, Meng Xu, Peng Zhang
Drug delivery systems have become an integral part of anticancer drugs today. Design of novel drug carriers may lead to significant enhancement in antineoplastic therapy. Glycyrrhizic acid (GL), which is the most important active ingredient extracted from the licorice root shows great potential as a carrier material in this field. Recent studies have indicated that the combination of GL and first-line drugs had better therapeutic effects on cancers. GL showed a series of anti-cancer-related pharmacological activities, such as broad-spectrum anti-cancer ability, resistance to the tissue toxicity caused by chemotherapy and radiation, drug absorption enhancing effects and anti-multidrug resistance (MDR) mechanisms, as a carrier material in drug delivery systems. This review introduced the current research progress on pharmacological mechanisms of GL and development of GL-based drug carriers in anti-cancer field to provide basis for the application prospects of GL. The design of novel GL-based drug delivery systems will bring new opportunities and challenges to anti-cancer therapy.

Graphical abstract

http://ift.tt/2wMg3sI

MDR1 polymorphisms affect the outcome of Chinese multiple myeloma patients

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Zhengrui Xiao, Guangli Yin, Ying Ni, Xiaoyan Qu, Hanxin Wu, Hua Lu, Sixuan Qian, Lijuan Chen, Jianyong Li, Hairong Qiu, Kourong Miao
ObjectiveTo illustrate the association of MDR1 (Multidrug Resistance 1) polymorphisms at loci 1236, 2677, 3435 and the prognosis of multiple myeloma (MM) in Jiangsu population.MethodsA total of 129 MM patients were recruited from Jiangsu Province, China. The DNA was extracted from white blood cells (WBC) of peripheral blood and was amplified by polymerase chain reaction-allele specific primers (PCR-ASP). MDR1 polymorphisms at 3 loci were analyzed by electrophoresis followed by photograph or DNA direct sequencing. The association between the MDR1 and clinical outcomes were calculated by Graphpad and SPSS.ResultsMDR1 alleles at locus C1236T with T had significant lower calcium level in MM patients compared with C. The genotype CT had a significantly prolonged progress free survival (PFS) compared genotype CC at locus C1236T (median time: 48 months vs. 28 months, respectively; p=0.0062; HR=0.21; 95%CI0.061–0.715) while patients carrying T allele (CT and TT) at locus C3435T had a longer PFS than patients without T allele (CC) (median time: 60 months vs. 29 months, respectively; p=0.038; HR=0.508; 95%CI 0.264–0.978). And a borderline significance was found in haplotype at loci 2677-3435 and PFS. No significant findings were revealed between OS and MDR1 polymorphisms.ConclusionMDR1 polymorphisms could affect the prognosis of multiple myeloma whereas more samples and a longer follow-up are also needed.

http://ift.tt/2wMjAaG

Peroxisome proliferator-activated receptors as therapeutic targets for heart failure

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Abdelrahman Ibrahim Abushouk, Mostafa Wanees Ahmed El-Husseny, Eshak I. Bahbah, Ahmed Elmaraezy, Aya Ashraf Ali, Asmaa Ashraf, Mohamed M. Abdel-Daim
Heart failure (HF) is a common clinical syndrome that affects more than 23 million individuals worldwide. Despite the marked advances in its management, the mortality rates in HF patients have remained unacceptably high. Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription regulators, involved in the regulation of fatty acid and glucose metabolism. PPAR agonists are currently used for the treatment of type II diabetes mellitus and hyperlipidemia; however, their role as therapeutic agents for HF remains under investigation. Preclinical studies have shown that pharmacological modulation of PPARs can upregulate the expression of fatty acid oxidation genes in cardiomyocytes. Moreover, PPAR agonists were proven able to improve ventricular contractility and reduce cardiac remodelling in animal models through their anti-inflammatory, anti-oxidant, anti-fibrotic, and anti-apoptotic activities. Whether these effects can be replicated in humans is yet to be proven. This article reviews the interactions of PPARs with the pathophysiological mechanisms of HF and how the pharmacological modulation of these receptors can be of benefit for HF patients.

http://ift.tt/2wddlJv

Antibody-cytokine fusion proteins for improving efficacy and safety of cancer therapy

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Zahra Valedkarimi, Hadi Nasiri, Leili Aghebati-Maleki, Jafar Majidi
Cytokines are key players in the regulation of immune responses both in physiological and pathological states. A number of cytokines have been evaluated in clinical trials and shown promising results in the treatment of different malignancies. Despite this, the clinical application of these molecules may be plagued by undesirable side effects The development of recombinant antibody–cytokine fusion proteins, which offer a means for target delivery of cytokines toward the tumor site, has significantly improved the therapeutic index of these immunomodulatory molecules. Selective tumor localization is provided by the monoclonal antibody component of the fusion protein that binds to the molecules present on the surface of tumor cells or accumulated preferentially in the diseased site. In this manner, the cytokine element is specifically located at the tumor site and can stimulate immune cells with appropriate cytokine receptors. Over the recent years, several antibody–cytokine fusion proteins have been developed with the capacity to target a wide variety of cancers whose application, in some cases, has led to complete rejection of the tumor. These findings support the notion that antibody–cytokine fusion proteins represent huge potential for cancer therapy. This review presents an overview of the advances made in the field of targeted cytokine delivery, which is made possible by genetically engineering antibody–cytokine fusion proteins.

http://ift.tt/2wMog07

Secondary Linburg-Comstock syndrome: a case report

Abstract

Linburg-Comstock syndrome is characterized by an inability to flex the interphalangeal joint of the thumb without simultaneous flexion of the distal interphalangeal joint of the index finger due to hereditary interconnections between the flexor pollicis longus (FPL) and the index flexor digitorum profundus (iFDP) resulting in discomfort and symptoms of flexor tenosynovitis. In addition to this anatomic anomaly, our clinical findings suggest that the interconnection can also result secondarily as a consequence of tenosynovial hyperplasia producing adhesions from any cause including previous surgery or trauma using the example of forearm laceration with dissection of the two tendons.

Level of Evidence: Level V, diagnostic study.

http://ift.tt/2wcItsG

Cryopreserved Cadaveric Arterial Allograft for Arterial Reconstruction in Patients with Prosthetic Infection

Publication date: Available online 7 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Anne Lejay, Charline Delay, Elie Girsowicz, Bettina Chenesseau, Emilie Bonnin, Mohamed-Zied Ghariani, Fabien Thaveau, Yannick Georg, Bernard Geny, Nabil Chakfe
ObjectiveThe aim of this study was to report outcomes of cryopreserved arterial allografts used as a vascular substitute in the setting of prosthetic material infection.MethodsA retrospective analysis of prospectively collected data was conducted including all consecutive interventions performed with cryopreserved arterial allografts used for vascular reconstruction in the setting of prosthetic material infection between January 2005 and December 2014. Five year outcomes included allograft related re-interventions, survival, primary patency, and limb salvage rates.ResultsFifty-three procedures were performed using cryopreserved allografts for vascular prosthetic infection: 25 procedures (47%) were performed at aorto-iliac level (Group 1) and 28 procedures (53%) at peripheral level (Group 2). The mean follow-up was 52 months. Five year allograft related re-intervention was 55% in Group 1 (6 allograft ruptures and 5 allograft aneurysm degenerations) and 33% in Group 2 (2 allograft ruptures and 7 allograft aneurysm degenerations). Five year survival was 40% and 68%, primary patency was 89% and 59% and limb salvage was 100% and 89% for Group 1 and 2 respectively.ConclusionUse of cryopreserved arterial allografts provides acceptable results but is tempered by suboptimal 5 year outcomes with high re-intervention rates.

http://ift.tt/2eQ0Zob

Development of a standard reference material containing 22 chlorinated hydrocarbon gases at 1 μmol/mol in nitrogen

Abstract

A gas standard mixture containing 22 chlorinated hydrocarbons in high purity nitrogen was prepared using a two-step weighing method and a gasifying apparatus developed in-house. The concentration of each component was determined using a gas chromatograph with flame ionization detection (GC/FID). Linear regression analysis of every component was performed using the gas standard mixture with concentrations ranging from 1 to 10 μmol/mol, showing the complete gasification of volatile organic compound (VOCs) species in a selected cylinder. Repeatability was also examined to ensure the reliability of the preparation method. In addition, no significant difference was observed between domestic treated and imported treated cylinders, which were conducive to reduction of the cost of raw materials. Moreover, the results of stability testing at different pressures and long-term stability tests indicated that the gas standard at 1 μmol/mol level with relative expanded uncertainties of 5% was stable above 2 MPa for a minimum of 12 months. Finally, a quantity comparison was conducted between the gas standard and a commercial gas standard from Scott Specialty Gases (now Air Liquide America Specialty Gases). The excellent agreement of every species suggested the favorable accuracy of our gas standard. Therefore, this reference material can be applied to routine observation of VOCs and for other purposes.

http://ift.tt/2wcW3w1

River biofilm community changes related to pharmaceutical loads emitted by a wastewater treatment plant

Abstract

Wastewater treatment plants (WWTP) are the main sources of a broad spectrum of pharmaceuticals found in freshwater ecosystems. These pollutants raise environmental health concerns because of their highly bioactive nature and their chronic releases. Despite this, pharmaceuticals' effects on aquatic environments are poorly defined. Biofilms represent a major part of the microbial life in rivers and streams. They can drive key metabolic cycles and their organizations reflect exposures to changing chemical, physical, and biological constraints. This study estimated the concentrations, over a 3-year period, of ten pharmaceuticals and five nutrients in a river contaminated by a conventional WWTP fed by urban and hospital wastewaters. Variations in these concentrations were related to biofilm bacterial community dynamics. Rock biofilms had developed over defined periods and were harvested at four locations in the river from the up- and downstream WWTP discharge point. Pharmaceuticals were found in all locations in concentrations ranging from not being detected to 192 ng L⁻¹. Despite the high dilution factor of the WWTP effluents by the receiving river, pharmaceuticals were found more concentrated downstream than upstream the WWTP. Shifts in bacterial community structures linked to the environmental emission of pharmaceuticals were superior to seasonal community changes. A community structure from a site located downstream but close to the WWTP was more strongly associated with high pharmaceutical loads and different from those of biofilm samples from the WWTP upstream or far downstream sites. These latter sites were more strongly associated with high nutrient contents. Low environmental concentrations of pharmaceuticals can thus be transferred from WWTP effluents to a connected stream and induce bacterial aquatic community changes over time.

http://ift.tt/2wMlt74

Letter to the editor: Response

We thanks the readers for their valuable comments on our study "KTP laser assisted endoscopic tissue fibrin glue biocauterization for congenital pyriform sinus fistula in children" [1]. The authors did propose an uncommon but sometimes happened incidentally clinical conditions, which is congenital pyriform sinus fistula (CPSF) with thyroid cyst. As in a retrospective clinical review of 165 cases by Xian et al. [2], there were only 12 cases presented with cervical cyst, especially in neonates and young infants less than 3 months.

http://ift.tt/2wNlZQT

Endoscopic management for congenital pyriform sinus fistula

We read the article "KTP laser assisted endoscopic tissue fibrin glue biocauterization for congenital pyriform sinus fistula in children" by Huang et al. [1] with great interest. The study presents a novel surgical management that is considered to be less invasive, safe, and effective. The innovation spirit is highly commendable and we appreciate their contribution to the treatment of pyriform sinus fistula. Yet we think one point is in doubt.

http://ift.tt/2wMwi9w

The relationship between the GJB3 c.538C>T variant and hearing phenotype in the Chinese population

Mutations in GJB3 were originally shown to underlie an autosomal dominant form of non-syndromic deafness in Chinese patients and the c.538C > T (p.R180*) variants caused high-frequency hearing loss. But after that, few reports have reported this mutation. This study investigated the relationship between the GJB3 c.538C > T variant and hearing phenotype in Chinese to assist with risk assessment and genetic counseling for hearing loss patients and their families.

http://ift.tt/2wNld6r

Introducing nerve-sparing approach during minimally invasive radical hysterectomy for locally-advanced cervical cancer: a multi-institutional experience

Publication date: Available online 7 September 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Francesco Raspagliesi, Giorgio Bogani, Arsenio Spinillo, Antonino Ditto, Stefano Bogliolo, Jvan Casarin, Umberto Leone Roberti Maggiore, Fabio Martinelli, Mauro Signorelli, Barbara Gardella, Valentina Chiappa, Cono Scaffa, Simone Ferrero, Antonella Cromi, Domenica Lorusso, Fabio Ghezzi
ObjectiveTo evaluate the impact of nerve-sparing (NS) approach on outcomes of patients undergoing minimally invasive radical hysterectomy (MRH) for locally advanced stage cervical cancer (LACC).MethodsData of consecutive patients undergoing minimally invasive surgery for LACC were retrospectively retrieved in a multi-institutional setting from 2009 to 2016. All patients included had minimally invasive class III radical hysterectomy (MRH or NS-MRH). Propensity matching algorithm was used to decrease possible allocation bias when comparing outcomes between groups.ResultsOverall, 83 patients were included. The prevalence of patients undergoing NS approach increased aver the study period (from 7% in the year 2009-2010 to 97% in the year 2015-2016; p-for-trend<.001). NS-MRH and MRH were performed in 47 (57%) and 36 (43%) patients, respectively. After the application the propensity-matching algorithm, we compared 35 patients' pair (total 70 patients). Postoperative complications rate was similar between groups. Patients undergoing NS-LRH experienced shorter hospital stay than patients undergoing LRH (3.6 vs. 5.0 days). 60-day pelvic floor dysfunction rates, including voiding, fecal and sexual alterations, were lower in the NS group in comparison to control group (p=.02). Five-year disease-free (p=.77) and overall (p=.36) survivals were similar comparing NS-MRH with MRH.ConclusionsThe implementation of NS approach in the setting of LACC improves patients' outcomes, minimizing pelvic dysfunction rates. NS approach has not detrimental effects on survival outcomes.

http://ift.tt/2wLUwl6

Perioperative Therapies – Enhancing the Impact of Cancer Surgery with Repurposed Drugs

Publication date: Available online 7 September 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Pan Pantziarka, Gauthier Bouche, Richard Sullivan, André M. Ilbawi, Anna J. Dare, Lydie Meheus
Surgical resection remains the major modality for modern curative treatment for solid tumours. However, post-surgical recurrence, even following clear-margin resection and adjuvant treatment, remains common in many types of cancer. Reducing recurrence rates, therefore, offers the potential to increase cure rates and increase overall survival. Perioperative therapies, simple interventions during the perioperative period, are designed to address some of the factors which influence post-surgical recurrence. A range of perioperative therapies are introduced and the rationale for further clinical investigation outlined.

http://ift.tt/2f83uyX

Frequency and Prognostic Significance of Incidental Prostate Cancer at Radical Cystectomy: Results from an international retrospective study

Publication date: Available online 7 September 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Rieken Malte, Luis A. Kluth, Dharam Kaushik, Stephen A. Boorjian, Mohammad Abufaraj, Beat Foerster, Michael Rink, Kilian Gust, Florian Roghmann, Joachim Noldus, Dimitri Vordos, Masayuki Hagiwara, Eiji Kikuchi, Masaomi Ikeda, Kazumasa Matsumoto, Pierre I. Karakiewicz, Morgan Rouprêt, Alberto Briganti, Douglas S. Scherr, Shahrokh F. Shariat, Veronika Seebacher
ObjectivesTo analyze the frequency of incidental prostate cancer (PC) at radical cystoprostatectomy (RC) for urothelial carcinoma of the bladder (UCB) and its association with survival outcomes in an international cohort.Patients and MethodsIn this retrospective study, we included 2114 who underwent RC and lymphadenectomy for UCB between 1976 and 2012 male patients from seven institutions. Univariable and multivariable Cox regression models addressed the association of incidental PC with cancer-specific mortality and overall mortality after RC.ResultsOverall, incidental PC was found in 513 (24.3%) patients with the lowest frequency in a Japanese center (23/164, 11.2%) and the highest frequency in a North American center (122/325, 37.5%), respectively (p<0.001). Within a median follow up of 27 months (IQR: 50 months), 20 patients (3.9%) were diagnosed with biochemical recurrence (BCR) and none of the patients died of PC. PC pathological tumor stage was more advanced in patients experiencing BCR (p<0.001). In multivariable Cox regression analyses adjusted for standard clinicopathologic features, incidental PC was not associated with cancer-specific (HR: 1.11, 95% CI: 0.91-1.35, p=0.30) or overall mortality (HR: 1.06, 95% CI: 0.83-1.35, p=0.65).ConclusionsIncidental PC at RC for UCB is a frequent event. However, the majority of PC cases are well-differentiated and organ-confined. Presence of incidental PC shows significant geographic differences. The risk of BCR after incidental PC is low and incidental PC is not associated with survival in UCB patients treated with RC.

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Hostility and cognitive control: Evidence of increased cardiovascular reactivity as a function of exposure to affective stress using a dichotic listening paradigm

Publication date: Available online 7 September 2017
Source:International Journal of Psychophysiology
Author(s): Alissa K. Holland, Gina A. Mitchell, Angela Steele, Jessica Bunting, David W. Harrison
Indices of cognitive control were examined in men with high and low levels of trait hostility as a function of exposure to affective and cognitive stress. A dual concurrent task paradigm was used whereby participants intentionally directed focus to the left or right ear under dichotic listening conditions before and after exposure to angry infant vocalizations. Analysis of the behavioral data supports the prediction of reduced right frontal regulatory control in men with high levels of hostility as indicated by diminished capacity to suppress report of phonemes presented to the language dominant left hemisphere (right ear) in the Focus Left condition. This diminishment in the capacity to suppress report of phonemes presented to the right ear in the Focus Left condition is suggestive of reduced cognitive control. With respect to the neurophysiological data, heart rate increased for only men with high levels of hostility in the Focus Left condition, and this was especially evident in the post-affective stress condition. This increase in right hemisphere arousal provides additional evidence of reduced cognitive control and support for the capacity model of hostility by implicating poor right frontal regulatory control over right posterior cerebral regions under dual task conditions. The results are discussed in terms of integrating the construct of cognitive control into the capacity model as well as providing implications regarding reductions in the capacity to suppress predominant aggressive responses in domestic settings.

http://ift.tt/2wOcnFy

Role of B cells in T helper cell responses in a mouse model of asthma

B cells efficiently take up HDM antigens independently of their B cell receptor specificity and serve as potent antigen presenting cells, influencing both propagation and initiation of T helper cell response in vivo.

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Impaired Humoral and Cellular Immune Responses to Influenza Vaccination in COPD Patient

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Ormdl3 Upregulates Airway Smooth Muscle Proliferation, Contraction, and Ca2+ Oscillations in Asthma

This study demonstrates that an intrinsic increase in ORMDL3 in ASM can induce increased ASM proliferation and contractility which might contribute to increased AHR in the absence of airway inflammation in asthma.

http://ift.tt/2xfBdB5

miRNA-155 mediates down-regulation of the high-affinity receptor for IgE via Toll-like receptor signaling

miRNA-155 contributes to the inflammatory process in AD by regulating the expression of the high-affinity receptor for IgE (FcεRI) via its transcription factor PU.1. miRNA-155 may represent an interesting new target in AD therapy.

http://ift.tt/2xfIdhe

Digital intraoral impression technique for edentulous jaws

Publication date: Available online 6 September 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Jing-Huan Fang, Xueyin An, Seung-Mi Jeong, Byung-Ho Choi
Few studies have evaluated direct digital impressions of edentulous jaws using intraoral scanners because it is difficult to scan edentulous sites that are smooth and devoid of features. A scanning technique is introduced for making direct digital impressions of edentulous jaws with intraoral scanners in patients with a broad palate.

http://ift.tt/2eQpilL

Three-dimensional printing in contemporary fixed prosthodontics: A technique article

Publication date: Available online 6 September 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Sarah Bukhari, Brian J. Goodacre, Abdulaziz AlHelal, Mathew T. Kattadiyil, Paul M. Richardson
Digital dentistry has gained in popularity among clinicians and laboratory technicians because of its versatile applications. Three-dimensional (3D) printing has been applied in many areas of dentistry as it offers efficiency, affordability, accessibility, reproducibility, speed, and accuracy. This article describes a technique where 3D printing is used to fabricate a die-trimmed cast and to replicate gingival tissue and implant analogs. The digital workflow that replaces the conventional laboratory procedure is outlined.

http://ift.tt/2gLBRf2

A chairside technique to add customized anterior acrylic resin teeth to a surgical obturator

Publication date: Available online 6 September 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Kamarul Hisham Kamarudin, Mariko Hattori, Yuka I. Sumita, Hisashi Taniguchi
A surgical obturator may need to be modified during the healing process after tissue resection. Apart from relining the fitting surfaces to accommodate the healing wound and changes in the surrounding tissues, other modifications such as adding teeth are sometimes required to improve esthetics and speech. This article describes a chairside technique to add customized acrylic resin teeth to an existing surgical obturator.

http://ift.tt/2eQp0vb

Maxillofacial prosthetic treatment factors affecting oral health-related quality of life after surgery for patients with oral cancer

Publication date: Available online 6 September 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Miki Hagio, Ken Ishizaki, Masahiro Ryu, Takeshi Nomura, Nobuo Takano, Kaoru Sakurai
Statement of problemAfter oral cancer surgery, tissue defects can cause deformity and limited mobility, complicating many essential functions. For patients with mandibular, tongue, and oral floor defects, evidence regarding the effects of maxillofacial prosthetics on their oral health-related quality of life (OHRQoL) is lacking. Therefore, maxillofacial prosthetic reconstruction has been implemented with no clear treatment goals.PurposeThe purpose of this study was to identify factors affecting the improvement of OHRQoL by using maxillofacial prosthetic treatment after surgery to repair maxillary, mandibular, tongue, and oral floor defects.Material and methodsAll individuals who agreed to maxillofacial prosthetics after surgery for oral cancer were enrolled. Oral function and OHRQoL were evaluated before maxillofacial prosthesis placement and 1 month after final adjustments. The oral functions evaluated included masticatory function, swallowing function, and articulatory function. The Oral Health Impact Profile (OHIP-J54) was used to evaluate OHRQoL. Factors affecting changes in the OHIP-J54 score for participants' background and oral functions before and after treatment were analyzed through logistic regression analysis (stepwise method).ResultsParticipants included 34 men and 16 women with an average age of 72.4 ±8.7 years. "Psychological discomfort" was correlated with the patient's sex and masticatory function. "Physical disability" was related to articulatory function. "Handicap" was related to the swallowing function. "Additional Japanese questions" were related to the patient's sex.ConclusionsParticipants' sex and their oral functions, including masticatory, swallowing, and articulatory functions, were associated with improved OHRQoL because of maxillofacial prosthetics after surgery for oral cancer.

http://ift.tt/2gLuHY1

A risk-based decision making tree for managing fractured abutment and prosthetic screws: A systematic review

Publication date: Available online 6 September 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Ryan M. Mizumoto, Faris Z. Jamjoom, Burak Yilmaz
Statement of problemIn implant dentistry, a variety of techniques are used to manage fractured abutment and prosthetic screws. All of them pose various degrees of difficulty to both the clinician and patient and risk involving damage to the implants and prostheses.PurposeThe purpose of this systematic review was to classify and organize the various reported techniques for managing fractured abutment and or prosthetic screws into a risk-based, decision making tree that could be used to guide the clinician through this difficult and time-consuming clinical procedure.Material and methodsA systematic search of the PubMed/MEDLINE database for articles published before June 2016 was performed by 2 independent reviewers. Studies published in English that described a clinical technique to retrieve or manage a fractured abutment or prosthetic screws were included. Techniques were classified according to risk of irreversible damage to the implant. Low-risk techniques were defined as those involving the use of basic hand instruments and instrument modification; moderate-risk techniques were defined as those involving the use of screw retrieval kits, rotary instruments, and screw modification; and high-risk techniques were defined as those involving modification of the implant. Published techniques were then organized into a decision-making tree.ResultsA total of 35 articles were included. The reported techniques ranged from straightforward instrumentation and instrument modification to screw or implant modifications. Seven techniques were considered low risk, 17 moderate risk, and 11 high risk.ConclusionsThe proposed risk-based decision tree is a useful tool in helping clinicians choose the most appropriate strategy or sequence of strategies that offers maximum benefit to the patient while minimizing associated risks.

http://ift.tt/2ePmQMg

3D-printed cone-beam computed tomography scans: A tool for patient education

Publication date: Available online 6 September 2017
Source:The Journal of Prosthetic Dentistry
Author(s): A. Brian Urtula, João Malta Barbosa, Gonçalo Bártolo Caramês, Ali Alper Çomut

http://ift.tt/2gLCuW0

Use of silver diamine fluoride for the maintenance of dental prostheses in a high caries-risk patient: A medical management approach

Publication date: Available online 6 September 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Lola Giusti, Cathrine Steinborn, Maya Steinborn
A technique for using silver diamine fluoride (SDF) as part of a regimen to help maintain dental prostheses in a patient with scleroderma and at high risk of caries is presented. Medically compromised, xerostomic, or elderly patients generally face greater risk of caries and specifically with prosthetic retainer teeth. SDF is a minimally invasive solution to this problem. A technique is described for using SDF to arrest and prevent new caries with the goal of maintaining fixed and removable prostheses and supporting teeth in a cost-effective manner.

http://ift.tt/2eQ6rHg

Evaluation of the multi-slice computed tomography outcomes in diaphragmatic injuries related to penetrating and blunt trauma

Publication date: Available online 6 September 2017
Source:Clinical Imaging
Author(s): Mehmet Turmak, Muhammed Akif Deniz, Cihan Akgül Özmen, Aydın Aslan
PurposeTraumatic diaphragmatic rupture is a diagnostic challenge for both surgeons and radiologists and generally occurs secondary to blunt and penetrating trauma of thoracoabdominal region.Material and methods56 patients who underwent surgical procedure due to blunt or penetrating trauma were included to the study.ResultsThere were 37 diaphragmatic ruptures in the left side and 19 patients in the right side. The most common radiological finding was "the direct monitoring of defect" (54,3%).ConclusionFindings suggestive of diaphragmatic rupture must be carefully evaluated in patients with blunt or penetrating thoracoabdominal trauma.

http://ift.tt/2wN67Oc

Altered expression of the FMR1 splicing variants landscape in premutation carriers

Publication date: Available online 7 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Elizabeth Tseng, Hiu-Tung Tang, Reem Rafik AlOlaby, Luke Hickey, Flora Tassone
FMR1 premutation carriers (55–200 CGG repeats) are at risk for developing Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), an adult onset neurodegenerative disorder. In addition, 20% of female carriers will develop Fragile X-associated Primary Ovarian Insufficiency (FXPOI), in addition to a number of clinical problems affecting premutation carriers throughout their life span. Marked elevation in FMR1 mRNA levels have been observed with premutation alleles resulting in RNA toxicity, the leading molecular mechanism proposed for the FMR1 associated disorders observed in premutation carriers.The FMR1 gene undergoes alternative splicing and we have recently reported that the relative abundance of all FMR1 mRNA isoforms is significantly increased in premutation carriers.In this study, we further investigated the transcriptional FMR1 isoforms distribution pattern in different tissues and identified a total of 49 isoforms, some of which observed only in premutation carriers and which might play a role in the pathogenesis of FXTAS.Further, we investigated the distribution pattern and expression levels of the FMR1 isoforms in asymptomatic premutation carriers and in those with FXTAS and found no significant difference between the two groups.Our findings suggest that the characterization of the expression levels of the different FMR1 isoforms is fundamental for understanding the regulation of the FMR1 gene as imbalance in their expression could lead to an altered functional diversity with neurotoxic consequences. Their characterization will also help to elucidating the mechanism(s) by which "toxic gain of function" of the FMR1 mRNA may play a role in FXTAS and/or in the other FMR1-associated conditions.

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Resveratrol, piceatannol and analogs inhibit activation of both wild-type and T877A mutant androgen receptor

Publication date: Available online 6 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Johan Lundqvist, Corrado Tringali, Agneta Oskarsson
Prostate cancer growth and progression is mainly dependent on androgens and many current prostate cancer treatment options target the synthesis or function of androgens. We have previously reported that resveratrol and synthetic analogs of resveratrol with a higher bioavailability inhibit the synthesis of androgens in human adrenocortical H295R cells. Now we have studied the antiandrogenic properties of resveratrol, piceatannol and analogs in two different prostate cell lines; LNCaP and RWPE. LNCaP carry a T877A mutation in the androgen receptor while RWPE has a wild-type androgen receptor. We found that resveratrol, piceatannol and all studied analogs were able to inhibit a dihydrotestosterone-induced activation of the androgen receptor, showing that they act as antiandrogens. In LNCaP cells, all studied compounds were able to statistically significantly decrease the androgenic signaling in concentrations ≥1μM and the synthetic analogs trimethylresveratrol (RSVTM) and tetramethylpiceatannol (PICTM) were the most potent compounds. RWPE cells were not as responsive to the studied compounds as the LNCaP cells. A statistically significant decrease in the androgenic signaling was observed at concentrations ≤5μM for most compounds and RSVTM was found to be the most potent compound. Further, we studied the effects of resveratrol, piceatannol and analogs on the levels of prostate-specific antigen (PSA) in LNCaP cells and found that all studied compounds decreased the level of PSA and that the synthetic analogs diacetylresveratrol (RSVDA), triacetylresveratrol (RSVTA) and RSVTM were the most potent compounds, decreasing the PSA level by approx. 50% at concentrations ≥10μM. In a cell-free receptor binding assay we were unable to show binding of resveratrol or analogs to the ligand binding domain of the androgen receptor, indicating that the observed effects are mediated via other mechanisms than direct ligand competition. We conclude that the resveratrol, piceatannol and analogs are highly interesting for chemoprevention of prostate cancer, since they have a high potency both as inhibitors of androgen synthesis and androgen receptor activation.

http://ift.tt/2eJFGAA