Head and Neck Diseases by Alexandros G.Sfakianakis: 01/04/17

Τετάρτη 4 Ιανουαρίου 2017

Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases–sponsored expert panel

Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.

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Discovery of a novel series of N-hydroxypyridone derivatives protecting astrocytes against hydrogen peroxide-induced toxicity via improved mitochondrial functionality

Publication date: Available online 3 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Sarbjit Singh, Ja-Il Goo, Hyojin Noh, Sung Jae Lee, Myoung Woo Kim, Hyejun Park, Hitesh B. Jalani, Kyeong Lee, Chunsook Kim, Won-Ki Kim, Chung Ju, Yongseok Choi
Astrocytes play a key role in brain homeostasis, protecting neurons against neurotoxic stimuli such as oxidative stress. Therefore, the neuroprotective therapeutics that enhance astrocytic functionality has been regarded as a promising strategy to reduce brain damage. We previously reported that ciclopirox, a well-known antifungal N-hydroxypyridone compound, protects astrocytes from oxidative stress by enhancing mitochondrial function. Using the N-hydroxypyridone scaffold, we have synthesized a series of cytoprotective derivatives. Mitochondrial activity assay showed that N-hydroxypyridone derivatives with biphenyl group have comparable to better protective effects than ciclopirox in astrocytes exposed to H2O2. N-hydroxypyridone derivatives, especially 11g, inhibited H2O2-induced detrioration of mitochondrial membrane potential and oxygen consumption rate, and significantly improved cell viability of astrocytes. The results indicate that the N-hydoxypyridone motif can provide a novel cytoprotective scaffold for astrocytes via enhancing mitochondrial functionality.

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3,4-dihydropyrimidinone-coumarin analogues as a new class of selective agent against S. aureus: Synthesis, biological evaluation and molecular modeling study

Publication date: Available online 5 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Nirmala S. Naik, Lokesh A. Shastri, Shrinivas D. Joshi, Sheshagiri R. Dixit, Bahubali M. Chougala, S. Samundeeswari, Megharaj Holiyachi, Farzanabi Shaikh, Jyoti Madar, Rashmi Kulkarni, Vinay Sunagar
Bacterial infections are increasingly difficult to combat as bacteria evolve resistance to antibiotic drugs and have severely compromised the arsenal of antibiotic drugs. On the other hand matrix metalloproteinases (MMPs) play a fundamental role in inflammation and extracellular matrix degradation in physiological and pathological conditions. In search of potent antibiotic, taking coumarin and dihydropyrimidinone as lead compound, a green, eco-friendly and efficient protocol has been developed and synthesized the dihydropyrimidin-2(1H)-one/thione derivatives of coumarin 3/4 from substituted 4-formylcoumarins 2 and ethylacetoacetate using urea/thiourea in the presence of catalytic amount of ceric ammonium nitrate is reported. All the synthesized compounds were evaluated for their antibacterial activity against four bacterial strains by broth dilution method. The tested compounds have exhibited promising in vitro potency with low MIC values against the drug susceptive S. aureus strain with low MIC values ranging from 0.2-6.25 μg/mL. The in vivo anti-inflammatory potency of 3a-e and 4a-e by gelatin zymography is comparable to that of tetracycline. Molecular docking study performed for all the synthesized compounds with S. aureus DNA gyrase and results obtained were quite promising.

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Development of 111In-labeled Exendin(9-39) Derivatives for Single-Photon Emission Computed Tomography Imaging of Insulinoma

Publication date: Available online 3 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Hiroyuki Kimura, Hirokazu Matsuda, Yu Ogawa, Hiroyuki Fujimoto, Kentaro Toyoda, Naotaka Fujita, Kenji Arimitsu, Keita Hamamatsu, Yusuke Yagi, Masahiro Ono, Nobuya Inagaki, Hideo Saji
Insulinoma is a tumor derived from pancreatic β-cells, and the resulting hyperinsulinemia leads to characteristic hypoglycemia. Recent studies have reported the frequent overexpression of glucagon-like peptide-1 receptor (GLP-1R) in human insulinomas, suggesting that the binding of a radiolabeled compound to GLP-1R is useful for the imaging of such tumors. Exendin(9-39), a fragment peptide of exendin-3 and -4, binds GLP-1R with high affinity and acts as an antagonist. Accordingly, radiolabeled exendin(9-39) derivatives have also been investigated as insulinoma imaging probes that might be less likely to induce hypoglycemia. In this study, we synthesized a novel indium-111 (¹¹¹In)-benzyl-diethylenetriaminepentaacetic acid (¹¹¹In-BnDTPA)-conjugated exendin(9-39), ¹¹¹In-BnDTPA-exendin(9-39), and evaluated its utility as a probe for the SPECT imaging of insulinoma. ^natIn-BnDTPA-exendin(9-39) exhibited a high affinity for GLP-1R (IC50 = 2.5 nM), stability in plasma, and a specific activity that improved following reactions with a solvent and solubilizer. Regarding the in vivo biodistribution of ¹¹¹In-BnDTPA-exendin(9-39) in INS-1 tumor-bearing mice, high uptake levels were observed in tumors (14.6% ID/g at 15 min), with corresponding high tumor-to-blood (T/B), tumor-to-muscle (T/M), and tumor-to-pancreas (T/P) ratios (T/B = 2.55, T/M = 22.7, T/P = 2.7 at 1 h). The pre-administration of excess nonradioactive exendin(9-39) significantly reduced accumulation in both the tumor and pancreas (76% and 68% inhibition, respectively) at 1 h after ¹¹¹In-BnDTPA-exendin(9-39) injection, indicating that the GLP-1R mediated a majority of ¹¹¹In-BnDTPA-exendin(9-39) uptake in the tumor and pancreas. Finally, ¹¹¹In-BnDTPA-exendin(9-39) SPECT/CT studies in mice yielded clear images of tumors at 30 min post-injection. These results suggest that ¹¹¹In-BnDTPA-exendin(9-39) could be a useful SPECT molecular imaging probe for the detection and exact localization of insulinomas.

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The 6-minute mastication test: a unique test to assess endurance of continuous chewing; normal values, reliability, reproducibility and usability in patients with mitochondrial disease

Abstract

In patients with mitochondrial disease, fatigue and muscle problems are the most common complaints. They also experience these complaints during mastication. To measure endurance in continuous mastication in patients with mitochondrial diseases the 6-minute mastication test (6MMT) was developed. This study included the collection of normal data for the 6MMT in a healthy population (children and adults). During 6 minutes of continuous mastication on a chew tube chewing cycles per minute, total amount of chewing cycles and the difference between minute 1 (M₁) and minute 6 (M₂) were collected in 271 healthy participants (5 - 80 years old). These results were compared with those of 9 pediatric and 25 adult patients with a mitochondrial disease. Visual Analogue Scale (VAS) scores were collected directly after the test and after 5 minutes. A qualitative rating was made on masticatory movements. The reproducibility of the 6MMT in the healthy population with an interval of approximately two weeks was good. The interrater reliability for the observations was excellent. The patient group demonstrated lower total amount of chewing cycles or had greater differences between M₁ and M₆. The 6MMT is a reliable and objective test to assess endurance in continuous chewing. It demonstrates the ability of healthy children and adults to chew during 6 minutes with a highly stable frequency of mastication movements. The test may give an explanation for the masticatory problems in patient groups, who are complaining of pain and fatigue during mastication.

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The role of molecular pain biomarkers in temporomandibular joint internal derangement

Summary

There is evidence that low-grade inflammation may be responsible for pain and development of degenerative changes in temporomandibular joint internal derangement. This article reviews the current knowledge of the molecular mechanisms behind TMJ internal derangements. A non-systematic search was carried out in PubMed, Embase, and the Cochrane library for studies regarding pathophysiological mechanisms behind internal derangements focusing on pain mediating inflammatory and cartilage degrading molecules. Recent data suggests that release of cytokines may be the key event for pain and cartilage destruction in TMJ internal derangements. Cytokines promote the release of matrix metalloproteinases (MMPs) and due to hypoxia, vascular endothelial growth factor (VEGF) is released. This activates chondrocytes to produce MMPs and reduce their tissue inhibitors (TIMPs) as well as the recruitment of osteoclasts, ultimately leading to cartilage and bone resorption. Also proteoglycans have an important role in this process. Several cytokines, MMPs, TIMPs, and VEGF have been identified in higher concentrations in the TMJ synovial fluid of patients with painful internal derangements and shown to be associated with the degree of degeneration. Other molecules that show elevated levels include hyaluronic acid synthase, disintegrin, and metalloproteinase with thrombospondin motifs (ADAMTs), aggrecan, fibromodulin, biglycan, and lumican. Taken together more or less pronounced inflammation of TMJ structures with release of cytokines, MMPs and other molecular markers that interact in a complex manner may be responsible for tissue degeneration in internal derangements. As internal derangements may be symptom-free, the degree of inflammation, but also other mechanisms, may be important for pain development.

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Three-dimensional, computer simulated navigation in endoscopic neurosurgery

Publication date: Available online 4 January 2017
Source:Interdisciplinary Neurosurgery
Author(s): Roberta K. Sefcik, Jonathan Rasouli, Joshua B. Bederson, Raj K. Shrivastava
BackgroundIn order to address the pre- and perioperative need for visualization and prediction of patient-specific anatomy for surgical planning, endoscopic neurosurgeons have increasingly relied on computerized navigation devices to guide their surgical approaches.ObjectiveThis manuscript aims to review: 1) the use of neuronavigation in endoscopic neurosurgery for pre-operative planning, 2) the intraoperative advantages of neuronavigation in endoscopic neurosurgery, and 3) the effects of navigation guidance on operative time, registration accuracy, brain shift, and avoidance of complications. Limitations of the current neuroendoscopic navigation literature will be discussed.MethodsWe conducted a search using PubMed-MEDLINE; the keywords "stereotactic navigation AND endoscopic surgery" and "simulation AND endoscopic neurosurgery". 36 studies were identified that addressed the use of neuronavigation in endoscopic neurosurgery. These studies were then further analyzed for topics relevant to computerized neuroendoscopy and reviewed for the purposes of this article.ConclusionThree-dimensional, frameless neuronavigation systems are useful in endoscopic neurosurgery to assist in the pre-operative planning of potential trajectories and to help localize the pathology of interest. Neuronavigation appears to be accurate to <1–2mm without issues related to brain shift. Further work is necessary in the investigation of the effect of neuronavigation on operative time, cost, and patient-centered outcomes.

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A mathematical model for the determination of forming tissue moduli in needled-nonwoven scaffolds

Publication date: Available online 5 January 2017
Source:Acta Biomaterialia
Author(s): Joao S. Soares, Will Zhang, Michael S. Sacks
Formation of engineering tissues (ET) remains an important scientific area of investigation for both clinical translational and mechanobiological studies. Needled-nonwoven (NNW) scaffolds represent one of the most ubiquitous biomaterials based on their well-documented capacity to sustain tissue formation and the unique property of substantial construct stiffness amplification, the latter allowing for very sensitive determination of forming tissue modulus. Yet, their use in more fundamental studies is hampered by the lack of (1) substantial understanding of the mechanics of the NNW scaffold itself under finite deformations and means to model the complex mechanical interactions between scaffold fibers, cells, and de novo tissue; and (2) rational models with reliable predictive capabilities describing their evolving mechanical properties and their response to mechanical stimulation. Our objective is to quantify the mechanical properties of the forming ET phase in constructs that utilize NNW scaffolds. We present herein a novel mathematical model to quantify their stiffness based on explicit considerations of the modulation of NNW scaffold fiber-fiber interactions and effective fiber stiffness by surrounding de novo ECM. Specifically, fibers in NNW scaffolds are effectively stiffer than if acting alone due to extensive fiber-fiber cross-over points that impart changes in fiber geometry, particularly crimp wavelength and amplitude. Fiber-fiber interactions in NNW scaffolds also play significant role in the bulk anisotropy of the material, mainly due to fiber buckling and large translational out-of-plane displacements occurring to fibers undergoing contraction. To calibrate the model parameters, we mechanically tested impregnated NNW scaffolds with polyacrylamide (PAM) gels with a wide range of moduli with values chosen to mimic the effects of surrounding tissues on the scaffold fiber network. Results indicated a high degree of model fidelity over a wide range of planar strains. Lastly, we illustrated the impact of our modeling approach quantifying the stiffness of engineered ECM after in vitro incubation and early stages of in vivo implantation obtained in a concurrent study of engineered tissue pulmonary valves in an ovine model.Statement of Significance"A mathematical model for the determination of forming tissue moduli in needled-nonwoven scaffolds" Regenerative medicine has the potential to fully restore diseased tissues or entire organs with engineered tissues. Needled-nonwoven scaffolds can be employed to serve as the support for their growth. However, there is a lack of understanding of the mechanics of these materials and their interactions with the forming tissues. We developed a mathematical model for these scaffold-tissue composites to quantify the mechanical properties of the forming tissues. Firstly, these measurements are pivotal to achieve functional requirements for tissue engineering implants; however, the theoretical development yielded critical insight into particular mechanisms and behaviors of these scaffolds that were not possible to conjecture without the insight given by modeling, let alone describe or foresee a priori.

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The Effect of Polyanhydride Chemistry in Particle-based Cancer Vaccines on the Magnitude of the Antitumor Immune Response

Publication date: Available online 4 January 2017
Source:Acta Biomaterialia
Author(s): Emad I. Wafa, Sean M. Geary, Jonathan T. Goodman, Balaji Narasimhan, Aliasger K. Salem
The goal of this research is to study the effect of polyanhydride chemistry on the immune response induced by a prophylactic cancer vaccine based on biodegradable polyanhydride particles. To achieve this goal, different compositions of polyanhydride copolymers based on 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG), 1,6-bis-(p-carboxyphenoxy)-hexane (CPH), and sebacic anhydride (SA) were synthesized by melt polycondensation, and polyanhydride copolymer particles encapsulating a model antigen, ovalbumin (OVA), were then synthesized using a double emulsion solvent evaporation technique. The ability of three different compositions of polyanhydride copolymers (50:50 CPTEG:CPH, 20:80 CPTEG:CPH, and 20:80 CPH:SA) encapsulating OVA to elicit immune responses was investigated. In addition, the impact of unmethylated oligodeoxynucleotides containing deoxycytidyl-deoxyguanosine dinucleotides (CpG ODN), an immunological adjuvant, on the immune response was also studied. The immune response to cancer vaccines was measured after treatment of C57BL/6J mice with two subcutaneous injections, seven days apart, of 50 μg OVA encapsulated in particles composed of different polyanhydride copolymers with or without 25 μg CpG ODN. In vivo studies showed that 20:80 CPTEG:CPH particles encapsulating OVA significantly stimulated the highest level of CD8⁺ T lymphocytes, generated the highest serum titers of OVA-specific IgG antibodies, and provided longer protection against tumor challenge with an OVA-expressing thymoma cell line in comparison to formulations made from other polyanhydride copolymers. The results also revealed that vaccination with CpG ODN along with polyanhydride particles encapsulating OVA did not enhance the immunogenicity of OVA. These results accentuate the crucial role of the copolymer composition of polyanhydrides in stimulating the immune response and provide important insights on rationally designing efficacious cancer vaccines.Statement of SignificanceCompared to soluble cancer vaccine formulations, tumor antigens encapsulated in biodegradable polymeric particles have been shown to sustain antigen release and provide long-term protection against tumor challenge by improving the immune response towards the antigen. Treatment of mice with cancer vaccines based on different polyanhydride copolymers encapsulating OVA resulted in stimulation of tumor-specific immune response with different magnitudes. This clearly indicates that polyanhydride chemistry plays a substantial role in stimulating the immune response. Vaccination with 20:80 CPTEG:CPH/OVA, the most hydrophobic formulation, stimulated the strongest cellular and humoral immune responses and provided the longest survival outcome without adding any other adjuvant. The most important finding in this study is that the copolymer composition of polyanhydride particle-based vaccines can have a direct effect on the magnitude of the antitumor immune response and should be selected carefully in order to achieve optimal cancer vaccine efficacy.

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Engineered extracellular microenvironment with a tunable mechanical property for controlling cell behavior and cardiomyogenic fate of cardiac stem cells

Publication date: Available online 4 January 2017
Source:Acta Biomaterialia
Author(s): Min-Young Choi, Jong-Tae Kim, Won-Jin Lee, Yunki Lee, Kyung Min Park, Young-Il Yang, Ki Dong Park
Endogenous cardiac stem cells (CSCs) are known to play a certain role in the myocardial homeostasis of the adult heart. The extracellular matrix (ECM) surrounding CSCs provides mechanical signals to regulate a variety of cell behaviors, yet the impact in the adult heart of these mechanical properties of ECM on CSC renewal and fate decisions is mostly unknown. To elucidate CSC mechanoresponses at the individual cell and myocardial level, we used the sol-to-gel transitional gelatin-poly(ethylene glycol)-tyramine (GPT) hydrogel with a tunable mechanical property to construct a three-dimensional (3D) matrix for culturing native myocardium and CSCs. The elastic modulus of the GPT hydrogel was controlled by adjusting cross-linking density using hydrogen peroxide. The GPT hydrogel showed an ability to transduce integrin-mediated signals into the myocardium and to permit myocardial homeostatic processes in vitro, including CSC migration and proliferation into the hydrogel from the myocardium. Decreasing the elastic modulus of the hydrogel resulted in upregulation of phosphorylated integrin-mediated signaling molecules in CSCs, which were associated with significant increases in cell spreading, migration, and proliferation of CSCs in a modulus-dependent manner. However, increasing the elastic modulus of hydrogel induced the arrest of cell growth but led to upregulation of cardiomyocyte-associated mRNAs in CSCs. This work demonstrates that tunable 3D-engineered microenvironments created by GPT hydrogel are able to control CSC behavior and to direct cardiomyogenic fate. Our system may also be appropriate for studying the mechanoresponse of CSCs in a 3D context as well as for developing therapeutic strategies for in situ myocardial regeneration.Statement of SignificanceThe extracellular matrix (ECM) provides a physical framework of myocardial niches in which endogenous cardiac stem cells (CSCs) reside, renew, differentiate, and replace cardiac cells. Interactions between ECM and CSCs might be critical for the maintenance of myocardial homeostasis in the adult heart. Yet most studies done so far have used irrelevant cell types and have been performed at the individual cell level, none able to reflect the in vivo situation. By the use of a chemically defined hydrogel to create a tunable 3D microenvironment, we succeeded in controlling CSC behavior at the myocardial and individual cell level and directing the cardiomyogenic fate. Our work may provide insight into the design of biomaterials for in situ myocardial regeneration as well as for tissue engineering.

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Efficient tuning of siRNA dose response by combining mixed polymer nanocarriers with simple kinetic modeling

Publication date: Available online 4 January 2017
Source:Acta Biomaterialia
Author(s): Chad T. Greco, Victoria G. Muir, Thomas H. Epps III, Millicent O. Sullivan
Two of the most prominent challenges that limit the clinical success of siRNA therapies are a lack of control over cargo release from the delivery vehicle and an incomplete understanding of the link between gene silencing dynamics and siRNA dosing. Herein, we address these challenges through the formulation of siRNA polyplexes containing light-responsive polymer mixtures, whose varied compositions and triggered release behavior provide enhanced gene silencing and controlled dose responses that can be predicted by simple kinetic models. Through the straightforward mixing of two block copolymers, the level of gene knockdown was easily optimized to achieve the maximum level of GAPDH protein silencing in NIH/3T3 cells (70%) using a single siRNA dose. The kinetic model was used to describe the dynamic changes in mRNA and protein concentrations in response to siRNA treatment. These predictions enabled the application of a second dose of siRNA to maximally suppress gene expression over multiple days, leading to a further 50% reduction in protein levels relative to those measured following a single dose. Furthermore, polyplexes remained dormant in cells until exposed to the photo-stimulus, demonstrating the complete control over siRNA activity as well as the stability of the nanocarriers. Thus, this work demonstrates that pairing advances in biomaterials design with simple kinetic modeling provides new insight into gene silencing dynamics and presents a powerful strategy to control gene expression through siRNA delivery.Statement of SignificanceOur manuscript describes two noteworthy impacts: (1) we designed mixed polymer formulations to enhance gene silencing, and (2) we simultaneously developed a simple kinetic model for determining optimal siRNA dose responses to maintain silencing over several days. These advances address critical challenges in siRNA delivery and provide new opportunities in therapeutics development. The structure-function relationships of these formulations were established to enable tuning and forecasting of nanocarrier efficiency a priori, leading to siRNA dosing regimens able to maximally suppress gene expression. Our advances are significant because the mixed polymer formulations provide a straightforward and scalable approach to tailor siRNA delivery regimens. Moreover, the implementation of accurate dosing frameworks addresses a major knowledge gap that has hindered clinical implementation of siRNA.

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Evidence of structurally continuous collagen fibrils in tendon

Publication date: Available online 5 January 2017
Source:Acta Biomaterialia
Author(s): Rene B. Svensson, Andreas Herchenhan, Tobias Starborg, Michael Larsen, Karl E. Kadler, Klaus Qvortrup, S. Peter Magnusson
Tendons transmit muscle-generated force through an extracellular matrix of aligned collagen fibrils. The force applied by the muscle at one end of a microscopic fibril has to be transmitted through the macroscopic length of the tendon by mechanisms that are poorly understood. A key element in this structure-function relationship is the collagen fibril length. During embryogenesis short fibrils are produced but they grow rapidly with maturation. There is some controversy regarding fibril length in adult tendon, with mechanical data generally supporting discontinuity while structural investigations favor continuity. This study initially set out to trace the full length of individual fibrils in adult human tendons, using serial block face-scanning electron microscopy. But even with this advanced technique the required length could not be covered. Instead a statistical approach was used on a large volume of fibrils in shorter image stacks. Only a single end was observed after tracking 67.5 mm of combined fibril lengths, in support of fibril continuity. To shed more light on this observation, the full length of a short tendon (mouse stapedius, 125 μm) was investigated and continuity of individual fibrils was confirmed. In light of these results, possible mechanisms that could reconcile the opposing findings on fibril continuity are discussed.Statement of SignificanceConnective tissues hold all parts of the body together and are mostly constructed from thin threads of the protein collagen (called fibrils). Connective tissues provide mechanical strength and one of the most demanding tissues in this regard are tendons, which transmit the forces generated by muscles. The length of the collagen fibrils is essential to the mechanical strength and to the type of damage the tissue may experience (slippage of short fibrils or breakage of longer ones). This in turn is important for understanding the repair processes after such damage occurs. Currently the issue of fibril length is contentious, but this study provides evidence that the fibrils are extremely long and likely continuous.

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Upconversion nanoparticles mediated deep-penetrating photodynamic therapy of KillerRed

Publication date: Available online 4 January 2017
Source:Acta Biomaterialia
Author(s): Liuen Liang, Yiqing Lu, Run Zhang, Andrew Care, Tiago A. Ortega, Sergey M. Deyev, Yi Qian, Andrei V. Zvyagin
The fluorescent protein KillerRed, a new type of biological photosensitizer, is considered as a promising substitute for current synthetic photosensitizes used in photodynamic therapy (PDT). However, broad applications of this photosensitiser in treating deep-seated lesions is challenging due to the limited tissue penetration of the excitation light with the wavelength falling in the visible spectral range. To overcome this challenge, we employ upconversion nanoparticles (UCNPs) that are able to convert deep-penetrating near infrared (NIR) light to green light to excite KillerRed locally, followed by the generation of reactive oxygen species (ROS) to kill tumour cells under centimetre-thick tissue. The photosensitizing bio-nanohybrids, KillerRed-UCNPs, are fabricated through covalent conjugation of KillerRed and UCNPs. The resulting KillerRed-UCNPs exhibit excellent colloidal stability in biological buffers and low cytotoxicity in the dark. Cross-comparison between the conventional KillerRed and UCNP-mediated KillerRed PDT demonstrated superiority of KillerRed-UCNPs photosensitizing by NIR irradiation, manifested by the fact that ∼70% PDT efficacy was achieved at 1-cm tissue depth, whereas that of the conventional KillerRed dropped to ∼7%.Statement of SignificanceKillerRed is a protein photosensitizer that holds promise as an alternative for the existing hydrophobic photosensitizers that are widely used in clinical photodynamic therapy (PDT). However, applications of KillerRed to deep-seated tumours are limited by the insufficient penetration depth of the excitation light in highly scattering and absorbing biological tissues. Herein, we reported the deployment of upconversion nanoparticles (UCNPs) to enhance the treatment depth of KillerRed by converting the deep-penetrating near-infrared (NIR) light to upconversion photoluminescence and activating the PDT effect of KillerRed under deep tissues. This work demonstrated clear potential of UCNPs as the NIR-to-visible light converter to overcome the light penetration limit that has plagued PDT application for many years.

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Burst-suppression Pattern on EEG Secondary to Valproic Acid-Induced Hyperammonemic Encephalopathy

Publication date: Available online 4 January 2017
Source:Pediatric Neurology
Author(s): Koshi Cherian, Alan Legatt

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Agenesis of the Corpus Callosum and Aicardi Syndrome: a neuroimaging and clinical comparison

Publication date: Available online 4 January 2017
Source:Pediatric Neurology
Author(s): T. Govil-Dalela, A. Kumar, R. Agarwal, H.T. Chugani
ObjectiveAgenesis of the corpus callosum (ACC) can be seen in patients with epilepsy, either in isolation or as part of various neurologic conditions, such as Aicardi syndrome. In this study, we evaluated the clinical and neuroradiological differences between children with non-syndromic ACC and those with Aicardi syndrome.MethodsWe evaluated 31 children with epilepsy and ACC (11 males: 20 females), 14 of whom had Aicardi syndrome (all females). We compared their clinical histories, radiologic and electrophysiologic findings, treatments, and their outcome.ResultsMedian age at seizure onset was lower in the Aicardi syndrome group compared to non-syndromic ACC (2 vs 5 months, p=0.006). The developmental impairment in terms of verbalization and ambulation was significantly worse in patients with Aicardi syndrome. The extent of magnetic resonance imaging (MRI) as well as glucose metabolism positron emission tomography (PET) involvement was more extensive in children with Aicardi syndrome than in non-syndromic ACC. In both groups, the PET scan showed a much more extensive area of involvement than suggested by the MRI scan. Four children underwent epilepsy surgery with significant improvement, but were not seizure free. Outcome was worse in those with PET showing abnormalities in the non-surgical hemisphere despite normal appearance on MRI. All children who did not undergo surgery also continued to have seizures at last follow-up.ConclusionsChildren with Aicardi syndrome have earlier seizure onset, worse developmental outcome and larger areas of brain abnormalities on neuroimaging as compared to non-syndromic ACC patients. PET reveals larger area of abnormalities, compared to MRI. Although epilepsy surgery in ACC may offer some palliative benefit in seizure frequency, none of our patients became seizure free.

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Safety of Transcranial Magnetic Stimulation in Children: A Systematic Review of the Literature

Publication date: Available online 4 January 2017
Source:Pediatric Neurology
Author(s): Corey H. Allen, Benzi M. Kluger, Isabelle Buard
ContextData and best practice recommendations for transcranial magnetic stimulation (TMS) use in adults is largely available. While there is less data in pediatric populations and no published guidelines, its practice in children continues to grow.MethodsWe performed a literature search through PubMed to review all TMS studies from 1985-2016 involving children and documented any adverse events. Crude risks were calculated per session.ResultsFollowing data screening, we identified 42 single pulse (spTMS) and/or paired pulse (ppTMS) TMS studies involving 639 healthy children (HC), 482 children with CNS disorders, and 84 epileptic children (EP). Adverse events (AEs) occurred at rates of 3.42%, 5.97%, and 4.55% respective to population and number of sessions. We also report 23 repetitive TMS (rTMS) studies involving 230 CNS and 24 EP with AE rates of 3.78% and 0.0% respectively. We finally identified three theta-burst stimulation (TBS) studies involving 90 HC, 40 CNS and no EP, with AE rates of 9.78% and 10.11% respectively. Three seizures were found to have occurred in CNS individuals during rTMS, with a risk of 0.14% per session. There was no significant difference in frequency of AEs by group (p = .988) nor modality (p = .928).ConclusionsAvailable data suggests that risk from TMS/TBS in children is similar to adults. We recommend that TMS users in this population follow the most recent adult safety guidelines until sufficient data are available for pediatric specific guidelines. We also encourage continued surveillance through surveys and assessments on a session-basis.

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Common and distinctive patterns of cognitive dysfunction in children with benign epilepsy syndromes

Publication date: Available online 4 January 2017
Source:Pediatric Neurology
Author(s): Dazhi Cheng, Xiuxian Yan, Zhijie Gao, Keming Xu, Xinlin Zhou, Qian Chen
BACKGROUNDChildhood absence epilepsy (CAE) and benign childhood epilepsy with centrotemporal spikes (BECTs) are the most common forms of benign epilepsy syndromes. Although cognitive dysfunctions occur in children with CAE or BECTs, the similarity between their patterns of underlying cognitive impairments is not well understood. To describe these patterns, we examined multiple cognitive functions in children with CAE and BECTs.METHODSIn this study, 43 children with CAE, 47 children with BECTs, and 64 controls were recruited; all received a standardized assessment (i.e., computerized test battery) assessing processing speed, spatial skills, calculation, language ability, intelligence, visual attention and executive function. Groups were compared in these cognitive domains. Simple regression analysis was used to analyze the effects of epilepsy-related clinical variables on cognitive test scores.RESULTSCompared to controls, children with CAE and BECTs showed cognitive deficits in intelligence and executive function, but performed normally in language processing. Impairment in visual attention was specific to patients with CAE, whereas impaired spatial ability was specific to the children with BECTs. Simple regression analysis showed syndrome-related clinical variables did not affect cognitive functions.CONCLUSIONSThis study provides evidence of both common and distinctive cognitive features underlying the relative cognitive difficulties in children with CAE and BECTs. It is suggested that clinicians should pay particular attention to the specific cognitive deficits in children with CAE and BECTs, to allow for more discriminative and potentially more effective interventions.

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Alternating upper limb monoplegia due to ATP1A3 mutation

Publication date: Available online 5 January 2017
Source:Pediatric Neurology
Author(s): Cécile Delorme, Elodie Hainque, Emmanuel Roze

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Association between the 20210G>A prothrombin gene polymorphism and arterial ischemic stroke in children and young adults – two meta-analyses of 3586 cases and 6440 controls in total

Publication date: Available online 4 January 2017
Source:Pediatric Neurology
Author(s): Beata Sarecka-Hujar, Ilona Kopyta, Michal Skrzypek, Joanna Sordyl
BackgroundPrevious data have shown that the 20210G>A polymorphism of the Factor II gene is related to an elevated prothrombin level, which may in turn lead to a procoagulant state. The heterogeneous and multifactorial character of arterial ischemic stroke (AIS) often results in contradictory reports describing the association between the 20210G>A polymorphism and AIS in different populations. We performed a meta-analysis of available data addressing the relation between the FII 20210G>A polymorphism and AIS, both in young adults and children.MethodsWe searched PubMed using appropriate keywords. The inclusion criteria for the study were as follows: case-control study, study population consisting of children, study population consisting of young adults, AIS confirmed by magnetic resonance imaging (MRI) or computed tomography (CT), English language. The exclusion criteria included: lack of genotype or allele frequencies, study design other than a case-control study, outcome definition other than AIS, previously overlapped patient groups. Finally, 30 case-control studies (14 in children and 16 in young adults) were included. Statistical analyses were conducted using R software. Heterogeneity between the studies was evaluated using the Dersimonian and Laird's Q test. In the case of significant between-studies heterogeneity, the pooled odds ratio (OR) was estimated with a random effects model, otherwise a fixed effects model was used.ResultsThe pooled analysis showed that carriers of 20210A allele (GA+AA genotypes) of the prothrombin gene are more common in AIS patients, both in children and young adults, than in controls (p=0.006,OR=1.83 95%CI 1.19-2.80 and p=0.001,OR=1.69 95%CI 1.25-2.28, respectively).ConclusionsThe results of the present meta-analysis have proven that the FII 20210G>A polymorphism is associated with AIS in both paediatric and young adult patients.

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Editorial Board/Reviewing Committee

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Calendar of Events

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Examining Effects of Physical Exertion on the Dynamic Visual Acuity Test in Collegiate Athletes

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Evaluation of a Wind Noise Attenuation Algorithm on Subjective Annoyance and Speech-in-Wind Performance

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The Effect of Conventional and Transparent Surgical Masks on Speech Understanding in Individuals with and without Hearing Loss

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Interrupted Monosyllabic Words: The Effects of Ten Interruption Locations on Recognition Performance by Older Listeners with Sensorineural Hearing Loss

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Auditory Processing Disorder as the Sole Manifestation of a Cerebellopontine and Internal Auditory Canal Lesion

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A Response to Dr. Jerger regarding “On Diagnostic Accuracy in Audiology: Central Site of Lesion and Central Auditory Processing Disorder Studies”

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JAAA CEU Program

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Aspartylglucosaminuria caused by a novel homozygous mutation in the AGA gene was identified by an exome-first approach in a patient from Japan

Publication date: Available online 4 January 2017
Source:Brain and Development
Author(s): Toshiyuki Yamamoto, Keiko Shimojima, Mayumi Matsufuji, Ryuichi Mashima, Eri Sakai, Torayuki Okuyama
BackgroundAspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disorder caused by a deficiency of the lysosomal enzyme, aspartylglucosaminidase (AGA). This disorder is rare in the general population except in Finland. Since the most characteristic feature of this disorder is a progressive developmental regression, patients often show no specific symptoms in the initial stages, and thus early diagnosis is often challenging.Case reportWe encountered a 16-year-old boy who began to show difficulties in his speech at the age of 6years. Due to a mild regression in his development, he gradually lost common daily abilities. His diagnosis was first obtained through exome sequencing that identified a novel homozygous mutation in the AGA gene. This result was reasonable because of parental consanguinity. Reduced enzymatic activity of AGA was then confirmed. His urine was retrospectively screened by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and a specific pattern of abnormal metabolites was identified.ConclusionsBecause both exome sequencing and MALDI-TOF-MS screening are adaptable and comprehensive, future combinatory use of these methods would be useful for diagnosis of rare inborn errors of metabolism such as AGU.

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Symmetrical thalamic calcification: A trio whole exome sequencing negative series

Publication date: Available online 4 January 2017
Source:Brain and Development
Author(s): Kathleen Mary Gorman, John James Aird, Judith Conroy, Deirdre Devaney, Michael Farrell, Mary Dolores King
Symmetrical thalamic calcification or bilateral symmetrical thalamic gliosis presents at delivery with hypertonia, fixed flexion contractures and prominent bulbar signs, without preceding perinatal asphyxia. At post-mortem, there is evidence of bilateral symmetrical selective thalamic neuronal encrustation and gliosis. To date, 27 cases are published with no underlying diagnosis identified. Two affected children from singleton pregnancies were reported and therefore, a genetic cause proposed. No previous reports have performed genetic testing to confirm or reject this hypothesis.We report three additional cases of this rare condition, expanding the clinical and pathological phenotype. We performed trio whole exome sequencing, the first in this cohort of patients, and did not identify a pathogenic variant. As postulated in the original report, the likely underlying mechanism is antenatal hypoxia in the third trimester.

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Preclinical uPAR-targeted multimodal imaging of locoregional oral cancer

Publication date: March 2017
Source:Oral Oncology, Volume 66
Author(s): M.C. Boonstra, P.B.A.A. Van Driel, S. Keereweer, H.A.J.M. Prevoo, M.A. Stammes, V.M. Baart, C.W.G.M. Löwik, A.P. Mazar, C.J.H. van de Velde, A.L. Vahrmeijer, C.F.M. Sier
ObjectivesEstablishing adequate resection margins and lymphatic mapping are crucial for the prognosis of oral cancer patients. Novel targeted imaging modalities are needed, enabling pre- and intraoperative detection of tumour cells, in combination with improved post-surgical examination by the pathologist. The urokinase-receptor (uPAR) is overexpressed in head and neck cancer, where it is associated with tumour progression and metastasis.Material and methodsTo determine suitability of uPAR for molecular imaging of oral cancer surgery, human head and neck tumours were sectioned and stained for uPAR to evaluate the expression pattern compared to normal mucosa. Furthermore, metastatic oral squamous carcinoma cell line OSC-19 was used for targeting uPAR in in vivo mouse models. Using anti-uPAR antibody ATN-658, equipped with a multimodal label, the in vivo specificity was investigated and the optimal dose and time-window were evaluated.ResultsAll human oral cancer tissues expressed uPAR in epithelial and stromal cells. Hybrid ATN-658 clearly visualized tongue tumours in mice using either NIRF or SPECT imaging. Mean fluorescent TBRs over time were 4.3±0.7 with the specific tracer versus 1.7±0.1 with a control antibody. A significant difference in TBRs could be seen between 1nmol (150μg) and 0.34nmol (50μg) dose groups (n=4, p<0.05). Co-expression between BLI, GFP and the NIR fluorescent signals were seen in the tongue tumour, whereas human cytokeratin staining confirmed presence of malignant cells in the positive cervical lymph nodes.ConclusionThis study shows the applicability of an uPAR specific multimodal tracer in an oral cancer model, combining SPECT with intraoperative guidance.

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Systemic Inflammatory Response and Severe Thrombocytopenia after Endovascular Thoracic Aortic Aneurysm Repair

After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm. Treatment with prednisone (50 mg/bid) for two weeks did not improve the clinical and laboratory findings. We utilized danazol, a weak androgen that has been shown to be effective in the treatment of immune and idiopathic thrombocytopenic purpura, and after 12 days of treatment with danazol (200 mg/bid), the patient improved progressively and platelet number increased up to 53,000/μL. Patients undergoing endovascular repair of thoracic aortic aneurysm should be carefully monitored for the development of postimplantation syndrome. This clinical condition is relatively common after the endovascular repair of aortic aneurysm but is rarely observed after endovascular repair of thoracic aortic aneurysms. The different known therapeutical approaches are still empiric, with reported beneficial effects with the use of NSAID, corticosteroids, and danazol.

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Nasopharyngeal Angiofibroma: Paradigm Shift in Management

Abstract

To report on a series of patients of nasopharyngeal angiofibroma of varied ages with different stages and management algorithm which reduced morbidity associated with this tumour. Retrospective. We report a series of ten patients who presented to a tertiary care institution and were diagnosed to have NA from 2012 to 2014. Patients were categorized by Radkowski staging and data was collected to document differences in terms of presentation, operative technique, and postoperative course. All patients underwent preoperative embolization. Stage I and selected stage II lesions were approached endoscopically while the remainder underwent open resection. In comparison with open procedures, endoscopic procedures had less intraoperative blood loss (350 vs. 630 cc), operative time (90 vs. 150 min) and the average hospital stay was one day less (3 vs. 4 days). Proper preoperative work up including nonsurgical intervention in the form of embolisation and selecting proper surgical approach is rewarding in case of angiofibromas of all stages which help to reduce morbidity associated with these benign tumours.

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Neck Trauma: ENT Prospects

Abstract

Neck trauma is a very important surgical emergency faced by ENT surgeons in day to day practice. They are potentially life threatening conditions due to the presence of many vital structures in this area. Timely presentation to the referral centre and proper multidisciplinary approach towards management plays a pivotal role in the healing pattern of the wound and prevention of serious complication like shock, sepsis, laryngeal stenosis or fistula formation. A retrospective study was done in ENT Department, NSCB Medical College, Jabalpur, Madhya Pradesh, India during the period of 2014–2016. 17 patients were included in the study. All the records regarding symptoms at presentation, type and mode of injury, level of injury were analyzed. Management plan undertaken were thoroughly studied and post operative complications like hoarseness, stenosis or fistula formation were noted carefully. 14 out of 17 patients were male, all 17 patients belonged to lower socioeconomic status. Most common age group presenting with neck trauma was between 22 and 40 years. 7 case were homicidal, 5 cases were suicidal and 4 were of accidental injury. Most cases reached hospital within 2–6 h of injury except 3 cases which took more than 8 h. Bleeding from wound site was most common symptom at presentation. Most injuries in 13 out of 17 cases were at thyroid cartilage level. Penetrating neck trauma was most common followed by blunt neck trauma. Most cases required emergency tracheostomy along with primary laryngotracheal repair. Most common post operative complication seen was wound dehiscence, subglottic stenosis and fistula formation. Neck trauma and cut throat injuries are potentially life threatening emergency that require multidisciplinary approach. Timely intervention can be crucial in preventing fatal complications and reducing morbidity period of the patient.

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Juvenile ‘Perinasal’ Angiofibroma

Abstract

The extranasopharyngeal angiofibroma is a separate clinical entity but those involving infratemporal fossa and cheek resemble juvenile nasopharyngeal angiofibroma (JNA) and hence have been labelled as juvenile perinasal angiofibroma (JPA) in this paper. This paper presents a 7th case of JPA and attempts to review the world literature on JPA, along with a proposal of staging the disease. A 16 year male presented with a painless compressible facial swelling since 7 months without any epistaxis or nasal obstruction. Initially a vascular lesion was suspected but JNA without nasal extension was strongly suspected on imaging. A deep trucut biopsy confirmed the histopathology. The vascular enhancement was significant and the tumour was excised through open approach (Weber Fergusson). JPA that can be regarded as a variant of JNA that fails to extend medially. Imaging demonstrates classical JNA findings with a clear nose/nasopharynx. A deep trucut biopsy under control in inpatient settings may sometimes help. JPA presents most commonly in Stage II where an open facial approach preferably following selective preoperative embolization is indicated. Hence with painless compressible (or non-compressible) cheek swelling suspected to be of a vascular etiology, a high degree of clinical suspicion for JPA needs to maintained in order to prevent a misdiagnosis.

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Unilateral blue rubber bleb naevus syndrome with Chiari malformation

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Clinical features of shiitake dermatitis: a systematic review

Summary

Shiitake dermatitis is a rare cutaneous reaction to lentinan, a polysaccharide component in the cell walls of shiitake mushrooms (Lentinula edodes). Herein, we systematically review the case report and case series English-language literature on shiitake dermatitis, which refers to a total of 50 patients (38 males, 12 females; mean age: 44.58 years). The majority of cases occurred after the consumption of raw mushrooms, whereas 22% of cases were caused by the eating of lightly or undercooked mushrooms. The most common clinical presentations, localized symptoms, and systemic findings include linear flagellated dermatitis (98%), pruritus (78%), and fever, diarrhea, and mucosal ulcers, respectively. The diagnosis of this entity continues to be based on clinical findings as laboratory abnormalities, and the findings of skin biopsies and patch/prick tests are nonspecific and inconsistent. The condition is self-limiting, resolving in approximately 12.5 d without treatment. Based on the included case reports, it appears that medical treatment may slightly shorten the course of disease (to 9–11 d, varying by therapy) but should be considered on an individual patient basis. However, the treatment of symptoms, reassurance, and the avoidance of re-exposure are sufficient treatment recommendations for this condition.

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Toll-like receptor (TLR)7 expression in mycosis fungoides and psoriasis: a case–control study

Summary

Background

Toll-like receptors (TLRs) have been implicated in various dermatological diseases. TLR agonists have the capacity to potently activate the innate immune cells of patients with advanced, refractory, cutaneous T-cell lymphoma (CTCL).

Aim

To detect TLR7 gene expression in mycosis fungoides (MF) (a neoplastic skin condition) and to compare it with psoriasis (an inflammatory skin condition) in an attempt to clarify the pathogenic role played by TLR7 in both conditions.

Methods

This case–control study enrolled 28 patients with MF: 30 patients with psoriasis, and 30 age- and sex-matched healthy controls (HCs). A 4-mm punch skin biopsy was obtained from lesional skin of patients and from normal skin of HCs for detection of TLR7 gene expression using real-time PCR.

Results

Mean TLR7 level in patients with MF (0.4 ± 0.23) was significantly lower than in patients with psoriasis (1.49 ± 0.46) and in HCs (1.22 ± 0.44) (P < 0.001), and mean TLR7 level in patients with psoriasis was significantly higher than in HCs (P < 0.03). Based on MF staging, 21.4% of patients had stage Ia, 28.6% had stage Ib, 28.6% had stage IIa and 21.4% had stage IIb disease. Comparing the TLR7 levels in relation to MF staging revealed the lowest mean value was in stage IIb and highest mean value in stage Ia, and this was significant (P < 0.001).

Conclusion

Disturbed innate immunity might play a role in the pathogenesis of neoplastic and inflammatory skin conditions. TLR7 could be useful as a prognostic factor in MF.

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Effects of age of onset on disease characteristics in non-segmental vitiligo

Abstract

In patients with vitiligo, the clinical and laboratory features of the disease may vary according to time of onset. This is addressed in the literature by only a few studies with conflicting results. The aim of this study was to determine the demographic and clinical features of patients with non-segmental vitiligo and to establish the association between vitiligo and autoimmune diseases with a focus on time of disease onset. A total of 224 vitiligo patients for whom complete medical records were available were evaluated retrospectively. Demographic data, scores on the Vitiligo Area Score Index (VASI), clinical features, vitiligo disease activity, repigmentation status, presence of any accompanying autoimmune disease, antinuclear antibody (ANA) titers, serum levels of glucose, thyroid-stimulating hormone (TSH), thyroxine (T4) hormone, anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-TG) were recorded. The prevalence of halo nevi was significantly higher (P < 0.001) among children than in other patient groups. The prevalence of leukotrichia was higher in adults with adult-onset disease than in either pediatric patients or adults with childhood-onset disease (P = 0.002). Both anti-TG and anti-TPO levels were significantly higher in adults with adult-onset disease than in pediatric patients and adult patients with childhood-onset disease. The prevalence of autoimmune disease was 22.2%. Anti-TG levels were significantly higher in patients with treatment-related repigmentation than in those without repigmentation. This study shows that clinical features and associations with autoimmune disease may vary according to the age of onset of vitiligo.

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Ferrochelatase gene mutation in Singapore and a novel frame-shift mutation in an Asian boy with erythropoietic protoporphyria

Abstract

Background

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused by decreased activity of the enzyme ferrochelatase (FECH ). The frequency of the hypomorphic c.333-48C allele in a population directly contributes to the prevalence of EPP in the same population. This study sought to identify the molecular basis of EPP in a Chinese patient from Singapore and the c.333-48C allele frequency among the Chinese population in Singapore.

Materials and methods

FECH gene was screened for mutation in the patient's DNA sample by polymerase chain reaction amplification and DNA sequencing. To validate the identified mutation, the FECH region harboring the mutation was screened in DNA samples from all healthy controls. One patient and 46 ethnically matched healthy controls were included in the study.

Results

A novel c.474dupC which leads to a frameshift and premature stop codon was identified in one allele, while the other allele showed to carry c.333-48C and c.337C>T variants in the patient's FECH. The frequency of the c.333-48C hypomorphic allele is 27% among Chinese population in Singapore.

Conclusions

c.474dupC in one allele trans to hypomorphic c.333-48C and c.337C>T allele in FECH gene may be the underlying cause of the clinical EPP of the studied patient. The FECH hypomorphic c.333-48C allele frequency in Singapore is lower than the Han Chinese (41.3%) and Japanese (43%) populations but nearly the same as the Southeast Asian (31%) population and higher than the European (2.7–11%) population.

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Hidradenitis suppurativa treated with tetracycline in combination with colchicine: a prospective series of 20 patients

Abstract

Background

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of the follicular epithelium.

Objectives

The objective of the present study was to evaluate the effectiveness of the combination of tetracycline with colchicine in the treatment of HS.

Methods

Twenty patients (10 women and 10 men) with HS were included in an open, prospective, pilot study. All patients were treated with 100 mg minocycline administered orally once per day in combination with 0.5 mg colchicine administered twice per day for 6 months followed by a maintenance regimen of 0.5 mg colchicine administered orally twice per day for 3 months. Patients were examined at baseline and thereafter every 3 months for a total of 9 months. The efficacy of the treatment was evaluated using a physician's global assessment (PGA) scale, the Hurley scoring system, and the Dermatology Life Quality Index (DLQI).

Results

A significant improvement in clinical manifestation was reflected in scores on the Hurley scoring system and DLQI. According to the PGA, patients achieved substantial improvement or complete remission. Clinically, all patients started to show signs of improvement within the first 3 months of therapy and continued to improve over the next 6 months.

Conclusions

This study indicates that the combination of the anti-inflammatory actions of colchicine and minocycline is effective in disease control in HS. Colchicine emerged as a safe option for the maintenance of the obtained result.

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Unilateral blue rubber bleb naevus syndrome with Chiari malformation

http://ift.tt/2hUUJdt

Toll-like receptor (TLR)7 expression in mycosis fungoides and psoriasis: a case–control study

Summary

Background

Aim

Methods

Results

Conclusion

Disturbed innate immunity might play a role in the pathogenesis of neoplastic and inflammatory skin conditions. TLR7 could be useful as a prognostic factor in MF.

http://ift.tt/2j6C0cr

Nasopharyngeal Angiofibroma: Paradigm Shift in Management

Abstract

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Neck Trauma: ENT Prospects

Abstract

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Juvenile ‘Perinasal’ Angiofibroma

Abstract

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Masthead

Publication date: January–February 2017
Source:Practical Radiation Oncology, Volume 7, Issue 1

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Editorial Board

Publication date: January–February 2017
Source:Practical Radiation Oncology, Volume 7, Issue 1

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Publication date: January–February 2017
Source:Practical Radiation Oncology, Volume 7, Issue 1

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The Impact of Tumor Biology on Survival and Response to Radiation Therapy among Patients with Non-Small Cell Lung Cancer Brain Metastases

Publication date: Available online 5 January 2017
Source:Practical Radiation Oncology
Author(s): Jacob A. Miller, Rupesh Kotecha, Manmeet S. Ahluwalia, Alireza M. Mohammadi, John H. Suh, Gene H. Barnett, Erin S. Murphy, Michael A. Vogelbaum, Lilyana Angelov, Samuel T. Chao
PurposeTo investigate the natural history and response to radiation therapy among ALK-rearranged, EGFR-mutated, wild-type adenocarcinoma, and squamous cell non-small cell lung cancer (NSCLC) brain metastases.Materials and MethodsPatients with NSCLC brain metastasis diagnosed from 1989–2014 at a single tertiary-care institution were included. The primary outcome was overall survival, while secondary outcomes included local failure, distant intracranial failure, and radiation necrosis. Cox proportional hazards regression was used to model overall survival, while multivariate competing risks regression was used to model secondary outcomes.ResultsWithin the study period, 1920 patients presented with 6312 brain metastases. Squamous histology was associated with poorer median survival compared with adenocarcinomas (5.4 vs. 8.8 mo., p<0.01). Median survival was greatest among ALK+ patients (49.2 mo.), followed by EGFR+ (20.3 mo.), and wild-type adenocarcinomas (10.0 mo., p<0.01). Treatment with EGFR inhibitors (HR 0.66, p<0.01) and VEGF antibodies (HR 0.65, p<0.01) increased survival independent of mutational status.Among 2056 lesions treated with stereotactic radiosurgery, the 12-month cumulative incidence of local failure was significantly greater among squamous cell carcinomas relative to adenocarcinomas (15% vs. 10%, HR 1.26, p=0.04). Patients with ALK+ metastases experienced higher rates of local failure (10%, HR 2.00, p=0.05), distant failure (39%, HR 2.94, p<0.01), and radiation necrosis (18%, HR 5.77, p<0.01), while EGFR+ patients experienced the lowest rates of local failure (5%, HR 0.46, p=0.04) and distant failure (3%, HR 0.13, p=0.04).ConclusionsAdvances in precision medicine have increased survival among select patients with NSCLC. In the present investigation, ALK+ and EGFR+ status were associated with improved survival. However, patients with ALK+ metastases have poor intracranial control relative to EGFR+ metastases, possibly due to limited intracranial penetration of crizotinib compared to EGFR inhibitors. Future investigations are warranted to determine the optimal management of ALK+ brain metastases with the introduction of second-generation ALK inhibitors.

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A Model of Electrically Stimulated Auditory Nerve Fiber Responses with Peripheral and Central Sites of Spike Generation

Abstract

A computational model of cat auditory nerve fiber (ANF) responses to electrical stimulation is presented. The model assumes that (1) there exist at least two sites of spike generation along the ANF and (2) both an anodic (positive) and a cathodic (negative) charge in isolation can evoke a spike. A single ANF is modeled as a network of two exponential integrate-and-fire point-neuron models, referred to as peripheral and central axons of the ANF. The peripheral axon is excited by the cathodic charge, inhibited by the anodic charge, and exhibits longer spike latencies than the central axon; the central axon is excited by the anodic charge, inhibited by the cathodic charge, and exhibits shorter spike latencies than the peripheral axon. The model also includes subthreshold and suprathreshold adaptive feedback loops which continuously modify the membrane potential and can account for effects of facilitation, accommodation, refractoriness, and spike-rate adaptation in ANF. Although the model is parameterized using data for either single or paired pulse stimulation with monophasic rectangular pulses, it correctly predicts effects of various stimulus pulse shapes, stimulation pulse rates, and level on the neural response statistics. The model may serve as a framework to explore the effects of different stimulus parameters on psychophysical performance measured in cochlear implant listeners.

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Pulse sequence considerations for simulation and postimplant dosimetry of prostate brachytherapy

Publication date: Available online 4 January 2017
Source:Brachytherapy
Author(s): Jingfei Ma, Marinus A. Moerland, Aradhana M. Venkatesan, Tharakeswara K. Bathala, Rajat J. Kudchadker, Kristy K. Brock, Steven J. Frank
PurposeThe purpose of this work is to present a brief review of MRI physics principles pertinent to prostate brachytherapy, and a summary of our experience in optimizing protocols for prostate brachytherapy applications.Methods and MaterialsWe summarized essential MR imaging characteristics and their interplays that need to be considered for prostate brachytherapy applications. These include spatial resolution, signal-to-noise ratio, image contrast, artifacts, geometric distortion, specific absorption rate, and total scan time. We further described the optimization of the protocols for three pulse sequences: three-dimensional (3D) fast-spoiled gradient echo sequence for T1-weighted imaging, 3D fast-spin echo sequence for T2-weighted imaging, and 3D fast imaging in steady-state precession sequence for combined T1 and T2-weighed imaging. The utilization of an endorectal coil was also described.ResultsUsing the optimized protocols, we acquired high-quality images of the entire prostate within 3–5 minutes for each sequence. These images display the desired image contrasts and a spatial resolution that is equal to or better than 0.59 mm × 0.73 mm × 1.2 mm. While 3D fast-spoiled gradient echo sequence and 3D fast-spin echo sequence depict radioactive seed markers and anatomic structures separately, 3D fast imaging in steady-state precession sequence demonstrates great promise for imaging both seed markers and prostate anatomy simultaneously in a single acquisition.ConclusionsWe have optimized current MRI protocols and demonstrated that the anatomic structures and positive contrast radioactive seed markers for prostate post-implant dosimetry can be adequately imaged either separately or simultaneously using different pulse sequences within a total scan time of 3–5 minutes each.

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Trends in the use of implantable accelerated partial breast irradiation for ductal carcinoma in situ: Implications of the recent amendments to the American Society for Radiation Oncology consensus guidelines

Publication date: Available online 4 January 2017
Source:Brachytherapy
Author(s): Waqar Haque, Vivek Verma, Anam Haque, E. Brian Butler, Bin S. Teh
PurposeIn 2009, the American Society for Radiation Oncology (ASTRO) published consensus recommendations that stated ductal carcinoma in situ (DCIS) patients were in a "cautionary" group for accelerated partial breast irradiation (APBI) and should not receive APBI outside of a clinical trial. However, very recently, ASTRO placed low-risk DCIS patients in the "suitable" category. Given this recent change, we aimed to use the Surveillance, Epidemiology, and End Results (SEER) database to evaluate past patterns of implantable APBI (IAPBI) utilization in women with DCIS.Methods and MaterialsThe Surveillance, Epidemiology, and End Results database was queried for patients from 2000 to 2012 with DCIS that underwent lumpectomy and adjuvant radiation therapy. Patients receiving IAPBI were differentiated from those receiving whole breast radiation therapy. Trends based on treatment year and patient demographics were collected, and multivariable logistic regression determined factors independently predictive of use of IAPBI.ResultsOf 52,012 eligible patients, 49,450 (95%) underwent external beam radiation and 2562 (5%) received APBI. Though IAPBI utilization steadily increased from 2000 (0.2% of the study population) to 2008 (9.4%), it abruptly declined in 2009 (7.9%, p = 0.009) and yearly thereafter. The 40–49 age group was proportionally most associated with this decline (8.6% in 2008 to 4.3% in 2009). Factors independently associated with IAPBI receipt included increasing age, hormone receptor negative status, and women living in the South.ConclusionsPatterns of IAPBI administration in DCIS are described. These trends are important to consider as a benchmark going forward, in light of the very recent change in ASTRO recommendations to include low-risk DCIS patients.

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A Model of Electrically Stimulated Auditory Nerve Fiber Responses with Peripheral and Central Sites of Spike Generation

Abstract

http://ift.tt/2iFPMUm

Anthropometric factors have significant influence on the outcome of the GHRH-arginine test: establishment of normative data for an automated immunoassay specifically measuring 22 kDa human growth hormone

Context

Adult growth hormone (GH) deficiency (GHD) is diagnosed by provocative testing of GH secretion.

Objective

To improve the diagnostic accuracy of GH-releasing hormone (GHRH) plus arginine (GARG) testing, we evaluated the influence of age, BMI and sex and established normative data for an automatic immunoassay specifically measuring 22 kDa human GH.

Design/setting

Prospective multicenter study.

Participants

Eighty-seven patients with hypothalamic–pituitary disease and 200 healthy controls. Patients were classified according to the number of pituitary hormone deficiencies (PHD). GHD was assumed when ≥2 PHD (in addition to GH) were present (n = 51); 36 patients with <2 PHD were considered GH sufficient (GHS). ROC analysis identified cutoffs with ≥95% specificity for GHD. Controls were prospectively stratified for sex, age and BMI.

Interventions

All participants received GHRH and l-arginine.

Main outcome measures

GH was measured by immunoassay (iSYS, IDS).

Results

In controls, multiple stepwise regression analysis showed that BMI (21%, P < 0.0001), sex (20%, P < 0.0001) and age (5%, P < 0.001), accounted for 46% of GH peak level variability during GARG. Comparison of peak GH during GARG (GHD vs GHS + controls) revealed an overall cutoff of 3.9 ng/mL (sensitivity 86%, specificity 95%). After adjustment for BMI and sex, optimal cutoffs (male vs female) were 6.5 vs 9.7 ng/mL in lean, 3.5 vs 8.5 ng/mL in overweight and 2.2 vs 4.4 ng/mL in obese subjects respectively.

Conclusion

BMI and sex account for most of the variability of peak GH levels during GARG. Consequently, diagnostic accuracy of the GARG test is significantly improved by use of adjusted cutoffs.

http://ift.tt/2jcjRy1

Increased prevalence of obstructive sleep apnea in patients with Cushings syndrome compared with weight- and age-matched controls

Objective

Diabetes mellitus and obesity are well-known risk factors associated with obstructive sleep apnea (OSA). Cushing's syndrome (CS) is also characterized by obesity and diabetes mellitus. However, the association between CS and OSA remains unclear. Therefore, we investigated the possible associations between CS and OSA in this study.

Patients and methods

Thirty female patients with newly diagnosed active CS and 30 age-, gender- and body mass index (BMI)-matched controls were included in this study. All participants were evaluated by overnight polysomnography. OSA was defined as having an apnea–hypopnea index (AHI) score of ≥5 events/h. Insulin resistance was calculated by homeostasis model assessment (HOMA) scores. Fasting serum cortisol was also determined.

Results

The prevalence of OSA was higher (50% vs 23%, P = 0.003) in patients with CS compared with the control subjects. The mean HOMA (P = 0.046) and AHI (P = 0.028) scores were higher in patients with CS compared with the control subjects. AHI was positively correlated with the HOMA scores (r = 0.281, P = 0.046) in both groups. Linear regression analysis showed that serum cortisol remained as an independent predictor for AHI after controlling for BMI and HOMA score (P < 0.001).

Conclusions

The prevalence of OSA increased in patients with CS compared with control subjects with similar ages and BMI levels. Hypercortisolemia is an independent risk factor for developing OSA. The presence of OSA needs to be considered in patients with CS.

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Jakob and Spillner1 commented on our comparison of 2 different diagnostic assays for insect venom allergy, namely ImmunoCAP and Immulite.2 Their sophisticated and partially ambiguous arguments are well taken. However, we disagree on some quite critical aspects.

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Comparing sensitivity of Hymenoptera allergen components on different diagnostic assay systems: Comparing apples and oranges?

In a recent letter to the editor published in the Journal, Schrautzer et al1 reported the comparison of 2 different diagnostic assays, namely ImmunoCAP (Thermo Fisher Scientific, Waltham, Mass) and Immulite (Siemens, Tarrytown, NY), for the detection of specific IgE (sIgE) responses to allergen components in a population of patients with Hymenoptera venom allergy. The study reports a higher rate of positive test results (≥0.35 kUA/L) on the Immulite compared with the ImmunoCAP system for sIgE to rApi m 1 in patients with bee venom allergy and for sIgE to rVes v 5 in patients with vespid venom allergy and concludes that the Immulite system displays a higher sensitivity for the detection of sIgE to these Hymenoptera venom allergens.

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Ultrasound Measurements of Skeletal Muscle Architecture Are Associated with Strength and Functional Capacity in Older Adults

Publication date: Available online 4 January 2017
Source:Ultrasound in Medicine & Biology
Author(s): Isaac Selva Raj, Stephen R. Bird, Anthony J. Shield
The goal of this study was to determine whether ultrasound measures of muscle architecture can be used to infer strength and functional capacity in older adults. Thirty-six healthy older adults (aged 68.2 ± 5.3 y) undertook isokinetic dynamometry for isometric and isokinetic concentric knee extensor strength, the 6-m fast walk, timed up and go, stair climb and descent and vertical jump tests. Longitudinal brightness-mode ultrasound scans (probe frequency, 10 MHz) of the vastus lateralis, vastus intermedius, rectus femoris and gastrocnemius medialis were obtained, and muscle architecture measures (thickness, fascicle pennation angle and fascicle length) were correlated with the aforementioned strength and functional measures. Quadriceps thickness was a significant (p < 0.05) independent predictor of isometric and isokinetic knee extensor strength (R² ≥ 0.630). Gastrocnemius medialis thickness was a significant independent predictor of 6-m fast walk test (R² = 0.216, p < 0.05), timed up and go test (R² = 0.455, p < 0.01), stair climb power (R² = 0.591, p < 0.01), stair descent power (R² = 0.608, p < 0.01) and vertical jump height (R² = 0.579, p < 0.01). Ultrasound is a safe, non-invasive and efficient tool for inferring the strength and functional capacity of older adults.

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The Role of Myeloid-Derived Suppressor Cells in Viral Infection

Viral Immunology , Vol. 0, No. 0.

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IFN-γ Attenuates Spontaneous Lymphocyte Proliferation by Fuelling Regulatory T Cells in HIV-1-Infected Patients

Viral Immunology , Vol. 0, No. 0.

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GluR3B Ab’s induced oligodendrocyte precursor cells excitotoxicity via mitochondrial dysfunction

Publication date: Available online 4 January 2017
Source:Brain Research Bulletin
Author(s): Yi Liu, Yan Chen, Wan Tong Du, Xiu Xiang Wu, Fu Xing Dong, Xue Bin Qu, Hong Bin Fan, Rui Qin Yao
Studies have indicated that glutamate receptor subunit 3 peptide B antibodies (GluR3B Ab's) by directing against a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype glutamate receptors (AMPARs) subunit 3 (GluR3B) was involved in the hippocampal neuron damage in the pathogenesis of epilepsy. Glutamate accumulation is critical for oligodendrocyte precursors (OPCs) excitotoxic injury. However, remarkably little is known about whether GluR3B Ab's causes OPCs excitotoxicity, and the underlying mechanisms remain unclear. In this study, we found that the survival rate of OPCs decreased, apoptosis increased and the release of LDH increased with GluR3B Ab's treatment. GluR3B Ab's enhanced the level of intracellular Ca²⁺ and reactive oxygen species (ROS), caused mitochondrial potential collapse measured by JC-1 and promoted mitochondrial cytochrome C release. AMPARs antagonist NBQX reversed OPCs apoptosis caused by GluR3B Ab's. Taken together, these data suggests that AMPAR was involved in GluR3B Ab's-induced OPCs toxicity by mitochondrial dysfunction. The study revealed a new mechanism for OPCs excitotoxicity in many central nervous system diseases such as epilepsy.

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Early Stage Alterations of Catecholamine and Adrenocorticotropic Hormone Levels in Posttraumatic Acute Diffuse Brain Swelling

Publication date: Available online 4 January 2017
Source:Brain Research Bulletin
Author(s): Weiqiang Chen, Jiangtao Sheng, Guoyi Peng, Jinhua Yang, Shousen Wang, Kangsheng Li
Posttraumatic acute diffuse brain swelling (PADBS) is characterized by serious brain bulk enlargement rapidly following trauma and is a major cause of elevated intracranial pressure and thus mortality. The pathogenesis of PADBS is not clearly understood, and the early stage alterations of catecholamine (CA) and adrenocorticotropic hormone (ACTH) levels in PADBS also remain largely unknown. The objective of this study was to investigate CA and ACTH levels in the patients with PADBS in the early stage and discuss the possible roles CA and ACTH in the pathogenesis of PADBS. It is a cross-sectional study. A group of patients with PADBS (n=10) was compared with a group of patients with severe brain injury (SBI) (n=33). A control group of healthy adults (n=25) was also included. Blood samples were obtained to measure levels of epinephrine (EPI), norepinephrine (NE), dopamine (DA), and ACTH as soon as the patients arrived at the neurosurgery department, which was done within 4hours after trauma. Both SBI and PADBS groups of patients had higher levels of EPI, NE, DA, and ACTH than the control group. The PADBS group had significantly higher levels of EPI, NE, and ACTH than the SBI group. CA and ACTH levels are significantly increased in early stage PADBS. These results imply that CA and ACTH may play important roles in the pathogenesis of PADBS. To eliminate the effects of CA and ACTH at the early stage, and thereby protect the hypothalamus and brain stem, might be critical measures for treating patients with PADBS.

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Effect of Almond Supplementation on Glycemia and Cardiovascular Risk Factors in Asian Indians in North India with Type 2 Diabetes Mellitus: A 24-Week Study

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.

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De l’influence de scandales sanitaires sur la réglementation des produits cosmétiques

Publication date: Available online 3 January 2017
Source:Médecine & Droit
Author(s): Laurence Coiffard, Céline Couteau
Les différentes affaires sanitaires qui ont eu lieu en France depuis une quarantaine d'années ont influencé la réglementation des produits cosmétiques. L'influence la plus évidente est celle de « L'affaire du talc Morhange » qui a initié leur réglementation. Par la suite, « L'Affaire du sang contaminé », par le biais de la création de l'Afssaps, a donné aux produits cosmétiques une autorité de tutelle et les fait désormais classer comme des produits de santé. Enfin, plus récemment « L'Affaire Médiator » a entraîné, entre autres, une prise de conscience de la notion de conflits d'intérêt dans le domaine des produits de santé, donc des produits cosmétiques.The various health scandals which have happened in France over the past 40 years have influenced the regulation of cosmetic products. The most obvious influence is the "Talc Morhange Scandal" which triggered their regulation. Then, "the Infected Blood Scandal", through the creation of Afssaps, provided a regulatory authority for cosmetics products and from then onwards, they were classed as health products. Lastly, one of the effects of the more recent "Médiator scandal" was to bring about an awareness concerning the notion of conflicts of interests in the field of health products, therefore including cosmetic products.

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Population-Based National Prevalence of Thyroid Dysfunction in Spain and Associated Factors: Di@bet.es Study

Thyroid , Vol. 0, No. 0.

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Future Meetings

Thyroid Jan 2017, Vol. 27, No. 1: 132-133.

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A Novel Gel Pad Laryngeal Ultrasound for Vocal Cord Evaluation

Thyroid , Vol. 0, No. 0.

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Population-Based National Prevalence of Thyroid Dysfunction in Spain and Associated Factors: Di@bet.es Study

Thyroid , Vol. 0, No. 0.

http://ift.tt/2idb9vb

A Novel Gel Pad Laryngeal Ultrasound for Vocal Cord Evaluation

Thyroid , Vol. 0, No. 0.

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Lessons Learned After 1000 Cases of Transcutaneous Laryngeal Ultrasound (TLUSG) with Laryngoscopic Validation: Is There a Role of TLUSG in Patients Indicated for Laryngoscopic Examination Before Thyroidectomy?

Thyroid Jan 2017, Vol. 27, No. 1: 88-94.

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Future Meetings

Thyroid Jan 2017, Vol. 27, No. 1: 132-133.

http://ift.tt/2iderif

Lessons Learned After 1000 Cases of Transcutaneous Laryngeal Ultrasound (TLUSG) with Laryngoscopic Validation: Is There a Role of TLUSG in Patients Indicated for Laryngoscopic Examination Before Thyroidectomy?

Thyroid Jan 2017, Vol. 27, No. 1: 88-94.

http://ift.tt/2jcnXq4

Gene expression signature: a powerful approach for drug discovery in diabetes

Type 2 diabetes (T2D) is increasing in prevalence at an alarming rate around the world. Much effort has gone into the discovery and design of antidiabetic drugs; however, those already available are unable to combat the underlying causes of the disease and instead only moderate the symptoms. The reason for this is that T2D is a complex disease, and attempts to target one biological pathway are insufficient to combat the full extent of the disease. Additionally, the underlying pathophysiology of this disease is yet to be fully elucidated making it difficult to design drugs that target the mechanisms involved. Therefore, the approach of designing new drugs aimed at a specific molecular target is not optimal and a more expansive, unbiased approach is required. In this review, we will look at the current state of diabetes treatments and how these target the disease symptoms but are unable to combat the underlying causes. We will also review how the technique of gene expression signatures (GESs) has been used successfully for other complex diseases and how this may be applied as a powerful tool for the discovery of new drugs for T2D.

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Absence of 11-keto reduction of cortisone and 11-ketotestosterone in the model organism zebrafish

Zebrafish are widely used as model organism. Their suitability for endocrine studies, drug screening and toxicity assessements depends on the extent of conservation of specific genes and biochemical pathways between zebrafish and human. Glucocorticoids consist of inactive 11-keto (cortisone and 11-dehydrocorticosterone) and active 11β-hydroxyl forms (cortisol and corticosterone). In mammals, two 11β-hydroxysteroid dehydrogenases (11β-HSD1 and 11β-HSD2) interconvert active and inactive glucocorticoids, allowing tissue-specific regulation of glucocorticoid action. Furthermore, 11β-HSDs are involved in the metabolism of 11-oxy androgens. As zebrafish and other teleost fish lack a direct homologue of 11β-HSD1, we investigated whether they can reduce 11-ketosteroids. We compared glucocorticoid and androgen metabolism between human and zebrafish using recombinant enzymes, microsomal preparations and zebrafish larvae. Our results provide strong evidence for the absence of 11-ketosteroid reduction in zebrafish. Neither human 11β-HSD3 nor the two zebrafish 11β-HSD3 homologues, previously hypothesized to reduce 11-ketosteroids, converted cortisone and 11-ketotestosterone (11KT) to their 11β-hydroxyl forms. Furthermore, zebrafish microsomes were unable to reduce 11-ketosteroids, and exposure of larvae to cortisone or the synthetic analogue prednisone did not affect glucocorticoid-dependent gene expression. Additionally, a dual-role of 11β-HSD2 by inactivating glucocorticoids and generating the main fish androgen 11KT was supported. Thus, due to the lack of 11-ketosteroid reduction, zebrafish and other teleost fish exhibit a limited tissue-specific regulation of glucocorticoid action, and their androgen production pathway is characterized by sustained 11KT production. These findings are of particular significance when using zebrafish as a model to study endocrine functions, stress responses and effects of pharmaceuticals.

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Very low-density lipoprotein (VLDL)-induced signals mediating aldosterone production

Aldosterone, secreted by the adrenal zona glomerulosa, enhances sodium retention, thus increasing blood volume and pressure. Excessive production of aldosterone results in high blood pressure and contributes to cardiovascular and renal disease, stroke and visual loss. Hypertension is also associated with obesity, which is correlated with other serious health risks as well. Although weight gain is associated with increased blood pressure, the mechanism by which excess fat deposits increase blood pressure remains unclear. Several studies have suggested that aldosterone levels are elevated with obesity and may represent a link between obesity and hypertension. In addition to hypertension, obese patients typically have dyslipidemia, including elevated serum levels of very low-density lipoprotein (VLDL). VLDL, which functions to transport triglycerides from the liver to peripheral tissues, has been demonstrated to stimulate aldosterone production. Recent studies suggest that the signaling pathways activated by VLDL are similar to those utilized by AngII. Thus, VLDL increases cytosolic calcium levels and stimulates phospholipase D (PLD) activity to result in the induction of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2) expression. These effects seem to be mediated by the ability of VLDL to increase the phosphorylation (activation) of their regulatory transcription factors, such as the cAMP response element-binding (CREB) protein family of transcription factors. Thus, research into the pathways by which VLDL stimulates aldosterone production may identify novel targets for the development of therapies for the treatment of hypertension, particularly those associated with obesity, and other aldosterone-modulated pathologies.

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Antihyperglycemic activity of the bark methanolic extract of Syzygium mundagam in diabetic rats

Publication date: Available online 3 January 2017
Source:Alexandria Journal of Medicine
Author(s): Rahul Chandran, Thangaraj Parimelazhagan, Blassan P. George
The present study was designed to investigate the free radical defence and antihyperglycemic property of S. mundagam. Petroleum ether, ethyl acetate, methanol and hot water extracts of bark were determined for the total phenolic, tannin, flavonoid content and antioxidant property using DPPH, ABTS⁺, phosphomolybdenum, FRAP, superoxide, nitric oxide and metal chelating assays. The antioxidant response was best observed in ABTS⁺ (109686.87μM TE/g extract), phosphomolybdenum (268.54g AAE/100g extract) and superoxide radical scavenging assays (84.30%). Bark methanol extract was found highly efficient in scavenging the free radicals than other extracts. The higher phenolic content (54.44g GAE/100 extract) could be attributed to this effect. The glucose homeostasis was observed till 180th min in glucose loaded rats treated with the bark methanol extract. The extract could also induce potent hypoglycaemia in STZ induced diabetic rats. The antioxidant defence system could be one of the prime mechanisms of S. mundagam leaf and bark extracts that needs to be studied further for the exact molecular action leading to antidiabetic effect.

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Clinical Practice Guidelines for the Use of Video Capsule Endoscopy

Publication date: Available online 4 January 2017
Source:Gastroenterology
Author(s): Robert A. Enns, Lawrence Hookey, David Armstrong, Charles N. Bernstein, Steven J. Heitman, Christopher Teshima, Grigorios I. Leontiadis, Frances Tse, Daniel Sadowski
Background & AimsVideo capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice.MethodsA systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach.ResultsThe consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined.ConclusionsCE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.

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Custom-made fibular “cradle” plate to optimise bony height, contour of the lower border, and length of the pedicle in reconstruction of the mandible

The fibular free flap has become the standard method of reconstruction of the body of the mandible since it was first reported in 1989.1

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Microvascular reconstruction of facial defects in settings where resources are limited

The surgical treatment of defects caused by noma is challenging for the surgeon and the patient. Local flaps are preferred, but sometimes, because of the nature of the disease, there is not enough local tissue available. We describe our experience of free tissue transfer in Ethiopia. Between 2008 and 2014, 34 microsurgical procedures were done over 11 missions with the charity Facing Africa, predominantly for the treatment of defects caused by noma (n=32). The mean duration of operation was 442minutes (range 200 – 720).

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Editorial board

Publication date: January 2017
Source:Microbes and Infection, Volume 19, Issue 1

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Nitro-oleic acid regulates growth factor-induced differentiation of bone marrow-derived macrophages

Publication date: Available online 4 January 2017
Source:Free Radical Biology and Medicine
Author(s): Hana Verescakova, Gabriela Ambrozova, Lukas Kubala, Tomas Perecko, Adolf Koudelka, Ondrej Vasicek, Tanja K. Rudolph, Anna Klinke, Steven R. Woodcock, Bruce A. Freeman, Michaela Pekarova
Many diseases accompanied by chronic inflammation are connected with dysregulated activation of macrophage subpopulations. Recently, we reported that nitro-fatty acids (NO2-FAs), products of metabolic and inflammatory reactions of nitric oxide and nitrite, modulate macrophage and other immune cell functions. Bone marrow cell suspensions were isolated from mice and supplemented with macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with NO2-OA for different times. RAW 264.7 macrophages were used for short-term (1–5min) experiments. We discovered that NO2-OA reduces cell numbers, cell colony formation, and proliferation of macrophages differentiated with colony-stimulating factors (CSFs), all in the absence of toxicity. In a case of GM-CSF-induced bone marrow-derived macrophages (BMMs), NO2-OA acts via downregulation of signal transducer and activator of transcription 5 (STAT5) and extracellular signal-regulated kinase (ERK) activation. In the case of M-CSF-induced BMMs, NO2-OA decreases activation of M-CSFR and activation of related PI3K and ERK. Additionally, NO2-OA also attenuates activation of BMMs. In aggregate, we demonstrate that NO2-OA regulates the process of macrophage differentiation and that NO2-FAs represent a promising therapeutic tool in the treatment of inflammatory pathologies linked with increased accumulation of macrophages in inflamed tissues.

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Linking lipid peroxidation and neuropsychiatric disorders: focus on 4-hydroxy-2-nonenal

Publication date: Available online 4 January 2017
Source:Free Radical Biology and Medicine
Author(s): Adele Romano, Gaetano Serviddio, Silvio Calcagnini, Rosanna Villani, Anna Maria Giudetti, Tommaso Cassano, Silvana Gaetani
4-hydroxy-2-nonenal (HNE) is considered to be a strong marker of oxidative stress; the interaction between HNE and cellular proteins leads to the formation of HNE-protein adducts able to alter cellular homeostasis and cause the development of a pathological state.By virtue of its high lipid concentration, oxygen utilization, and the presence of metal ions participating to redox reactions, the brain is highly susceptible to the formation of free radicals and HNE-related compounds.A variety of neuropsychiatric disorders have been associated with elevations of HNE concentration. For example, increased levels of HNE were found in the cortex of bipolar and schizophrenic patients, while HNE plasma concentrations resulted high in patients with major depression. On the same line, high brain concentrations of HNE were found associated with Huntington's inclusions. The incidence of high HNE levels is relevant also in the brain and cerebrospinal fluid of patients suffering from Parkinson's disease. Intriguingly, in this case the increase of HNE was associated with an accumulation of iron in the substantia nigra, a brain region highly affected by the pathology.In the present review we recapitulate the findings supporting the role of HNE in the pathogenesis of different neuropsychiatric disorders to highlight the pathogenic mechanisms ascribed to HNE accumulation.The aim of this review is to offer novel perspectives both for the understanding of etiopathogenetic mechanisms that remain still unclear and for the identification of new useful biological markers.We conclude suggesting that targeting HNE-driven cellular processes may represent a new more efficacious therapeutical intervention.

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Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τετάρτη 4 Ιανουαρίου 2017

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Αρχειοθήκη ιστολογίου