A hyperpigmented rash on face and chest

http://ift.tt/2EF54Gt

Using a Dihydrofolate Reductase-Based Strategy for Producing the Biosimilar Version of Pertuzumab in CHO-S Cells

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


http://ift.tt/2soT07a

Asymptomatic facial nodules

http://ift.tt/2EYuRqJ

Role of solid lipid nanoparticles as photoprotective agents in cosmetics

Summary

Background

Novel drug delivery systems have gained popularity since last two decades because of its advantages over conventional dosage forms. Effect of UV radiation on skin can cause either acute or chronic damage to our skin. Solid lipid nanoparticles (SLNs) were developed as novel carrier over the conventional carrier systems like liposomes and emulsions. The SLNs were selected as a carrier for the formulation because of its ability to protect the labile drug particles, the ability to make the drug release in a controlled manner, and occlusive property of the SLNs.

Objective

The current review is an attempt to focus on the characteristics of solid lipid nanoparticles, methods for the preparations, and their cosmetic applications along with some future perspectives of the nanodrug delivery systems.

Methods

A review of the current literature of solid lipid nanoparticles (SLNs) as novel carrier showed better photoprotection in sunscreens.

Results and conclusions

The disadvantages of conventional sunscreens can be overcome by incorporation of solid lipid nanoparticles. On comparing the lipid nanobased systems with traditional cosmetic products, the occlusion can be achieved without the use of paraffin and other greasy oils. The film formed by lipid nanoparticles will be smooth as compared to the inflexible films formed by the paraffin. Newer approaches may lead to even better results. They also possess excellent UV-blocking activity and showed better photoprotection.

http://ift.tt/2BqOqIu

Avoiding the Trap of Misdiagnosis: Valuable Teaching Points Derived from a Case of Longstanding Popliteal Artery Entrapment Syndrome

Popliteal artery entrapment syndrome (PAES), a condition predominantly affecting young individuals, is a rare clinical entity that can result in significant morbidity. The presence of lower limb pain and claudication in young, physically active individuals should prompt consideration for PAES. Early diagnosis and management is crucial to prevent long-term complications; however, diagnosis is fraught with challenges due to the rarity of the disease and its similar clinical presentation with more common conditions. We present a case of a young female with PAES who was misdiagnosed and underwent a tarsal tunnel release for suspected tarsal tunnel syndrome and subsequent fasciotomies for presumed chronic exertional compartment syndrome (CECS) without any relief. We outline the insidious undiagnosed course of her condition over a period of 12 years, discuss teaching points of how to recognize key differences of PAES and associated conditions, and provide recommendations for how to make the right diagnosis.

http://ift.tt/2BZmGvT

Bronchoalveolar Lavage Fluid in Children: Comparative Proteomic Analysis in Infectious and Non-Infectious Lung Disease

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2o3KdCl

Cribriform plate width is highly variable within and between subjects

All successful endonasal surgery, including functional endoscopic sinus surgery (FESS), depends on knowledge of both anatomy and the specific variations that can occur between and within patients. Familiarity with these structures is a critical component in preventing complications from these procedures, and failure to understand subtle variation can have disastrous results. The aim of this study was to characterize the anatomical variations (if any) of the cribriform plate using a large cadaveric sample set.

http://ift.tt/2HceXd6

The highs and lows of marijuana use in allergy

In November 2012, Colorado and Washington became the first states to pass initiatives legalizing marijuana use. Since then, voters in 8 states and the district of Columbia have passed similar legislation and Vermont recently announced plans to do so. It is likely that this trend will continue since marijuana sales in legalized states have added significant revenue to state economies. This rapid expansion highlights the need for studies that measure health effects of marijuana use in the population.

http://ift.tt/2su9iMg

Real world evaluation of a mobile health application in children with asthma

Asthma is one of the most prevalent chronic pediatric conditions, affecting approximately 9% of children in the United States.1 Asthma morbidity is significant as exacerbations are a leading cause of emergency department (ED) visits and hospitalizations.2,3 Successful management of asthma, including prevention of ED visits, requires proper diagnosis and treatment, comprehensive patient and family education, and development and utilization of self-management skills. Children and parents must learn to identify and avoid triggers, remain adherent to daily controller therapy, ensure access to rescue medications, and recognize and treat symptoms promptly and appropriately.

http://ift.tt/2BYvVwb

Shifting the Focus: The Primary Role of IL-23 in Psoriasis and other Inflammatory Disorders

Abstract

Insights into the pathophysiology of autoimmune inflammatory diseases including psoriasis have advanced considerably in recent years, and in parallel, so too have the available treatment options. Current clinical paradigms for the treatment of psoriasis have evolved to include targeted biologic therapies, starting with tumor necrosis factor-alpha (TNF-α) inhibitors and later, agents targeting interleukin (IL)-12/23 and IL-17. The most recent evidence suggests that IL-23 might be an even more potent target for the effective treatment of psoriasis and other autoimmune inflammatory disorders. This review will describe recent developments leading to the current understanding of the key role of IL-23 as a 'master regulator' of autoimmune inflammation, and the clinical evidence for agents that specifically target this modulator in the context of treating psoriasis, spondyloarthropathy, and inflammatory bowel disease.

This article is protected by copyright. All rights reserved.

http://ift.tt/2GbwvF2

Large-scale total synthesis of 13 C 3 -labeled citrinin and its metabolite dihydrocitrinone

Abstract

The analysis of the nephrotoxic mycotoxin citrinin in food, feed, and physiological samples is still challenging. Nowadays, liquid chromatography coupled with mass spectrometry is the method of choice for achieving low limits of detection. But matrix effects can present impairments for this method. Stable isotope dilution analysis can prevent some of these problems. Therefore, a stable isotopically labeled standard of citrinin for use in stable isotope dilution analysis was synthesized on large scale. The improved diastereoselective total synthetic strategy offered the possibility to introduce three ¹³C-labels in two steps by ortho-toluate anion chemistry. This led to a mass difference of 3 Da, sufficient for preventing spectral overlap. Additionally, a stable isotopically labeled form of dihydrocitrinone, the main urinary metabolite of citrinin, was synthesized with the same mass difference. This was achieved by a sequence of cyclisation, oxidation, deprotection, and carboxylation reactions starting from a protected intermediate of the labeled citrinin synthesis. Thus, this method also offers a complete way to synthesize dihydrocitrinone from citrinin on large scale.

http://ift.tt/2EpaIJD

Reply to Raison and Raichlen: Why does nutrition impact social decision making? [Social Sciences]

In our PNAS article (1), we show how the macronutrient composition of a meal can impact social decision making. Specifically, with a greater protein intake, participants' plasma tyrosine levels were elevated, which resulted in a more tolerant participants' response toward unfair offers. In other words, with a greater carbohydrate intake,...

http://ift.tt/2EBOnfc

Reply to Lund: Where does the gravitostat fit in? [Biological Sciences]

We appreciate the thoughtful reflection by Jens Lund (1) on different aspects of our recent article in PNAS (2). Lund is right to point out that results from studies of the effects of hypergravity on body mass and body fat in rodents support the gravitostat hypothesis (2). Hypergravity and increased...

http://ift.tt/2stRiS3

An evolutionary perspective on nutrition and social decision making [Social Sciences]

We were intrigued by findings reported by Strang et al. (1) that the balance of carbohydrate to protein in a breakfast preparation influenced subsequent human social decision making. Specifically, compared with a low-carbohydrate/high-protein breakfast, consumption of a high-carbohydrate/low-protein breakfast increased participants' tendency to punish violations of social norms, assessed as...

http://ift.tt/2EESebm

Weighing the evidence for a body mass-regulating gravitostat [Biological Sciences]

The intriguing paper by Jansson et al. (1) reports the identification of a body mass-regulating homeostat that operates in rodents independently of leptin. In response to implantation of capsules weighing 15% of body weight the authors observed that ∼80% of this load was offset by a reduction in biological body...

http://ift.tt/2BueYsE

Phosphatidylinositol-(4, 5)-bisphosphate regulates calcium gating of small-conductance cation channel TMEM16F [Physiology]

TMEM16F, which is activated by elevation of intracellular calcium to trigger phospholipid scrambling and the collapse of lipid bilayer asymmetry to mediate important cellular functions such as blood coagulation, also generates a small-conductance calcium-activated cation current. How TMEM16F activation may be regulated is an open question. By recording TMEM16F Ca2+-activated...

http://ift.tt/2EBO2cq

Stimulus generalization as a mechanism for learning to trust [Psychological and Cognitive Sciences]

How do humans learn to trust unfamiliar others? Decisions in the absence of direct knowledge rely on our ability to generalize from past experiences and are often shaped by the degree of similarity between prior experience and novel situations. Here, we leverage a stimulus generalization framework to examine how perceptual...

http://ift.tt/2swWncC

Proȷecting one’s own spatial bias onto others during a theory-of-mind task [Psychological and Cognitive Sciences]

Many people show a left-right bias in visual processing. We measured spatial bias in neurotypical participants using a variant of the line bisection task. In the same participants, we measured performance in a social cognition task. This theory-of-mind task measured whether each participant had a processing-speed bias toward the right...

http://ift.tt/2EDOreg

Correction for Sanderman et al., Soil carbon debt of 12,000 years of human land use [Correction]

SUSTAINABILITY SCIENCE Correction for "Soil carbon debt of 12,000 years of human land use," by Jonathan Sanderman, Tomislav Hengl, and Gregory J. Fiske, which was first published August 21, 2017; 10.1073/pnas.1706103114 (Proc Natl Acad Sci USA 114:9575–9580). The authors would like to note the following: "We regret that two small...

http://ift.tt/2BsbW7W

Correction for Das, Unfounded assumptions in linking crop-damaging temperature and suicide in India [Correction]

LETTER Correction for "Unfounded assumptions in linking crop-damaging temperature and suicide in India," by Saudamini Das, which was first published December 29, 2017; 10.1073/pnas.1715331115 (Proc Natl Acad Sci USA 115:E116). The editors note that, in the first paragraph, line 2, "suicides during 1987–2013" should instead appear as "suicides during 1980–2013."...

http://ift.tt/2EDOfM4

Economic value of ecological information in ecosystem-based natural resource management depends on exploitation history [Sustainability Science]

Ecosystem approaches to natural resource management are seen as a way to provide better outcomes for ecosystems and for people, yet the nature and strength of interactions among ecosystem components is usually unknown. Here we characterize the economic benefits of ecological knowledge through a simple model of fisheries that target...

http://ift.tt/2BrQWhK

Restoring GABAergic inhibition rescues memory deficits in a Huntington’s disease mouse model [Neuroscience]

Huntington's disease (HD) is classically characterized as a movement disorder, however cognitive impairments precede the motor symptoms by ∼15 y. Based on proteomic and bioinformatic data linking the Huntingtin protein (Htt) and KCC2, which is required for hyperpolarizing GABAergic inhibition, and the important role of inhibition in learning and memory,...

http://ift.tt/2EGiTo8

On the complex dynamics of savanna landscapes [Applied Mathematics]

Simple mathematical models can exhibit rich and complex behaviors. Prototypical examples of these drawn from biology and other disciplines have provided insights that extend well beyond the situations that inspired them. Here, we explore a set of simple, yet realistic, models for savanna–forest vegetation dynamics based on minimal ecological assumptions....

http://ift.tt/2Bs2TnB

Anti-PD-1/anti-CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8+ T cell trafficking [Immunology and Inflammation]

Inhibition of immune checkpoints programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on T cells results in durable antitumor activity in melanoma patients. Despite high frequency of melanoma brain metastases (BrM) and associated poor prognosis, the activity and mechanisms of immune checkpoint inhibitors (ICI) in metastatic tumors...

http://ift.tt/2EGNAJR

RNA force field with accuracy comparable to state-of-the-art protein force fields [Biophysics and Computational Biology]

Molecular dynamics (MD) simulation has become a powerful tool for characterizing at an atomic level of detail the conformational changes undergone by proteins. The application of such simulations to RNA structures, however, has proven more challenging, due in large part to the fact that the physical models ("force fields") available...

http://ift.tt/2st8Td0

Farming the mitochondrial ancestor as a model of endosymbiotic establishment by natural selection [Evolution]

The origin of mitochondria was a major evolutionary transition leading to eukaryotes, and is a hotly debated issue. It is unknown whether mitochondria were acquired early or late, and whether it was captured via phagocytosis or syntrophic integration. We present dynamical models to directly simulate the emergence of mitochondria in...

http://ift.tt/2EAYTDp

Landau-Ginzburg theory of cortex dynamics: Scale-free avalanches emerge at the edge of synchronization [Biophysics and Computational Biology]

Understanding the origin, nature, and functional significance of complex patterns of neural activity, as recorded by diverse electrophysiological and neuroimaging techniques, is a central challenge in neuroscience. Such patterns include collective oscillations emerging out of neural synchronization as well as highly heterogeneous outbursts of activity interspersed by periods of quiescence,...

http://ift.tt/2BrJ3J5

Pyruvate cycle increases aminoglycoside efficacy and provides respiratory energy in bacteria [Microbiology]

The emergence and ongoing spread of multidrug-resistant bacteria puts humans and other species at risk for potentially lethal infections. Thus, novel antibiotics or alternative approaches are needed to target drug-resistant bacteria, and metabolic modulation has been documented to improve antibiotic efficacy, but the relevant metabolic mechanisms require more studies. Here,...

http://ift.tt/2EGOF4a

Superresolution imaging of individual replication forks reveals unexpected prodrug resistance mechanism [Chemistry]

Many drugs require extensive metabolism en route to their targets. High-resolution visualization of prodrug metabolism should therefore utilize analogs containing a small modification that does not interfere with its metabolism or mode of action. In addition to serving as mechanistic probes, such analogs provide candidates for theranostics when applied in...

http://ift.tt/2BsbvdU

TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain [Pharmacology]

The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in nociceptors where, when activated by chemical or thermal stimuli, it functions as an important transducer of painful and itch-related stimuli. Although the interaction of TRPV1 with proteins that regulate its function has been previously explored, their modulation by...

http://ift.tt/2EGOvd4

Wireless optoelectronic photometers for monitoring neuronal dynamics in the deep brain [Engineering]

Capabilities for recording neural activity in behaving mammals have greatly expanded our understanding of brain function. Some of the most sophisticated approaches use light delivered by an implanted fiber-optic cable to optically excite genetically encoded calcium indicators and to record the resulting changes in fluorescence. Physical constraints induced by the...

http://ift.tt/2spTWs9

Editorial Board

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106





http://ift.tt/2Cimq6K

In Memoriam: Jun-Ichi Suzuki, MD, PhD, 1929 to 2017

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): Kimitaka Kaga




http://ift.tt/2EsLHAY

Whole exome sequencing identifies a pathogenic mutation in WFS1 in two large Chinese families with autosomal dominant all-frequency hearing loss and prenatal counseling

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): Hongbo Cheng, Qin Zhang, Wenbin Wang, Qingxia Meng, Fuxin Wang, Minjuan Liu, Jun Mao, Yichao Shi, Wei Wang, Hong Li
ObjectivesTo identify the pathogenic mutation and provide prenatal counseling and diagnosis in two large Chinese families with autosomal dominant all-frequency hearing loss.MethodsWhole exome sequencing technology was used to identify the pathogenic mutation of the two families. In addition, 298 patients with sporadic hearing loss and 400 normal controls were studied to verify the mutation/polymorphism nature of the identified variant. Prenatal diagnosis was carried out.ResultsA rare missense mutation c.2389G > A (p.D572N) in the Wolframin syndrome 1 (WFS1) gene was identified. It was reported in only one previous Chinese study, and never in other populations/ethnicities. The mutation was also found in one patient with sporadic hearing loss (1/298, 0.3%). A healthy baby was born after prenatal diagnosis.ConclusionOur findings strongly suggest that the c.2389G > A mutation in WFS1 is associated with all-frequency hearing loss, rather than low- or high-frequency loss. So far, the mutation is only reported in Chinese. Prenatal diagnosis and prenatal counseling is available for these two Chinese families.



http://ift.tt/2ChOmrq

Total congenital sternal cleft isolated in a newborn of 20 days: Rare case

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): Dounia Basraoui, Badia Bannar, Mohamed Ouladsaiad, Hicham Jalal
Sternal clefts are rare malformations, especially in their complete form, which results from a lack of fusion of the sternal bars, which is normally done at the 9th week of intra uterine life. The incomplete form is often associated with other malformations of the chest wall, or falling within the framework of a polymalformative syndrome, the diagnosis is easy, being done with the inspection and the palpation, the paraclinical examinations are useful for confirming the diagnosis. We report the case of a total congenital sternal cleft isolated in an asymptomatic 20-day-old newborn. Thoracic CT, with threedimensional reconstructions, without injection of the contrast product confirmed the diagnosis, showing the presence of two hemistonids hypoplastic.The aim of our work is to draw attention to this pathology from birth because surgery must be undertaken during the first weeks of life to protect the heart and large vessels from any trauma, to improve respiratory dynamics and for aesthetic reasons.



http://ift.tt/2Eozr4B

Prognostic value of age, subglottic, and anterior commissure involvement for early glottic carcinoma treated with CO 2 laser transoral microsurgery: a retrospective, single-center cohort study of 261 patients

Abstract

Purpose

 CO₂ laser transoral microsurgery for glottic carcinoma, when indicated, has the well-established advantages of low morbidity and positive oncological outcomes. The present study aims to determine how patient age, and tumor site could negatively impact prognosis; other variables such as the status of the margins of resection, tobacco and alcohol intake, and the grade of differentiation of the tumors have been evaluated.

Methods

This was a retrospective analysis on 261 patients with a glottic carcinoma who underwent CO₂ laser transoral microsurgery. The impact of different variables was calculated using univariate and multivariate analyses.

Results

The study included 248 males and 13 females. The median follow-up period was 4.3 years. Five-year disease-specific survival, recurrence-free survival, local control with laser alone, overall laryngeal preservation, and overall survival rates were 99.4, 92.2, 93.8, 97.6, and 85.5%, respectively. Equivalent results were observed in young and elderly patients. Patients with positive margins after CO₂ laser transoral microsurgery showed a reduced local control with laser alone. T2 patients with true subglottic spreading and patients with anterior commissure involvement of grade 3 (Rucci's classification) experienced worse local control rates, despite free surgical margins confirmed by histology.

Conclusions

 CO₂ laser transoral microsurgery is an effective and reproducible single-stage modality therapy for young and elderly patients with glottic carcinoma. Superficial close margins can be managed by a careful wait-and-see policy, while positive margins should undergo surgical enlargement. In our experience, undifferentiated tumors, true subglottic extension, and anterior commissure involvement of grade 3 were associated with worse outcomes.

http://ift.tt/2Hb7g75

Open access: is there a predator at the door?

http://ift.tt/2EDx65a

INDEX

http://ift.tt/2srOdSt

International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis

Background

Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).

Methods

Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.

Results

The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR.

Conclusion

This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

http://ift.tt/2EG2bVR

Issue Information

http://ift.tt/2suHw2a

International consensus statement on allergy and rhinology: allergic rhinitis—executive summary

Background

The available allergic rhinitis (AR) literature continues to grow. Critical evaluation and understanding of this literature is important to appropriately utilize this knowledge in the care of AR patients. The International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR) has been produced as a multidisciplinary international effort. This Executive Summary highlights and summarizes the findings of the comprehensive ICAR:AR document.

Methods

The ICAR:AR document was produced using previously described methodology. Specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.

Results

Over 100 individual topics related to AR diagnosis, pathophysiology, epidemiology, disease burden, risk factors, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR were addressed in the comprehensive ICAR:AR document. Herein, the Executive Summary provides a synopsis of these findings.

Conclusion

In the ICAR:AR critical review of the literature, several strengths were identified. In addition, significant knowledge gaps exist in the AR literature where current practice is not based on the best quality evidence; these should be seen as opportunities for additional research. The ICAR:AR document evaluates the strengths and weaknesses of the AR literature. This Executive Summary condenses these findings into a short summary. The reader is also encouraged to consult the comprehensive ICAR:AR document for a thorough description of this work.

http://ift.tt/2EGuYJZ

Neutrophils drive type-I interferon production and autoantibodies in Wiskott-Aldrich syndrome

Publication date: Available online 13 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): K.E. Cervantes-Luevano, N. Caronni, M.C. Castiello, E. Fontana, G. Piperno, A. Naseem, P. Uva, M. Bosticardo, G.E. Marcovecchio, L.D. Notarangelo, M.P. Cicalese, A. Aiuti, A. Villa, F. Benvenuti
BackgroundWiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency caused by mutations in WASp, a key regulator of cytoskeletal dynamics in hematopoietic cells. A high proportion of patients develop autoimmunity due to a breakdown in T and B cell tolerance. Moreover, excessive production of type-I interferon by plasmacytoid DCs contribute to autoimmune signs, however, the factors that triggers excessive innate activation have not been defined.ObjectiveNeutrophils extracellular traps (NETs) emerged as major initiating factors in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In this study, we explored the possible involvement of aberrant neutrophil functions in WAS.MethodsWe evaluated the expression of a set of granulocyte genes associated with NETs in a cohort of WAS patients and the presence of NET-inducers in sera. Using a mouse model of WAS, we analyzed NET release by WASp-null neutrophils, and we evaluated the composition and homeostasis of neutrophils in vivo. By means of depletion experiments, we assessed the impact of neutrophils in promoting inflammation and reactivity against auto-antigens.ResultsTranscripts of genes encoding neutrophil enzymes and antimicrobial peptides were elevated in granulocytes of WAS patients, and serum soluble factors triggered NET release. WASp-null neutrophils showed increased spontaneous NETosis, induced type-I interferon production by plasmacytoid DCs (pDCs), and activated B cells via BAFF. Consistently, their depletion abolished constitutive pDCs activation, normalized circulating IFN-I levels and, importantly, abolished production of autoantibodies directed against dsDNA, nucleosomes and MPO.ConclusionsThese findings reveal that neutrophils are involved in the pathogenic loop that causes excessive activation of innate cells and autoreactive B cell, thus identifying novel mechanisms that contribute to the autoimmunity of WAS.

Graphical abstract

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Diagnostic flexible pharyngo-laryngoscopy: development of a procedure specific assessment tool using a Delphi methodology

Abstract

Purpose

Proper training and assessment of skill in flexible pharyngo-laryngoscopy are central in the education of otorhinolaryngologists. To facilitate an evidence-based approach to curriculum development in this field, a structured analysis of what constitutes flexible pharyngo-laryngoscopy is necessary. Our aim was to develop an assessment tool based on this analysis.

Methods

We conducted an international Delphi study involving experts from twelve countries in five continents. Utilizing reiterative assessment, the panel defined the procedure and reached consensus (defined as 80% agreement) on the phrasing of an assessment tool.

Results

Fifty panelists completed the Delphi process. The median age of the panelists was 44 years (range 33–64 years). Median experience in otorhinolaryngology was 15 years (range 6–35 years). Twenty-five were specialized in laryngology, 16 were head and neck surgeons, and nine were general otorhinolaryngologists. An assessment tool was created consisting of twelve distinct items.

Conclusion

The gathering of validity evidence for assessment of core procedural skills within Otorhinolaryngology is central to the development of a competence-based education. The use of an international Delphi panel allows for the creation of an assessment tool which is widely applicable and valid. This work allows for an informed approach to technical skills training for flexible pharyngo-laryngoscopy and as further validity evidence is gathered allows for a valid assessment of clinical performance within this important skillset.

http://ift.tt/2EGh8XQ

A comparison of Dysphonia Severity Index and Acoustic Voice Quality Index measures in differentiating normal and dysphonic voices

Abstract

Purpose

The aim of the study was to investigate and compare the feasibility and robustness of the Acoustic Voice Quality Index (AVQI) and the Dysphonia Severity Index (DSI) in diagnostic accuracy, differentiating normal and dysphonic voices.

Methods

A group of 264 subjects with normal voices (n = 105) and with various voice disorders (n = 159) were asked to read aloud a text and to sustain the vowel /a/. Both speech tasks were concatenated, and perceptually rated for dysphonia severity by five voice clinicians. They rated the Grade (G) and the overall dysphonia severity with a visual analog scale (VAS). All concatenated voice samples were acoustically analyzed to receive an AVQI score. For DSI analysis, the required voice parameters were obtained from the sustained phonation of the vowel /a/.

Results

The results achieved significant and marked concurrent validity between both auditory-perceptual judgment procedures and both acoustic voice measures. The DSI threshold (i.e., DSI = 3.30) pertaining to G_mean obtained reasonable sensitivity of 85.8% and specificity of 83.4%. For VAS_mean, the DSI threshold of 3.30 was determined also with reasonable sensitivity of 70.3% and excellent specificity of 93.9%. Also, the AVQI threshold (i.e., AVQI = 3.31) pertaining to G_mean demonstrated reasonable sensitivity of 78.1% and excellent specificity of 92.0%. For VAS_mean, an AVQI threshold of 3.33 was determined with excellent sensitivity of 97.0% and reasonable specificity of 81.8%.

Conlusion

The outcomes of the present study indicate comparable results between DSI and AVQI with a high level of validity to discriminate between normal and dysphonic voices. However, a higher level of accuracy was yielded for AVQI as a correlate of auditory perceptual judgment suggesting a reliable voice screening potential of AVQI.

http://ift.tt/2o7cKqS

Medical Cannabis During Chemoradiation for Head and Neck Cancer

Condition:   Head and Neck Cancer
Intervention:   Other: Certification of medical cannabis
Sponsor:   Albert Einstein College of Medicine, Inc.
Not yet recruiting

http://ift.tt/2o4aXCF

TAK228 With Carbo and Taxol in Advanced Malignancies

Conditions:   Malignant Neoplasm of Breast;   Malignant Neoplasms of Bone and Articular Cartilage;   Malignant Neoplasms of Digestive Organs;   Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System;   Malignant Neoplasms of Female Genital Organs;   Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites;   Malignant Neoplasms of Independent (Primary) Multiple Sites;   Malignant Neoplasms of Lip Oral Cavity and Pharynx;   Malignant Neoplasms of Male Genital Organs;   Malignant Neoplasms of Mesothelial and Soft Tissue;   Malignant Neoplasms of Respiratory and Intrathoracic Organs;   Malignant Neoplasms of Thyroid and Other Endocrine Glands;   Malignant Neoplasms of Urinary Tract;   Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic
Interventions:   Drug: TAK-228;   Drug: Paclitaxel;   Drug: Carboplatin
Sponsors:   M.D. Anderson Cancer Center;   Takeda
Not yet recruiting

http://ift.tt/2nWsHAI

A Study of BGB-A317 Versus Chemotherapy as Second Line Treatment in Patients With Advanced Esophageal Squamous Cell Carcinoma

Condition:   Esophageal Squamous Cell Carcinoma (ESCC)
Interventions:   Drug: BGB-A317;   Drug: Paclitaxel, or Docetaxel, or Irinotecan
Sponsor:   BeiGene
Recruiting

http://ift.tt/2o2CMeP

Study of REGN2810 in Adults With Cervical Cancer

Condition:   Recurrent or Metastatic, Platinum-refractory Cervical Cancer
Interventions:   Drug: REGN2810;   Drug: Investigator Choice (IC) Chemotherapy
Sponsors:   Regeneron Pharmaceuticals;   Sanofi
Recruiting

http://ift.tt/2nUcA6P

SNOT-22–based clusters in chronic rhinosinusitis without nasal polyposis exhibit distinct endotypic and prognostic differences

Background

Endotypic and prognosticating features of chronic rhinosinusitis without nasal polyposis (CRSsNP) are poorly understood. Our objectives were to use an unbiased symptom-based approach to: (1) study symptoms, clinical and endotypic features; and (2) identify features predicating outcomes from endoscopic sinus surgery (ESS).

Methods

Clinical, computed tomography (CT), histopathology, and 22-item Sino-Nasal Outcome Test (SNOT-22) data was collected on 146 adult CRSsNP patients who underwent ESS. Unsupervised network modeling of presurgical SNOT-22 scores was performed to classify symptom-based clusters. Subject characteristics and post-ESS SNOT-22 scores were compared between clusters.

Results

Baseline characteristics of the subject population were as follows: females, 56.2%; revision ESS status in 35%; asthma prevalence, 32.6%; median Lund-Mackay CT score, 8; and median SNOT-22 total score, 43. Network mapping and unsupervised clustering of preoperative SNOT-22 scores revealed 4 clusters: (A) severely burdened with high scores in all 4 subdomains; (B) moderately burdened with high scores in the rhinologic subdomain; (C) moderately burdened with high scores in psychological-sleep subdomains; and (D) mildly burdened. The number of previous ESS and asthma prevalence differed significantly between clusters; CT scores were similar. Asthma burden and tissue eosinophilia were greatest in cluster A (p = 0.03). All groups showed significant improvement at 3 months post-ESS (p < 0.0001). At 6 months, patients in cluster C tended to worsen.

Conclusion

SNOT-22–based network modeling of CRSsNP patients yielded 4 clusters with distinct features. Asthma prevalence and tissue eosinophilia were highest in the cluster with highest SNOT-22 scores. All patients showed significant improvement from ESS at 3 months; those with high sleep-psychosocial symptoms tended to show worsening at 6 months.

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Media Tip Sheet: Making the Call and Giving Out the Gold: How Our Brains Judge Value in an Instant

As the Winter Olympics begin, the world will be marveling at feats performed by athletes at the top of their game. But how do judges distinguish, in just a split second, a gold medal-winning performance from a silver?

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Interrater variability in ASA physical status assignment: an analysis in the pediatric cancer setting

Abstract

Background

The American Society of Anesthesiologists (ASA) physical status is a universal classification system that helps clinicians to categorize their patients preoperatively. However, there is a lack of both inter-rater and intra-rater reliability among clinicians for the ASA physical status classification. Our study focuses on testing these reliabilities within pediatric anesthesia providers in the cancer setting.

Methods

In our retrospective observational study, a total of 1177 anesthesia records were reviewed. The cohort included all pediatric patients (≤ 18 years old) diagnosed with either retinoblastoma or neuroblastoma who had two or more anesthesia procedure within a 14-day time period.

Results

Overall, the ASA physical status score among two different anesthesia providers for the same patient treated at different times had very little inter-rater reliability, κ = − 0.042 (95% CI − 0.17; 0.09). Of the 1177-patient anesthesia records, only 25% had two or more ASA physical status score assigned by the same anesthesiologist within a 14-day time period. There was moderate intra-rater reliability κ = 0.48 (95% CI 0.29; 0.68) for patients who were assigned an ASA physical status score by the identical anesthesia provider at different times points within a 14 day period.

Conclusion

In contrast to observations in earlier studies, findings indicate poor agreement in inter-rater reliability. Although there was moderate agreement in intra-rater reliability, one would expect to find stronger, even perfect, intra-rater reliability. These findings suggest the need to develop a specific physical status classification system directed toward patients with a systemic illness such as cancer in both young and adult patients.

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Anterosuperior anchoring myringoplasty using cyanoacrylate glue can prevent packing gelfoam in the middle ear cavity

Publication date: Available online 12 February 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): Y. Li, J. Liang, Y. Cheng, Q. Zhang, X. Ren, Y. Sheng
ObjectivesAlthough a number of methods have been attempted to improve securing the graft, packing gelfoam in the middle ear cavity cannot be avoided, which could obstruct the tympanic ostium of the Eustachian tube and affect inner ear function. Myringoplasty using tissue adhesive has gained traction because tissue adhesives can effectively stabilise the graft and act as scaffolding to improve the graft uptake. The aim of this prospective study was to explore myringoplasty using cyanoacrylate glue with no packing in the middle ear cavity for the repair of subtotal tympanic membrane (TM) perforations.MethodsBetween March 2014 and November 2015, 71 patients with subtotal TM perforations were randomly and prospectively divided into a glue group and a control group. Two securing techniques were performed using only cyanoacrylate glue or using only filling gelfoam in the middle ear cavity, respectively, during an anterosuperior anchoring myringoplasty operated by a single surgeon.ResultsAt a 6-month follow-up, the graft uptake rate was 87% in the glue group and 89% in the control group. A significant hearing improvement was found in both groups postoperatively when compared to the preoperative values (P<0.05 for both). There was no significant difference in the graft uptake rate and hearing improvement between the 2 groups (P>0.05). Similar complications were found in each group.ConclusionCyanoacrylate glue is a helpful material for graft stabilisation and can substitute for filling gelfoam in the middle ear cavity during anterosuperior anchoring myringoplasty for subtotal TM perforation.



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Pregnancy outcome in a pregnant patient with idiopathic Pulmonary Arterial Hypertension: a case report and review of the literature

Idiopathic pulmonary arterial hypertension is a rare and progressive condition which is aggravated by the physiologic changes during pregnancy. Because of high mortality rate, most physicians recommend early t...

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Definition and diagnosis of asthma–COPD overlap (ACO)

Publication date: Available online 9 February 2018
Source:Allergology International
Author(s): Satoru Yanagisawa, Masakazu Ichinose
It is now widely recognized that asthma and COPD can coexist as asthma–COPD overlap (ACO), but the preliminary attempts at providing universal guidelines for the diagnosis of ACO still need to be improved. We believe that a case can be made for devising guidelines for the diagnosis of this increasingly common disease that are specific to Japan. In this paper, we present our consensus-based description of ACO which we believe is realistic for use in our country. In addition, we cite the scientific evidence for our own "objective" features used to develop the criteria for COPD and asthma diagnosis. We acknowledge that they will need to be validated and updated over time, but hope the results will encourage further research on the characteristics and treatment of this commonly encountered clinical problem.



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A case of contact dermatitis and contact urticaria syndrome due to multiple allergens observed in a professional baseball player

Publication date: Available online 1 February 2018
Source:Allergology International
Author(s): Kaoru Nishiwaki, Yuka Matsumoto, Kosuke Kishida, Muneaki Kaku, Ryoji Tsuboi, Yukari Okubo




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The optimal age for epicutaneous sensitization following tape-stripping in BALB/c mice

Publication date: Available online 10 February 2018
Source:Allergology International
Author(s): Masato Tamari, Keisuke Orimo, Kenichiro Motomura, Ken Arae, Akio Matsuda, Susumu Nakae, Hirohisa Saito, Hideaki Morita, Kenji Matsumoto
BackgroundDirect contact of food proteins with eczematous lesions is thought to be the main cause of epicutaneous sensitization. To further investigate the development and pathogenesis of food allergy in vivo, a good mouse model of epicutaneous sensitization is needed. However, a fundamental problem in that regard is that the optimal age for epicutaneous sensitization of mice is unknown. In this study, we attempted to elucidate that optimal age.MethodsDorsal skin of wild-type BALB/c female mice (1, 3, 8 and 24 weeks old) was shaved, depilated and tape-stripped. A Finn chamber containing a 20-μl-aliquot of 20-mg/ml (OVA) was applied to the tape-stripped skin on 3 consecutive days/week, for 3 weeks. The body temperature was measured after intraperitoneal OVA challenge. Serum OVA-specific IgE titers and OVA-induced cytokine production by spleen cells were measured by ELISA. Dendritic cells (DCs) that migrated to the draining lymph nodes were quantified by FITC-labeled OVA and flow cytometry. The mRNA expression levels in the dorsal skin were measured by qPCR.ResultsA significant age-dependent body temperature decline was observed after OVA challenge. The serum OVA-specific IgE titer, OVA-induced cytokine production (i.e., IL-4, IL-5 and IL-13) by spleen cells, and number of FITC-OVA-engulfing DCs increased with age. In addition, mRNA for IL-33, but not TSLP or IL-25, was significantly induced in the skin by tape-stripping and increased with age.ConclusionsTwenty-four-week-old mice showed the greatest DC migration, Th2 polarization, IgE production and body temperature decline. Skin-derived IL-33 is likely to play key roles in those changes.



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Spontaneous alveolar bone loss after 4NQO exposure in Wistar rats

Publication date: May 2018
Source:Archives of Oral Biology, Volume 89
Author(s): Harry J.R. Oballe, Francisco Wilker M.G. Muniz, Cheyenne C. Bueno, Isadora P. Klein, Vinicius C. Carrard, Cassiano K. Rösing, Eduardo J. Gaio
ObjectiveThis study evaluated the effect of an experimental carcinogenic, 4-Nitroquinoline 1-oxide (4NQO), in the spontaneous alveolar bone loss (ABL) in an animal model.DesignTwenty-two male Wistar rats were included in this study. They were randomly divided into two groups: the control group (n = 10) received food and water ad libitum, and the test group (n = 12) receive the same food; however, 25 ppm of 4NQO was diluted in the drinking water. All animals were euthanized after 20 weeks, and the tongues were removed and analyzed macroscopically to determine the presence of oral mucosal lesions. All specimens were paraffin-embedded and histological sections were obtained. The microscopic analysis was based on routine procedure (haematoxylin and eosin stain). The analysis of spontaneous ABL was performed by a calibrated examiner using standardized photographs and imaging software. Differences in spontaneous ABL were assessed among the three resulting groups: control, 4NQO with oral squamous cell carcinoma (OSCC), and 4NQO without OSCC.ResultsIn the 4NQO-treated group, nine animals developed OSCC. The animals in the 4NQO with OSCC group presented significantly more spontaneous ABL (0.65 ± 0.21 mm) than the control group (0.34 ± 0.05) (p < 0.001). The animals in the 4NQO without OSCC group showed a mean spontaneous ABL of 0.47 ± 0.13 mm, which was not statistically significant different when compared to the control group (p = 0.096).ConclusionsIt was concluded that the presence of OSCC enhanced spontaneous ABL in Wistar rats when compared to control animals. Additionally, it was shown that, solely, administration of 4NQO may not be considered responsible for alveolar bone destruction.



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Laparoscopic endoscopic combined surgery for removal of migrated coil after embolization of ruptured splenic artery aneurysm

Abstract

Splenic artery aneurysm is the most common visceral arterial aneurysm. Rupture of aneurysm is a rare event but associated with a high mortality. Endovascular coil embolization of bleeding splenic artery aneurysm has emerged as a promising minimal invasive treatment and considered safer than open surgery in selected patients. Nevertheless, several complications related to coils have been reported, the rarest being coil migration and erosion. We report a case of splenic artery coil migration into the stomach and its successful removal by laparoscopic endoscopy combined surgery.

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Solitary pancreatic head metastasis from tibial adamantinoma: a rare indication to pancreaticoduodenectomy

Abstract

Pancreatic metastases are rare, <2% of all pancreatic neoplasia. This is the first case of pancreatic metastasis from adamantinoma, a rare, low grade and slow growing tumor which is frequently localized in long bones. We describe a case of a 45-year-old woman presenting with increased bilirubin level. Computed tomography and ecoendoscopic ultra sonography revealed a pancreatic head mass. Fine-needle aspiration biopsy was consistent with metastatic adamantinoma. The patient was submitted to a standard pancreaticoduodenectomy. As in the case presented, standard pancreatic resections are safe and feasible options to treat non-pancreatic primary tumor improving patient's survival and quality of life.

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A case of chronic left main trunk occlusion treated with off-pump coronary artery bypass grafting

Abstract

Ischemic heart disease presents with various symptoms, and chest pain is a chief complaint. Occlusion of the left main trunk often results in serious symptoms such as cardiogenic shock. However, while extremely rare, left main trunk occlusion can present with only slight chronic symptoms. In the present case, a 62-year-old woman with few risk factors for ischemic heart disease visited our hospital complaining of exertional chest pain, which had gradually intensified over the past several years. Coronary artery computed tomography revealed total occlusion of the left main trunk, which was examined closely using coronary angiography. Coronary angiography showed that the left coronary artery was perfused by collateral pathways from the right coronary artery. The patient was thus diagnosed with chronic occlusion of the left main trunk. She underwent off-pump coronary artery bypass grafting, which proved to be an effective treatment.

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Asthma mobile applications: are they ready for prime time?

Publication date: Available online 12 February 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Michael S. Blaiss




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Face-to-face anti-tobacco intervention lowered cotinine level in asthmatic children

Publication date: Available online 12 February 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Stelmach Włodzimierz, Mitał Marcin, Stelmach Iwona, Jerzyńska Joanna, Krakowiak Jan




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Interleukin-25 and eosinophils progenitor cell mobilization in allergic asthma

Eosinophil-lineage committed progenitor cells (EoP) migrate from the bone marrow and differentiate locally to provide an ongoing source of mature eosinophils in asthmatic inflammatory responses in the airways....

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A review of the role of estrogen in dermal aging and facial attractiveness in women

Summary

Estrogens are known to have protective and favorable influences on skin health; conversely, androgens oppose the actions of estrogens. Estrogen's chemical messages are transmitted via the classical nuclear hormone estrogen receptors (ER) alpha and beta and the rapid-acting G-coupled membrane estrogen receptor. Androgens [both testosterone and 5α-dihydrotestosterone (5α-DHT)] bind the same androgen receptor. Estrogen levels peak in the mid- to late 20s in women and then decline by 50% by 50 years of age and dramatically decrease further after menopause. The loss of estrogens with aging contributes to diminished dermal health, whereas estrogen hormone therapy [eg, oral conjugated equine estrogens (CEE)] restores skin health. Several reports suggest positive correlations between the levels of circulating estrogens and: (1) perceived age, (2) attractiveness, (3) enhanced skin health, and (4) facial coloration in women. Based upon a psychological dermato-endocrine perspective, the positive correspondence of high estrogens levels with perceived age and facial attractiveness in women especially with aging demonstrates the importance of hormonal influences on observed dermal health and youthful appearance.

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Urethral Caruncle Presented as Premature Menarche in a 4-Year-Old Girl

Urethral caruncle (UC) is a benign fleshy outgrowth at the urethral meatus. It was first described by Samuel Sharp in 1750 and occurs mainly at the posterior lip of the urethra, and the exact aetiology is still uncertain. More often it was seen in the postmenopausal women, and only few cases are reported in young girls. Patients may be asymptomatic and could find this as an incidental finding or they may present with symptoms such as dysuria, bleeding per vagina, haematuria, a mass protruding through vagina, and acute retention of urine. Here, we report the case history of a 4-year-old girl presented with vaginal bleeding which was taken as she has attended menarche and found to have urethral caruncle which was the cause for bleeding. Histology confirmed the diagnosis, and girl was completely cured following surgical excision.

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Laryngeal recurrence sites in patients previously treated with transoral laser microsurgery for squamous cell carcinoma

The laryngeal framework provides a natural barrier preventing tumour spread to extralaryngeal structures. Transoral laser microsurgery (TLM) for laryngeal squamous cell carcinoma (SCC) may violate these bounda...

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Accuracy and feasibility of a dedicated image guidance solution for endoscopic lateral skull base surgery

Abstract

Objective

We aimed to design, build and validate a surgical navigation system which fulfills the accuracy requirements for surgical procedures on the ear and the lateral skull base, and which integrates with the endoscopic workflow and operating room setup.

Materials and Methods

The navigation system consists of portable tablet computer (iPad Pro, Apple Computer, USA) and an optical tracking system (Cambar B1, Axios3D, Germany), both connected via a wireless Bluetooth link and attached directly to the OR table. Active optical tracking references are rigidly fixed to both the patient and surgical tools. Software to support image import, registration and 2D/3D visualization has been developed. Two models were used for targeting accuracy assessment: a technical phantom model and an ex vivo temporal bone model. Additionally, workflow integration and usability of the navigation system during endoscopic lateral skull base procedures was investigated in ex vivo experiments on 12 sides of cadaver head specimens.

Results

The accuracy experiments revealed a target registration error in the technical phantom model of 0.20 ± 0.10 mm (n = 36) and during the ex vivo assessment of 0.28 ± 0.10 mm (n = 21). Navigation was successfully carried out in n = 36 procedures (infracochlear, suprageniculate and transpromontorial approach), with navigated instruments usable without interference with the endoscope. The system aided in the successful and accurate identification of vital anatomical structures.

Conclusions

Useful surgical navigation is, to a large extent, a result of sufficiently accurate tracking technology. We have demonstrated sufficient accuracy and a potentially suitable integration for surgical application within endoscopic lateral skull base procedures.

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