Medicine by Sfakianakis Alexandros: 04/20/17

Πέμπτη 20 Απριλίου 2017

US antibiotic stewardship and penicillin allergy.

Purpose of review: The purpose of this review is to improve otolaryngologists' antibiotic stewardship by detailing current approaches to penicillin allergy. Recent findings: Although up to 15% of hospitalized patients in the United States have a penicillin allergy recorded on their charts, fewer than 10% of these have a true penicillin allergy. Summary: Using a combination of a detailed allergy history, skin testing and graded-dose administration, many patients whose charts say 'penicillin-allergic' can safely be treated with penicillin and cross-reacting antibiotics. This permits use of narrower-spectrum antibiotics and saves money. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Steroid Resistance of Airway Type 2 Innate Lymphoid Cells (ILC2s) from Severe Asthma: The Role of Thymic Stromal cell Lymphopoietin (TSLP)

Publication date: Available online 20 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Sucai Liu, Mukesh Verma, Lidia Michalec, Weimin Liu, Anand Sripada, Donald Rollins, James Good, Yoko Ito, HongWei Chu, Magdalena M. Gorska, Richard J. Martin, Rafeul Alam
BackgroundILC2s represent an important type 2 immune cell. Glucocorticoid regulation of human ILC2s is largely unknown.ObjectiveTo assess steroid resistance of human blood and airway ILC2s from asthmatic patients and examine its mechanism of induction.MethodsWe studied human blood and lung ILC2s from asthmatic and control subjects by flow cytometry and ELISA.ResultsDexamethasone (Dex) inhibited (P=0.04) CRTH2 and type 2 cytokine expression by blood ILC2s stimulated with IL25 and IL33. However, it failed to do so when ILC2s were stimulated with IL7 and TSLP, two ligands of IL7Rα. Unlike blood ILC2s, BAL ILC2s from asthmatic patients were resistant to Dex. BAL from the asthmatic patients had elevated TSLP but not IL7. The BAL TSLP level correlated (r=0.74) with steroid resistance of ILC2s. TSLP was synergistically induced in epithelial cells by IL13 and human rhinovirus. Mechanistically, Dex upregulated ILC2 expression of IL7Rα , which augmented and sustained STAT5 signaling by TSLP. TSLP induced MEK, c-Fos, ID3, pSTAT3 and pSTAT5—molecules linked to steroid resistance. Dex inhibited c-Fos, ID3 and pSTAT3, but not pSTAT5 and MEK. The MEK inhibitor Trametinib, the JAK-STAT inhibitor Tofacitinib and the STAT5 inhibitor Pimozide reversed steroid resistance of BAL ILC2s.ConclusionsDex inhibited type 2 cytokine production by blood ILC2s. IL7 and TSLP abrogated this inhibition and induced steroid resistance of ILC2s in a MEK and STAT5-dependent manner. BAL ILC2s from asthmatic patients with elevated TSLP were steroid resistant, which was reversed by clinically available inhibitors of MEK and STAT5.

Teaser

Dexamethasone inhibited CRTH2 and IL5 but promoted IL7Rα expression by ILC2s, which led to the development of steroid resistance This steroid resistance was reversed by MEK and STAT5 inhibitors.

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Type 3 innate lymphoid cells induce proliferation of CD94+ NK cells

Publication date: Available online 20 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Shuo Li, Hideaki Morita, Beate Rückert, tadech boonpiyathad, Avidan Neumann, Cezmi Akdis

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Direct monitoring of basophil degranulation by using avidin-based probes

Publication date: Available online 20 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Régis Joulia, Claire Mailhol, Salvatore Valitutti, Alain Didier, Eric Espinosa

Teaser

We show that fluorescent avidin binds to basophil cell surface upon degranulation and can be used to set up a new basophil activation test (BAT). This new assay provides results comparable to those provided by the CD63 exposure-based BAT, but has the advantage to directly monitor granule exteriorization.

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Asthma: the past, the future, the environment, and the costs

Publication date: Available online 20 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Eyal Shemesh, Lawrence C. Kleinman

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Vitamin D downregulates the IL-23 receptor pathway in human mucosal ILC3

Publication date: Available online 20 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Viktoria Konya, Paulo Czarnewski, Marianne Forkel, Anna Rao, Efthymia Kokkinou, Eduardo J. Villablanca, Sven Almer, Ulrik Lindforss, Danielle Friberg, Charlotte Höög, Peter Bergman, Jenny Mjösberg
BackgroundVitamin D deficiency is a risk factor for inflammatory bowel disease (IBD). The IL-23-driven tissue-resident ILC3 play essential roles in intestinal immunity, and targeting IL-23/12 is a promising approach in IBD therapy.ObjectiveWe set out to define the role of 1α,25-dihydroxy vitamin D3 (1,25D) in regulating functional responses of human mucosal ILC3 to IL-23 plus IL-1β stimulation.MethodsTranscriptomes of sorted tonsil ILC3 were assessed by microarray analysis. ILC3 cytokine production, proliferation and differentiation were determined by flow cytometry, ELISA and multiplex immunoassay. Intestinal cell suspensions and ILC3 sorted from gut biopsies of IBD patients were also analyzed along with plasma 25-hydroxy vitamin D3 (25D) detection.ResultsILC3 stimulated with IL-23 plus IL-1β upregulated the vitamin D receptor (VDR) and responded to 1,25D with downregulation of the IL-23 receptor (IL-23R) pathway. Consequently, 1,25D suppressed the IL-22, IL-17F and GM-CSF production from tonsil and gut ILC3. In parallel, 1,25D upregulated genes linked to the IL-1β signaling pathway as well as the IL-1β-inducible cytokines IL-6, IL-8 and MIP-1α/β. The 1,25D-triggered skewing in ILC3 function was not accompanied or caused by changes in viability, proliferation or phenotype. Finally, we confirmed low 25D plasma levels in IBD patients with active inflammation.ConclusionIn the light of the beneficial targeting of IL-23/12 in IBD, 1,25D appears as an interesting therapeutic agent that inhibits the IL-23R pathway, providing a novel mechanism for how ILC3 could be manipulated to regulate intestinal inflammation.

Teaser

We have unraveled the detailed mechanisms behind how vitamin D efficiently suppresses IL-23 receptor signaling in gut innate lymphoid cells, providing incitement for vitamin D supplementation as a therapeutic approach in IBD.

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Allergens involved in the cross-reactivity of Aedes aegypti with other arthropods

Publication date: Available online 20 April 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Jose Fernando Cantillo, Leonardo Puerta, Sylvie Lafosse-Marin, Jose Luis Subiza, Luis Caraballo, Enrique Fernandez-Caldas
BackgroundCross-reactivity between Aedes aegypti and mites, cockroaches, and shrimp has been previously suggested, but the involved molecular components have not been fully described.ObjectiveTo evaluate the cross-reactivity between A aegypti and other arthropods.MethodsThirty-four serum samples from patients with asthma and/or allergic rhinitis were selected, and specific IgE to A aegypti, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis, Periplaneta americana. and Litopenaeus vannamei was measured by enzyme-linked immunosorbent assay. Cross-reactivity was investigated using pooled serum samples from allergic patients, allergenic extracts, and the recombinant tropomyosins (Aed a 10.0201, Der p 10, Blo t 10, Lit v 1, and Per a 7). Four IgE reactive bands were further characterized by matrix-assisted laser desorption/ionization tandem time of flight.ResultsFrequency of positive IgE reactivity was 82.35% to at least one mite species, 64.7% to A aegypti, 29.4% to P americana, and 23.5% to L vannamei. The highest IgE cross-reactivity was seen between A aegypti and D pteronyssinus (96.6%) followed by L vannamei (95.4%), B tropicalis (84.4%), and P americana (75.4%). Recombinant tropomyosins from mites, cockroach, or shrimp inhibited the IgE reactivity to the mosquito at a lower extent than the extracts from these arthropods. Several bands of A aegypti cross-reacted with arthropod extracts, and 4 of them were identified as odorant binding protein, mitochondrial cytochrome C, peptidyl-prolyl cis-trans isomerase, and protein with hypothetical magnesium ion binding function.ConclusionWe identified 4 novel cross-reactive allergens in A aegypti allergenic extract. These molecules could influence the manifestation of allergy to environmental allergens in the tropics.

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An Innovative Cooling Jacket to Combat Heat Intolerance in Children with Anhidrosis

Abstract

Hyperthermia and heat intolerance are distressing symptoms in patients with anhidrosis. Body cooling devices are an integral part of management of these patients. A cooling jacket made from easily available materials has been invented for a girl with congenital insensitivity to pain and anhidrosis with severe heat intolerance. This innovative cooling jacket may be helpful for anhidrotic children in resource-poor situations.

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Management of a case of myopic foveoschisis with phakic intraocular lens (pIOL) in situ: intraoperative challenges

We describe the case of a 30-year-old man with pathological myopia with a phakic intraocular lens (IOL) (Visian ICL V4c model; STAAR, Monrovia, California, USA) in situ having complaints of metamorphopsia in the left eye with documented myopic foveoschisis on swept-source optical coherence tomography (DRI OCT Triton; Topcon, Tokyo, Japan). The patient underwent pars plana vitrectomy with internal limiting membrane peeling. This report discusses the intraoperative challenges occurring as a result of increased optical aberrations in the presence of a phakic IOL.

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Exogenous Cushing's syndrome due to a Chinese herbalists prescription of ointment containing dexamethasone

Eczema in children is a chronic disabling condition. The impact of this condition on the lives of families is often underestimated by conventional physicians. As a consequence parents may investigate complementary treatment options. Close monitoring by a paediatrician is essential, considering that a variety of adverse effects can occur during the use of complementary treatment. We present a 5-year-old girl with eczema. She visited a Chinese herbalist who prescribed an ointment. The parents noticed that the eczema resolved fast, itching decreased and she was finally sleeping well. However, her behaviour changed and appetite increased. Undetectable levels of serum cortisol were found, which was indicative of exogenous Cushing's syndrome. Analysis of the ointment revealed the presence of dexamethasone. Hydrocortisone substitution and subsequently a reduction schedule were implemented, after which endogenous cortisol production recovered after 4 months. Physicians should be aware that unregistered herbal medicine can contain potent drugs such as glucocorticoids.

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Sir Charles Bell: Unheralded laryngologist

Sir Charles Bell is renowned and revered as an outstanding surgeon, anatomist, clinician and teacher and his many contributions to various medical fields have been amply described. What are less well-known are his contributions to the field of laryngology.

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Primary mucosal melanoma of the palatine tonsil: Report of a case and review of the literature

Mucosal melanoma of the palatine tonsil is extremely rare. Due to its poor prognosis, primary tonsillar melanoma requires prompt recognition and treatment.

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A Novel Recombinant Canine Adenovirus Type 1 Detected from Acute Lethal Cases of Infectious Canine Hepatitis

Viral Immunology , Vol. 0, No. 0.

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Brodie abscess of the femoral capital epiphysis in a 2-year-old child caused by Kingella kingae

We report the case of a Brodie abscess of the femoral capital epiphysis from which Kingella kingae was isolated. This is to the best of our knowledge the first report of a Brodie abscess of the femoral capital epiphysis from which K. kingae was isolated.

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Delayed LGI1 seropositivity in voltage-gated potassium channel (VGKC)-complex antibody limbic encephalitis

We utilise a clinical case to highlight why exclusion of voltage-gated potassium channel (VGKC)-complex autoantibody testing in serological evaluation of patients may delay or miss the diagnosis. A 68-year-old man presented with increasing involuntary movements consistent with faciobrachial dystonic seizures (FBDS). Initial evaluation demonstrated VGKC antibody seropositivity with leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) seronegativity. Aggressive immunotherapy with methylprednisolone and plasmapheresis was started early in the course of his presentation. Following treatment with immunotherapy, the patient demonstrated clinical improvement. Repeat serum evaluation 4 months posthospitalisation remained seropositive for VGKC-complex antibodies, with development of LGI1 autoantibody seropositivity. VGKC-complex and LGI1 antibodies remained positive 12 months posthospitalisation. Our findings suggest that clinical symptoms can predate the detection of the antibody. We conclude that when suspicion for autoimmune encephalitis is high in the setting of VGKC autoantibody positivity, regardless of LGI1 or CASPR2 seropositivity, early immunotherapy and repeat testing should be considered.

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Syndrome of inappropriate antidiuretic hormone accompanied by bilateral hypothalamic and anterior thalamic lesions with serum antiaquaporin 4 antibody

We described a rare case of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and severe unconsciousness accompanied by bilateral hypothalamic and anterior thalamic lesions with positive serum antiaquaporin 4 (AQP4) antibody. A 29-year-old man was admitted to our hospital due to the subacute progression of an unconscious state. He was observed to be hyponatraemic secondary to SIADH. Brain MRI showed bilateral hypothalamic and anterior thalamic lesions. Anti-AQP4 antibody was detected in his serum. After the administration of intravenous methylprednisolone pulse therapy, his symptoms improved with complete recovery from SIADH and regression of the hypothalamic and anterior thalamic lesions. The patient was transferred to another hospital for rehabilitation with 20 mg/day of oral prednisolone 127 days after admission. This case highlights the importance of testing for anti-AQP4 antibody in patients with unexplainable SIADH, subacute progressive unconsciousness and bilateral hypothalamic and anterior thalamic lesions.

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Transoesophageal three-dimensional echocardiographic diagnosis of Barlows disease

Description

A 67-year-old man with a year history of palpitations and dyspnoea presented to the physician's office. His blood pressure was 140/80 mm Hg and pulse was 80 beats/min. Heart auscultation revealed a loud systolic click followed by a holosystolic murmur. The ECG showed sinus rhythm, P wave +/– in V1 and P wave duration 140 ms in DII. The Holter monitoring showed atrial extrasystoles and an episode of atrial tachycardia (figure 1A).

Figure 1

(A) The Holter monitoring showed atrial extrasystoles and an episode of atrial tachycardia. (B) M-mode echocardiogram showed late systolic sagging of the mitral valve. (C) Transoesophageal echocardiogram showed clearly the prolapsing mitral leaflets and severe mitral regurgitation. (D,E) Three-dimensional echocardiographic imaging demonstrated bileaflet prolapse. Mitral model showed prolapse of the P1, P2, P3 and A1, A2, A3.

The transthoracic echocardiogram M-mode showed late systolic sagging of the mitral...

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Chronic Candidiasis in Children

Abstract

Purpose of Review

Healthy children may develop candidal infections as the result of exposure to antibiotics or corticosteroids, but chronic candidiasis in children after the newborn period is unusual. Chronic mucocutaneous candidiasis (CMC) refers to a group of conditions characterized by recurrent or persistent infections with Candida species, particularly Candida albicans. CMC is a phenotype observed in a spectrum of immunologic disorders, some with endocrinologic and autoimmune features.

Recent Findings

CMC can arise secondary to inherited or acquired T cell deficiencies, but in children is largely due to inborn errors impairing the dectin pathway and IL-17 immunity. We review the current understanding of the pathogenesis of chronic mucocutaneous candidiasis and discuss the immunologic pathways by which the immune system handles Candida. We highlight the historical and recent knowledge of CMC in children, emphasizing recent insights into basic science aspects of the dectin pathway, IL-17 signaling, consequences of AIRE gene defects, and clinical aspects of inheritance, and features that distinguish the different syndromes.

Summary

The clinical phenotype of CMC has many underlying genetic causes. Genetic testing is required for definitive diagnosis.

http://ift.tt/2oVrjgV

Emerging Approaches to Food Desensitization in Children

Abstract

Purpose of Review

The purpose of this review is to highlight the recent advances in food desensitization in children with food allergy.

Recent Findings

Recent advancements in epicutaneous, sublingual, and oral immunotherapy for food allergy in the future may offer children with food allergy and their families a viable option to reduce risk or severity of anaphylaxis with phase III trials ongoing for two of these treatment modalities.

Summary

Food allergy prevalence in children is estimated to be up to 8%. These children are at risk of significant allergic reactions and anaphylaxis. Food avoidance and use of antihistamines or epinephrine has been the standard of care for these patients. This approach also has a significant socioeconomic effects on patients and their families. Recent advancements in understanding food allergy have allowed for exploring new methods of treatment. There is an increasing interest in oral immunotherapy, epicutaneous immunotherapy, or sublingual immunotherapy for food allergy. There have been also innovative approaches to immunotherapy by modification of food allergens (to make them less allergenic while maintain their immunogenicity) or adding adjunctive treatments (probiotics, anti-IgE, etc.) to increase efficacy or safety.

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In response to stomal maturation does not increase the rate of tracheocutaneous fistulas

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Allergens involved in the cross-reactivity of Aedes aegypti with other arthropods

Cross-reactivity between Aedes aegypti and mites, cockroaches, and shrimp has been previously suggested, but the involved molecular components have not been fully described.

http://ift.tt/2orPjXV

US antibiotic stewardship and penicillin allergy.

MuPeXI: prediction of neo-epitopes from tumor sequencing data

Abstract

Personalization of immunotherapies such as cancer vaccines and adoptive T cell therapy depends on identification of patient-specific neo-epitopes that can be specifically targeted. MuPeXI, the mutant peptide extractor and informer, is a program to identify tumor-specific peptides and assess their potential to be neo-epitopes. The program input is a file with somatic mutation calls, a list of HLA types, and optionally a gene expression profile. The output is a table with all tumor-specific peptides derived from nucleotide substitutions, insertions, and deletions, along with comprehensive annotation, including HLA binding and similarity to normal peptides. The peptides are sorted according to a priority score which is intended to roughly predict immunogenicity. We applied MuPeXI to three tumors for which predicted MHC-binding peptides had been screened for T cell reactivity, and found that MuPeXI was able to prioritize immunogenic peptides with an area under the curve of 0.63. Compared to other available tools, MuPeXI provides more information and is easier to use. MuPeXI is available as stand-alone software and as a web server at http://ift.tt/2pIfAoY.

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Evaluation of tinnitus retraining therapy for patients with normal audiograms versus patients with hearing loss

A few chronic tinnitus patients show normal hearing thresholds in the pure tone audiometry from 125Hz to 8000Hz (≤20dB). We report the characteristics of the course of those patients underwent tinnitus retraining therapy (TRT) compared with other patients suffering from chronic and severe tinnitus.

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JAMA Otolaryngology–Head & Neck Surgery Peer Reviewers in 2016

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Unilateral Neck Swelling in a Pediatric Patient

A young child had persistent unilateral neck swelling; examination revealed a firm, immobile, and nontender mass fixed to the underlying right mandible with cortical destruction, extending into the submandibular and sublingual spaces. What is your diagnosis?

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March 2017 Issue Highlights

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Association Between Laryngeal Cancer and Asbestos Exposure

This systematic review assesses the literature to determine whether an association exists between laryngeal cancer and asbestos exposure.

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Lymph Node Biopsy in Patients With Papillary Thyroid Cancer

To the Editor Recently Cabrera et al published a prospective study on 37 patients with papillary thyroid cancer (PTC) who underwent radioguided sentinel lymph node biopsy (SLNB), aimed to correlate the presence of lymph node metastasis with patient and tumor characteristics. The authors stated that this is the first study in which that evaluation has been performed. However, in the largest prospective study of 345 patients with PTC who underwent SLNB with 3-year follow-up, we have already demonstrated that the presence of multifocal or infiltrating PTC was associated with increased nodal metastases.

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The Changing Cochlear Implant Center

This Viewpoint summarizes the origins, challenges, and future of the cochlear implant center.

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JAMA Otolaryngology–Head & Neck Surgery —The Year in Review, 2016

As I complete my first year as Editor of JAMA Otolaryngology–Head & Neck Surgery, I would like to take this opportunity to thank our authors, editors, staff, reviewers, and readers for the many substantial contributions they made to the journal. Without our authors producing the research and sharing their thoughts, experiences, and observations, we would not have the content to create our fine journal. I thank my Deputy Editors, Neal Futran and Sukgi Choi, and Associate Editors, Timothy Smith and Timothy Hullar. I also owe much thanks to Karen Dodson, Editorial Manager, for her wonderful organizational skills and professional support during this past year. And finally, I acknowledge the support of the superb JAMA Network publication staff in Chicago.

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Slowly Growing Neck Mass With Progressive Dysphagia

A man with history of smoking and alcohol use had neck tenderness and dysphagia; computed tomography revealed a heterogeneously enhancing mass in the right side of the neck. What is your diagnosis?

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Ciprofloxacin Plus Fluocinolone in Otitis Media With Tympanostomy Tubes

This randomized clinical trial evaluates the efficacy and safety of topical ciprofloxacin plus fluocinolone acetonide otic solution vs ciprofloxacin otic solution alone and fluocinolone acetonide otic solution alone for acute otitis media in children with tympanostomy tubes.

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Identifying Intraoperative Nerve Monitoring in Thyroid Surgery

To the Editor I read with interest the article titled "Analysis of Variations in the Use of Intraoperative Nerve Monitoring in Thyroid Surgery" by Al-Qurayshi et al. This was a cross-sectional study on the impact of patient demographic factors and surgeon and hospital thyroidectomy volume on the use of intraoperative nerve monitoring (IONM), using the State Inpatient Database for Florida, New York, and Washington. They found that IONM was used in only 8.3% of thyroidectomies. White patients were more likely to undergo IONM than racial minority patients. They also found that use of IONM was higher in thyroidectomies performed by low-volume surgeons, and in low-volume hospitals.

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Association of Iron Deficiency Anemia With Hearing Loss

This population-based cohort study examines the association between iron deficiency anemia and sensorineural, conductive, or combined hearing loss in young to elderly adults.

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Additional Data for Figures

In the Original Investigation titled "Association of Extracapsular Spread With Survival According to Human Papillomavirus Status in Oropharynx Squamous Cell Carcinoma and Carcinoma of Unknown Primary Site," published in the July 2106 issue of JAMA Otolaryngology–Head & Neck Surgery,¹ Figures 1 through 4 were missing the number of patients at risk for the Kaplan-Meier curves. The numbers at risk have now been added. This article was corrected online.

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Individualized Bioselection Treatment Methods in Laryngeal Cancer

This cohort study evaluates the association between individualized bioselection treatment decision criteria and survival of patients with laryngeal cancer.

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Individualized Treatment of Laryngeal Cancer

In this issue of JAMA Otolaryngology–Head & Neck Surgery, Wolf et al describe very high survival rates in an unselected cohort of 247 patients with advanced laryngeal cancer. These patients were treated with a program of individualized bioselection. All of us invested in the care of patients with advanced laryngeal cancer must breathe a deep sigh of relief. Only 10 years ago, Hoffman et al, in a landmark review of the national cancer database, evaluated the outcome of 158 426 patients with laryngeal cancer. Between the years of 1985 and 2001, the survival rate had gone down. So what has changed?

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Distant Metastases Following Postoperative Intensity-Modulated Radiotherapy

This study examines the characteristics and risk factors of distant metastases following postoperative intensity-modulated radiotherapy in oral squamous cell carcinoma and the clinicopathological characteristics that could be associated with distant-only failure.

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A Congenital Nasal Mass Causing Respiratory Distress

A neonate had noisy breathing and nasal congestion; physical examination revealed significant distress,and retractions, and a mucosalized mass filling the left nasal cavity was visualized on anterior rhinoscopy, requiring nasal stenting to relieve obstruction. What is your diagnosis?

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Complications of Bilateral Neck Dissection in Thyroid Cancer

This study delineates the specific complications arising from bilateral neck dissection for thyroid cancers at a single high-volume center.

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Retropharyngeal Mass

A woman had a sore throat, globus sensation, and dysphagia; she had a hyperintense, enhancing mass in the retropharyngeal and prevertebral spaces with marrow replacement of the C2 vertebral body extending to the odontoid. What is your diagnosis?

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Determinants of Failure and Survival in Patients With Node-Negative Oral Tongue Cancers

This study assesses the association of lymphovascular space invasion with locoregional failure and survival in patients with node-negative oral tongue cancers treated with upfront definitive surgical resection.

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Laryngeal Immunoglobulin G4-Related Disease Resulting in Severe Airway Obstruction

A woman in her 70s with a history of Sjogrens syndrome associated with rheumatoid arthritis complicated by Felty syndrome had progressive shortness of breath for over a decade that rapidly worsened over the course of 1 month.

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Mitochondrial Function in Allergic Disease

Abstract

Purpose of the Review

The connections between allergy, asthma and metabolic syndrome are becoming increasingly clear. Recent research suggests a unifying mitochondrial link between the diverse phenotypes of these interlinked morbidities. The scope of this review is to highlight cellular mechanisms, epidemiology and environmental allergens influencing mitochondrial function and its importance in allergy and asthma. We briefly also consider the potential of mitochondria-targeted therapies in prevention and cure.

Recent Findings

Recent research has shown allergy, asthma and metabolic syndrome to be linked to mitochondrial dysfunction. Environmental pollutants and allergens are observed to cause mitochondrial dysfunction, primarily by inducing oxidative stress and ROS production. Malfunctioning mitochondria change the bioenergetics of the cell and its metabolic profile to favour systemic inflammation, which drives all three types of morbidities.

Summary

Given the existing experimental evidence, approaches targeting mitochondria (e.g. antioxidant therapy and mitochondrial replacement) are being conducted in relevant disease models—with some progressing towards clinical trials, making mitochondrial function the focus of translational therapy research in asthma, allergy and linked metabolic syndrome.

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Chronic Candidiasis in Children

Abstract

Purpose of Review

Recent Findings

Summary

The clinical phenotype of CMC has many underlying genetic causes. Genetic testing is required for definitive diagnosis.

http://ift.tt/2oVrjgV

The Role of Macrolides in Chronic Rhinosinusitis (CRSsNP and CRSwNP)

Abstract

Purpose of Review

We assess the literature on the pharmacokinetics, indications, important considerations, and effectiveness of long-term, low-dose macrolide antibiotics in chronic rhinosinusitis (CRS).

Recent Findings

The key to effective implementation of macrolide therapy in CRS is appropriate patient selection. Macrolides have demonstrated the most benefit in Th1-mediated non-eosinophilic CRS when used for durations of at least 3 months.

Summary

Macrolide antibiotics have demonstrated great benefit when used for their anti-inflammatory or immunomodulatory properties, which include the blockage of pro-inflammatory cytokines, such as interleukin (IL)-8 and tumor necrosis factor-α (TNF-α). They have been used in CRS patients not responding to traditional corticosteroid-based treatment regimens, but appear to be most effective specifically in Th1-mediated non-eosinophilic CRS in long durations and low doses. Further research is needed to better identify characteristics known to correlate with macrolide response so early directed therapy can be implemented.

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Natural Evolution of IgE Responses to Mite Allergens and Relationship to Progression of Allergic Disease: a Review

Abstract

Purpose of Review

Allergenic molecules of the house dust mite (HDM) are crucially important indoor allergens, contributing to allergic rhinitis and asthma around the globe. In the past years, recombinant molecules for diagnostics opened new pathways to investigate individual sensitization profiles and new chances for the prevention and treatment of HDM allergy. This review summarizes the latest findings on the evolution of IgE responses towards mite allergens.

Recent Findings

Several cross-sectional and longitudinal studies confirmed the role of Der p 1 and Der p 2 as major allergenic proteins of the HDM. A newly identified player is the major allergen Der p 23. Apart from identifying the early sensitization towards this molecule as a risk factor for asthma in school age, a recent longitudinal study described sensitization patterns showing that the production of IgE usually starts towards a group of initiator proteins and may stay monomolecular or expand to an oligo- or even polymolecular stage. This phenomenon also correlates to clinical symptoms. A relation between a broad sensitization pattern and symptom severity has also been shown cross-sectionally.

Summary

Individual sensitization profiles towards HDM allergens provide important information to evaluate a patient's current stage and risk for clinical symptoms. This knowledge paves the way for an early and adequate prevention and/or treatment.

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Emerging Approaches to Food Desensitization in Children

Abstract

Purpose of Review

The purpose of this review is to highlight the recent advances in food desensitization in children with food allergy.

Recent Findings

Summary

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New Perspectives on the Diagnosis of Allergy to Anisakis spp.

Abstract

Purpose of Review

To compare the prevalence of sensitization in different countries based on specific IgE values and to evaluate the use of isolated native or recombinant allergens for diagnosis.

Recent Findings

Isolated allergens help in the diagnosis of truly sensitized patients avoiding false positives due to cross-reactions. Their use is therefore highly recommended, especially when used as a combination of several relevant allergens.

Summary

The use of purified allergens allows an accurate diagnosis and this has led to three important findings: (1) in addition to the digestive route of sensitization, occupational and non-digestive exposure seems to be clinically relevant. (2) The parasite appears as an important agent for chronic urticaria. And (3) in endemic countries, the amount of highly sensitized subjects in the general population could be as high as 7%. Adequate information to asymptomatic patients on fish consumption habits would avoid new contacts with parasite allergens and decrease their specific IgE levels and consequently the appearance of acute or chronic episodes induced by the parasite.

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Ultrastructure of pheochromocytoma: undescribed morphologic features

Abstract

We examined samples of human pheochromocytoma from 11 patients aged 30–70 years including one case of malignant pheochromocytoma with a view to identifying previously unreported ultrastructural details.

We identified two types of nuclear inclusions consisting of irregularly shaped singular or multiple granulofibrillar formations with a typical concentric halo, on the one hand, and accumulations of egg-shaped structures consisting of granules and microfilaments, on the other. In some of the tumor cells, membrane-covered inclusions containing parallel laminar elements arranged in a paracrystalline, periodic fashion, or mega-mitrochondriae characterized by increased electrodensity of their matrix, and fibrillary material in the spaces between the cristae were present. A frequent finding consisted of typical ciliary formations, while rough/smooth tubular aggregates of different size occurred less frequently. Finally, we were able to demonstrate the uptake of norepinephrine by smooth muscle fibers in the periphery of arterial vessels as evidenced by linear accumulations of membrane-covered granules separating bands of contractile smooth muscle components in the peripheral layers of arterial vessels close to norepinephrine producing neoplastic cells.

These findings represent ultrastructural features that contribute to further elucidating the ultrastructural characteristics of the human pheochromocytoma.

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Providing anesthesia in resource-limited settings.

Purpose of review: The article reviews the reality of anesthetic resource constraints in low and middle-income countries (LMICs). Understanding these limitations is important to volunteers from high-income countries who desire to teach or safely provide anesthesia services in these countries. Recent findings: Recently published information on the state of anesthetic resources in LMICs is helping to guide humanitarian outreach efforts from high-income countries. The importance of using context-appropriate anesthesia standards and equipment is now emphasized. Global health experts are encouraging equal partnerships between anesthesia health care providers working together from different countries. The key roles that ketamine and regional anesthesia play in providing well tolerated anesthesia for cesarean sections and other common procedures is increasingly recognized. Summary: Anesthesia can be safely given in LMICs with basic supplies and equipment, if the anesthesia provider is trained and vigilant. Neuraxial and regional anesthesia and the use of ketamine as a general anesthetic appear to be the safest alternatives in low-resource countries. Environmentally appropriate equipment should be encouraged and pulse oximeters should be in every anesthetizing location. LMICs will continue to need support from outside sources until capacity building has made more progress. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2oVqLYE

Diminished capacity of opsonization and immune complex solubilization, and detection of anti-C1q antibodies in sera from patients with hereditary angioedema

Publication date: Available online 20 April 2017
Source:Allergology International
Author(s): Daisuke Honda, Isao Ohsawa, Nobuyuki Sato, Hiroyuki Inoshita, Satoshi Mano, Yasuhiko Tomino, Yusuke Suzuki
BackgroundHereditary angioedema (HAE) is an autosomal dominant disease caused by deficiency of C1 esterase inhibitor. Symptoms of HAE include edema, which can potentially cause suffocation. Some patients with HAE exhibit immunological abnormalities, which could prevent an accurate diagnosis. Low levels of complement components are characteristic of HAE and in other settings are thought to reduce elimination of apoptotic cells and immune complex (IC). Thus, we aimed to experimentally clarify the mechanism of immunological abnormalities using sera from HAE patients.MethodsSerum samples from 18 patients with HAE were collected when free from angioedema attack and compared with normal human pooled sera (NHPS) from 20 healthy volunteers. Opsonization was measured as the rate of phagocytosis of apoptotic Jurkat cells by macrophages differentiated from THP-1 cells incubated with serum. IC solubilization in serum was analyzed by quantifying peroxidase released from a synthetic IC composed of peroxidase and anti-peroxidase antibodies. Anti-C1q antibody levels were detected using an enzyme-linked immunosorbent assay.ResultsSerological immunological abnormalities were detected in 12 patients. Opsonization in serum samples from each patient with HAE was lower than that in NHPS (∼20% versus 70%, respectively). The rate of IC solubilization was lower in serum from HAE patients than NHPS. Some patients had high serum anti-C1q antibody levels with increased serum IC levels.ConclusionsSera from patients with HAE exhibit anti-C1q antibodies, with a lower capacity for opsonization and IC solubilization. This may be associated with immunological abnormalities and should be investigated further to facilitate accurate diagnosis of HAE.

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Measuring the impact of dermatological conditions on family and caregivers: a review of dermatology-specific instruments

Abstract

The patient is the centre of a web of relationships and the impact of his/her disease on family members and caregivers must be taken into account. The aim of this study was to identify the specific instruments that measure the impact of a dermatological disease on the quality of life (QoL) of family members, by performing a systematic search of the literature. Fifteen papers were identified, describing the creation and validation of nine instruments. Four of them concerned atopic dermatitis (Dermatitis Family Index, DFI; Parents' Index QoL Atopic Dermatitis, PiQoL-AD; QoL in Primary Caregivers of children with Atopic Dermatitis, QPCAD; Childhood Atopic Dermatits Impact Scale, CADIS), two measured the impact of psoriasis in family members (Psoriasis Family Index, PFI; FamilyPso), one the impact of epidermolysis bullosa (Epidermolysis Bullosa Burden of Disease, EB-BoD), one of ichthyosis (Family Burden Ichthyosis, FBI), and one was generic for dermatological conditions (Family Dermatology Life Quality Index, FDLQI). The EADV quality of life taskforce recommends that the impact of a skin disease on family and caregivers should be measured as part of any thorough evaluation of the burden of a disease. Guidelines are given to choose the most appropriate instruments.

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Frontal fibrosing alopecia: clinical and prognostic classification

Abstract

Background

Frontal fibrosing alopecia (FFA) is a chronic scarring alopecia with an unpredictable evolution. There are no current classifications of this disease that may predict its prognosis.

Objective

To analyze the differences in clinical presentation and evolution of FFA patients and to create a clinical and prognostic classification

Methods

We conducted a retrospective analytical study of FFA patients. Clinical characteristics of frontal hairline recession were used as the sorting variable between patterns of presentation. A cohort of 106 patients homogenously treated with oral dutasteride and topical corticosteroid was followed 12 months.

Results

In all, 242 female patients with a mean age of 61.4 years were included. Patients were classified in three clinical patterns (118 (48.8%) patients as pattern I (linear), 109 patients (45%) as pattern II (diffuse) and 15 patients (6.2%) as pattern III (double-line)). Stabilization was achieved in 37.3% of the 106 patients treated with oral dutasteride and topical corticosteroid. Pattern III patients had less hairline recession and eyebrow involvement at the diagnosis and after treatment.

Limitations

Retrospective design.

Conclusions

FFA patients can be classified in three different clinical patterns with different prognosis. Pattern III patients have the best prognosis, while pattern II patients have the worst prognosis.

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Acantholytic dyskeratotic acanthoma: a possible skin adverse event of vemurafenib treatment

Abstract

Acantholytic dyskeratotic acanthoma (ADA) is a solitary small papule that is pathologically characterized by dyskeratosis with acantholytic acanthosis (1). Vemulafenib is a specific inhibitor of BRAF protein kinase with V600E mutation and is administered to treat metastatic melanoma. Various skin adverse events associated with vemurafenib, including acantholysis and flare up of Darier's disease, have been reported (2, 3). Here we report a case of ADA that developed during vemulafenib treatment for metastatic melanoma. Our case suggests a possibility that vemurafenib may affect epidermal structures which induces acantholysis and dyskeratosis.

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A case of toxic epidermal necrolysis and vanishing bile duct syndrome, requiring liver transplantation

Abstract

A 52-year-old woman presented with a five-day history of headache, fevers and a diffuse, macular erythematous rash. Ten days prior she received cephalexin for a urinary-tract infection. She had a history of gastro-oesophageal reflux disorder and took omeprazole.

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Introducing ORL Notes

As we ended last year and began to contemplate our priorities for the current year, we reviewed ORL Progress Notes, which was first released in 2008. Our newsletter has had both print and email distribution; however, over the past several years, the digital reads have become much more popular than the print version. We also observed that the bulk of readers are relying upon "small screens" (i.e., smart phones and tablets) to read our material. Finally, while our email newsletter had been optimized for mobile devices a few years ago, it still did not fulfill current aesthetic and functional expectations. Thus, we concluded that we needed new design.

One obvious change is that the newsletter has a new name—ORL Notes—in place of ORL Progress Notes. We have also chosen to recognize both Memorial Hermann-Texas Medical Center and UTHealth prominently in the header; our Department works at the intersection of these two great institutions, and our success is a result of a collaborative effort. Finally, the new format will allow us to include an image for each post so that readers can get a glimpse into the article.

We have also chosen to end production of the print journal. In its place, we will develop more content for posting on our website—which will also be re-released with a new design later this year.

Regardless of these changes, the newsletter's purpose remained the same. ORL Notes will continue to provide a window into the daily work of the Department—its clinical activities (with an emphasis on the patients under the care of the Department's physicians), educational activities and research endeavors.

We hope that you enjoy ORL Notes. Feel free to share your views by emailing us at UTHealthORL@uth.tmc.edu.

Martin J. Citardi, MD
Professor & Chair, UTHealth Otorhinolaryngology
Chief of Otorhinolaryngology-Head & Neck Surgery, Memorial Hermann-TMC

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Diffuse normolipemic plane xanthoma on striae

Abstract

Diffuse normolipemic plane xanthoma (DNPX) is a rare skin disorder characterized by the presence of symmetric, asymptomatic, flat, yellow plaques of different size.¹ As it is commonly located on the eyelids, xanthelesma may be a differential diagnostic consideration, but the lesions of DNPX are usually larger and other parts of the face, neck, flexural folds and trunk may also be involved.¹

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High dose pulsed corticosteroid therapy combined with Methotrexate for Severe Alopecia Areata of Childhood

Abstract

Alopecia areata (AA) in childhood can run a chronic course and worsen over time(1). Spontaneous hair regrowth is rarely appreciated in chronic severe AA(2-4). Our centre described the ineffective use of high dose pulsed corticosteroid therapy (HDPCT) in the long term(1). Methotrexate (MTX) as a maintenance therapy following HDPCT showed some success in adults(5). Although the evidence for using either drug individually was weak(6), the combination of using both was not well studied.

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Ultrasonographic features of intravascular fasciitis: case report and review of the literature

Abstract

Intravascular fasciitis (IF), a variant of nodular fasciitis (NF), is a reactive intravascular proliferation of myofibroblasts. IF is an indolent subcutaneous or intramuscular nodule that is most commonly found on the extremities, head and neck.^{1, 2}

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Videodermoscopy supports the diagnosis of eyelash trichotillomania

Abstract

37-year-old woman presented with extensive erythematous and ulcerative eruptions on the face and chest with concomitant isolated eyelash alopecia. Skin problems started during adolescence; eyelash loss several years before hospital admission.

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Immunotherapy and Stereotactic Body Radiotherapy (SBRT) for Metastatic Anaplastic Thyroid Cancer

Condition: Metastatic Anaplastic Thyroid Cancer
Interventions: Drug: durvalumab; Drug: tremelimumab; Radiation: Stereotactic Body Radiotherapy (SBRT)
Sponsors: Memorial Sloan Kettering Cancer Center; AstraZeneca
Not yet recruiting - verified April 2017

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Pain Management in Head and Neck Surgery Patients

Condition: Pain Management
Interventions: Drug: Oxycodone; Drug: Acetaminophen; Drug: Gabapentin; Drug: Celecoxib; Drug: Hydrocodone-Acetaminophen
Sponsor: University of Alabama at Birmingham
Not yet recruiting - verified April 2017

http://ift.tt/2pHt44f

Acceptability and Tolerance of Hysteroscopy and Hysterosonography in Consultation

Condition: Metrorrhagia
Interventions: Device: Hysteroscopy; Device: Hysterosonography
Sponsor: Brugmann University Hospital
Not yet recruiting - verified April 2017

http://ift.tt/2oUseyf

A Study to Evaluate the Safety and Efficacy of Using the Combination Treatment of SHR-1210, Gemcitabine and Cis-platinum by Recurrent and Metastatic NPC Subjects

Condition: Nasopharyngeal Carcinoma
Interventions: Biological: SHR-1210; Drug: Gemcitabine; Drug: cis-platinum
Sponsor: Jiangsu HengRui Medicine Co., Ltd.
Not yet recruiting - verified April 2017

http://ift.tt/2oUAdvr

Discovering the Basics of “Active Touch”

Working with genetically engineered mice — and especially their whiskers — Johns Hopkins researchers report they have identified a group of nerve cells in the skin responsible for what they call "active touch," a combination of motion and sensory feeling needed to navigate the external world. The discovery of this basic sensory mechanism, described online April 20 in the journal Neuron, advances the search for better "smart" prosthetics for people, ones that provide more natural sensory feedback to the brain during use.

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Alcohol intake and risk of rosacea in US women

The epidemiologic association between alcohol and rosacea is unclear and inconsistent based on the previous cross-sectional or case-control studies.

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Unilateral Hearing Loss and Otorrhea

A man in his 70s had painless left-sided otorrhea, aural fullness, and hearing loss; temporal bone computed tomography demonstrated near-complete opacification of the left mastoid air cells and middle ear. What is your diagnosis?

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Surgeon Volume in Parathyroid Surgery

This study examines the association between surgeon volume and 30-day rates of complications, mortality, and postdischarge utilization among patients undergoing parathyroidectomy.

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Surgery and Radiotherapy vs Chemoradiotherapy for Oral Cavity Cancer

This study compares the differences in survival between patients with locally advanced oral cavity squamous cell carcinoma treated with surgery followed by postoperative radiotherapy vs chemoradiotherapy.

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Risks and Harms of Management of Incidental Thyroid Nodules

This review assesses the clinical dilemma of the incidental thyroid nodule, the risk for missing a significant cancer, and the potential harms of examination and reviews management recommendations for patients with these findings.

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Detectie en behandeling van suïcidaal gedrag. Richtlijn en website ondersteunen hulpverleners

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Heterologous prime-boost vaccination with H3N2 influenza viruses of swine favors cross-clade antibody responses and protection

The emergence of multiple novel lineages of H1 and H3 influenza A viruses in swine has confounded control by inactivated vaccines. Because of substantial genetic and geographic heterogeneity among circulating swine influenza viruses, one vaccine strain per subtype cannot be efficacious against all of the current lineages. We have performed vaccination-challenge studies in pigs to examine whether priming and booster vaccinations with antigenically distinct H3N2 swine influenza viruses could broaden antibody responses and protection. We prepared monovalent whole inactivated, adjuvanted vaccines based on a European and a North American H3N2 swine influenza virus, which showed 81.5% aa homology in the HA1 region of the hemagglutinin and 83.4% in the neuraminidase. Our data show that (i) Priming with European and boosting with North American H3N2 swine influenza virus induces antibodies and protection against both vaccine strains, unlike prime-boost vaccination with a single virus or a single administration of bivalent vaccine. (ii) The heterologous prime-boost vaccination enhances hemagglutination inhibiting, virus neutralizing and neuraminidase inhibiting antibody responses against H3N2 viruses that are antigenically distinct from both vaccine strains. Antibody titers to the most divergent viruses were higher than after two administrations of bivalent vaccine. (iii) However, it does not induce antibodies to the conserved hemagglutinin stalk or to other hemagglutinin subtypes. We conclude that heterologous prime-boost vaccination might broaden protection to H3N2 swine influenza viruses and reduce the total amount of vaccine needed. This strategy holds potential for vaccination against influenza viruses from both humans and swine and for a better control of (reverse) zoonotic transmission of influenza viruses.

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Towards a better understanding of the antecedents, generalizability, and measurement of psychological need satisfaction and frustration

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Sputum basophils are increased in eosinophilic asthma compared with non-eosinophilic asthma phenotypes

Abstract

Sputum basophil numbers are increased in allergic asthmatics, but it is unclear what role airway basophils play in "TH2-low" asthma phenotypes. Using flow cytometry we found that basophils were significantly increased in all asthmatics (n=26) compared with healthy controls (n=8) (p=0.007) with highest levels observed in eosinophilic asthma (EA; median 0.22%, IQR 0.11-0.47%; n=14) compared with non-EA (0.06%, 0.00-0.20%; n=12; p<0.05). In asthmatics, basophils were positively correlated with sputum eosinophils (r=0.54; p<0.005), and inversely with sputum neutrophils (r=-0.46: p<0.05), but not with FEV₁ (% predicted), FEV₁/FVC, or bronchodilator reversibility. In a subgroup initially identified as inadequately controlled asthma (n=7), there was a trend (p=0.08) towards a reduction in sputum basophils following increased ICS treatment. Our findings suggest that basophils may be particularly important in eosinophilic asthma, and that sputum basophil assessment could be a useful additional indicator of 'TH2-high' asthma.

http://ift.tt/2pVOW8A

Protease-activated receptor-2 suppresses interleukin (IL)-10 expression in B cells via up regulating Bcl2L12 in patients with allergic rhinitis

Abstract

Background and aims

The function of interleukin (IL)-10 producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease-activated receptor (PAR)-2 has immune regulatory functions. This study aims to elucidate the role of PAR2 in the suppression of IL-10 expression in peripheral B cells.

Methods

Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2 like protein 12 (Bcl2L12) and IL-10 in the B cells was analyzed. An AR mouse model was developed.

Results

We observed that the expression of IL-10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL-10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS-induced IL-10 expression, which was abolished by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12-shRNA carrying liposomes reversed the capability of IL-10 expression and the immune suppressor function. Administration of Bcl2L12 shRNA-carrying liposomes attenuated experimental AR in mice.

Conclusions

Activation of PAR2 inhibits the expression of IL-10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA-carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment of AR.

http://ift.tt/2pHbahV

Incremental Burden of Cardiovascular Comorbidity and Psoriatic Arthritis among Adults with Moderate-to-Severe Psoriasis in Five European Countries

Abstract

Background

Moderate-to-severe psoriasis is associated with reduced health-related quality of life (HRQoL). Individuals with psoriasis are at increased risk for other medical conditions, but little information quantifies the incremental burden of psoriasis-associated comorbidity among European adults, and data have generally been limited to clinical samples.

Objective

To quantify the incremental burden of cardiovascular comorbidity and psoriatic arthritis among adults with moderate-to-severe psoriasis in the general population of France, Germany, Italy, Spain, and the United Kingdom (EU5).

Methods

All measures were self-reported and came from the 2010-2013 EU5 National Health and Wellness Surveys (NHWS). Moderate-to-severe psoriasis was identified by >10% body surface area affected by psoriasis and/or use of therapies for moderate-severe disease. Outcomes were SF-12v2/SF-36v2 mental and physical component summary scores (MCS & PCS, respectively), SF-6D health utility, Work Productivity and Activity Impairment (WPAI) questionnaire, and healthcare use in the past 6 months. Generalized linear models compared across CV or PsA groups vs. non-CV or non-PsA groups with appropriate link functions to adjust for covariates.

Results

Among moderate-to-severe psoriasis respondents (n=957), 19.8% (n=190) reported CV comorbidity, and 12.3% (n=118) reported PsA. After adjustment for covariates, CV comorbidity was associated with 3.0 points lower MCS, 3.4 points lower PCS, and 0.05 points lower SF-6D (all p<0.01). Likewise, they had greater mean work impairment (48% vs. 33%), more activity impairment (48% vs. 37%), more healthcare provider visits (8.8 vs. 6.9), emergency room visits (0.65 vs. 0.31) and hospitalizations (0.61 vs. 0.22) (all p<0.05). Compared to non-PsA respondents, PsA respondents also had worse mean MCS (2.6 points), PCS (6.3 points), and SF-6D scores (0.07 points), more work impairment (52% vs. 34%), activity impairment (54% vs. 38%), and healthcare provider visits (10.5 vs. 6.9) (all p<0.05).

Conclusion

CV comorbidity and PsA were associated with significant incremental burden among EU5 adults with moderate-to-severe psoriasis.

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Mitochondrial Function in Allergic Disease

Abstract

Purpose of the Review

Recent Findings

Summary

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New Perspectives on the Diagnosis of Allergy to Anisakis spp.

Abstract

Purpose of Review

To compare the prevalence of sensitization in different countries based on specific IgE values and to evaluate the use of isolated native or recombinant allergens for diagnosis.

Recent Findings

Summary

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The Role of Macrolides in Chronic Rhinosinusitis (CRSsNP and CRSwNP)

Abstract

Purpose of Review

We assess the literature on the pharmacokinetics, indications, important considerations, and effectiveness of long-term, low-dose macrolide antibiotics in chronic rhinosinusitis (CRS).

Recent Findings

Summary

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Natural Evolution of IgE Responses to Mite Allergens and Relationship to Progression of Allergic Disease: a Review

Abstract

Purpose of Review

Recent Findings

Summary

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A Generalization of the Banach-Steinhaus Theorem for Finite Part Limits

It is well known, as follows from the Banach-Steinhaus theorem, that if a sequence $\left\{ y_{n}\right\} _{n=1}^{\infty}$ of linear continuous functionals in a Fr\'{e}chet space converges pointwise to a linear functional $Y,$ $Y\left( x\right) =\lim_{n\rightarrow\infty}\left\langle y_{n} ,x\right\rangle $ for all $x,$ then $Y$ is actually continuous. In this article we prove that in a Fr\'{e}chet space\ the continuity of $Y$ still holds if $Y$ is the \emph{finite part} of the limit of $\left\langle y_{n},x\right\rangle $ as $n\rightarrow\infty.$ We also show that the continuity of finite part limits holds for other classes of topological vector spaces, such as \textsl{LF}-spaces, \textsl{DFS}-spaces, and \textsl{DFS} $^{\ast}$-spaces,\ and give examples where it does not hold.

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Morphological Properties of Mass–Spring Networks for Optimal Locomotion Learning

Robots have proven very useful in automating industrial processes. Their rigid components and powerful actuators, however, render them unsafe or unfit to work in normal human environments such as schools or hospitals. Robots made of compliant, softer materials may offer a valid alternative. Yet, the dynamics of these compliant robots are much more complicated compared to normal rigid robots of which all components can be accurately controlled. It is often claimed that, by using the concept of morphological computation, the dynamical complexity can become a strength. On the one hand, the use of flexible materials can lead to higher power efficiency and more fluent and robust motions. On the other hand, using embodiment in a closed-loop controller, part of the control task itself can be outsourced to the body dynamics. This can significantly simplify the additional resources required for locomotion control. To this goal, a first step consists in an exploration of the trade-offs between morphology, efficiency of locomotion, and the ability of a mechanical body to serve as a computational resource. In this work, we use a detailed dynamical model of a Mass–Spring–Damper (MSD) network to study these trade-offs. We first investigate the influence of the network size and compliance on locomotion quality and energy efficiency by optimizing an external open-loop controller using evolutionary algorithms. We find that larger networks can lead to more stable gaits and that the system's optimal compliance to maximize the traveled distance is directly linked to the desired frequency of locomotion. In the last set of experiments, the suitability of MSD bodies for being used in a closed loop is also investigated. Since maximally efficient actuator signals are clearly related to the natural body dynamics, in a sense, the body is tailored for the task of contributing to its own control. Using the same simulation platform, we therefore study how the network states can be successfully used to create a feedback signal and how its accuracy is linked to the body size.

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Editorial: Dendritic cell and macrophage nomenclature and classification

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Current status and perspectives of immune-based therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a frequent cancer with a high mortality. For early stage cancer there are potentially curative treatments including local ablation, resection and liver transplantation. However, for more advanced stage disease, there is no optimal treatment available. Even in the case of a "curative" treatment, recurrence or development of a new cancer in the precancerous liver is common. Thus, there is an urgent need for novel and effective (adjuvant) therapies to treat HCC and to prevent recurrence after local treatment in patients with HCC. The unique immune response in the liver favors tolerance, which remains a genuine challenge for conventional immunotherapy in patients with HCC. However, even in this "immunotolerant" organ, spontaneous immune responses against tumor antigens have been detected, although they are insufficient to achieve significant tumor death. Local ablation therapy leads to immunogenic tumor cell death by inducing the release of massive amounts of antigens, which enhances spontaneous immune response. New immune therapies such as dendritic cell vaccination and immune checkpoint inhibition are under investigation. Immunotherapy for cancer has made huge progress in the last few years and clinical trials examining the use of immunotherapy to treat hepatocellular carcinoma have shown some success. In this review, we discuss the current status of and offer some perspectives on immunotherapy for hepatocellular carcinoma, which could change disease progression in the near future.

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Evaluative concerns perfectionism and coping with failure : effects on rumination, avoidance, and acceptance

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The impeding role of self-critical perfectionism on therapeutic alliance during treatment and eating disorder symptoms at follow-up in patients with an eating disorder

This study examines the impeding role of self-critical perfectionism at onset of treatment on therapeutic alliance during treatment and eating disorder symptoms at follow-up in patients with an eating disorder. Participants were 53 female patients with a mean age of 21.1 years treated for an eating disorder in a specialized inpatient treatment unit. Self-critical perfectionism was assessed at admission, therapeutic alliance was assessed during treatment (after three months of treatment), and eating disorder symptoms were assessed at admission, after three months and one year later. Self-critical perfectionism negatively related to treatment alliance with the therapist. Although self-critical perfectionism was not directly predictive of subsequent changes in eating disorder symptoms, it was indirectly related to less reduction in body dissatisfaction through the therapeutic alliance. These results point to the importance of self-critical perfectionism in the therapeutic alliance and in changes in body image problems. Treatment implications are discussed.

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Commentaar art. VI. 64 WER - Voorlopige maatregelen

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The short-time Fourier transform of distributions of exponential type and tauberian theorems for shift-asymptotics

We study the short-time Fourier transform on the space $\mathcal{K}_{1}'(\mathbb{R}^n)$ of distributions of exponential type. We give characterizations of $\mathcal{K}_{1}'(\mathbb{R}^n)$ and some of its subspaces in terms of modulation spaces. We also obtain various Tauberian theorems for the short-time Fourier transform.

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Generation and characterization of feline arterial and venous endothelial cell lines for the study of the vascular endothelium

Background: The in vitro culture of endothelial cells (ECs) is an indispensable tool for studying the role of the endothelium in physical and pathological conditions. Primary ECs, however, have a restricted proliferative lifespan which hampers their use in long-term studies. The need for standardized experimental conditions to obtain relevant and reproducible results has increased the demand for well-characterized, continuous EC lines that retain the phenotypic and functional characteristics of their non-transformed counterparts. Results: Primary feline ECs from aorta and vena cava were successfully immortalized through the successive introduction of simian virus 40 large T (SV40LT) antigen and the catalytic subunit of human telomerase (hTERT). In contrast to the parental ECs, the transformed cells were able to proliferate continuously in culture. Established cell lines exhibited several inherent endothelial properties, including typical cobblestone morphology, binding of endothelial cell-specific lectins and internalization of acetylated low-density lipoprotein. In addition, the immortalization did not affect the functional phenotype as demonstrated by their capacity to rapidly form cord-like structures on matrigel and to express cell adhesion molecules following cytokine stimulation. Conclusion: The ability to immortalize feline ECs, and the fact that these cells maintain the EC phenotype will enable a greater understanding of fundamental mechanisms of EC biology and endothelial-related diseases. Furthermore, the use of cell lines is an effective implementation of the 3-R principles formulated by Russel and Burch.

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Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages

Sialoadhesin is exclusively expressed on specific subpopulations of macrophages. Since sialoadhesin-positive macrophages are involved in inflammatory autoimmune diseases, such as multiple sclerosis, and potentially in the generation of immune responses, targeted delivery of drugs, toxins or antigens via sialoadhesin-specific immunoconjugates may prove a useful therapeutic strategy. Originally, sialoadhesin was characterized as a lymphocyte adhesion molecule, though recently its involvement in internalization of sialic acid carrying pathogens was shown, suggesting that sialoadhesin is an endocytic receptor. In this report, we show that porcine sialoadhesin-specific antibodies and F(ab')(2) fragments trigger sialoadhesin internalization, both in primary porcine macrophages and in cells expressing recombinant porcine sialoadhesin. Using chemical inhibitors, double immunofluorescence stainings and dominant-negative constructs, porcine sialoadhesin internalization was shown to be clathrin-and Eps15-dependent and to result in targeting to early endosomes but not lysosomes. Besides characterizing the sialoadhesin endocytosis mechanism, two sialoadhesin-specific immunoconjugates were evaluated. We observed that porcine sialoadhesin-specific immunotoxins efficiently kill sialoadhesin-expressing macrophages. Furthermore, porcine sialoadhesin-specific albumin immunoconjugates were shown to be internalized in macrophages and immunization with these immunoconjugates resulted in a rapid and robust induction of albumin-specific antibodies, this compared to immunization with albumin alone. Together, these data expand sialoadhesin functionality and show that it can function as an endocytic receptor, a feature that cannot only be misused by sialic acid carrying pathogens, but that may also be used for specific targeting of toxins or antigens to sialoadhesin-expressing macrophages.

http://ift.tt/2oZ60NF

Interferon alpha induces establishment of Alphaherpesvirus latency in sensory neurons in vitro

Background: Several alphaherpesviruses, including herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV), establish lifelong latency in neurons of the trigeminal ganglion (TG). Although it is thought that efficient establishment of alphaherpesvirus latency is based on a subtle interplay between virus, neurons and the immune system, it is not clear which immune components are of major importance for the establishment of latency. Methodology/Principal Findings: Here, using an in vitro model that enables a natural route of infection, we show that interferon alpha (IFNalpha) has the previously uncharacterized capacity to induce a quiescent HSV-1 and PRV infection in porcine TG neurons that shows strong similarity to in vivo latency. IFNalpha induced a stably suppressed HSV-1 and PRV infection in TG neurons in vitro. Subsequent treatment of neurons containing stably suppressed virus with forskolin resulted in reactivation of both viruses. HSV and PRV latency in vivo is often accompanied by the expression of latency associated transcripts (LATs). Infection of TG neurons with an HSV-1 mutant expressing LacZ under control of the LAT promoter showed activation of the LAT promoter and RT-PCR analysis confirmed that both HSV-1 and PRV express LATs during latency in vitro. Conclusions/Significance: These data represent a unique in vitro model of alphaherpesvirus latency and indicate that IFNalpha may be a driving force in promoting efficient latency establishment.

http://ift.tt/2pGmok1

Transmission of pseudorabies virus from immune-masked blood monocytes to endothelial cells

Pseudorabies virus (PRV) may cause abortion, even in the presence of vaccination-induced immunity. Blood monocytes are essential to transport the virus in these immune animals, including transport to the pregnant uterus. Infected monocytes express viral proteins on their cell surface. Specific antibodies recognize these proteins and should activate antibody-dependent cell lysis. Previous work showed that addition of PRV-specific polyclonal antibodies to PRV-infected monocytes induced internalization of viral cell surface proteins, protecting the cells from efficient antibody-dependent lysis in vitro (immune-masked monocytes). As a first step to reach the pregnant uterus, PRV has to cross the endothelial cell barrier of the maternal blood vessels. The current aim was to investigate in vitro whether immune-masked PRV-infected monocytes can transmit PRV in the presence of virus-neutralizing antibodies via adhesion and fusion of these monocytes with endothelial cells. Porcine blood monocytes, infected with a lacZ-carrying PRV strain were incubated with PRV-specific antibodies to induce internalization. Then, cells were co-cultivated with endothelial cells for different periods of time. Only PRV-infected monocytes with internalized viral cell surface proteins adhered efficiently to endothelial cells. LacZ transmission to endothelial cells, as a measure for monocyte-endothelial cell fusion, could be detected after co-cultivation from 30 min onwards. Virus transmission was confirmed by the appearance of plaques. Adhesion of immune-masked PRV-infected monocytes to endothelial cells was mediated by cellular adhesion complex CD11b-CD18 and subsequent fusion was mediated by the virus. In conclusion, immune-masked PRV-infected monocytes can adhere and subsequently transmit virus to endothelial cells in the presence of PRV-neutralizing antibodies.

http://ift.tt/2oZdwbr

Pseudorabies virus (PRV)-specific antibodies suppress intracellular viral protein levels in PRV-infected monocytes

Blood monocytes infected with pseudorabies virus (PRV), a swine alphaherpesvirus, are not eliminated efficiently by anti body-dependent immunity and may occasionally transport PRV to the pregnant uterus of vaccinated animals. This study examines in vitro the long-term fate of PRV-infected monocytes cultivated in the presence of porcine PRV-specific antibodies. All monocytes were infected and expressed viral late proteins, and 30 % of PRV-infected monocytes cultivated with PRV-specific antibodies survived up to 194 h post-infection (p.i.), the end of the experiment (compared to 0 % for cells cultivated with PRV-negative antibodies). Of these surviving cells, +/- 75 % no longer expressed microscopically detectable viral late proteins from 144 h p.i. onwards. Remarkably, monocytes infected with a PRV gB-null virus did not survive in the presence of PRV-specific; antibodies. These data suggest that PRV-specific antibodies suppress viral protein levels in infected monocytes, perhaps helping the virus to persist and reach internal organs in vaccinated animals.

http://ift.tt/2pGMi7s

Anti body-induced internalization of viral glycoproteins and gE-gl Fc receptor activity protect pseudorabies virus-infected monocytes from efficient complement-mediated lysis

Pseudorabies virus (PRV)-infected blood monocytes are able to transport virus throughout the body of vaccination-immune pigs. PRV-infected monocytes express viral glycoproteins in their plasma membrane that can be recognized by virus-specific antibodies. Recently, it has been shown that addition of PRV-specific polyclonal immunoglobulins to PRV-infected monocytes at 37degreesC induces internalization of the majority of plasma membrane-expressed viral glycoproteins. This study investigated whether this process may interfere with efficient antibody-dependent complement-mediated lysis (ADCML) of infected monocytes. Therefore, an ADCML assay was set up in vitro. A significant decrease in the percentage of cells lysed by ADCML was observed when antibody-induced internalization of PRV glycoproteins occurred (P<0.005). Furthermore, it is shown (i) that the PRV gE-gl complex, which, like certain other alphaherpesvirus orthologues, possesses IgG-binding capacity, aids in avoiding efficient ADCML of PRV-infected monocytes and (ii) that the efficiency of PRV gE-gl-mediated evasion of ADCML can be decreased by the presence of gE-gl-specific antibodies.

http://ift.tt/2oYYOB0

Virus complement evasion strategies

The immune system has a variety of tools at its disposal to combat virus infections. These can be subdivided roughly into two categories: 'first line defence', consisting of the non-specific, innate immune system, and 'adaptive immune response', acquired over time following virus infection or vaccination. During evolution, viruses have developed numerous, and often very ingenious, strategies to counteract efficient recognition of virions or virus-infected cells by both innate and adaptive immunity. This review will focus on the different strategies that viruses use to avoid recognition by one of the components of the immune system: the complement system. Complement evasion is of particular importance for viruses, since complement activation is a crucial component of innate immunity (alternative and mannan-binding lectin activation pathway) as well as of adaptive immunity (classical, anti body-dependent complement activation).

http://ift.tt/2pGKprp

Characterization of different plaque-forming and defective temperate phages in Agrobacterium strains

http://ift.tt/2oZmXaF

Johns Hopkins Center for Inherited Disease Research Receives $213 Million of New Funding

The Johns Hopkins Center for Inherited Disease Research (CIDR) marked its 20-year history supporting large-scale scientific collaboration by securing funding to the center through 2023. CIDR successfully competed for a seven-year contract from the National Institutes of Health (NIH) providing up to $213 million in research funding. The renewal contract enables NIH-funded researchers to use CIDR's sequencing, high-throughput genotyping, analysis and informatics services for a wide array of studies exploring genetic contributions to human health and disease.

http://ift.tt/2pGvVrr

Sinonasal Undifferentiated Carcinoma in a Patient Previously Treated for an Intestinal-Type Adenocarcinoma: Metachronous Neoplasms or Recurrence of a Different Tumor Type?

Abstract

A case of a sinonasal undifferentiated carcinoma occurring 2 years after a successfully surgically treated intestinal-type adenocarcinoma has never been reported. Treatment modality of paranasal sinus cancer strictly depends on histology so it is important to recognize a different tumor type in the follow-up of these patients.

http://ift.tt/2pGmxUu

Factors Affecting the Outcome of Stapes Surgery

Abstract

To study the outcome of stapes surgery based on the Clinical, Audiometry, and Surgical pre- and postoperative factors. This study is a prospective study of factors affecting the outcome of stapes surgery in otosclerosis patients. From February 2010 to June 2011, 57 patients of confirmed clinical otosclerosis were analysed. Out of them, 31 patients were included in our study as were available for follow-up. Clinical, audiometry and surgery-related parameters were included to assess the surgery outcome. Results were reported as suggested by AAO-HNS (American Association of Otolaryngology and Head and Neck Surgery) guidelines for stapes surgery, 1995. The paired t-test and analysis of variables test (ANOVA) were used to evaluate the results. A p value of <0.05 was considered significant. There was statistically significant improvement in ABG (air bone gap) closure at 3 months of surgery (p value <0.001). Among all cases, PTA BC (pure tone average bone conduction) at 3 months of surgery was found in the range of 7.5 dB to 43.75 dB. ABG closure was achieved in the range of 0 dB to 27.5 dB among all cases. Variables like gender, degree of hearing loss, type of footplate, sealing material, and piston diameter were definitely predicting the outcome of stapes surgery. Pure tone audiometry plays an important role to diagnose the otosclerosis, to evaluate degree and type of hearing loss and to assess hearing outcome after surgery. Our results may improve knowledge of predictive factors, providing the surgeon with useful information to plan surgery with a better case selection as well as to counsel the patient on the likelihood of success of the procedure.

http://ift.tt/2oZ0j22

Transnasal Stabilization in Naso-orbito-ethmoid Fractures: The Easy Way!

Abstract

Effective management of naso orbito ethmoidal fractures involves both functional and esthetic correction. While functional correction is routinely achieved, in our experience, most secondary deformities resulted from inadequate nasal bridge projection. We hereby suggest a simple technique to stabilize the nasal bridge after mild overcorrection thereby improving the esthetic outcome in naso orbito ethmoidal fractures.

http://ift.tt/2pGuDwz

Protocol for Combined Analysis of FOXFIRE, SIRFLOX, and FOXFIRE-Global Randomized Phase III Trials of Chemotherapy +/- Selective Internal Radiation Therapy as First-Line Treatment for Patients With Metastatic Colorectal Cancer.

Virdee, PS; Moschandreas, J; Gebski, V; Love, SB; Francis, EA; Wasan, HS; van Hazel, G; Virdee, PS; Moschandreas, J; Gebski, V; Love, SB; Francis, EA; Wasan, HS; van Hazel, G; Gibbs, P; Sharma, RA; - view fewer (2017) Protocol for Combined Analysis of FOXFIRE, SIRFLOX, and FOXFIRE-Global Randomized Phase III Trials of Chemotherapy +/- Selective Internal Radiation Therapy as First-Line Treatment for Patients With Metastatic Colorectal Cancer. JMIR Res Protoc , 6 (3) , Article e43. 10.2196/resprot.7201 . Green open access

http://ift.tt/2pW0Fnz

L-ornithine L-aspartate for people with cirrhosis and hepatic encephalopathy

Stokes, CS; Goh, ET; Vilstrup, H; Morgan, MY; Gluud, LL; (2016) L-ornithine L-aspartate for people with cirrhosis and hepatic encephalopathy. Cochrane Database of Systematic Reviews , 2016 (10) , Article CD012410. 10.1002/14651858.CD012410 .

http://ift.tt/2pjh0pX

Price-based controller for quality-fair HTTP adaptive streaming

D'Aronco, S; Frossard, P; Toni, L; (2017) Price-based controller for quality-fair HTTP adaptive streaming. In: (In press).

http://ift.tt/2pW4o4E

Computationally viable handling of beliefs in arguments for persuasion

Hadoux, E; Hunter, A; (2017) Computationally viable handling of beliefs in arguments for persuasion. In: Proceedings of the 28th International Conference on Tools with Artificial Intelligence (ICTAI). (pp. pp. 319-326). IEEE Green open access

http://ift.tt/2pjh09r

Ammonia scavenging agents for people with cirrhosis and hepatic encephalopathy

Zacharias, HD; Zacharias, AP; Oliveira Ferreira, A; Morgan, MY; Gluud, LL; (2016) Ammonia scavenging agents for people with cirrhosis and hepatic encephalopathy. Cochrane Database of Systematic Reviews , 2016 (8) , Article CD012334. 10.1002/14651858.CD012334 .

http://ift.tt/2pVTN9z

An Ensemble-Based Protocol for the Computational Prediction of Helix-Helix Interactions in G Protein-Coupled Receptors using Coarse-Grained Molecular Dynamics

Altwaijry, NA; Baron, M; Wright, DW; Coveney, PV; Townsend-Nicholson, A; (2017) An Ensemble-Based Protocol for the Computational Prediction of Helix-Helix Interactions in G Protein-Coupled Receptors using Coarse-Grained Molecular Dynamics. Journal of Chemical Theory and Computation 10.1021/acs.jctc.6b01246 . (In press).

http://ift.tt/2pjm5P4

Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease

Mattsson, N; Andreasson, U; Zetterberg, H; Blennow, K; Alzheimer's Disease Neuroimaging Initiative, ; (2017) Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease. JAMA Neurology 10.1001/jamaneurol.2016.6117 . (In press).

http://ift.tt/2pVJgLF

Post-operative efficacy, predictability, safety and visual quality of laser corneal refractive surgery: a network meta-analysis.

Wen, D; McAlinden, C; Flitcroft, I; Tu, R; Wang, Q; Alió, J; Marshall, J; Wen, D; McAlinden, C; Flitcroft, I; Tu, R; Wang, Q; Alió, J; Marshall, J; Huang, Y; Song, B; Hu, L; Zhao, Y; Zhu, S; Gao, R; Bao, F; Yu, A; Yu, Y; Lian, H; Huang, J; - view fewer (2017) Post-operative efficacy, predictability, safety and visual quality of laser corneal refractive surgery: a network meta-analysis. Am J Ophthalmol , 178 pp. 65-78. 10.1016/j.ajo.2017.03.013 .

http://ift.tt/2pjgzfh

Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer's Disease.

Brownjohn, PW; Smith, J; Portelius, E; Serneels, L; Kvartsberg, H; De Strooper, B; Blennow, K; Brownjohn, PW; Smith, J; Portelius, E; Serneels, L; Kvartsberg, H; De Strooper, B; Blennow, K; Zetterberg, H; Livesey, FJ; - view fewer (2017) Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer's Disease. Stem Cell Reports , 8 (4) pp. 870-882. 10.1016/j.stemcr.2017.02.006 . Green open access

http://ift.tt/2pVIZIM

Delivering the world's most intense muon beam

Cook, S; D'Arcy, R; Edmonds, A; Fukuda, M; Hatanaka, K; Hino, Y; Kuno, Y; Cook, S; D'Arcy, R; Edmonds, A; Fukuda, M; Hatanaka, K; Hino, Y; Kuno, Y; Lancaster, M; Mori, Y; Ogitsu, T; Sakamoto, H; Sato, A; Tran, NH; Truong, NM; Wing, M; Yamamoto, A; Yoshida, M; - view fewer (2017) Delivering the world's most intense muon beam. Physical Review Accelerators and Beams , 20 , Article 030101. 10.1103/PhysRevAccelBeams.20.030101 . Green open access

http://ift.tt/2pj4ZRA

Cardiorespiratory fitness alters the influence of a polygenic risk score on biomarkers of AD

Schultz, SA; Boots, EA; Darst, BF; Zetterberg, H; Blennow, K; Edwards, DF; Koscik, RL; Schultz, SA; Boots, EA; Darst, BF; Zetterberg, H; Blennow, K; Edwards, DF; Koscik, RL; Carlsson, CM; Gallagher, CL; Bendlin, BB; Asthana, S; Sager, MA; Hogan, KJ; Hermann, BP; Cook, DB; Johnson, SC; Engelman, CD; Okonkwo, OC; - view fewer (2017) Cardiorespiratory fitness alters the influence of a polygenic risk score on biomarkers of AD. Neurology 10.1212/WNL.0000000000003862 . (In press).

http://ift.tt/2pVJS3W

Sinonasal Undifferentiated Carcinoma in a Patient Previously Treated for an Intestinal-Type Adenocarcinoma: Metachronous Neoplasms or Recurrence of a Different Tumor Type?

Abstract

http://ift.tt/2pGmxUu

Factors Affecting the Outcome of Stapes Surgery

Abstract

http://ift.tt/2oZ0j22

Transnasal Stabilization in Naso-orbito-ethmoid Fractures: The Easy Way!

Abstract

http://ift.tt/2pGuDwz

Exact and Efficient Algorithms for Pairwise Learning

http://ift.tt/2pGTxit

Het vroege christendom en de antiekemysterieculten

http://ift.tt/2oTwAWt

Design considerations for robust noise rejection in otoacoustic emissions measured in-field using adaptive filtering

Otoacoustic emission (OAE) measurement is a sensitive and effective technique to monitor changes in the inner ear potentially induced by noise exposure. However, outside a controlled testing environment, measurements are challenging since the level of ambient noise might be higher than the low-level OAE response. Therefore, an OAE system was designed, suitable to measure OAEs repeatedly on an individual worker in noisy test conditions. This system features a left and right earpiece, each equipped with a pair of miniature loudspeakers, an external and an internal microphone. In addition to the passive attenuation of the earpiece, adaptive filtering on the distortion product OAE (DPOAE) signals is used to further enhance the ratio between the measured OAE signal and interfering noise. The adaptive filtering technique uses the sound captured by the ipsilateral external and internal microphones as well as from the contralateral internal and external microphones. In this paper, the accuracy of DPOAE signals are studied using different combinations of the four microphones in single and dual adaptive filter topologies, as well as the benefits of adding a fixed transfer function in the adaptive filtering algorithm topology to estimate the acoustic path. Side-by-side comparison shows that a dual-stage adaptive filtering algorithm, using a combination of the contralateral internal microphone with the ipsilateral external microphone, is the most promising approach to denoise the DPOAE signal.

http://ift.tt/2pGpdEM

Siberian sturgeon (Acipenser baerii) larvae fed Artemia nauplii enriched with poly-β-hydroxybutyrate (PHB) : effect on growth performance, body composition, digestive enzymes, gut microbial community, gut histology and stress tests

The effects of feeding Artemia nauplii enriched with or without poly--hydroxybutyrate (PHB) and/or highly unsaturated fatty acids (HUFA) on Siberian sturgeon (Acipenser baerii) larvae were investigated. Feeding larvae with PHB-enriched nauplii (PHB, PHB + HUFA) decreased the growth performance of the larvae. PHB affected the body composition by increasing the lipid content of the whole body and decreasing total saturated, monoenoic, n3, n6 and decosahexanoeic acid (DHA) in the larvae, indicating that the PHB addition affected lipid metabolism. A high activity of pepsin was observed in the digestive extracts of PHB treatments (PHB, PHB + HUFA), while PHB suppressed amylase activity in the intestine of the larvae. Based on molecular analysis, PHB changed the microbial community in the distal intestine of the larvae. The highest counts of goblet cells were observed in the HUFA-containing treatments (HUFA, PHB + HUFA), indicating that HUFA addition may improve the mucosal barrier defence system. The overall quality of the larvae was evaluated by exposing them to different salinities and ammonia stress levels. PHB decreased survival rates in these challenges. Our results show that optimal PHB doses for bio-encapsulation into Artemia remain to be determined for further application at the earliest larval stages of sturgeon.

http://ift.tt/2oTta66

UVA 1 laser in the treatment of patients with vitiligo

http://ift.tt/2pGpjMo

Medium-sized nevus spilus of the neck treated with pulsed dye laser

Abstract

Patients with large benign melanocytic lesions located on the neck represent a therapeutic challenge since the neck is a high-risk area for hypertrophic scarring and/or retraction. When treating a benign, extensive and visible melanocytic lesion, the choice of therapy mainly depends on the likelihood of improved cosmesis. We report a case of a 33-year-old woman with a medium-sized Nevus Spilus located on the neck, successfully treated with four sessions of pulsed dye laser. We achieved an excellent clinical and cosmetic result in such a challenging area. No scarring, distortion or significant dyscromia were observed after 24 months.

http://ift.tt/2ouDnnC

Non-cosmetic dermatological use of botulinum neurotoxin

http://ift.tt/2pGyH2K

Fractured politics? The comparative regulation of shale gas in Europe

http://ift.tt/2oYzzyY

RIMA-Dependent Nuclear Accumulation of IYO Triggers Auxin-Irreversible Cell Differentiation in Arabidopsis

http://ift.tt/2oSOSHg

PHR1 Balances between Nutrition and Immunity in Plants

Plants assemble beneficial root-associated microbiomes to support growth, especially in nutrient-poor conditions. To do so, however, plants have to suppress their immune system. Reporting in Nature, Castrillo et al. (2017) identified PHOSPHATE STARVATION RESPONSE1 (PHR1) as a central regulator in this balance between nutrient stress response and immune regulation.

http://ift.tt/2oNTwYC

Dynamic control of lateral root positioning

In dicot root systems, lateral roots are in general regularly spaced along the longitudinal axis of the primary root to facilitate water and nutrient uptake. Recently, recurrent programmed cell death in the root cap of the growing root has been implicated in lateral root spacing. The root cap contains an auxin source that modulates lateral root patterning. Periodic release of auxin by dying root cap cells seems to trigger lateral root specification at regular intervals. However, it is currently unclear through which molecular mechanisms auxin restricts lateral root specification to specific cells along the longitudinal and radial axes of the root, or how environmental signals impact this process.

http://ift.tt/2oT0H0c

The Origin of Floral Organ Identity Quartets

The origin of flowers has puzzled plant biologists ever since Darwin referred to their sudden appearance in the fossil record as an abominable mystery. Flowers are considered to be an assembly of protective, attractive, and reproductive male and female leaf-like organs. Their origin cannot be understood by a morphological comparison to gymnosperms, their closest relatives, which develop separate male or female cones. Despite these morphological differences, gymnosperms and angiosperms possess a similar genetic toolbox consisting of phylogenetically related MADS domain proteins. Using ancestral MADS domain protein reconstruction, we trace the evolution of organ identity quartets along the stem lineage of crown angiosperms. We provide evidence that current floral quartets specifying male organ identity, which consist of four types of subunits, evolved from ancestral complexes of two types of subunits through gene duplication and integration of SEPALLATA proteins just before the origin of flowering plants. Our results suggest that protein interaction changes underlying this compositional shift were the result of a gradual and reversible evolutionary trajectory. Modeling shows that such compositional changes may have facilitated the evolution of the perfect, bisexual flower.

http://ift.tt/2oO1v8c

Herausforderungen in der Behandlung älterer Patienten mit akuter myeloischer Leukämie

Zusammenfassung

Hintergrund

Die akute myeloische Leukämie (AML) ist eine Erkrankung des älteren Patienten mit steigender Inzidenz bis in die 8. Lebensdekade. Die Prognose verschlechtert sich mit zunehmenden Alter drastisch und ist mit einer Fünfjahresüberlebensrate von unter 10 % für Patienten über 60 Jahre unbefriedigend.

Ergebnisse

Die Standardtherapien der AML sind zumeist für jüngere Patienten etabliert und nur bedingt auf ältere Patienten übertragbar. Publizierte Daten haben folgende Ergebnisse darstellen können: Es zeigt sich ein Nutzen für eine intensive Induktionstherapie mit Daunorubicin und Ara-C für fitte Patienten bis zum 80. Lebensjahr hinsichtlich des Gesamtüberlebens, aber auch bezogen auf die Lebensqualität in großen Registerstudien. Die Herausforderung im klinischen Alltag bleibt, ältere Patienten, die einer intensiven Chemotherapie unterzogen werden sollten, prätherapeutisch zu identifizieren; dies sollte ggf. in spezialisierten Zentren erfolgen. Die Bedeutung der Postremissionstherapie für ältere Patienten ist in Diskussion und abhängig vom Risikoprofil: 1–2 Zyklen Hochdosis-Ara-C können als Standard angesehen werden. Eine allogene Stammzelltransplantation mit reduzierten Konditionierungsschemata sollte für geeignete Patienten ebenso in Betracht gezogen werden. Zudem stellen hypomethylierende Substanzen wertvolle, zusätzliche Therapieoptionen für ältere AML-Patienten dar, die zunehmend mit neuen Medikamente in klinischen Studien in Kombinationen getestet werden.

Schlussfolgerung

Für jeden älteren Patienten soll eine umfassende AML-Diagnostik durchgeführt und sorgfältig die Eignung für eine intensive Induktionschemotherapie abgewogen werden. Der Einschluss von älteren Patienten in klinische Studien ist für den weiteren Erkenntnisgewinn dieser doch schwierigen Behandlungssituation wesentlich.

http://ift.tt/2pG0yNr

Αρχειοθήκη ιστολογίου

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Πέμπτη 20 Απριλίου 2017

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