Rational Approach to Allergy Testing

Allergy testing is commonly used when symptoms of allergic rhinitis are refractory to symptoms and there is potential for treatment with institution of avoidance measures or immunotherapy. Once the decision for testing has been made, the method of testing by either in vivo skin testing by prick/puncture or intradermal testing or in vitro testing of serum-specific IgE is dictated by factors in the clinical history and an informed decision by the patient. Because there is no perfect testing method, understanding the benefits and limitations of each method is important in selecting the best testing option for each patient.

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Clinical Applications of Sublingual Immunotherapy

Sublingual immunotherapy (SLIT) is effective for the treatment of allergic rhinitis and allergic asthma in adults and children. In a limited number of studies, SLIT efficacy has been demonstrated for the treatment of food allergy. SLIT has a higher safety profile versus subcutaneous immunotherapy, although some systemic reactions have been reported. Appropriate patient selection, meticulous patient education, and routine follow-up are key for the safe and effective administration of SLIT. With organization and attention to detail, adding SLIT to one's practice can provide a highly valued patient service.

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Contents

Sujana S. Chandrasekhar

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Management of Anaphylaxis

Anaphylaxis is a severe systemic reaction that can be managed appropriately with expedient diagnosis and treatment. Intramuscular epinephrine continues to be the mainstay of treatment of anaphylaxis; however, it is still underused in the community and in the medical setting. Further education and counseling of patients and health care providers is required to prevent and manage anaphylaxis successfully. In-office management of anaphylaxis includes training of staff, preparedness with the necessary supplies and medication, and an effective action plan.

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Copyright-Page

Elsevier

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Allergy for the Otolaryngologist

The diagnosis and treatment of allergic disease is an integral part of otolaryngology practice, where care for inflammatory disorders of the nose, sinuses, and upper airway is common. This issue of Otolaryngologic Clinics of North America is designed to bring the practicing otolaryngologist up to date by focusing on where developments have occurred.

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CME Accreditation Page

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Allergy as Part of the Unified Otolaryngologic Practice

The management of allergic disorders is an integral part of the specialty of otolaryngology–head and neck surgery. Its importance in the comprehensive management of the ENT patient has become more and more apparent over time. In 1985, 58% of Otolaryngology residency programs offered no formal training in allergy. That situation had improved by 2006, when 62% of programs had active allergy programs, and the remainder were adding them.1,2

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Contributors

SUJANA S. CHANDRASEKHAR, MD

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Allergy for the Otolaryngologist

OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA

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Forthcoming Issues

Congenital Vascular Lesions of the Head and Neck

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Copyright

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4





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Forthcoming Issues

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4





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Anesthesia Outside the Operating Room

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Mark S. Weiss, Wendy L. Gross




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Anesthesia Outside the Operating Room

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Mark S. Weiss, Wendy L. Gross




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Safety of Non–Operating Room Anesthesia

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Zachary G. Woodward, Richard D. Urman, Karen B. Domino

Teaser

Malpractice claims for non–operating room anesthesia care (NORA) had a higher proportion of claims for death than claims in operating rooms (ORs). NORA claims most frequently involved monitored anesthesia care. Inadequate oxygenation/ventilation was responsible for one-third of NORA claims, often judged probably preventable by better monitoring. Fewer malpractice claims for NORA occurred than for OR anesthesia as assessed by the relative numbers of in NORA versus OR procedures. The proportion of claims in cardiology and radiology NORA locations were increased compared with estimates of cases in these locations. Although NORA is safe, adherence to safe clinical practice is important.


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Implementation and Use of Anesthesia Information Management Systems for Non–operating Room Locations

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Jason T. Bouhenguel, David A. Preiss, Richard D. Urman

Teaser

Non–operating room anesthesia (NORA) encounters comprise a significant fraction of contemporary anesthesia practice. With the implemention of an aneshtesia information management system (AIMS), anesthesia practitioners can better streamline preoperative assessment, intraoperative automated documentation, real-time decision support, and remote surveillance. Despite the large personal and financial commitments involved in adoption and implementation of AIMS and other electronic health records in these settings, the benefits to safety, efficacy, and efficiency are far too great to be ignored. Continued future innovation of AIMS technology only promises to further improve on our NORA experience and improve care quality and safety.


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Monitoring for Nonoperating Room Anesthesia

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Stylianos Voulgarelis, John P. Scott

Teaser

Procedures requiring nonoperating room anesthesia (NORA) continue to increase in quantity and complexity. The roles of anesthesiologists as members of care teams in nonoperating room locations continue to evolve. The safe provision of NORA requires strict adherence to standardized monitoring guidelines including pulse oximetry, capnography, electrocardiogram, and noninvasive blood pressure ampliflier. Body temperature should also be measured in appropriate scenarios. High-risk anesthetics require advanced preparation and monitoring.


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An Anesthesiologist’s View of Tumor Ablation in the Radiology Suite

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Annie Amin, Jason Lane, Thomas Cutter

Teaser

The advent of radiology image–guided tumor ablation procedures has opened up a new era in minimally invasive procedures. Using CT, MRI, ultrasound, and other modalities, radiologists and surgeons can now ablate a tumor through percutaneous entry sites. What traditionally was done in an operating room via large open incisions, with multiple days in the hospital recovering, is now becoming an outpatient procedure via these new techniques. Anesthesiologists play a critical role in optimizing outcome in these patients. Knowledge by anesthesiologists of procedural goals, technology used, and inherit safety concerns of anesthetizing patients in the radiology suite are all critical to patients and proceduralists.


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A Radiologist’s View of Tumor Ablation in the Radiology Suite

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Sharath K. Bhagavatula, Jason Lane, Paul Shyn

Teaser

Image-guided percutaneous, minimally invasive ablation techniques offer a wide variety of new modalities to treat tumors in some of the most medically complicated patients coming to our hospitals. The use of computed tomography, PET, ultrasound imaging, and MRI to guide radiofrequency ablation, microwave ablation, and cryoablation techniques now makes it possible to treat patients on a short stay or outpatient basis with very good immediate outcomes. This rapid expansion of new tumor ablation techniques often presents challenges for the non–operating room anesthesia team. Collaboration and communication between the radiologist and anesthesiologist are key to safety and excellent patient outcomes.


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Catheterization Laboratory

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Paul N. Fiorilli, Saif Anwaruddin, Elizabeth Zhou, Ronak Shah

Teaser

The cardiac catheterization laboratory is advancing medicine by performing procedures on patients who would usually require sternotomy and cardiopulmonary bypass. These procedures are done percutaneously, allowing them to be performed on patients considered inoperable. Patients have compromised cardiovascular function or advanced age. An anesthesiologist is essential for these procedures in case of hemodynamic compromise. Interventionalists are becoming more familiar with transcatheter aortic valve replacement and the device has become smaller, both contributing to less complications. Left atrial occlusion and the endovascular edge-to-edge mitral valve repair devices were approved. Although these devices require general anesthesia, an invasive surgery and cardiopulmonary bypass machine are not necessary for deployment.


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Anesthesia in the Electrophysiology Laboratory

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Jeff E. Mandel, William G. Stevenson, David S. Frankel

Teaser

The electrophysiology suite is a foreign location to many anesthesiologists. The initial experience was with shorter procedures under conscious sedation, and the value of greater tailoring of the sedation/anesthesia by anesthesiologists was not perceived until practice patterns had already been established. Although better control of ventilation with general anesthesia may be expected, suppression of arrhythmias, blunting of the hemodynamic adaptation to induced arrhythmias, and interference by muscle relaxants with identification of the phrenic nerve may be seen. We review a range of electrophysiology procedures and discuss anesthetic approaches that balance patient safety and favorable outcomes.


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Cardioversions and Transthoracic Echocardiography

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Ronak Shah, Elizabeth Zhou

Teaser

Patients with atrial fibrillation and flutter routinely require transesophageal echocardiography with cardioversion. It is not uncommon to encounter patients with reduced ejection fractions, coronary artery disease, prior cardiac surgery, or obstructive sleep apnea. The anesthesiologist must carefully evaluate the patient and any available laboratory and study findings to assess for potential complications after anesthesia. Appropriate anesthetics must be chosen based on the preoperative evaluation. Additionally, because most of these cases are done without a secured airway, emergency medications and airway equipment must be readily available.


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Anesthesia for Routine and Advanced Upper Gastrointestinal Endoscopic Procedures

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Christopher D. Sharp, Ezekiel Tayler, Gregory G. Ginsberg

Teaser

This article aims to detail the breadth and depth of advanced upper gastrointestinal endoscopic procedures. It will focus on sedation and airway management concerns pertaining to this emerged and emerging class of minimally invasive interventions. The article will also cover endoscopic hemostasis, endoscopic resection, stenting and Barrett eradication therapy plus endoscopic ultrasound. It additionally will address the nuances of endoscopic retrograde cholangiopancreatography and new natural orifice transluminal endoscopic surgery procedures including endoscopic cystgastrostomy and the per-oral endoscopic myotomy procedure.


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Anesthesia for Colonoscopy and Lower Endoscopic Procedures

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): John Michael Trummel, Vinay Chandrasekhara, Michael L. Kochman

Teaser

Demand for anesthesiologist-assisted sedation is expanding for gastrointestinal lower endoscopic procedures and may add to the cost of these procedures. Most lower endoscopy can be accomplished with either no, moderate, or deep sedation; general anesthesia and active airway management are rarely needed. Propofol-based sedation has advantages in terms of satisfaction and recovery over other modalities, but moderate sedation using benzodiazepines and opiates work well for low-risk patients and procedures. No sedation for routine colonoscopy works well for selected patients and eliminates sedation-related risks. There is no difference in outcome measures based on sedation received.


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CORRECTION

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Isotretinoin treatment for acne and risk of depression: A systematic review and meta-analysis

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Treatment of seasonal allergic rhinitis

Allergic rhinitis (AR) is a prevalent disorder responsible for a significant and often underappreciated health burden for individuals and society (see Burden of Disease section). Guidelines to improve care for patients with AR have been evolving in an effort to respond to the introduction of new treatment approaches, to address the availability of additional studies that compare treatment options, and to incorporate the use of more standardized, evidence-based medicine methods to analyze data and make recommendations.

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Guiding principles for use of newer biologics and bronchial thermoplasty for patients with severe asthma

Severe asthma poses significant disease-related and economic burdens in the United States. Challenges in practice include how to define "severe asthma" for a given patient, knowing which are the right tests to perform and when, and having a better understanding of a patient's asthma phenotype. Furthermore, current guidelines do not address a clear, practical approach to treatment that is based on a patient's asthma phenotype.

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American College of Allergy, Asthma & Immunology Position Paper on the Use of Telemedicine for Allergists

The integration of telecommunications and information systems in health care first began 4 decades ago with 500 patient consultations performed via interactive television. The use of telemedicine services and technology to deliver health care at a distance is increasing exponentially. Concomitant with this rapid expansion is the exciting ability to provide enhancements in quality and safety of care. Telemedicine enables increased access to care, improvement in health outcomes, reduction in medical costs, better resource use, expanded educational opportunities, and enhanced collaboration between patients and physicians.

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Allergy and immunology practice parameters and guidelines

It's spring break, and you're seeing a college student who has a history of moderate-to-severe spring and summer rhinoconjunctivitis. Skin testing shows remarkable wheal and flare reactions to tree and grass pollens. In addition to recommending aeroallergen avoidance measures, which initial treatment has the highest likelihood of helping this patient: intranasal corticosteroid monotherapy or intranasal corticosteroid combined with intranasal antihistamine? Previous practice parameters tended to outline treatments with good evidence of effectiveness, but they rarely provided specific recommendations for these types of questions.

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P236 Comorbidities associated with poor short-acting beta-agonist inhaler handling among united states respiratory patients

Short-acting beta-agonists (SABA), in asthma and chronic obstructive pulmonary disease (COPD) are commonly administered using pressurized metered-dose inhalers (pMDI). Hand-breath coordination is a common challenge with pMDIs demonstrated to result in worse outcomes. This study evaluated the prevalence of comorbidities potentially affecting device handling in asthma and/or COPD patients using SABAs, including albuterol multidose dry powder inhaler (MDPI), the only MDPI not requiring hand-breath coordination.

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The Use of Regional or Neuraxial Anesthesia for Below-Knee Amputations May Reduce the Need for Perioperative Blood Transfusions.

Background and Objectives: Amputations of the lower extremity remain a common procedure in a high-risk population. Perioperative morbidity and mortality reach as high as 14.1% in below-knee amputations. We aimed to determine whether regional, or neuraxial, anesthesia, when compared with general anesthesia (GA), would be associated with reduced perioperative morbidity and mortality. Methods: We queried the American College of Surgeons National Surgical Quality Improvement Program data set. The study population was divided into 2 groups: patients undergoing regional anesthesia (RA) and those undergoing GA. The primary end point for our study was 30-day mortality. The secondary end points were return to the operating room, surgical site infections, pulmonary complications, acute kidney injury, urinary tract infection, cardiac arrest, myocardial infarction, perioperative transfusions, thromboembolisms, sepsis, composite measure of postoperative complications, and days from operation to discharge. Results: Twelve thousand seven hundred twenty-three patients were identified. Older patients, white patients, patients with a higher body mass index, patients without dyspnea, patients with independent functional status, smokers, patients with sepsis, and patients with bleeding disorders were associated with receiving GA. Hispanic patients, patients with chronic obstructive pulmonary disease, and patients with congestive heart failure were associated with receiving RA. Our study did not reveal a 30-day mortality difference between RA and GA. Regional anesthesia was associated with a significantly decreased need for perioperative blood transfusions (11.8% vs 16.5%, P

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Challenging Conventions to Make a Difference in Patient Care: The 2017 Gaston Labat Award Lecture.

No abstract available

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Long-term management and outcomes after repair of cerebrospinal fluid rhinorrhea related to idiopathic intracranial hypertension.

Purpose of review: To identify long-term management strategies and outcomes for the treatment of spontaneous cerebrospinal fluid (CSF) rhinorrhea related to idiopathic intracranial hypertension (IIH). Recent findings: Adjuvant treatments following surgical repair of spontaneous CSF leaks are aimed at normalizing intracranial pressure (ICP) to minimize the risk of recurrence. IIH is closely linked to obesity, and growing evidence suggests that weight loss, both through conservative and surgical approaches, is effective at addressing the root cause of this disorder. Recent data also support the use of acetazolamide and dural venous sinus stenting as adjuncts for reducing ICP. Summary: Spontaneous CSF rhinorrhea associated with IIH represents a challenging clinical entity, with an increased risk of recurrence compared to CSF leaks because of other causes. Adjunct therapies intended to reduce ICP likely improve outcomes after surgical repair, but further research is necessary to better characterize the effects of these treatment modalities. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Updates in the management of sinonasal mucosal melanoma.

Purpose of review: Sinonasal mucosal melanoma (SNMM) is an aggressive cancer with a poor prognosis. Although there is significant study surrounding the treatment of sinonasal malignancies and cutaneous melanomas, the rarity of this tumor has largely precluded robust outcomes analyses. The authors of this review seek to provide an overview of the recent literature related to the treatment of SNMM with added context from our institutional experience with this disease. Recent findings: In the surgical management of sinonasal malignancies and SNMM specifically, resection via endoscopic endonasal technique appears to offer comparable oncologic outcomes versus an open approach. The role of adjuvant therapy continues to be debated, but there is strong evidence for improved rates of local control with radiotherapy after complete resection. In the last few years, significant developments have been made in the study of systemic therapies for cutaneous melanoma. The identification of genetic mutations common to mucosal melanoma has allowed for early trials of targeted therapies, but study is ongoing. Summary: Although the study of SNMM is largely limited to small retrospective case series, treatment continues to evolve. Until effective systemic therapies can be identified, endoscopic resection with adjuvant radiotherapy may offer the best disease-free survival with acceptably low morbidity. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The role of frontal sinus drillouts in nasal polyposis.

Purpose of review: Historically, the common frontal sinusotomy has been reserved only for salvage frontal sinus surgery in patients with severely recalcitrant inflammatory sinus disease. By understanding the pathophysiology of inflammatory sinus disease and the long-term role of topical medication in their treatment, the indications for Draf3 have expanded. Recent findings: A major therapeutic impact from endoscopic sinus surgery for inflammatory sinus disease is imparted by allowing sinus access to topical therapies to work. Although traditionally, the Draf3 frontal sinus procedure has been reserved for revision surgery in severe cases, advancements in technology, instrumentation, and techniques has allowed the Draf3 to evolve to efficient and safe procedure, often applied primarily in select patients. There is evidence to support the indication for Draf3 in primary surgery for severe cases. Summary: In inflammatory sinus disease, the goal of endoscopic sinus surgery is to convert the complex and limited frontal sinus outflow tracts into a simple common cavity. This allows for local, topical anti-inflammatory treatments to control the disease. When patients have broader inflammatory airway disease and asthma, the Draf3, as part of a neo-sinus cavity, is commonly applied early in surgical care. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Local allergic rhinitis: evolution of concepts

The discovery of an exclusive local production of IgE antibodies dates back to the 1970s, but only recently the pathophysiology of such phenomenon was deeply investigated, leading to the concept of local aller...

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Updates in the management of sinonasal mucosal melanoma.

Purpose of review: Sinonasal mucosal melanoma (SNMM) is an aggressive cancer with a poor prognosis. Although there is significant study surrounding the treatment of sinonasal malignancies and cutaneous melanomas, the rarity of this tumor has largely precluded robust outcomes analyses. The authors of this review seek to provide an overview of the recent literature related to the treatment of SNMM with added context from our institutional experience with this disease. Recent findings: In the surgical management of sinonasal malignancies and SNMM specifically, resection via endoscopic endonasal technique appears to offer comparable oncologic outcomes versus an open approach. The role of adjuvant therapy continues to be debated, but there is strong evidence for improved rates of local control with radiotherapy after complete resection. In the last few years, significant developments have been made in the study of systemic therapies for cutaneous melanoma. The identification of genetic mutations common to mucosal melanoma has allowed for early trials of targeted therapies, but study is ongoing. Summary: Although the study of SNMM is largely limited to small retrospective case series, treatment continues to evolve. Until effective systemic therapies can be identified, endoscopic resection with adjuvant radiotherapy may offer the best disease-free survival with acceptably low morbidity. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2xQJ0lB

The role of frontal sinus drillouts in nasal polyposis.

Purpose of review: Historically, the common frontal sinusotomy has been reserved only for salvage frontal sinus surgery in patients with severely recalcitrant inflammatory sinus disease. By understanding the pathophysiology of inflammatory sinus disease and the long-term role of topical medication in their treatment, the indications for Draf3 have expanded. Recent findings: A major therapeutic impact from endoscopic sinus surgery for inflammatory sinus disease is imparted by allowing sinus access to topical therapies to work. Although traditionally, the Draf3 frontal sinus procedure has been reserved for revision surgery in severe cases, advancements in technology, instrumentation, and techniques has allowed the Draf3 to evolve to efficient and safe procedure, often applied primarily in select patients. There is evidence to support the indication for Draf3 in primary surgery for severe cases. Summary: In inflammatory sinus disease, the goal of endoscopic sinus surgery is to convert the complex and limited frontal sinus outflow tracts into a simple common cavity. This allows for local, topical anti-inflammatory treatments to control the disease. When patients have broader inflammatory airway disease and asthma, the Draf3, as part of a neo-sinus cavity, is commonly applied early in surgical care. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2AdiQLq

Hair Loss: Common Causes and Treatment

This review summarizes common causes of, and diagnostic approaches to, nonscarring alopecia. How should each be managed?
American Family Physician

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Glomangiomyoma of the neck in a child in Nepal: a rare case report and literature review

Glomangiomyoma is a rare histological variant of glomus tumour. Clinically, it mimicks as a haemangioma and is challenging to diagnose. Its occurrence in the neck of a child has not been previously described.

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Pylephlebitis presenting as spontaneous coronary sinus thrombosis: a case report

Coronary sinus thrombosis is a rare phenomenon. When identified, it most often is a complication of infective endocarditis or procedural intervention. We present an unusual and unreported case of spontaneous c...

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Bioabsorbable Steroid-Releasing Implant in the Frontal Sinus After Endoscopic Sinus Surgery

This randomized clinical trial assess the safety and efficacy of an hourglass-shaped, bioabsorbable, steroid-releasing sinus implant in improving postoperative outcomes when placed in the frontal sinus ostia following endoscopic sinus surgery in patients with chronic rhinosinusitis.

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Association of Treatment at High-Volume Facilities With Survival in Nasopharyngeal Cancer

Using the National Cancer Database, this study examines the association of treatment at high-volume facilities with survival in patients receiving chemotherapy for nasopharyngeal cancer.

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Frontal Sinus Drug-Eluting Implants—Effective, but for Which Patients and at What Cost?

Surgical intervention for chronic rhinosinusitis (CRS) is an important treatment option for patients refractory to medical therapy. Despite advances in surgical techniques and operative technology, revision endoscopic sinus surgery (ESS) is necessary in 6% to 19% of patients. Reasons for revision surgery include scarring and adhesion formation, recurrent polyposis, and persistent inflammation. These issues are especially problematic in the frontal recess given the narrow anatomic boundaries that limit the size of the surgical sinusotomy that can be created. Long-term patency rates are reported in the range of 67% to 92%. Attempts to improve the success of frontal sinus surgery by decreasing scarring and inflammation have been long standing and a variety of stenting options exist. Recent advancements in bioabsorbable and drug-eluting stents provide a new possibility for improving postoperative sinus surgery outcomes.

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Hypoglossal Nerve Stimulation for Children With Down Syndrome and Sleep Apnea

This case series examines whether hypoglossal nerve stimulation is safe and effective in children with Down syndrome and obstructive sleep apnea.

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Adjuvant External Beam Radiotherapy in Differentiated Thyroid Cancer

This cohort study investigates the role of adjuvant external beam radiotherapy in locally advanced differentiated thyroid cancer.

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Newborn susceptibility to infection vs. disease depends on complex in vivo interactions of host and pathogen

Abstract

The burden of newborn infectious disease has long been recognized as the highest across the entire human life span. The precise underlying cause is unfortunately still far from clear. A substantial body of data derived mostly from in vitro experimentation indicates "lower" host immune responses in early vs. adult life and is briefly summarized within this review. However, emerging data derived mostly from in vivo experimentation reveal that the newborn host also exhibits an exuberant immune and inflammatory response following infection when compared to the adult. In this context, it is important to emphasize that "infection" does not equate "infectious disease," as for many infections it is the host response to the infection that causes disease. This simple insight readily arranges existing evidence into cause-effect relationships that explain much of the increase in clinical suffering from infection in early life. We here briefly summarize the evidence in support of this paradigm and highlight the important implications it has for efforts to ameliorate the suffering and dying from infection in early life.

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Ästhetische Psychodermatologie

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HIV and Cancer Interaction Highlights Need to Address Disease Stigma

The global landscape of disease highlights disparities that exist between nations. An estimated 36 million people worldwide live with HIV and AIDS, of which only 1 million are located within the United States. While the diagnosis of a life-threatening disease can be devastating, individuals with HIV and AIDS frequently bear an additional burden of stigma and discrimination.

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Johns Hopkins Researchers Launch Interdisciplinary Effort for Breast Cancer

What do math, physics and engineering tell us about breast cancer? They could tell us a lot, say Johns Hopkins scientists. They're using a $5 million grant from the National Cancer Institute to unite biologists, clinicians and engineers at the new Johns Hopkins Center for Cancer Target Discovery and Development, or CTD².

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The Lancet Oncology: Major Report Sets Out How to Accelerate Cancer Research and Care, Delivering on US Cancer Moonshot Initiative

A fundamental shift in how cancer research is conducted and how cancer care is delivered in the U.S. is required in order to deliver on the Cancer Moonshot initiative, according to a major new report published today in The Lancet Oncology journal.

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Praxis-HNO

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Die neue Klassifikation des M. Menière in der Diskussion

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Stati limite e costo economico, ecco gli elementi da valutare per attribuire le classi di rischio

Freddi, F; Dall'Asta, A; (2017) Stati limite e costo economico, ecco gli elementi da valutare per attribuire le classi di rischio. Edilizia e Territorio: Dossier SISMABONUS: Guida alla diagnosi e agli interventi, n. 3 , 2017 (3)

http://ift.tt/2A1OMlc

When immiscible becomes miscible-Methane in water at high pressures

Pruteanu, CG; Ackland, GJ; Poon, WCK; Loveday, JS; (2017) When immiscible becomes miscible-Methane in water at high pressures. Science Advances , 3 (8) , Article e1700240. 10.1126/sciadv.1700240 . Green open access

http://ift.tt/2hx0GfJ

Customized microscale approach for optimizing two-phase bio-oxidations of alkanes with high reproducibility

Kolmar, JF; Thum, O; Baganz, F; (2017) Customized microscale approach for optimizing two-phase bio-oxidations of alkanes with high reproducibility. Microbial Cell Factories , 16 , Article 174. 10.1186/s12934-017-0788-4 . Green open access

http://ift.tt/2A1sC27

A Three-Stage Approach for Segmenting Degraded Color Images: Smoothing, Lifting and Thresholding (SLaT)

Cai, X; Chan, R; Nikolova, M; Zeng, T; (2017) A Three-Stage Approach for Segmenting Degraded Color Images: Smoothing, Lifting and Thresholding (SLaT). Journal of Scientific Computing , 72 (3) pp. 1313-1332. 10.1007/s10915-017-0402-2 .

http://ift.tt/2hxJJlx

Another problem for alternative-based theories of plurality inferences: the case of reduplicated plural nouns in Japanese

Sudo, Y; (2017) Another problem for alternative-based theories of plurality inferences: the case of reduplicated plural nouns in Japanese. Snippets (31) pp. 27-29. 10.7358/snip-2017-031-sudo . Green open access

http://ift.tt/2A0uxUX

Cause of death and predictors of mortality in a community-based cohort of people with epilepsy: Author response

Sander, JW; Bell, GS; Keezer, MR; (2016) Cause of death and predictors of mortality in a community-based cohort of people with epilepsy: Author response. Neurology , 87 (8) p. 853. 10.1212/01.wnl.0000494744.36250.46 . Green open access

http://ift.tt/2hyMva9

Patient aggression and the wellbeing of nurses: A cross-sectional survey study in psychiatric and non-psychiatric settings

Pekurinen, V; Willman, L; Virtanen, M; Kivimäki, M; Vahtera, J; Välimäki, M; (2017) Patient aggression and the wellbeing of nurses: A cross-sectional survey study in psychiatric and non-psychiatric settings. International Journal of Environmental Research and Public Health , 14 (10) , Article 1245. 10.3390/ijerph14101245 . Green open access

http://ift.tt/2A0yZCX

Patients With Normal Tension Glaucoma Have Relative Sparing of the Relative Afferent Pupillary Defect Compared to Those With Open Angle Glaucoma and Elevated Intraocular Pressure

Lawlor, M; Quartilho, A; Bunce, C; Nathwani, N; Dowse, E; Kamal, D; Gazzard, G; (2017) Patients With Normal Tension Glaucoma Have Relative Sparing of the Relative Afferent Pupillary Defect Compared to Those With Open Angle Glaucoma and Elevated Intraocular Pressure. Investigative Ophthalmology & Visual Science , 58 (12) pp. 5237-5241. 10.1167/iovs.17-21688 . Green open access

http://ift.tt/2hz1ml9

Mentalizing impairment as a mediator between reported childhood abuse and outcome in nonaffective psychotic disorder

Fonagy, P; Weijers, JG; Eurelings-Bontekoe, E; Termorshuizen, F; Viechtbauer, W; Selten, JP; (2018) Mentalizing impairment as a mediator between reported childhood abuse and outcome in nonaffective psychotic disorder. Psychiatry Research (In press).

http://ift.tt/2zZtRiy

On (Not) Reading Wales In W.G. Sebald's Austerlitz (2001)

Davies, MP; (2018) On (Not) Reading Wales In W.G. Sebald's Austerlitz (2001). Oxford German Studies (In press).

http://ift.tt/2hz1iBV

Drivers of abundance and spatial distribution of reef-associated sharks in an isolated atoll reef system

Tickler, DM; Letessier, TB; Koldewey, HJ; Meeuwig, JJ; (2017) Drivers of abundance and spatial distribution of reef-associated sharks in an isolated atoll reef system. PLoS ONE , 12 (5) , Article e0177374. 10.1371/journal.pone.0177374 . Green open access

http://ift.tt/2A0Sknu

Sampling mobile oceanic fishes and sharks: implications for fisheries and conservation planning

Letessier, TB; Bouchet, PJ; Meeuwig, JJ; (2017) Sampling mobile oceanic fishes and sharks: implications for fisheries and conservation planning. Biological Reviews , 92 (2) pp. 627-646. 10.1111/brv.12246 . Green open access

http://ift.tt/2hxVtEs

The dynamical control of subduction parameters on surface topography

Crameri, F; Lithgow-Bertelloni, CR; Tackley, PJ; (2017) The dynamical control of subduction parameters on surface topography. Geochemistry, Geophysics, Geosystems , 18 (4) pp. 1661-1687. 10.1002/2017GC006821 . Green open access

http://ift.tt/2A1sBv5

Continental-scale hotspots of pelagic fish abundance inferred from commercial catch records

Bouchet, PJ; Meeuwig, JJ; Huang, Z; Letessier, TB; Nichol, SL; Caley, MJ; Watson, RA; (2017) Continental-scale hotspots of pelagic fish abundance inferred from commercial catch records. Global Ecology and Biogeography , 26 (10) pp. 1098-1111. 10.1111/geb.12619 .

http://ift.tt/2hy0InA

Cross-Listing of Real Estate Investment Trust

Addae-Dapaah, K; (2017) Cross-Listing of Real Estate Investment Trust. Journal of Property Investment and Finance , 35 (5) pp. 509-527. 10.1108/JPIF-08-2016-0063 . Green open access

http://ift.tt/2zZtQeu

Study of serial markers of biological response in rectal cancer patients receiving preoperative chemoradiotherapy with or without biological agents

Khan, AA; (2017) Study of serial markers of biological response in rectal cancer patients receiving preoperative chemoradiotherapy with or without biological agents. Doctoral thesis , UCL (University College London). Green open access

http://ift.tt/2hyJuGK

Developing a quality enhancement culture in Maltese education

Spiteri, A; (2017) Developing a quality enhancement culture in Maltese education. Doctoral thesis , UCL (University College London).

http://ift.tt/2A0uYi5

Exploring professional development for older workers in the higher education workplace.

Bingham, DM; (2017) Exploring professional development for older workers in the higher education workplace. Doctoral thesis , UCL (University College London). Green open access

http://ift.tt/2hy0i0u

Neighborhood Social Capital in Relation to Late HIV Diagnosis, Linkage to HIV Care, and HIV Care Engagement

Ransome, Y; Kawachi, I; Dean, LT; (2017) Neighborhood Social Capital in Relation to Late HIV Diagnosis, Linkage to HIV Care, and HIV Care Engagement. AIDS and Behavior , 21 (3) pp. 891-904. 10.1007/s10461-016-1581-9 . Green open access

http://ift.tt/2A0JoPb

Leadership experience of London-based Advanced Nurse Practitioners (ANP): A case study analysis

Anderson, C; (2017) Leadership experience of London-based Advanced Nurse Practitioners (ANP): A case study analysis. Doctoral thesis , UCL (University College London). Green open access

http://ift.tt/2hy00GW

Cathelicidin modulates synthesis of Toll-like Receptors (TLRs) 4 and 9 in colonic epithelium

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Maia Marin, Ravi Holani, Chaitanya B. Shah, Anselmo Odeón, Eduardo R. Cobo
Cathelicidin are innate antimicrobial peptides with broad immunomodulatory functions; however, their role in regulating intestinal defenses is not well characterized. This study aimed to investigate the role of cathelicidin modulating expression of Toll-like receptors (TLRs) 4 and 9 in colonic epithelium in response to bacterial patterns. We demonstrated herein that intestinal epithelial cells, when primed by bacterial lipopolysaccharide (LPS), responded to cathelicidin by increased transcription and protein synthesis of TLR4. This cathelicidin-induced response required the interaction of LPS-TLR4 and activation of MAPK signalling pathways. However, cathelicidin blocked TLR9 responses induced by TLR9 ligand CpG oligodeoxynucleotide (CpG ODN) in these colonic epithelial cells. Modulations of TLRs triggered by cathelicidin in intestinal epithelium occurred mainly in the apical compartment of intestinal cells. Activation of TLR4 by ligands in combination with cathelicidin promoted CXCL8 chemokine secretion and epithelial antimicrobial defenses against Escherichia coli. We concluded that cathelicidin selectively modulated synthesis of TLR4 and 9 in intestinal epithelium, but only when cells were exposed to virulence factors, mostly from apical surfaces. Enhanced TLR4 expression promoted by cathelicidin in intestinal epithelium may be crucial for controlling enteric infectious diseases.



http://ift.tt/2zqTIUm

Tumor cryoablation in combination with natural killer cells therapy and Herceptin in patients with HER2-overexpressing recurrent breast cancer

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Shuzhen Liang, Lizhi Niu, Kecheng Xu, Xiaohua Wang, Yingqing Liang, Mingjie Zhang, Jibing Chen, Mao Lin
In this study, we investigated the clinical benefits of a combination of tumor cryoablation with natural killer (NK) cells therapy and Herceptin for human epidermal growth factor (HER) 2-overexpressing recurrent breast cancer. From May 2015 to May 2016, 48 patients who met the enrollment criteria were assigned to three groups (n=16): cryoablation group (group I), cryoablation-NK cells therapy group (group II) and cryoablation-NK cells therapy-Herceptin group (group III). Safety and short-term effects were evaluated. All the adverse effects were manageable and acceptable. The three-therapy combination treatment not only yielded good clinical efficacy, it also improved the quality of life; reduced levels of circulating tumor cells (CTCs); reduced carcino-embryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) expression; enhanced immune function significantly. Furthermore, it can resulte in significant prolongation of progression free survival (PFS). This is the first clinical study to demonstrate the benefit of the three-therapy combination of tumor cryoablation, NK cells therapy, and Herceptin for HER2-overexpressing recurrent breast cancer.



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Functional analyses of the interaction of chicken interleukin 23 subunit p19 with IL-12 subunit p40 to form the IL-23 complex

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Anh Duc Truong, Cong Thanh Hoang, Yeojin Hong, Janggeun Lee, Kyungbaek Lee, Hyun S. Lillehoj, Yeong Ho Hong
This study represents the first description of the cloning of chicken IL-23p19 (ChIL-23α) and the function of the IL-23 complex in birds. Multiple alignment of ChIL-23α with other known IL-23α amino acid sequences revealed regions of amino acid conservation. The homologies of ChIL-23α, IL-12p35, and similar mammalian subunits ranged between 26% and 42%. ChIL-23α consisted of four exons and three introns; similar to those in humans and mice, and limited conservation of synteny between the human and chicken genomes was observed. Using bioinformatics tools, we identified the NF-κB, C/EBPα-β, c-Jun, c-Rel, AP-1, GATA-1, and ER promoter sites in ChIL-23α. Moreover, IL-23α mRNA was more highly expressed than IL-12p40 and IL-12p35 mRNA in several organs of chickens infected with Salmonella. In addition, ChIL-23 complex are associated with IL-23R, IL-12Rβ1 receptors; activate the JAK2/TYK2, STAT1/3, SOCS1 genes, and induced proinflammatory cytokines in immune cells. Collectively, these results indicate that ChIL-23 is a member of the IL-12 family, has proinflammatory properties related to IL-23R and IL-12Rβ1 receptor expression, and activates the JAK/STAT signaling pathway that results in the interaction of ChIL-23α with ChIL-12p40 to form the novel ChIL-23 complex. Our results provide novel insights into the regulation of immunity, inflammation, and immunopathology.



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Leptin reduces microRNA-122 level in hepatic stellate cells in vitro and in vivo

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Xuguang Zhai, Fangyun Cheng, Li Ji, Xiaofei Zhu, Qing Cao, Yali Zhang, Xin Jia, Qian Zhou, Wei Guan, Yajun Zhou
Obese patients, often accompanied by hyperleptinemia, are more likely to develop liver fibrosis. Leptin, an adipocyte-derived hormone, augments inflammatory in liver and promotes hepatic stellate cell (HSC) activation (a key step for liver fibrogenesis) and liver fibrosis. microRNA-122 (miR-122) is the most abundant liver-specific miRNA and can attenuate liver fibrosis. This study examined the effect of leptin on miR-122 level in HSCs in vivo and in vitro. Results demonstrated that leptin reduced the levels of both miR-122 (mature miR-122) and primary miR-122 (pri-miR-122). The effects of leptin on the levels of miR-122 and pri-miR-122 were through at least hedgehog pathway. Leptin-induced decrease in sterol regulatory element-binding protein-1c (SREBP-1c) has been shown to contribute to leptin-induced HSC activation. We revealed a mutual promotional effect between SREBP-1c and miR-122. Further experiments indicated that miR-122 inhibited leptin-induced liver fibrosis in leptin-deficient mouse model. These data have potential implications for clarifying the mechanisms of hepatic fibrogenesis associated with elevated leptin level in human such as obese patients

Graphical abstract

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Conformational analysis of the human chemokine receptor CXCR3

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Raffaele Raucci, Andrea Polo, Alfredo Budillon, Giovanni Colonna, Susan Costantini
In the last years, some studies showed the patho-genetic role of CXCR3 bound to its ligands in many human inflammatory diseases and cancers. Thus, the blockage of the CXCR3 interaction site to its ligands is seen as a possible therapeutic target for the treatment of cancer. The presence of flexible regions in the chemokine receptors determines their capability to develop specific mechanisms of action. We have recently focused on the features of the N-terminal region of human CXCR3 free in solution, where we demonstrate the presence of numerous conformational ensembles, dynamically stabilized by H-bonds. Since up to now no structure was experimentally determined for CXCR3, we decided to approach the study of its conformational behavior by molecular dynamics simulations, in a lipid bilayer, surrounded of water, at neutral pH and 300K. Furthermore, we modeled the CXCR3/CXCL11 complex, where CXCL11 is one of its natural ligands. The aim of this work is to have a vision as realistic as possible in dynamic terms of the biological mechanism that drives the search for the ligand, its interaction and the formation of a stable complex between CXCR3 and CXCL11.Overall, our approach has been able to describe the structural events which dynamically characterize the molecular mechanisms involved in the binding of CXCR3 to CXCL11 and the critical role exerted by its N-terminal region in "hunting" and capturing the ligand.



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A mannose-specific C-type lectin from Fenneropenaeus merguiensis exhibited antimicrobial activity to mediate shrimp innate immunity

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Phanthipha Runsaeng, Peerapong Puengyam, Prapaporn Utarabhand
Being one type of pattern recognition receptors (PRRs), lectins exhibit a crucial role in the defense mechanism of invertebrates which are deficient in an adaptive immune system. A new C-type lectin called FmLC3 was isolated from hepatopancreas of Fenneropenaeus merguiensis by cloning approaches, RT-PCR and 5′ and 3′ RACE (rapid amplification of cDNA ends). A full-length cDNA of FmLC3 contains 607 bp with one open reading frame of 480bp, encoding a 159-amino acids peptide. The predicted primary structure of FmLC3 is composed of a signal peptide, a carbohydrate recognition domain with an EPN motif and one Ca²⁺ binding site-2, including a double-loop region assisted by two conserved disulfide linkages. FmLC3 had a molecular mass of 17.96kDa and pI of 4.92. In normal or unchallenged shrimp, the mRNA expression of FmLC3 was detected only in hepatopancreas whilst its native proteins were found in hemolymph, heart, stomach and intestine but not in the expressed tissue, indicating that after being synthesized in hepatopancreas, FmLC3 would be secreted to other tissues. The significant up-regulation of FmLC3 was manifested in shrimp challenged with Vibrio harveyi or white spot syndrome virus. After knockdown with gene-specific double-stranded RNA and following by co-pathogenic inoculation, the FmLC3 expression was severely suppressed with coherence of increasing in cumulative mortality and reduction of the median lethal time. Recombinant FmLC3 (rFmLC3) had agglutinating activity towards diverse bacterial strains in a Ca²⁺-dependent manner. Its activity was inhibited by lipopolysaccharide and mannose, implying that FmLC3 was mannose-binding C-type lectin. Moreover, rFmLC3 could bind directly to various microbial strains with Ca²⁺-requirement. Otherwise, rFmLC3 exhibited the antimicrobial activity by inhibiting effectively the microbial growth in vitro. All these results signified that FmLC3 might act as PRR to recognize with a broad specificity for diverse pathogens, and contribute in shrimp immune response via the agglutination, binding and antimicrobial activity.



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Deletion of the transcriptional regulator GntR down regulated the expression of Genes Related to Virulence and Conferred Protection against Wild-Type Brucella Challenge in BALB/c Mice

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Zhi-Qiang Li, Jin-Liang Zhang, Li Xi, Guang-Li Yang, Shu-Li Wang, Xiao-Gen Zhang, Jun-Bo Zhang, Hui Zhang
Brucellosis, which is caused by Brucella spp., is a zoonotic infectious disease that can cause great hazard to public health and safety. The virulence of Brucella is essential for survive and multiply in host macrophages. GntR is a transcriptional regulator in Brucella that is required for virulence in macrophages and mice, and involved in resistance to stress responses. To determine the expression levels of target genes of GntR, we detected the expression levels of the GntR target genes in Brucella infected BALB/c mice. The results showed that several genes related to virulence, including omp25, virB1, vjbR, dnaK, htrA and hfq, were regulated by GntR during infection in BALB/c mice. Moreover, the 2308ΔgntR mutant induced high protective immunity in BALB/c mice challenge with B. abortus 2308 (S2308), and elicited an anti-Brucella-specific immunoglobulin G (IgG) response and induced the secretion of gamma interferon (IFN-γ) and interleukin-4 (IL-4). All together, these results indicated that gntR promoted the virulence of Brucella. The 2308ΔgntR was significantly attenuated in macrophages and mice and induced protective immune response during infection, suggested that 2308ΔgntR mutant is an attractive candidate for the design of a live attenuated vaccine against Brucella.



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The effect of loss of O-antigen ligase on phagocytic susceptibility of motile and non-motile Pseudomonas aeruginosa

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Sally Demirdjian, Kristin Schutz, Matthew J. Wargo, Joseph S. Lam, Brent Berwin
The bacterial pathogen Pseudomonas aeruginosa undergoes adaptation and selection over the course of chronic respiratory tract infections which results in repeatedly-observed phenotypic changes that are proposed to enable its persistence. Two of the clinically significant P. aeruginosa phenotypic changes are loss of flagellar motility and modifications to LPS structure, including loss of O-antigen expression. The effect of loss of O-antigen, frequently described as conversion from smooth to rough LPS, and the combined effect of loss of motility and O-antigen on phagocytic susceptibility by immune cells remain unknown. To address this, we generated genetic deletion mutants of waaL, which encodes the O-antigen ligase responsible for linking O-antigen to lipid A-core oligosaccharide, in both motile and non-motile P. aeruginosa strains. With the use of these bacterial strains we provide the first demonstration that, despite a progressive selection for P. aeruginosa with rough LPS during chronic pulmonary infections, loss of the LPS O-antigen does not confer phagocytic resistance in vitro. However, use of the waaLmotABmotCD mutant revealed that loss of motility confers resistance to phagocytosis regardless of the smooth or rough LPS phenotype. These findings reveal how the O-antigen of P. aeruginosa can influence bacterial clearance during infection and expand our current knowledge about the impact of bacterial phenotypic changes during chronic infection.



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Recombinant small glutamine-rich tetratricopeptide repeat-containing protein of Leishmania infantum: Potential vaccine and diagnostic application against visceral leishmaniasis

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Daniel S. Dias, Patrícia A.F. Ribeiro, Vívian T. Martins, Daniela P. Lage, Áquila S.B. Portela, Lourena E. Costa, Beatriz C.S. Salles, Mariana P. Lima, Fernanda F. Ramos, Thaís T.O. Santos, Rachel B. Caligiorne, Miguel A. Chávez-Fumagalli, Julia A.G. Silveira, Danielle F. Magalhães-Soares, Denise U. Gonçalves, Jamil S. Oliveira, Bruno M. Roatt, Mariana C. Duarte, Daniel Menezes-Souza, Eduardo S. Silva, Alexsandro S. Galdino, Ricardo A. Machado-de-Ávila, Antonio L. Teixeira, Eduardo A.F. Coelho
Different Leishmania proteins have been evaluated in order to find a potential vaccine candidate or diagnostic marker capable of providing long lasting protection against infection or helping to identify infected mammalian hosts, respectively. However, just few molecules have fulfilled all the requirements to be evaluated. In the current study, we evaluated the prophylactic and diagnostic value against visceral leishmaniasis (VL) of a small glutamine-rich tetratricopeptide repeat-containing (SGT) protein from Leishmania infantum species. In a first step, the immune response elicited by the immunization using the recombinant protein (rSGT) plus saponin was evaluated in BALB/c mice. Immunized animals had a low parasitism in all evaluated organs. They developed a specific Th1 immune response, which was based on protein-specific production of IFN-γ, IL-12 and GM-CSF, and a humoral response dominated by antibodies of the IgG2a isotype. Both CD4⁺ and CD8⁺ T cells contributed to the IFN-γ production, showing that both T cell subtypes contribute to the resistance against infection. Regarding its value as a diagnostic marker, rSGT showed maximum sensitivity and specificity to serologically identify L. infantum-infected dog and human sera. No cross-reactivity with sera from humans or dogs that had other diseases was found. Although further studies are necessary to validate these findings, data showed here suggest immunogenicity of rSGT and its protective effect against murine VL, as well as its potential for the serodiagnosis of human and canine VL.

Graphical abstract

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Inhibition of Notch signalling has ability to alter the proximal and distal TCR signalling events in human CD3+ αβ T-cells

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Asif A. Dar, Sajad A. Bhat, Dimpu Gogoi, Abhiram Gokhale, Shubhada V. Chiplunkar
The Notch signalling pathway is an important regulator of T cell function and is known to regulate the effector functions of T cells driven by T cell receptor (TCR). However, the mechanism integrating these pathways in human CD3⁺ αβ T cells is not well understood. The present study was carried out to investigate how Notch and TCR driven signalling are synchronized in human αβ T cells. Differential expression of Notch receptors, ligands, and target genes is observed on human αβ T cells which are upregulated on stimulation with α-CD3/CD28 mAb. Inhibition of Notch signalling by GSI-X inhibited the activation of T cells and affected proximal T cell signalling by regulating CD3-ζ chain expression. Inhibition of Notch signalling decreased the protein expression of CD3-ζ chain and induced expression of E3 ubiquitin ligase (GRAIL) in human αβ T cells. Apart from affecting proximal TCR signalling, Notch signalling also regulated the distal TCR signalling events. In the absence of Notch signalling, α-CD3/CD28 mAb induced activation and IFN-γ production by αβ T cells was down-modulated. The absence of Notch signalling in human αβ T cells inhibited proliferative responses despite strong signalling through TCR and IL-2 receptor. This study shows how Notch signalling cooperates with TCR signalling by regulating CD3-ζ chain expression to support proliferation and activation of human αβ T cells.



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Comprehensive approach to study complement C4 in systemic lupus erythematosus: Gene polymorphisms, protein levels and functional activity

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): M.W.P. Tsang-A-Sjoe, I.E.M. Bultink, L.A. Korswagen, A. van der Horst, I. Rensink, M. de Boer, D. Hamann, A.E. Voskuyl, D. Wouters
Genetic variation of the genes encoding complement component C4 is strongly associated with systemic lupus erythematosus (SLE), a chronic multi-organ auto-immune disease. This study examined C4 and its isotypes on a genetic, protein, and functional level in 140 SLE patients and 104 healthy controls. Gene copy number (GCN) variation, silencing CT-insertion, and the retroviral HERV-K(C4) insertion) were analyzed with multiplex ligation-dependent probe amplification. Increased susceptibility to SLE was found for low GCN (≪2) of C4A. Serositis was the only clinical manifestation associated with low C4A GCN. One additional novel silencing mutation in the C4A gene was found by Sanger sequencing. This mutation causes a premature stop codon in exon 11. Protein concentrations of C4 isoforms C4A and C4B were determined with ELISA and were significantly lower in SLE patients compared to healthy controls. To study C4 isotypes on a functional level, a new C4 assay was developed, which distinguishes C4A from C4B by its binding capacity to amino or hydroxyl groups, respectively. This assay showed high correlation with ELISA and detected crossing over of Rodgers and Chido antigens in 3.2% (8/244) of individuals. The binding capacity of available C4 to its substrates was unaffected in SLE. Our study provides, for the first time, a complete overview of C4 in SLE from genetic variation to binding capacity using a novel test. As this test detects crossing over of Rodgers and Chido antigens, it will allow for more accurate measurement of C4 in future studies.



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Distinct pattern of immune tolerance in dendritic cells treated with lipopolysaccharide or lipoteichoic acid

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Hyo Shin Yoon, Girak Kim, Young Jun Ju, In Su Cheon, Sun Woong Hong, Dong Wook Kim, Byung-Chul Park, Seung Hyun Han, Cheol-Heui Yun
Cytokine induction is often critical for the host defense during acute immune responses while, if not tightly regulated, it may cause an immunological pathology coincident with tissue damage. Despite the fact that gram-positive bacterial infection has become increasingly prevalent, immune modulation induced by lipoteichoic acid (LTA), the major cell wall component of gram-positive bacteria has not been studied thoroughly at the cellular level. In the current study, tolerance induction in mouse bone marrow-derived dendritic cells (BMDCs) treated with single or repeated stimulation of Staphylococcus aureus LTA was compared with those of Escherichia coli lipopolysaccharide (LPS). The results showed that repeated LTA stimulation significantly suppressed pro-inflammatory cytokine (TNF-α and IL-6) production in BMDCs, comparable to that of LPS, but with less extent, down-regulated IL-10 and enhanced the inhibitory molecule, LAG-3-associated protein (LAP). Furthermore, we observed a sustained expression of unique negative regulators, Toll interacting protein (TOLLIP) and Indoleamine 2,3-dioxygenase (IDO), in BMDCs treated with LTA.A transient hyporesponsiveness period appeared when DCs were treated repeatedly with LTA or LPS showing a distinctive pattern. Intriguingly, LPS exposure induced cross tolerance to LTA while LTA exposure did not to LPS, implicating that a distinct signaling components are involved in response to LTA. Collectively, a distinct immune regulation appeared to be responsible for the LPS- and LTA-induced tolerance on cytokine production, expression of surface markers and intracellular proteins.



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Two types of TNFα in meagre (Argyrosomus regius): Discovery, distribution and expression modulation

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): D.J. Milne, C. Campoverde, K.B. Andree, J. Zou, C.J. Secombes
TNFα is a key cytokine involved in systemic inflammation and regulation of immune cells and is important during development. In the present study, 2 isoforms of TNFα were discovered in meagre, an emerging species in aquaculture. Phylogenetic analysis suggests these isoforms represent the type I and type II TNFα classes previously described in other teleost species. This study is the first to compare how these 2 types of TNFα behave in meagre and aims to provide insights into their expression in teleost fish by interrogating expression in whole tissues and isolated cell populations in four immunologically important sites (gills, intestine, head kidney and spleen) following PAMP stimulation, as well as monitoring gene expression during meagre development. Differential expression was seen in head kidney and gills, where TNFα1 was more highly expressed. Both isoforms increased in head kidney of meagre following injection with LPS, but this was not seen in other tissues or after injection with other PAMPs. However, in vitro studies hinted at a possible mucosal bias for TNFα1, which was more highly induced in gill and intestinal cell suspensions by PAMPs. In contrast TNFα2 was more highly induced in cells from systemic tissues. Through early development expression of both types of TNFα decreased as the meagre matured, with the exception of a transient increase shortly after the move to a dry feed diet. However, during the later stages of development expression of both isoforms increased in the gills. This data demonstrates a degree of differential expression of TNFα1 and TNFα2 in meagre with regard to expression regulation, and highlights the importance of TNFα during early development of teleost fish.



http://ift.tt/2zqTsES

Crystal structure determination and analysis of 11S coconut allergen: Cocosin

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): S. Vajravijayan, N. Nandhagopal, K. Gunasekaran
Allergy is an abnormal immune response against an innocuous target. Food allergy is an adverse reaction caused by common foods most well-known being those involving peanuts. Apart from mono sensitized food allergy, cross-reactivity with other food allergens is also commonly observed. To understand the phenomenon of cross-reactivity related to immune response, three dimensional structures of the allergens and their antigenic epitopes has to be analysed in detail. The X-ray crystal structure of Cocosin, a common 11S food allergen from coconut, has been determined at 2.2Å resolution using molecular replacement technique. The monomer of 52kDa is composed of two β-jelly roll domains, one with acidic and the other with basic character. The structure shows hexameric association with two trimers facing each other. Though the overall structure of Cocosin is similar to other 11S allergens, the occurrence of experimentally determined epitopes of the peanut allergen Ara h 3 at flexible as well as variable regions could be the reason for the clinically reported result of cross-reactivity that the peanut allergic patients are not sensitized with coconut allergen.

Graphical abstract

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Lunasin abrogates monocytes to endothelial cells

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Yongjun Zhu, Hui Li, Xuezhen Wang
The adherence of monocytes to endothelial cells plays a causal role in the early development of atherosclerosis and is driven by several inflammatory stimuli, which includes oxidized low-density lipoprotein (ox-LDL). Lunasin, a natural peptide identified in soybean seeds, soy-derived food products, other grains and herbal plants, has been found to exert numerous biological activities, including anti-inflammatory and antioxidant properties. However, little is known regarding the mechanism of action of lunasin in ox-LDL-induced endothelial inflammation. The results of the present study indicate that lunasin significantly ameliorated ox-LDL-induced adhesion of THP-1 monocytes to the surface of human umbilical vein endothelial cells (HUVECs). Lunasin also suppressed expression of the adhesion molecules VCAM-1 and E-selectin, but not ICAM-1. Notably, the inhibitory mechanism of lunasin is associated with its stimulatory effects on expression of the KLF2 transcriptional factor. In addition, lunasin treatment could reverse the effects of ox-LDL on the expression of eNOS and PAI-1, the direct target genes of KLF2. Mechanistically, it was proven that the MEK5/ERK5 pathway mediates the effects of lunasin on KLF2 expression. Taken together, the results of this study suggest that dietary or supplementary intake of lunasin may have a prophylactic or therapeutic capacity in cardiovascular diseases such as atherosclerosis.



http://ift.tt/2zduoQW

MOTS-c peptide increases survival and decreases bacterial load in mice infected with MRSA

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Dongsheng Zhai, Zichen Ye, Yinghao Jiang, Chengming Xu, Banjun Ruan, Yuan Yang, Xiaoying Lei, An Xiang, Huanyu Lu, Zheng Zhu, Zhao Yan, Di Wei, Qingyang Li, Li Wang, Zifan Lu
Sepsis is a life-threatening disease characterized by uncontrolled inflammatory responses upon pathogen infections, especially for the antibiotic-resistant strains, such as Methicillin-resistant S. aureus (MRSA). Here we demonstrated that a Mitochondria-derived peptide (MOTS-c) could significantly improve the survival rate and decrease bacteria loads in MRSA-challenged mice, accompanied with declined levels of pro-inflammatory cytokines, such as TNF-α, IL-6 and IL-1β, but with increased level of anti-inflammatory cytokine IL-10. Moreover this peptide enhanced bactericidal capacity of macrophages. Meanwhile, MOTS-c inhibited the phosphorylation mitogen-activated protein kinases (MAPK), and enhanced the expression of aryl hydrocarbon receptor (AhR) and signal transducer and activator of transcriptional 3 (STAT3) in macrophages. Overall, MOTS-c plays a beneficial role in curbing the overwhelming inflammatory bursts in the fight against MRSA infection. It may serve as a potential therapeutic agent in sepsis treatment.Highlight• MOTS-c improved survival status in mice during MRSA infection.• MOTS-c strongly enhanced bactericidal capacity of macrophages.• MOTS-c exerted an anti-inflammatory effect via suppressing MAPKs and increasing Ahr/STAT3 signaling pathways.



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Editorial Board/ Publication Information

Publication date: November 2017
Source:Molecular Immunology, Volume 91





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Innate immune transcriptomic evaluation of PBMC isolated from sheep after infection with E. ruminantium Welgevonden strain

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): T. Nefefe, J. Liebenberg, M. van Kleef, H.C. Steyn, A. Pretorius
Heartwater is a tick-borne non-infectious fatal disease of wild and domestic ruminants caused by the bacterium Ehrlichia ruminantium, transmitted by Amblyomma ticks. Although there is evidence that interferon-gamma (IFN-γ) controls E. ruminantium growth and that cellular immune responses could be protective, an effective recombinant vaccine for this disease is lacking. An overall analysis of which immune pathways are up- or down-regulated in sheep peripheral blood mononuclear cells is expected to lead to a better understanding of the global immune response of sheep to E. ruminantium infection. Therefore, a systems biology oriented approach following the infection with E. ruminantium was investigated from peripheral blood mononuclear cells to aid recombinant vaccine development. In this study, heartwater naïve sheep were infected and challenged by allowing E. ruminantium infected ticks to feed on them. After primary infection, all the animals were treated with antibiotic during the resulting febrile response. Blood was collected daily for E. ruminantium detection by qPCR (pCS20 assay). The pCS20 assay only detected the pathogen in the blood one day prior to and during the febrile stage of infection confirming infection of the sheep. IFN-γ real-time PCR indicated that this cytokine was expressed at specific time points: post infection, during the febrile stage of the disease and after challenge. These were used as a guide to select samples for transcriptome sequencing. This paper focuses on transcripts that are associated with innate activating pathways that were identified to be up- and down-regulated after primary infection and the subsequent challenge. These included the CD14 monocyte marker, toll-like receptor (TLR), nod-like receptor, chemokine, cytosolic and cytokine–cytokine interaction receptor pathways. In particular, TLR4, TLR9 and CD14 were activated together with DNA detection pathways, suggesting that vaccine formulations may be improved if CpG motifs and lipopolysaccharides are included. This data indicates that innate immune activation, perhaps by using adjuvants, should be an important component for consideration during future heartwater recombinant vaccine development.



http://ift.tt/2zrqdBY

Johne’s disease in cattle: an in vitro model to study early response to infection of Mycobacterium avium subsp. paratuberculosis using RNA-seq.

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Rosanna Marino, Rossana Capoferri, Simona Panelli, Giulietta Minozzi, Francesco Strozzi, Erminio Trevisi, Gustavo G.M. Snel, Paolo Ajmone-Marsan, John L. Williams
Johne's disease is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratubercolosis (MAP) which affects ruminants worldwide and has a significant economic impact. MAP has also been associated with human Crohn's disease, although this connection is not well established. MAP is highly adapted for survival within host macrophages and prevents macrophage activation, blocks phagosome acidification and maturation, and attenuates presentation of antigens to the immune system. The consequence is a very long silent infection before clinical signs are observed.The present work examined the transcriptome of bovine monocyte-derived macrophages (MDM) infected with the L1 strain of MAP at 2h, 6h and 24h post infection using RNA-seq. Pathway over-representation analysis of genes differentially expressed between infected vs. control MDM identified that immune related pathways were affected. Genes belonging to the cytokine-cytokine receptor interaction pathway and members of the JAK-STAT pathway, which is involved in the regulation of immune response, were up-regulated. However, in parallel inhibitors of immune functions were activated, including suppressor of cytokine signaling (SOCS) and cytokine-inducible SH2-containing protein (CISH), which most likely suppresses IFNγ and the JAK/STAT signaling cascade in infected MDM, which may favour MAP survival.After exposure, macrophages phagocytise pathogens, activate the complement cascade and the adaptive immune system through the antigen presentation process. However, data presented here suggest that genes related to phagocytosis and lysosome function are down regulated in MAP infected MDM. Genes of MHC class II and complement pathway were also down-regulated. This study therefore shows that MAP infection is associated with changes in expression of genes related to the host immune response that may affect its ability to survive and multiply inside the host cell.



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Nanogel-based nasal vaccines for infectious and lifestyle-related diseases

Publication date: Available online 31 October 2017
Source:Molecular Immunology
Author(s): Tatsuhiko Azegami, Yoshikazu Yuki, Rika Nakahashi, Hiroshi Itoh, Hiroshi Kiyono
Because the mucosa is the major entry route for most pathogens, the development of mucosal vaccines is a rational approach for protecting against these undesired agents. Mucosal administration of vaccine antigen is useful for non-infectious chronic diseases as well, because of its advantages over injection routes, including comparable efficacy in the induction of systemic immune responses, less pain, and no risk of adverse events at the injection site. However, because it is difficult to effectively induce and regulate antigen-specific mucosal and systemic immune responses when antigen alone is mucosally administered, an appropriate form of mucosal delivery vehicle must be used. Antigen delivery systems involving nanogels, which act as artificial chaperones and mucosal adhesives, are a promising approach to overcoming this problem. Here, we introduce current perspectives regarding the development of nanogel-based nasal vaccines for both infectious and lifestyle-related diseases.



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Glomangiomyoma of the neck in a child in Nepal: a rare case report and literature review

Abstract

Background

Glomangiomyoma is a rare histological variant of glomus tumour. Clinically, it mimicks as a haemangioma and is challenging to diagnose. Its occurrence in the neck of a child has not been previously described.

Case presentation

A 3 year old girl presented with the complaints of painless progressive neck swelling in the right side for one and half year. Sonography, computed tomography (CT), magnetic resonance imaging (MRI), CT neck angiography and fine needle aspiration cytology (FNAC) were suggestive of vacular malformation i.e. giant haemangioma or arteriovenous malformation. The mass was removed in toto under general anaesthesia without postoperative complications. The histopathology confirmed it to be glomangiomyoma with haemangiopericytoma like features.

Conclusion

It's an extremely rare variant of glomus tumour and may be the first report of a glomangiomyoma in the neck of a child. Despite a rare entity, it should be borne in mind during differential diagnosis.

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Programme des posters

Publication date: Available online 1 November 2017
Source:Annales de Dermatologie et de Vénéréologie





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TOP 12 des juniors

Publication date: Available online 1 November 2017
Source:Annales de Dermatologie et de Vénéréologie





http://ift.tt/2zc76e8

Usefulness of Endoscopic Managements in Patients with Ceftriaxone-Induced Pseudolithiasis Causing Biliary Obstruction

Ceftriaxone (CTRX) is known to cause reversible biliary stones/sludge, which is called biliary pseudolithiasis. We report two rare cases of biliary obstruction by pseudolithiasis shortly after completing CTRX treatment. Stones and sludge, which had not been detected before CTRX administration, appeared in the gallbladder and common bile duct and led to biliary obstruction and acute cholangitis. The obstructions were successfully treated with endoscopic retrograde biliary drainage and endoscopic sphincterotomy. CTRX-induced biliary pseudolithiasis has been reported mainly in children and adolescents but is also seen in adults with similar incidence rate. Although CTRX-induced biliary pseudolithiasis is usually asymptomatic and disappears spontaneously after discontinuing the drug, some patients develop biliary obstruction. Endoscopic managements should be considered in such cases.

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The Complete Guide to Starting Solids

 

I will never forget watching the transition happen with both of my children – that moment when I started to bring a spoonful of food to my own mouth, and they opened their mouths wide, too. A sure sign theses exclusively breast-fed babies were ready to start solids. What are the other signs and how do you make that introduction? Here are my tips – both as a mom and a newborn medicine physician.

The post The Complete Guide to Starting Solids appeared first on ChildrensMD.

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Comparing perilymph proteomes across species

Objectives/Hypothesis

Biological components of perilymph affect the electrical performance of cochlear implants. Understanding the perilymph composition of common animal models will improve the understanding of this impact and improve the interpretation of results from animal studies and how it relates to humans.

Study Design

Analysis and comparison of the proteomes of human, guinea pig, and cat perilymph.

Methods

Multiple perilymph samples from both guinea pigs and cats were analysed via liquid chromatography with tandem mass spectrometry. Proteins were identified using the Mascot database. Human data were obtained from a published dataset. Proteins identified were refined to form a proteome for each species.

Results

Over 200 different proteins were found per species. There were 81, 39, and 64 proteins in the final human, guinea pig, and cat proteomes, respectively. Twenty-one proteins were common to all three species. Fifty-two percent of the cat proteome was found in the human proteome, and 31% of the guinea pig was common to human. The cat proteome had similar complexity to the human proteome in three protein classes, whereas the guinea pig had a similar complexity in two. The presence of albumin was significantly higher in human perilymph than in the other two species. Immunoglobulins were more abundant in the human than in the cat proteome.

Conclusions

Perilymph proteomes were compared across three species. The degree of crossover of proteins of both guinea pig and cat with human indicate that these animals suitable models for the human cochlea, albeit the cat perilymph is a closer match.

Level of Evidence

NA Laryngoscope, 2017

http://ift.tt/2lEWorg

Long-term effects of Internet-supported cognitive behavior therapy

Shafran, RL; Andersson, G; Rozental, A; Carlbring, P; (2017) Long-term effects of Internet-supported cognitive behavior therapy. Expert Review of Neurotherapeutics (In press).

http://ift.tt/2z6ycRC

The Mood and Learning in navigation-Based Serious Games

Nazry, NNM; Romano, DM; (2017) The Mood and Learning in navigation-Based Serious Games. Computers in Human Behavior , 73 pp. 596-604. 10.1016/j.chb.2017.03.040 .

http://ift.tt/2iURXHU

Biocompatibility Assessment of Potential Materials for Use in an Ophthalmic Drug Delivery Device

Alband, M; (2017) Biocompatibility Assessment of Potential Materials for Use in an Ophthalmic Drug Delivery Device. Masters thesis , UCL (University College London).

http://ift.tt/2z6y0lm

Migration in the Anthropocene: how collective navigation, environmental system, and taxonomy shape the vulnerability of migratory species

Hardesty-Moore, M; Deinet, S; Freeman, R; Titcomb, GC; Dillon, EM; Stears, K; Klope, M; ... McCauley, DJ; + view all Hardesty-Moore, M; Deinet, S; Freeman, R; Titcomb, GC; Dillon, EM; Stears, K; Klope, M; Bui, A; Orr, D; Young, HS; Miller-ter-Kuile, A; Hughey, LF; McCauley, DJ; - view fewer (2018) Migration in the Anthropocene: how collective navigation, environmental system, and taxonomy shape the vulnerability of migratory species. Philosophical Transactions B: Biological Sciences 10.1098/rstb.2017.0017 . (In press).

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Does ovarian suspension during laparoscopic surgery for endometriosis reduce postoperative adhesions? A randomised controlled trial

Hoo, WL; (2017) Does ovarian suspension during laparoscopic surgery for endometriosis reduce postoperative adhesions? A randomised controlled trial. Masters thesis , UCL (University College London). Green open access

http://ift.tt/2z6xPXe

Perioperative neutrophil immune function

Cain, DJ; (2017) Perioperative neutrophil immune function. Doctoral thesis , UCL (University College London). Green open access

http://ift.tt/2iVDuvo

A Cohort Examination to Establish Reporting of the Remit and Function of Trial Steering Committees in Randomised Controlled Trials

Conroy, JC; Arch, B; Harman, N; Lane, JA; Norrie, J; Sydes, MR; Gamble, C; (2017) A Cohort Examination to Establish Reporting of the Remit and Function of Trial Steering Committees in Randomised Controlled Trials. Trials (In press).

http://ift.tt/2z8ITDx

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Milne, RL; Kuchenbaecker, KB; Michailidou, K; Beesley, J; Kar, S; Lindström, S; Hui, S; ... Simard, J; + view all Milne, RL; Kuchenbaecker, KB; Michailidou, K; Beesley, J; Kar, S; Lindström, S; Hui, S; Lemaçon, A; Soucy, P; Dennis, J; Jiang, X; Rostamianfar, A; Finucane, H; Bolla, MK; McGuffog, L; Wang, Q; Aalfs, CM; ABCTB Investigators, .; Adams, M; Adlard, J; Agata, S; Ahmed, S; Ahsan, H; Aittomäki, K; Al-Ejeh, F; Allen, J; Ambrosone, CB; Amos, CI; Andrulis, IL; Anton-Culver, H; Antonenkova, NN; Arndt, V; Arnold, N; Aronson, KJ; Auber, B; Auer, PL; Ausems, MGEM; Azzollini, J; Bacot, F; Balmaña, J; Barile, M; Barjhoux, L; Barkardottir, RB; Barrdahl, M; Barnes, D; Barrowdale, D; Baynes, C; Beckmann, MW; Benitez, J; Bermisheva, M; Bernstein, L; Bignon, Y-J; Blazer, KR; Blok, MJ; Blomqvist, C; Blot, W; Bobolis, K; Boeckx, B; Bogdanova, NV; Bojesen, A; Bojesen, SE; Bonanni, B; Børresen-Dale, A-L; Bozsik, A; Bradbury, AR; Brand, JS; Brauch, H; Brenner, H; Bressac-de Paillerets, B; Brewer, C; Brinton, L; Broberg, P; Brooks-Wilson, A; Brunet, J; Brüning, T; Burwinkel, B; Buys, SS; Byun, J; Cai, Q; Caldés, T; Caligo, MA; Campbell, I; Canzian, F; Caron, O; Carracedo, A; Carter, BD; Castelao, JE; Castera, L; Caux-Moncoutier, V; Chan, SB; Chang-Claude, J; Chanock, SJ; Chen, X; Cheng, T-YD; Chiquette, J; Christiansen, H; Claes, KBM; Clarke, CL; Conner, T; Conroy, DM; Cook, J; Cordina-Duverger, E; Cornelissen, S; Coupier, I; Cox, A; Cox, DG; Cross, SS; Cuk, K; Cunningham, JM; Czene, K; Daly, MB; Damiola, F; Darabi, H; Davidson, R; De Leeneer, K; Devilee, P; Dicks, E; Diez, O; Ding, YC; Ditsch, N; Doheny, KF; Domchek, SM; Dorfling, CM; Dörk, T; Dos-Santos-Silva, I; Dubois, S; Dugué, P-A; Dumont, M; Dunning, AM; Durcan, L; Dwek, M; Dworniczak, B; Eccles, D; Eeles, R; Ehrencrona, H; Eilber, U; Ejlertsen, B; Ekici, AB; Eliassen, AH; EMBRACE, .; Engel, C; Eriksson, M; Fachal, L; Faivre, L; Fasching, PA; Faust, U; Figueroa, J; Flesch-Janys, D; Fletcher, O; Flyger, H; Foulkes, WD; Friedman, E; Fritschi, L; Frost, D; Gabrielson, M; Gaddam, P; Gammon, MD; Ganz, PA; Gapstur, SM; Garber, J; Garcia-Barberan, V; García-Sáenz, JA; Gaudet, MM; Gauthier-Villars, M; Gehrig, A; GEMO Study Collaborators, .; Georgoulias, V; Gerdes, A-M; Giles, GG; Glendon, G; Godwin, AK; Goldberg, MS; Goldgar, DE; González-Neira, A; Goodfellow, P; Greene, MH; Alnæs, GIG; Grip, M; Gronwald, J; Grundy, A; Gschwantler-Kaulich, D; Guénel, P; Guo, Q; Haeberle, L; Hahnen, E; Haiman, CA; Håkansson, N; Hallberg, E; Hamann, U; Hamel, N; Hankinson, S; Hansen, TVO; Harrington, P; Hart, SN; Hartikainen, JM; Healey, CS; HEBON, .; Hein, A; Helbig, S; Henderson, A; Heyworth, J; Hicks, B; Hillemanns, P; Hodgson, S; Hogervorst, FB; Hollestelle, A; Hooning, MJ; Hoover, B; Hopper, JL; Hu, C; Huang, G; Hulick, PJ; Humphreys, K; Hunter, DJ; Imyanitov, EN; Isaacs, C; Iwasaki, M; Izatt, L; Jakubowska, A; James, P; Janavicius, R; Janni, W; Jensen, UB; John, EM; Johnson, N; Jones, K; Jones, M; Jukkola-Vuorinen, A; Kaaks, R; Kabisch, M; Kaczmarek, K; Kang, D; Kast, K; kConFab/AOCS Investigators, .; Keeman, R; Kerin, MJ; Kets, CM; Keupers, M; Khan, S; Khusnutdinova, E; Kiiski, JI; Kim, S-W; Knight, JA; Konstantopoulou, I; Kosma, V-M; Kristensen, VN; Kruse, TA; Kwong, A; Lænkholm, A-V; Laitman, Y; Lalloo, F; Lambrechts, D; Landsman, K; Lasset, C; Lazaro, C; Le Marchand, L; Lecarpentier, J; Lee, A; Lee, E; Lee, JW; Lee, MH; Lejbkowicz, F; Lesueur, F; Li, J; Lilyquist, J; Lincoln, A; Lindblom, A; Lissowska, J; Lo, W-Y; Loibl, S; Long, J; Loud, JT; Lubinski, J; Luccarini, C; Lush, M; MacInnis, RJ; Maishman, T; Makalic, E; Kostovska, IM; Malone, KE; Manoukian, S; Manson, JE; Margolin, S; Martens, JWM; Martinez, ME; Matsuo, K; Mavroudis, D; Mazoyer, S; McLean, C; Meijers-Heijboer, H; Menéndez, P; Meyer, J; Miao, H; Miller, A; Miller, N; Mitchell, G; Montagna, M; Muir, K; Mulligan, AM; Mulot, C; Nadesan, S; Nathanson, KL; NBSC Collaborators, .; Neuhausen, SL; Nevanlinna, H; Nevelsteen, I; Niederacher, D; Nielsen, SF; Nordestgaard, BG; Norman, A; Nussbaum, RL; Olah, E; Olopade, OI; Olson, JE; Olswold, C; Ong, K-R; Oosterwijk, JC; Orr, N; Osorio, A; Pankratz, VS; Papi, L; Park-Simon, T-W; Paulsson-Karlsson, Y; Lloyd, R; Pedersen, IS; Peissel, B; Peixoto, A; Perez, JIA; Peterlongo, P; Peto, J; Pfeiler, G; Phelan, CM; Pinchev, M; Plaseska-Karanfilska, D; Poppe, B; Porteous, ME; Prentice, R; Presneau, N; Prokofieva, D; Pugh, E; Pujana, MA; Pylkäs, K; Rack, B; Radice, P; Rahman, N; Rantala, J; Rappaport-Fuerhauser, C; Rennert, G; Rennert, HS; Rhenius, V; Rhiem, K; Richardson, A; Rodriguez, GC; Romero, A; Romm, J; Rookus, MA; Rudolph, A; Ruediger, T; Saloustros, E; Sanders, J; Sandler, DP; Sangrajrang, S; Sawyer, EJ; Schmidt, DF; Schoemaker, MJ; Schumacher, F; Schürmann, P; Schwentner, L; Scott, C; Scott, RJ; Seal, S; Senter, L; Seynaeve, C; Shah, M; Sharma, P; Shen, C-Y; Sheng, X; Shimelis, H; Shrubsole, MJ; Shu, X-O; Side, LE; Singer, CF; Sohn, C; Southey, MC; Spinelli, JJ; Spurdle, AB; Stegmaier, C; Stoppa-Lyonnet, D; Sukiennicki, G; Surowy, H; Sutter, C; Swerdlow, A; Szabo, CI; Tamimi, RM; Tan, YY; Taylor, JA; Tejada, M-I; Tengström, M; Teo, SH; Terry, MB; Tessier, DC; Teulé, A; Thöne, K; Thull, DL; Tibiletti, MG; Tihomirova, L; Tischkowitz, M; Toland, AE; Tollenaar, RAEM; Tomlinson, I; Tong, L; Torres, D; Tranchant, M; Truong, T; Tucker, K; Tung, N; Tyrer, J; Ulmer, H-U; Vachon, C; van Asperen, CJ; Van Den Berg, D; van den Ouweland, AMW; van Rensburg, EJ; Varesco, L; Varon-Mateeva, R; Vega, A; Viel, A; Vijai, J; Vincent, D; Vollenweider, J; Walker, L; Wang, Z; Wang-Gohrke, S; Wappenschmidt, B; Weinberg, CR; Weitzel, JN; Wendt, C; Wesseling, J; Whittemore, AS; Wijnen, JT; Willett, W; Winqvist, R; Wolk, A; Wu, AH; Xia, L; Yang, XR; Yannoukakos, D; Zaffaroni, D; Zheng, W; Zhu, B; Ziogas, A; Ziv, E; Zorn, KK; Gago-Dominguez, M; Mannermaa, A; Olsson, H; Teixeira, MR; Stone, J; Offit, K; Ottini, L; Park, SK; Thomassen, M; Hall, P; Meindl, A; Schmutzler, RK; Droit, A; Bader, GD; Pharoah, PDP; Couch, FJ; Easton, DF; Kraft, P; Chenevix-Trench, G; García-Closas, M; Schmidt, MK; Antoniou, AC; Simard, J; - view fewer (2017) Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nature Genetics 10.1038/ng.3785 . (In press).

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Human responses and non-responses to climatic variations during the last Glacial-Interglacial transition in the eastern Mediterranean

Roberts, N; Woodbridge, J; Bevan, A; Palmisano, A; Shennan, S; Asouti, E; (2017) Human responses and non-responses to climatic variations during the last Glacial-Interglacial transition in the eastern Mediterranean. Quaternary Science Reviews 10.1016/j.quascirev.2017.09.011 . (In press).

http://ift.tt/2z7AUWY

Eye-Tracking Causality

Gerstenberg, T; Peterson, MF; Goodman, ND; Lagnado, DA; Tenenbaum, JB; (2017) Eye-Tracking Causality. Psychological Science 10.1177/0956797617713053 . (In press). Green open access

http://ift.tt/2iUPk8S

Applications of the periodic electrostatic embedded cluster method to solid state actinide chemistry

Wellington, Joseph Paul William; (2017) Applications of the periodic electrostatic embedded cluster method to solid state actinide chemistry. Doctoral thesis , UCL (University College London). Green open access

http://ift.tt/2z8IC3t

Problem solving, confidence and frustration when carrying out familiar tasks on non-familiar mobile devices

Attard, C; Mountain, G; Romano, DM; (2016) Problem solving, confidence and frustration when carrying out familiar tasks on non-familiar mobile devices. Computers in Human Behavior , 61 pp. 300-312. 10.1016/j.chb.2016.03.001 .

http://ift.tt/2iUSlpK

Deprivation-Induced Homeostatic Spine Scaling In Vivo Is Localized to Dendritic Branches that Have Undergone Recent Spine Loss

Keck, T; Barnes, SB; Franzoni, E; Jacobsen, RI; Clopath, C; Keller, GB; (2017) Deprivation-Induced Homeostatic Spine Scaling In Vivo Is Localized to Dendritic Branches that Have Undergone Recent Spine Loss. Neuron (In press). Green open access

http://ift.tt/2z7AG24

Infrastructure as a Financial Asset Class

Panayiotou, Athina; (2017) Infrastructure as a Financial Asset Class. Doctoral thesis , UCL (University College London). Green open access

http://ift.tt/2iUShq0

International multi-centre study of pregnancy outcomes with interleukin-1 inhibitors

Youngstein, T; Hoffmann, P; Gül, A; Lane, T; Williams, R; Rowczenio, DM; Ozdogan, H; ... Lachmann, HJ; + view all Youngstein, T; Hoffmann, P; Gül, A; Lane, T; Williams, R; Rowczenio, DM; Ozdogan, H; Ugurlu, S; Ryan, J; Harty, L; Riminton, S; Headley, AP; Roesler, J; Blank, N; Kuemmerle-Deschner, JB; Simon, A; Woolf, AS; Hawkins, PN; Lachmann, HJ; - view fewer (2017) International multi-centre study of pregnancy outcomes with interleukin-1 inhibitors. Rheumatology 10.1093/rheumatology/kex305 .

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MMS observation of magnetic reconnection in the turbulent magnetosheath

Voros, ZVR; Yordanova, E; Varsani, A; Genestreti, KJ; Khotyaintsev, YV; Li, W; Graham, DB; ... Saito, Y; + view all Voros, ZVR; Yordanova, E; Varsani, A; Genestreti, KJ; Khotyaintsev, YV; Li, W; Graham, DB; Norgren, C; Nakamura, R; Narita, Y; Plaschke, F; Magnes, W; Baumjohann, W; Fischer, D; Vaivads, A; Eriksson, E; Lindqvist, P-A; Marklund, G; Ergun, RE; Leitner, M; Leubner, MP; Strangeway, RJ; Contel, OL; Pollock, C; Giles, BJ; Torbert, RB; Burch, JL; Avanov, LA; Dorelli, JC; Gershman, DJ; Paterson, WR; Lavraud, B; Saito, Y; - view fewer (2017) MMS observation of magnetic reconnection in the turbulent magnetosheath. Journal of Geophysical Research: Space Physics 10.1002/2017ja024535 . (In press).

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Scanning Tunnelling Microscopy and Electron Spectroscopy studies of Gold Nanoparticles dispersed Over Rutile TiO₂ (110)

Mellor, AG; (2017) Scanning Tunnelling Microscopy and Electron Spectroscopy studies of Gold Nanoparticles dispersed Over Rutile TiO₂ (110). Doctoral thesis , UCL (University College London). Green open access

http://ift.tt/2z8YrqS

Feasibility assessment and informed survey design of cavity detection by forward geophysical modelling

James, PM; (2017) Feasibility assessment and informed survey design of cavity detection by forward geophysical modelling. Doctoral thesis , UCL (University College London). Green open access

http://ift.tt/2iUIakY

Role of microRNAs in cone photoreceptor development and during retinal degeneration

Zabala Aldunate, E; (2017) Role of microRNAs in cone photoreceptor development and during retinal degeneration. Doctoral thesis , UCL (University College London).

http://ift.tt/2z6rjzJ

Taste evaluation of a novel midazolam tablet for pediatric patients: in vitro drug dissolution, in vivo animal taste aversion and clinical taste perception profiles

Tuleu, C; Cheung, LC; Nguyen, M; Tang, E; von Ungern Sternberg, BS; Salman, S; Mohamed Ahmed, AHA; ... Lim, LY; + view all Tuleu, C; Cheung, LC; Nguyen, M; Tang, E; von Ungern Sternberg, BS; Salman, S; Mohamed Ahmed, AHA; Soto, J; Lim, LY; - view fewer (2017) Taste evaluation of a novel midazolam tablet for pediatric patients: in vitro drug dissolution, in vivo animal taste aversion and clinical taste perception profiles. International Journal of Pharmaceutics (In press).

http://ift.tt/2iSAOP0

Kommentar zur Leitlinie Rhinosinusitis – was ist wichtig, was ist neu?

http://ift.tt/2zrbLtB

Vestibularisschwannomchirurgie – mehr Gleichgewichtsdiagnostik zum verbesserten Hörerhalt?

http://ift.tt/2zZbCd6

Dermoscopic ‘Chaos and Clues’ in the diagnosis of melanoma in situ

Abstract

Background/Objective

To describe the dermoscopic features of melanoma in situ using the Chaos and Clues method.

Method

Histologically proven primary melanoma in situ (MIS) diagnosed through a specialist teledermoscopy clinic were reviewed by three dermatologists. By consensus they agreed on the global dermoscopic pattern, colours, presence of chaos (asymmetry of colour and structure and more than one pattern), and each of the nine clues described for malignancy.

Results

One hundred MIS in 92 patients of European ethnicity (45 males) were assessed. Mean age was 67.3 years (range 20–95). The mean dimensions of the lesions were 11.1 × 12.0 mm (range 2.5–31.3 × 2.3–32.3 mm). Using pattern analysis, 82% of the lesions had three or more patterns (multicomponent) and the rest had 2 patterns. Colours included light brown (100%), dark brown (98%) and grey (75%). All MIS demonstrated chaos. The most prevalent clues were thick lines (88%), eccentric structureless areas (88%), and grey or blue structures (75%).

Conclusion

Dermoscopy can be very helpful in the early diagnosis of melanoma and MIS. The Chaos and Clues method is simple to use. Its unambiguous descriptors can be successfully used to describe MIS. The presence of chaos and clues to malignancy (including thick lines, eccentric structureless areas, and blue/grey structures) should raise a red flag and lead to referral or excision.

http://ift.tt/2zdm3wq

Intraoperative administration of dexmedetomidine reduced the postoperative catheter-related bladder discomfort and pain in patients undergoing lumbar microdiscectomy

Abstract

Purpose

We aimed to evaluate the effect of the intraoperative dexmedetomidine (DEX) on the incidence and severity of catheter-related bladder discomfort (CRBD) after non-urologic surgery. The secondary aim was to find the correlation between the levels of CRBD and postoperative pain sensation.

Methods

Adult male patients undergoing lumbar microdiscectomy were enrolled. Patients were randomized into two groups. After propofol administration, group D (n = 35) received DEX at a loading dose of 1 μg/kg over 10 min, followed by a continuous infusion of 0.3–0.5 μg/kg/h until the end of surgery. In group C (n = 35), an identical volume of 0.9% saline was infused in the same manner. Induction and maintenance of anesthesia were standardized. The incidence and severity of CRBD, postoperative pain, and adverse effects were assessed at 1, 3, and 6 h after surgery.

Results

The incidence of CRBD was significantly lower in group D than in group C at 1 h (34.3 vs. 62.9%, P = 0.017), 3 h (25.7 vs. 60%, P = 0.004), and 6 h (17.1 vs. 54.3%. P = 0.001) postoperatively. The severity of CRBD at 1, 3, and 6 h postoperatively was less in group D than in group C. Postoperative pain score was significantly lower in group D than in group C at 3 and 6 h postoperatively. Adverse events were comparable between two groups. There was a significant correlation between the severity of CRBD and postoperative pain score.

Conclusions

Intraoperative administration of DEX is a safe and effective practice for the prevention of CRBD after lumbar microdiscectomy and can reduce postoperative pain.

http://ift.tt/2xOtS8a

Clinical Research in Dermatology in Spain

P. Dávila Seijo
Actas Dermosifiliogr.2017;108:797

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A Selfie of Mohs Micrographic Surgery in Spain

M. de Troya-Martín
Actas Dermosifiliogr.2017;108:797-8

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Dermoscopy Can Indicate the Grade of Actinic Keratoses

P. Zaballos Diego
Actas Dermosifiliogr.2017;108:798

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Psoriasis Protects Against a Low Minimal Erythema Dose

M.V. de Gálvez
Actas Dermosifiliogr.2017;108:798-9

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Clinical, Diagnostic, and Therapeutic Implications in Psoriasis Associated With Cardiovascular Disease

C. Bonanad, E. González-Parra, R. Rivera, J.M. Carrascosa, E. Daudén, A. Olveira, R. Botella-Estrada
Actas Dermosifiliogr.2017;108:800-8

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Nonsurgical Therapies for Basal Cell Carcinoma: A Review

S. Ariza, S. Espinosa, M. Naranjo
Actas Dermosifiliogr.2017;108:809-17

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Novel Additions to the AJCC's New Staging Systems for Skin Cancer

J. Cañueto, C. Román-Curto
Actas Dermosifiliogr.2017;108:818-26

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Professor Joaquín Piñol Aguadé: An Important Figure in Dermatology

C. Herrero-Mateu
Actas Dermosifiliogr.2017;108:827-9

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A Map of Clinical Dermatology Research Centers in Spain: Results of the MaIND Study

A. Molina-Leyva, M.A. Descalzo, I. García-Doval
Actas Dermosifiliogr.2017;108:830-5

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Characterization of Surgical Procedures in the Spanish Mohs Surgery Registry (REGESMOHS) for 2013-2015

E. de Eusebio Murillo, A. Martín Fuentes, V. Ruiz-Salas, J.R. Garcés, R. Miñano Medrano, J.L. López-Estebaranz, T. Alonso-Alonso, M.Á. Rodríguez-Prieto, Y. Delgado Jiménez, V. Morales, P. Redondo Bellón, E. Manubens-Mercadé, O. Sanmartín-Jiménez, C. Guillén Barona, R. Cabeza, N. Cano, A. Toll-Abelló, R. Navarro Tejedor, J.L. Artola Igarza, I. Allende Markixana, A. Alfaro Rubio, C. Ciudad Blanco, H. Vázquez-Veiga, L. Barchino Ortiz, M.A. Descalzo, I. García-Doval
Actas Dermosifiliogr.2017;108:836-43

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Dermoscopy of Pigmented Actinic Keratosis of the Face: A Study of 232 Cases

A. Kelati, H. Baybay, E. Moscarella, G. Argenziano, S. Gallouj, F.Z. Mernissi
Actas Dermosifiliogr.2017;108:844-51

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Is it Useful to Calculate Minimal Erythema Dose Before Narrowband UV-B Phototherapy?

M.T. Rodríguez-Granados, A. Estany-Gestal, M. Pousa-Martínez, J. Labandeira, R. Gato Otero, V. Fernández-Redondo
Actas Dermosifiliogr.2017;108:852-8

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Congenital Melanocytic Nevus Syndrome: A Case Series

A. Recio Linares, A.I. Sánchez Moya, V. Félix, Y. Campos
Actas Dermosifiliogr.2017;108:e57-62

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Alopecia, Follicular Papules, and Short Stature

L. González-Lara, P. Gonzalvo-Rodríguez, E. Rodríguez-Díaz
Actas Dermosifiliogr.2017;108:859-60

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Nodules on the Hands and Musculoskeletal Abnormalities

C. Sanchis-Sánchez, A. Mateu-Puchades, F. García-Herreros
Actas Dermosifiliogr.2017;108:861-2

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Dermoscopic Features of Facial Trichilemmoma

B. Lozano-Masdemont, I.M. de Lara Simón, L. González López
Actas Dermosifiliogr.2017;108:863-4

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RF-The METOP Study: Further Evidence for the Use of Subcutaneous Methotrexate in Psoriasis

D. Morgado-Carrasco, X. Fustà-Novell, J. Riera-Monroig, J.M. Mascaró Galy
Actas Dermosifiliogr.2017;108:865-6

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The Single-Stage Paramedian Forehead Flap

A. Martinez-Lopez, I. Perez-Lopez, E. Garcia-Dura, J. Tercedor-Sanchez
Actas Dermosifiliogr.2017;108:867-8

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Spontaneous Change in a Common Melanocytic Nevus

C. Mendoza, P. Zamberk, P. Cortina
Actas Dermosifiliogr.2017;108:869

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Cutaneous Blisters in a Patient With Systemic Lupus Erythematosus

M.Á. Flores-Terry, M.P. Sánchez-Caminero, R. Cruz-Conde de Boom, D. Bellido Pastrana
Actas Dermosifiliogr.2017;108:870

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Wireless Neuromodulation for Chronic Back Pain: Delivery of High-Frequency Dorsal Root Ganglion Stimulation by a Minimally Invasive Technique

Objective. To evaluate the analgesic effect of a dorsal root ganglion (DRG) stimulation technology utilizing high-frequency pulse rates to treat intractable chronic back and leg pain. Methods. This case study presents the outcomes, with a novel, wireless, minimally invasive miniature neurostimulator system in a case of chronic back pain. The subject was implanted bilaterally with a Freedom 4A quadripolar electrode array at the L2 dorsal root ganglion. Stimulation was applied using 10 kHz pulse rate and 30 μs pulse width. A VAS pain-rating scale, Oswestry Disability Index (ODI), EQ-5D-5L Quality of Life Questionnaire 5 dimensions, and Patients' Global Impression of Change (PGIC) scale were evaluated at 12 weeks and 6 months post implantation. Results. VAS pain scores for back pain reduced from 91 to 31 mms and 80 to 35 mms for leg pain. Additionally, while stimulation remained paresthesia-free, there were a marked decrease in pain medications and an increase in quality of life. Also, an increase in functionality from crippled to moderate was reported. There were no adverse reactions related to the procedure or device. Conclusion. The minimally invasive, wireless approach to deliver high-frequency, paresthesia-free DRG stimulation for treatment of chronic back and leg pain associated with FBSS was effective and encouraging.

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Pancreatic Laceration in a Pediatric Patient: An Unexpected Diagnosis

Pediatric pancreatic injuries are rare. We present an atypical case that occurred in a 4-year-old male. The child presented with a twenty-four-hour history of vomiting that had progressed to right lower quadrant abdominal pain on examination in the emergency department. The initial differential was gastroenteritis versus appendicitis. An abnormality on the ultrasonography and an elevated lipase level eventually led to an MRI showing a complete transection through the posterior margin of the pancreas. The patient was admitted to pediatric surgery and underwent a successful distal pancreatectomy with preservation of the spleen. On further inquiry specific to trauma, the child disclosed that his older brother had punched him in his abdomen the night before. The child's parents were separated due to intimate partner violence, and this older sibling recently had been very stressed. The sibling was referred for mental health evaluation and counseling, and the case reported to the county children and youth investigative services system. A low threshold for considering trauma and child abuse in the pediatric population is recommended when significant intra-abdominal injury is diagnosed.

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