Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Πέμπτη 27 Απριλίου 2017
Preliminary investigation of preoperative pregabalin and total intravenous anesthesia doses: a randomized controlled trial
To determine the efficacy of 2 different doses (150-300mg) of preoperative pregabalin on propofol and remifentanil doses for total intravenous anesthesia in laparoscopic cholecystectomy.
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Thymus neuroendocrine tumors with CTNNB1 gene mutations, disarrayed ß-catenin expression, and dual intra-tumor Ki-67 labeling index compartmentalization challenge the concept of secondary high-grade neuroendocrine tumor: a paradigm shift
Abstract
We herein report an uncommon association of intimately admixed atypical carcinoid (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus, occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by maximal thymectomy. The younger patient presented with a synchronous lesion and died of disease after 9 months, while the other patient was associated with a recurrent ectopic adrenocorticotropic hormone Cushing's syndrome and is alive with disease at the 2-year follow-up. MEN1 syndrome was excluded in either case. Immunohistochemically, disarrayed cytoplasmic and nuclear ß-catenin expression was seen alongside an intra-tumor Ki-67 antigen labeling index (LI) ranging from 2 to 80% in the younger patient's tumor and from 3 to 45% in the other. Both exhibited upregulated cyclin D1 and retinoblastoma, while vimentin was overexpressed in the recurrent LCNEC only. Next-generation sequencing revealed CTNNB1, TP53, and JAK3 mutations in the synchronous tumor and CTNNB1 mutation alone in the metachronous tumor (the latter with the same mutation as the first tumor of 17 years prior). None of the 23 T-NET controls exhibited this hallmarking triple alteration (p = 0.003). These findings suggested that LCNEC components developed from pre-existing CTNNB1-mutated AC upon loss-of-function TP53 and gain-of-function JAK3 mutations in one case and an epithelial-mesenchymal transition upon vimentin overexpression in the other case. Both tumors maintained intact cyclin D1–retinoblastoma machinery. Our report challenges the concept of secondary LCNEC as an entity that develops from pre-existing AC as a result of tumor progression, suggesting a paradigm shift to the current pathogenesis of NET.
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Aims & Scope/Editorial board
Source:Archives of Oral Biology, Volume 79
http://ift.tt/2oCohkQ
Promoter methylation of MGMT in oral carcinoma: A population-based study and meta-analysis
Source:Archives of Oral Biology, Volume 80
Author(s): Chinchu Jayaprakash, Raghu Radhakrishnan, Satadru Ray, Kapaettu Satyamoorthy
IntroductionThe relevance of DNA methylation of O6-methylguanine-DNA methyltransferase (MGMT) in relation to several cancers and other disorders has been extensively explored in several cancer types.AimsTo ascertain the significance of DNA methylation of MGMT promoter in oral squamous cell carcinoma (OSCC), we undertook a study to a) analyse the methylation patterns of MGMT gene promoter in afflicted and normal population of coastal Karnataka, b) determine the expression status of MGMT in oral cancer cell lines (CAL-27 and SCC-4) and its relationship to DNA methylation and c) performed a meta-analysis of the published data.MethodsBisulfite sequencing of MGMT promoter region was performed on non-malignant/malignant oral samples, and oral cancer cell lines, followed by gene expression studies. Further, using a systematic search, 1024 publications were retrieved from PubMed, Scopus, Google Scholar and Web of Science and 23 relevant articles were reviewed.ResultsSignificant association of MGMT promoter methylation with OSCC (p<0.0001) was observed in the case-control study. The studies chosen for meta-analysis showed predictive significance of MGMT gene promoter. Overall, we obtained a statistically significant (p<0.0001) association for both sensitivity and specificity of MGMT DNA promoter methylation in oral cancer cases without publication bias. Gene expression was significantly elevated in both oral cancer cell lines (p<0.03) after treatment with a demethylating agent (5-Aza-2′-deoxycytidine).ConclusionDNA promoter hypermethylation and gene expression of MGMT may associate with recursive mutagenesis and is a promising biomarker for OSCC prediction. Studies suggest further validation in large distinct cohorts to facilitate translation to clinics.
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Synchrotron X-ray diffraction to understand crystallographic texture of enamel affected by Hunter syndrome
Source:Archives of Oral Biology, Volume 80
Author(s): Malik Arshman Khan, Owen Addison, Alison James, Christian J. Hendriksz, Maisoon Al-Jawad
ObjectiveTo determine whether Hunter syndrome (MPS II) affects the crystallographic texture (preferred orientation) of enamel.DesignSynchrotron X-ray diffraction, being a state of the art technique, has been used to determine the enamel crystallite orientation in enamel affected by Hunter syndrome (MPS II). The incisal, lingual and cervical regions of the MPS II affected tooth were observed and compared to healthy tooth.ResultsIt was observed that there is a loss of organization of crystallites in deciduous incisal enamel affected by Hunter syndrome (MPS II) as compared to healthy deciduous enamel tissue. Generally it was observed that, in contrast to the healthy enamel, the enamel affected by MPS II possessed a lower crystallographic preferred orientation, with a more uniform spatial distribution; however, the enamel at the incisal tip was relatively unaffected.ConclusionHunter syndrome affects the enamel texture in the lingual and cervical regions of the tooth.
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Frequency of MCP-1 (rs1024611) and CCR2 (rs1799864) gene polymorphisms and its effect on gene expression level in patients with AgP
Source:Archives of Oral Biology, Volume 80
Author(s): Sadiye Gunpinar, Nilgun Ozlem Alptekin, V. Betul Ucar, Hasan Acar
ObjectiveTo identify the genetic risk markers of aggressive periodontitis (AgP), researchers focus on genetic components that regulate the immune response. Therefore the purpose of this study was to investigate genetic impact of monocyte chemoattractant protein (MCP)-1–2518A/G and CC chemokine receptor 2 (CCR2) −190G/A gene polymorphisms on AgP susceptibility and the effect of this polymorphism on MCP-1 gene expression in patients with AgP.Material and methodsA total of 215 subjects, 108 AgP and 107 periodontally healthy (H) were recruited in this cross-sectional study (NCT02817568). Gene polymorphisms of MCP-1–2518A/G and CCR2–190G/A were analyzed by a standard polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. MCP-1 messenger (m) RNA expression was measured using quantitative real-time (RT)-PCR in peripheral blood leukocytes from 26 AgP and 16H controls. Threshold cycles (Ct) values were obtained from the RT-PCR analysis based on SYBR Green detection and data was normalized via ΔCt.ResultsThere were no differences between AgP and H groups with regard to MCP-1 and CCR2 genotype distribution and allele frequencies (p>0.05). In contrast, the MCP-1 mRNA expression levels were higher in homozygous "AA" control subjects than having G+ genotype and AA homozygous AgP patients.ConclusionsIt can be concluded that MCP-1 and CCR2 polymorphisms are not associated with AgP in Turkish population. Although in AgP patients, there was AA genotype with MCP-1 mRNA expression it can be speculated that gene expression levels in peripheral blood may not reflect the cytokine/chemokine levels of local tissues.
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Metabolite-Sensing G Protein–Coupled Receptors—Facilitators of Diet-Related Immune Regulation
Annual Review of Immunology, Volume 35, Issue 1, Page 371-402, April 2017.
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Protective and Harmful Immunity to RSV Infection
Annual Review of Immunology, Volume 35, Issue 1, Page 501-532, April 2017.
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Immunobiology of Long Noncoding RNAs
Annual Review of Immunology, Volume 35, Issue 1, Page 177-198, April 2017.
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Disorders of the JAK/STAT Pathway in T Cell Lymphoma Pathogenesis: Implications for Immunotherapy
Annual Review of Immunology, Volume 35, Issue 1, Page 533-550, April 2017.
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Mucosal Ecological Network of Epithelium and Immune Cells for Gut Homeostasis and Tissue Healing
Annual Review of Immunology, Volume 35, Issue 1, Page 119-147, April 2017.
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Understanding Human Autoimmunity and Autoinflammation Through Transcriptomics
Annual Review of Immunology, Volume 35, Issue 1, Page 337-370, April 2017.
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Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities
Annual Review of Immunology, Volume 35, Issue 1, Page 229-253, April 2017.
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Th2 Cells in Health and Disease
Annual Review of Immunology, Volume 35, Issue 1, Page 53-84, April 2017.
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Microbes and Cancer
Annual Review of Immunology, Volume 35, Issue 1, Page 199-228, April 2017.
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Intracellular Nucleic Acid Detection in Autoimmunity
Annual Review of Immunology, Volume 35, Issue 1, Page 313-336, April 2017.
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A Perspective on the Role of Computational Models in Immunology
Annual Review of Immunology, Volume 35, Issue 1, Page 403-439, April 2017.
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Microglia Function in the Central Nervous System During Health and Neurodegeneration
Annual Review of Immunology, Volume 35, Issue 1, Page 441-468, April 2017.
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Antigen-Presenting Cells in the Skin
Annual Review of Immunology, Volume 35, Issue 1, Page 469-499, April 2017.
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Signaling by Antibodies: Recent Progress
Annual Review of Immunology, Volume 35, Issue 1, Page 285-311, April 2017.
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Genetics of Infectious and Inflammatory Diseases: Overlapping Discoveries from Association and Exome-Sequencing Studies
Annual Review of Immunology, Volume 35, Issue 1, Page 1-30, April 2017.
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Thymic Epithelial Cells
Annual Review of Immunology, Volume 35, Issue 1, Page 85-118, April 2017.
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The Lymphatic System: Integral Roles in Immunity
Annual Review of Immunology, Volume 35, Issue 1, Page 31-52, April 2017.
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Memory B Cells of Mice and Humans
Annual Review of Immunology, Volume 35, Issue 1, Page 255-284, April 2017.
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The Biology and Underlying Mechanisms of Cross-Presentation of Exogenous Antigens on MHC-I Molecules
Annual Review of Immunology, Volume 35, Issue 1, Page 149-176, April 2017.
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Unique features in the presentation of insulin epitopes in autoimmune diabetes: an update
Xiaoxiao Wan | Emil R Unanue
http://ift.tt/2oOquoJ
Mortality of Necrotising Fasciitis: relative influence of individual and hospital-level factors, a Nationwide Multi-Level Study, France, 2007-2012
Abstract
Background
Necrotising soft-tissue infections (NSTI) are rare, life-threatening conditions.
Objectives
We aimed to assess whether admitting hospital characteristics were associated with NSTI mortality.
Methods
We studied the French nationwide hospital discharge database (retrospective national cohort). All patients admitted in 2007-2012 with an ICD-10 code of necrotising fasciitis were eligible. We extracted data on the patients (age, sex, ICU admission, co-morbidities) and hospitals (public vs private proprietary; for public hospitals, teaching, yes/no; and number of NSTI admissions, ≥3 NSTI cases/year, yes/no). Multivariable analyses were performed to identify independent predictors of day-28 mortality and in-hospital mortality using mixed logistic regression and Cox proportional hazards models, respectively.
Results
We identified 1537 patients (915 males) with a median age of 60 (IQR, 48-75) years, admitted to 326 hospitals, public (82%) and admitting fewer than three NSTI cases/year (93%). Overall, 364 patients died (23·7%; 95%CI, 21·6-25·9). Patients treated in public teaching centres with ≥3NSTI cases annually had lower day-28 mortality (adjusted odds ratio [aOR], 0·68; 95%CI, 0·46-0·99; p=0·045) and in-hospital mortality rates than patients treated in local hospitals, even after adjusting for potentially relevant individual risk factors. No significant association was found between mortality and inter-hospital transfer.
Conclusions
Our finding highlighted an increased survival in teaching centres with high NSTI volume procedures. If confirmed in other settings, these findings reinforce the importance of expertise in early diagnosis and management of this condition.
This article is protected by copyright. All rights reserved.
http://ift.tt/2qcEOt8
Duration and exclusiveness of breastfeeding and risk of childhood atopic diseases
Abstract
Background
Breastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease-related modification of the exposure or modified by maternal history of maternal history of allergy, eczema or asthma.
Methods
This study among 5,828 children was performed in a population-based prospective cohort from fetal life onwards. We collected information on duration (<2 months, 2-4 months, 4-6 months and ≥6 months) and exclusiveness (non-exclusive vs. exclusive for 4 months) of breastfeeding in infancy by postal questionnaires. At age 10 years, inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by a postal questionnaire. Data on parental-reported eczema were available from birth until age 10 years.
Results
We observed no association of breastfeeding with any allergic sensitization, physician-diagnosed allergy, or combination of these outcomes. Shorter breastfeeding duration was associated with an overall increased risk of eczema (p-value for trend <0.05). Non-exclusively breastfed children had an overall increased risk of eczema (aOR (95% CI): 1.11 (1.01, 1.23)), compared with children exclusively breastfed for 4 months. Risk period-specific sensitivity analyses, additional adjustment for ointment use for eczema at age 2 months, and cross-lagged modeling showed no consistent results for disease-related modification of the exposure. Results were not modified by maternal history of allergy, eczema or asthma (lowest p-value for interaction =0.13).
Conclusions
Shorter duration or non-exclusiveness of breastfeeding is associated with a weak overall increased risk of eczema but not allergic sensitization or physician-diagnosed allergy at age 10 years
This article is protected by copyright. All rights reserved.
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Anesthetic consideration for neuromuscular diseases.
Purpose of review: The aim of this review is to examine data relating to perioperative management of the patient with neuromuscular disorders Recent findings: Patients with pre-existing neuromuscular disorders are at risk for a number of postoperative complications that are related to anesthetic drugs that are administered intraoperatively. Careful preoperative assessment is necessary to reduce morbidity and mortality. In particular, the risk of postoperative respiratory failure and need for long-term ventilation should be reviewed with patients. The use of succinylcholine should be avoided in muscular dystrophies, motor neuron diseases, and intrinsic muscle disease due to a risk of malignant hyperthermia, hyperkalemia, rhabdomyolysis, and cardiac arrest. The use of quantitative neuromuscular monitoring should be strongly considered whenever nondepolarizing neuromuscular blocking agents are administered. A number of case series and reports have been recently published demonstrating that sugammadex can be safely used in patients with neuromuscular disease; the risk of residual neuromuscular is nearly eliminated when this agent is administered intraoperatively. Summary: Careful assessment and management of patients with underlying neuromuscular diseases is required to reduce postoperative complications. This article reviews the anesthetic implications of patients undergoing surgery with neuromuscular disorder. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.
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How to treat a patulous Eustachian tube
Source:American Journal of Otolaryngology
Author(s): Zhengcai Lou
http://ift.tt/2qkPFjN
Severe food allergies: can they be considered rare diseases?
No abstract availablehttp://ift.tt/2qkNf4R
Apheresis in food allergies
Purpose of review: The prevalence of IgE-mediated food allergy and anaphylaxis has risen rapidly in developed countries, and countries with rapid industrialization may follow. Therapies include elimination diets, Oral ImmunoTherapy, and the administration of biologics, but high serum IgE levels may preclude their use. Consequently, decreasing IgE becomes a rational approach and could be obtained by immunoapheresis. The aim of this review is to evaluate the rationale and advantages of immunoapheresis. Recent findings: The majority of the available adsorbers remove aspecifically all classes of immunoglobulins. Recently, IgE-specific adsorbers have been approved. Data on immunoapheresis for the treatment of allergic diseases with pathologically elevated IgE levels are emerging. In atopic dermatitis, this therapy alone seems to be beneficial. IgE-selective apheresis appears to be sufficient to reduce the risk of anaphylaxis in multiple food allergy (MFA) and, when IgE titers are high, to open the way to treatment with Omalizumab. Summary: Prospective studies, with well designed protocols, are needed to assess the efficacy, tolerability, and cost-effectiveness of immunoapheresis in the field of food allergy.http://ift.tt/2qkKnof
Novel immunotherapy and treatment modality for severe food allergies
Purpose of review: In recent years, many studies on oral immunotherapy (OIT) have been conducted; however, few have focused on severe food allergies. The purpose of this review was to assess the efficacy and safety of oral immunotherapies for patients with severe food allergy. Recent findings: We reviewed multiple immunotherapy reports published within a few years or reports focusing on severe food allergies. We also investigated recent studies on OIT and novel food allergy management. Summary: Immunotherapies targeting low-dose antigen exposure and oral food challenges using low-dose target volumes may be safer than conventional OIT. It is necessary to consider which immunotherapy regimen is appropriate based on allergy severity of the patient.http://ift.tt/2prvaow
Outstanding animal studies in allergy I. From asthma to food allergy and anaphylaxis
Purpose of review: Animal models published within the past 18 months on asthma, food allergy and anaphylaxis, all conditions of rising public health concern, were reviewed. Recent findings: While domestic animals spontaneously develop asthma, food allergy and anaphylaxis, in animal models, divergent sensitization and challenge routes, dosages, intervals and antigens are used to induce asthmatic, food allergic or anaphylactic phenotypes. This must be considered in the interpretation of results. Instead of model antigens, gradually relevant allergens such as house dust mite in asthma, and food allergens like peanut, apple and peach in food allergy research were used. Novel engineered mouse models such as a mouse with a T-cell receptor for house dust mite allergen Der p 1, or with transgenic human hFcγR genes, facilitated the investigation of single molecules of interest. Whole-body plethysmography has become a state-of-the-art in-vivo readout in asthma research. In food allergy and anaphylaxis research, novel techniques were developed allowing real-time monitoring of in-vivo effects following allergen challenge. Networks to share tissues were established as an effort to reduce animal experiments in allergy which cannot be replaced by in-vitro measures. Summary: Natural and artificial animal models were used to explore the pathophysiology of asthma, food allergy and anaphylaxis and to improve prophylactic and therapeutic measures. Especially the novel mouse models mimicking molecular aspects of the complex immune network in asthma, food allergy and anaphylaxis will facilitate proof-of-concept studies under controlled conditions.http://ift.tt/2prDVyJ
Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy
Purpose of review: Animal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases. Recent findings: Allergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment. Summary: In atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles.http://ift.tt/2prKNMt
Food labeling issues in patients with severe food allergies: solving a hamlet-like doubt
Purpose of review: We review the laws on labeling in the international community, the difficulties they pose to the food manufacturers to prepare the food labels and the methodologies to determine the concentration of potential allergens in foods. Recent findings: European Food Safety Authority and International Life Sciences Institute Europe are evaluating strategies to identify the threshold level of allergen that can trigger a reaction in individuals. The most used techniques to detect the presence of protein in food are Enzyme-linked immunosorbent assay, polymerase chain reaction and real time polymerase chain reaction. Researchers are now trying to apply proteomics to estimate the amount of protein within the food. In order to protect the health of consumers, the Codex Alimentarius Commission updates constantly the list of allergens. In response to these regulations, some industries have also added some precautionary allergen labeling (PAL). It was generally agreed that PAL statements needed to be visible, simple, and safe. It was suggested that PAL be standardized, an action that would occur if the 'Voluntary Incidental Trace Allergen Labelling' process was made mandatory. Summary: So far, no laboratory technique is able to reassure the consumers about the composition of foods found on the packaging. International authorities produced increasingly stringent laws, but more is still to do.http://ift.tt/2prDfJw
Asthma prevalence and severity in low-resource communities
Purpose of review: The prevalence of asthma was thought to be low in most low-income countries, but several reports have indicated this is not always true. This is a narrative review of recent publications on the burden of asthma in low and middle-income countries (LMIC) and underprivileged communities from developed countries. Recent findings: Several studies have reported a low prevalence of asthma is LMIC, but indicate it is increasing. In the last few years, however, many surveys demonstrated this may not always be true. An analysis of the International Study for Asthma and Allergy in Childhood phase III database indicated although the prevalence of asthma among children and adolescents is higher in the developed countries, symptoms of asthma are often more severe in less affluent nations. The rate of uncontrolled asthma is also higher among underprivileged communities of developed countries. Secondary analysis of data generated by the WHO's world health survey performed among adults of 70 countries indicate symptoms of asthma are less frequent in middle-income countries and more frequent in the extremes, low income and high income. This sort of U shaped distribution suggests the disease (or syndrome) comprise more than one major phenotype related to diverse underlying mechanisms. In fact, recent reports show symptoms of asthma among the poor are associated with unhygienic living conditions, which may reduce the risk of atopy but increase the risk of nonatopic wheezing. Urbanization and exposure to air pollution also seem to contribute to an increasing prevalence severity of asthma in LMIC. Access to proper diagnosis and treatment with controller medications for asthma, specially with inhaled corticosteroids is feasible and cost-effective, reduce symptoms, health resource utilization, improves quality of life, and reduce mortality in low-resource settings. Summary: Prevalence of asthma was thought to be low in low-income countries, but several reports have indicated this is not always true. Under diagnosis, under treatment, exposure to air pollution, and unhygienic living conditions may contribute to a higher frequency and severity of symptoms of asthma among the poor. Proper diagnosis and treatment with controller medications for asthma is feasible and cost-effective in low-resource settings.http://ift.tt/2prv14f
Impact of elimination diets on nutrition and growth in children with multiple food allergies
Purpose of review: Growth and nutritional intake of children with cows' milk allergy and other food allergens has been thoroughly investigated in recent years across many different countries and age groups. An impaired growth in atopic children should not be attributed only to a high number of allergens and foods to be avoided, but to a general condition of 'sub-inflammation', which unfavorably affects the absorption and utilization of fuel and substrates. Atopic study participants may represent a good target for personalized nutrition and in this review we sought to outline many of the issues that should be taken into account when dietitians advise patients regarding food avoidance and expected effects on growth. Recent findings: The dietary management of food allergy requires appropriate dietary choices to maintain adequate growth, starting with special formulas in infancy. An emerging area of research is the fussy eating related to the exclusion of cow's milk and other foods during infancy and the long-term effects on eating habits and food preferences. Summary: Study participants with either mono or polyallergic diseases should ideally undergo the definition of their allergic and metabolic characteristics, to precisely adjust dietary interventions on an individual basis to support the genetic potential of growth and prevent unfavorable outcomes.http://ift.tt/2prHN2S
Behavioral interventions to improve asthma outcomes: a systematic review of recent publications
Purpose of review: Asthma outcomes are influenced by factors at multiple ecological levels: the individual and his/her family, home, medical care, and community. This systematic review describes recently published single-level and multilevel behavioral interventions to improve asthma outcomes. Recent findings: Of the 23 total title/abstracts reviewed in the original systematic search of PubMed, Ovid, Scopus, PsychINFO, and CIHAHL reference review databases, six met inclusion criteria. Five of the studies focused on low-income and/or minority populations. Promising interventions include culturally tailored online asthma self-management programs and family-centered asthma education delivered at the bedside during hospitalization for an acute asthma exacerbation. Summary: Culturally, tailored online self-management programs offer difficult-to-reach populations asthma support that can be completed at the time and pace most convenient for the individual user. Family-focused asthma education, delivered at the bedside during an acute asthma hospitalization by highly motivated lay volunteers, is an efficacious and low-cost approach to improving pediatric asthma self-management.http://ift.tt/2prDft0
Use of biologics in severe food allergies
Purpose of review: Severe cases of food allergy account for the majority of the burden in terms of risks, quality of life, and resource expenditure. The traditional approach to these forms has been strict avoidance. More recently, Oral ImmunoTherapy (OIT) has gained a role in their management. However, in severe food allergies OIT is often infeasible. Recent findings: Case reports, observational, and prospective studies have recently proposed different approaches to severe food allergy. The majority of them include the use of biologics. Omalizumab has been the most studied drug for severe food allergies, and its role as adjuvant treatment to OIT is well established. Interest has been raised on other biologics, as dupilumab, reslizumab, and mepolizumab. Toll-like receptor agonists, and gene therapy using adeno-associated virus coding for Omalizumab are promising alternatives. Summary: The recent studies are deeply influencing the clinical practice. We review the modifications of the clinical approach to severe food allergies so far available. We indicate the possible evolutions of treatment with biologics in severe food allergies.http://ift.tt/2prsI14
Apremilast for a psoriasis patient with HIV and hepatitis C
Abstract
A 46-year old male with HIV, hepatitis C, and moderate psoriasis was resistant to starting ultra violet B phototherapy due to scheduling issues. The patient had 8% body surface area (BSA) affected on the dorsal hands, elbows, and legs, did not have associated psoriatic arthritis, and had not tried any systemic therapy in the past. He was initiated on an apremilast starter pack (dosages titrated up from 10 mg to 30 mg over the course of one week) and maintained on 30 mg twice a day after one week.
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Adalimumab is a safe option for psoriasis patients with concomitant hepatitis B or C infection: a multicentre cohort study of 37 patients and review of the literature. Reply to Dr. Ricceri letter
Abstract
We thank Ricceri et al. for their comments (1) and interest in our study (2). Despite the recent advances in prevention and treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, these two chronic infections still represent the most common cause of chronic liver disease. Dermatologists are frequently encountering patients with psoriatic disease who have concomitant HBV or HCV infection in daily clinical practice.
Dr Ricceri provided in his letter further long-term follow-up data (60 months) on the use of etanercept or adalimumab in 17 psoriatic patients affected by past HBV infection or chronic HCV infection.
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Pediatric melanoma
Abstract
Pediatric melanoma, although rare, is the most common skin cancer in children. Our current knowledge on pediatric melanoma incidence trends is expanding, as several studies have addressed this issue with conflicting results. Known risk factors for pediatric melanoma include family history of melanoma, a previous history of malignancy, large congenital nevi, numerous melanocytic nevi, sunburns, increased UV exposure and a sun-sensitive phenotype. In younger children melanoma more often presents with atypical features, such as a changing, amelanotic or uniformly colored, often bleeding lesion, not fulfilling in most cases the conventional ABCDE criteria. The major differential diagnoses are melanocytic nevi, proliferative nodules in congenital nevi and atypical Spitz tumors. Moreover, in the younger age group non Caucasian children are over-represented, tumors tend to be thicker and lymph nodes are often involved. Despite the frequent diagnosis at an advanced stage, the overall survival is fair in pediatric melanoma. Specific guidelines for management of melanoma in children do not exist, and most often the disease is treated similarly to melanoma in adults.
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Reply: Adalimumab is a safe option for psoriasis patients with concomitant hepatitis B or C infection: a multicentre cohort study of 37 patients and review of the literature
Abstract
We have read with interest the article by Piaserico et al. concerning the use of tumour necrosis factor-alpha (TNF-alpha) blocking agent adalimumab in psoriatic patients with concomitant hepatitis B virus (HBV) or hepatitis C virus (HCV). The authors describe 17 psoriatic patients affected by chronic HBV infection and 20 affected by chronic HCV who were successfully treated with adalimumab with no evidence of HBV or HCV reactivation in a mean follow-up period of 27 and 40 months, respectively.
We have previously described our successful experience of treatment with anti-TNF-alpha therapy in 17 psoriatic patients (11 with past HBV infection, 5 with chronic HCV infection and one affected by both HBV and HCV) without the use of lamivudine or adenofovir, and can now report on long-term follow-up data (mean follow-up period of 60 months).
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Assessment of Sun-Protective Attitudes and Behaviours of Australian Medical Students
Abstract
Skin cancer is a major public health concern in Australia and around the world, and UV radiation exposure is accepted as the most readily modifiable risk factor for the disease1. The attitudes and behaviours of young adults towards sun protection play an important role in their future risk of skin cancer, and are thus an important target for sun-safety messaging.
A cross-sectional study aiming to investigate the sun-protective behaviours and attitudes of Australian medical students during both everyday outdoor activities and while travelling for leisure was conducted via an online questionnaire.
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Breast milk IgA to foods has different epitope-specificity than serum IgA – Evidence for entero-mammary link for food-specific IgA?
Abstract
Background
We have previously shown that maternal cow's milk (CM) elimination results in down-regulation of CM-specific IgA antibody levels in BM, but not in serum, suggesting that an entero-mammary link may exist for food-specific antibody-secreting cells.
Objective
We sought to investigate whether food-specific IgA epitope profiles differ intra-individually between mother's serum and BM. We also examined how infants' food epitope-specific IgA develops in early infancy and the relationship of IgA epitope recognition with development of cow's milk allergy (CMA).
Methods
We measured specific IgA to a series of overlapping peptides in major CM allergens (αs1-, αs2 -, β- and κ-caseins and β-lactoglobulin) in paired maternal and infant serum as well as BM samples in 31 mother-infant dyads within the first 15 postpartum months utilizing peptide microarray.
Results
There was significant discordance in epitope specificity between BM and maternal sera ranging from only 13% of sample pairs sharing at least one epitope in αs1-casein to 73% in κ-casein. Epitope-specific IgA was detectable in infants' sera starting at less than 3 months of age. Sera of mothers with a CMA infant had increased binding of epitope-specific IgA to CM proteins compared to those with a non-CMA infant.
Conclusion & Clinical Relevance
These findings support the concept that mother's milk has a distinct anti-food antibody repertoire when compared to the antibody repertoire of the peripheral blood. Increased binding of serum epitope-specific IgA to CM in mothers of infants with CMA may reflect inherited systemic immunogenicity of CM proteins in these families, although specific IgA in breast milk was not proportionally upregulated.
This article is protected by copyright. All rights reserved.
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A Retrospective Study to Evaluate the Effect of Concentration of Hypertonic Saline on Efficacy and Safety of Epidural Adhesiolysis.
BACKGROUND: Percutaneous epidural adhesiolysis (PEA) is a minimally invasive procedure that is performed to relieve low back and/or lower limb pain secondary to adhesions or scarring in the epidural space that is refractory to conservative treatment. The optimal concentration of hypertonic saline might be an important factor in the safety and efficacy of PEA. We evaluated differences in the efficacy and safety of 2 concentrations of hypertonic saline (5% and 10%) used in lumbar PEA at our institutions in a retrospective study. METHODS: Patients who received lumbar PEA between January 2009 and June 2014 at either of 2 large civilian teaching institutions in South Korea were assigned to the 5% or 10% groups according to the osmolality of saline. The primary outcome of this study was the difference in change in the 11-point numerical rating scale (NRS) scores of low back and leg pain from baseline to 6 months after PEA between patients in the 2 groups. The number of additional epidural injections, patients' satisfaction with PEA, and any complications that occurred within 6 months after PEA were reviewed. RESULTS: This study included 543 patients (5% group, 333; 10% group, 210). Post-PEA NRS pain scores were significantly lower compared with those at baseline in both groups; however, there were no significant differences between the 2 groups at 6 months or any time point after PEA with regard to any of the clinical characteristics, except infusion-related pain, which exhibited borderline significance for greater scores in the 10% group compared with those in the 5% group (P = .041). Multivariable linear regression analysis with adjustments for covariates, including the number of additional epidural injections, revealed no significant association between patient group and the decrease in NRS pain scores at 6 months of follow-up. Transient adverse events related to PEA were recorded in 3 patients (10% group, 2; 5% group, 1). CONCLUSIONS: In PEA, 5% hypertonic saline exhibited similar positive outcomes after 6 months of follow-up as 10% hypertonic saline, with less infusion-related pain. This result suggests that infusion of 5% hypertonic saline may be considered as an alternative to 10% hypertonic saline in lumbar PEA. Further prospective randomized studies are required to better appreciate the outcome with regard to the use of different concentrations of hypertonic saline for PEA. (C) 2017 International Anesthesia Research Society
http://ift.tt/2p8URJH
http://ift.tt/2p8URJH
Prophylactic Pentazocine Reduces the Incidence of Pruritus After Cesarean Delivery Under Spinal Anesthesia With Opioids: A Prospective Randomized Clinical Trial.
BACKGROUND: The incidence of pruritus after cesarean delivery under spinal anesthesia with opioids is high, ranging from 50% to 100%. Pruritus is difficult to prevent; however, pentazocine has been shown to be an effective treatment. Despite this, the prophylactic effect of pentazocine on pruritus has not been defined. This randomized double-blind trial aimed to evaluate the effect of intraoperative IV pentazocine on the incidence of opioid-induced pruritus within the first 24 hours after administration of neuraxial opioids. METHODS: We obtained institutional review board approval and written informed consent from the 122 patients (American Society of Anesthesiologists [ASA] physical status II; aged 20-40 years) scheduled for elective cesarean delivery who were included in this study. Spinal anesthesia was performed with 10 mg of 0.5% hyperbaric bupivacaine, 10 [mu]g of fentanyl, and 100 [mu]g of morphine. After delivery of the baby and placenta, the parturient women were randomized to intravenously receive 15 mg (1 mL) of pentazocine or 1 mL of saline. All women received postoperative analgesia with the epidural infusion of 0.15% levobupivacaine. The presence of pruritus within the first 24 hours after intrathecal administration of opioids was recorded, and severity of itch, numerical rating scale (NRS) for pain, and adverse effects were also recorded at the time of the arrival on the ward, as well as 3, 6, 12, and 24 hours after the intrathecal administration of opioids. RESULTS: A total of 119 women completed the study. IV pentazocine reduced the overall incidence of pruritus within the first 24 hours compared to IV saline, with an estimated relative risk of 69% (95% confidence interval [CI], 52%, 90%; P = .007). IV pentazocine also reduced the severity of pruritus. The incidence of nausea and vomiting was not significantly different. There were no significant differences in postoperative NRS scores. CONCLUSIONS: A single 15-mg dose of IV pentazocine after delivery can reduce both the incidence and severity of pruritus in women who have received subarachnoid opioids during cesarean delivery. (C) 2017 International Anesthesia Research Society
http://ift.tt/2pndYyt
http://ift.tt/2pndYyt
Intrathecal Morphine Versus Extended-Release Epidural Morphine for Postoperative Pain Control in Pediatric Patients Undergoing Posterior Spinal Fusion.
BACKGROUND: Posterior spinal fusion for scoliosis is one of the most painful elective pediatric surgeries. Good postoperative pain control allows early ambulation and return of ability to tolerate oral intake. Options for analgesia in this patient population are suboptimal. We hypothesized that extended-release epidural morphine (EREM) would provide better pain control and less adverse effects compared to intrathecal (IT) morphine. METHODS: The primary outcome was total IV morphine consumption during 0-48 hours postoperatively. Secondary outcomes included time until first patient-controlled analgesia (PCA) demand, pain scores, and adverse opioid effects. After institutional review board approval, 71 subjects undergoing posterior spinal fusion for idiopathic scoliosis completed the study. The subjects were randomly allocated to 7.5 [mu]g/kg IT morphine or 150 [mu]g/kg EREM. The final IT morphine and EREM groups contained 37 and 34 subjects, respectively. Postoperative pain was treated with morphine PCA, ketorolac, oral oxycodone, and acetaminophen. Morphine consumption, pain scores, nausea and vomiting, pruritus, and respiratory depression were measured every 4 hours. Parents completed a caregiver questionnaire about their child's pain control regimen after the first postoperative day. RESULTS: There was no difference in total morphine consumption over the first 48 hours between subjects in the EREM and IT morphine groups: median (range) 42.2 (5.5-123.0) and 34.0 (4.5-128.8) mg, respectively (P = .27). EREM and IT morphine groups had no difference in time until first PCA demand. Pain scores were no different between the groups from 8 to 24 hours after surgery. Compared to IT morphine, EREM subjects had lower pain scores from 28 to 36 hours after surgery. The reported incidence of pruritus was lower in the EREM subjects. CONCLUSIONS: There was no difference in total morphine consumption or time until first PCA demand between the EREM and IT morphine groups. EREM provides a longer duration of analgesia after posterior spinal fusion for scoliosis and may be associated with less opioid-induced pruritus. (C) 2017 International Anesthesia Research Society
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http://ift.tt/2pE62eZ
Quality Assessment of Meta-analyses Published in Leading Anesthesiology Journals From 2005 to 2014.
Meta-analysis, when preceded by a systematic review, is considered the "gold standard" in data aggregation; however, the quality of meta-analyses is often questionable, leading to uncertainty about the accuracy of results. In this study, we evaluate the quality of meta-analyses published in 5 leading anesthesiology journals from 2005 to 2014. A total of 220 meta-analyses published in Anesthesiology, Pain, British Journal of Anaesthesia, Anaesthesia, or Anesthesia & Analgesia were identified for inclusion. The quality of each meta-analysis was determined using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR). R-AMSTAR rated 11 questions related to systematic reviews and meta-analyses on a scale of 1-4, with 4 representing the highest quality. Overall meta-analyses quality was evaluated using a Spearmen regression analysis and found to positively correlate with time (rs = 0.24, P
http://ift.tt/2p8D997
http://ift.tt/2p8D997
Comparison of Postoperative Respiratory Monitoring by Acoustic and Transthoracic Impedance Technologies in Pediatric Patients at Risk of Respiratory Depression.
BACKGROUND: In children, postoperative respiratory rate (RR) monitoring by transthoracic impedance (TI), capnography, and manual counting has limitations. The rainbow acoustic monitor (RAM) measures continuous RR noninvasively by a different methodology. Our primary aim was to compare the degree of agreement and accuracy of RR measurements as determined by RAM and TI to that of manual counting. Secondary aims include tolerance and analysis of alarm events. METHODS: Sixty-two children (2-16 years old) were admitted after tonsillectomy or receiving postoperative patient/parental-controlled analgesia. RR was measured at regular intervals by RAM, TI, and manual count. Each TI or RAM alarm resulted in a clinical evaluation to categorize as a true or false alarm. To assess accuracy and degree of agreement of RR measured by RAM or TI compared with manual counting, a Bland-Altman analysis was utilized showing the average difference and the limits of agreement. Sensitivity and specificity of RR alarms by TI and RAM are presented. RESULTS: Fifty-eight posttonsillectomy children and 4 patient/parental-controlled analgesia users aged 6.5 +/- 3.4 years and weighting 35.3 +/- 22.7 kg (body mass index percentile 76.6 +/- 30.8) were included. The average monitoring time per patient was 15.9 +/- 4.8 hours. RAM was tolerated 87% of the total monitoring time. The manual RR count was significantly different from TI (P = .007) with an average difference +/- SD of 1.39 +/- 10.6 but were not significantly different from RAM (P = .81) with an average difference +/- SD of 0.17 +/- 6.8. The proportion of time when RR measurements differed by >=4 breaths was 22% by TI and was 11% by RAM. Overall, 276 alarms were detected (mean alarms/patient = 4.5). The mean number of alarms per patient were 1.58 +/- 2.49 and 2.87 +/- 4.32 for RAM and TI, respectively. The mean number of false alarms was 0.18 +/- 0.71 for RAM and 1.00 +/- 2.78 for TI. The RAM was found to have 46.6% sensitivity (95% confidence interval [CI], 0.29-0.64), 95.9% specificity (95% CI, 0.90-1.00), 88.9% positive predictive value (95% CI, 0.73-1.00), and 72.1% negative predictive value (95% CI, 0.61-0.84), whereas the TI monitor had 68.5% sensitivity (95% CI, 0.53-0.84), 72.0% specificity (95% CI, 0.60-0.84), 59.0% positive (95% CI, 0.44-0.74), and 79.5% negative predictive value (95% CI, 0.69-0.90). CONCLUSIONS: In children at risk of postoperative respiratory depression, RR assessment by RAM was not different to manual counting. RAM was well tolerated, had a lower incidence of false alarms, and had better specificity and positive predictive value than TI. Rigorous evaluation of the negative predictive value is essential to determine the role of postoperative respiratory monitoring with RAM. (C) 2017 International Anesthesia Research Society
http://ift.tt/2oNSLM2
http://ift.tt/2oNSLM2
Maxillofacial prosthodontics practice profile: a survey of non-United States prosthodontists
This study surveyed non-United States maxillofacial prosthodontists (MFP) to determine their practice profile and rationale for pursuing an MFP career.
http://ift.tt/2oQWBoo
Does medical school research productivity predict a resident’s research productivity during residency?
Research productivity is an important component of the CanMEDS Scholar role and is an accreditation requirement of Canadian Otolaryngology training programs. Our objective was to determine if an association ex...
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Nivolumab in Recurrent or Metastatic Salivary Gland Carcinoma of the Head and Neck
Conditions: Salivary Gland Carcinoma; Metastatic Cancer; Recurrent Cancer
Intervention: Drug: Nivolumab
Sponsor: UNICANCER
Recruiting - verified April 2017
http://ift.tt/2oBdDee
Intervention: Drug: Nivolumab
Sponsor: UNICANCER
Recruiting - verified April 2017
http://ift.tt/2oBdDee
A Study of Alectinib in RET-rearranged Non-small Cell Lung Cancer or RET-mutated Thyroid Cancer
Conditions: ALK-positive Non-small Cell Lung Cancer (NSCLC); RET-positive Non-small Cell Lung Cancer (NSCLC); RET-positive Thyroid Cancer
Intervention: Drug: Alectinib
Sponsors: Dana-Farber Cancer Institute; Genentech, Inc.
Not yet recruiting - verified April 2017
http://ift.tt/2oQA0Iv
Intervention: Drug: Alectinib
Sponsors: Dana-Farber Cancer Institute; Genentech, Inc.
Not yet recruiting - verified April 2017
http://ift.tt/2oQA0Iv
Public perception of dermatology and dermatologists in Italy: Results from a population-based national survey
Abstract
Introduction
The public perception of Dermatology and dermatologists may be very relevant in guiding strategies for improving dermatologic care but it has been poorly investigated in Europe.
Objective
To investigate the public's perception of Dermatology and dermatologists in Italy.
Methods
A representative sampling of Italian adults (n=1500, aged 18-70 years), residing throughout the national territory was interviewed through a population-based telephone survey using a structured questionnaire.
Results
The majority of interviewed aged between 35 and 54 years (45%) and had an intermediate educational level (57%), were employed (56%), and had at least one child in the family (68%). 70% of the interviewed knew at least one skin disease, particularly psoriasis, dermatitis, urticaria, skin tumors and nevi. The general practitioner resulted to be the first health care provider to consult in the case of skin problems for 73% of surveyed, with only 27% referring directly the private dermatologist. The dermatologist was the main referral specialist for psoriasis, pruritus and skin tumors by 66%, 54% and 53% of the sample, respectively. The most common reason for dermatological consultation was the control of nevi. In the case of childhood dermatitis, 52% indicated the paediatrician and 38% the dermatologist as the reference specialist. Almost half of the surveyed turned out to have a trusted dermatologist to consult in the case of skin problems. Finally, among those visited at least one time by a dermatologist, 46% were promoters, i.e. they would recommend their dermatologist to a friend (net promoter score, 27).
Conclusions
The general population has a wide-ranging understanding of skin diseases and the central role of dermatologists in skin care. Patients are looking for technical competence and loyalty, because this lead to more trusted and satisfactory physician-patient relationship. Public campaigns may be relevant in increasing awareness on curability of common skin diseases.
This article is protected by copyright. All rights reserved.
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Topical Antiviral and Antifungal Medications in Pregnancy: A Review of Safety Profiles
Abstract
Medications should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Compared to oral or parenteral agents, topical medications have limited systemic absorption and are deemed safer. However, their safety profile must be assessed cautiously due to the limited available data. In this article, we aggregate human and animal studies to provide recommendations on utilizing topical antiviral and antifungal medications in pregnancy. For antiviral medications, acyclovir and trichloroacetic acid are safe to use in pregnancy. Docosanol, imiquimod, and penciclovir are likely safe, but should be utilized as second-line agents. Podofilox and podophyllin resin should be avoided. For antifungal medications, clotrimazole, miconazole and nystatin are considered first line agents. Butenafine, ciclopirox, naftifine, oxiconazole, and terbinafine may be utilized after the above agents. Econazole should be avoided during the first trimester and used sparingly during 2nd and 3rd trimester. Ketoconazole and selenium sulfide are likely safe, but should be employed in limited areas for brief periods.
This article is protected by copyright. All rights reserved.
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Consensus statement on prevention and management of adverse effects following rejuvenation procedures with Hyaluronic acid based fillers
Abstract
Facial fillers play an important role in the correction of facial changes associated with ageing. They offer quick treatments in the outpatient setting with minimal subsequent downtime that provide predictable, natural-looking, long-lasting results. Hyaluronic acid soft tissue injectables have established their role as the fillers of choice for patients over the last 2 decades. Hyaluronic acid fillers are rarely associated with adverse reactions, and those that do occur tend to be mild and temporary. However, as with all injected or implanted biomaterials, adverse events can occur and patients must be fully informed of potential risks prior to undergoing treatment. A panel of experts from Germany (D), Austria (A) and Switzerland (CH) developed recommendations and this paper provides the 'DACH Consensus Recommendations' from this group specifically on the use of hyaluronic acid fillers. The aim is to help clinicians recognise potential risks and to provide guidance on how best to treat adverse events if they arise. Contra-indications to hyaluronic acid fillers are also detailed and ways to prevent adverse events occurring are discussed. Hyaluronic acid-based products are claimed by some to be very close to fulfilling many of the requirements of an ideal tissue augmentation agent, nevertheless, the potential benefits of treatment must be carefully weighed against the risk of potential adverse events.
This article is protected by copyright. All rights reserved.
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HPV16 E7 DNA tattooing: safety, immunogenicity, and clinical response in patients with HPV-positive vulvar intraepithelial neoplasia
Abstract
Background
Usual type vulvar intraepithelial neoplasia (uVIN) is caused by HPV, predominantly type 16. Several forms of HPV immunotherapy have been studied, however, clinical results could be improved. A novel intradermal administration route, termed DNA tattooing, is superior in animal models, and was tested for the first time in humans with a HPV16 E7 DNA vaccine (TTFC-E7SH).
Methods
The trial was designed to test safety, immunogenicity, and clinical response of TTFC-E7SH in twelve HPV16+ uVIN patients. Patients received six vaccinations via DNA tattooing. The first six patients received 0.2 mg TTFC-E7SH and the next six 2 mg TTFC-E7SH. Vaccine-specific T-cell immunity was evaluated by IFNγ-ELISPOT and multiparametric flow cytometry.
Results
Only grade I-II adverse events were observed upon TTFC-E7SH vaccination. The ELISPOT analysis showed in 4/12 patients a response to the peptide pool containing shuffled E7 peptides. Multiparametric flow cytometry showed low CD4+ and/or CD8+ T-cell responses as measured by increased expression of PD-1 (4/12 in both), CTLA-4 (2/12 and 3/12), CD107a (5/12 and 4/12), or the production of IFNγ (2/12 and 1/12), IL-2 (3/12 and 4/12), TNFα (2/12 and 1/12), and MIP1β (3/12 and 6/12). At 3 months follow-up, no clinical response was observed in any of the twelve vaccinated patients.
Conclusion
DNA tattoo vaccination was shown to be safe. A low vaccine-induced immune response and no clinical response were observed in uVIN patients after TTFC-E7SH DNA tattoo vaccination. Therefore, a new phase I/II trial with an improved DNA vaccine format is currently in development for patients with uVIN.
http://ift.tt/2qbWnw1
KRAS mutation-induced upregulation of PD-L1 mediates immune escape in human lung adenocarcinoma
Abstract
It was reported that PD-L1 expression was correlated with genetic alterations. Whether PD-L1 was regulated by mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) in non-small-cell lung cancer (NSCLC) and the underlying molecular mechanism were largely unknown. In this study, we investigated the correlation between PD-L1 expression and KRAS mutation and the functional significance of PD-1/PD-L1 blockade in KRAS-mutant lung adenocarcinoma. We found that PD-L1 expression was associated with KRAS mutation both in the human lung adenocarcinoma cell lines and tissues. PD-L1 was up-regulated by KRAS mutation through p-ERK but not p-AKT signaling. We also found that KRAS-mediated up-regulation of PD-L1 induced the apoptosis of CD3-positive T cells which was reversed by anti-PD-1 antibody (Pembrolizumab) or ERK inhibitor. PD-1 blocker or ERK inhibitor could recover the anti-tumor immunity of T cells and decrease the survival rates of KRAS-mutant NSCLC cells in co-culture system in vitro. However, Pembrolizumab combined with ERK inhibitor did not show synergistic effect on killing tumor cells in co-culture system. Our study demonstrated that KRAS mutation could induce PD-L1 expression through p-ERK signaling in lung adenocarcinoma. Blockade of PD-1/PD-L1 pathway may be a promising therapeutic strategy for human KRAS-mutant lung adenocarcinoma.
http://ift.tt/2oNkMmI
Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy
Abstract
Tumor-associated fibrosis is characterized by unchecked pro-fibrotic and pro-inflammatory signaling. The components of fibrosis including significant numbers of cancer-associated fibroblasts, dense collagen deposition, and extracellular matrix stiffness, are well appreciated regulators of tumor progression but may also be critical regulators of immune surveillance. While this suggests that the efficacy of immunotherapy may be limited in highly fibrotic cancers like pancreas, it also suggests a therapeutic opportunity to target fibrosis in these tumor types to reawaken anti-tumor immunity. This review discusses the mechanisms by which fibrosis might subvert tumor immunity and how to overcome these mechanisms.
http://ift.tt/2oPSuZQ
Cover Image
The cover image, by C. B. Mathias et al., is based on the Original Article IL-15-deficient mice develop enhanced allergic responses to airway allergen exposure, DOI 10.1111/cea.12886
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Dermoscopy use by Canadian dermatologists and dermatology residents: a cross sectional nationwide study
Abstract
Dermoscopy has demonstrated clinical benefits in improving early melanoma diagnosis and reducing unnecessary biopsies. Despite this, the prevalence of dermoscopy use by dermatologists varies from 81% to 98% worldwide, with a lack of training being a commonly cited reason for non-use of dermoscopy. To date there are no studies examining the prevalence of dermoscopy use in Canada. Our study aimed to examine the use and learning of dermoscopy by Canadian dermatologists and dermatology residents, as well as the current state of dermoscopy teaching within Canadian dermatology residency programs.
This article is protected by copyright. All rights reserved.
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Frailty index: Intensive care unit complications in head and neck oncologic regional and free flap reconstruction
Abstract
Background
Head and neck extirpations requiring reconstruction are challenging surgeries with high postoperative complication risk.
Methods
Regional and free flap reconstructions of head and neck defects were collected from the 2006-2013 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. The modified frailty index was made of 15 variables, with increasing index scores indicative of frailer patients. Intensive care unit (ICU)-level complications were defined by Clavien-Dindo classification IV and analyzed with multivariable logistic regression.
Results
There were 266 flap reconstructions (126 regional and 140 free) with 86 (7.2%) Clavien-Dindo classification IV complications. As modified frailty index increased, a moderate correlation was demonstrated for Clavien-Dindo classification IV complications (R2 = 0.30). Increasing modified frailty index score was correlated on linear regression with free versus regional flaps: Clavien-Dindo classification IV (R2 = 0.09; 0.60), morbidity (R2 = 0.04; 0.59), and mortality (R2 = 0.07; 0.46), respectively. On multivariable analysis, the modified frailty index was associated with Clavien-Dindo classification IV complications for all flaps (odds ratio [OR] 4.38; 95% confidence interval [CI] 1.33-14.48) and free flaps (OR 6.60; 95%CI 1.02-42.52), but not regional flaps (OR 9.05; 95%CI 0.60-137.10).
Conclusion
The modified frailty index score is predictive of critical care support in head and neck resections necessitating reconstruction, specifically for free flaps.
http://ift.tt/2pmD5B8
Impact of metformin on patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy
Abstract
Background
The purpose of this study was to evaluate the impact of metformin on toxicities and survival in patients with head and neck cancer undergoing concurrent chemoradiotherapy (CRT).
Methods
We retrospectively analyzed and compared the clinical characteristics, treatment tolerance, toxicities, and survival of 252 patients with stages III, IVA, and IVB head and neck cancer undergoing concurrent CRT with and without metformin treatment between 2007 and 2010.
Results
Among all patients, 39 patients received metformin whereas 219 patients did not. Both groups had similar clinical characteristics and nearly identical disease-free survival and overall survival. However, the metformin group was less likely to tolerate cisplatin, experienced more weight loss, had a tendency to receive lower doses of radiotherapy, required more feeding tube support, and had grade ≥3 nausea/vomiting and hematological toxicities.
Conclusion
Patients with head and neck cancer undergoing concurrent CRT along with metformin treatment require more careful multidisciplinary assessment and supportive care to ensure successful completion of treatment and avoid treatment-related toxicities.
http://ift.tt/2pDN9Ji
Increased risk of paclitaxel-induced peripheral neuropathy in patients using clopidogrel: a retrospective pilot study
Abstract
Paclitaxel-induced peripheral neuropathy (PIPN) is one of the serious adverse events associated with paclitaxel-based cancer treatments. A recent case study showed that the antiplatelet agent clopidogrel inhibits paclitaxel metabolism via cytochrome P450 (CYP) 2C8, resulting in severe PIPN. The aim of this study was to determine the impact of clopidogrel as a risk factor for the development of PIPN, using a retrospective cohort study. Data from paclitaxel-treated patients with or without clopidogrel and low-dose aspirin treatment were retrieved from medical charts. A total of 161 adult patients were included in this study: 135 were controls, 9 were clopidogrel-treated and 17 were aspirin-treated. The clopidogrel group had a greater proportion of males and a higher rate of comorbidities, such as diabetes mellitus and dyslipidemia, than the control group. However, patient characteristics were similar between the clopidogrel and aspirin groups. Severe PIPN was diagnosed in 3 (2.2%) and 2 (22.2%) patients in the control and clopidogrel groups, respectively (odds ratio: 12.0; p = 0.031). No patients in the aspirin group presented with severe neuropathy. These pilot data suggest that concomitant treatment with clopidogrel leads to a greater risk of PIPN. The avoidance of concomitant clopidogrel use may be effective in reducing clopidogrel-associated PIPN.
http://ift.tt/2pDBLwO
Middle meatal packing in endoscopic sinus surgery—to pack or not to pack?—a decision-analysis model
Background
Packing of the middle meatus and ethmoid cavities is a common practice in endoscopic sinus surgery (ESS), but its necessity recently has been challenged. The aim of this study was to formulate a decision-analysis model to determine the need for packing in ESS and identify variables affecting the decision.
Methods
A systematic review of the literature was conducted for all randomized control trials comparing packing to no packing in ESS, and a decision-analysis model was generated. Probabilities and utilities were derived from the literature. Sensitivity analysis was used to determine which variables most affected the model.
Results
No packing was associated with better expected utilities than packing. On sensitivity analysis, packing was preferred when the disutility of no packing outweighed the disutility of packing, and when the probability for synechiae was greater than 35% without packing or lower than 2% with packing. When the component of packing removal was subtracted from the overall disutility simulating absorbable packing, the results favored packing.
Conclusion
Our decision-analysis model indicates that middle meatal packing is not advantageous for patients undergoing ESS. Absorbable packing materials have a less adverse effect on quality of life than nonabsorbable materials.
Level of Evidence
1a. Laryngoscope, 2016
http://ift.tt/2oARqgh
Sarcopenia and Wound Complication After Total Laryngectomy
This study examines the incidence of sarcopenia in patients with squamous cell carcinoma undergoing total laryngectomy.
http://ift.tt/2p89H3c
http://ift.tt/2p89H3c
With Experience Comes Wisdom
What a pleasure it is to be able to comment on the Viewpoint by Grundfast et al, "The 10 Commandments of Management for Acute Upper Airway Obstruction in Infants and Children." Having just finished Michael Lewis's book The Undoing Project, which tells the story of Daniel Kahneman, Amos Tversky, and the birth of a new form of behavioral psychology and decision analysis, I am, of course, concerned about the inherent biases in trusting at face value the words of a senior statesman just because he looks and acts the part. Do we hold with heuristic beliefs that with an author's age and experience comes wisdom? I am now "trained" not to ask "who the author is" but "what has he or she actually done" before I trust the narrator that speaks to me.
http://ift.tt/2oNp4KR
http://ift.tt/2oNp4KR
Frontal Sinus Lesion
A woman with allergic rhinitis experienced progressive periorbital edema and proptosis of the left eye, with nasal congestion, altered sense of smell, supraorbital pain, proptosis, and periorbital edema; a CT scan revealed extensive thickening of the left frontal bone. What is your diagnosis?
http://ift.tt/2p85NY9
http://ift.tt/2p85NY9
Exclusion of Eligible Indeterminate Thyroid Nodules in Estimates of Negative Predictive Value for the Gene Expression Classifier
To the Editor Al-Qurayshi et al calculated the negative predictive value (NPV) of the Gene Expression Classifier (GEC) in 154 indeterminate thyroid nodules (ITNs). We reviewed 12 articles that evaluated the diagnostic accuracy of the GEC. In those studies, as with that of Al-Quyrashi et al, estimates for test performance were unreliable, owing to serious methodologic flaws in the authors' approach. The most impactful of these flaws was the exclusion of unexcised GEC-benign ITNs from the analysis, resulting in the calculation of NPV on a nonrepresentative sample GEC-benign ITNs selected for excision. A better method would have been to include GEC-benign ITNs that do not develop ultrasound findings suspicious for malignant neoplasm as true-negative results in the calculation of NPV (Table). We can assume the 22 unexcised GEC-benigns did not have suspicious findings on ultrasound, given that the authors imply that GEC-benign ITNs that "…developed indications for surgery…" underwent excision. Using previously published estimates of the diagnostic accuracy of the TIRADS in ultrasound reporting, we can estimate that about 3 (15%) unexcised 22 GEC-benign ITNs may have also been malignant. Therefore, the observed NPV of the GEC in this study can be estimated to be 44 of 58 (76%).
http://ift.tt/2oNjAjq
http://ift.tt/2oNjAjq
Survival After Salvage Surgery for Recurrent Oral Cavity Cancer
This cohort study evaluates overall survival in patients who undergo salvage surgery for recurrent oral cavity squamous cell cancer.
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http://ift.tt/2oNl1y8
Exclusion of Eligible Indeterminate Thyroid Nodules in Estimates of Negative Predictive Value for the Gene Expression Classifier
In Reply We appreciate all scientific efforts to improve care for patients with indeterminate nodules. The Afirma assay has been an excellent addition to this endeavor, and our study helpful in understanding test characteristics in a unique patient population.
http://ift.tt/2p8bOUD
http://ift.tt/2p8bOUD
The 10 Commandments of Management for Acute Upper Airway Obstruction
This Viewpoint recommends 10 commandments or rules to follow when managing an acute upper airway obstruction in an infant or child.
http://ift.tt/2oNl116
http://ift.tt/2oNl116
Evaluation of Ecological Momentary Assessment for Tinnitus Severity
This observational study uses an ecological momentary assessment to measure tinnitus disability and associated constructs.
http://ift.tt/2p8tfob
http://ift.tt/2p8tfob
Clinical Outcomes Among Patients Who Contract to Abstain From Alcohol
This case-control study evaluates the association of alcohol abstinence with postoperative outcome in alcohol misusers undergoing major surgical procedures of the head and neck by using an alcohol abstinence contract.
http://ift.tt/2oNl78Y
http://ift.tt/2oNl78Y
Morbus Still im Kindes- und Erwachsenenalter
Zusammenfassung
Die systemische juvenile idiopathische Arthritis (sJIA) ist durch Fieber, Arthritis und weitere Symptome systemischer Inflammation gekennzeichnet. Historisch ist sie nach ihrem Erstbeschreiber George Frederic Still als Morbus Still benannt. Tritt die Erkrankung bei Erwachsenen auf, wird sie als adulte Still-Erkrankung („adult onset Still's disease", AOSD) bezeichnet. Die Pathophysiologie der sJIA und der AOSD wird inkomplett verstanden. Die gesteigerte Aktivierung von Inflammasomen und die Expression proinflammatorischer Zytokine spielen eine zentrale Rolle. S100-Proteine, die durch die Aktivierung von Toll-like-Rezeptoren als positiver Verstärker wirken, sind ebenso erhöht im Serum von sJIA-Patienten messbar. Reduzierte Produktion des immunmodulatorischen Zytokins IL-10 könnte zudem zur Aktivierung von Immunzellen und der Produktion inflammatorischer Botenstoffe beitragen. In diesem Beitrag werden die klinische Präsentation, die Differenzialdiagnostik, der aktuelle Wissensstand zur Pathophysiologie sowie Therapieoptionen der sJIA und der AOSD diskutiert.
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Interventionelle Radiologie im Kopf-Hals-Bereich
Zusammenfassung
Gefäßverschließende Maßnahmen neuroradiologischer Interventionen sind ein wichtiges und hilfreiches Werkzeug in der Behandlung verschiedener Erkrankungen im Kopf-Hals-Bereich. Diese interventionellen Maßnahmen erfolgen einerseits in kurativer Intention, zur Reduktion des Operationsrisikos im Rahmen eines multimodalen Therapiekonzepts oder auch zur Verbesserung oder zumindest zum Erhalt einer guten Lebensqualität. Essenziell für die erfolgreiche Behandlung ist neben dem Verständnis der Erkrankung das Wissen um die Gefäßanatomie sog. gefährlicher Anastomosen zwischen extra- und intrakraniellen Gefäßen und der Einsatz geeigneter Techniken und Materialien. Indikationen für einen transarteriellen Gefäßverschluss sind einerseits unkontrollierbare Blutungen unterschiedlicher Genese (traumatisch, vaskuläre Malformation, Tumor), andererseits die Reduktion des intraoperativen Blutverlusts bei hypervaskularisierten Tumoren durch eine präoperative Embolisationsbehandlungen und drittens die Induktion einer Tumornekrose zur regionalen Tumorkontrolle im Rahmen palliativer Embolisationen. Gravierende Komplikationen wie z. B. Schlaganfall, Erblindung und Hirnnervenlähmungen sind nicht selten auf eine unzureichende präinterventionelle Evaluation zurückzuführen. Bei Interventionen im Versorgungsgebiet der A. carotis externa liegt die Komplikationsrate für schwere neurologische Defizite unter 1 %.
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PET-CT bei Karzinomen im Kopf‑Hals‑Bereich
Zusammenfassung
Die 18F-Fluordeoxyglukose-Positronenemissionstomographie (FDG-PET) gewinnt zunehmenden Stellenwert in der Diagnostik onkologischer Erkrankungen, was zum einen auf der hohen Sensitivität der Methode und zum anderen auf der Möglichkeit einer Ganzkörperuntersuchung beruht. Insbesondere bei der Diagnostik von Kopf-Hals-Karzinomen können sich hierdurch Vorteile ergeben, da ein präzises Primärstaging entscheidender Prognoseparameter ist, woraus letzten Endes das Therapieregime für den Patienten resultiert. Die vorliegende Arbeit stellt die verschiedenen Einsatzmöglichkeiten der Untersuchung mittels Kombination aus PET und Computertomographie (CT) im Rahmen der Diagnostik von Kopf-Hals-Karzinomen dar. Besonderes Augenmerk wird hierbei auf das Primärstaging und die Tumornachsorge gelegt sowie den Stellenwert bei der Diagnostik des CUP-Syndroms („cancer of unknown primary origin"); auch der Einsatz bei der Strahlentherapieplanung sowie neue Aspekte in der PET-Technologie werden beschrieben.
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Indications and extent of central neck dissection for papillary thyroid cancer: An American Head and Neck Society Consensus Statement
ABSTRACT
Background
The primary purposes of this interdisciplinary consensus statement were to review the relevant indications for central neck dissection (CND) in patients with papillary thyroid cancer (PTC) and to outline the appropriate extent and relevant techniques required to accomplish a safe and effective CND.
Methods
A writing group convened by the American Head and Neck Society (AHNS) Endocrine Committee was tasked with identifying the important clinical elements to consider when managing the central neck compartment in patients with PTC based on available evidence in the literature, and the group's collective experience. The position statement paper was then submitted to the full Endocrine Committee, Education Committee, and AHNS Council.
Results
This consensus statement was developed to inform the clinical decision-making process when managing the central neck compartment in patients with PTC from the AHNS. This document is intended to provide clarity through definitions as well as a basic guideline from which to manage the central neck. It is our hope that this improves the quality and reduces variation in management of the central neck, facilitates communication, and furthers research for patients with thyroid cancer.
Conclusion
This represents, in our opinion, contemporary optimal surgical care for this patient population and is endorsed by the American Head and Neck Society. © 2017 Wiley Periodicals, Inc. Head Neck, 2017
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Xiaoqin Wang Receives $12 Million Award to Lead Research on Speedier Learning
Xiaoqin Wang, Ph.D., a professor of biomedical engineering, neuroscience and otolaryngology–head and neck surgery, and director of the Laboratory of Auditory Neurophysiology at The Johns Hopkins University, has won a $12 million award from the Defense Advanced Research Projects Agency (DARPA) for work with a multi-university team that will focus on targeted neuroplasticity training.
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Media Advisory: Dedication Ceremony for John G. Bartlett Specialty Practice, a New Facility Bringing Together Services for Patients with Infectious Diseases
A dedication ceremony and ribbon cutting with Johns Hopkins leadership and an open house of the new John G. Bartlett Specialty Practice at The Johns Hopkins Hospital.
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Position of the verb in simultaneous interpreting: a corpus-based comparative study
In Dutch and German subordinate clauses, the verb is generally placed after the clausal constituents (Subject-Object-Verb structure) and creates a middle field with the subordinate conjunction (also called verbal brace). This field makes interpreting from SOV into SVO languages particularly challenging as it increases the processing and memory effort and often requires the interpreter to use specific strategies (e.g. anticipation) (Lederer, 1981; Van Besien 1999; Setton, 1999; Liontou, 2016). However few studies have tackled the issue from the point of view of interpreters working into SOV languages. Producing SOV structures requires some specific cognitive effort as, for instance, subject properties need to be stored in memory in order to ensure correct subject-verb agreement across a span of 10 or 20 words. Speakers therefore often opt for a strategy called extraposition placing specific elements after the verb in order to shorten the brace (Bevilacqua, 2009; Hawkins, 1994). Dutch speakers are claimed to do so to a larger extent than German speakers (Haeseryn, 1990). Given the additional cognitive load generated by the interpreting process (Gile, 1999), it may be assumed that interpreters will shorten the verbal brace to a larger extent than speakers. The present study is based on a corpus of original speeches and interpretations at the European Parliament and compares middle field lengths in Dutch and German interpreted and non-interpreted varieties. Preliminary results from sets of 1273 German and 1826 Dutch subordinates confirm that interpreters shorten the middle field more than speakers and that Dutch interpreters shorten the middle field more frequently than German interpreters.
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Sex Differences in Simultaneous Interpreting: a Corpus-Based Study
Sex differences in memory tasks have been widely documented. Previous research has shown that women perform better than men in verbal and nonverbal memory tasks (Kimura and Seal, 2003, Loonstra et al., 2001). These differences are observed on subjects aged 5 to 85 (Kramer et al.,1997, Maitland, 2004). As memory plays a key role in simultaneous interpreting (Darò and Fabbro, 1994 inter alia), the question arises whether the differences are also observable in simultaneous interpreting. Drawing on data from consecutive interpreting, Mason (2008) suggests that the higher number of omissions in men's interpretations is due to memory limitations. Defrancq (2013) observed a longer EVS in female interpreters than in male interpreters. The present study investigates potential sex differences in several indicators of working memory capacity in simultaneous interpreting: EVS length, midfield and afterfield length in German and Dutch subordinate clauses, rendition of numbers and lists of items and production of hesitations and disfluencies. Assuming interpreters make full use of their cognitive capacities (Gile's tight-rope hypothesis, 1995), women are expected to have a longer EVS, to place fewer items in the afterfield, to render more numbers and items and to produce fewer hesitations than men. This study builds on Defrancq (2013), but is carried out with a significantly improved dataset, both in terms of accuracy and metadata. Results are drawn from an annotated and time-aligned sub-corpus of the European Parliament Interpreting Corpus Ghent and currently consists of 150 interpretations from and into English, French, Dutch and German. The first study on EVS confirms Defrancq's (2013) findings: female interpreters on average have a longer EVS and the difference with male interpreters is statistically significant. The influence of possible distorting factors, such as language, delivery rate and interpreter's fatigue is insignificant. Similar studies will be carried out to test the remaining hypotheses. References Darò, V. & Fabbro, F. (1994). Verbal memory during simultaneous interpretation: Effects of phonological interference. Applied Linguistics 15. Defrancq, B. (2013). "Women and men interpreting" Paper read at "Talking to the World" Conference, Newcastle, September 2013. Gile D. (1999), Testing the Efforts Models' tightrope hypothesis in simultaneous interpreting', Hermes 23. Kimura, D., and Seal, B. (2003). Sex differences in recall of real or nonsense words. Pychological Reports, 93, pp. 263-264. Kramer, J., Delis, D., & Daniel, M. (1988). Sex differences in verbal learning. Journal of Clinical Psychology, 44, pp. 907-915. Loonstra, A., A. Tarlow & A. Sellers (2001). COWAT metanorms across age, education and gender. Applied neuropsychology, 8(3), pp 161-166 Maitland, S.B., Herlitz A., Nynberg L., Nilsson L-G. (2004). Selective sex differences in declarative memory. Memory & Cognition, 2004, 32(7), pp. 1160-1169 Mason, M. (2008). Courtroom interpreting. Maryland: UPA
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New microbleed after blood-brain barrier leakage in intracerebral haemorrhage
Cerebral microbleeds are increasingly recognised as biomarkers of small vessel disease. Several preclinical and clinical studies have suggested that chronic disruption of the blood–brain barrier is one of the mechanisms for the development of cerebral microbleeds.
A 51-year-old man experienced two left parieto-occipital lobar intracerebral haemorrhages (ICHs) in the timespan of 2 years. Multiple microbleeds surrounding the two haemorrhages were found on MRI, but not at location distant from the haemorrhages. Ten months after the last haemorrhage, an MRI demonstrated a right occipital focus of contrast enhancement. Twenty months after the last ICH, a new cerebral microbleed had developed exactly at the location of the earlier contrast enhancement.
This case demonstrates that blood–brain barrier disruption may be an important factor preceding the development of cerebral microbleeds.
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Leiomyosarcoma: a rare but fatal tumour of the inferior vena cava
Description
Leiomyosarcomas (LMS) of the inferior vena cava (IVC) are a rare entity. Signs and symptoms vary greatly, such as abdominal pain, weight loss/gain, fever, weakness, anorexia or vomiting. CT scan is the imaging modality of choice for evaluation of retroperitoneal LMS, but biopsy is necessary to establish the diagnosis.
A 62-year-old woman presented with intermittent, diffuse, dull and sharp abdominal pain radiating to the lower back, associated with nausea, bloating and constipation. She also had a 15-pound weight gain in 6 months. Prior work-up did not reveal any acute abnormalities and she received treatment for constipation.
Due to persistent symptoms, CT of the abdomen and pelvis was ordered and demonstrated heterogeneously enhancing mass of the IVC extending into the right atrium (figure 1A,B). CT of the chest was done and confirmed the extension of the tumour to the right atrium (figure 1C,D). Figure...
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PK/PD Modelling of the QT Interval: a Step Towards Defining the Translational Relationship Between In Vitro, Awake Beagle Dogs, and Humans
Inhibiting the human ether-a-go-go-related gene (hERG)-encoded potassium ion channel is positively correlated with QT-interval prolongation in vivo, which is considered a risk factor for the occurrence of Torsades de Pointes (TdP). A pharmacokinetic/pharmacodynamic model was developed for four compounds that reached the clinic, to relate drug-induced QT-interval change in awake dogs and humans and to derive a translational scaling factor a (1). Overall, dogs were more sensitive than humans to QT-interval change, an a (1) of 1.5 was found, and a 10% current inhibition in vitro produced a higher percent QT-interval change in dogs as compared to humans. The QT-interval changes in dogs were predictive for humans. In vitro and in vivo information could reliably describe the effects in humans. Robust translational knowledge is likely to reduce the need for expensive thorough QT studies; therefore, expanding this work to more compounds is recommended.
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Hydrofluorination of alkynes catalysed by gold bifluorides
We report the synthesis of nine new N-heterocyclic carbene gold bifluoride complexes starting from the corresponding N-heterocyclic carbene gold hydroxides. A new methodology to access N,N'-bis(2,6-diisopropylphenyl)imidazol-2-ylidene gold(I) fluoride starting from N, N'-bis(2,6-diisopropylphenyl)imidazol-2-ylidene gold(I) hydroxide and readily available potassium bifluoride is also reported. These gold bifluorides were shown to be efficient catalysts in the hydrofluorination of symmetrical and unsymmetrical alkynes, thus affording fluorinated stilbene analogues and fluorovinyl thioethers in good to excellent yields with high stereo-and regioselectivity. The method is exploited further to access a fluorinated combretastatin analogue selectively in two steps starting from commercially available reagents.
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Exercise and Vitamin D Better Together for Heart Health
Johns Hopkins researchers report that an analysis of survey responses and health records of more than 10,000 American adults for nearly 20 years suggests a "synergistic" link between exercise and good vitamin D levels in reducing the risk of heart attacks and strokes.
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Temporoparietal encoding of space and time during vestibular-guided orientation.
Kaski, D; Quadir, S; Nigmatullina, Y; Malhotra, PA; Bronstein, AM; Seemungal, BM; (2016) Temporoparietal encoding of space and time during vestibular-guided orientation. Brain , 139 (2) pp. 392-403. 10.1093/brain/awv370 . Green open access
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Myopic Selection
Geroski, PA; Mazzucato, M; (2002) Myopic Selection. Metroeconomica , 53 (2) pp. 181-199. 10.1111/1467-999X.00139 . Green open access
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Patients with Vestibular Loss, Tullio Phenomenon, and Pressure-induced Nystagmus: Vestibular Atelectasis?
Kaski, D; Bronstein, AM; (2016) Patients with Vestibular Loss, Tullio Phenomenon, and Pressure-induced Nystagmus: Vestibular Atelectasis? Otol Neurotol , 37 (1) pp. 115-116. 10.1097/MAO.0000000000000679 .
http://ift.tt/2qc16hn
Modelling the dynamics of industry populations
Geroski, PA; Mazzucato, M; (2001) Modelling the dynamics of industry populations. International Journal of Industrial Organization , 19 (7) pp. 1003-1022. 10.1016/S0167-7187(01)00060-1 . Green open access
http://ift.tt/2oPIrUB
(68)Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0.
Fendler, WP; Eiber, M; Beheshti, M; Bomanji, J; Ceci, F; Cho, S; Giesel, F; Fendler, WP; Eiber, M; Beheshti, M; Bomanji, J; Ceci, F; Cho, S; Giesel, F; Haberkorn, U; Hope, TA; Kopka, K; Krause, BJ; Mottaghy, FM; Schöder, H; Sunderland, J; Wan, S; Wester, H-J; Fanti, S; Herrmann, K; - view fewer (2017) (68)Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging , 44 (6) pp. 1014-1024. 10.1007/s00259-017-3670-z .
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A computational model of economies of scale and market share instability
Mazzucato, M; (1998) A computational model of economies of scale and market share instability. Structural Change and Economic Dynamics , 9 (1) pp. 55-83. 10.1016/S0954-349X(97)00037-4 . Green open access
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Decompression sickness ('the bends') in sea turtles
Garcia-Parraga, D; Crespo-Picazo, JL; Bernaldo de Quiros, Y; Cervera, V; Marti-Bonmati, L; Diaz-Delgado, J; Arbelo, M; Garcia-Parraga, D; Crespo-Picazo, JL; Bernaldo de Quiros, Y; Cervera, V; Marti-Bonmati, L; Diaz-Delgado, J; Arbelo, M; Moore, MJ; Jepson, PD; Fernandez, A; - view fewer (2014) Decompression sickness ('the bends') in sea turtles. Diseases of Aquatic Organisms , 111 (3) pp. 191-205. 10.3354/dao02790 . Green open access
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Why School Choice Reforms in Denmark Fail: The Blocking Power of the Teacher Unions
Wiborg, S; Larsen, KR; (2017) Why School Choice Reforms in Denmark Fail: The Blocking Power of the Teacher Unions. European Journal of Education. Research, Development and Policy , 52 (1) pp. 92-103. 10.1111/ejed.12203 .
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The Physics of the B Factories
Bevan, AJ; Golob, B; Mannel, T; Prell, S; Yabsley, BD; Abe, K; Aihara, H; Bevan, AJ; Golob, B; Mannel, T; Prell, S; Yabsley, BD; Abe, K; Aihara, H; Anulli, F; Arnaud, N; Aushev, T; Beneke, M; Beringer, J; Bianchi, F; Bigi, II; Bona, M; Brambilla, N; Brodzicka, J; Chang, P; Charles, MJ; Cheng, CH; Cheng, H-Y; Chistov, R; Colangelo, P; Coleman, JP; Drutskoy, A; Druzhinin, VP; Eidelman, S; Eigen, G; Eisner, AM; Faccini, R; Flood, KT; Gambino, P; Gaz, A; Gradl, W; Hayashii, H; Higuchi, T; Hulsbergen, WD; Hurth, T; Iijima, T; Itoh, R; Jackson, PD; Kass, R; Kolomensky, YG; Kou, E; Krizan, P; Kronfeld, A; Kumano, S; Kwon, YJ; Latham, TE; Leith, DWGS; Uth, VL; Martinez-Vidal, F; Meadows, BT; Mussa, R; Nakao, M; Nishida, S; Ocariz, J; Olsen, SL; Pakhlov, P; Pakhlova, G; Palano, A; Pich, A; Playfer, S; Poluektov, A; Porter, FC; Robertson, SH; Roney, JM; Roodman, A; Sakai, Y; Schwanda, C; Schwartz, AJ; Seidl, R; Sekula, SJ; Steinhauser, M; Sumisawa, K; Swanson, ES; Tackmann, F; Trabelsi, K; Uehara, S; Uno, S; van de Water, R; Vasseur, G; Verkerke, W; Waldi, R; Wang, MZ; Wilson, FF; Zupan, J; Zupanc, A; Adachi, I; Albert, J; Banerjee, S; Bellis, M; Ben-Haim, E; Biassoni, P; Cahn, RN; Cartaro, C; Chauveau, J; Chen, C; Chiang, CC; Cowan, R; Dalseno, J; Davier, M; Davies, C; Dingfelder, JC; Echenard, B; Epifanov, D; Fulsom, BG; Gabareen, AM; Gary, JW; Godang, R; Graham, MT; Hafner, A; Hamilton, B; Hartmann, T; Hayasaka, K; Hearty, C; Iwasaki, Y; Khodjamirian, A; Kusaka, A; Kuzmin, A; Lafferty, GD; Lazzaro, A; Li, J; Lindemann, D; Long, O; Lusiani, A; Marchiori, G; Martinelli, M; Miyabayashi, K; Mizuk, R; Mohanty, GB; Muller, DR; Nakazawa, H; Ongmongkolkul, P; Pacetti, S; Palombo, F; Pedlar, TK; Piilonen, LE; Pilloni, A; Poireau, V; Prothmann, K; Pulliam, T; Rama, M; Ratcliff, BN; Roudeau, P; Schrenk, S; Schroeder, T; Schubert, KR; Shen, CP; Shwartz, B; Soffer, A; Solodov, EP; Somov, A; Staric, M; Stracka, S; Telnov, AV; Todyshev, KY; Tsuboyama, T; Uglov, T; Vinokurova, A; Walsh, JJ; Watanabe, Y; Won, E; Wormser, G; Wright, DH; Ye, S; Zhang, CC; Abachi, S; Abashian, A; Abe, K; Abe, K; Abe, N; Abe, R; Abe, T; Abe, T; Abrams, GS; Adam, I; Adamczyk, K; Adametz, A; Adye, T; Agarwal, A; Ahmed, H; Ahmed, M; Ahmed, S; Ahn, BS; Ahn, HS; Aitchison, IJR; Akai, K; Akar, S; Akatsu, M; Akemoto, M; Akhmetshin, R; Akre, R; Alam, MS; Albert, JN; Aleksan, R; Alexander, JP; Alimonti, G; Allen, MT; Allison, J; Allmendinger, T; Alsmiller, JRG; Altenburg, D; Alwyn, KE; An, Q; Anderson, J; Andreassen, R; Andreotti, D; Andreotti, M; Andress, JC; Angelini, C; Anipko, D; Anjomshoaa, A; Anthony, PL; Antillon, EA; Antonioli, E; Aoki, K; Arguin, JF; Arinstein, K; Arisaka, K; Asai, K; Asai, M; Asano, Y; Asgeirsson, DJ; Asner, DM; Aso, T; Aspinwall, ML; Aston, D; Atmacan, H; Aubert, B; Aulchenko, V; Ayad, R; Azemoon, T; Aziz, T; Azzolini, V; Azzopardi, DE; Baak, MA; Back, JJ; Bagnasco, S; Bahinipati, S; Bailey, DS; Bailey, S; Bailly, P; Van Bakel, N; Bakich, AM; Bala, A; Balagura, V; Baldini-Ferroli, R; Ban, Y; Banas, E; Band, HR; Banerjee, S; Baracchini, E; Barate, R; Barberio, E; Barbero, M; Bard, DJ; Barillari, T; Barlow, NR; Barlow, RJ; Barrett, M; Bartel, W; Bartelt, J; Bartoldus, R; Batignani, G; Battaglia, M; Bauer, JM; Bay, A; Beaulieu, M; Bechtle, P; Beck, TW; Becker, J; Becla, J; Bedny, I; Behari, S; Behera, PK; Behn, E; Behr, L; Beigbeder, C; Beiline, D; Bell, R; Bellini, F; Bellodi, G; Belous, K; Benayoun, M; Benelli, G; Benitez, JF; Benkebil, M; Berger, N; Bernabeu, J; Bernard, D; Bernet, R; Bernlochner, FU; Berryhill, JW; Bertsche, K; Besson, P; Best, DS; Bettarini, S; Bettoni, D; Bhardwaj, V; Bhimji, W; Bhuyan, B; Bhuyan, B; Biagini, ME; Biasini, M; Van Bibber, K; Biesiada, J; Bingham, I; Bionta, RM; Bischofberger, M; Bitenc, U; Bizjak, I; Blanc, F; Blaylock, G; Blinov, VE; Bloom, E; Bloom, PC; Blount, NL; Blouw, J; Bly, M; Blyth, S; Boeheim, CT; Bomben, M; Bondar, A; Bondioli, M; Bonneaud, GR; Bonvicini, G; Booke, M; Booth, J; Borean, C; Borgland, AW; Borsato, E; Bosi, F; Bosisio, L; Botov, AA; Bougher, J; Bouldin, K; Bourgeois, P; Boutigny, D; Bowerman, DA; Boyarski, AM; Boyce, RF; Boyd, JT; Bozek, A; Bozzi, C; Bracko, M; Brandenburg, G; Brandt, T; Brau, B; Brau, J; Breon, AB; Breton, D; Brew, C; Briand, H; Bright-Thomas, PG; Brigljevic, V; Britton, DI; Brochard, F; Broomer, B; Brose, J; Browder, TE; Brown, CL; Brown, CM; Brown, DN; Brown, DN; Browne, M; Bruinsma, M; Brunet, S; Bucci, F; Buchanan, C; Buchmueller, OL; Unger, CB; Bugg, W; Bukin, AD; Bula, R; Bulten, H; Burchat, PR; Burgess, W; Burke, JP; Button-Shafer, J; Buzykaev, AR; Buzzo, A; Cai, Y; Calabrese, R; Calcaterra, A; Calderini, G; Camanzi, B; Campagna, E; Campagnari, C; Capra, R; Carassiti, V; Carpinelli, M; Carroll, M; Casarosa, G; Casey, BCK; Cason, NM; Castelli, G; Cavallo, N; Cavoto, G; Cecchi, A; Cenci, R; Cerizza, G; Cervelli, A; Ceseracciu, A; Chai, X; Chaisanguanthum, KS; Chang, MC; Chang, YH; Chang, YW; Chao, DS; Chao, M; Chao, Y; Charles, E; Chavez, CA; Cheaib, R; Chekelian, V; Chen, A; Chen, A; 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