Mohs micrographic surgery is a specialized a form of skin cancer surgery in which the Mohs surgeon acts as both surgeon and pathologist. The procedure is characterized by its histopathologic margin control and ability to spare tissue, particularly in cosmetically sensitive locations. Mohs surgery is known for both limiting the size of the final defect and its high cure rate. In this review, the authors highlight indications for the procedure, detail the technique itself, discuss cutaneous tumors for which Mohs micrographic surgery is indicated, and present the economic benefit of Mohs surgery.
http://ift.tt/2qJLUGc
Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 20 Μαΐου 2017
Mohs Micrographic Surgery for the Management of Cutaneous Malignancies
Allergen immunotherapy for the treatment of respiratory allergies in the elderly.
Purpose of review: Respiratory allergies, including asthma and allergic rhinitis can also occur in the elderly. Allergen immunotherapy for allergic diseases is the only disease-modifying treatment for patients with allergies available thus far. Here, we review current evidence supporting the use of allergen immunotherapy in the elderly and discuss its efficacy and utility for the treatment of respiratory allergic diseases in this setting. Recent findings: Subcutaneous and/or sublingual immunotherapy are effective therapeutic options in not only young but also older patients. Allergen immunotherapy reduces medication and symptom scores in the elderly and can thus be safely prescribed in this population. Summary: Elderly individuals with proven, clinically relevant immunoglobulin E sensitization to inhalant allergens may benefit from allergen immunotherapy for respiratory allergic diseases. Older patients without contraindications should therefore be considered for treatment, with the additional benefit of reduced medication and symptom scores. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2rDGVa2
http://ift.tt/2rDGVa2
Prognostic value of lymph node density in buccal squamous cell carcinoma
Lymph node density(LND) has been shown to be a better prognosticator than conventional nodal classification to predict prognosis for squamous cell carcinoma(SCC) of the oral cavity. However, studies focusing on subsites of oral cancer are meager. The role of LND for buccal SCC was evaluated in this study.
http://ift.tt/2rDuUBr
A survey of inpatient practitioner knowledge of penicillin allergy at 2 community teaching hospitals
The negative effect of the penicillin allergy label on antibiotic use and patient outcomes has brought to light the need for thorough penicillin allergy assessments and heightened practitioner education.
http://ift.tt/2q7UrR1
Frequency of untreated hypogammaglobulinemia in bronchiectasis
Bronchiectasis is found in approximately one fourth of patients with common variable immune deficiency, with 14% in 1 study having bronchiectasis at the time of diagnosis,1 and lower respiratory tract symptoms are associated with a lower quality of life and require increased immunoglobulin (Ig) usage.2,3 Additional primary immune deficiencies also are associated with a high rate of bronchiectasis, including IgA deficiency, IgG subclass deficiency, and specific antibody deficiency against polysaccharide antigen despite normal levels of quantitative immunoglobulins.
http://ift.tt/2qCTcwG
Prognostic value of lymph node density in buccal squamous cell carcinoma
Source:American Journal of Otolaryngology
Author(s): Tam-Lin Chow, Wilson W.Y. Kwan, Siu-Chung Fung, Lai-In Ho
PurposeLymph node density(LND) has been shown to be a better prognosticator than conventional nodal classification to predict prognosis for squamous cell carcinoma(SCC) of the oral cavity. However, studies focusing on subsites of oral cancer are meager. The role of LND for buccal SCC was evaluated in this study.MethodsA total of 39 patients with buccal SCC primarily treated surgically with neck dissection were identified. LND was defined as the number of positive nodes over the number of nodal yield. The cut-off of LND was ≤0.07 or >0.07. Patient demographic data and clincopathologic parameters were described. Survival was expressed by Kaplan-Meier method and correlation with survival is analyzed with log-rank test. IBM SPSS Statistics version 22 was used for data computation.ResultsThe median follow-up was 79.0months and median nodes removed was 23 (range 8–93). Positive nodal involvement was found in 19(48.7%) patients. The 5-year and 10-year OS were 67.4% and 42.5% whilst for DSS were 69.2% and 65.5%, respectively. When pT-, pN-, LND-classification and AJCC stage were analyzed for the whole series, only pN- (p=0.006) and LND-classification (p=0.002) were significant factors for OS, while pT-, pN-, LND-classification and AJCC stage were all significant factors for DSS. When only cases with positive nodal spread were considered, the pN-classification (pN1 vs pN2) was not a significant risk factor for either OS (p=0.075, HR 3.10(CI 0.89–10.76)) and DSS (p=0.074, HR 3.58(CI 0.88–14.56)). By contrast, LND-classification (≤0.07 vs >0.07) remained a significant predictor for OS (p=0.03, HR 3.95(CI 1.15–13.63)), but not for the DSS (p=0.112, HR 2.92(CI 0.78–10.99)).ConclusionThe prognostic value of LND on buccal SCC is supported in this study. The results also suggest that LND is better than the conventional pN-classification to predict OS. Further studies on LND with big sample size for buccal SCC or other subsites of OSCC are worthwhile.
http://ift.tt/2q53BP0
Allergen immunotherapy for the treatment of respiratory allergies in the elderly.
Purpose of review: Respiratory allergies, including asthma and allergic rhinitis can also occur in the elderly. Allergen immunotherapy for allergic diseases is the only disease-modifying treatment for patients with allergies available thus far. Here, we review current evidence supporting the use of allergen immunotherapy in the elderly and discuss its efficacy and utility for the treatment of respiratory allergic diseases in this setting. Recent findings: Subcutaneous and/or sublingual immunotherapy are effective therapeutic options in not only young but also older patients. Allergen immunotherapy reduces medication and symptom scores in the elderly and can thus be safely prescribed in this population. Summary: Elderly individuals with proven, clinically relevant immunoglobulin E sensitization to inhalant allergens may benefit from allergen immunotherapy for respiratory allergic diseases. Older patients without contraindications should therefore be considered for treatment, with the additional benefit of reduced medication and symptom scores. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2rDGVa2
http://ift.tt/2rDGVa2
Invasive lobular carcinoma with extracellular mucin production—a novel pattern of lobular carcinomas of the breast. Clinico-pathological description of eight cases
Abstract
Invasive lobular carcinoma of the breast is known to produce intracellular mucin and has been recognized in single-case reports to show extracellular mucin production, as well. This latter morphology is not only rare but must also be under- or misdiagnosed. The aim was to better characterize this entity. Cases of lobular cancers demonstrating extracellular mucin formation were identified in a multi-institutional effort and their clinical and morphologic features were assessed. Immunohistochemistry was used to characterize the E-cadherin-membrane complex, neuroendocrine differentiation, and to some extent, mucin formation. All but one of the eight cases occurred in postmenopausal patients. Extracellular mucin production was present in 5 to 50% of the tumour samples and rarely also appeared in nodal and distant metastases. The tumours were completely E-cadherin negative and showed cytoplasmic p120 positivity. The majority (n = 6/8) was also completely negative for β-catenin, but two tumours displayed focal β-catenin positivity in the mucinous area. MUC1 and MUC2 expression was observed in all and 7/8 tumours, respectively; neuroendocrine differentiation was present in only one. Invasive lobular carcinoma with extracellular mucin formation is a rare morphologic variant of lobular carcinoma prone to be misdiagnosed and warranting further studies.
http://ift.tt/2rD1Qdd
Immunogenomics: using genomics to personalize cancer immunotherapy
Abstract
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy. A T cell-dependent mechanism of cancer progression was discovered in 2012, providing a potential link to cancer immunotherapy. Since then, an antibody against cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), ipilimumab, and three programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, pembrolizumab (Keytruda), nivolumab (Opdivo), and atezolizumab (Tecentriq), were approved by the Food and Drug Administration (FDA) in the USA. In this review article, based on evidence that has been emerging in the literature over the last decade, we will discuss the basis for including genomic data in immunotherapy regimens, the current progress in identifying biomarkers targetable by immune checkpoint blockade, and the application of these therapies in modern oncology programs. Going forward, the clinical application of NGS in personalized oncology programs could include dose monitoring and adjustment or the development of individualized vaccines or other personalized therapies based on the mutational landscape. The continued identification of new neoantigens and the efficient mobilization of tumor-reactive lymphocytes in patients with cancer will promote the advancement of immunotherapy using personalized NGS-guided technologies.
http://ift.tt/2rDL8JK
Targeting EGFR/HER2 heterodimerization with a novel anti-HER2 domain II/III antibody
Source:Molecular Immunology, Volume 87
Author(s): Xiaojie Yu, Lingfei Wang, Yafeng Shen, Chao Wang, Yajun Zhang, Yanchun Meng, Yang Yang, Beibei Liang, Bo Zhou, Huajing Wang, Huafeng Wei, Changhai Lei, Shi Hu, Bohua Li
HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Here, we describe a novel anti-HER2 antibody, 7C3, which was developed using hybridoma technique. Structural analysis confirms that the epitope of this antibody is in domain II/III of HER2. Moreover, a structural conformation change was observed in HER2 in complex with 7C3. Interestingly, this novel anti-HER2 antibody exhibits efficacy in blocking HER2/EGFR heterodimerization and signaling. The results highlight the different function role of HER2 domains and the unique potential of 7C3 to inhibit the HER2/EGFR heterodimer, which may complement current anti-HER2 treatments.
http://ift.tt/2q7bYc5
Immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells
Source:Molecular Immunology, Volume 87
Author(s): Hao Zhang, Yanling Tao, Haihui Liu, Saisai Ren, Bin Zhang, Hu Chen
Bone marrow derived mesenchymal stem cells (MSCs) play a critical role in immune modulation. However, immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells (UC-MSCs) remains unclear. In this study, UC-MSCs were separated from whole umbilical cord using a single enzyme digestion. UC-MSCs (CD73+, CD90+, CD105+, and CD34−, CD45−, HLA-DR−) were differentiated into adipocytes, osteocytes and chondrocytes in vitro under specific stimulatory environments. UC-MSCs suppressed umbilical cord blood lymphocyte proliferation stimulated by mitogen, and ELISA showed that the secretion of INF-γ was downregulated, and the secretion of IL-4 was upregulated, with CD8+ T cells markedly decreased and CD4+ T cells changed lightly. Moreover, the infusion of UC-MSCs in recipient mice transplanted with donor bone marrow cells ameliorated acute graft-versus host disease (aGVHD) and extended survival. In conclusion, UC-MSCs might negatively modulate immunoreactions, and have application potential in the treatment of aGVHD caused by allogeneic stem cells transplantation.
http://ift.tt/2qCoOm9
Chicken interleukin-1β mutants are effective single-dose vaccine adjuvants that enhance mucosal immune response
Source:Molecular Immunology, Volume 87
Author(s): Wen-Ting Chen, Hao-Kai Chang, Cheng-Chung Lin, Shan-Min Yang, Hsien-Sheng Yin
The use of cytokines as adjuvants in poultry is promising because they may enhance immune responses to antigens. In this study, we created two mutants, chicken interleukin-1 beta (ChIL-1β) Q19A and R140A, which exhibited significantly increased in vivo biological activity compared with wild-type ChIL-1β. The potential mucosal adjuvant activity of the mutants Q19A and R140A was evaluated in chickens through the intranasal coadministration of a single dose of the Newcastle disease virus (NDV) vaccine with Q19A or R140A. Compared with chickens vaccinated with only the NDV vaccine or the NDV vaccine plus wild-type recombinant ChIL-1β, chickens vaccinated with Q19A or R140A had significantly increased serum hemagglutination-inhibition antibody titers and anti-NDV-specific IgA antibody levels 1 week later, a high amount of interferon-γ secretion from splenocytes, and increased secretory IgA accumulated in nasal tissues. In addition, molecular dynamics simulations of the mutant R140A bound to its receptor (IL-1RI) and receptor accessory protein (IL-1RAcP) were more energetically favorable than the analogous wild-type ternary complex resulting in a decreased energy, which may stabilize the R140A/IL-1RI/IL-1RAcP complex. In conclusion, the mutants Q19A and R140A are effective adjuvants that accelerate and enhance chicken mucosal immunity when co-administered with one dose of the NDV vaccine.
http://ift.tt/2q77Bhp
Streptococcus pneumoniae Otitis Media Pathogenesis and How It Informs Our Understanding of Vaccine Strategies
Abstract
Purpose of Review
This study aimed to review the literature regarding the mechanisms of transition from asymptomatic colonization to induction of otitis media and how the insight into the pathogenesis of otitis media has the potential to help design future otitis media-directed vaccines.
Recent Findings
Respiratory viruses have long been shown to predispose individuals to bacterial respiratory infections, such as otitis media. Recent information suggests that Streptococcus pneumoniae, which colonize the nasopharynx asymptomatically, can sense potentially "threatening" changes in the nasopharyngeal environment caused by virus infection by upregulating specific sets of genes involved in biofilm release, dissemination from the nasopharynx to other sites, and protection against the host immune system. Furthermore, an understanding of the transcriptional and proteomic changes occurring in bacteria during transition to infection has led to identification of novel vaccine targets that are disease-specific and will not affect asymptomatic colonization. This approach will avoid major changes in the delicate balance of microorganisms in the respiratory tract microbiome due to elimination of S. pneumoniae.
Summary
Our recent findings are reviewed in the context of the current literature on the epidemiology and pathogenesis of otitis media. We also discuss how other otopathogens, such as Haemophilus influenzae and Moraxella catarrhalis, as well as the normal respiratory microbiome, can modulate the ability of pneumococci to cause infection. Furthermore, the unsatisfactory protection offered by the pneumococcal conjugate vaccines is highlighted and we review potential future strategies emerging to confer a more specific protection against otitis media.
http://ift.tt/2rDCSK3
Clinical Thyroidology High-Impact Articles
FREE ACCESS through May 30, 2017
Read Now:
Surgery for Neck Recurrence of Thyroid Cancer Can Achieve Complete Remission in a Majority of Patients
Jerome M. Hershman, Masha J. Livhits
How Often Does a Thyroid Cancer Patient Need to Undergo Surveillance with Cervical Ultrasound?
Martin Biermann
A New Assessment of the Prevalence and Risk Factors of Liver Abnormalities in Hyperthyroidism
Jacques Orgiazzi
Higher Preconception TSH Values Are Associated With Adverse Obstetric Outcomes
Elizabeth N. Pearce
The post Clinical Thyroidology High-Impact Articles appeared first on American Thyroid Association.
http://ift.tt/2pWIbHT
Turning the tide: Clinical utility of PD-L1 expression in squamous cell carcinoma of the head and neck
Source:Oral Oncology, Volume 70
Author(s): Astrid De Meulenaere, Tijl Vermassen, Sandrine Aspeslagh, Wouter Huvenne, Jo Van Dorpe, Liesbeth Ferdinande, Sylvie Rottey
The use of cytotoxic and/or targeted agents is the gold standard in first- and second-line treatment of metastatic head and neck cancer. Currently the focus of oncologic research is shifting to the implementation of immune checkpoint inhibitor regimens. Many trials are being performed evaluating the survival benefit of various PD-1/PD-L1 blocking antibodies in both solid and haematological malignancies. Also, evaluation of the predictive value of PD-L1 expression on tumour cells and immune cells is being explored.We first review the current knowledge and possible pitfalls for PD-L1 expression in squamous cell carcinoma of the head and neck. Next, we provide an update on the therapeutic use of PD-1/PD-L1 blocking antibodies as treatment modality for patients with squamous cell carcinoma of the head and neck and we assess the predictive value of tumour PD-L1 positivity. Finally, we elaborate on other promising predictive biomarkers of interest in this patient population.
http://ift.tt/2qDOiQD
SMAD3 expression and regulation of fibroplasia in vocal fold injury
Objective
Recent reports highlight the efficacy of small interfering RNA (siRNA) targeting SMAD3 to regulate transforming growth factor β (TGF-β)-mediated fibroplasia in vocal fold fibroblasts. The current study sought to investigate SMAD3 expression during wound healing in vivo and quantify the downstream transcriptional events associated with SMAD3 knockdown in vitro.
Study Design
In vivo and in vitro.
Methods
Unilateral vocal fold injury was created in a rabbit model. SMAD3 and SMAD7 mRNA expression was quantified at 1 hour and 1, 3, 7, 14, 30, 60, and 90 days following injury. In vitro, multi-gene analysis technology was employed in our immortalized human vocal-fold fibroblast cell line following TGF-β1 stimulation ± SMAD3 knockdown across time points.
Results
SMAD3 mRNA expression increased following injury; upregulation was significant at 3 and 7 days compared to control (both P < 0.001). SMAD7 mRNA was also upregulated at 3, 7, and 14 days (P = 0.02, P < 0.001, and P < 0.001, respectively). In vitro, SMAD3 knockdown reduced the expression of multiple profibrotic, TGF-β signaling, and extracellular matrix metabolism genes at 6 and 24 hours following TGF-β1 stimulation.
Conclusion
Cumulatively, these data support SMAD3 as a potential master regulator of TGF-β-mediated fibrosis. SMAD3 transcription peaked 7 days following injury. Multi-gene analysis indicated that the therapeutic effectiveness of SMAD3 knockdown may be related to regulation of downstream mediators of fibroplasia and altered TGF-β signaling.
Level of Evidence
NA. Laryngoscope, 2017
http://ift.tt/2pWqUic
Severe polyserositis induced by the 13-valent pneumococcal conjugate vaccine: a case report
The United States Advisory Committee on Immunization Practices recommends administration of the 13-valent pneumococcal conjugate vaccine in series with the 23-valent pneumococcal polysaccharide vaccine for pre...
http://ift.tt/2rCQo1k
Erosive pustular dermatosis of the leg: A prospective, multicentre, observational study of 36 cases
Publication date: Available online 19 May 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): P. Nicol, G. Perceau, C. Barbe, P. Bernard
BackgroundErosive pustular dermatosis of the leg (EPDL) is a poorly understood entity first described by Lanigan and Cotteril in 1987. Its clinical diagnosis is based on exclusion since the physiopathology is unknown. The primary objective of this investigation was to specify the clinical aspects and outcomes in a prospective study. The secondary objectives were to describe associated diseases, the circumstances of occurrence, and the laboratory tests used.Patients and methodsThis was a prospective study that included 45 patients selected by members of the Angiology-Dermatology Group of the SFD (French Dermatology Society) at 13 centres between 01/09/2013 and 31/10/2014. There was a 180-day monitoring period. The records of 36 patients were analysed. Clinical and laboratory data were collected.ResultsMean patient age was 79.6±9.9 years with a M/F sex ratio of 0.2. Among the patients, 16.7% had skin cancer and 91.7% had venous insufficiency. The proportion of patients wearing venous compression hose was constant between inclusion and D180. Lesions were bilateral (53%), affected the middle third of the leg, and were on the anterior aspect. Complete healing was achieved in 77.8% of cases with time to healing of 2.4±1.2 months, and under topical corticosteroids in 97.3% of cases. During follow-up, relapse occurred in 38.9% of cases after a mean time of 2.4±1.2 months.ConclusionEPDL appears to be an idiopathic inflammatory dermatosis with a particular topographic expression. The physiopathology could be related to chronic inflammation associated with venous insufficiency and with certain trigger factors. Currently, there are few therapeutic alternatives to topical corticosteroids.
http://ift.tt/2rCJtEh
Dectin-1 plays a critical role in HDM-induced PGE2 production in macrophages
Publication date: Available online 20 May 2017
Source:Allergology International
Author(s): Takashi Ito, Koichi Hirose, Ayako Norimoto, Aiko Saku, Hiroshi Nakajima
http://ift.tt/2rBRQRn
Homozygous TCF3 mutation is associated with severe hypogammaglobulinemia and B-cell acute lymphoblastic leukemia
Source:Journal of Allergy and Clinical Immunology
Author(s): Meriem Ben-Ali, Jing Yang, Koon Wing Chan, Imen Ben-Mustapha, Najla Mekki, Chaouki Benabdesselem, Fethi Mellouli, Mohamed Bejaoui, WanLing Yang, Lamia Aissaoui, Yu Lung Lau, Mohamed-Ridha Barbouche
Teaser
The identification of a homozygous TCF3 gene mutation in a patient presenting with severe hypogammaglobulinemia and acute lymphoblastic leukemia supports the crucial role of this transcription factor in normal B-lymphocyte development.http://ift.tt/2qE1oNR
Flexible IgE epitope containing domains of Phl p 5 cause high allergenic activity
Publication date: Available online 19 May 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Christoph Göbl, Margarete Focke-Tejkl, Nazanin Najafi, Evelyne Schrank, Tobias Madl, Simone Kosol, Christoph Madritsch, Yulia Dorofeeva, Sabine Flicker, Josef Thalhamer, Rudolf Valenta, Klaus Zangger, Nico Tjandra
This is the first study determining the three-dimensional structure of Phl p 5a which reveals a novel mechanism for high allergenic activity based on flexibly connected IgE-reactive domains which cross-link effector cell-bound IgE more efficiently than isolated rigid globular proteins. These findings may also form a basis for specific immunotherapy strategies.
http://ift.tt/2rCuxq1
The IL-33/ST2 axis is crucial in type 2 airway responses induced by the Staphylococcus aureus protease SplD
Publication date: Available online 19 May 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Andrea R. Teufelberger, Maria Nordengrün, Harald Braun, Tania Maes, Katrien De Grove, Gabriele Holtappels, Clara O'Brien, Sharen Provoost, Hamida Hammad, Amanda Gonçalves, Rudi Beyaert, Wim Declercq, Peter Vandenabeele, Dmitri V. Krysko, Barbara M. Bröker, Claus Bachert, Olga Krysko
BackgroundChronic airway inflammatory diseases such as chronic rhinosinusitis with nasal polyps and asthma showed increased nasal Staphylococcus aureus (S. aureus) colonization. Serine protease like protein D (SplD) and other closely related proteases secreted by S. aureus have recently been identified as inducers of allergic asthma in humans and mice but their mechanism of action is largely unknown.ObjectiveWe investigated the role of recombinant SplD in driving Th2-biased responses and IgE formation in a murine model of allergic asthma.MethodsAllergic asthma was induced in C57BL/6 J wild type mice, TLR4 knockout mice (TLR4-/-) and Rag2 knockout mice (Rag2-/-) by repeated intratracheal applications of SplD. Inflammatory parameters in the airways were assessed by flow cytometry, ELISA, Luminex and immunohistochemistry. Serum SplD-specific IgE levels were analysed by ELISA.ResultsWe observed that repeated intratracheal exposure to SplD led to IL-33 and eotaxin production, eosinophilia, bronchial hyperreactivity and goblet cell hyperplasia in the airways. Blocking the IL-33 activity using a soluble ST2 receptor (sST2) significantly decreased the numbers of eosinophils, IL-13+ILC2s, IL-13+CD4+ T cells, and IL-5 and IL-13 production by lymph node cells but had no effect on IgE production. SplD-induced airway inflammation and IgE production were largely dependent on the presence of the functional adaptive immune system and independent of TLR4 signalling.ConclusionThe S. aureus-derived protein SplD is a potent allergen of S. aureus and induces a Th2-biased inflammatory response in the airways in an IL-33-dependent, but TRL4-independent manner. sST2 could be an efficient strategy to interfere with SplD-induced Th2 inflammation, but does not prevent the allergic sensitization.
Graphical abstract
Teaser
S.aureus protein SplD acts as an allergen and an adjuvant inducing asthma features via inducing IL-33 production by airway epithelial cells. Soluble IL-33 receptor is a promising treatment option as it interferes with SplD-induced inflammation.http://ift.tt/2qE3MnV
Mechanistic Link between Diesel Exhaust Particles and Respiratory Reflexes
Publication date: Available online 19 May 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Ryan K. Robinson, Mark A. Birrell, John J. Adcock, Michael A. Wortley, Eric D. Dubuis, Shu Chen, Catriona M. McGilvery, Sheng Hu, Milo SP. Shaffer, Sara J. Bonvini, Sarah A. Maher, Ian S. Mudway, Alexandra E. Porter, Chris Carlsten, Teresa D. Tetley, Maria G. Belvisi
BackgroundDiesel exhaust particles (DEP) are a major component of particulate matter in Europe's largest cities and epidemiological evidence links exposure with respiratory symptoms and asthma exacerbations. Respiratory reflexes are responsible for symptoms and are regulated by vagal afferent nerves which innervate the airway. It is not known how DEP exposure activates airway afferents to elicit symptoms such as cough and bronchospasm.ObjectiveTo identify the mechanisms involved in the activation of airway sensory afferents by DEPs.MethodsIn this study we utilize in vitro and in vivo electrophysiological techniques including a unique model which assess depolarization (a marker of sensory nerve activation) of human vagus.ResultsWe demonstrate a direct interaction between DEP and airway C-fiber afferents. In anaesthetized guinea pigs, intratracheal administration of DEP activated airway C-fibers. The organic extract (DEP-OE), and not the cleaned particles, evoked depolarization of guinea-pig and human vagus and this was inhibited by a TRPA1 antagonist and the antioxidant N-acetyl cysteine (NAC). Polycyclic aromatic hydrocarbons (PAHs), major constituents of DEP, were implicated in this process via activation of the aryl hydrocarbon receptor (AhR) and subsequent mitochondrial ROS production, which is known to activate TRPA1 on nociceptive C-fibers.ConclusionsThis study provides the first mechanistic insights into how exposure to urban air pollution leads to activation of guinea-pig and human sensory nerves which are responsible for respiratory symptoms. Mechanistic information will enable the development of appropriate therapeutic interventions and mitigation strategies for those susceptible individuals who are most at risk.
Graphical abstract
Teaser
These findings provide the first mechanistic insights into how exposure to urban air pollution leads to the activation of human sensory nerves which are responsible for respiratory symptoms.http://ift.tt/2qE4UHO
Big data in facial plastic and reconstructive surgery: from large databases to registries.
Purpose of review: There are many limitations to performing clinical research with high levels of evidence in facial plastic and reconstructive surgery (FPRS), such as randomization into surgical groups and sample size recruitment. Therefore, additional avenues for exploring research should be explored using big data, from databases to registries. Other organizations have developed these tools in the evolving landscape of outcomes measurement and value in healthcare, which may serve as models for our specialty. Recent findings: Over the last 5 years, FPRS literature of large-scale outcomes research, utilizing several administrative databases, has steadily grown. Our objectives are to describe key administrative databases, strengths and weaknesses of each, and identify recent FPRS publications utilizing big data. A registry with FPRS defined outcomes has the most potential. Summary: Although FPRS research has trended to a more evidence-based approach in the modern healthcare era, gaps persist. Several large administrative databases or registries can address voids in outcomes research within FPRS. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2rBZtGQ
http://ift.tt/2rBZtGQ
Free 25(OH)D concentrations are associated with atopy and lung function in children with asthma
Publication date: Available online 19 May 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Suzanne L. Pollard, John J. Lima, Edward Mougey, Karina Romero, Carla Tarazona-Meza, Katherine Tomaino, Gary Malpartida Guzmán, Nadia N. Hansel, William Checkley
BackgroundEvidence suggests free mono-hydroxyvitamin D (25[OH]D) concentrations are more strongly linked to certain outcomes than total concentrations; however, no studies have examined the relation between free 25(OH)D and respiratory or allergic disease.ObjectiveTo examine associations between total and free 25(OH)D concentrations and asthma outcomes.MethodsWe quantified total and free 25(OH)D concentrations in 137 Peruvian children with asthma and 152 children without asthma and examined associations with asthma outcomes.ResultsMean age ± SD was 13 ± 2.5 years, and 50.2% were boys. Mean total and measured free 25(OH)D concentrations were 29 ± 9.5 ng/mL and 5.0 ± 1.3 pg/mL, respectively. Lower free but not total 25(OH)D concentrations were significantly associated with atopy in all children (total, odds ratio [OR] 1.3 per 10-ng/mL decrease, 95% confidence interval [CI] 0.95–1.7, P = .12; vs free, OR 1.3 per 1-pg/mL decrease, 95% CI 1.0–1.6, P = .02) and children with asthma (total, OR 1.1 per 10-ng/mL decrease, 95% CI 0.75–1.7, P = .57; vs free, OR 1.6 per 1-pg/mL decrease, 95% CI 1.0–2.5, P = .04). Free but not total 25(OH)D levels were significantly associated with pre-bronchodilator forced expiratory volume in 1 second (total, 0.11 L, −0.12 to 0.34, P = .34; vs free, 0.20 L, 0.021–0.39, P = .03) and forced vital capacity (total, 0.13 L, −0.12 to 0.37, P = .31; vs free, 0.22 L, 0.026–0.42, P = .03) Z-scores in children with asthma.ConclusionAtopy, forced expiratory volume in 1 second, and forced vital capacity were more strongly linked to free than to total 25(OH)D concentrations, suggesting the free form might be more relevant in modulating allergic disease risk and pulmonary function in children with asthma.
http://ift.tt/2rBVdXJ
Big data in facial plastic and reconstructive surgery: from large databases to registries.
Purpose of review: There are many limitations to performing clinical research with high levels of evidence in facial plastic and reconstructive surgery (FPRS), such as randomization into surgical groups and sample size recruitment. Therefore, additional avenues for exploring research should be explored using big data, from databases to registries. Other organizations have developed these tools in the evolving landscape of outcomes measurement and value in healthcare, which may serve as models for our specialty. Recent findings: Over the last 5 years, FPRS literature of large-scale outcomes research, utilizing several administrative databases, has steadily grown. Our objectives are to describe key administrative databases, strengths and weaknesses of each, and identify recent FPRS publications utilizing big data. A registry with FPRS defined outcomes has the most potential. Summary: Although FPRS research has trended to a more evidence-based approach in the modern healthcare era, gaps persist. Several large administrative databases or registries can address voids in outcomes research within FPRS. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2rBZtGQ
http://ift.tt/2rBZtGQ
Teachers of mathematics to mathematics teachers: a TDA Mathematics Development Programme for Teachers
Crisan, C; Rodd, M; (2011) Teachers of mathematics to mathematics teachers: a TDA Mathematics Development Programme for Teachers. In: Proceedings of the British Society for Research into Learning Mathematics, 31(3). (pp. pp. 29-34). British Society for the Learning of Mathematics: Oxford, UK. Green open access
http://ift.tt/2q5Qvk0
Haptoglobin Administration in Cardiovascular Surgery Patients: Its Association With the Risk of Postoperative Acute Kidney Injury
http://ift.tt/2rnWEMW
Red Cell Transfusion–Associated Hemolysis in Cardiac Surgery: An Observational Cohort Study
http://ift.tt/2qDRuf9
Chronic Amphetamine Users Do Not Need More Drugs During General Anesthesia
http://ift.tt/2qE2hWv
Magic Mirror, on the Wall—Which Is the Right Study Design of Them All?—Part I
http://ift.tt/2qDGNJk
An Observational Assessment of Anesthesia Capacity in Madagascar as a Prerequisite to the Development of a National Surgical Plan
http://ift.tt/2qDZDjs
Cross-Disciplinary Perceptions of Structured Interprofessional Rounds in Promoting Teamwork Within an Academic Tertiary Care Obstetric Unit
http://ift.tt/2rBWG0c
Exercise Combined With Ultrasound Attenuates Neuropathic Pain in Rats Associated With Downregulation of IL-6 and TNF-α, but With Upregulation of IL-10
http://ift.tt/2rBW2zW
A Retrospective Study to Evaluate the Effect of Concentration of Hypertonic Saline on Efficacy and Safety of Epidural Adhesiolysis
http://ift.tt/2qDUqZ2
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