Head and Neck Diseases by Alexandros G.Sfakianakis: 02/13/17

Δευτέρα 13 Φεβρουαρίου 2017

Differences in eosinophil molecular profiles between children and adults with eosinophilic esophagitis

Abstract

Background

Eosinophilic esophagitis (EoE) afflicts both children and adults. It has been debated whether pediatric and adult EoE represent different disease entities. The objectives of this study were to determine if the blood eosinophil molecular pattern of children with EoE is: 1) distinct from that of healthy children; and 2) different from that of adults with EoE.

Methods

Blood eosinophils from children and adults with EoE, and healthy controls, were analyzed with flow cytometry regarding levels of CD23, CD44, CD54, CRTH2, FOXP3 and galectin-10. Eosinophil FOXP3 and galectin-10 mRNA levels were determined by qPCR. The data was analyzed by using a multivariate method of pattern recognition.

Results

An eosinophil molecular pattern capable of distinguishing children with EoE from control children was identified. A smaller fraction of eosinophils from children with EoE expressed CD44 and a larger fraction expressed CRTH2 than the controls. Eosinophils from children with EoE also had higher levels of galectin-10 mRNA and lower levels of FOXP3 mRNA. The eosinophils from children with EoE had lower levels of surface CD54 and of FOXP3 mRNA compared with the eosinophils from the adult patients. A key finding was the detection in healthy individuals of age-related differences in the levels of several eosinophil markers.

Conclusions

Children with EoE can be distinguished from healthy children based on the molecular patterns of their blood eosinophils. Age-related physiologic differences in eosinophil molecular patterns may partly explain the different blood eosinophil phenotypes in children versus adults with EoE.

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Differences in eosinophil molecular profiles between children and adults with eosinophilic esophagitis

Abstract

Background

Methods

Results

Conclusions

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Anti-Cancer Phytometabolites Targeting Cancer Stem Cells

Medicinal plants are a plentiful source of bioactive molecules with much structural diversity. In cancer treatment, molecules obtained from plants represent an attractive alternative to other treatments because several plant-derived compounds have exhibited lower toxicity and higher selectivity against cancer cells. In this review, we focus on the possible application of bioactive molecules obtained from plants against more primitive cell populations in cancers, cancer stem cells. Cancer stem cells are present in several kinds of tumors and are responsible for recurrences and metastases. Common anticancer drugs exhibit lower effectiveness against cancer stem cells because of their biological features. However, recently discovered natural phytometabolites exert cytotoxic effects on this rare population of cells in cancers. Therefore, this review presents the latest research on promising compounds from plants that can act as antitumor drugs and that mainly affect stem cell populations in cancers.

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Phase I trial of low-dose interleukin 2 therapy in patients with Wiskott-Aldrich syndrome

Publication date: Available online 14 February 2017
Source:Clinical Immunology
Author(s): Soma Jyonouchi, Brenda Gwafila, Lavesh A. Gwalani, Maria Ahmad, Chistopher Moertel, Cecil Holbert, Ji Young Kim, Nathan Kobrinsky, Sumita Roy-Ghanta, Jordan S. Orange
BackgroundLow dose IL-2 can restore the function of T and NK cells from Wiskott-Aldrich (WAS) patients. However, the safety of in vivo IL-2 in WAS is unknown.ObjectivesA phase-I study to assess safety of low dose IL-2 in WAS.MethodsPatients received 5 daily subcutaneous IL-2 injections, every 2months, for three courses. A "3+3" dose escalation method was used.Results6 patients received the 0.5millionunits/m²/day dose without serious adverse events. However, 2 of 3 patients receiving the 1millionunits/m²/day dose developed thrombocytopenia requiring platelet transfusions. A statistically significant platelet increase occurred in patients receiving the 0.5millionunits/m²/day dose. A trend toward higher T, B and NK cell numbers and higher T regulatory cell percentages was observed.ConclusionWe have identified a safe IL-2 dose for WAS patients. Additional trials are indicated to study the efficacy of this immunostimulant as a therapy for WAS.

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Screening for breast cancer

Publication date: Available online 13 February 2017
Source:Seminars in Oncology
Author(s): Kimberly S. Peairs, Youngjee Choi, Rosalyn W. Stewart, Heather F. Sateia
This review will give a general overview of the impact of breast cancer, as well as breast cancer risk factors, identification of high-risk groups, screening modalities, and guidelines for screening average-risk and high-risk individuals, including a case discussion of the primary care provider's approach to screening.

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Phase I trial of low-dose interleukin 2 therapy in patients with Wiskott-Aldrich syndrome

Decision Support for the Capacity Management of Bronchoscopy Devices: Optimizing the Cost-Efficient Mix of Reusable and Single-Use Devices Through Mathematical Modeling.

BACKGROUND: Increasing costs of material resources challenge hospitals to stay profitable. Particularly in anesthesia departments and intensive care units, bronchoscopes are used for various indications. Inefficient management of single- and multiple-use systems can influence the hospitals' material costs substantially. Using mathematical modeling, we developed a strategic decision support tool to determine the optimum mix of disposable and reusable bronchoscopy devices in the setting of an intensive care unit. METHODS: A mathematical model with the objective to minimize costs in relation to demand constraints for bronchoscopy devices was formulated. The stochastic model decides whether single-use, multi-use, or a strategically chosen mix of both device types should be used. A decision support tool was developed in which parameters for uncertain demand such as mean, standard deviation, and a reliability parameter can be inserted. Furthermore, reprocessing costs per procedure, procurement, and maintenance costs for devices can be parameterized. RESULTS: Our experiments show for which demand pattern and reliability measure, it is efficient to only use reusable or disposable devices and under which circumstances the combination of both device types is beneficial. CONCLUSIONS: To determine the optimum mix of single-use and reusable bronchoscopy devices effectively and efficiently, managers can enter their hospital-specific parameters such as demand and prices into the decision support tool. The software can be downloaded at: http://ift.tt/2lejUcI. (C) 2017 International Anesthesia Research Society

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Investigation on cellular uptake and pharmacodynamics of DOCK2-inhibitory peptides conjugated with cell-penetrating peptides

Publication date: Available online 13 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yusuke Adachi, Kotaro Sakamoto, Tadashi Umemoto, Yasunori Fukuda, Akiyoshi Tani, Taiji Asami
Protein–protein interaction between dedicator of cytokinesis 2 (DOCK2) and Ras-related C3 botulinum toxin substrate 1 (Rac1) is an attractive intracellular target for transplant rejection and inflammatory diseases. Recently, DOCK2-selective inhibitory peptides have been discovered, and conjugation with oligoarginine cell-penetrating peptide (CPP) improved inhibitory activity in a cell migration assay. Although a number of CPPs have been reported, oligoarginine was only one example introduced to the inhibitory peptides. In this study, we aimed to confirm the feasibility of CPP-conjugation approach for DOCK2-inhibitory peptides, and select preferable sequences as CPP moiety. First, we evaluated cell permeability of thirteen known CPPs and partial sequences of influenza A viral protein PB1-F2 using an internalization assay system based on luciferin–luciferase reaction, and then selected four CPPs with efficient cellular uptake. Among four conjugates of these CPPs and a DOCK2-inhibitory peptide, the inhibitory activity of a novel CPP, PB1-F2 fragment 5 (PF5), conjugate was comparable to oligoarginine conjugate and higher than that of the non-conjugated peptide. Finally, internalization assay revealed that oligoarginine and PF5 increased the cellular uptake of inhibitory peptides to the same extent. Hence, we demonstrated that CPP-conjugation approach is applicable to the development of novel anti-inflammatory drugs based on DOCK2 inhibition by investigating both cellular uptake and bioactivity.

Graphical abstract

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In vitro anticancer activity evaluation of new cationic platinum(II) complexes based on imidazole moiety

Publication date: Available online 14 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Isabella Rimoldi, Giorgio Facchetti, Giorgio Lucchini, Elisa Castiglioni, Silvia Marchianò, Nicola Ferri
The development and the synthesis of cationic platinum(II) complexes were realized and their cytotoxic activity was tested on triple negative breast cancer MDA-MB-231 cell line and in two cell lines poorly responsive to cisplatin (DLD-1 and MCF-7). The complex 2c resulted the most potent cytotoxic agent in MDA-MB-231 (IC50=61.9 µM) and more effective than cisplatin on both DLD-1 (IC50=57.4 µM) and MCF-7 (IC50=79.9 µM) cell lines. 2c showed different cellular uptake and pharmacodynamic properties than cisplatin, interfering with the progression of the M phase of the cell cycle. Thus, 2c represents a lead compound of a new class of cytotoxic agents with promising antitumor activity.

Graphical abstract

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Human carbonic anhydrase inhibitory profile of mono- and bis-sulfonamides synthesized via a direct sulfochlorination of 3-and 4-(hetero)arylisoxazol-5-amine scaffolds

Publication date: Available online 13 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mikhail Krasavin, Mikhail Korsakov, Zhanna Zvonaryova, Evgenii Semyonychev, Tiziano Tuccinardi, Stanislav Kalinin, Muhammet Tanç, Claudiu T. Supuran
Three distinct series of isoxazole-based primary mono- and bis-sulfonamides have been synthesized via direct sulfochlorination, each of them delivering nanomolar inhibitors of human carbonic anhydrase. Certain pronounced SAR trends have been established and rationalized by in silico docking. These findings expand the structure-activity knowledge base for heterocycle-containing sulfonamide carbonic anhydrase inhibitors and further validate the power of direct electrophilic sulfochlorination as a means of introducing the pharmacophoric primary sulfonamide group into structurally diverse aromatic precursors.

Graphical abstract

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5-Ethynylarylnaphthalimides as Antitumor Agents: Synthesis and Biological Evaluation

Publication date: Available online 13 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Patricia Quintana-Espinoza, Pedro Martín-Acosta, Ángel Amesty, Patricia Martín-Rodríguez, Isabel Lorenzo-Castrillejo, Leandro Fernández-Pérez, Félix Machín, Ana Estévez-Braun
A set of 5-ethynylarylnaphthalimides was synthesized by Sonogashira cross-coupling reactions and evaluated for antiproliferative and antitopoisomerase II in vitro activities. Furthermore docking studies of these molecules as DNA-intercalators were carried out and the in vivo DNA-damaging activity was also determined with the model organism Saccharomyces cerevisiae. From the obtained results three naphthalimides 6, 13 and 14 showed strong topoisomerase II inhibitory activity. These three molecules also presented good docking scores as DNA-intercalators using a self-complementary oligodeoxynucleotide d(ATGCAT)2 as a model, and compounds 13 and 14 were among the most cytotoxic in the in vivo DNA-damaging activity.

Graphical abstract

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Synthesis and Biological Evaluation of Novel N3-substituted Dihydropyrimidine Derivatives as T-Type Calcium Channel Blockers and Their Efficacy as Analgesics in Mouse Models of Inflammatory Pain

Publication date: Available online 13 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mohamed Teleb, Fang-Xiong Zhang, Junting Huang, Vinicius M Gadotti, Ahmed M. Farghaly, Omaima M. AboulWafa, Gerald W. Zamponi, Hesham Fahmy
Low-voltage-activated calcium channels are important regulators of neurotransmission and membrane ion conductance. A plethora of intracellular events rely on their modulation. Accordingly, they are implicated in many disorders including epilepsy, Parkinson's disease, pain and other neurological diseases. Among different subfamilies, T-type calcium channels, and in particular the CaV3.2 isoform, were shown to be involved in nociceptive neurotransmission. The role of CaV3.2 in pain modulation was supported by demonstrating selective antisense oligonucleotide-mediated CaV3.2 knockdown, in vivo antinociceptive effects of T-type blockers, and pain attenuation in CaV3.2 knockout formalin-induced pain model. These Emerging investigations have provided new insights into targeting T-type calcium channels for pain management. Within this scope, various T-type calcium channel blockers have been developed such as mibefradil and ethosuximide. Although being active, most of these molecules interact with other receptors as well. This addresses the need for T- selectivity. Few selective T-type channel blockers of diverse chemical classes were developed such as ABT-639 and TTA-P2. Interestingly, R(-) efonidipine which is a dihydropyridine (DHP) showed T-channel selectivity. Systematic modification of 1,4-dihydropyridine scaffold introduced novel derivatives with 40 fold T-type selectivity over L-type calcium channels. Along these lines, substitution of the DHP core with various analogues favored T-selectivity and may serve as novel pharmacophores. Several dihydropyrimidine (DHPM) mimics were introduced by Squibb as potential candidates. As a continuation of this approach, the current study describes the synthesis of Novel N3 substituted DHPMs with structure similarities to the active DHPs. Different functional groups were introduced to the N3 position through a spacer to gain more information about activity and selectivity. Furthermore, the spacer aims at improving the metabolic stability of the molecules. Initial screening data by whole patch clamp technique showed a robust inhibition of Cav3.2 T-type channels by eleven compounds. Interestingly, four compounds of these were efficient selective T-type blockers. Based on selectivity and efficiency, two compounds were selected for in vivo evaluation in mouse models of inflammatory pain. Results showed effective attenuation of nociception and mechanical hypersensitivity.

Graphical abstract

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Berberine as a chemical and pharmacokinetic marker of the butanol-extracted Food Allergy Herbal Formula-2

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Nan Yang, Kamal Srivastava, Ying Song, Changda Liu, Sool Cho, Yujuan Chen, Xiu-Min Li
RationaleFood Allergy Herbal Formula 2 (FAHF-2) provided protection against peanut anaphylaxis in a murine model and induced beneficial immune-modulation in humans. Butanol-refined FAHF-2, B-FAHF-2, retained safety and efficacy in the peanut allergic murine model at only 1/5 of FAHF-2 dosage. One compound, berberine, was isolated and identified in vitro as a bioactive component present in FAHF-2 and B-FAHF-2. The aim of this study was to investigate berberine as a chemical and pharmacokinetic marker of B-FAHF-2.MethodsThe consistency of constituents between B-FAHF-2 and FAHF-2 was tested. Peanut allergic C3H/HeJ mice were orally administered with 1mg of berberine or B-FAHF-2 containing anequivalent amount of berberine, and the ability to protect against peanut anaphylaxis and pharmacokinetic parameters were determined. Human intestinal epithelial cells (Caco-2) were cultured with berberine with or without the nine individual herbal constituents in B-FAHF-2, and the absorbed berberine levels were determined.ResultsBerberine is one of the major components in B-FAHF-2 and FAHF-2 formula. In a peanut allergic mouse model, B-FAHF-2, but not berberine, protected mice from anaphylaxis reactions. Pharmacokinetic profiles showed that the Cmax of B-FAHF-2 fed mice was 289.30±185.40ng/mL; whereas berberine alone showed very low bioavailability with Cmax value of 35.13±47.90ng/mL. Caco-2 cells influx assay showed that 7 of 9 herbal constituents in B-FAHF-2 increased berberine absorption at rates ranging from 18 to 205%.ConclusionsB-FAHF-2 remarkably increased the bioavailability of berberine. Berberine can be used as chemical and pharmacokinetic marker of B-FAHF-2. Other herbal components in B-FAHF-2 may facilitate the absorption of berberine.

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Peristomal psoriasis

Summary

Background

Psoriasis is a common skin condition, affecting 1.3–2.2% of the population. The prevalence of psoriasis has previously been reported as 11.2% in patients with Crohn disease (CD) and 5.7% in patients with ulcerative colitis.

Aim

To assess the prevalence of psoriasis around stoma sites and identify the most effective treatment.

Methods

A departmental database of all patients attendings stoma clinic was accessed between 1 May 2003 and 15 October 2015. Psoriasis response was determined by clinical resolution of psoriatic plaques in terms of erythema, induration, scaling and stoma bag adherence.

Results

Of 1665 patients, 78 (4.7%) had psoriasis affecting their abdominal stoma. In 8 patients (11.5%), a thicker hydrocolloid stoma bag barrier was sufficient to resolve the peristomal psoriasis. For 75 patients (96.2%), initial management was with nongreasy topical steroid scalp preparations and their usual barrier in the form of their stoma bag. Patients who did not respond to topical treatments initially or who experienced secondary failure (n = 16; 20.5%) received different systemic treatments [ciclosporin (n = 2), methotrexate (n = 2; 1 patient did not respond) or ultraviolet B narrowband phototherapy (n = 8; 2 nonresponders). One patient received infliximab and four patients received adalimumab for treatment of their CD, and their peristomal psoriasis also responded to these treatments. A further patient was prescribed adalimumab by the dermatology departmetn for the management of psoriasis vulgaris, with good response.

Conclusion

Peristomal psoriasis is common but potentially under-recognized. Selecting effective treatment that does not hinder bag appliance is crucial for effective management. Effective treatments include hydrocolloid dressings and topical corticosteroid regimens.

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Peristomal psoriasis

Summary

Background

Aim

To assess the prevalence of psoriasis around stoma sites and identify the most effective treatment.

Methods

Results

Conclusion

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Verrucous discoid lupus erythematosus in a child

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Verrucous discoid lupus erythematosus in a child

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Assessment of 105 Patients with Angiotensin Converting Enzyme-Inhibitor Induced Angioedema

Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study Design. Cohort study. Methods. This was a retrospective cohort study of 105 patients with angiotensin converting enzyme-inhibitor induced angioedema in the period 1995–2014. Results. The cohort consisted of 67 females and 38 males (F : M ratio 1.8), with a mean age of 63 [range 26–86] years. Female gender was associated with a significantly higher risk of angiotensin converting enzyme-inhibitor induced angioedema. 6.7% had a positive family history of angioedema. Diabetes seemed to be a protective factor with regard to angioedema. 95% experienced angioedema of the head and neck. 4.7% needed intubation or tracheostomy. 74 admissions took place during the study period with a total of 143 days spent in the hospital. The diagnosis codes most often used for this condition were "DT783 Quincke's oedema" and "DT78.4 Allergy unspecified". Complement C1 inhibitor was normal in all tested patients. Conclusion. Female gender predisposes to angiotensin converting enzyme-inhibitor induced angioedema, whereas diabetes seems to be a protective factor.

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Effectiveness of a commercial leptospiral vaccine on urinary shedding in naturally exposed sheep in New Zealand

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Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Emilie Vallée, Anne L. Ridler, Cord Heuer, Julie M. Collins-Emerson, Jackie Benschop, Peter R. Wilson
L. borgpetersenii serovar Hardjo and L. interrogans serovar Pomona are endemic in New Zealand sheep. An effective vaccine and vaccination strategy would protect both humans and livestock.Four to 12 lambs were selected from each of eight farms (total=84, vaccinated group), while four to 16 lambs (total=98) served as unvaccinated controls. A commercial Hardjo/Pomona vaccine was given at 1–6 weeks of age, 5–11 weeks later and 33–67 weeks later on seven farms and at 18 weeks of age and 5 weeks later on the eighth farm. Vaccinates and controls were grazed together. Blood was regularly collected from the control group to assess flock exposure. Urine was collected from both groups 26–82 weeks after the second vaccination and tested by quantitative PCR.Seroprevalence in controls at the time of urine sampling ranged from 2.7 to 98.2% for Hardjo and from 0 to 54.1% for Pomona with seroconversion occurring 13 to 67 weeks after the second vaccination in all but one farm where exposure had happened by the time of vaccination. The shedding prevalence adjusted for clustering in farms was 45.1% [95% CI 17.6–72.7] (for an observed number of 50/98) in the control animals and 1.8% [95% CI 0.0–10.1] (for an observed number of 5/84) in the vaccinated animals. The vaccine was 100% effective on five farms where animals were vaccinated before 12 weeks of age and before natural exposure occurred, but the effectiveness was 80% [0–97] on one farm where the lambs were exposed before vaccination and 65% [9–87] to 80% [0–97] on one farm where the animals were fully vaccinated by 24 weeks of age. The overall vaccine effectiveness was 86.3% [63.6–94.8%] despite maternal antibodies in some flocks at first vaccination. Vaccination timing seemed to be crucial in achieving optimum reduction in shedding in urine in vaccinated sheep.

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On the need to wait 4 weeks between two live attenuated vaccines

Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Luiz Antonio Bastos Camacho

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Editorial Board/Aims and Scope

Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9

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Comparison of platform technologies for assaying antibody to Ebola virus

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Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Dianna E. Wilkinson, Mark Page, Giada Mattiuzzo, Mark Hassall, Thomas Dougall, Peter Rigsby, Lindsay Stone, Philip Minor
BackgroundThe recent Ebola outbreak in West Africa led to the use of a variety of different platform technologies for assaying antibodies because of the difficulties of handling the live virus. The same types of method could be applied rapidly to other infections when they emerge. There is a need to compare quantitative results of different assays, which means that the assays must measure similar parameters and give comparable results.MethodsA collaborative study was carried out to establish an International Reference Reagent through WHO. Nine samples were sent to 16 laboratories and the results from 22 different assays compared to those obtained by neutralisation assays using the wild type virus.FindingsQuantitative correlation with the wild type neutralisation assays was very variable but generally poor, with only five of the twenty-two assays giving a correlation coefficient of 0.7 or greater; the five best assays included methods based on wild type and VSV pseudotype neutralisation and ELISA. They could be applicable to other rapidly emerging diseases. The remaining assays including neutralisation of lentiviral pseudotypes need further development.InterpretationThe assay platform should be chosen with care to ensure that it is fit for purpose. Many of the assays were not suitable for quantitation of antibody levels, a finding that is not surprising given the urgency with which they had to be implemented but some may be of generic value. Antibody titres in samples from a vaccine trial were comparable to those from convalescent patients or lower.FundingFunding was from the UK DoH and the Wellcome Tust.

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Placebo use in vaccine trials: Caution when using active vaccines as placebo

Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Stine Byberg, Christine Stabell Benn

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US medical students’ willingness to offer the HPV vaccine by vaccination status

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Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Abbey B. Berenson, Jacqueline M. Hirth, Erika L. Fuchs
We surveyed third-year medical students to assess whether personal vaccination status was associated with willingness to recommend the human papillomavirus vaccine to patients. A total of 231 students completed an anonymous survey evaluating their knowledge, attitudes, and personal vaccine history. Of 122 female students, 81 (66.4%) reported initiating the vaccine, as did 16 of 109 males (14.7%). Females and students ⩽25years old were more likely to be vaccinated. Knowledge did not vary by vaccination status, but anticipated behaviors did. Vaccinated students reported greater willingness to vaccinate adolescents before 15–16years of age (92.1% vs. 78.6%, p=0.008) and discuss vaccination at any type of medical visit (100% vs. 89.7%, p<0.001). Our findings suggest that prior experiences with the HPV vaccine may influence a provider's future actions. Thus, interventions that increase awareness of this relationship as well as vaccination rates among health care students may be beneficial.

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Tick-borne encephalitis in China: A review of epidemiology and vaccines

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Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Yi Xing, Heinz-Josef Schmitt, Adriano Arguedas, Junfeng Yang
Tick-borne encephalitis (TBE) has been shown to be endemic in northern and western China, including the three mountain areas in Heilongjiang, Jilin, Inner Mongolia, and Xinjiang. In addition, serology evidence shows that there is human infection in south-west provinces of China, including Xizang (Tibet) and Yunnan. TBE in China is caused by the Far Eastern TBE virus subtype and there is no biphasic course for disease presentation. The majority of TBE cases in China have occurred in people who were living or working in forests. TBE vaccines became available in China soon after the virus was identified in the country and they have been used for more than 60years to date, with different vaccine types used in different periods. Currently, an inactivated and purified whole-virus vaccine produced in a primary hamster kidney (PHK) cell line is used. Clinical trials have shown this vaccine to have higher immunogenicity and fewer adverse reactions than previous TBE vaccines. This paper provides a review on the epidemiology of TBE and the history of TBE vaccination in China.

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Integration of data from a safety net health care system into the Vaccine Safety Datalink

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Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Simon J. Hambidge, Colleen Ross, Jo Ann Shoup, Kris Wain, Komal Narwaney, Kristin Breslin, Eric S. Weintraub, Michael M. McNeil
BackgroundIn 2013 the Institute of Medicine suggested that the Vaccine Safety DataLink (VSD) should broaden its population by including data of more patients from low income and racially and ethnically diverse backgrounds. In response, Kaiser Permanente Colorado (KPCO) partnered with Denver Health (DH), an integrated safety net health care system, to explore the integration of DH data.MethodsWe compared three different methods (reference date of September 1, 2013): "Empanelment" (any patient who has had a primary care visit in the past 18months), "Proxy-enrollment" (two health care visits in 3years separated by 90days), and "Enrollment" in a managed care plan. For each of these methods, we compared cohort size, vaccination rates, socio-demographic characteristics, and health care utilization.ResultsThe empaneled population at DH provided the best comparison to KPCO. DH's empaneled population was 111,330 (57,173 adults; 54,157 children), while KPCO had 436,290 empaneled patients (336,462 adults; 99,828 children). Vaccination rates in both health care systems for empaneled patients were comparable. Two year-old up-to-date coverage rates were 83.2% (KPCO) and 86.9% (DH); rates for adolescent Tdap and MCV4 were 85.5% (KPCO) and 90.6% (DH). There were significant differences in the two populations in age, gender, race, preferred language, and % Federal Poverty Level (FPL) (DH 70.7%<100% FPL; KPCO 17.4%), as well as in healthcare utilization – for example pediatric emergency department utilization was twice as high at DH.ConclusionsUsing a cohort of "empaneled" patients, it is possible to integrate data from a safety net health care system that does not have a uniform managed care population into the VSD, and to compare vaccination rates, socio-demographic characteristics, and health care utilization across the two systems. The KPCO-DH collaboration may serve as a model for incorporating data from a safety net healthcare system into the VSD.

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Recommendations and offers for adult influenza vaccination, 2011–2012 season, United States

Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Katharine M. Benedict, Tammy A. Santibanez, Carla L. Black, Helen Ding, Samuel B. Graitcer, Carolyn B. Bridges, Erin D. Kennedy
BackgroundProvider recommendations and offers for influenza vaccination improve adult influenza vaccination coverage. Analysis was performed to describe receipt of influenza vaccination recommendations and offers among adults who visited a healthcare provider (HCP) during the 2011–2012 influenza season and describe differences between those receiving and not receiving recommendations and offers for influenza vaccination. Associations between influenza vaccination and receipt of recommendations and offers were examined.MethodsRespondents to a random digit dial telephone survey who had visited a HCP since July 1, 2011 were asked if they had received a recommendation for influenza vaccination. Those receiving a recommendation were asked if they received an offer for vaccination. Participants were characterized by demographic and access to health care variables. Logistic regression was used to examine the relationships between participant characteristics and recommendation alone, between participant characteristics and recommendation and offer, and between influenza vaccination and recommendation and offer.ResultsOf those who reported visiting a HCP, 43.8% reported receiving a recommendation for influenza vaccination. Of those who reported receiving a recommendation, 76.6% reported receiving an offer for influenza vaccination. Persons with high-risk conditions and persons over 65 years were more likely to receive recommendations for influenza vaccination when compared to those without high-risk conditions and 18–49 year olds, respectively. Those reporting receipt of a recommendation and offer for influenza vaccination were 1.76 times more likely and those reporting receipt of a recommendation but no offer were 1.72 times more likely to report being vaccinated for influenza controlling for all patient characteristics.ConclusionsLess than half of respondents reported receipt of recommendations and offers of influenza vaccination during the 2011–2012 influenza season and disparities exist between groups. All healthcare providers seeing adults should recommend or offer influenza vaccination for all patients at every visit during the influenza season.

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Vaccine draining lymph nodes are a source of antigen-specific B cells

Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Stephanie C. Pero, Yu-Jing Sun, Girja S. Shukla, Chelsea L. Carman, Christopher C. Krag, Cory Teuscher, Dimitry N. Krementsov, David N. Krag
PurposeOur research is focused on using vaccine draining lymph nodes as a source of immune cells to better understand the immune response and to attempt to generate new anti-cancer reagents. Following a vaccine, harvesting the lymph node can only be done once. We endeavored to determine the range of times that B cells secreting anti-KLH antibodies were present in the node of KLH-vaccinated mice.ResultsFollowing vaccination the total number of mononuclear cells (MNCs) increased in the vaccine-draining lymph node (VDN). The percentage of MNCs that were B cells nearly doubled. B cells recovered from the node that secreted anti-KLH antibodies were evident by day 7. The number continued to increase and then slowly decreased over the observed time range to 28days after vaccination. The VDN, compared to the spleen, the bone marrow and the nonVDN, contained a higher percentage of B cells that secreted anti-KLH antibodies.ConclusionsAfter a vaccine, there is a multi-week window of time when an increasing number of B cells are present in a VDN that secrete anti-KLH antibodies. These results support using the VDN as a source for B cells that secrete anti-vaccine antibodies.

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Introduction of inactivated poliovirus vaccine leading into the polio eradication endgame strategic plan; Hangzhou, China, 2010–2014

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Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Yan Liu, Jun Wang, Shijun Liu, Jian Du, Liang Wang, Wenwen Gu, Yuyang Xu, Shuyan Zuo, Erping Xu, Zhijie An
BackgroundChina's Expanded Program on Immunization (EPI) has provided 4 doses of oral poliovirus vaccine (OPV) since the 1970s. Inactivated poliovirus vaccine (IPV) became available in 2010 in Hangzhou as a private-sector, parent-chosen alternative to OPV. In 2015, WHO recommended that countries with all-OPV vaccination schedules introduce at least one dose of IPV, to mitigate risk associated with the withdrawal of type 2 OPV. We analyzed polio vaccine coverage and utilization in Hangzhou to determine patterns of IPV use and the occurrence of vaccine-associated paralytic polio (VAPP) in the various patterns identified.MethodsChildren born between 2010 and 2014 and registered in Hangzhou's Immunization Information System (HZIIS) were included. VAPP cases were detected through the acute flaccid paralysis surveillance system. We used descriptive epidemiological methods to determine IPV and OPV usage patterns and VAPP occurrence.ResultsHZIIS data from 566,894 children were analyzed. Coverage levels of polio vaccine were greater than 92% for each birth cohort. Percentages of children using OPV-only, IPV-only, and IPV/OPV sequential schedules were 70.57%, 27.01% and 2.41%, respectively. IPV-only schedule utilization increased by birth cohort regardless of geographical area or whether the child was locally-born. The highest use of an all-IPV schedule (79.85%) was among urban, locally-born children in the 2014 birth cohort. Five VAPP cases were identified during the study years; all cases occurred following the first polio vaccine dose, which was always OPV for the cases. Type 2 vaccine virus was isolated from 2 VAPP cases, and type 2 and type 3 vaccine virus was isolated from one VAPP case. The incidence of VAPP in the 2010–2014 birth cohorts was 3.76 per 1million doses of OPV.ConclusionChildren in Hangzhou had high polio vaccination coverage. IPV-only schedule use increased by year, and was highest in urban areas among locally-born children. All cases of VAPP were associated with the first dose of OPV.

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The rise and fall of pneumococcal serotypes carried in the PCV era

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Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Vanessa T. Devine, David W. Cleary, Johanna M.C. Jefferies, Rebecca Anderson, Denise E. Morris, Andrew C. Tuck, Rebecca A. Gladstone, Grace O'Doherty, Priyasharmila Kuruparan, Stephen D. Bentley, Saul N. Faust, Stuart C. Clarke
Streptococcus pneumoniae is a major cause of meningitis, sepsis and pneumonia worldwide. Vaccination using pneumococcal conjugate vaccines (PCV) has therefore been part of the UK's childhood immunisation programme since 2006. Here we describe pneumococcal carriage rates in children under five years of age attending the paediatric department of a large UK hospital in response to vaccine implementation over seven winter seasons from 2006 to 2013. S. pneumoniae (n=696) were isolated from nasopharyngeal swabs (n=2267) collected during seven consecutive winters, October to March, 2006/7 to 2012/13. This includes the period immediately following the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in 2006 in addition to pre- and post-PCV13 introduction in 2010. We show a decrease in PCV13 vaccine serotypes (VT) in the three years following PCV13 vaccine implementation (2010/11 to 2012/13). Serotype 6A represented the only observed VT following PCV13 implementation with all others (including PCV7 serotypes) absent from carriage. Overall pneumococcal carriage, attributable to non-VT (NVT), was consistent across all sampling years with a mean of 31·1%. The ten most frequently isolated NVTs were 6C, 11A, 15B, 23B, 15A, 21, 22F, 35F, 23A and 15C. Fluctuations in the prevalence of each were however noted. Comparing prevalence at 2006/07 with 2012/13 only 15A was shown to have increased significantly (p value of 0·003) during the course of PCV implementation. These data support the increasing evidence that the primary effect of PCVs is due to population immunity by reducing or eliminating the carriage of invasive VT serotypes. With IPD being increasingly attributed to non-vaccine serotypes, surveillance of carriage data continues to act as an early warning system for vaccine design and public health policy that require continual data of both carried pneumococcal serotypes and IPD attributed serotype data.

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IL-17A and complement contribute to killing of pneumococci following immunization with a pneumococcal whole cell vaccine

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Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Ivana B. Campos, Muriel Herd, Kristin L. Moffitt, Ying-Jie Lu, Michelle Darrieux, Richard Malley, Luciana C.C. Leite, Viviane M. Gonçalves
The pneumococcal whole cell vaccine (PWCV) has been investigated as an alternative to polysaccharide-based vaccines currently in use. It is a non-encapsulated killed vaccine preparation that induces non-capsular antibodies protecting mice against invasive pneumococcal disease (IPD) and reducing nasopharyngeal (NP) carriage via IL-17A activation of mouse phagocytes. Here, we show that PWCV induces antibody and IL-17A production to protect mice against challenge in a fatal aspiration-sepsis model after only one dose. We observed protection even with a boiled preparation, attesting to the stability and robustness of the vaccine. PWCV antibodies were shown to bind to different encapsulated strains, but complement deposition on the pneumococcal surface was observed only on serotype 3 strains; using flow cytometer methodology, variations in PWCV quality, as in the boiled vaccine, were detected. Moreover, anti-PWCV induces phagocytosis of different pneumococcal serotypes by murine peritoneal cells in the presence of complement or IL-17A. These findings suggest that complement and IL-17A may participate in the process of phagocytosis induced by PWCV antibodies. IL-17A can stimulate phagocytic cells to kill pneumococcus and this is enhanced in the presence of PWCV antibodies bound to the bacterial cell surface. Our results provide further support for the PWCV as a broad-range vaccine against all existing serotypes, potentially providing protection for humans against NP colonization and IPD. Additionally, we suggest complement deposition assay as a tool to detect subtle differences between PWCV lots.

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Control of infestations by Ixodes ricinus tick larvae in rabbits vaccinated with aquaporin recombinant antigens

Publication date: 1 March 2017
Source:Vaccine, Volume 35, Issue 9
Author(s): Marinela Contreras, José de la Fuente
BackgroundTick-borne diseases greatly impact human and animal health worldwide, and vaccines are an environmentally friendly alternative to acaricides for their control. Recent results have suggested that aquaporin (AQP) water channels have a key function during tick feeding and development, and constitute good candidate antigens for the control of tick infestations.MethodsHere we describe the effect of vaccination with the Ixodes ricinus AQP1 (IrAQP) and a tick AQP conserved region (CoAQP) on I. ricinus tick larval mortality, feeding and molting.ResultsWe demonstrated that vaccination with IrAQP and CoAQP had an efficacy of 32% and 80%, respectively on the control of I. ricinus larvae by considering the cumulative effect on reducing tick survival and molting.ConclusionsThe effect of the AQP vaccines on larval survival and molting is essential to reduce tick infestations, and extended previous results on the effect of R. microplus AQP1 on the control of cattle tick infestations. These results supports that AQP, and particularly CoAQP, might be a candidate protective antigen for the control of different tick species.

http://ift.tt/2krzrSp

Three-dimensional growth of human endothelial cells in an automated cell culture experiment container during the SpaceX CRS-8 ISS space mission – The SPHEROIDS project

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Jessica Pietsch, Samuel Gass, Stefano Nebuloni, David Echegoyen, Stefan Riwaldt, Christin Baake, Johann Bauer, Thomas J. Corydon, Marcel Egli, Manfred Infanger, Daniela Grimm
Human endothelial cells (ECs) were sent to the International Space Station (ISS) to determine the impact of microgravity on the formation of three-dimensional structures. For this project, an automatic experiment unit (EU) was designed allowing cell culture in space. In order to enable a safe cell culture, cell nourishment and fixation after a pre-programmed timeframe, the materials used for construction of the EUs were tested in regard to their biocompatibility. These tests revealed a high biocompatibility for all parts of the EUs, which were in contact with the cells or the medium used. Most importantly, we found polyether ether ketones for surrounding the incubation chamber, which kept cellular viability above 80% and allowed the cells to adhere as long as they were exposed to normal gravity. After assembling the EU the ECs were cultured therein, where they showed good cell viability at least for 14 days. In addition, the functionality of the automatic medium exchange, and fixation procedures were confirmed. Two days before launch, the ECs were cultured in the EUs, which were afterwards mounted on the SpaceX CRS-8 rocket. 5 and 12 days after launch the cells were fixed. Subsequent analyses revealed a scaffold-free formation of spheroids in space.

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Killing colon cancer cells through PCD pathways by a novel hyaluronic acid-modified shell-core nanoparticle loaded with RIP3 in combination with chloroquine

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Xueyan Hou, Chengli Yang, Lijing Zhang, Tingting Hu, Dan Sun, Hua Cao, Fan Yang, Gang Guo, Changyang Gong, Xiaoning Zhang, Aiping Tong, Rui Li, Yu Zheng
Due to extensive apoptosis defects and multidrug resistance, there is great interest regarding non-apoptotic programmed cell death (PCD) pathways, such as lysosomal-mediated programmed cell death (LM-PCD), necroptosis and autophagy. Because there is an intricate effector network among these PCD pathways, it is expected that they may act synergistically in cancer therapy. In this study, chloroquine (CQ) was found to significantly upregulate receptor-interacting protein kinase 3 (RIP3) expression, and RIP3 were involved in CQ-related autophagy. Overexpressed-eGFP-RIP3 co-localized with the selective autophagy receptor p62. mRIP3 overexpression in combination with CQ markedly increased the inhibition rate relative to that observed in the CQ-treatment group. Several experiments, including Hoechst staining, transmission electron microscopy (TEM) observation, the high-mobility group box 1 (HMGB1) release assay, Annexin V/PI staining and immunoblotting of proteins included in PCD pathways, verified that mRIP3 overexpression in combination with CQ induced lysosomal membrane permeabilization (LMP) and necroptosis of cancer cells, leading to cancer cell death. For tumor-targeted delivery, hyaluronic acid (HA)-modified, lipid-coated PLGA nanoparticles loaded with mRIP3-pDNA were prepared and characterized using a particle sizer, differential scanning calorimetry (DSC) and TEM. The nanoparticles exhibited ideal biocompatibility and good tumor-targeting efficiency, and the tumor inhibition rate of HA-Lip-PEI-mRIP3-PLGA-NPs + CQ was 80.2% in the CT26 mouse model. In this study, we attempted to treat tumors by inducing several alternative PCD pathways to shed light on the combination therapy of alternative PCD inducers.

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Ultrastructural Characterization of Mammary Analogue Secretory Carcinoma of the Salivary Glands: A Distinct Entity from Acinic Cell Carcinoma?

Abstract

Mammary analogue secretory carcinoma (MASC) of the salivary glands is a recently described neoplasm of the salivary glands with a characteristic morphology complemented by a specific cytogenetic translocation and gene rearrangements. Although immunophenotypic and cytogenetic differences allow for a more reliable distinction, ultrastructural features can also provide important information about the relationship between MASC, classic acinic cell carcinoma (AciCC), and AciCC intercalated duct cell-predominant variant. Following approval from the hospital's institutional review board, 7 cases of MASC, 8 cases of classic AciCC, and 4 cases of AciCC intercalated duct cell-predominant variant were retrieved from the pathology files of Massachusetts General Hospital from 2012 to 2015. Electron microscopy was performed using formalin-fixed, paraffin-embedded tissue. Ultrastructural features of all 19 neoplasms of the salivary glands were recorded. The predominant cell-types observed in MASC are those with intercalated/striated duct cell differentiation. These features include prominent invaginations of the cell surface studded with microvilli, and some intra- and intercellular lumina also with a microvillous surface. Classic AciCC dominant cell-type recapitulates acinar cell differentiation. These cells contain large intracytoplasmic zymogen-like granules. AciCC intercalated duct cell-predominant variant showed both cell populations in various proportions with the intercalated/striated duct cell type usually being the dominant one. MASC presents with distinctive ultrastructural features that allows its proper differentiation from classic AciCC. However, significant ultrastructural features overlaps between both AciCC intercalated duct cells-predominant and classic AciCC and MASC. These findings indicate a very close proximity between these tumors.

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Nonsurgical Laser Treatment (NSLT) of Central and Peripheral Nervous System Injuries

Photomedicine and Laser Surgery , Vol. 0, No. 0.

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Identification of differentially expressed proteins in retinoblastoma tumors using mass spectrometry-based comparative proteomic approach

Publication date: Available online 13 February 2017
Source:Journal of Proteomics
Author(s): Jasmine Naru, Ritu Aggarwal, Ashok Kumar Mohanty, Usha Singh, Deepak Bansal, Nandita Kakkar, Navneet Agnihotri
In India, retinoblastoma is among the top five childhood cancers. Children mostly present with extraocular extension and high risk features that results in unsatisfactory treatment and low survival rate. In addition, lack of potential therapeutic and prognostic targets is another challenge in the management of retinoblastoma. We studied comparative proteome of retinoblastoma patients (HPV positive and negative (n=4 each) and controls (n=4), in order to identify potential retinoblastoma-specific protein targets. 2D-DIGE coupled MALDI-TOF/TOF mass spectrometry identified 39 unique proteins. Highly deregulated proteins were GFAP,RBP3,APOA1,CRYAA,CRABP1,SAG and TF. Gene ontology (Panther 7.0) revealed majority of proteins to be associated with metabolic processes (26%) and catalytic activity (38%). 8 proteins were significantly upregulated in HPV positive vis-a-vis HPV negative cases. Patient group exhibited 12 upregulated and 18 downregulated proteins compared to controls. Pathway and network analysis (IPA software) revealed CTNNB1 as most significantly regulated signalling pathway in HPV positive than HPV negative retinoblastoma. The trends in transcriptional change of 9 genes were consistent with those at proteomic level. The Western blot analysis confirmed the expression pattern of RBP3,GFAP and CRABP1. We suggest GFAP,RBP3,CRABP1,CRYAAA,APOA1 and SAG as prospective targets that could further be explored as potential candidates in therapy and may further assist in studying the disease mechanism.SignificanceIn this study we evaluated tumor tissue specimens from retinoblastoma patients and identified 39 differentially regulated proteins compared to healthy retina. From these, we propose RBP3, CRABP1, GFAP, CRYAA, APOA1 and SAG as promising proteomic signatures that could further be explored as efficient prognostic and therapeutic targets in retinoblastoma. The present study is not only a contribution to the ongoing endeavour for the discovery of proteomic signatures in retinoblastoma, but, may also act as a starting point for future studies aimed at uncovering novel targets for further therapeutic interventions and improving patient outcomes.

Graphical abstract

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Immune checkpoint receptors in cancer: redundant by design?

Jing Li | Ling Ni | Chen Dong

http://ift.tt/2kNopdJ

Dendritic cells in cancer: the role revisited

Filippo Veglia | Dmitry I Gabrilovich

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Assessment of operating room airflow using air particle counts and direct observation of door openings

Publication date: Available online 13 February 2017
Source:American Journal of Infection Control
Author(s): Jonathan Teter, Isabella Guajardo, Tamrah Al-Rammah, Gedge Rosson, Trish M. Perl, Michele Manahan
BackgroundThe role of the operating room (OR) environment has been thought to contribute to surgical site infection rates. The quality of OR air, disruption of airflow, and other factors may increase contamination risks. We measured air particulate counts (APCs) to determine if they increased in relation to traffic, door opening, and other common activities.MethodsDuring 1 week, we recorded APCs in 5-minute intervals and movement of health care workers. Trained observers recorded information about traffic, door openings, job title of the opener, and the reason for opening.ResultsAt least 1 OR door was open during 47% of all readings. There were 13.4 door openings per hour during cases. Door opening rates ranged from 0.19-0.28 per minute. During this time, a total of 660 air measurements were obtained. The mean APCs were 9,238 particles (95% confidence interval [CI], 5,494- 12,982) at baseline and 14,292 particles (95% CI, 12,382-16,201) during surgery. Overall APCs increased 13% when either door was opened (P < .15). Larger particles that correlated to bacterial size were elevated significantly (P < .001) on door opening.ConclusionsWe observed numerous instances of verbal communication and equipment movement. Improving efficiency of communication and equipment can aid in reduction of traffic. Further study is needed to examine links between microbiologic sampling, outcome data, and particulate matter to enable study of risk factors and effects of personnel movement.

http://ift.tt/2le3Tnr

A randomized trial to determine the impact of a 5 moments for patient hand hygiene educational intervention on patient hand hygiene

Publication date: Available online 13 February 2017
Source:American Journal of Infection Control
Author(s): Herleen Rai, Shanina Knighton, Trina F. Zabarsky, Curtis J. Donskey
We conducted a randomized trial of a simple educational intervention encouraging patients to perform hand hygiene at 5 specific moments, including on entry of health care personnel into their room as a reminder of the importance of hand hygiene. The intervention resulted in a significant increase in patient hand hygiene.

http://ift.tt/2le8yWp

Atrial natriuretic peptide: a novel mediator for TGF-β1-induced epithelial-mesenchymal transition in 16HBE-14o and A549 cells

Publication date: Available online 13 February 2017
Source:Peptides
Author(s): Shuyuan Chu, Xiufeng Zhang, Yabing Sun, Yuanyuan Yu, Yaxi Liang, Ming Jiang, Jianwei Huang, Libing Ma
Atrial natriuretic peptide (ANP) is increasingly expressed on airway and inhibits pulmonary arterial remodeling. However, the role of ANP in remodeling of respiratory system is still unclear. The role of ANP on airway remodeling and the possible mechanism was explored in this study. Both human bronchial epithelial 16HBE-14o cells and alveolar epithelial A549 cells were stimulated by TGF-β1, ANP, cGMP inhibitor, PKG inhibitor, and cGMP analogue. The expressions of epithelial markers, mesenchymal markers, and Smad3 were assessed by quantitative real-time PCR and western blotting., Immunohistochemical staining was employed to assess Smad3 expression once it was silenced by siRNA in 16HBE-14o or A549 cells. Our results showed that the mRNA and protein expressions of E-Cadherin were decreased, whereas α-SMA expressions were increased after induction by TGF-β1 in 16HBE-14o and A549 cells. The E-Cadherin expressions were increased and α-SMA expressions were decreased after ANP stimulation. Inhibition of cGMP or PKG dexcrased E-Cadherin expression but increased α-SMA expression, which could be reversed by cGMP analogue. Moreover, the phosphorylated Smad3 expression was consistent with α-SMA expression. After smad3 was silenced, smad3 was mostly expressed in cytoplasm instead of nucleus as non-silenced cells during epithelial-mesenchymal transition (EMT). In conclusion, ANP inhibits TGF-β1-induced EMT in 16HBE-14o and A549 cells through cGMP/PKG signaling, by which it targets TGF-β1/Smad3 via attenuating phosphorylation of Smad3. These findings suggest the potential of ANP in the treatment on pulmonary diseases with airway remodeling.

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Complete Obstruction of Endotracheal Tube in an Infant with a Retropharyngeal and Anterior Mediastinal Abscess

Intraoperative ventilatory failure is not an uncommon complication; however, acute endotracheal obstruction by a foreign body or blood clot can be difficult to quickly discriminate from other causes. Once the diagnosis is made, quick action is needed to restore ventilation. The ultimate solution is to exchange the endotracheal tube; however, there can be other ways of resolving this in situations where reintubation would be difficult or unsafe. This case report discusses such an event in an infant with multiple airway challenges including a retropharyngeal and anterior mediastinal abscess. We have also formulated a pathway based on various case reports involving complete ETT obstruction.

http://ift.tt/2kNpBOt

Scratch behavior of epoxy coating containing self-assembled zirconium phosphate smectic layers

Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): Fan Lei, Marouen Hamdi, Peng Liu, Peng Li, Michael Mullins, Hongfeng Wang, Jiang Li, Ramanan Krishnamoorti, Shaoyun Guo, Hung-Jue Sue
A facile but efficient spray-coating method was recently developed to manufacture thin, flexible, and transparent epoxy films reinforced with well-exfoliated and highly-aligned α-zirconium phosphate (ZrP) nanoplatelets in smectic liquid crystalline order. Here, we investigate the scratch resistance of ZrP/epoxy nanocomposites prepared following the same spray-coating process. Comparison was made with neat epoxy coating to determine the impact of ZrP nanofillers. Tests were conducted with accordance to ASTM D7027/ISO 19252 scratch standard and scratch mechanisms were studied using different experimental tools. Results show that scratch resistance is considerably improved after introducing ZrP nanofillers to the epoxy coating. This was reflected by the delay in microcracking and plowing damages and the decrease of scratch coefficient of friction. This result is attributed to the significant role of exfoliated and aligned ZrP nanofillers in enhancing the mechanical properties of the epoxy matrix. The usefulness of the current study in developing new coating systems for high-performance applications is discussed.

Graphical abstract

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Adamantammonium as a novel functional group for anion exchange membranes with excellent comprehensive performances

Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): Jinlei Wang, Ying Chen, Qi Wei, Shanzhong Yang, Huagao Fang, Haibing Wei, Yunsheng Ding
In the pursuit of alkali stable cation as functional group for anion exchange membranes (AEMs), a novel adamantammonium (AdA) cation, which replacing methyl group of conventional trimethylammonium by an adamantyl group, was synthesized and investigated. ¹H NMR spectroscopy was employed to quantify the extent of decomposition and the results showed that > 99% adamantammonium remaining after 7 days immersion in 2 M NaOH (in D2O) at 80 °C. The AdA functionalized benzyl type poly(2,6-dimethyl phenylene oxide) polyelectrolytes, PPO-AdAs, were further prepared and characterized the AEM properties. Not only the chemical durability of these new PPO-AdA membranes, interestingly, but the conductivity and dimensional stability (water uptake and in-plane swelling) are superior to the benzylmethylammonium-benchmark PPO-based AEM (PPO-TMA). With the similar IEC values, the water uptake of PPO-AdA-41 sample is much lower than PPO-TMA-28, however, the conductivity of the former (15.7 mS cm^-1, chloride conductivity at 50 °C) is higher than the latter (13.3 mS cm^-1). Overall, the results of this study offer a base-stable cation, adamantammonium, and the corresponding adamantammonium-based AEMs for fuel cell applications with the advantages of chemical stability, enhanced conductivity and excellent dimensional stability as well as facial functionalization technique.

Graphical abstract

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A ‘grafting from’ approach to polymer nanorods for pH-triggered intracellular drug delivery

Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): Théophile Pelras, Hien T.T. Duong, Byung J. Kim, Brian S. Hawkett, Markus Müllner
We report the use of the 'grafting from' approach to produce inherently rod-shaped polymer nanoparticles with triggered drug release. Cylindrical polymer brushes (CPBs) can be directly used to yield functional polymer nanorods for pH-sensitive drug release of doxorubicin (DOX). Water-soluble CPBs have been produced via a straightforward one-step grafting of vinyl benzaldehyde (VBA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) comonomers, in which the VBA distributed throughout the CPBs provides a cost-effective and simple functionality for the subsequent conjugation of DOX using imine chemistry. Atomic force microscopy (AFM) underlined the rod-like conformation of the CPBs prior and after drug conjugation. Fluorescence spectroscopy studies revealed faster drug release in acidic environments (pH 5.0) compared to physiological pH conditions (pH 7.4). Fluorescence lifetime imaging microscopy (FLIM) and in vitro cell studies further highlighted the intracellular DOX release from the CPB drug carriers within MCF-7 breast cancer cells.

Graphical abstract

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Segregated network formation of multiwalled carbon nanotubes in natural rubber through surfactant assisted latex compounding: A novel technique for multifunctional properties

Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): Neena George, P.K. Bipinbal, Bhavya Bhadran, A. Mathiazhagan, Rani Joseph
In the present study Vulcastab VL (polyethylene oxide condensate) has been used as a non-ionic surfactant to get stable aqueous dispersions of multiwalled carbon nanotubes (MWCNTs). Sonication time and surfactant concentration were optimised by UV-vis spectroscopy and dynamic light scattering technique. Homogeneously dispersed surfactant coated individual MWCNTs in water were clearly evident from Transmission electron microscopy (TEM). Natural rubber –Multiwalled carbon nanotube (NR-MWCNT) nanocomposites were prepared by latex stage mixing. Instead of being randomly dispersed, MWCNTs were found to retain at the boundary of rubber particles resulting in a segregated network as evidenced from TEM. Addition of very small amount of MWCNT showed remarkable improvement in mechanical, thermal, electrical and barrier properties of NR. Segregated network of CNTs resulted in very low electrical percolation threshold (0.043 vol%) for the composite with enhanced dielectric properties.

Graphical abstract

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Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers

Background.

Metastatic recurrence after treatment for locoregional cancer is a major cause of morbidity and cancer-specific mortality. Distinguishing metastatic recurrence from the development of a second primary cancer has important prognostic and therapeutic value and represents a difficult clinical scenario. Advances beyond histopathological comparison are needed. We sought to interrogate the ability of comprehensive genomic profiling (CGP) to aid in distinguishing between these clinical scenarios.

Materials and Methods

We identified three prospective cases of recurrent tumors in patients previously treated for localized cancers in which histologic analyses suggested subsequent development of a distinct second primary. Paired samples from the original primary and recurrent tumor were subjected to hybrid capture next-generation sequencing-based CGP to identify base pair substitutions, insertions, deletions, copy number alterations (CNA), and chromosomal rearrangements. Genomic profiles between paired samples were compared using previously established statistical clonality assessment software to gauge relatedness beyond global CGP similarities.

Results.

A high degree of similarity was observed among genomic profiles from morphologically distinct primary and recurrent tumors. Genomic information suggested reclassification as recurrent metastatic disease, and patients received therapy for metastatic disease based on the molecular determination.

Conclusions.

Our cases demonstrate an important adjunct role for CGP technologies in separating metastatic recurrence from development of a second primary cancer. Larger series are needed to confirm our observations, but comparative CGP may be considered in patients for whom distinguishing metastatic recurrence from a second primary would alter the therapeutic approach. The Oncologist 2017;22:000–000

Implications for Practice: Distinguishing a metastatic recurrence from a second primary cancer can represent a difficult clinicopathologic problem but has important prognostic and therapeutic implications. Approaches to aid histologic analysis may improve clinician and pathologist confidence in this increasingly common clinical scenario. Our series provides early support for incorporating paired comprehensive genomic profiling in clinical situations in which determination of metastatic recurrence versus a distinct second primary cancer would influence patient management.

http://ift.tt/2kNirtg

Fluorescent carbon dots and their sensing applications

Publication date: Available online 13 February 2017
Source:TrAC Trends in Analytical Chemistry
Author(s): Xiangcheng Sun, Yu Lei
Fluorescent carbon dots (CDs) are a new class of carbon nanomaterials and have demonstrated excellent optical properties, good biocompatibility, great aqueous solubility, low cost, simple synthesis, etc. Since their discovery, various synthesis methods using different precursors were developed, which were mainly classified as top-down and bottom-up approaches. CDs have presented many applications, and this review article mainly focuses on the development of CDs based fluorescent sensors in recent 5 years. The sensing mechanisms, senor design and sensing properties to various targets are summarized. A broad range of analytes including cations, anions, small molecules, macromolecules, cells and bacteria have been discussed. In addition, the challenges and future directions for CDs as sensing materials are also presented.

Graphical abstract

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Cholesterol Levels Should Play a More Important Role in Identifying Statin Recipients.

Author: Durrington, Paul N. MD; Soran, Handrean MSc, MD

Page: 627-629

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Potential for Net Benefit Should Guide Preventive Therapy.

Author: Stone, Neil J. MD; Robinson, Jennifer G. MD, MPH

Page: 630-632

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Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial.

Author: Hernaez, Alvaro PharmD, MSc; Castaner, Olga MD, PhD; Elosua, Roberto MD, PhD; Pinto, Xavier MD, PhD; Estruch, Ramon MD, PhD; Salas-Salvado, Jordi MD, PhD; Corella, Dolores PharmD, PhD; Aros, Fernando MD, PhD; Serra-Majem, Lluis MD, PhD; Fiol, Miquel MD, PhD; Ortega-Calvo, Manuel MD, PhD; Ros, Emilio MD, PhD; Martinez-Gonzalez, Miguel Angel MD, PhD; de la Torre, Rafael PharmD, PhD; Lopez-Sabater, M. Carmen PharmD, PhD; Fito, Montserrat MD, PhD

Page: 633-643

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Response by Bakris to Letter Regarding Article, "The Implications of Blood Pressure Measurement Methods on Treatment Targets for Blood Pressure".

Author: Bakris, George MD

Page: e47

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Mediterranean Approach to Improving High-Density Lipoprotein Function.

Author: Rader, Daniel J. MD

Page: 644-647

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Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients: An APEX Trial Substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban).

Author: Gibson, C. Michael MS, MD; Chi, Gerald MD; Halaby, Rim MD; Korjian, Serge MD; Daaboul, Yazan MD; Jain, Purva MPH; Arbetter, Douglas MPH; Goldhaber, Samuel Z. MD; Hull, Russel MBBS; Hernandez, Adrian F. MD; Gold, Alex MD; Bandman, Olga MD; Harrington, Robert A. MD; Cohen, Alexander T. MD; On Behalf of the APEX Investigators

Page: 648-655

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Is There a Role for Betrixaban to Prevent Stroke in Medically Ill Patients?.

Author: Quinlan, Daniel J. MBBS; Eikelboom, John W. MBBS; Hart, Robert G. MD

Page: 656-658

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Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial.

Author: Saito, Yoshihiko MD, PhD; Okada, Sadanori MD, PhD; Ogawa, Hisao MD, PhD; Soejima, Hirofumi MD, PhD; Sakuma, Mio MD, PhD; Nakayama, Masafumi MD, PhD; Doi, Naofumi MD, PhD; Jinnouchi, Hideaki MD, PhD; Waki, Masako MD, PhD; Masuda, Izuru MD, PhD; Morimoto, Takeshi MD, PhD; For the JPAD Trial Investigators

Page: 659-670

http://ift.tt/2lDT3Id

Neurological Injury and Cerebral Blood Flow in Single Ventricles Throughout Staged Surgical Reconstruction.

Author: Fogel, Mark A. MD; Li, Christine BS; Elci, Okan U. PhD; Pawlowski, Tom BS; Schwab, Peter J. BS; Wilson, Felice RN, BSN; Nicolson, Susan C. MD; Montenegro, Lisa M. MD; Diaz, Laura MD; Spray, Thomas L. MD; Gaynor, J. William MD; Fuller, Stephanie MD; Mascio, Christopher MD; Keller, Marc S. MD; Harris, Matthew A. MD; Whitehead, Kevin K. MD; Bethel, Jim PhD; Vossough, Arastoo MD; Licht, Daniel J. MD

Page: 671-682

http://ift.tt/2lJeRy0

Stress-Activated Kinase Mitogen-Activated Kinase Kinase-7 Governs Epigenetics of Cardiac Repolarization for Arrhythmia Prevention.

Author: Chowdhury, Sanjoy K. MBBS, PhD; Liu, Wei PhD, MD; Zi, Min MD; Li, Yatong PhD, MD; Wang, Shunyao MSc; Tsui, Hoyee PhD; Prehar, Sukhpal MSc; Castro, Simon PhD; Zhang, Henggui PhD; Ji, Yong PhD, MD; Zhang, Xiuqin PhD, MD; Xiao, Ruiping PhD, MD; Zhang, Rongli MD; Lei, Ming PhD, MD; Cyganek, Lukas PhD; Guan, Kaomei PhD; Millar, Catherine B. PhD; Liao, Xudong PhD; Jain, Mukesh K. MD; Boyett, Mark R. PhD; Cartwright, Elizabeth J. PhD; Shiels, Holly A. PhD; Wang, Xin PhD, MD

Page: 683-699

http://ift.tt/2lDT3rH

Cardiovascular and Ventilatory Consequences of Laparoscopic Surgery.

Author: Atkinson, Tamara M. MD; Giraud, George D. MD, PhD; Togioka, Brandon M. MD; Jones, Daniel B. MD; Cigarroa, Joaquin E. MD

Page: 700-710

http://ift.tt/2lJapiQ

Recommendations for the Implementation of Telehealth in Cardiovascular and Stroke Care: A Policy Statement From the American Heart Association.

Author: Schwamm, Lee H. MD, FAHA, Chair; Chumbler, Neale PhD; Brown, Ed MD; Fonarow, Gregg C. MD, FAHA; Berube, David PhD; Nystrom, Karin MSN, APRN, FAHA; Suter, Robert DO, MHA, FAHA; Zavala, Mirian DNS, RN; Polsky, Daniel PhD; Radhakrishnan, Kavita RN, MSEE, PhD; Lacktman, Nathaniel JD; Horton, Katherine RN, MPH, JD; Malcarney, Mary-Beth MPH, JD; Halamka, John MS, MD; Tiner, A. Colby MA; On behalf of the American Heart Association Advocacy Coordinating Committee

Page: e24-e44

http://ift.tt/2lE0xL8

Is This Pacemaker Functioning Abnormally?.

Author: Garcia-Izquierdo, Eusebio MD; Vilches, Silvia MD; Castro, Victor MD

Page: 711-713

http://ift.tt/2lJlhgI

Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease Other Than Significant Mitral Stenosis and Mechanical Valves: A Meta-Analysis.

Author: Siontis, Konstantinos C. MD; Yao, Xiaoxi PhD; Gersh, Bernard J. MB, ChB, DPhil; Noseworthy, Peter A. MD

Page: 714-716

http://ift.tt/2lDT133

Letter by Messerli et al Regarding Article, "The Implications of Blood Pressure Measurement Methods on Treatment Targets for Blood Pressure".

Author: Messerli, Franz H. MD; Bangalore, Sripal MD, MHA; Kjeldsen, Sverre E. MD

Page: e45-e46

http://ift.tt/2lJ5xdM

Correction to: Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

Author:

Page: e48

http://ift.tt/2lJkT1L

Correction to: Use of Sodium Glucose Cotransporter 2 Inhibitors in the Hands of Cardiologists: With Great Power Comes Great Responsibility.

Author:

Page: e49

http://ift.tt/2lE1Rhr

Beneficial Effects on Pregnancy Outcomes of Thyroid Hormone Replacement for Subclinical Hypothyroidism

Background. Hypothyroidism and raised thyroid antibody levels have been associated with adverse obstetrical outcomes. Several studies have investigated causal associations, but results have been inconsistent and few studies have reported the effects of thyroxine replacement therapy on pregnancy outcomes in hypothyroid patients. Objective. The primary study objective was to determine the outcome of pregnancies in women diagnosed with overt and subclinical hypothyroidism (SCH) (serum TSH > 2.5 mIU/L) and those with elevated circulating thyroid autoantibody levels in the first trimester of pregnancy and after the institution of appropriate thyroxine replacement therapy to maintain the serum TSH ≤ 2.5 mIU/L. Study Design. This prospective observational study was undertaken between 2013 and 2016. Blood samples were taken from 1025 women at presentation for thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies (TGAb), and thyroid peroxidase antibodies (TPOAb). Those with a TSH > 2.5 mIU/L were treated with thyroxine and managed appropriately to ensure that the TSH was maintained ≤2.5 mIU/L. Outcomes in these patients were compared to those in euthyroid patients. Maternal antenatal complications and perinatal outcomes were recorded. Results. There were a total of 1025 patients of whom 382 (37.5%) were nulliparous. 10.1% had a TSH level > 2.5 mIU/L and 18.2% had at least one raised thyroid antibody level. No differences in adverse outcomes of pregnancy were evident in women treated for SCH or overt hypothyroidism compared to the euthyroid group. There was also no association between raised thyroid antibodies and adverse pregnancy outcomes in either group. Conclusion. There were no adverse outcomes of pregnancy found in pregnant women who had been diagnosed and treated with thyroxine for SCH at the time of presentation when compared to euthyroid patients. There was also no relationship with thyroid antibodies and adverse pregnancy outcomes in the two groups. It is not possible to unequivocally advocate for thyroxine replacement in pregnant women with subclinical and overt hypothyroidism until large scale randomized controlled trials are performed.

http://ift.tt/2klgtSs

When and Where Learning is Taking Place: Multisynaptic Changes in Strength During Different Behaviors Related to the Acquisition of an Operant Conditioning Task by Behaving Rats

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Although it is generally assumed that brain circuits are modified by new experiences, the question of which changes in synaptic efficacy take place in cortical and subcortical circuits across the learning process remains unanswered. Rats were trained in the acquisition of an operant conditioning in a Skinner box provided with light beams to detect animals' approaches to lever and feeder. Behaviors such as pressing the lever, eating, exploring, and grooming were also recorded. Animals were chronically implanted with stimulating and recording electrodes in hippocampal, prefrontal, and subcortical sites relevant to the task. Field synaptic potentials were evoked during the performance of the above-mentioned behaviors and before, during, and after the acquisition process. Afferent pathways to the hippocampus and the intrinsic hippocampal circuit were slightly modified in synaptic strength during the performance of those behaviors. In contrast, afferent and efferent circuits of the medial prefrontal cortex were significantly modified in synaptic strength across training sessions, mostly at the moment of the largest change in the learning curve. Performance of behaviors nondirectly related to the acquisition process (exploring, grooming) also evoked changes in synaptic strength across training. This study helps to understand when and where learning is being engraved in the brain.</span>

http://ift.tt/2l29BX8

Beneficial Effects on Pregnancy Outcomes of Thyroid Hormone Replacement for Subclinical Hypothyroidism

High-efficiency breeding of early-maturing rice cultivars via CRISPR/Cas9-mediated genome editing

Publication date: Available online 13 February 2017
Source:Journal of Genetics and Genomics
Author(s): Xiufeng Li, Wenjia Zhou, Yuekun Ren, Xiaojie Tian, Tianxiao Lv, Zhenyu Wang, Jun Fang, Chengcai Chu, Jie Yang, Qingyun Bu

http://ift.tt/2kEAteQ

Formal mentorship in a surgical residency training program: a prospective interventional study

Otolaryngology-Head and Neck surgery resident physicians (OHNSR) have a high prevalence of burnout, job dissatisfaction and stress as shown within the literature. Formal mentorship programs (FMP) have a proven...

http://ift.tt/2lJPcWZ

Developing a new diagnostic algorithm for human papilloma virus associated oropharyngeal carcinoma: an investigation of HPV DNA assays

Human papilloma virus (HPV) has been implicated in the development of a large proportion of oropharyngeal squamous cell carcinoma (OPSCC). Current techniques used to diagnose HPV etiology require histopatholog...

http://ift.tt/2kNnni1

Does drug-induced sleep endoscopy change the surgical decision in surgically naïve non-syndromic children with snoring/sleep disordered breathing from the standard adenotonsillectomy? A retrospective cohort study

Adenotonsillectomy is the most commonly performed operation for pediatric snoring/sleep disordered breathing (S/SDB). However, 20–40% of patients will fail to improve. Drug-induced sleep endoscopy (DISE) may p...

http://ift.tt/2lKfGHF

Formal mentorship in a surgical residency training program: a prospective interventional study

Developing a new diagnostic algorithm for human papilloma virus associated oropharyngeal carcinoma: an investigation of HPV DNA assays

Does drug-induced sleep endoscopy change the surgical decision in surgically naïve non-syndromic children with snoring/sleep disordered breathing from the standard adenotonsillectomy? A retrospective cohort study

Placeboeffekt in Studien zur allergenspezifischen Immuntherapie mit Inhalationsallergenen

Zusammenfassung

Placeboeffekte spielen bei der Therapie allergischer Erkrankungen eine wesentliche Rolle. In dieser Arbeit wurden die doppelblind-placebokontrollierten Studien zur allergenspezifischen Immuntherapie (ASIT) mit Inhalationsallergenen (Birke, Gräser, Milben), die in den im Juli 2016 aktualisierten Tabellen zur deutschen S2k-Leitlinie zur ASIT IgE-vermittelter Erkrankungen aufgelistet werden, gezielt hinsichtlich ihrer beschriebenen Placeboeffekte analysiert. Als Placebo wurde meist Verum ohne Allergen eingesetzt, bei subkutaner Applikation teilweise Histamin zugefügt. Detaillierte Aussagen zum reinen Placeboeffekt sind in keiner der untersuchten 33 Studien zu finden. Lediglich in einer Studie wurde der Symptom-Medikations-Score (SMS) in einer adäquaten Baseline-Periode untersucht. Ein unbehandelter Arm war in keiner Studie zu finden. Indirekte Hinweise zeigen bei retrospektiven, subjektiven Parametern deutliche Placeboeffekte bei bis zu 77 % der Probanden. Bekannte Einflussfaktoren auf den Placeboeffekt wie Alter, Geschlecht, Applikationsart/Zusammensetzung des Placebos, individuelle und kulturelle Unterschiede, Symptomschwere zu Beginn und Wahrscheinlichkeit, das Verum zu erhalten, wurden nicht adressiert und konnten anhand der verfügbaren Daten nicht bewertet werden. Zusammenfassend wurde der Placeboeffekt in ASIT-Studien bisher nicht ausreichend untersucht. Trotz des erheblichen Zeit- und Kostenaufwands sollten zukünftige ASIT-Studien den SMS in einer adäquaten Baseline-Periode vor Studienbeginn erheben und möglichst einen unbehandelten Vergleichsarm integrieren. Ein besseres Verständnis der Placeboeffekte in Studien zur allergenspezifischen Immuntherapie wird zu einem optimierten Studiendesign und einer verbesserten Einschätzung des Therapieeffekts führen.

http://ift.tt/2lIUn8T

Merkelzellkarzinom: kutane Manifestation einer hochmalignen Prä-/pro-B-Zell-Neoplasie?

Zusammenfassung

Das Merkelzellkarzinom (MZK) ist eine relativ seltene, jedoch hochmaligne neoplastische Proliferation der Haut, die v. a. bei älteren und immunsupprimierten Patienten vorkommt. Die Identifizierung des Merkelzell-Polyomavirus (MCPyV) 2008 hat das Verständnis der Ätiopathogenese des MZK grundlegend verändert. Etwa 80 % der MZK sind MCPyV-positiv, und das Virus ist zumeist klonal in die Tumor-DNA integriert. Die kürzlich veröffentlichen Ergebnisse klinischer Studien zur Blockade des „PD-1 immune checkpoint pathway" sind vielversprechend für zukünftige Therapieoptionen des MZK. Trotz dieser grundlegenden Erkenntnisgewinne bleibt der zelluläre Ursprung des MZK bis heute unbekannt. Aufgrund der Histologie, Genexpression und molekularer Analysen haben wir kürzlich die Hypothese formuliert, dass MZK ihren zellulären Ursprung in Prä-/pro-B-Zellen nehmen. In dieser Arbeit werden die derzeitigen Konzepte zum zellulären Ursprung des MZK diskutiert, d. h. die Merkelzelle, die (epi)dermale Stammzelle und die Prä‑/pro-B-Zelle. Der Fokus dieser Arbeit liegt auf dem Konzept der Prä‑/pro-B-Zellen als zellulärer Ursprung der MZK, da dieses – nach Meinung der Autoren – möglicherweise auch als Grundlage dienen könnte zum besseren Verständnis anderer kleinzelliger Tumoren unbekannten zellulären Ursprungs, z. B. kleinzellige Karzinome der Lunge, und anderer anatomischer Lokalisationen. Zudem eröffnet es möglicherweise neue Therapieoptionen für klinisch weit fortgeschrittene MZK.

http://ift.tt/2lJbzuM

Paravirale Exantheme

Zusammenfassung

Unter paraviralen Exanthemen sind distinkte Hauterkrankungen aufzufassen, die auf Infektionen mit unterschiedlichen Viren zurückzuführen sind. Auch wenn sich bisher bei einigen Exanthemerkrankungen kein Virus identifizieren ließ, sprechen doch das Manifestationsalter der Patienten, der klinische Verlauf des Exanthems und extrakutane Symptome für eine virale Genese. Während viele Virusexantheme direkte Folge der Infektion darstellen, reflektieren paravirale Exantheme die Antwort des Immunsystems auf die Infektionserreger. Viren lassen sich dann nicht in der Haut nachweisen. Zu typischen paraviralen Exanthemen gehören Gianotti-Crosti-Syndrom, Pityriasis rosea, Pityriasis lichenoides, „papular-purpuric gloves and socks syndrome" sowie das asymmetrische periflexurale Exanthem. Das unilaterale mediothorakale Exanthem und die eruptive Pseudoangiomatose sind selten, und die eruptive Hypomelanose wurde erst kürzlich beschrieben.

http://ift.tt/2kN6FiA

Genetic and biochemical changes of the serotonergic system in migraine pathobiology

Migraine is a brain disorder characterized by a piercing headache which affects one side of the head, located mainly at the temples and in the area around the eye. Migraine imparts substantial suffering to the...

http://ift.tt/2lDPe60

Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study

In the emergency setting, non-traumatic headache is a benign symptom in 80% of cases, but serious underlying conditions need to be ruled out.

http://ift.tt/2ldK13C

Effect of Vitamin D Deficiency on the laryngo-pharyngeal Tract

To investigate the effect of vitamin D deficiency on the laryngopharyngeal tract.

http://ift.tt/2kNpUZx

Bilateral Sinonasal Extramedulary Plasmacytoma treated with radiotherapy and a Medial Maxillectomy with a Denker's procedure

Extramedullary plasmacytoma (EMP), multiple myeloma (MM), and solitary plasmacytoma of the bone (SPB) are each classified as distinct manifestations of a disease continuum with varying symptoms, treatment regimens, and prognostic implications. While the etiology for each of these neoplastic entities is due to a derangement of plasma cells, these B-cell neoplasms are indistinguishable histologically [1] [1]. EMP, a rare neoplasm, accounts for approximately 2–3% of all plasma cell tumors, SPB accounts for up to 4–6% of cases, and multiple myeloma for 91–94% [1] [2] [3].

http://ift.tt/2l28tTk

Lobular capillary hemangiomas: Case report and review of literature of vascular lesions of the nasal cavity

Vascular tumors of the nasal cavity can represent a variety of pathologies. In this case report, we discuss two patients presenting with a large vascular lesion occupying the nasal cavity. Significant bleeding was encountered during the initial attempts for endoscopic surgical resection. One lesion was successfully excised following preoperative embolization while a second following sphenopalatine artery ligation vascular ligation. In both cases, final pathology showed lobular capillary hemangioma (LCH).

http://ift.tt/2kN9lgt

Is histopathological diagnosis useful in choosing treatments for tumors of the temporal bone?

We were pleased to read the article by Olcott C. andStrasnick B. titled "A blue middle ear mass: Cholesterol granuloma mimicking a glomus tumor and endolymphatic sac tumor". Am J Otolaryngol.2017;38(1):100-102 [1], which presents very important clinical observations. Based on our experience and the literature review, we would like to present some comments on this problem. The benign tumors of the temporal bone (TB) have been divided into three groups: cholesterol granuloma (CG), glomus tumor (GT) and endolymphatic sac tumor (ELST) [1].

http://ift.tt/2l28vea

Effect of Vitamin D Deficiency on the laryngo-pharyngeal Tract

To investigate the effect of vitamin D deficiency on the laryngopharyngeal tract.

http://ift.tt/2kNpUZx

Bilateral Sinonasal Extramedulary Plasmacytoma treated with radiotherapy and a Medial Maxillectomy with a Denker's procedure

Lobular capillary hemangiomas: Case report and review of literature of vascular lesions of the nasal cavity

Is histopathological diagnosis useful in choosing treatments for tumors of the temporal bone?

Tinnitus – Klinik und Therapie

Laryngo-Rhino-Otol 2017; 96: 47-59
DOI: 10.1055/s-0042-119419

Tinnitus ist ein Phantomgeräusch, das ein Symptom verschiedener Störungen sein kann, z. B. durch Hörverlust, kardiovaskuläre oder neurologische Erkrankungen, Diabetes oder Tumoren. Bei dekompensiertem Tinnitus leiden die Patienten aufgrund ihrer Unfähigkeit, die auditive Aufmerksamkeit vom Tinnitus-Ton abzulenken, an Schlaflosigkeit, Konzentrationsproblemen und anderen psychologischen Störungen. In extremen Fällen kann es zu Symptomen einer manifesten Depression kommen. Der auditorische Charakter des Tinnitus veranlasst die Patienten überwiegend, Hilfe bei HNO-Ärzten zu suchen. Das erste Ziel der Behandler besteht darin, die Ursache des Tinnitus zu bestimmen und seine audiologischen Eigenschaften zu messen. Das zweite Ziel ist es, die tinnitusinduzierte Belastung einzuschätzen, den Schweregrad zu bewerten und u. U. weiterführende Therapien einzuleiten. Der Artikel beschreibt die audiologischen und psychologischen Eigenschaften des Tinnitus, derzeitige Klassifikationsmodelle und die therapeutischen Ansätze auf diesem Gebiet.
[...]

Article in Thieme eJournals:
Table of contents | Abstract | CME online | Full text

http://ift.tt/2kEiN2R

Eosinophile Ösophagitis – Neues zur Pathogenese, Diagnostik und Therapie

Laryngo-Rhino-Otol 2017; 96: 11-21
DOI: 10.1055/s-0042-119417

Die eosinophile Ösophagitis (EoE) ist eine Krankheitsentität, der man erst im letzten Jahrzehnt eine erhöhte Aufmerksamkeit gewidmet hat und seitdem wird sie mit deutlich erhöhter Frequenz diagnostiziert. Sie stellt eine chronisch immunvermittelte Entzündung des Ösophagus dar. Bei Erwachsenen ist die Dysphagie das Leitsymptom. Die Diagnose wird durch die Ösophago-Gastro-Duodenoskopie mit Entnahme von Stufenbiopsien aus dem Ösophagus gestellt. Die charakteristischen histopathologischen Veränderungen mit eosinophilen Infiltraten der ösophagealen Mukosa sind der diagnostischen Goldstandard. Bislang gibt es weltweit keine zugelassene Therapie für die EoE, auch wenn topische und systemisch wirkende Kortikosteroide eine hohe Wirksamkeit zeigen. Weitere therapeutische Optionen stellt die Eliminationsdiät und in ausgewählten Fällen die endoskopische Dilatation dar.
[...]

Article in Thieme eJournals:
Table of contents | Abstract | Full text

http://ift.tt/2kEnLg2

Tinnitus – Klinik und Therapie

Laryngo-Rhino-Otol 2017; 96: 47-59
DOI: 10.1055/s-0042-119419

Article in Thieme eJournals:
Table of contents | Abstract | CME online | Full text

http://ift.tt/2kEiN2R

The diagnostic accuracy of a laser fluorescence device and digital radiography in detecting approximal caries lesions in posterior permanent teeth: an in vivo study

Abstract

The aim of this in vivo study was to test the diagnostic accuracy of a pen-type laser fluorescence (LFpen) device in detecting approximal caries lesions, in posterior permanent teeth, at the cavitation and non-cavitation thresholds, and compare it with that of digital bitewing radiography. Thirty patients (aged 18–37), who attended the Faculty of Dentistry at Damascus University for a dental examination, were consecutively screened. Ninety approximal surfaces of posterior permanent teeth without frank cavitations, enamel hypoplasia or restorations were selected and examined using the LFpen (DIAGNOdent pen) and digital bitewing radiography. The reference standard was the visual-tactile inspection, after performing temporary tooth separation, using orthodontic rubber rings, placed for 7 days. The status of included approximal surfaces was recorded as intact/sound, with white/brown spots or cavitated. One trained examiner performed all examinations. There were statistically significant differences in LFpen readings between the three types of approximal surface status (P < 0.001). The optimal cut-off values for detecting approximal caries lesions in posterior permanent teeth were >16 and 8 at the cavitation and non-cavitation thresholds respectively. The sensitivity, specificity and accuracy (measured by the area under the receiver-operating characteristic curve) were 100, 85 and 95 and 92, 90 and 95% at the cavitation and non-cavitation thresholds respectively. The intra-class correlation coefficient for intra-examiner reliability was 0.95. The diagnostic accuracy of the LFpen was significantly higher than that of digital bitewing radiography (P < 0.001). The LFpen's diagnostic performance was accurate and significantly better than digital bitewing radiography in detecting approximal caries lesions, in posterior permanent teeth.

http://ift.tt/2lIKMyw

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Δευτέρα 13 Φεβρουαρίου 2017

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Αρχειοθήκη ιστολογίου