Publication date: Available online 4 January 2018
Source:Journal of Voice
Author(s): Ihab Atallah, Manjunath MK, Ahmad Al Omari, Christian Adrien Righini, Paul F. Castellanos
ObjectiveThis study aimed to describe a graduated approach for effective transoral mobilization of cricoarytenoid joint ankylosis (CJA) in the context of the Bogdasarian system of classifying posterior glottic web-based stenosis (PGWS).Study DesignThis is a retrospective cohort study through data from medical records and operative notes. A consecutive series of 23 patients who underwent reconstructive transoral laser microsurgery for PGWS with a significant degree of CJA (Bogdasarian grade III–IV) was included in the study.MethodsTechniques necessary to remobilize their cricoarytenoid joints were reviewed in the context of the extent of scar tissue found.ResultsArytenoids with CJA were successfully mobilized by resection of the fused portion of the cricoid and arytenoid cartilages achieving respiratory improvements as well as decannulation of tracheostomy-dependent patients. The majority (83%) of patient's voices improved. All patients tolerated a full diet after the procedures. Cases with Bogdasarian grade III PGWS with minor unilateral fixation should be classified as IIIa. If the fixation is severe, the case should be classified as a grade IIIb. Grade IVa would indicate that both sides were mildly to moderately ankylosed, and grade IVb involves ankylosis of both joints with subtotal or complete fusion of at least one; it presents the greatest surgical challenge.ConclusionWe provided effective transoral techniques for the re-mobilization of cricoarytenoid joint, along with a classification of CJA that aims to standardize the severity of disease in the context of the existing and widely accepted Bogdasarian scale.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2m013lk
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- Cricoarytenoid Joint Ankylosis: Classification and...
- Multidose Botulinum Toxin A for Intralaryngeal Inj...
- Vocal Tract Discomfort Scale (VTDS) and Voice Symp...
- Neutrophilic superficial eccrine ductitis: Proposa...
- Incidence of unexpected positive histology in kyph...
- Significance of poor performance status after rese...
- Augmentation surgery on the cartilaginous portion ...
- Pharmacokinetics of dacarbazine (DTIC) in pregnancy
- Cricoarytenoid Joint Ankylosis: Classification and...
- Multidose Botulinum Toxin A for Intralaryngeal Inj...
- Vocal Tract Discomfort Scale (VTDS) and Voice Symp...
- Light attenuation versus evolved carbon (AVEC) – A...
- Ozone impact minimization through coordinated sche...
- Emission factors of greenhouse gases from layer an...
- Contribution of microenvironments to personal expo...
- Assessment of trace metal levels in size-resolved ...
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Πέμπτη 4 Ιανουαρίου 2018
Cricoarytenoid Joint Ankylosis: Classification and Transoral Laser Microsurgical Treatment
Multidose Botulinum Toxin A for Intralaryngeal Injection: A Cost Analysis
Publication date: Available online 4 January 2018
Source:Journal of Voice
Author(s): Mark R. Gilbert, VyVy N. Young, Libby J. Smith, Clark A. Rosen
ObjectivesBotulinum toxin A (BtxA) injection is the mainstay treatment for laryngeal dystonias. BtxA product labeling states that reconstituted toxin should be used within 4 hours on a single patient despite several studies that have demonstrated multidose BtxA to be safe and effective. Many insurance carriers mandate the use of an outside pharmacy which necessitates a single-use approach. This study compares the cost savings of multidose BtxA for laryngeal dystonia compared to single-use.Study DesignThis is a retrospective review and projected cost savings analysis.MethodsRecords and billing information were reviewed for patients receiving BtxA for intralaryngeal injection at a single laryngology division in 2015. Inclusion criteria included CPT 64617 or J0585; exclusion criteria included CPT 64616. The price of BtxA 100 unit vial for calculation was $670.ResultsA total of 142 patients were seen for intralaryngeal BtxA injection resulting in 337 visits over 1 year. The average BtxA dose per visit was 2.86 units with an average of 3.06 procedure visits per year. The calculated cost of BtxA treatment using a single vial approach was found to be $2,050 per patient per year. If billed instead for $7/unit with 5 units wastage charge per visit, the yearly per patient charge is $168. Single vial-use of BtxA injection thus represents a 1,118% price increase versus multidose use. When estimated for yearly prevalence of spasmodic dysphonia, multidose BtxA use would save almost $100 million annually.ConclusionsMultidose botulinum toxin A application utilizing per unit billing is significantly less expensive than per single-use vial billing and would save the health-care system significant amount of money without any sacrifice in safety or effectiveness.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2qnRt0h
Vocal Tract Discomfort Scale (VTDS) and Voice Symptom Scale (VoiSS) in the Evaluation of Patients With Voice Disorders
Publication date: Available online 4 January 2018
Source:Journal of Voice
Author(s): Leonardo Wanderley Lopes, Vanessa de Oliveira Florencio, Priscila Oliveira Costa Silva, Ana Celiane da Nóbrega e Ugulino, Anna Alice Almeida
ObjectivesWe aimed to correlate the Vocal Tract Discomfort Scale (VTDS) with the Voice Symptom Scale (VoiSS) for evaluation of patients with dysphonia. In addition, we aimed to compare vocal tract discomfort symptoms in patients with and without self-reported voice problem.Study designThis is a descriptive, cross-sectional, and retrospective study. We analyzed 143 women and 62 men with voice disorders, as confirmed by endoscopic larynx examination. All patients completed the VTDS and VoiSS at vocal evaluation. Descriptive statistics and the Spearman correlation test were applied to all variables. The degree of covariance of variables was noted. The Mann-Whitney U test was used to compare the average number of discomfort symptoms among patients with and without self-reported voice problems.ResultsA weak to moderate positive correlation was observed between the average number, frequency, and intensity of comfort symptom and the total score, physical domain score, and limitation domain score of the VoiSS. The vocal tract discomfort symptoms and the emotional domain score of the VoiSS were weakly correlated. Patients with self-reported voice problems had a higher number, frequency, and intensity of vocal tract discomfort symptoms.ConclusionThere is correlation between the VTDS and VoiSS scales, with greater references to vocal tract discomfort symptom in patients with self-reported voice problems. Therefore, the discomfort symptoms seem to influence the perception of the impact of a voice problem.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2lZ2GzK
Neutrophilic superficial eccrine ductitis: Proposal of a new disease concept
Abstract
A 3-year-old Japanese boy presented with a 3-month history of itchy erythematous papules on his trunk and forearms, the histologic findings of which were characterized by predominantly neutrophilic inflammation within and around the eccrine sweat ducts and obliteration and disruption of the superficial eccrine sweat ducts. Although the skin disorder had some clinical and histopathologic similarity to miliaria and neutrophilic eccrine hidradenitis, it was ultimately conformed to be neither disorder. Based on this and a case report in the Japanese literature of a 1-year-old boy with erythematous eruptions whose clinical and histopathologic findings were similar to those in our case, we propose the skin disorder in our case, referred to as "neutrophilic superficial eccrine ductitis," as a unique entity.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CHqpOA
Incidence of unexpected positive histology in kyphoplasty
Abstract
Objective
Kyphoplasty and vertebroplasty have become one of the most frequent surgical procedures in the treatment of vertebral compression fractures. Often, the cause of compression fractures is lowered bone mineral density as in osteoporosis. In the differential workup, also pathologic vertebral compression fractures need to be ruled out. Importantly, imaging techniques alone cannot safely differentiate between invasive lymphatic and osteoporotic vertebral fracture. Our goal was to identify the degree of unexpected positive histology in kyphoplasty for presumed osteoporotic vertebral compression fracture.
Methods
We retrospectively analyzed all kyphoplasties performed between 2007 and 2015 at our institution. The data were acquired by reviewing our medical documentation system. The data analysis was done using Microsoft Excel. The statistical analysis was done using the Chi-squared test.
Results
We performed 130 kyphoplasties/vertebroplasties. A biopsy was taken in 97 (74.6%) cases. In 10 (10.3%) cases, the histology revealed a pathological fracture. From these patients, only in 3 (30%) cases, a positive histology was not expected. Meaning that there was no history of cancer and the radiological findings presumed an osteoporotic fracture.
Conclusions
Therefore, we could demonstrate that the incidence of unexpected positive histology in vertebral compression fracture treated with kyphoplasty is significant (3.1%). As a conclusion, if a kyphoplasty is performed due to assumed osteoporotic vertebral compression fracture, a biopsy should be taken to safely rule out a pathological fracture caused by lymphatic bony invasion.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Eb3lox
Significance of poor performance status after resection of colorectal liver metastases
Abstract
Background
Performance status (PS) is known as one of the strongest prognostic factors for survival in metastatic colorectal cancer patients. The aim of the present study was to analyze factors associated with poor PS assessed after resection for colorectal liver metastases and the impact on survival.
Methods
All patients undergoing curative resection for colorectal liver metastases between 2010 and 2015 in a single center were reviewed retrospectively.
Results
A total of 284 patients were included, out of whom 74 patients (26%) presented with a postoperative PS WHO > 2 precluding administration of adjuvant chemotherapy. These patients had a shorter recurrence-free survival (P = 0.002) and shorter overall survival (P < 0.001). Multivariable analysis showed that patients with PS > 2 after surgery had higher preoperative ASA score, had a higher frequency of major complications after surgery, and had more frequently synchronous liver and lung metastases. PS was found to be the strongest independent factor predicting survival (hazard ratio 0.45). When patients with postoperative PS > 2 developed recurrent disease (54 of 74), 43 (80%) received tumor specific treatment.
Conclusions
Patients with postoperative PS > 2 who did not receive adjuvant chemotherapy had decreased recurrence-free and overall survival after liver resection for colorectal liver metastases. After recurrence, a large majority of these patients had had improvement in PS allowing for administration of tumor specific treatment.
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Augmentation surgery on the cartilaginous portion of the vocal fold in a patient with cricoarytenoid joint ankylosis
Source:Auris Nasus Larynx
Author(s): Mioko Fukahori, Shun-ichi Chitose, Kiminori Sato, Hiroyuki Kamimura, Kiminobu Sato, Ririko On, Hirohito Umeno
Surgical management of cricoarytenoid joint (CAJ) ankylosis is challenging and has the risk of worsening voice quality. In the present case, augmentation surgery was performed on the cartilaginous portion of the vocal fold in a patient with CAJ ankylosis. A 24-year-old man sustained blunt trauma to the anterior neck three years prior to developing severe breathiness. Posterior glottal insufficiency resulting from lateral fixation of the right vocal fold was observed during phonation under laryngoscopy. In addition, electromyography and CT scan revealed severe ankylosis of the right CAJ. Type I thyroplasty performed on the right vocal fold did not improve postoperative vocal function. Therefore, augmentation surgery on the cartilaginous portion of the right vocal fold was performed via endolaryngeal microsurgery under general anesthesia with jet ventilation. A piece of temporalis fascia was autotransplanted into the submucosal space created at the posterior cartilaginous portion of the right vocal fold. This resulted in the narrowing of the posterior glottal gap during phonation, leading to improvement in hoarseness. Microsurgical management with autologous fascia augmentation of the cartilaginous portion of the vocal fold can be effective in patients with lateral vocal fold fixation due to CAJ ankylosis.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CTvxwL
Pharmacokinetics of dacarbazine (DTIC) in pregnancy
Abstract
Purpose
The purpose of this report is to describe, for the first time, the pharmacokinetics of dacarbazine (DTIC) and its metabolites [5-[3-methyl-triazen-1-yl]-imidazole-4-carboxamide (MTIC), 5-[3-hydroxymethyl-3-methyl-triazen-1-yl]-imidazole-4-carboxamide (HMMTIC) and 5-aminoimidazole-4-carboxamide (AIC)] during pregnancy (n = 2) and postpartum (n = 1).
Methods
Non-compartmental DTIC, MTIC, HMMTIC, and AIC pharmacokinetics (PK) were estimated in one case at 29 week gestation and 18 day postpartum and a second case at 32 week gestation, in women receiving DTIC in combination with doxorubicin, bleomycin, and vinblastine for treatment of Hodgkin's lymphoma. Drug concentrations were measured by HPLC.
Results
In the subject who completed both pregnancy and postpartum study days, DTIC area under the concentration–time curve (AUC) was 27% higher and metabolite AUCs were lower by 27% for HMMTIC, 38% for MTIC, and 83% of AIC during pregnancy compared to postpartum. At 7 and 9 year follow-up, both subjects were in remission of their Hodgkin's lymphoma.
Conclusions
Based on these two case reports, pregnancy appears to decrease the metabolism of the pro-drug dacarbazine, likely through inhibition of CYP1A2 activity. Lower concentrations of active metabolites and decreased efficacy may result, although both these subjects experienced long-term remission of their Hodgkin's lymphoma.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CGrt5a
Cricoarytenoid Joint Ankylosis: Classification and Transoral Laser Microsurgical Treatment
Source:Journal of Voice
Author(s): Ihab Atallah, Manjunath MK, Ahmad Al Omari, Christian Adrien Righini, Paul F. Castellanos
ObjectiveThis study aimed to describe a graduated approach for effective transoral mobilization of cricoarytenoid joint ankylosis (CJA) in the context of the Bogdasarian system of classifying posterior glottic web-based stenosis (PGWS).Study DesignThis is a retrospective cohort study through data from medical records and operative notes. A consecutive series of 23 patients who underwent reconstructive transoral laser microsurgery for PGWS with a significant degree of CJA (Bogdasarian grade III–IV) was included in the study.MethodsTechniques necessary to remobilize their cricoarytenoid joints were reviewed in the context of the extent of scar tissue found.ResultsArytenoids with CJA were successfully mobilized by resection of the fused portion of the cricoid and arytenoid cartilages achieving respiratory improvements as well as decannulation of tracheostomy-dependent patients. The majority (83%) of patient's voices improved. All patients tolerated a full diet after the procedures. Cases with Bogdasarian grade III PGWS with minor unilateral fixation should be classified as IIIa. If the fixation is severe, the case should be classified as a grade IIIb. Grade IVa would indicate that both sides were mildly to moderately ankylosed, and grade IVb involves ankylosis of both joints with subtotal or complete fusion of at least one; it presents the greatest surgical challenge.ConclusionWe provided effective transoral techniques for the re-mobilization of cricoarytenoid joint, along with a classification of CJA that aims to standardize the severity of disease in the context of the existing and widely accepted Bogdasarian scale.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2m013lk
Multidose Botulinum Toxin A for Intralaryngeal Injection: A Cost Analysis
Source:Journal of Voice
Author(s): Mark R. Gilbert, VyVy N. Young, Libby J. Smith, Clark A. Rosen
ObjectivesBotulinum toxin A (BtxA) injection is the mainstay treatment for laryngeal dystonias. BtxA product labeling states that reconstituted toxin should be used within 4 hours on a single patient despite several studies that have demonstrated multidose BtxA to be safe and effective. Many insurance carriers mandate the use of an outside pharmacy which necessitates a single-use approach. This study compares the cost savings of multidose BtxA for laryngeal dystonia compared to single-use.Study DesignThis is a retrospective review and projected cost savings analysis.MethodsRecords and billing information were reviewed for patients receiving BtxA for intralaryngeal injection at a single laryngology division in 2015. Inclusion criteria included CPT 64617 or J0585; exclusion criteria included CPT 64616. The price of BtxA 100 unit vial for calculation was $670.ResultsA total of 142 patients were seen for intralaryngeal BtxA injection resulting in 337 visits over 1 year. The average BtxA dose per visit was 2.86 units with an average of 3.06 procedure visits per year. The calculated cost of BtxA treatment using a single vial approach was found to be $2,050 per patient per year. If billed instead for $7/unit with 5 units wastage charge per visit, the yearly per patient charge is $168. Single vial-use of BtxA injection thus represents a 1,118% price increase versus multidose use. When estimated for yearly prevalence of spasmodic dysphonia, multidose BtxA use would save almost $100 million annually.ConclusionsMultidose botulinum toxin A application utilizing per unit billing is significantly less expensive than per single-use vial billing and would save the health-care system significant amount of money without any sacrifice in safety or effectiveness.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2qnRt0h
Vocal Tract Discomfort Scale (VTDS) and Voice Symptom Scale (VoiSS) in the Evaluation of Patients With Voice Disorders
Source:Journal of Voice
Author(s): Leonardo Wanderley Lopes, Vanessa de Oliveira Florencio, Priscila Oliveira Costa Silva, Ana Celiane da Nóbrega e Ugulino, Anna Alice Almeida
ObjectivesWe aimed to correlate the Vocal Tract Discomfort Scale (VTDS) with the Voice Symptom Scale (VoiSS) for evaluation of patients with dysphonia. In addition, we aimed to compare vocal tract discomfort symptoms in patients with and without self-reported voice problem.Study designThis is a descriptive, cross-sectional, and retrospective study. We analyzed 143 women and 62 men with voice disorders, as confirmed by endoscopic larynx examination. All patients completed the VTDS and VoiSS at vocal evaluation. Descriptive statistics and the Spearman correlation test were applied to all variables. The degree of covariance of variables was noted. The Mann-Whitney U test was used to compare the average number of discomfort symptoms among patients with and without self-reported voice problems.ResultsA weak to moderate positive correlation was observed between the average number, frequency, and intensity of comfort symptom and the total score, physical domain score, and limitation domain score of the VoiSS. The vocal tract discomfort symptoms and the emotional domain score of the VoiSS were weakly correlated. Patients with self-reported voice problems had a higher number, frequency, and intensity of vocal tract discomfort symptoms.ConclusionThere is correlation between the VTDS and VoiSS scales, with greater references to vocal tract discomfort symptom in patients with self-reported voice problems. Therefore, the discomfort symptoms seem to influence the perception of the impact of a voice problem.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2lZ2GzK
Light attenuation versus evolved carbon (AVEC) – A new way to look at elemental and organic carbon analysis
Publication date: February 2018
Source:Atmospheric Environment, Volume 175
Author(s): E.M.G. Nicolosi, P. Quincey, A. Font, G.W. Fuller
The Attenuation Versus Evolved Carbon (AVEC) plot is a new way to represent thermal-optical organic carbon/elemental carbon (OC/EC) analysis data. The accumulated carbon concentration is plotted against the attenuation (ln (I0/I)). Unlike the thermogram, it provides information about the sample properties rather than the instantaneous instrument sensor status.The plot can be used to refine the determination of OC and EC split point, either from consideration of laser instability or transit time within the instrument; to investigate the optical properties of the particles; and to spot the early evolution of pyrolysed carbon (PC) and/or EC during the inert phase.168 samples from three sites were studied. The gradient of the AVEC plot curve in the oxygenated phase provides information about the mass absorption cross section (σ) of the particles leaving the filter. The σ of the PC generated in the higher temperature Quartz protocol was greater than the PC generated in the lower temperature EUSAAR_2 protocol. Also, in both cases the PC evolved at a lower temperature in the oxygenated phase than the native EC.To minimise the shadowing effect, σ was also measured for the particles leaving the filter at the end of the analysis. These σ values, which are expected to be a combination of inherent σ together with fixed instrumental factors, were consistent between the different sites (45 ± 10 m2 g−1 in rural samples, 42 ± 8 m2 g−1 in urban samples and 35 ± 14 m2 g−1 in roadside samples).The AVEC plot can be generated from the data routinely produced by the analytical instrument using the R-code supplied in the supplementary material.
Graphical abstract
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Ozone impact minimization through coordinated scheduling of turnaround operations from multiple olefin plants in an ozone nonattainment area
Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): Sijie Ge, Sujing Wang, Qiang Xu, Thomas Ho
Turnaround operations (start-up and shutdown) are critical operations in olefin plants, which emit large quantities of VOCs, NOx and CO. The emission has great potentials to impact the ozone level in ozone nonattainment areas. This study demonstrates a novel practice to minimize the ozone impact through coordinated scheduling of turnaround operations from multiple olefin plants located in Houston, Texas, an ozone nonattainment area. The study considered two olefin plants scheduled to conduct turnaround operations: one start-up and one shutdown, simultaneously on the same day within a five-hour window. Through dynamic simulations of the turnaround operations using ASPEN Plus Dynamics and air quality simulations using CAMx, the study predicts the ozone impact from the combined effect of the two turnaround operations under different starting-time scenarios. The simulations predict that the ozone impact from planned turnaround operations ranges from a maximum of 11.4 ppb to a minimum of 1.4 ppb. Hence, a reduction of up to 10.0 ppb can be achieved on a single day based on the selected two simulation days. This study demonstrates a cost-effective and environmentally benign ozone control practice for relevant stakeholders, including environmental agencies, regional plant operators, and local communities.
Graphical abstract
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Emission factors of greenhouse gases from layer and broiler barns in Cameroon
Source:Atmospheric Environment, Volume 176
Author(s): N. Martin Ngwabie, Ada N. Acobta, Veronica E. Manga, Andrew C. VanderZaag
Limited information is available in the literature on greenhouse gas (GHG) quantification from livestock production systems in Africa. Therefore, this project was carried out to generate baseline emission factors of methane (CH4), nitrous oxide (N2O) and carbon dioxide (CO2) from broiler and layer barns with building design typical of Cameroon. Emissions were measured from two broiler barns during the entire production cycles and a layer barn for a limited period using flux chambers. Methane emission factors from the broiler barns with mud and cement floors were 0.96 ± 1.04 and 0.36 ± 0.17 mg bird−1 hr−1 respectively, and 0.76 ± 0.56 mg bird−1 hr−1 from the layer barn with cement floor. Nitrous oxide emission from the broiler barns with mud and cement floors were 12.94 ± 10.11 and 1.68 ± 1.02 mg bird−1 hr−1 respectively, and 0.21 ± 0.28 mg bird−1 hr−1 from the layer barn. Carbon dioxide emission factors from the broiler barns with mud and cement floors were 9327 ± 3508 and 25526 ± 6904 mg bird−1 hr−1 respectively, and 8942 ± 36756 mg bird−1 hr−1 from the layer barn. When scaled per livestock unit (LU), where 1 LU is 500 kg bird weight, CH4 emissions were 0.16 ± 0.17 and 0.06 ± 0.03 g LU−1 hr−1 from the broiler barns, and 0.19 ± 0.14 g LU−1 hr−1 from the layer barn. Nitrous oxide emissions were 2.16 ± 1.69 and 0.28 ± 0.17 g LU−1 hr−1 from the broiler barns, and 0.05 ± 0.07 g LU−1 hr−1 from the layer barn. Broilers reared in management systems with wood shavings on mud floor had relatively high CH4 and N2O emissions compared to broilers on wood shavings and cement floor, with the contrary observed for CO2. The emissions N2O were significantly higher from broiler barns compared to layer barns. Emissions were higher in the mornings compared to later periods of the day. Given the observed results, GHG emission mitigation strategies need to be customised for each building design and management system.
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Contribution of microenvironments to personal exposures to PM10 and PM2.5 in summer and winter
Source:Atmospheric Environment, Volume 175
Author(s): Yunhyung Hwang, Kiyoung Lee
Personal exposure to particulate matter (PM) can be affected by time–activity patterns and microenvironmental concentrations. Particle size is closely associated with potential health problems, where smaller particles have greater effects on health. We investigated the effects of time–activity patterns on personal exposure and the contribution of the microenvironment to personal exposure to PM with maximal diameters of 10 μm and 2.5 μm (PM10 and PM2.5, respectively) in summer and winter. Technicians carried a nephelometer to detect various sizes of PM while engaging in one of nine scripted time–location–activity patterns. The scripted activities were based on the time–activity patterns of nine groups of inhabitants of Seoul, Korea. The monitoring was repeated in summer and winter to assess seasonal variation. The differences of personal exposures to PM10 and PM2.5 in summer and winter were not significant. The greatest PM concentrations occurred in restaurants. The PM2.5/PM10 ratios were varied from 0.35 at schools to 0.92 at stores. In both seasons, the residential indoor microenvironment was the largest contributor to personal PM exposure. The other major contributors were restaurants, offices, schools, buses, and walking, although their contributions differed by season and particle size. The different microenvironmental contributions among the activity pattern groups suggest that personal exposure significantly differs according to activity pattern.
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Assessment of trace metal levels in size-resolved particulate matter in the area of Leipzig
Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): Khanneh Wadinga Fomba, Dominik van Pinxteren, Konrad Müller, Gerald Spindler, Hartmut Herrmann
Size-resolved trace metal concentrations at four sites in Leipzig (Germany) and its surrounding were assessed between the winter of 2013 and the summer of 2015. The measurements were performed in parallel at; traffic dominated (Leipzig – Mitte, LMI), traffic and residential dominated (Eisenbahnstrasse, EIB), urban background (TROPOS, TRO) and regional background (Melpitz, MEL) sites. In total, 19 trace metals, i.e. K, Ca, Ti, Mn, Fe, Cu, Zn, As, Se, Ba, V, Pb, Ni, Cr, Sr, Sn, Sb, Co and Rb were analysed using total reflection x-ray fluorescence (TXRF). The major metals were Fe, K and Ca with concentrations ranging between; 31–440 ng/m3, 42–153 ng/m3 and 24–322 ng/m3, respectively, while the trace metals with the lowest concentrations were Co, Rb and Se with concentrations of; < 0.3 ng/m3, <0.5 ng/m3 and 0.5–0.7 ng/m3, respectively. PM10 trace metal concentrations during easterly air mass inflow especially at the background sites were in average 70% higher in the winter and 30% higher in the summer in comparison to westerly air mass inflow.Traffic at LMI contributed to about 75% of Cr, Ba, Cu, Sb, Sn, Ca, Co, Mn, Fe and Ti concentrations while regional activities contributed to more than 70% of K, Rb, Pb, Se, As and V concentrations. Traffic dominated trace metals were often observed in the coarse mode while the regional background dominated trace metals were often observed in the fine mode. Trace metal sources were related to crustal matter and road dust re-suspension for metals such as Ca, Fe, Co, Sr, and Ti, brake and tire wear (Cu, Sb, Ba, Fe, Zn, Pb), biomass burning (K, Rb), oil and coal combustion (V, Zn, As, Pb). Crustal matter contributed 5–12% in winter and 8–19% in summer of the PM10 mass. Using Cu and Zn as markers for brake and tire wear, respectively, the estimated brake and tire wear contributions to the PM10 mass were 0.1–0.8% and 1.7–2.9%, respectively. The higher contributions were observed at the traffic sites while the lower contributions were observed at the regional background site. In total, non-exhaust emissions could account for about 10–22% of the PM10 mass in the summer and about 7–15% of the PM10 mass in the winter.
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Biogenic volatile organic compound emissions from senescent maize leaves and a comparison with other leaf developmental stages
Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): A. Mozaffar, N. Schoon, A. Bachy, A. Digrado, B. Heinesch, M. Aubinet, M.-L. Fauconnier, P. Delaplace, P. du Jardin, C. Amelynck
Plants are the major source of Biogenic Volatile Organic Compounds (BVOCs) which have a large influence on atmospheric chemistry and the climate system. Therefore, understanding of BVOC emissions from all abundant plant species at all developmental stages is very important. Nevertheless, investigations on BVOC emissions from even the most widespread agricultural crop species are rare and mainly confined to the healthy green leaves. Senescent leaves of grain crop species could be an important source of BVOCs as almost all the leaves senesce on the field before being harvested. For these reasons, BVOC emission measurements have been performed on maize (Zea mays L.), one of the most cultivated crop species in the world, at all the leaf developmental stages. The measurements were performed in controlled environmental conditions using dynamic enclosures and proton transfer reaction mass spectrometry (PTR-MS). The main compounds emitted by senescent maize leaves were methanol (31% of the total cumulative BVOC emission on a mass of compound basis) and acetic acid (30%), followed by acetaldehyde (11%), hexenals (9%) and m/z 59 compounds (acetone/propanal) (7%). Important differences were observed in the temporal emission profiles of the compounds, and both yellow leaves during chlorosis and dry brown leaves after chlorosis were identified as important senescence-related BVOC sources. Total cumulative BVOC emissions from senescent maize leaves were found to be among the highest for senescent Poaceae plant species. BVOC emission rates varied strongly among the different leaf developmental stages, and senescent leaves showed a larger diversity of emitted compounds than leaves at earlier stages. Methanol was the compound with the highest emissions for all the leaf developmental stages and the contribution from the young-growing, mature, and senescent stages to the total methanol emission by a typical maize leaf was 61, 13, and 26%, respectively. This study shows that BVOC emissions from senescent maize leaves cannot be neglected and further investigations in field conditions are recommended to further constrain the BVOC emissions from this important C4 crop species.
Graphical abstract
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Comparison of two different dust emission mechanisms over the Horqin Sandy Land area: Aerosols contribution and size distributions
Source:Atmospheric Environment, Volume 176
Author(s): Tingting Ju, Xiaolan Li, Hongsheng Zhang, Xuhui Cai, Yu Song
Dust aerosols (PM10) emission fluxes due to convective turbulent dust emissions (CTDE) and saltation-bombardment and/or aggregation-disintegration dust emissions (SADE) events were comparatively studied using the data obtained from the Naiman station over the Horqin Sandy Land area in Inner Mongolia, China from 2011 to 2015. The annual cumulative dust fluxes released by CTDE events was about one third of that by SADE events, with the order of 103∼104 μg m−2 s−1. The particle size distributions (PSDs) with diameter between 0.1 and 20 μm during CTDE and SADE events over the Horqin Sandy Land area were simulated based on the fragmentation theory, respectively. The results indicated that an improved equation based on fragmentation theory could be applied to describe the PSDs over the Horqin site which may be because the scale-invariant fragmentation theory mainly explains the PSDs of free dust particles on the surface, which differ from the PSDs of suspend airborne dust and the improved equation was more applicable to the PSDs of SADE events because the dust emission mechanism of SADE are saltation bombardment and aggregation disintegration. The number-related mean aerosol diameters (DN) barely varied under different friction velocity (u*) for SADE events, while the volume-related mean aerosol diameters (DV) changed distinctly with the change of u*. For CTDE events, the DN and DV had no obvious relationship with the change of u* because the dominating influence factor during CTDE event was thermal convection rather than u*. The mass-related PSDs usually exhibited a peak between 0.45 and 0.70 μm during SADE events, while for CTDE events there was a wide peak in the range of 0.10~0.70μm. The results suggest that DN should be not be recommended as an individual parameter to describe the PSDs. The mass-related PSDs can effectively distinguish the SADE and CTDE events.
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Atmospheric depositions of natural and anthropogenic trace elements on the Guliya ice cap (northwestern Tibetan Plateau) during the last 340 years
Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): M. Roxana Sierra-Hernández, Paolo Gabrielli, Emilie Beaudon, Anna Wegner, Lonnie G. Thompson
A continuous record of 29 trace elements (TEs) has been constructed between 1650 and 1991 CE (Common Era) from an ice core retrieved in 1992 from the Guliya ice cap, on the northwestern Tibetan Plateau. Enrichments of Pb, Cd, Zn and Sb were detected during the second half of the 19th century and the first half of the 20th century (∼1850–1950) while enrichments of Sn (1965–1991), Cd and Pb (1975–1991) were detected during the second half of the 20th century. The EFs increased significantly by 20% for Cd and Sb, and by 10% for Pb and Zn during 1850–1950 relative to the pre-1850s. Comparisons of the Guliya TEs data with other ice core-derived and production/consumption data suggest that Northern Hemisphere coal combustion (primarily in Western Europe) is the likely source of Pb, Cd, Zn, and Sb during the 1850–1950 period. Coal combustion in Europe declined as oil replaced coal as the primary energy source. The European shift from coal to oil may have contributed to the observed Sn enrichment in ∼1965 (60% EF increase in 1975–1991), although regional fossil fuel combustion (coal and leaded gasoline) from western China, Central Asia, and South Asia (India, Nepal), as well as Sn mining/smelting in Central Asia, may also be possible sources. The post-1975 Cd and Pb enrichments (40% and 20% EF increase respectively in 1975–1991) may reflect emissions from phosphate fertilizers, fossil fuel combustion, and/or non-ferrous metal production, from western China, Central Asia, and/or South Asia. Leaded gasoline is likely to have also contributed to the post-1975 Pb enrichment observed in this record. The results strongly suggest that the Guliya ice cap has recorded long-distance emissions from coal combustion since the 1850s with more recent contributions from regional agriculture, mining, and/or fossil fuel combustion. This new Guliya ice core record of TEs fills a geographical gap in the reconstruction of the pollution history of this region that extends well beyond modern instrumental records.
Graphical abstract
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Oxidative potential of ambient fine aerosol over a semi-urban site in the Indo-Gangetic Plain
Source:Atmospheric Environment, Volume 175
Author(s): Anil Patel, Neeraj Rastogi
Indo-Gangetic Plain (IGP) receives emissions from variety of pollutant sources such as post-harvest crop residue burning, vehicles, industries, power plants, and bio-fuel burning. Several studies have documented physical, chemical and optical properties of aerosol over the IGP; however, their oxidative potential (OP) has not yet documented. Present study reports the OP (measured through dithiothreitol (DTT) assay) of soluble particulate matter smaller than 2.5 μm aerodynamic diameter (PM2.5) over Patiala (30.3°N, 76.4°E, 249 m amsl), a semi-urban site located in the IGP, during winter 2014. Volume-normalized OP (range: 1.3–7.2 nmol DTT min−1 m−3, average: 3.8 ± 1.4, 1σ) is found to be ∼3 to 20 times higher, and mass-normalized OP (range: 13-50 pmol DTT min−1 μg−1, average: 27 ± 8, 1σ) is found to be similar or higher than those documented in literature. Further, observed OP is found to depend more on PM2.5 composition rather than mass concentration. Mass fractions of organic carbon (OC), elemental carbon (EC) and water-soluble organic carbon (WSOC) correlate positively whereas that of secondary inorganic aerosol (SIA, sum of the concentrations of SO42−, NO3− and NH4+) correlate negatively with OP μg−1 at considerable significance level (p < 0.05). Negative correlation of SIA with OP μg−1 has been assessed in laboratory experiment and attributed to their DTT inactive nature. It is suggested to use WSOC/SIA ratio as a measure of DTT activity of secondary particles over the study region. Further, biomass burning derived species are observed to be more DTT active than those derived from fossil fuel burning. It was also observed that the slope of OP μg−1 and WSOC/SIA ratio linear relationship enhances significantly in samples collected during days following foggy nights in comparison to that in samples collected during non-foggy period, which may be due to the production of redox-active species by fog processing. Such studies have implications in assessing the effect of ambient aerosol on atmospheric chemistry, air quality and human health.
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Use of cameras for monitoring visibility impairment
Source:Atmospheric Environment, Volume 175
Author(s): William Malm, Scott Cismoski, Anthony Prenni, Melanie Peters
Webcams and automated, color photography cameras have been routinely operated in many U.S. national parks and other federal lands as far back as 1988, with a general goal of meeting interpretive needs within the public lands system and communicating effects of haze on scenic vistas to the general public, policy makers, and scientists. Additionally, it would be desirable to extract quantifiable information from these images to document how visibility conditions change over time and space and to further reflect the effects of haze on a scene, in the form of atmospheric extinction, independent of changing lighting conditions due to time of day, year, or cloud cover. Many studies have demonstrated a link between image indexes and visual range or extinction in urban settings where visibility is significantly degraded and where scenes tend to be gray and devoid of color. In relatively clean, clear atmospheric conditions, clouds and lighting conditions can sometimes affect the image radiance field as much or more than the effects of haze. In addition, over the course of many years, cameras have been replaced many times as technology improved or older systems wore out, and therefore camera image pixel density has changed dramatically. It is shown that gradient operators are very sensitive to image resolution while contrast indexes are not. Furthermore, temporal averaging and time of day restrictions allow for developing quantitative relationships between atmospheric extinction and contrast-type indexes even when image resolution has varied over time. Temporal averaging effectively removes the variability of visibility indexes associated with changing cloud cover and weather conditions, and changes in lighting conditions resulting from sun angle effects are best compensated for by restricting averaging to only certain times of the day.
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City-level variations in NOx emissions derived from hourly monitoring data in Chicago
Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): Benjamin de Foy
Control on emissions of nitrogen oxides (NOx) in the United States of America have led to reductions in concentrations in urban areas by up to a factor of two in the last decade. The Air Quality System monitoring network provides surface measurements of concentrations at hourly resolution over multiple years, revealing variations at the annual, seasonal, day of week and diurnal time scales. A multiple linear regression model was used to estimate the temporal profiles in the NOx concentrations as well as the impact of meteorology, ozone concentrations, and boundary layer heights. The model is applied to data from 2005 to 2016 available at 6 sites in Chicago, Illinois. Results confirm the 50% decrease in NOx over the length of the time series. The weekend effect is found to be stronger in more commercial areas, with 32% reductions on Saturdays and 45% on Sundays and holidays; and weaker in more residential areas with 20% reductions on Saturdays and 30% reductions on Sundays. Weekday diurnal profiles follow a double hump with emission peaks during the morning and afternoon rush hours, but only a shallow drop during the middle day. Difference in profiles from the 6 sites suggest that there are different emission profiles within the urban area. Diurnal profiles on Saturdays have less variation throughout the day and more emissions in the evening. Sundays are very different from both weekdays and Saturdays with a gradual increase until the early evening. The results suggest that in addition to vehicle type and vehicle miles traveled, vehicle speed and congestion must be taken into account to correctly quantify morning rush hour emissions and the weekend effect.
Graphical abstract
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Identification and semi-quantification of biogenic organic nitrates in ambient particulate matters by UHPLC/ESI-MS
Source:Atmospheric Environment, Volume 176
Author(s): Rui Li, Xinfeng Wang, Rongrong Gu, Chunying Lu, Fanping Zhu, Likun Xue, Huijun Xie, Lin Du, Jianmin Chen, Wenxing Wang
Particulate biogenic organic nitrates (PBONs) are important components of secondary organic aerosols and play an important role in the tropospheric atmosphere chemistry. However, the concentrations and the chemistry of PBONs remain poorly understood due to the lack of accurate measurement techniques on specific organic nitrates. In this study, ultra high performance liquid chromatography/electrospray mass spectrometry was applied in detection of individual PBONs in ambient atmosphere. Total five kinds of PBONs were identified in PM2.5 samples collected in urban Ji'nan in spring according to characteristic fragments of NO2, NO3, HNO3, CO2, and H2O, including monoterpene hydroxyl nitrate (MW = 215, MHN215), pinene keto nitrate (MW = 229, PKN229), limonene di-keto nitrate (MW = 247, LDKN247), oleic acid keto nitrate (MW = 359, OAKN359), and oleic acid hydroxyl nitrate (MW = 361, OAHN361). Among them, three kinds of PBONs originated from biogenic volatile organic compounds of pinene and limonene and two kinds of PBONs came from chemical conversion of oleic acid. The concentrations of these PBONs were roughly quantified with surrogate standards of (1R,2R,5R)-(+)-2-hydroxy-3-pinanone and ricinoleic acid. The average concentrations of MHN215, PKN229, LDKN247, OAKN359, and OAHN361 were 111.6 ± 23.0, 93.1 ± 49.6, 55.3 ± 7.4, 23.4 ± 14.5, 36.8 ± 18.3 ng m−3, respectively. The total concentration of these PBONs was 325.4 ± 116.7 ng m−3, contributing to 1.64 ± 0.34‰ of PM2.5.
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Genotoxic effects of daily personal exposure to particle mass and number concentrations on buccal cells
Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): Daniela S. de Almeida, Silvano César da Costa, Marcos Ribeiro, Camila A.B. Moreira, Alexandra Beal, Rafaela Squizzato, Anderson Paulo Rudke, Sameh Adib Abou Rafee, Jorge A. Martins, Graciana Freitas Palioto, Prashant Kumar, Leila D. Martins
The aim of this study is to assess personal exposure to Particle Number Concentrations (PNC) in four size ranges between 0.3 and 10 μm, and particulate matter (PM1; PM2.5; PM4; PM10) in order to evaluate possible genotoxic effects through a comet assay in buccal cells. A convenience cohort of 30 individuals from a Brazilian medium-sized city was selected. These individuals aged between 20 and 61 and worked in typical job categories (i.e., administrative, commerce, education, general services and transport). They were recruited to perform personal exposure measurements during their typical daily routine activities, totaling 240 h of sampling. The 8-h average mass concentrations in air for volunteers ranged from 2.4 to 31.8 μg m−3 for PM1, 4.2–45.1 μg m−3 for PM2.5, 7.9–66.1 μg m−3 for PM4 and from 23.1 to 131.7 μg m−3 for PM10. The highest PNC variation was found for 0.3–0.5 range, between 14 and 181 particles cm−3, 1 to 14 particles cm−3 for the 0.5–1.0 range, 0.2 to 2 particles cm−3 for the 1.0–2.5 range, and 0.06 to 0.7 particles cm−3 for the 2.5–10 range. Volunteers in the 'education' category experienced the lowest inhaled dose of PM2.5, as opposed to those involved in 'commercial' activities with the highest doses for PM10 (1.63 μg kg−1 h−1) and PM2.5 (0.61 μg kg−1 h−1). The predominant cause for these high doses was associated with the proximity of the workplace to the street and vehicle traffic. The comet assay performed in buccal cells indicated that the volunteers in 'commerce' category experienced the highest damage to their DeoxyriboNucleic Acid (DNA) compared with the control category (i.e. 'education'). These results indicate the variability in personal exposure of the volunteers in different groups, and the potential damage to DNA was much higher for those spending time in close proximity to the vehicle sources (e.g. commercial services) leading to exposure to a higher fraction of fine particles. This study builds understanding on the exposure of people in different job categories, and provide policy makers with useful information to tackle this neglected issue.
Graphical abstract
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Black carbon emissions from biomass and coal in rural China
Source:Atmospheric Environment, Volume 176
Author(s): Weishi Zhang, Zifeng Lu, Yuan Xu, Can Wang, Yefu Gu, Hui Xu, David G. Streets
Residential solid fuel combustion makes a major contribution to black carbon (BC) emissions in China. A new estimation of BC emissions from rural solid biomass and coal consumption has been derived from field survey data. The following new contributions are made: (1) emission factors are collected and reviewed; (2) household energy data are collected from field survey data and from the literature; (3) a new extrapolation method is developed to extend the field survey data to other locations; (4) the ownership and usage of two stove types are estimated and considered in the emission calculations; and (5) uncertainties associated with the estimation results are quantified. It is shown that rural households with higher income will consume less biomass but more coal. Agricultural acreage and temperature also significantly influence the amount of solid fuel consumed in rural areas. It is estimated that 640 ± 245 Gg BC/y were emitted to the atmosphere due to residential solid fuel consumption in rural China in 2014. Emissions of BC from straw, wood, and coal contributed 42 ± 13%, 36 ± 15%, and 22 ± 10% of the total, respectively. We show that effective BC mitigation (a reduction of 47%) could be obtained through widespread introduction of improved stoves in rural households.
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Tracer element for indoor PM2.5 in China migrated from outdoor
Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): Wenjing Ji, Hongyu Li, Bin Zhao, Furong Deng
Sulfur and nickel have been widely used as tracers of outdoor PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm) in the United States and Europe; however, their feasibility as tracers has not been verified yet in China. We aim to verify whether sulfur or nickel could be used as a tracer element and, if not, to identify a suitable tracer element for outdoor PM2.5 in China. We conduct two types of experiments, namely, preliminary and main-study experiments. We analyze 102 pairs of indoor and outdoor PM2.5 samples in Beijing. The correlation between the I/O (indoor/outdoor) ratio of an element and the I/O ratio of total PM2.5 is one of the criteria used to test whether this element can be used as a tracer element. The average concentrations of nickel are found to be below the detection limits in both preliminary and main-study tests. Thus, nickel cannot be used as a tracer element in China. Based on the correlations of elemental I/O ratios and the I/O ratio of total PM2.5 in the preliminary and main-study tests, sulfur also cannot be used as a tracer element; however, it should be feasible to use iron as a tracer element in Beijing according to the test results. The estimated infiltration factor obtained by using iron as tracer is extremely consistent with the calculations based on the mass balance model. In summary, iron is found to be more suitable as a tracer for outdoor PM2.5 in Beijing than sulfur or nickel.
Graphical abstract
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Emissions of volatile organic compounds from maize residue open burning in the northern region of Thailand
Source:Atmospheric Environment, Volume 176
Author(s): Duanpen Sirithian, Sarawut Thepanondh, Melanie L. Sattler, Wanna Laowagul
Emission factors for speciated volatile organic compounds (VOCs) from maize residue burning were determined in this study based on chamber experiments. Thirty-six VOC species were identified by Gas Chromatography/Mass Spectrometer (GC/MS). They were classified into six groups, including alkanes, alkenes, oxygenated VOCs, halogenated VOCs, aromatics and other. The emission factor for total VOCs was estimated as about 148 mg kg−1 dry mass burned. About 68.4% of the compounds were aromatics. Field samplings of maize residues were conducted to acquire the information of fuel characteristics including fuel loading, fraction of maize residues that were actually burned as well as proximate and elemental analysis of maize residues. The emission factors were then applied to estimate speciated VOC emissions from maize residue open burning at the provincial level in the upper-northern region of Thailand for the year 2014. Total burned area of maize covered an area of about 500,000 ha which was about 4.7% of the total area of upper-northern region of the country. It was found that total VOC emissions released during the burning season (January–April) was about 79.4 tons. Ethylbenzene, m,p-xylene, 1,2,4-trimethylbenzene, acetaldehyde and o-xylene were the major contributors, accounting for more than 65% of total speciated VOC emissions.
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Analysis of reaction products formed in the gas phase reaction of E,E-2,4-hexadienal with atmospheric oxidants: Reaction mechanisms and atmospheric implications
Source:Atmospheric Environment, Volume 176
Author(s): I. Colmenar, P. Martin, B. Cabañas, S. Salgado, E. Martinez
An analysis of reaction products for the reaction of E,E-2,4-hexadienal with chlorine atoms (Cl) and OH and NO3 radicals has been carried out at the first time with the aim of obtaining a better understanding of the tropospheric reactivity of α,β-unsaturated carbonyl compounds. Fourier Transform Infrared (FTIR) spectroscopy and Gas Chromatography-Mass Spectrometry with a Time of Flight detector (GC-TOFMS) were used to carry out the qualitative and/or quantitative analyses. Reaction products in gas and particulate phase were observed from the reactions of E,E-2,4- hexadienal with all oxidants. E/Z-Butenedial and maleic anhydride were the main products identified in gas phase. E-butenedial calculated molar yield ranging from 4 to 10%. A significant amount of multifunctional compounds (chloro and hydroxy carbonyls) was identified. These compounds could be formed in particulate phase explaining the ∼90% of unaccounted carbon in gas phase. The reaction with Cl atoms in the presence of NOx with a long reaction time gave Peroxy Acetyl Nitrate (PAN) as an additional product, which is known for being an important specie in the generation of the photochemical smog. Nitrated compounds were the major organic products from the reaction with the NO3 radical. Based on the identified products, the reaction mechanisms have been proposed. In these mechanisms a double bond addition of the atmospheric oxidant at C4/C5 of E,E-2,4-hexadienal is the first step for tropospheric degradation.
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The global impact of the DRACMA guidelines cow’s milk allergy clinical practice
The 2010 Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow's milk aller...
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Vascular Anomalies of the Head and Neck Region
Abstract
Vascular anomalies of the head and neck region are a complex group of lesions that challenge the head and neck physicians. From the very understanding of the difference between its two distinct forms, hemangiomas and vascular malformations to its management remain confusing. The review of this anomaly attempts at comprehensively understanding the disease. Vascular anomalies are easily diagnosed by their clinical presentation, but choice of imaging and management for this spectrum of lesions is varied. The author attempts to categorize the required imaging for the lesion with suggestions on the management of both hemangiomas and vascular malformations. The available treatment options are discussed, and a comprehensive algorithm for management is suggested. Further research in developing drugs that could restrict the growth of these lesions would be the future of the management of vascular lesions.
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Evaluation of Endoglin (CD105) expression in pediatric rhabdomyosarcoma
Abstract
Background
The Intratumoral Microvessel Density (IMVD) is commonly used to quantify tumoral vascularization and is usually assessed by pan-endothelial markers, such as CD31. Endoglin (CD105) is a protein predominantly expressed in proliferating endothelium and the IMVD determined by this marker measures specifically the neovascularization. In this study, we investigated the CD105 expression in pediatric rhabdomyosarcoma and assessed the neovascularization by using the angiogenic ratio IMVD-CD105 to IMVD-CD31.
Methods
Paraffin-embedded archival tumor specimens were selected from 65 pediatric patients affected by rhabdomyosarcoma. The expression levels of CD105, CD31 and Vascular Endothelial Growth Factor (VEGF) were investigated in 30 cases (18 embryonal and 12 alveolar) available for this study. The IMVD-CD105 to IMVD-CD31 expression ratio was correlated with clinical and pathologic features of these patients.
Results
We found a specific expression of endoglin (CD105) in endothelial cells of all the rhabdomyosarcoma specimens analyzed. We observed a significant positive correlation between the IMVD individually measured by CD105 and CD31. The CD105/CD31 expression ratio was significantly higher in patients with lower survival and embryonal histology. Indeed, patients with a CD105/CD31 expression ratio < 1.3 had a significantly increased OS (88%, 95%CI, 60%–97%) compared to patients with higher values (40%, 95%CI, 12%–67%). We did not find any statistical correlation among VEGF and EFS, OS and CD105/CD31 expression ratio.
Conclusion
CD105 is expressed on endothelial cells of rhabdomyosarcoma and represent a useful tool to quantify neovascularization in this tumor. If confirmed by further studies, these results will indicate that CD105 is a potential target for combined therapies in rhabdomyosarcoma.
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Inhibition of neddylation facilitates cell migration through enhanced phosphorylation of caveolin-1 in PC3 and U373MG cells
Abstract
Background
Protein neddylation is a post-translational modification by a covalent conjugation with the neural precursor cell expressed, developmentally downregulated 8 (NEDD8). Although this process has been reported to participate in diverse cellular signaling, little is known about its role in cancer cell migration. Given a recent proteomics report showing that NEDD8 is downregulated in prostate cancer tissues versus normal prostate tissues, we tested the possibility that neddylation plays a role in cancer evolution, and then tried to identify target proteins of the neddylation.
Methods
The neddylation process was inhibited by transfecting cancer cells with NEDD8-targeting siRNAs or by treating the cells with a NAE1 inhibitor MLN4924. Cell migration was evaluated by an in vitro wound-healing assay and a Transwell migration assay. His/NEDD8-conjugated proteins were pulled down with nickel-affinity beads under a denaturing condition, and identified by Western blotting. All data were processed using the Microsoft Excel program and analyzed statistically by two-sided, unpaired Student's t-test.
Results
Caveolin-1, which plays a critical role in cell migration, was identified to be conjugated with NEDD8. When the neddylation was inhibited, the phosphorylation of caveolin-1 at Tyr14 was augmented in PC3 and U373MG cells, thereby leading to increased cell migration. Such consequences by neddylation inhibition were abolished in the presence of a Src family kinase inhibitor PP2.
Conclusions
NEDD8 seems to inhibit the Src-mediated phosphorylation of caveolin-1 by modifying the structure of caveolin-1 protein, which blocks the migration of cancer cells. Although the neddylation process is currently regarded as an emerging target for cancer therapy, our results suggest the possibility that the inhibition of neddylation could facilitate cancer invasion or metastasis at least in some types of cancers.
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Evolutionary aspects of non-metastatic breast cancer after primary treatment in a sub-Saharan African setting: a 16-year retrospective review at the Douala general hospital, Cameroon
Abstract
Background
Breast cancer has a high case fatality rate in sub-Saharan Africa, and this is chiefly because of late detection and inadequate treatment resources. Progressive renovations in diagnostic and management modalities of non-metastatic breast cancer (NMBC) have been noted in the region but there is paucity of data describing the clinical progress of patients with NMBC. This study sought to determine the rates of local relapse, distant metastasis and sequelae and the time span from initial treatment to the occurrence of these adverse events among patients with NMBC.
Methods
This was a retrospective review of medical records of patients with histologically confirmed NMBC at the department of radiation therapy and oncology of the Douala General Hospital in Cameroon from the January 1997 to December 2012 period. Clinicopathological and treatment characteristics as well as occurrences of adverse events were studied.
Results
A total of 260 cases were reviewed of which 224/260 (86.2%) had invasive ductal carcinoma. Surgery was performed on 258/260 cases (99.2%) with 187/258 (72.5%) being modified radical mastectomies. Various treatment combinations were used in up to 228/260 patients (87.5%) while surgery alone was the treatment in the remaining 32 cases (12.5%). Metastasis occurred in 142/260 cases (54.6%) of which 68/142 (26.2%) were local relapses and 74/142 (28.5%) were distant metastases. Among the cases of distant metastasis, 9.2% were bone, 8.5% lungs, 6.9% nodal, and 5.4% brain. Metastasis to multiple organs was noted in 4.7% of these cases. The median periods of occurrence of local relapse and distant metastases were 13 and 12 months respectively. Sequelae occurred in 26/260 cases (10%) and were noted after an average of 30 months. The main sequelae were lymphoedema (6.5%) and lung fibrosis (1.5%). At the end of the period under review, 118/260 patients (45.4%) were alive and disease-free with a median follow up time of 24 months.
Conclusions
Adverse events were frequent among patients who received primary treatment for NMBC. Available cancer therapeutic modalities ought to be supplemented with efficient strategies of follow-up and monitoring so as to optimize the care provided to these patients and improve on their survival.
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Prognostic value of the Glasgow Prognostic Score for patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy
Abstract
Background
The aim of the present study was to evaluate the prognostic significance of the Glasgow Prognostic Score (GPS) in metastatic renal cell carcinoma (mRCC) patients treated by cytoreductive nephrectomy (CN), and the accuracy of the GPS as a prognostic factor.
Methods
We retrospectively analyzed the data of patients who underwent CN for mRCC between March 1984 and August 2015. In accordance with the GPS criteria, the patients were classified into three groups: GPS 0: C-reactive protein (CRP) ≤ 1.0 mg/dl and albumin ≥ 3.5 g/dl; GPS 1: CRP > 1.0 mg/dl or albumin < 3.5 g/dl; and GPS 2: CRP > 1.0 mg/dl and albumin < 3.5 g/dl.
Results
We enrolled 170 patients (72% male; median age 63.5 years). Fifty-six (33%), 67 (39%), and 47 (28%) patients had a GPS of 0, 1, and 2, respectively. The median overall survivals after CN were 52.4, 19.1, and 8.9 months for patients with a GPS of 0, 1, and 2, respectively (P < 0.0001). In addition to the GPS, Eastern Cooperative Oncology Group performance status (ECOG-PS), Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification, histology, sarcomatoid change, clinical T stage, primary tumor size, number of metastatic organs, non-regional lymph node metastasis, and liver metastasis were included in the Cox hazards regression model. Multivariate analysis of these factors revealed that the GPS was an independent prognostic factor of overall survival (P < 0.0001). Harrell's concordance index in the multivariate prognostic model based on ECOG-PS, MSKCC risk criteria, histology, sarcomatoid change, clinical T stage, primary tumor size, number of metastatic organs, non-regional lymph node metastasis, and liver metastasis was 0.609, which increased to 0.652 after the inclusion of the GPS.
Conclusions
GPS represents an independent prognostic factor for patients who undergo CN for mRCC.
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Delayed facial nerve decompression for severe refractory cases of Bell’s palsy: a 25-year experience
This study aims to assess the effectiveness of delayed facial nerve decompression for Bell's palsy (BP).
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Pediatric psoriasis: Evolving perspectives
Abstract
Background/Objectives
Childhood-onset psoriasis is a common skin disorder that has recently received increasing attention, particularly because of its significant medical, social, financial, and psychological burdens and its associated comorbidities. With limited data available and lack of standardized management guidelines for pediatric psoriasis, an expert panel desired to provide an updated critical overview and practical guidance for management of the affected population.
Methods
A panel of pediatric dermatologists with extensive experience in pediatric psoriasis defined and prioritized a core set of topics, performed an English-language literature review, prepared critical evaluations and presentations of topic areas, and carried out a consensus meeting and follow-up consensus manuscript.
Results
The summation of evolving perspectives in pediatric psoriasis includes epidemiology and natural history of the disease, precipitating factors and comorbidities, quality of life and burden of disease, clinical features and disease presentation, differential diagnosis, pathogenesis and treatment, including topical, photo, and systemic therapies.
Conclusion
Pediatric psoriasis is an important immune-mediated inflammatory skin disease with potential for significant impact on affected individuals and their caregivers. Current state-of-the-art care is based primarily on experience and expert consensus, but pediatric data are accumulating and therapeutic options are rapidly evolving.
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Predicting postoperative language outcome using presurgical fMRI, MEG, TMS, and high gamma ECoG
Source:Clinical Neurophysiology
Author(s): Abbas Babajani-Feremi, Christen M. Holder, Shalini Narayana, Stephen P. Fulton, Asim F. Choudhri, Frederick A. Boop, James W. Wheless
ObjectiveTo predict the postoperative language outcome using the support vector regression (SVR) and results of multimodal presurgical language mapping.MethodsEleven patients with epilepsy received presurgical language mapping using functional MRI (fMRI), magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), and high-gamma electrocorticography (hgECoG), as well as pre- and postoperative neuropsychological evaluation of language. We constructed 15 (24-1) SVR models by considering the extent of resected language areas identified by all subsets of four modalities as input feature vector and the postoperative language outcome as output. We trained and cross-validated SVR models, and compared the cross-validation (CV) errors of all models for prediction of language outcome.ResultsSeven patients had some level of postoperative language decline and two of them had significant postoperative decline in naming. Some parts of language areas identified by four modalities were resected in these patients. We found that an SVR model consisting of fMRI, MEG, and hgECoG provided minimum CV error, although an SVR model consisting of fMRI and MEG was the optimal model that facilitated the best trade-off between model complexity and prediction accuracy.ConclusionsA multimodal SVR can be used to predict the language outcome.SignificanceThe developed multimodal SVR models in this study can be utilized to calculate the language outcomes of different resection plans prior to surgery and select the optimal surgical plan.
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The critical warning sign of real-time brainstem auditory evoked potentials during microvascular decompression for hemifacial spasm
Source:Clinical Neurophysiology
Author(s): Sang-Ku Park, Byung-Euk Joo, Seunghoon Lee, Jeong-A Lee, Jeong-Ho Hwang, Doo-Sik Kong, Dae-Won Seo, Kwan Park, Hoon-Taek Lee
ObjectiveThe aim of this study was to define the critical warning sign of real-time brainstem auditory evoked potential (BAEP) for predicting hearing loss (HL) after microvascular decompression (MVD) for hemifacial spasm (HFS).MethodsNine hundred and thirty-two patients with HFS who underwent MVD with intraoperative monitoring (IOM) of BAEP were analyzed. We used a 43.9 Hz/s stimulation rate and 400 averaging trials to obtain BAEP. To evaluate HL, pure-tone audiometry and speech discrimination scoring were performed before and one week after surgery. We analyzed the incidence for postoperative HL according to BAEP changes and calculated the diagnostic accuracy of significant warning criteria.ResultsOnly 11 (1.2 %) patients experienced postoperative HL. The group showing permanent loss of wave V showed the largest percentage of postoperative HL (p <0.001). No patient who experienced only latency prolongation (≥ 1 ms) had postoperative HL. Loss of wave V and latency prolongation (≥1 ms) with amplitude decrement (≥ 50%) were highly associated with postoperative HL.ConclusionsLoss of wave V and latency prolongation of 1 ms with amplitude decrement ≥ 50% were the critical warning signs of BAEP for predicting postoperative HL.SignificanceThese findings elucidate the critical warning sign of real-time BAEP.
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Pancreatic juice mutation concentrations can help predict the grade of dysplasia in patients undergoing pancreatic surveillance
Purpose: The measurement of mutations in pancreatic juice samples collected from the duodenum during endoscopic ultrasound (EUS) may improve the diagnostic evaluation of patients undergoing pancreatic surveillance. Our aim was to evaluate the accuracy of using pancreatic juice mutation concentrations to predict the presence and histologic grade of neoplasia in the pancreas.
Experimental Design: Digital next-generation sequencing (NGS) of pancreatic juice DNA using a targeted 12-gene panel was performed on 67 patients undergoing pancreatic evaluation during EUS including patients with pancreatic ductal adenocarcinoma, patients who subsequently underwent pancreatic resection for precursor lesions, patients undergoing surveillance for their familial/inherited susceptibility to pancreatic cancer, and normal pancreas disease controls.
Results: Patients with pancreatic cancer or high-grade dysplasia as their highest grade lesion had significantly higher pancreatic juice mutation concentrations than all other subjects (mean/s.d. digital NGS score; 46.6+/-69.7 vs. 6.2+/-11.6, p=0.02). Pancreatic juice mutation concentrations distinguished patients with pancreatic cancer or high-grade dysplasia in their resection specimen from all other subjects with a sensitivity, 72.2%, specificity, 89.4% (area under the curve, AUC 0.872). Mutant TP53/SMAD4 concentrations could distinguish patients with pancreatic cancer or high-grade dysplasia in their resection specimen, from all other subjects with 61.1% sensitivity, 95.7% specificity (AUC 0.819). Among 31 high-risk individuals under surveillance, 2 of the 3 individuals with most abnormal pancreatic juice mutation profiles also had the most abnormalities on pancreatic imaging.
Conclusions: Pancreatic juice mutation analysis using digital NGS has potential diagnostic utility in the evaluation of patients undergoing pancreatic surveillance.
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p53-reactive T cells are associated with clinical benefit in patients with platinum-resistant epithelial ovarian cancer after treatment with a p53 vaccine and gemcitabine chemotherapy
Purpose: To conduct a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer. Experimental Design: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses. Results: 11 patients were evaluated for p53MVA/gemcitabine toxicity, clinical outcome and immunological response. Toxicity: There were no DLTs but 3/11 patients came off study early due to gemcitabine-attributed adverse events (AEs). Minimal AEs were attributed to p53MVA vaccination. Immunological and Clinical Response: Enhanced in vitro recognition of p53 peptides was detectable after immunization in both the CD4+ and CD8+ T cell compartments in 5/11 and 6/11 patients respectively. Changes in peripheral T regulatory cells (Tregs) and myeloid derived suppressor cells (MDSC) did not correlate significantly with vaccine response or progression free survival (PFS). Patients with the greatest expansion of p53-reactive T cells had significantly longer PFS than patients with lower p53-reactivity post therapy. Tumor shrinkage or disease stabilization occurred in 4 patients. Conclusions: p53MVA was well tolerated, but gemcitabine without steroid pre-treatment was intolerable in some patients. However, elevated p53-reactive CD4+ and CD8+T cell responses post therapy correlated with longer PFS. Therefore, if responses to p53MVA could be enhanced with alternative agents, superior clinical responses may be achievable.
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Efficacy, safety and pharmacokinetics of axitinib in nasopharyngeal carcinoma: a preclinical and phase 2 correlative study
Purpose:We hypothesized that axitinib is active with improved safety profile in nasopharyngeal carcinoma (NPC). Experimental Design: We evaluated axitinib in preclinical models of NPC, and studied its efficacy in a phase 2 clinical trial in recurrent or metastatic NPC patients who progressed after at least one line of prior platinum-based chemotherapy. We excluded patients with local recurrence or vascular invasion. Axitinib was started at 5 mg twice-daily in continuous 4-weeks cycles. Primary endpoint was clinical benefit rate (CBR), defined as percent of patients achieving complete response (CR), partial response (PR) or stable disease (SD) by RECIST criteria for more than 3 months. Results:We recruited 40 patients, who received a median of 3 lines of prior chemotherapy. Axitinib was administered for a mean of 5.6 cycles, with 16 patients (40%) received ≥6 cycles. Of 37 patients evaluable for response, CBR was 78.4% (95% CI: 65.6-91.2%) at 3 months and 43.2% (30.4-56.1%) at 6 months. Grade 3/4 toxicities were uncommon, including hypertension (8%), diarrhea (5%), weight loss (5%) and pain (5%). All hemorrhagic events were grade 1 (15%) or grade 2 (3%). Elevated diastolic blood pressure during first 3 months of axitinib treatment was significantly associated with improved overall survival (HR=0.29, 95% C.I 0.13-0.64, P=0.0012). Patient reported fatigue symptom was associated with hypothyroidism (p=0.039). Axitinib PK parameters (C max and AUC(0-t)) were significantly correlated with tumor response, toxicity and serum thyroid-stimulating hormone (TSH) changes. Conclusions: Axitinib achieved durable disease control with a favorable safety profile in heavily pretreated NPC patients.
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Pharmacological inhibition of NOS activates ASK1/JNK pathway augmenting docetaxel-mediated apoptosis in triple negative breast cancer
Purpose: Chemoresistance in triple negative breast cancer (TNBC) is associated with the activation of a survival mechanism orchestrated by the endoplasmic reticulum (EnR) stress response and by inducible nitric oxide synthase (iNOS). Our aim was to determine the effects of pharmacological NOS-inhibition on TNBC. Experimental Design: TNBC cell lines, SUM-159PT, MDA-MB-436, and MDA-MB-468, were treated with docetaxel and NOS-inibitor (L-NMMA) for 24, 48 and 72 hours. Apoptosis was assessed by flow cytometry using Annexin-V and propidium iodide. Western Blot was used to assess ER-stress and apoptosis; rtPCR, to evaluate s-XBP1. TNBC patient derived xenografts (PDXs) were treated either with vehicle, docetaxel, or combination therapy (NOS-inhibition + docetaxel). Mouse weight and tumor volumes were recorded twice weekly. Docetaxel concentration was determined using mass spectrometry. To quantify proliferation and apoptosis PDX tumor samples were stained using Ki67 and TUNEL assay. Results: In-vitro, L-NMMA ameliorated the iNOS upregulation associated with docetaxel. Apoptosis increased when TNBC cells were treated with combination therapy. In TNBC PDXs, combination therapy significantly reduced tumor volume growth and increased survival proportions. In the BCM-5998 PDX model, intratumoral docetaxel concentration was higher in mice receiving combination therapy. Coupling docetaxel with NOS-inhibition increased EnR-stress response via co-activation of ATF4 and CHOP, which triggered pASK1/JNK proapoptotic pathway, promoting cleavage of caspases 3 and 9. Conclusion: iNOS is a critical target for docetaxel resistance in TNBC. Pharmacological inhibition of NOS enhanced chemotherapy response in TNBC PDX models. Combination therapy may improve prognosis and prevent relapse in TNBC patients who have failed conventional chemotherapy.
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Characterizing the effects of deep brain stimulation with magnetoencephalography: A review
Source:Brain Stimulation
Author(s): Irene E. Harmsen, Nathan C. Rowland, Richard A. Wennberg, Andres M. Lozano
BackgroundDeep brain stimulation (DBS) is an important form of neuromodulation that is being applied to patients with motor, mood, or cognitive circuit disorders. Despite the efficacy and widespread use of DBS, the precise mechanisms by which it works remain unknown. Over the last decade, magnetoencephalography (MEG) has become an important functional neuroimaging technique used to study DBS.ObjectiveThis review summarizes the literature related to the use of MEG to characterize the effects of DBS.MethodsPeer reviewed literature on DBS-MEG was obtained by searching the publicly accessible literature databases available on PubMed. The abstracts of all reports were scanned and publications which combined DBS-MEG in human subjects were selected for review.ResultsA total of 32 publications met the selection criteria, and included studies which applied DBS for Parkinson's disease, dystonia, chronic pain, phantom limb pain, cluster headache, and epilepsy. DBS-MEG studies provided valuable insights into network connectivity, pathological coupling, and the modulatory effects of DBS.ConclusionsAs DBS-MEG research continues to develop, we can expect to gain a better understanding of diverse pathophysiological networks and their response to DBS. This knowledge will improve treatment efficacy, reduce side-effects, reveal optimal surgical targets, and advance the development of closed-loop neuromodulation.
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The role of frontal sinus drillouts in nasal polyposis
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Quality of life outcomes after endoscopic approaches to intracranial tumors
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Long-term management and outcomes after repair of cerebrospinal fluid rhinorrhea related to idiopathic intracranial hypertension
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New instrumentations in the operating room for sinus surgery
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Review and update on postoperative opioid use after nasal and sinus surgery
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How does sinus surgery affect topical irrigation distribution?
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Updates in the management of sinonasal mucosal melanoma
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Odontogenic sinusitis: developments in diagnosis, microbiology, and treatment
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Delayed complications from expanded endonasal surgery for intracranial tumors
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Comment on ‘A meta-analysis of CXCL12 expression for cancer prognosis’
Comment on 'A meta-analysis of CXCL12 expression for cancer prognosis'
Comment on 'A meta-analysis of CXCL12 expression for cancer prognosis', Published online: 04 January 2018; doi:10.1038/bjc.2017.444
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Reply to ‘Comment on ‘A meta-analysis of CXCL12 expression for cancer prognosis”
Reply to 'Comment on 'A meta-analysis of CXCL12 expression for cancer prognosis"
Reply to 'Comment on 'A meta-analysis of CXCL12 expression for cancer prognosis", Published online: 04 January 2018; doi:10.1038/bjc.2017.445
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Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition
Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition
Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition, Published online: 04 January 2018; doi:10.1038/bjc.2017.429
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Therapy-educated mesenchymal stem cells enrich for tumor initiating cells
Stromal cells residing in the tumor microenvironment contribute to the development of therapy resistance. Here we show that chemotherapy-educated mesenchymal stem cells (MSCs) promote therapy resistance via crosstalk with tumor-initiating cells (TICs), a resistant tumor cell subset that initiates tumorigenesis and metastasis. In response to gemcitabine chemotherapy, MSCs colonized pancreatic adenocarcinomas in large numbers and resided in close proximity to TICs. Furthermore, gemcitabine-educated MSCs promoted the enrichment of TICs in vitro and enhance tumor growth in vivo. These effects were dependent on the secretion of CXCL10 by gemcitabine-educated MSCs and subsequent activation of the CXCL10-CXCR3 axis in TICs. In an orthotopic pancreatic tumor model, targeting TICs using nano-vesicles (called nano-ghosts) derived from MSC membranes and loaded with a CXCR3 antagonist enhanced therapy outcome and delayed tumor re-growth when administered in combination with gemcitabine. Overall, our results establish a mechanism through which MSCs promote chemoresistance, and propose a novel drug delivery system to target TICs and overcome this resistance.
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O-GlcNAcylation of the tumor suppressor FOXO3 triggers aberrant cancer cell growth
Post-translational modifications of tumor suppressors can induce abnormal cell growth. Here we identify site-specific O-GlcNAcylation as a critical block of FOXO3 that may abrogate a part of the p53 pathway, resulting in aberrant cancer cell growth. Of seven O-GlcNAcylation sites identified within the FOXO3 transactivation domain, we found that changes in O-GlcNAcylation at Ser284 modulated p21-mediated cancer cell growth. Overexpression of either O-GlcNAcylated FOXO3 (FOX-OV) or a Ser-to-Ala mutant (S284A) in PANC-1 cells indicated that S284 O-GlcNAc acts as a critical block of the FOXO tumor suppressor and induces proliferation in PANC-1 cancer cells by stimulating the MDM2-p53-p21 axis. Furthermore, S284A mutant cells lacking S284 O-GlcNAc and FOX-OV cells exhibited opposing MDM2-p53-p21 axis expression patterns at both the mRNA and protein levels. Thus, our study provides evidence to support a role for S284 O-GlcNAc as a critical block of FOXO3 to induce subsequent cancer cell growth via abrogation of the p53 regulatory circuit.
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Deletion of the von Hippel-Lindau gene in hemangioblasts causes hemangioblastoma-like lesions in murine retina
von Hippel-Lindau (VHL) disease is an autosomal dominant tumor predisposition syndrome characterized by the development of highly vascularized tumors and cysts. Loss of heterozygosity (LOH) of the VHL gene results in aberrant upregulation of hypoxia-inducible factors (HIF) and has been associated with tumor formation. Hemangioblastomas of the central nervous system and retina represent the most prevalent VHL-associated tumors, but no VHL animal model has reproduced retinal capillary hemangioblastomas (RCH), the hallmark lesion of ocular VHL. Here we report our work in developing a murine model of VHL-associated RCH by conditionally inactivating Vhl in a hemangioblast population using a Scl-Cre-ERT2 transgenic mouse line. In transgenic mice carrying the conditional allele and the Scl-Cre-ERT2 allele, 64% exhibited various retinal vascular anomalies following tamoxifen induction. Affected Vhl mutant mice demonstrated retinal vascular lesions associated with prominent vasculature, anomalous capillary networks, hemorrhage, exudates, and localized fibrosis. Histological analyses showed RCH-like lesions characterized by tortuous, dilated vasculature surrounded by "tumorlet" cell cluster and isolated foamy stromal cells, which are typically associated with RCH. Fluorescein angiography suggested increased vascular permeability of the irregular retinal vasculature and hemangioblastoma-like lesions. Vhl deletion was detected in "tumorlet" cells via microdissection. Our findings provide a phenotypic recapitulation of VHL-associated RCH in a murine model that may be useful to study RCH pathogenesis and therapeutics aimed at treating ocular VHL.
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