A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): Gilberto de Castro Junior, José Getúlio Segalla, Sérgio Jobim de Azevedo, Carlos José Andrade, Daniel Grabarz, Bruno de Araújo Lima França, Auro Del Giglio, Nicolas Silva Lazaretti, Maria Nunes Álvares, José Luiz Pedrini, Celio Kussumoto, João Nunes de Matos Neto, Nora Manoukian Forones, Hezio Jadir Fernandes Júnior, Giuliano Borges, Gustavo Girotto, Ismael Dale Cotrim Guerreiro da Silva, Fauze Maluf-Filho, Nils Gunnar Skare
PurposeChemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR).Patients and methodsUntreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated.ResultsWe enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44–1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm.ConclusionCombined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL.Clinical trialsIdentification number: EF024-201; Trial registry: NCT01249352.



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Farewell to monomodality treatment in patients with WHO lower grade glioma?

Publication date: Available online 24 November 2017
Source:European Journal of Cancer
Author(s): Emilie Le Rhun, Thierry Gorlia




http://ift.tt/2jodSUi

The effectiveness of topical colloidal silver in recalcitrant chronic rhinosinusitis: a randomized crossover control trial

Abstract

Background

Recalcitrant chronic rhinosinusitis without polyposis (CRSsP) is a challenging condition to manage as traditional medical therapies and surgery fail to provide satisfactory clinical improvements. Colloidal silver (CS), a widely used naturopathic agent, has recently shown anti-biofilm properties both in vitro and within a rhinosinusitis animal model. To date, no trials involving humans have been published in world literature. The purpose of this study was to assess the efficacy of CS as a topical nasal spray in patients with refractory CRSsP.

Methods

A prospective cohort study was conducted using a convenience sample of 20 randomized patients with crossover methodology, comparing nasal sprays with CS versus saline. Patients sprayed twice daily for six weeks with the first intervention and then switched to the second for the next six weeks, with measurements made at baseline and each time point. Primary outcomes were changes in SNOT-22 and Lund-Kennedy (LK) endoscopic scores. All analysis was non-parametric and was conducted using STATA 14.

Results

Twenty-two patients were enrolled in the study with 20 completing the entire protocol. Mean 6-week change in SNOT-22 scores were −2.8 and 1.0 for saline and CS, respectively (p = 0.373). Similarly, mean 6-week change in LK scores were −1.4 and −1.1 for saline and CS, respectively (p = 0.794). Significant period effects were observed with the SNOT-22 score between the randomized groups. No participants experienced negative health effects directly attributable to the administration of intranasal CS.

Conclusion

Commercially available CS nasal spray did not demonstrate any meaningful subjective or objective improvements in patients with recalcitrant CRSsP.

Trial registration

NCT02403479. Registered on March 1, 2015.

http://ift.tt/2A5w67p

The effectiveness of topical colloidal silver in recalcitrant chronic rhinosinusitis: a randomized crossover control trial

Abstract

Background

Recalcitrant chronic rhinosinusitis without polyposis (CRSsP) is a challenging condition to manage as traditional medical therapies and surgery fail to provide satisfactory clinical improvements. Colloidal silver (CS), a widely used naturopathic agent, has recently shown anti-biofilm properties both in vitro and within a rhinosinusitis animal model. To date, no trials involving humans have been published in world literature. The purpose of this study was to assess the efficacy of CS as a topical nasal spray in patients with refractory CRSsP.

Methods

A prospective cohort study was conducted using a convenience sample of 20 randomized patients with crossover methodology, comparing nasal sprays with CS versus saline. Patients sprayed twice daily for six weeks with the first intervention and then switched to the second for the next six weeks, with measurements made at baseline and each time point. Primary outcomes were changes in SNOT-22 and Lund-Kennedy (LK) endoscopic scores. All analysis was non-parametric and was conducted using STATA 14.

Results

Twenty-two patients were enrolled in the study with 20 completing the entire protocol. Mean 6-week change in SNOT-22 scores were −2.8 and 1.0 for saline and CS, respectively (p = 0.373). Similarly, mean 6-week change in LK scores were −1.4 and −1.1 for saline and CS, respectively (p = 0.794). Significant period effects were observed with the SNOT-22 score between the randomized groups. No participants experienced negative health effects directly attributable to the administration of intranasal CS.

Conclusion

Commercially available CS nasal spray did not demonstrate any meaningful subjective or objective improvements in patients with recalcitrant CRSsP.

Trial registration

NCT02403479. Registered on March 1, 2015.

http://ift.tt/2A5w67p

Drug-excipient compatibility assessment of solid formulations containing meloxicam

Publication date: 15 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 112
Author(s): Lucas Melo da Silveira, Ariadne Botto Fiorot, Thiago Padovani Xavier, Maria Irene Yoshida, Marcelo Antonio de Oliveira
Meloxicam (MLX) is a non-steroidal anti-inflammatory cyclooxygenase (COX) inhibitor that is used to relieve inflammation and pain. MLX has a preferential affinity for COX-2, which is associated with a lower incidence of gastrointestinal side effects. The drug belongs to Class II of the Biopharmaceutical Classification System (BCS) in which dissolution is the limiting step of its bioavailability. In view of this classification, carrying out further studies regarding the compatibility of MLX with excipients and the mechanisms and kinetics of its degradation reactions is fundamental because any changes would directly influence the quality of the product. The aim of the present work is to evaluate solid pharmaceutical formulations containing MLX found on the market to define the more suitable excipients to improve the stability of the pharmaceutical formulations. Thermal analysis techniques were used to characterize and evaluate the compatibility between the drug and the excipients present in the market formulations. In the evaluation of its solid-state kinetics, MLX raw material under inert conditions had a shelf life of approximately 6years. In the study of compatibility between the drug and excipients, MLX was found to be incompatible with magnesium stearate after DSC analysis under binary mixtures, which was confirmed by stress studies and chromatographic analyzes.

Graphical abstract

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Dual-route targeted vaccine protects efficiently against botulinum neurotoxin A complex

Publication date: Available online 24 November 2017
Source:Vaccine
Author(s): Bikash Sahay, Natacha Colliou, Mojgan Zadeh, Yong Ge, Minghao Gong, Jennifer L. Owen, Melissa Valletti, Christian Jobin, Mansour Mohamadzadeh
Clostridium botulinum readily persists in the soil and secretes life-threatening botulinum neurotoxins (BoNTs) that are categorized into serotypes A to H, of which, serotype A (BoNT/A) is the most commonly occurring in nature. An efficacious vaccine with high longevity against BoNT intoxication is urgent. Herein, we developed a dual-route vaccine administered over four consecutive weeks by mucosal and parenteral routes, consisting of the heavy chain (Hc) of BoNT/A targeting dendritic cell peptide (DCpep) expressed by Lactobacillus acidophilus as a secretory immunogenic protein. The administered dual-route vaccine elicited robust and long-lasting memory B cell responses comprising germinal center (GC) B cells and follicular T cells (Tfh) that fully protected mice from lethal oral BoNT/A fatal intoxication. Additionally, passively transferring neutralizing antibodies against BoNT/A into naïve mice induced robust protection against BoNT/A lethal intoxication. Together, a targeted vaccine employing local and systemic administrative routes may represent a novel formulation eliciting protective B cell responses with remarkable longevity against threatening biologic agents such as BoNTs.



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Nasopharyngeal s. pneumoniae carriage and density in Belgian infants after 9 years of pneumococcal conjugate vaccine programme

Publication date: Available online 24 November 2017
Source:Vaccine
Author(s): Ine Wouters, Liesbet Van Heirstraeten, Stefanie Desmet, Stéphanie Blaizot, Jan Verhaegen, Herman Goossens, Pierre Van Damme, Surbhi Malhotra-Kumar, Heidi Theeten
BackgroundIn Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007–2011) to PCV13 (2011–2015) and to PCV10 (2015–2016). A 3-year nasopharyngeal carriage study was initiated during the programme switch in 2016. Main objective of the year 1 assessment was to obtain a baseline measurement of pneumococcal carriage prevalence, carriage density, serotype distribution and antibiotic resistance.Materials/methodsTwo infant populations aged 6–30 months and without use of antibiotics in the seven days prior to sampling were approached: (1) attending one of 85 randomly selected day-care centres (DCC); (2) presenting with AOM at study-trained general practitioners and paediatricians. Demographic and clinical characteristics were documented and a single nasopharyngeal swab was taken. S. pneumoniae were cultured, screened for antibiotic resistance and serotyped, and quantitative Taqman real-time PCR (qRT-PCR) targeting LytA was performed.ResultsCulture-based (DCC: 462/760; 60.8% – AOM: 27/39; 69.2%) and LytA-based (DCC: 603/753; 80.1% – AOM: 32/39; 82.1%) carriage prevalence was high. Average pneumococcal DNA load in LytA-positive day-care samples was 6.5 × 10⁶ copies/µl (95%CI = 3.9–9.2 × 10⁶, median = 3.5 × 10⁵); DNA load was positively associated with signs of common cold and negatively with previous antibiotic use. Culture-based frequency of 13 pneumococcal vaccine (PCV) serotypes was 5.4% in DCC and 7.7% in AOM, with 19F and 14 being most frequent, and frequencies below 0.5% for serotypes 3, 6A, 19A in both populations. Predominant non-PCV serotypes were 23B and 23A in day-care and 11A in infants with AOM. In day-care, resistance to penicillin was rare (<0.5%) and absent against levofloxacin; 32.7% and 16.9% isolates were cotrimoxazole- and erythromycin-resistant respectively.ConclusionFour years after PCV13 introduction in the vaccination programme, PCV13 serotype carriage was rare in infants throughout Belgium and penicillin resistance was rare. Continued surveillance in the context of a PCV programme switch is necessary.

Graphical abstract

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Will we have new pertussis vaccines?

Publication date: Available online 24 November 2017
Source:Vaccine
Author(s): Camille Locht
Despite wide vaccination coverage with efficacious vaccines, pertussis is still not under control in any country. Two types of vaccines are available for the primary vaccination series, diphtheria/tetanus/whole-cell pertussis and diphtheria/tetanus/acellular pertussis vaccines, in addition to reduced antigen content vaccines recommended for booster vaccination. Using these vaccines, several strategies are being explored to counter the current pertussis problems, including repeated vaccination, cocoon vaccination and maternal immunization. With the exception of the latter, none have proven their effectiveness, and even maternal vaccination is not expected to ultimately control pertussis. Therefore, new pertussis vaccines are needed, and several candidates are in early pre-clinical development. They include whole-cell vaccines with low endotoxin content, outer membrane vesicles, new formulations, acellular vaccines with new adjuvants or additional antigens and live attenuated vaccines. The most advanced is the live attenuated nasal vaccine BPZE1. It provides strong protection in mice and non-human primates, is safe, even in immune compromised animals, and genetically stable after in vitro and in vivo passages. It also has interesting immunoregulatory properties without being immunosuppressive. It has successfully completed a first-in-man clinical trial, where it was found to be safe, able to transiently colonize the human respiratory tract and to induce immune responses in the colonized subjects. It is now undergoing further clinical development. As it is designed to reduce carriage and transmission of Bordetella pertussis, it may hopefully contribute to the ultimate control of pertussis.



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The efficacy of recombinant turkey herpesvirus vaccines targeting the H5 of highly pathogenic avian influenza virus from the 2014–2015 North American outbreak

Publication date: Available online 24 November 2017
Source:Vaccine
Author(s): Charles L. Balzli, Kateri Bertran, Dong-Hun Lee, Lindsay Killmaster, Nikki Pritchard, Perry Linz, Teshome Mebatsion, David E. Swayne
The outbreak of highly pathogenic avian influenza virus in North American poultry during 2014 and 2015 demonstrated the devastating effects of the disease and highlighted the need for effective emergency vaccine prevention and control strategies targeted at currently circulating strains. This study evaluated the efficacy of experimental recombinant turkey herpesvirus vector vaccines with three different inserts targeting the hemagglutinin gene of an isolate from the recent North American influenza outbreak. White leghorn chickens were vaccinated at one day of age and challenged with A/Turkey/Minnesota/12582/2015 H5N2 at 4 weeks of age. Birds were analyzed for survival, viral shedding at two and four days after infection, and specific antibody prior to challenge and from surviving birds. The three experimental vaccines demonstrated 100%, 45% and 15% survival with the most effective vaccine significantly reducing oral and cloacal viral shedding compared to all other groups and generated specific antibody prior to challenge with highly pathogenic avian influenza virus. More studies are needed using diverse H5Nx highly pathogenic virus isolates to fully determine the breadth of coverage against possible exposure strains, as well as possible impact of maternally derived antibody on protection and vaccine efficacy.



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Experimental assessment of the Advanced Collapsed-cone Engine for scalp brachytherapy treatments

Publication date: Available online 24 November 2017
Source:Brachytherapy
Author(s): Brie Cawston-Grant, Hali Morrison, Ron S. Sloboda, Geetha Menon
PurposeTo experimentally assess the performance of the Advanced Collapsed-cone Engine (ACE) for ¹⁹²Ir high-dose-rate brachytherapy treatment planning of nonmelanoma skin cancers of the scalp.Methods and MaterialsA layered slab phantom was designed to model the head (skin, skull, and brain) and surface treatment mold using tissue equivalent materials. Six variations of the phantom were created by varying skin thickness, skull thickness, and size of air gap between the mold and skin. Treatment planning was initially performed using the Task Group 43 (TG-43) formalism with CT images of each phantom variation. Doses were recalculated using standard and high accuracy modes of ACE. The plans were delivered to Gafchromic EBT3 film placed between different layers of the phantom.ResultsDoses calculated by TG-43 and ACE and those measured by film agreed with each other at most locations within the phantoms. For a given phantom variation, average TG-43– and ACE-calculated doses were similar, with a maximum difference of (3 ± 12)% (k = 2). Compared to the film measurements, TG-43 and ACE overestimated the film-measured dose by (13 ± 12)% (k = 2) for one phantom variation below the skull layer.ConclusionsTG-43– and ACE-calculated and film-measured doses were found to agree above the skull layer of the phantom, which is where the tumor would be located in a clinical case. ACE appears to underestimate the attenuation through bone relative to that measured by film; however, the dose to bone is below tolerance levels for this treatment.



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Dosimetric impact of inter-observer catheter reconstruction variability in ultrasound-based high-dose-rate prostate brachytherapy

Publication date: Available online 24 November 2017
Source:Brachytherapy
Author(s): Alexandru Nicolae, Jure Murgic, Ivan Kruljac, Lior Dubnitzky, Laura D'Alimonte, Lin Lu, Aaron Cumal, Niki Law, Gerard Morton, Andrew Loblaw, Hans T. Chung, Ananth Ravi
PurposeTo investigate the dosimetric impact of interobserver catheter reconstruction variability in transrectal ultrasound–guided prostate high-dose-rate (HDR) brachytherapy.Methods and MaterialsTwenty consecutive patients with intermediate- or high-risk prostate cancer were treated with a single, 15-Gy HDR brachytherapy boost as part of this study. The treated plan was used as the study reference plan (PR). Three expert treatment planners (observers) manually reconstructed the catheter paths on the static three-dimensional transrectal ultrasound images, and new plans were generated from the updated positions (POBS); subsequently, the dwell time and positions from the POBS plans were superimposed on the PR catheter paths to evaluate the dosimetric effect of the interobserver variations (PEVAL). Plans from each group were stratified by observer and by number of catheters (12 or 16) and then compared using a one-way Kruskal–Wallis H test with post hoc Mann–Whitney U tests reserved for significant variations (α = 0.05).ResultsGreater than 98.9% of catheter reconstruction variations were <3 mm. When stratified by observer, there was a significant decrease (p << 0.05) in planning target volume (PTV) V100% and increases in the urethral Dmax between the POBS plans propagated to the PR catheter paths and dosimetry evaluated and PR plans only. Stratification of plans by catheter number showed nonclinically significant decreases in PTV V100%, and D90% and increases in urethral Dmax for the 12-catheter plans.ConclusionsLimiting interobserver variability, and its effects on prostate HDR brachytherapy plan quality, is critical to achieving good dosimetric outcomes; small variations in catheter reconstruction may translate to inadequate PTV coverage, excessive urethral dose, or both.



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Biochar decreased the bioavailability of Zn to rice and wheat grains: Insights from microscopic to macroscopic scales

Publication date: 15 April 2018
Source:Science of The Total Environment, Volume 621
Author(s): Ping Wu, Pei-Xin Cui, Guo-Dong Fang, Yu Wang, Shen-Qiang Wang, Dong-Mei Zhou, Wei Zhang, Yu-Jun Wang
Zn deficiency is a critical problem for many crops and human populations worldwide. Soil biochar amendment has recently been promoted as a sustainable agricultural practice. However, its effect on the bioavailability of micronutrients (especially Zn) to crops has not been fully addressed. This study investigated the impact of long-term biochar application in soils on Zn bioavailability to rice and wheat, using field experiments, and batch sorption/desorption experiments, in combination with extended X-ray absorption fine structure spectroscopy (EXAFS). In field soils biochar amendment increased total Zn content, but significantly decreased CaCl2-extractable Zn concentrations. Intriguingly, the uptake of Zn to wheat and rice grains was decreased. At high biochar application rates of 124 and 270t/ha the Zn concentrations in wheat grains (36.6 and 37.5mg/kg) reached a deficient level, lower than the recommended concentration of 45mg/kg. The batch experiments showed that biochar application at a cumulative rate of 10.5, 15.8, 31.5, 124, and 270t/ha significantly increased soil pH and soil organic matter (SOM) content, resulting in greater sorption and lower desorption of Zn. The EXAFS results demonstrated that the main forms of sorbed Zn were outer-sphere Zn complexes, Zn-illite, Zn-kaolinite and Zn-OM. The proportion of Zn-OM increased with increasing biochar application rates, suggesting that higher SOM might be more effective in immobilizing Zn and thus decreasing the Zn bioavailability. These results on the microscopic and macroscopic scales improved our understanding of the Zn bioavailability to crops, and raised potential concerns on the Zn deficiency in agricultural soils with long-term biochar application.

Graphical abstract

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Effects of dam construction and increasing pollutants on the ecohydrological evolution of a shallow freshwater lake in the Yangtze floodplain

Publication date: 15 April 2018
Source:Science of The Total Environment, Volume 621
Author(s): Linghan Zeng, Suzanne McGowan, Yanmin Cao, Xu Chen
Large river-floodplain systems which provide a variety of societal, economic and biological benefits are undergoing extensive and intensive human disturbance. However, floodplain lakes responses to multiple stressors are poorly understood. The Yangtze River and its floodplain which provide water and food resources for more than 300 million people are an important region in China. Hydrological regulation as well as socio-economic development have brought profound negative influence on this ecologically important area. To improve understanding of decadal-scale responses of floodplain lakes to multiple stressors, lake sediment proxies including particle size, geochemical elements, diatoms and chironomids were analysed in a lead-210 dated core from Futou Lake. The analyses show that dams constructed in 1935 and the early 1970s stabilized hydrological conditions in Futou Lake and impeded the interaction with the Yangtze River, resulting in a decrease in major elements (e.g., Mg, Al, Fe) transported into the lake and an increase of macrophyte-related chironomids (C. sylvestris-type, P. penicillatus-type and Paratanytarsus sp.). After the late 1990s, further decreases in major elements and increases in median grain size are attributed to the erosion of the Yangtze riverbed and declining supply of major elements-enriched sediments from the upper Yangtze caused by the impoundment of the Three Gorges Dam. Chironomid and diatom assemblages indicate that hydrological stabilization caused by dam constructions stimulated the growth of macrophytes, which may be important in buffering against an ecosystem state change towards a phytoplankton-dominated and turbid state with ongoing eutrophication. However, a recent increase in Zn, TP and the emergence of eutrophic diatom and chironomid species indicate initial signs of water quality deterioration which may be related to the combined effects of hydrological stabilization and aquaculture. Over all, the sediment record from Futou Lake emphasizes the importance of interactions between hydrological change and pollutant loads in determining floodplain lake ecosystem state.

Graphical abstract

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Facile approach to synthesize highly fluorescent multicolor emissive carbon dots via surface functionalization for cellular imaging

Publication date: 1 March 2018
Source:Journal of Colloid and Interface Science, Volume 513
Author(s): Aniruddha Kundu, Jungpyo Lee, Byeongho Park, Chaiti Ray, K. Vijaya Sankar, Wook Sung Kim, Soo Hyun Lee, Il-Joo Cho, Seong Chan Jun
Luminescent nanomaterials are encouraging scaffolds for diverse applications such as chemical sensors and biosensors, imaging, drug delivery, diagnostics, catalysis, energy, photonics, medicine, and so on. Carbon dots (CDs) are a new class of luminescent carbonaceous nanomaterial that have appeared recently and reaped tremendous scientific interest. Herein, we have exploited a simple approach to prepare tuneable and highly fluorescent CDs via surface functionalization. The successful synthesis of CDs is manifested from several investigations like high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The CDs exhibit excellent water solubility and with increasing nitrogen content fluorescence quantum yield increases whereas cell toxicity decreases. The CD synthesized at high temperature (180 °C) shows very high quantum yield (more than 56%). The tuneable optical properties of CDs are systematically studied using UV-vis and fluorescence spectroscopy. The cell viability evaluation and in vitro imaging study reveals that the synthesized CDs can be employed as a potential fluorescent probe for bio-imaging without further modification.

Graphical abstract

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Nanoparticle-loaded Hydrogels as a Pathway for Enzyme-triggered Drug Release in Ophthalmic Applications

Publication date: Available online 24 November 2017
Source:International Journal of Pharmaceutics
Author(s): Michelle Åhlén, Gopi Krishna Tummala, Albert Mihranyan
The aim of this study was to develop nanoparticle loaded hydrogel based contact lenses that could be used for ocular drug delivery. Two potential contact lens platforms for controlled ophthalmic drug delivery were developed by incorporating chitosan-poly(acrylic acid) nanoparticles into polyvinyl alcohol (PVA) hydrogels and in-situ gelled nanoparticles and cellulose nanocrystals (CNC) in PVA lenses. The nanoparticles were shown to disintegrate in a physiological 0.2 mM concentration of lysozyme resulting from the hydrolysis of the chitosan chains by lysozyme. An extended release over a 28-hour period was demonstrated once the nanoparticles had been integrated into the composite lenses, with nanoparticle-CNC PVA lenses showing even greater potential for extended release. The platform shows great promise in developing enzyme-triggered ocular drug delivery systems.

Graphical abstract

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Infectious Complications following Breast Reconstruction Using Tissue Expanders in Patients with Atopic Dermatitis

Summary: Infectious complications represent one of the most prominent factors contributing to tissue expander (TE) loss in breast reconstruction procedures. Several patient characteristics that increase the risk for surgical-site infection or TE infection have been reported, but no study has focused on the relationship between atopic dermatitis (AD) and TE infection or surgical-site infection. Recently, we investigated 203 cases of breast reconstruction surgeries performed using TEs and noted that all 3 patients who had AD developed infectious complications that ultimately led to TE removal. Considering its pathophysiology, it is likely that patients with AD relatively easily develop infectious complications due to barrier dysfunction, abnormalities in innate immune responses, or colony formation by Staphylococcus aureus. Particular caution should be exercised for breast reconstruction using man-made materials in cases complicated by AD.

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Author Index

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Subject Index

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Instructions for Contributors

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TOC

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Calendar

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Editorial Board

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Calendar Listings

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Do Residency Selection Factors Predict Radiology Resident Performance?

Publication date: Available online 24 November 2017
Source:Academic Radiology
Author(s): Vikas Agarwal, Gregory M. Bump, Matthew T. Heller, Ling-Wan Chen, Barton F. Branstetter, Nikhil B. Amesur, Marion A. Hughes
Rationale and ObjectivesThe purpose of our study is to determine what information in medical student residency applications predicts radiology residency success as defined by objective clinical performance data.Materials and MethodsWe performed a retrospective cohort study of residents who entered our institution's residency program through the National Resident Matching Program as postgraduate year 2 residents and completed the program over the past 2 years. Medical school grades, selection to Alpha Omega Alpha (AOA) Honor Society, United States Medical Licensing Examination (USMLE) scores, publication in peer-reviewed journals, and whether the applicant was from a peer institution were the variables examined. Clinical performance was determined by calculating each resident's cumulative major discordance rate for on-call cases the resident read and gave a preliminary interpretation. A major discordance was defined as a difference between the preliminary resident and the final attending interpretations that could immediately impact the care of the patient. A multivariate logistic regression was performed to determine significant variables.ResultsTwenty-seven residents provided preliminary reports on call for 67,145 studies. The mean major discordance rate was 1.08% (range 0.34%–2.54%). Higher USMLE Step 1 scores, publication before residency, and election to AOA Honor Society were all statistically significant predictors of lower major discordance rates (P values 0.01, 0.01,  and <0.001, respectively).ConclusionsOverall resident performance was excellent. There are predictors that help select the better performing residents, namely higher USMLE Step 1 scores, one to two publications during medical school, and election to AOA in the junior year of medical school.



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Diagnostic Utility of 3T Lung MRI in Children with Interstitial Lung Disease

Publication date: Available online 24 November 2017
Source:Academic Radiology
Author(s): Kushaljit Singh Sodhi, Madhurima Sharma, Edward Y. Lee, Akshay Kumar Saxena, Joseph L. Mathew, Meenu Singh, Niranjan Khandelwal
Rationale and ObjectivesThe objective of this study was to assess the diagnostic utility of 3-tesla (3T) magnetic resonance imaging (MRI) of lungs in the detection of interstitial lung disease (ILD) in pediatric patients.Materials and MethodsTwelve children (mean: 8.5 years, range: 4–12 years) with ILD were consecutively enrolled in this prospective study. HRCT and 3T lung MRI were performed in all patients within 2 days of each other. The sensitivity, the specificity, the positive predictive value, and the negative predictive value of detecting lung abnormalities related to ILD with 3T lung MRI were calculated, with high-resolution computed tomography (HRCT) as a standard of reference. Agreement between HRCT and 3T lung MRI, as well as between two reviewers, was calculated with the kappa coefficient.Results3T lung MRI had low sensitivity (66.67%) and high specificity (97.33%) in the detection of abnormalities related to ILD when compared to HRCT in children. Although 3T lung MRI performed well in the detection of consolidation, parenchymal bands and fissural thickening with a sensitivity of 100%, the sensitivity of 3T lung MRI in the detection of septal thickening, ground-glass opacity, nodules, and cysts was relatively low (50.0%, 50.0%, 66.67%, and 25.0%, respectively). Substantial agreement was seen between HRCT and 3T lung MRI (k = 0.7), whereas perfect agreement was seen between two reviewers in detecting abnormalities related to pediatric ILD (k = 0.9–1.0).ConclusionsIn comparison to HRCT, 3T lung MRI with routinely available MRI protocols and sequences can also well detect abnormalities such as consolidation, parenchymal bands, and fissural thickening in children with ILD. However, evaluation of septal thickening, ground-glass opacity, nodules, and cysts is limited with 3T lung MRI.



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Clinical and genetic characteristics of xeroderma pigmentosum in Nepal

Summary

Background

Little is known about xeroderma pigmentosum (XP) in Himalayan countries.

Objective

To describe clinical characteristics of XP in Nepal and investigate its genetic bases.

Methods

This study was carried out on all consecutive patients referred for XP to a Nepalese tertiary referral centre in 2014-2015. Clinical data were collected using a standardized questionnaire. DNA was extracted from salivary samples and next generation sequencing (NGS) was conducted using a panel covering all 8 known XP genes (classical XP (XPA to XPG) and XP variant) and a skin cancer modifier gene, the melanocortin 1 receptor gene (MC1R).

Results

Seventeen patients (median age: 15 years; range: 1-32) were included. Twelve had skin cancers (including a total of 8 squamous cell carcinomas, 60 basal cell carcinomas, ocular carcinomas requiring an orbital exenteration in 3 patients, but no melanoma). Fifteen patients carried the same homozygous nonsense XPC mutation c.1243C>T, p.R415X. A homozygous nonsense XPA mutation (p.W235X) was found in the only patient with a history of early severe sunburn reaction and associated neurologic symptoms. Associated genetic alterations included heterozygous missense variants in XPD/ERCC2 gene and the presence of MC1R variant R163Q in 5 and 9 patients, respectively.

Conclusion

Although not previously reported, XP seems frequent in Nepal. Patients often presented with a very severe phenotype after a long history of excessive sun exposure without knowledge of the disease. 15/17 had the same p.R415X XPC mutation, which seems very specific of XP in Nepal, suggesting a founder effect. NGS analyses frequently revealed associated genetic alterations which could play a modifier role in the clinical expression of the disease.

This article is protected by copyright. All rights reserved.

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Non-melanoma Hutchinson's sign: A reappraisal of this important, remarkable melanoma simulant

Abstract

Background

More than 20 years ago our reappraisal of the Hutchinson Sign (HS) gave birth to the concept of the Pseudo-Hutchinson sign.

Objectives

We have found it interesting to emphasize some important histologic points and to expand the list of the numerous HS simulants.

Methods

We have examined the cutaneous samples taken from the pigmented skin of patients in association with nail matrix biopsy. We have also extended the long list of non-melanoma HS.

Results

Histologically HS may present only as an epidermal pigmentation, depending on the area sampled. Occasionally, there may be a sparse junctional melanocytic proliferation which does not demonstrate cytologic atypia due to an underlying melanocytic nevus of the nail matrix. However, early HS can show a melanoma in situ, with a HS at the proximal nail fold (PNF) and confluent atypical melanocytes in the nail matrix. Finally, involvement of the proximal nail fold, nail matrix and nail bed containing atypical melanocytes in irregular array may be seen.

Conclusion

The mere presence of periungual pigmentation is neither clinically nor histologically pathognomonic of subungual melanoma and justifies the usefulness of this work stressing the non-melanoma HS.

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In vivo Confocal Laser Microscopy for monitoring of actinic keratosis treatment: a comparison with histopathologic assessment after treatment with topical 5% 5-fluorouracil

Abstract

Background

Histological examination is the gold standard for actinic keratosis diagnosis; however, it is not always a feasible approach. Reflectance confocal microscopy (RCM) is a non-invasive technique that may be an alternative for monitoring actinic keratoses treatment response. Topical 5-fluorouracil is indicated for actinic keratosis multiple lesions and for field cancerization treatment.

Objectives

To assess the RCM accuracy, sensibility and specificity for actinic keratosis, considering as a gold-standard the histopathological examination; as well as to evaluate the efficacy of 5% 5-fluorouracil treatment.

Methods

This is a prospective study in actinic keratosis patients between August, 2014 and November, 2015. RCM analyses were performed in one randomly selected actinic keratosis lesion of the upper limbs by two independent observers before and after 5% 5-fluorouracil treatment. At the end of treatment and with clinical bleaching of treated lesions, histological examination was performed by two pathologists.

Results

A total of 50 lesions were enrolled, and 40 lesions presented complete clinical bleaching after treatment and were included in the final analysis. Accuracy, sensibility and specificity means among observers were 83.8%, 84.6% and 83.3%, respectively. After 5-fluorouracil treatment, actinic keratosis was diagnosed in 45.0% (observer 1) and 32.5% (observer 2) of subjects according to RCM and in 32.5% of subjects according to histological examination. Considering RCM observers diagnosis, the concordance was substantial (k 0,637, p<0,001). 5-fluorouracil led to a reduction in 55.0%-67.5% of actinic keratoses according to RCM analysis.

Conclusion

This study allows to validate of RCM as a non-invasive method capable of monitoring actinic keratosis therapeutic response to 5-fluorouracil, presenting efficacy comparable to histological examination. Additionally, the results suggest that 5-fluorouracil may be a satisfactory option for therapeutic control of this condition.

This article is protected by copyright. All rights reserved.

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Novel device-based acne treatments: comparison of a 1,450-nm diode laser and micro-needling radiofrequency on mild to moderate acne vulgaris and seborrhea in Korean patients through a 20-week prospective, randomized, split-face study

Abstract

Background

While device-based acne treatments are widely applied for patients not tolerating conventional medications, related controlled studies have been still limited. Recently, non-ablative 1,450-nm diode laser (DL) and fractional micro-needling radiofrequency (FMR) have been effectively used for acne, in addition to well-recognized dermal remodeling effects.

Objective

To compare the clinical course for acne treatment between DL and FMR.

Methods

Twenty five Korean patients with mild to moderate facial acne completed treatments with DL and FMR through a 20-week, randomized split-face study. One randomly assigned half side of each patient's face received DL and the other side by FMR. Treatments were scheduled to receive three consecutive sessions at 4-week intervals. Objective assessments including revised Leeds grades, lesion counts, sebum output measurements, and patients' subjective satisfaction were investigated.

Results

Both DL and FMR demonstrated steady improvement of acne and seborrhea during treatment sessions. While results between two devices were similar during treatment sessions, FMR was superior to DL in the 12-week follow up. Patients' subjective assessments for seborrhea improvement were similar between two devices, while those for acne, skin texture, and acne scars were more satisfactory for FMR. For safety proflie, no significant difference was observed between two regimens, while mild post inflammatory hyperpigmentation was observed only in DL side.

Conclusion

Both DL and FMR demonstrated efficacies for acne and seborrhea, with reasonable safety proflie. FMR was more effective than DL for the long-term maintenance, and subjective assessments for texture and scar improvements. Therefore, a few sessions of these devices would be a viable option for acne treatments.

This article is protected by copyright. All rights reserved.

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Educational and Practice Gaps in the Management of Volar Melanocytic Lesions

Abstract

Background

The benign and malignant patterns of acral melanocytic nevi (AMN) and acral melanomas (AM) have been defined in a series of retrospective studies. A 3-step algorithm was developed to determine when to biopsy acral melanocytic lesions. This algorithm has only been applied to a Japanese population.

Objectives

Our study aimed to review the current management strategy of acral melanocytic lesions and to investigate the utility of the 3-step algorithm in a predominately Caucasian cohort.

Methods

A retrospective search of the pathology and image databases at Mayo Clinic was performed between the years 2006 – 2016. Only cases located on a volar surface with dermoscopic images were included. Two dermatologists reviewed all dermoscopic images and assigned a global dermoscopic pattern. Clinical and follow-up data was gathered by chart review. All lesions with known diameter and pathological diagnosis were used for the 3-step algorithm.

Results

Regular fibrillar and ridge patterns were more likely to be biopsied (p=0.01). The majority of AMN (58.1%) and AM (60%) biopsied were due to physician-deemed concerning dermoscopic patterns. 39.2% of these cases were parallel furrow, lattice-like, or regular fibrillar. When patients were asked to follow-up within a 3-6-month period, only 16.7% of the patients returned within that interval. The 3-step algorithm would have correctly identified 4/5 AM for biopsy, missing a 6mm, multi-component, invasive melanoma.

Conclusion

We found one major educational gap in the recognition of low risk lesions with high rates of biopsy of the fibrillary pattern. Recognizing low-risk dermoscopic patterns could reduce the rate of biopsy of AMN by 23.3%. We identified two major practice gaps, poor patient compliance with follow up and the potential insensitivity of the 3-step algorithm to small multi-component acral melanocytic lesions.

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Cutaneous granuloma caused by Rhizopus oryzae with a novel mutation in the CYBB gene in a monozygotic male twin

Abstract

A 2-year-old Chinese boy presented to our institution with a large lump in the sacrococcygeal region for two months, along with fever for five days. The initial lesion presented as a red papule accompanied by itching, and then progressed to 10 cm in diameter (Fig. 1a). Five days previously, the patient had developed a fever.

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Response to – Bullous pemphigoid inguinalis?

Abstract

We appreciate the constructive comments by author Abdelmaksoud in response to our report of bullous pemphigoid (BP) presenting in association with metastatic penile squamous cell carcinoma (SCC). Though our patient had few blisters on the back, upper limbs and oral cavity, the chief brunt of the disease was on the inguinal area. Cases of localized BP, arising after radiotherapy for breast carcinoma have been reported. Our patient developed BP before receiving radiotherapy.

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Bullous Pemphigoid Inguinalis?

Abstract

I read with great interest a case report by Bishnoi et al. published recently in the journal of European Academy of Dermatology and Venereology. The authors presented a case of a 43-year old man who had history of penile SCC, presented with bullous pemphigoid (BP) lesions. Interestingly, the BP lesion was limited to the inguinal region, suprapubic area and inner aspect of the right thigh, that was predominantly on top of the bilateral metastatic inguinal lymphadenopathy(LN).

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Electrochemotherapy of unresectable cutaneous tumors with reduced dosages of intravenous bleomycin: analysis of 57 patients from the InspECT (International network for sharing practices of ElectroChemoTherapy) registry

Abstract

Background

Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumors of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable in order to ameliorate ECT safety profile.

Objective

The aim of this study was to evaluate the efficacy and toxicity of ECT with reduced chemotherapy dosages.

Methods

In a retrospective analysis of a prospectively maintained database (InspECT registry), we evaluated the outcome of patients who received ECT with reduced dosages of bleomycin (7.500, 10.000, or 13.500 IU/m², instead of the standard dose of 15.000 IU/m²). Tumor response in melanoma patients was compared with melanoma patients of the InspECT registry who received the standard dose of bleomycin.

Results

We identified 57 patients with 147 tumors (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma, 17.5%; breast cancer 7%, Kaposi sarcoma 7%, other histotypes, 7.1%. Per-tumor complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per-patient CR was 57.9% (partial, 21.1%). Local pain was the most frequently reported side effect (n=22 patients [39%], mostly mild; 2 patients experienced flu-like symptoms, 1 patient nausea. We observed the same CR rate (55%) in melanoma patients treated by reduced or conventional bleomycin dosages (p=1.00).

Conclusions

ECT performed with reduced bleomycin dosages could be as effective as with currently recommended dose. Patients with impaired renal function or candidate to multiple ECT cycles could benefit from a reduced dose protocol. Our findings need prospective confirmation before being adopted in clinical practice.

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Does obesity cause a distinct phenotype of hidradenitis suppurativa?

Abstract

I have read the article by Theut Riis et al proposing BMI based clinical subtypes of hidradenitis suppurativa (HS) patients with interest. In addition to giving valuable clinical information, the article is important in the discussion of the pathophysiology of such HS subgroups, with focus on the obese subtype. The papers main difference from earlier clinical proposals of subtyping is the focus on the body mass index (BMI) as a functional factor in the disease evolution.

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Association Between Pepsin in the Saliva and the Subjective Symptoms in Patients With Laryngopharyngeal Reflux

Our study was designed to further evaluate the relationships between the saliva pepsin level and the symptoms and quality of life of patients with laryngopharyngeal reflux (LPR).

http://ift.tt/2A5Odu4

A case of large cell neuroendocrine carcinoma of the uterine cervix misdiagnosed as adenocarcinoma in Thinprep cytology test

Jong-Hee Nam, Jongin Na, Nah-Ihm Kim, Ga-Eon Kim, Chang-Soo Park, Yoo-Duk Choi

CytoJournal 2017 14(1):28-28

Large cell neuroendocrine carcinoma (LCNEC) of uterine cervix is a rare malignancy with aggressive behavior and poor clinical outcome even in its early stage. Few cytopathologic features of cervical LCNEC have been reported previously. A 57-year-old postmenopausal African American female, presented to the local health department with a chief complaint of heavy vaginal bleeding. A 45-year-old female presented with 20 months of vaginal pruritus and foul odor. Cervical malignancy was suspected by pelvis magnetic resonance imaging. Thinprep cytology test demonstrated ball-like tumor cell clusters in a necrotic background. Cytologic diagnosis of adenocarcinoma was rendered. However, the histologic and immunohistochemical examination of cervical biopsy revealed the LCNEC of the uterine cervix. Due to its rarity, LCNEC may pose a diagnostic challenge in cervical cytology. Cytopathologists should pay attention to the cytological features of cervical LCNEC, such as rosettoid pattern, nuclear molding, and thin nuclear membrane for differentiation from other mimics.

http://ift.tt/2BjpSi6

Cytokeratin 20/p53 dual immunocytochemistry for improving the diagnostic accuracy of urine liquid-based cytology in the detection of urothelial neoplasm: A retrospective study

Hyun-Jung Kim, Ji-Hyeong Yoo

CytoJournal 2017 14(1):27-27

Backgrounds: Dual immunocytochemistry (DIC) with cytokeratin (CK) 20 and p53 in liquid-based cytology is a tool for improving the accuracy of urine cytology (UC). This study was conducted to compare the diagnostic accuracy of UC alone with that of UC combined with CK20/p53 DIC. Methods: We retrieved urine samples collected between January 2015 and March 2016 stored in PreservCyt®solution that were from cases categorized as malignant, highly suspicious, suspicious, and atypical and that were matched with a subsequent biopsy. We re-prepared 63 samples of 28 patients for DIC and blindly evaluated 63 pairs of original Papanicolaou smears and DIC. Results: Of the 63 samples, 11 could not be analyzed because of the low number of atypical urothelial cells, and the results of the remaining 52 samples were as follows: 34 positive and 18 negative. The positive predictive value of DIC was 100%, and the negative predictive value was 78%. Fifteen DIC-positive cases, histologically proven as malignant were originally diagnosed as highly suspicious (4), suspicious (8), and atypical (3), which were strongly suggestive of "urothelial carcinoma". Four negative cases, histologically confirmed as non-neoplastic cases, were filtered from false positivity. Conclusions: Despite the small sample size, this study demonstrated the diagnostic utility, high sensitivity, and positive predictive value of CK20/p53 DIC, especially in cases with a small number of single malignant cells or cellular clusters of reactive atypical urothelial cells. Thus, CK20/p53 DIC can be used for improving diagnostic accuracy of UC, either as an ancillary method to cytology or as a part of a potential future diagnostic panel to improve patient diagnosis and management.

http://ift.tt/2zkQUEu

Dysregulatory effects of retinoic acid isomers in late zebrafish embryos

Abstract

All-trans retinoic acid (atRA) and 9-cis retinoic acid (9cRA) are two natural derivatives of vitamin A that contribute to the normal vertebrate development by affecting gene expression through the retinoic acid signalling pathway. We show transcriptomic effects of the ectopic addition of atRA or 9cRA to zebrafish embryos at the posthatching embryonic stage. Exposure for 24 or 72 h to sublethal concentrations of both isomers resulted in characteristic transcriptome changes, in which many proliferation and development-related genes became underexpressed, whereas genes related to retinoid metabolism and some metabolic functions became overrepresented. While short and long exposures elicit essentially the same set of genes, atRA specifically induced expression of a specific subset of proteases, likely acting at the extracellular level, and of elements of the response to xenobiotics. These results reflect the well-known antiproliferative activity of retinoids, and they suggest a dysregulation of the developmental process at final stages of embryogenesis. They also indicate a potential role of endopeptidases as markers of developmental alterations, as well as their possible control by the retinoic signalling pathway. We propose to monitor mRNA levels of cyp16a, cyp16b, and cyp16c in zebrafish embryos as a bioassay for retinoid disruption.

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Volatile organic compounds and nitric oxide as responses of a Brazilian tropical species to ozone: the emission profile of young and mature leaves

Abstract

The emission profile of volatile organic compounds (VOCs) and nitric oxide (NO) in young and mature leaves of Croton floribundus was assessed in plants exposed to filtered air (FA) and ozone-enriched filtered air (FA+O₃). After the period of exposure, leaves were enclosed in polyethylene terephthalate bags and VOCs were collected in young and mature leaves. Both young and mature leaves constitutively emitted the same VOC, but the concentrations were higher in young leaves. O₃ exposure induced the emission of sesquiterpenes (mainly β-caryophyllene) known as antioxidant compounds that may scavenge O₃. Young leaves were the highest emitters of sesquiterpenes. O₃ induced a rapid accumulation of NO in different tissues and leaf developmental stages; this accumulation was marked in palisade and spongy parenchyma cells in young and mature leaves, respectively. O₃ altered the levels of the signaling compound methyl salicylate (MeSA). Moreover, our data showed that NO together with VOC emissions, such as geranyl acetate, α-cadiene, trans-farnesol, cis-β-farnesene, and MeSA, participate of plant defense mechanisms against the oxidative damage caused by O₃.

http://ift.tt/2mZdqBi

Enhanced phosphorus removal using acid-treated magnesium slag particles

Abstract

Magnesium-enriched magnesium slag particles (MSPs) can be used as an adsorption substrate as well as the magnesium source for struvite precipitation. In this study, an HCl treatment was used to enhance MSPs for phosphorus removal. After soaking in 1 mol/L HCl, an 11.27% decrease in median diameter (D50) and a 6.73% increase in specific surface area were observed when compared with the original MSPs. The improvement of the MSP surface properties resulted in 188.96 mg/kg increase in the PO₄³⁻ adsorption capacity. Irrespective of HCl treatment, the phosphorus adsorption process followed the Dubinin–Radushkevich (D–R) model much more accurately than the Langmuir and Freundlich equations with correlation coefficients higher than 0.94. The adsorption free energy obtained through the D–R model revealed a 9.75% decrease after HCl treatment. Sequential fraction extraction results indicated that 96% of the Mg²⁺ released from the HCl-treated MSPs came from acid-soluble magnesium (exchangeable and carbonate-bound). Mg²⁺ obtained from HCl-treated solutions provided a reliable magnesium source for struvite precipitation. The PO₄³⁻ removal rate can reach 53.63% with the optimal pH value of 10.0 and molar ratio of NH₄⁺ to PO₄³⁻ of 1:1. Struvite precipitation and adsorption can simultaneously occur in HCl-treated MSP solution. It contributed 63.19% to the overall PO₄³⁻ removal and is a major contributor compared with adsorption. Thus, HCl treatment greatly enhanced the potential of MSPs for phosphorus removal due to an improved adsorption capacity and is a reliable Mg²⁺ source for struvite precipitation.

http://ift.tt/2zB94Gt

PCDD/PCDF formation in the chlor-alkali process—laboratory study and comparison with patterns from contaminated sites

Abstract

Studies on the formation of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) during the electrolysis of sodium chloride solution (brine) using graphite or titanium electrodes were carried out at a laboratory scale. High concentrations of PCDFs but no PCDDs were formed in tests using graphite electrodes. With titanium electrodes, PCDFs were only formed when tar pitch was added and mainly originated from the dibenzofuran present in the tar. For the first time, a detailed assessment of the formation of mono- to octachlorinated PCDD/PCDF from tar pitch was investigated. The assessment included of the chlorination steps proved that PCDFs were formed by successive lateral chlorinated from dibenzofuran to MonoCDFs, DiCDFs, and TriCDFs to form the typical known "chlorine pattern" of TetraCDF to OctaCDF with a dominance of 1,2,7,8- and 2,3,7,8-TetraCDFs, 1,2,3,7,8-PentaCDF, and 1,2,3,4,7,8-HexaCDF as marker congeners. The final homologue distributions depended on reaction time and reaction temperature. In addition, electrolysis with non-chlorinated dibenzo-p-dioxins, dibenzofuran, and biphenyl was carried out. As a result, PCDDs, PCDFs, and PCB were formed at comparable yields. Congener patterns in soil samples from a PCDD/F-contaminated site where chlor-alkali electrolysis had been operated for decades in Japan had identical isomer distribution demonstrating the source and contamination potential and risk of these processes. Therefore, sites where in the past 120 years chlor-alkali electrolysis has been operated or where residues from chlor-alkali production or other chlorine using industries have been disposed should be assessed for their pollution level and exposure relevance. The assessment of total organohalogen content revealed that PCDF is only a small fraction of organohalogens in the contaminated soils. For an appropriate risk assessment, also other chlorinated aromatic compounds such as PCBs or PCNs need to be considered.

http://ift.tt/2n1VlSY

Dimensions of hard and soft tissue around adjacent, compared with single-tooth, zirconia implants

Preservation or regeneration of the papilla has always been a challenge around consecutive implants or with implants next to teeth, and many studies have evaluated the papilla's behaviour and patterns based on surgical technique and prosthetic design, though evidence about its behaviour around zirconia implants is scarce. The aim of this study was to evaluate papilla behaviour between implants and teeth (tooth-implant group) and between consecutive implants (implant–implant group). Ninety patients with 122 zirconia implants (Straumann® PURE Ceramic Implant) were examined at the one-year follow up.

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Recurrence of oral mucocoeles in adolescents after excision

Although mucocoeles can occur at any age, children and adolescents are most commonly affected, and excision is the most common treatment.1

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Upregulation of angiogenesis in oral lichen planus

Abstract

Objectives

Since angiogenesis is fundamental to the pathogenesis of many chronic inflammatory disorders this study investigated the expression of various vascular markers in oral lichen planus and non-specific oral mucosal inflammatory tissues.

Methods

Archival specimens of oral lichen planus (n=15) and inflamed tissues (n=13) were stained using immunohistochemistry with antibodies to CD34, vascular endothelial growth factor, vascular endothelial growth factor receptor and vasohibin. Nine representative sites at the epithelial-connective tissue junction and through the fibrous connective tissue were selected and automated analysis techniques were used to determine the extent of positivity expressed as the percentage of positive cells. Significance was denoted when p<0.05.

Results

The expression of pro-angiogenic factors was higher in lichen planus samples compared with inflamed controls. A higher level of CD34 was observed in the deeper parts of the connective tissue of OLP (p=0.04), whereas VEGF and VEGFR2 expression was higher all through the tissues (respectively p<0.02 and p<0.01). The expression of the anti-angiogenic VASH1 was higher in inflamed tissue compared with lichen planus in all sites evaluated (p<0.01).

Conclusions

The findings indicate that angiogenic factors are differentially expressed in oral lichen planus compared with inflamed controls, with increased expression of pro-angiogenic factors and decreased anti-angiogenic expression.

This article is protected by copyright. All rights reserved.

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Clinical effects of submucosal middle turbinectomy for eosinophilic chronic rhinosinusitis

The preservation or resection of the middle turbinate (MT) during endoscopic sinus surgery (ESS) currently remains a matter of debate. The present study aimed to investigate the effects of submucosal middle turbinectomy (SMT) in ESS for eosinophilic chronic rhinosinusitis (ECRS).

http://ift.tt/2hRZgfM

Clinical effects of submucosal middle turbinectomy for eosinophilic chronic rhinosinusitis

The preservation or resection of the middle turbinate (MT) during endoscopic sinus surgery (ESS) currently remains a matter of debate. The present study aimed to investigate the effects of submucosal middle turbinectomy (SMT) in ESS for eosinophilic chronic rhinosinusitis (ECRS).

http://ift.tt/2hRZgfM

The association between atopic dermatitis and hand eczema: a systematic review and meta-analysis

Abstract

Atopic dermatitis (AD) and hand eczema (HE) are common chronic and relapsing inflammatory skin conditions that often co-occur. While several studies have addressed their relationship, the exact association estimate is unknown. We systematically reviewed published literature on the association between AD and HE in PubMed, Embase, and Web of Science using the following search terms; (atopic dermatitis OR atopic eczema) AND (hand dermatitis OR hand eczema). Meta-analyses were then performed to examine the association between AD and the point-, one-year- and lifetime prevalence of HE, respectively. We identified 35 relevant studies, of which 26 were included in the meta-analyses. AD was associated with an increased prevalence of HE with regards to point- (odds ratio (OR) 2.35; 95% CI: 1.47-3.76), one-year- (OR 4.29; 95% CI: 3.13-5.88), and lifetime prevalence (OR 4.06; 95% CI: 2.72-6.06). Furthermore, positive associations between AD and occupational HE were identified when assessing the one-year- 4.31 (95% CI: 2.08-8.91) and lifetime prevalence (OR 2.81; 95% CI: 2.08-3.79). Similar positive associations were found in the general population studies, i.e. OR 4.19 (95% CI: 3.46-5.08) and OR 5.69 (95% CI: 4.41-7.36). Important study limitations include the wide use of questionnaire studies, and lack of prospective studies as well as poor clinical phenotype descriptions. In conclusion, our systematic review and meta-analysis showed that patients with AD had a strongly increased prevalence of HE. Clinicians should continue to guide patients with AD away from occupations with high risk of HE.

This article is protected by copyright. All rights reserved.

http://ift.tt/2BjZDYU

The association between atopic dermatitis and hand eczema: a systematic review and meta-analysis

Abstract

Atopic dermatitis (AD) and hand eczema (HE) are common chronic and relapsing inflammatory skin conditions that often co-occur. While several studies have addressed their relationship, the exact association estimate is unknown. We systematically reviewed published literature on the association between AD and HE in PubMed, Embase, and Web of Science using the following search terms; (atopic dermatitis OR atopic eczema) AND (hand dermatitis OR hand eczema). Meta-analyses were then performed to examine the association between AD and the point-, one-year- and lifetime prevalence of HE, respectively. We identified 35 relevant studies, of which 26 were included in the meta-analyses. AD was associated with an increased prevalence of HE with regards to point- (odds ratio (OR) 2.35; 95% CI: 1.47-3.76), one-year- (OR 4.29; 95% CI: 3.13-5.88), and lifetime prevalence (OR 4.06; 95% CI: 2.72-6.06). Furthermore, positive associations between AD and occupational HE were identified when assessing the one-year- 4.31 (95% CI: 2.08-8.91) and lifetime prevalence (OR 2.81; 95% CI: 2.08-3.79). Similar positive associations were found in the general population studies, i.e. OR 4.19 (95% CI: 3.46-5.08) and OR 5.69 (95% CI: 4.41-7.36). Important study limitations include the wide use of questionnaire studies, and lack of prospective studies as well as poor clinical phenotype descriptions. In conclusion, our systematic review and meta-analysis showed that patients with AD had a strongly increased prevalence of HE. Clinicians should continue to guide patients with AD away from occupations with high risk of HE.

This article is protected by copyright. All rights reserved.

http://ift.tt/2BjZDYU

Evidence for lattice softening of the Fe-Ga magnetostrictive alloy: Stress-induced local martensites

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): Xiaolian Liu, Meixun Li, Junming Gou, Qiaochu Li, Yunhao Lu, Tianyu Ma, Xiaobing Ren
The over tenfold magnetostriction enhancement by soluting nonmagnetic Ga into body centered cubic (BCC) Fe has been ascribed to crystal lattice softening, which indicates that the Fe-Ga solid solution lies in the crossover of martensitic transformation. Identifying the martensitic phase then becomes essential. Here we report the stress-induced local six-layer modulated monoclinic (6M) martensites in a Fe79Ga21 alloy solution-treated at 1373K. Although X-ray diffraction (XRD) and magnetic measurements reveal that the bulk sample exhibits BCC average structure, the transmission electronic microscopy (TEM) characterizations however show that the mechanically grinded foil sample contains local 6M phase. First principal calculations suggest that low formation energy barrier between the ordered D03 and the 6M phases are responsible for the stress-induced structural transformation. Our work provides evidence for the lattice softening of Fe-Ga solid solution, adding important insight into understanding the origin of its extraordinary magnetostriction enhancement.

Graphical abstract

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Compositional variation effects on the microstructure and properties of a refractory high-entropy superalloy AlMo0.5NbTa0.5TiZr

Publication date: 5 February 2018
Source:Materials & Design, Volume 139
Author(s): O.N. Senkov, J.K. Jensen, A.L. Pilchak, D.B. Miracle, H.L. Fraser
An AlMo0.5NbTa0.5TiZr baseline alloy was shown earlier to have good high temperature strength but poor ductility below 600°C due to coarse intermetallic grain boundary particles and a continuous ordered B2 matrix phase. Systematic composition changes intended to remove the deleterious microstructural features and to improve mechanical properties were explored in the present work. The baseline alloy and the new alloys studied here, AlMo0.5NbTa0.5TiZr0.5, AlNbTa0.5TiZr0.5, Al0.5Mo0.5NbTa0.5TiZr and Al0.25NbTaTiZr, all had an ordered B2 matrix crystal structure. Additionally, coherent BCC nanoscale precipitates were present at a high volume fraction inside the B2 matrix grains in AlMo0.5NbTa0.5TiZr, Al0.5Mo0.5NbTa0.5TiZr and Al0.25NbTaTiZr, and/or coarse, grain-boundary particles existed in AlMo0.5NbTa0.5TiZr and AlMo0.5NbTa0.5TiZr0.5. The mechanical properties were assessed with microhardness and compression testing at 25°C and 1000°C. Al0.5Mo0.5NbTa0.5TiZr showed the highest hardness (Hv=6.4GPa) and strength (σ0.2=2350MPa) at 25°C and modest strength (σ0.2=579MPa) at 1000°C. AlMo0.5NbTa0.5TiZr0.5 had the highest strength (σ0.2=935MPa) at 1000°C, but was brittle at 25°C. High-temperature deformation produced a desirable microstructure in Al0.5Mo0.5NbTa0.5TiZr and Al0.25NbTaTiZr alloys consisting of a continuous BCC phase and discontinuous B2 nano-precipitates. The relationships between the composition, microstructure, and properties were identified and discussed.

Graphical abstract

http://ift.tt/2jUY1AB

Ex-vivo flush of the limb allograft reduces inflammatory burden prior to transplantation

Passenger leukocytes and inflammatory debris transferred from the donor limb to the recipient can induce allorecognition, which activates the host immune response. This is the first study to evaluate whether the transfer of this inflammatory burden can be reduced via post-preservation flush prior to revascularisation, and whether this is influenced by ischaemia.

http://ift.tt/2jX4Em6

Erratum to “Reconstruction design before tumour resection: A new concept of through-and-through cheek defect reconstruction” [Oral Oncol. 74 (2017) 123–129]

The publisher regrets that the First Author's appears incorrectly in the publication. The First Author name should appear as above.

http://ift.tt/2zBeRM8

Dual loss of p110δ PI3-kinase and SKAP (KNSTRN) expression leads to combined immunodeficiency and multisystem syndromic features

Patients with Roifman-Chitayat syndrome suffer repeated infections due to combined immunodeficiency and display a wide array of syndromic features encompassing developmental delay, optic nerve atrophy and skeletal anomalies. We show here for the first time that complete SKAP and PI3K p110δ deficiencies lead to this complex syndrome.

http://ift.tt/2AtfBmt

Sensitivity and specificity of Frontal Assessment Battery in newly diagnosed and untreated Obstructive Sleep Apnea patients

Executive dysfunction (ED) is often observed in subjects diagnosed with obstructive sleep apnea (OSA), but their assessment requires facilities that are not always available. We aim to evaluate the extent to which Frontal Assessment Battery (FAB) discriminates ED in newly diagnosed, untreated and without comorbidities OSA patients.

http://ift.tt/2zmXKcP

Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: An IRLSSG task force report

Brain iron deficiency has been implicated in the pathophysiology of RLS, and current RLS treatment guidelines recommend iron treatment when peripheral iron levels are low. In order to assess the evidence on the oral and intravenous (IV) iron treatment of RLS and periodic limb movement disorder (PLMD) in adults and children, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force to review these studies and provide an evidence-based and consensus guidelines for the iron treatment of RLS in adults, and RLS and PLMD in children.

http://ift.tt/2BkKRRU

Validation study of the Vitiligo Extent Score-plus (VESplus)

http://ift.tt/2mZ2WBW

Estimating the cost of skin cancer detection by dermatology providers in a large healthcare system

Data on the cost and efficiency of skin cancer detection through total body skin examination (TBSE) are scarce.

http://ift.tt/2zBbuEZ

Future Considerations for Clinical Dermatology in the Setting of 21st Century American Policy Reform: The Relative Value Scale Update Committee

http://ift.tt/2zAR9jb

Lack of correlation of the patient derived vitiligo disease activity index (VIDA) with the clinician derived vitiligo activity severity index (VASI)

http://ift.tt/2mZ2Yd2

Drug survival of secukinumab in real-world plaque psoriasis patients: a 52-week, multicenter, retrospective study

http://ift.tt/2mYDs7x

Differentiating Merkel cell carcinoma of lymph nodes without a detectable primary skin tumor from other metastatic neuroendocrine carcinomas: the ELECTHIP criteria

-Merkel cell carcinoma may initially present in lymph nodes without an evident primary skin tumor.-When this occurs the tumor may be misdiagnosed as lymph node metastasis from other neuroendocrine carcinomas. -The ELECTHIP criteria assists in differentiating between these diagnoses and may help classify patients with neuroendocrine lymph node metastasis.

http://ift.tt/2zAcSHY

Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61
Author(s): Kirsten Thomsen, Takashi Yokota, Md Mahdi Hasan-Olive, Niloofar Sherazi, Nima Borhan Fakouri, Claus Desler, Christine Elisabeth Regnell, Steen Larsen, Lene Juel Rasmussen, Flemming Dela, Linda Hildegard Bergersen, Martin Lauritzen
Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB^m/m) and C57Bl/6 (WT) controls and comparing young (2–5 months) to middle-aged mice (13–14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB^m/m hippocampus, but not in CSB^m/m cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably, an inverse correlation between heterogeneity and CI was found in both genotypes, indicating that heterogeneity reflects mitochondrial dysfunction. The ratio between fission and fusion gene expression reflected age-related alterations in mitochondrial morphology but not heterogeneity. Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB^m/m compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging.



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NEK1 genetic variability in a Belgian cohort of ALS and ALS-FTD patients

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61
Author(s): Hung Phuoc Nguyen, Sara Van Mossevelde, Lubina Dillen, Jan L. De Bleecker, Matthieu Moisse, Philip Van Damme, Christine Van Broeckhoven, Julie van der Zee
We evaluated the genetic impact of the amyotrophic lateral sclerosis (ALS) risk gene never in mitosis gene a–related kinase 1 (NEK1) in a Belgian cohort of 278 patients with ALS (n = 245) or ALS with frontotemporal dementia (ALS-FTD, n = 33) and 609 control individuals. We identified 2 ALS patients carrying a loss-of-function (LOF) mutation, p.Leu854Tyrfs*2 and p.Tyr871Valfs*17, that was absent in the control group. A third LOF variant p.Ser1036* was present in 2 sibs with familial ALS but also in an unrelated control person. Missense variants were common in both patients (3.6%) and controls (3.0%). The missense variant, p.Arg261His, which was previously associated with ALS risk, was detected with a minor allele frequency of 0.90% in patients compared to 0.33% in controls. Taken together, NEK1 LOF variants accounted for 1.1% of patients, although interpretation of pathogenicity and penetrance is complicated by the observation of occasional LOF variants in unaffected individuals (0.16%). Furthermore, enrichment of additional ALS gene mutations was observed in NEK1 carriers, suggestive of a "second hit" model were NEK1 variants may modify disease presentation of driving mutations.



http://ift.tt/2zzFUY7

Thinner cortex in patients with subjective cognitive decline is associated with steeper decline of memory

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61
Author(s): Sander C.J. Verfaillie, Rosalinde E. Slot, Betty M. Tijms, Femke Bouwman, Marije R. Benedictus, Jozefien M. Overbeek, Teddy Koene, Hugo Vrenken, Philip Scheltens, Frederik Barkhof, Wiesje M. van der Flier
We aimed to investigate associations between regional cortical thickness and rate of decline over time in 4 cognitive domains in patients with subjective cognitive decline (SCD). We included 233 SCD patients with the total number of 654 neuropsychological assessments (median = 3, range = 2–8) and available baseline magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63 ± 9, Mini–Mental State Examination score: 28 ± 2). We assessed longitudinal cognitive functioning at baseline and follow-up in 4 cognitive domains (composite Z-scores): memory, attention, executive function, and language. Thickness (millimeter) was estimated using FreeSurfer for frontal, temporal, parietal, cingulate, and occipital cortices. We used linear mixed models to estimate effects of cortical thickness on cognitive performance (dependent variables). There were no associations between cortical thickness and baseline cognition, but a faster subsequent rate of memory loss was associated with thinner cortex of the frontal [β (SE) = 0.20 (0.07)], temporal [β (SE) = 0.18 (0.07)], and occipital [β (SE) = 0.22 (0.09)] cortices (all p < 0.05FDR). These findings illustrate that early cortical changes, particularly in the temporal cortex, herald incipient cognitive decline related to neurodegenerative diseases, most prominently Alzheimer's disease.



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Contents continued

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61





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Splenectomy protects aged mice from injury after experimental stroke

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61
Author(s): Anjali Chauhan, Abdullah Al Mamun, Gabriel Spiegel, Nia Harris, Liang Zhu, Louise D. McCullough
Elderly stroke patients and aged animals subjected to experimental stroke have significantly worse functional recovery and higher mortality compared to younger subjects. Activation of the peripheral immune system is known to influence stroke outcome. Prior studies have shown that splenectomy reduces ischemic brain injury in young mice. As immune function changes with aging, it is unclear whether splenectomy will confer similar benefits in aged animals. We investigated the contribution of spleen to brain injury after cerebral ischemia in aged male mice. Splenic architecture and immune cell composition were altered in aged mice. Splenectomy 2 weeks before stroke resulted in improved neurobehavioral and infarct outcomes in aged male mice. In addition, there was a reduction in peripheral immune cell infiltration into the brain and decreased levels of peripheral inflammatory cytokines after stroke in aged splenectomized mice. Splenectomy immediately after reperfusion also improved behavioral and infarct outcomes. This study suggests that inhibition of the splenic immune response is a translationally relevant target to pursue for stroke treatment in aged individuals.



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Editorial Advisory Board

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61





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Neuronal and behavioral effects of multi-day brain stimulation and memory training

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61
Author(s): Daria Antonenko, Nadine Külzow, Angelica Sousa, Kristin Prehn, Ulrike Grittner, Agnes Flöel
Strategies for memory enhancement, especially for the older population, are of great scientific and public interest. Here, we aimed at investigating neuronal and behavioral effects of transcranial direct current stimulation (tDCS) paired with memory training. Young and older adults were trained on an object-location-memory task on 3 consecutive days with either anodal or sham tDCS. Recall performance was assessed immediately after training, 1 day and 1 month later, as well as performance on trained function and transfer task. Resting-state functional magnetic resonance imaging was conducted at baseline and at 1-day follow-up to analyze functional coupling in the default mode network. Anodal tDCS led to superior recall performance after training, an associated increase in default mode network strength and enhanced trained function and transfer after 1 month. Our findings suggest that tDCS-accompanied multi-day training improves performance on trained material, is associated with beneficial memory network alterations, and transfers to other memory tasks. Our study provides insight into tDCS-induced behavioral and neuronal alterations and will help to develop interventions against age-related cognitive decline.



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Contents

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61





http://ift.tt/2zAdInY

Harmonization of cortical thickness measurements across scanners and sites

Publication date: 15 February 2018
Source:NeuroImage, Volume 167
Author(s): Jean-Philippe Fortin, Nicholas Cullen, Yvette I. Sheline, Warren D. Taylor, Irem Aselcioglu, Philip A. Cook, Phil Adams, Crystal Cooper, Maurizio Fava, Patrick J. McGrath, Melvin McInnis, Mary L. Phillips, Madhukar H. Trivedi, Myrna M. Weissman, Russell T. Shinohara
With the proliferation of multi-site neuroimaging studies, there is a greater need for handling non-biological variance introduced by differences in MRI scanners and acquisition protocols. Such unwanted sources of variation, which we refer to as "scanner effects", can hinder the detection of imaging features associated with clinical covariates of interest and cause spurious findings. In this paper, we investigate scanner effects in two large multi-site studies on cortical thickness measurements across a total of 11 scanners. We propose a set of tools for visualizing and identifying scanner effects that are generalizable to other modalities. We then propose to use ComBat, a technique adopted from the genomics literature and recently applied to diffusion tensor imaging data, to combine and harmonize cortical thickness values across scanners. We show that ComBat removes unwanted sources of scan variability while simultaneously increasing the power and reproducibility of subsequent statistical analyses. We also show that ComBat is useful for combining imaging data with the goal of studying life-span trajectories in the brain.



http://ift.tt/2mZJJA2

Characterization of epitope specificities of reference antibodies used for the quantification of the birch pollen allergen Bet v 1

Abstract

Background

Accurate allergen quantification is needed to document the consistency of allergen extracts used for immunotherapy. Herein, we characterize the epitope specificities of two monoclonal antibodies used in an ELISA for the quantification of the major birch pollen allergen Bet v 1, established as a reference by the BSP090 European project.

Methods

The ability of mAbs 5B4 and 6H4 to recognize Bet v 1 isoforms was addressed by immunochromatography. The capacity of each mAb to compete with patients' IgE for binding to Bet v 1 was measured by ELISA inhibition. Epitope mapping was performed by pepscan analysis, site-directed mutagenesis and hydrogen/deuterium exchange-mass spectrometry.

Results

The 5B4 epitope corresponds to a peptide sequence (I56-K68) overlapping with the binding sites of patients' serum IgEs. Mutation of residues P59, E60 and K65 abolishes 5B4 binding to Bet v 1 and reduces the level of IgE recognition. In contrast, 6H4 recognizes a conformational epitope lying opposite to the 5B4 binding site, involving residues located in segments I44-K55 and R70-F79. Substitution of E45 reduces the binding capacity of 6H4, confirming that it is critical for the interaction. Both mAbs interact with >90% of Bet v 1 content present in the birch pollen extract, while displaying a weak cross-reactivity with other allergens of the PR-10 family.

Conclusions

MAbs 5B4 and 6H4 recognize structurally distinct epitopes present in the vast majority of Bet v 1 isoforms. These results support the relevance as a reference method of the Bet v 1-specific quantitative ELISA adopted by the European Pharmacopoeia.

This article is protected by copyright. All rights reserved.

http://ift.tt/2zAEz34

Characterization of epitope specificities of reference antibodies used for the quantification of the birch pollen allergen Bet v 1

Abstract

Background

Accurate allergen quantification is needed to document the consistency of allergen extracts used for immunotherapy. Herein, we characterize the epitope specificities of two monoclonal antibodies used in an ELISA for the quantification of the major birch pollen allergen Bet v 1, established as a reference by the BSP090 European project.

Methods

The ability of mAbs 5B4 and 6H4 to recognize Bet v 1 isoforms was addressed by immunochromatography. The capacity of each mAb to compete with patients' IgE for binding to Bet v 1 was measured by ELISA inhibition. Epitope mapping was performed by pepscan analysis, site-directed mutagenesis and hydrogen/deuterium exchange-mass spectrometry.

Results

The 5B4 epitope corresponds to a peptide sequence (I56-K68) overlapping with the binding sites of patients' serum IgEs. Mutation of residues P59, E60 and K65 abolishes 5B4 binding to Bet v 1 and reduces the level of IgE recognition. In contrast, 6H4 recognizes a conformational epitope lying opposite to the 5B4 binding site, involving residues located in segments I44-K55 and R70-F79. Substitution of E45 reduces the binding capacity of 6H4, confirming that it is critical for the interaction. Both mAbs interact with >90% of Bet v 1 content present in the birch pollen extract, while displaying a weak cross-reactivity with other allergens of the PR-10 family.

Conclusions

MAbs 5B4 and 6H4 recognize structurally distinct epitopes present in the vast majority of Bet v 1 isoforms. These results support the relevance as a reference method of the Bet v 1-specific quantitative ELISA adopted by the European Pharmacopoeia.

This article is protected by copyright. All rights reserved.

http://ift.tt/2zAEz34

Time and motion studies of National Health Service cataract theatre lists to determine strategies to improve efficiency

Aim

To provide a quantitative assessment of cataract theatre lists focusing on productivity and staffing levels/tasks using time and motion studies.

Methods

National Health Service (NHS) cataract theatre lists were prospectively observed in five different institutions (four NHS hospitals and one private hospital). Individual tasks and their timings of every member of staff were recorded. Multiple linear regression analyses were performed to investigate possible associations between individual timings and tasks.

Results

140 operations were studied over 18 theatre sessions. The median number of scheduled cataract operations was 7 (range: 5–14). The average duration of an operation was 10.3 min±(SD 4.11 min). The average time to complete one case including patient turnaround was 19.97 min (SD 8.77 min). The proportion of the surgeons' time occupied on total duties or operating ranged from 65.2% to 76.1% and from 42.4% to 56.7%, respectively. The correlations of the surgical time to patient time in theatre was R²=0.95. A multiple linear regression model found a significant association (F(3,111)=32.86, P<0.001) with R²=0.47 between the duration of one operation and the number of allied healthcare professionals (AHPs), the number of AHP key tasks and the time taken to perform these key tasks by the AHPs.

Conclusions

Significant variability in the number of cases performed and the efficiency of patient flow were found between different institutions. Time and motion studies identified requirements for high-volume models and factors relating to performance. Supporting the surgeon with sufficient AHPs and tasks performed by AHPs could improve surgical efficiency up to approximately double productivity over conventional theatre models.

http://ift.tt/2Bkf9UM

Macular thickness profile and diabetic retinopathy: the Singapore Epidemiology of Eye Diseases Study

Background

To evaluate retinal thickness profiles in eyes with and without diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD-OCT) among individuals with diabetes.

Methods

Participants were recruited from the Singapore Epidemiology of Eye Diseases Study, a population-based study among Chinese, Malays and Indians aged 40 years or older residing in Singapore. All participants underwent standardised systemic and ophthalmic examinations. Average thickness of the macula, ganglion cell-inner plexiform layer and outer retina layer (from the outer plexiform layer to the retinal pigment epithelium layer) were measured using SD-OCT. DR status and severity were graded based on fundus photographs using the modified Airlie House classification system. Participants with macular oedema were excluded.

Results

2240 eyes from 1280 participants were included. Of these, 1764 (78.7%) eyes had no DR, 351 (15.7%) eyes had minimal or mild DR and 125 (5.6%) eyes had moderate or worse DR. After adjusting for age, gender, ethnicity, axial length, hypertension, glycated haemoglobin, body mass index, total cholesterol and diabetes duration, eyes with DR had thicker macula (245.44 µm vs 243.04 µm, P=0.03) and outer retina (124.26 µm vs 123.08 µm, P=0.01) than eyes without DR. When stratified by DR severity, thicker macula (250.24 µm vs 242.88 µm, P=0.011) and outer retina (126.4 µm vs 123.0 μm, P=0.006) were observed in eyes with moderate or worse, but not minimal or mild DR, compared with eyes without DR.

Conclusions

Even in the absence of macular oedema, eyes with DR, particularly those with more severe DR, had thicker macular and outer retinal layers than eyes without DR.

http://ift.tt/2zjsZVV

Dermoscopy of different stages of lymphomatoid papulosis

Abstract

A 47-year-old man presented with a 3-year history of asymptomatic, erythematous papules and nodules located on his trunk, buttocks and limbs (Fig.1). Lesions were at different stages of clinical development: some were crusted or ulcerated, other necrotic or cicatricial. The patient's medical history was not relevant.

This article is protected by copyright. All rights reserved.

http://ift.tt/2zzGwgk

All you should know about sunken eyes

A look at the condition of sunken eyes, where the eyes seem deep set and darkened. Included is detail on home remedies and when to see a doctor.

http://ift.tt/2A48Ir9

All you should know about sunken eyes

A look at the condition of sunken eyes, where the eyes seem deep set and darkened. Included is detail on home remedies and when to see a doctor.

http://ift.tt/2A48Ir9

A procedure to evaluate the factors determining the elemental composition of PM 2.5 . Case study: the Veneto region (northeastern Italy)

Abstract

The Po Valley is one of the most important hot spots in Europe for air pollution. Morphological features and anthropogenic pressures lead to frequent breaching of air quality standards and to high-pollution episodes in an ~46 × 10³-km²-wide alluvial lowland. Therefore, it is increasingly important to study the air quality in a wide geographical scale to better implement possible and successful mitigation measures. The Veneto region lies in the eastern part of the Po Valley and the elemental composition of PM has been mainly studied in the Venice area, whereas scarce data are available for the remaining territory of the region. In this study, the elemental composition of PM_2.5 was investigated over 1 year (2012–2013) at six major cities of the Veneto region. Samples were analyzed for 16 elements (Ca, Al, Fe, S, K, Mg, Ti, Mn, Zn, Ba, As, Ni, Pb, Sb, V, and Cu), and results were processed to investigate spatial and seasonal variations, the influence of meteorological factors, and the most probable sources by using a procedure based on (i) elemental ratios (Cu/Sb, Cu/Zn, Cu/Pb, Mn/V, V/Ni, and Zn/Pb), (ii) cluster analysis on wind data, and (iii) conditional probability function (CPF). The percentage of elements in PM_2.5 ranged between 11 and 20%, and Ca and S were the most abundant elements in the region. Typical seasonal variations and similar trends were exhibited by each element, especially in the lowland. Some elements such as Zn, K, Mn, Pb, and Sb were found at high concentrations during the cold period. However, no similar dispersion processes were observed throughout the region, and their concentrations were mostly depending on individual local sources. In the alpine and foothill parts of the region, lower concentrations were recorded with respect to the Po Valley cities, which resulted enriched of most of the elements considered in this study. The cluster analysis on wind data and the CPF of the ratio-related sources demonstrated that a widespread pollution condition exists in the region, apart from the coastal area. However, specific directions (e.g., a link with high-traffic roads, industrial areas, and airports) resulted the most probable explanation for each ratio-related source. In addition, the Veneto region hosts one of the most important Mediterranean ports for the cruise sector (Venice harbor), and its impact was previously demonstrated in the historical city center. In this study, the impact of Venice shipping emissions was estimated to be 3.5% of PM_2.5 in some particular days.

http://ift.tt/2hP5r4a

Evaluation of sources and fate of nitrates in the western Po plain groundwater (Italy) using nitrogen and boron isotopes

Abstract

Diffuse nitrate pollution in groundwater is currently considered one of the major causes of water quality degradation. Determining the sources of nitrate contamination is an important first step for a better management of water quality. Thus, the isotopic composition of nitrate (δ¹⁵N_NO3 and δ¹⁸O_NO3) and boron (δ¹¹B) were used to evaluate nitrate contamination sources and to identify geochemical processes occurring in the shallow and deep aquifers of the Turin-Cuneo plain (NW Italy). The study area is essentially an agricultural zone, where use of synthetic nitrogenous fertilizers and organic manure is a common practice and the connection to sewer services is locally lacking. Also livestock farming are highly developed. A groundwater sampling campaign was performed on 34 wells in the shallow aquifer and 8 wells in the deep aquifers, to analyze nitrate, chloride, boron, δ¹⁵N_NO3, δ¹⁸O_NO3 and δ¹¹B. Isotope data of nitrate indicate that nitrate contamination in the Turin-Cuneo plain originates from mixtures of synthetic and organic sources, slightly affected by denitrification, and manure or septic tank effluents. Moreover, boron isotopes were used to discriminate further among the main anthropogenic sources of pollution. The analyses results confirm that both animal manure and domestic sewage, especially under the city of Turin, can contribute to the nitrate contamination. The isotope analysis was also used for the evaluation of denitrification and nitrification processes: contrary to expectations, a significant denitrification phenomenon was assessed only in the shallow unconfined aquifer, especially in the Poirino Plateau, the most contaminated sector of the study area.

http://ift.tt/2A2rUoR

Risk of inferior alveolar nerve injury with coronectomy versus surgical extraction of mandibular third molars - A comparison of two techniques and review of the literature

Abstract

Background

The removal of mandibular third molar teeth is one of the most common oral surgical procedures. In a significant number of patients it carries a degree of associated morbidity, including damage to the inferior alveolar nerve (IAN). For this reason, practitioners desire the most up-to-date guidance on the most appropriate technique, informed by the best available evidence that will produce the lowest incidence of iatrogenic complications.

Objective

Perform a systematic review comparing the effect of coronectomy versus complete surgical extraction of mandibular third molar teeth on the risk of IAN injury and other complications in adults.

Data Sources

Studies were identified through Embase (1980-2015) and Ovid MEDLINE (1946-2015) database searches. Search terms included coronectomy, partial root removal, deliberate vital root retention, odontectomy, surgical removal, surgical extraction, complete tooth extraction, and extract*. Limits included humans, English language, and randomized controlled trials (RCTs).

Inclusion criteria

Only RCTs comparing IAN damage associated with surgical extraction of mandibular third molars versus coronectomy were included.

Results

From our database searches, we identified two unique RCTs matching the inclusion criteria. Both evaluated patients who had specific radiographic signs of intimate relationships with the IAN. Upon detailed analysis, the studies were noted to exhibit a high risk of bias in many categories, thereby rendering their results inconclusive.

Conclusion

Although evidence from two RCTs suggests that coronectomy can reduce the risk of IAN injury compared to surgical removal of high-risk mandibular third molars, the quality of evidence is insufficient to provide definitive conclusions regarding the preferred technique.

This article is protected by copyright. All rights reserved.

http://ift.tt/2zzsPxO

Fast trace determination of nine odorant and estrogenic chloro- and bromo-phenolic compounds in real water samples through automated solid-phase extraction coupled with liquid chromatography tandem mass spectrometry

Abstract

A fast and reliable method was developed for simultaneous trace determination of nine odorous and estrogenic chloro- and bromo-phenolic compounds (CPs and BPs) in water samples using solid-phase extraction (SPE) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS). For sample preparation, the extraction efficiencies of two widely applied cartridges Oasis HLB and Sep-Pak C18 were compared, and the Oasis HLB cartridge showed much better extraction performance; pH of water sample also plays important role on extraction, and pH = 2–3 was found to be most appropriate. For separation of the target compounds, small addition of ammonium hydroxide can obviously improve the detection sensitivity, and the optimized addition concentration was determined as 0.2%. The developed efficient method was validated and showed excellent linearity (R ² > 0.995), low limit of detection (LOD, 1.9–6.2 ng/L), and good recovery efficiencies of 57–95% in surface and tap water with low relative standard deviation (RSD, 1.3–17.4%). The developed method was finally applied to one tap and one surface water samples and most of these nine targets were detected, but all of them were below their odor thresholds, and their estrogen equivalent (EEQ) were also very low.

http://ift.tt/2zys5sT

Study on diesel vertical migration characteristics and mechanism in water-bearing sand stratum using an automated resistivity monitoring system

Abstract

Oil spills frequently occur on both land and sea. Petroleum in mobile phase will cause serious pollution in the sediment and can form a secondary pollution source. Therefore, it is very important to study the migration of petroleum in sediments ideally in a rapid and simplified approach. The release of diesel was simulated using fine beach sand to construct a model aquifer, and dynamic monitoring was carried out using an automated monitoring system including a resistivity probe originally developed by our research group. The mobile phase migration fronts were determined accurately using wavelet analysis method combined with resistivity curve method. Then, a relationship between resistivity and the joint oil–water content was established. The main conclusions were as follows. The seepage velocity of the diesel with high mobility at the initial stage of infiltration was faster, followed by a period when gravity seepage was dominant, and finally a redistribution period at the later stage, which was mainly an oil–water displacement process. The resistivity trends for diesel infiltration in different water-saturated soil layers varied with depth. The resistivity in the vadose zone fluctuated significantly, increasing initially and later decreasing. The resistivity change in the capillary zone was relatively small and constant in the initial stage; then, it increased and subsequently decreased. The resistivity in the saturated zone was basically unchanged with depth, and the value became slightly larger than the background value over time. Overall, for a large volume of mobile phase diesel leakage, the arrival migration fronts can be detected by wavelet analysis combined with resistivity curves. The thickness of the oil slick in the capillary zone can be estimated by resistivity changes. The relationships between resistivity and both the moisture content and oil–water joint saturation are in agreement with the linear models. The research results provide basic data and a new data processing method for monitoring of contaminated sites following major oil spills using the resistivity method.

http://ift.tt/2n0rDxJ