Editorial Board

Publication date: February 2017
Source:Clinical Immunology, Volume 175





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Intramammary 1,25-dihydroxyvitamin D3 treatment increases expression of host-defense genes in mammary immune cells of lactating dairy cattle.

Publication date: Available online 14 February 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Kathryn E. Merriman, Michael B. Poindexter, Mercedes F. Kweh, Jose E.P. Santos, Corwin D. Nelson
Bacterial infection of the mammary gland activates an intracrine vitamin D pathway in macrophages of dairy cows. The active hormone of the vitamin D pathway, 1,25-dihydroxyvitamin D3 (1,25D), stimulates nitric oxide and β-defensin responses in bovine monocyte cultures, but the effect of 1,25D on innate immune genes in the mammary gland remained unknown. Therefore, the objective of this study was to determine the effects intramammary 1,25D treatment on expression of vitamin D associated host-defenses of the bovine mammary gland. Intramammary treatment of normal, healthy mammary glands of lactating dairy cows (n=14) with 10μg 1,25D increased inducible nitric oxide synthase (iNOS) and β-defensin 7 (DEFB7) gene expression in total milk somatic cells more than two-fold relative to placebo-treated glands within 8h after treatment. The vitamin D 24-hydroxylase gene (CYP24A1) also was increased nearly 100-fold in 1,25D-treated glands within 4h after treatment but was not affected in placebo-treated glands. Both macrophages and neutrophils isolated from milk had increased CYP24A1 expression in response to 1,25D treatment but only macrophages had increased iNOS expression. Repeated intramammary 1,25D treatment, every 12h for 48h, of infected mammary glands of cows diagnosed with subclinical mastitis resulted in increased expression of CYP24A1, DEFB4, DEFB7 and iNOS genes compared to placebo-treated glands. The 1,25D treatment resulted in elevated serum 1,25D concentrations (55 vs 33pg/mL) compared to placebo but it did not change serum calcium concentrations or bacteria counts in milk of infected mammary glands. In conclusion, 1,25D upregulates iNOS and β-defensin genes in vivo in cattle and affirms earlier reports that vitamin D supports innate immune functions of cattle.



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HMBA is a putative HSP70 activator stimulating HEXIM1 expression that is down-regulated by estrogen

Publication date: Available online 14 February 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Rati Lama, Chunfang Gan, Nethrie Idippily, Viharika Bobba, David Danielpour, Monica Montano, Bin Su
Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is identified as a novel inhibitor of estrogen stimulated breast cell growth, and it suppresses estrogen receptor-α transcriptional activity. HEXIM1 protein level has been found to be downregulated by estrogens. Recently, HEXIM1 has been found to inhibit androgen receptor transcriptional activity as well. Researchers have used Hexamethylene bis-acetamide (HMBA) for decades to stimulate HEXIM1 expression, which also inhibit estrogen stimulated breast cancer cell gene activation and androgen stimulated prostate cancer gene activation. However, the direct molecular targets of HMBA that modulate the induction of HEXIM1 expression in mammalian cells have not been identified. Based on HMBA and its more potent analog 4a1, we designed molecular probes to pull down the binding proteins of these compounds. Via proteomic approach and biological assays, we demonstrate that HMBA and 4a1 are actually heat shock protein 70 (HSP70) binders. The known HSP70 activator showed similar activity as HMBA and 4a1 to induce HEXIM1 expression, suggesting that HMBA and 4a1 might be putative HSP70 activators. Molecular target identification of HMBA and 4a1 could lead to further structural optimization of the parental compound to generate more potent derivatives to stimulate HEXIM1 expression, which could be a novel approach for hormone dependent breast cancer and prostate cancer treatment.

Graphical abstract

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Lipophagic Panniculitis of Childhood: A Case Report and Comprehensive Review of the Literature.

Lipophagic panniculitis of childhood is a rare condition notable clinically for an inflammatory panniculitis followed by the development of permanent lipoatrophy. In this regard, the term lipoatrophic panniculitis has been used synonymously with lipophagic panniculitis. Additional designations include lipophagic lipoatrophic panniculitis and annular lipoatrophic panniculitis of the ankles. Although lipophagic panniculitis has been associated with a number of autoimmune phenomena, a paucity of reports and limited pathological analyses to date renders this disease an elusive one whose pathogenesis is not yet established. We describe the clinical, histopathologic, and immunohistochemical findings in a case of lipophagic panniculitis of childhood in a 7-year-old boy and present it in the context of a comprehensive review of the literature. Furthermore, we offer a hypothesis regarding the pathogenetic basis of lipophagic panniculitis of childhood, suggesting cellular immunity targeting the adipocyte at the crux of its pathogenesis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The histopathology of cutaneous polyarteritis nodosa and its relationship with lymphocytic thrombophilic arteritis

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Clinical use of magnetic resonance imaging across the prostate brachytherapy workflow

Publication date: Available online 30 January 2017
Source:Brachytherapy
Author(s): P. Blanchard, C. Ménard, S.J. Frank
MRI produces better soft tissue contrast than does ultrasonography or computed tomography for visualizing male pelvic anatomy and prostate cancer. Better visualization of the tumor and organs at risk could allow better conformation of the dose to the target volumes while at the same time minimizing the dose to critical structures and the associated toxicity. Although the use of MRI for prostate brachytherapy would theoretically result in an improved therapeutic ratio, its implementation been slow, mostly because of technical challenges. In this review, we describe the potential role of MRI at different steps in the treatment workflow for prostate brachytherapy: for patient selection, treatment planning, in the operating room, or for postimplant assessment. We further present the current clinical experience with MRI-guided prostate brachytherapy, both for permanent seed implantation and high–dose-rate brachytherapy.



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Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation?

Abstract

Background

After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation.

Materials and methods

In all, 12 consecutive stage I–IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a "selective" PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an "elective" PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a "selective" pleural irradiation plan (SPI plan) and an "elective" pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]).

Results

In the SPI plans, the average median dose to the S‑PTV was 53.6 Gy (range 41–63.6 Gy). In 4 of 12 patients, it was possible to escalate the dose to the S‑PTV to >58 Gy. In the EPI plans, the average median doses to the E‑PTV and to the S‑PTV were 48.6 Gy (range 38.5–58.7) and 49 Gy (range 38.6–59.5 Gy), respectively. No significant dose escalation was achievable.

Conclusion

The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49 Gy to more than 58 Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM.

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Prefraction displacement and intrafraction drift of the prostate due to perineal ultrasound probe pressure

Abstract

Objective

In image-guided EBRT of the prostate, transperineal ultrasound (US) probes exert pressure on the perineum both during planning and treatment. Through tissue deformation and relaxation, this causes target and risk organ displacement and drift. In this study, prefraction shift and intrafraction drift of the prostate are quantified during robotic transperineal 4DUS.

Methods

The position of the prostate was recorded for different positions of the probe before treatment in 10 patients (16 series of measurements). During treatment (15 patients, 273 fractions), intrafraction motion of the prostate was tracked (total of 27 h and 24 min) with the transperineal probe in place.

Results

Per 1 mm shift of the US probe in the cranial direction, a displacement of the prostate by 0.42 ± 0.09 mm in the cranial direction was detected. The relationship was found to be linear (R² = 0.97) and highly significant (p < 0.0001). After initial contact of the probe and the perineum (no pressure), a shift of the probe of about 5–10 mm was typically necessary to achieve good image quality, corresponding to a shift of the prostate of about 2–4 mm in the cranial direction. Tissue compression and prostate displacement were well visible. During treatment, the prostate drifted at an average rate of 0.075 mm/min in the cranial direction (p = 0.0014).

Conclusion

The pressure applied by a perineal US probe has a quantitatively similar impact on prostate displacement as transabdominal pressure. Shifts are predominantly in the cranial direction (typically 2–4 mm) with some component in the anterior direction (typically <1 mm). Slight probe pressure can improve image quality, but excessive probe pressure can distort the surrounding anatomy and potentially move risk organs closer to the high-dose area.

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Temozolomide during radiotherapy of glioblastoma multiforme

Abstract

Background

Temozolomide-(TMZ)-based chemoradiotherapy defines the current gold standard for the treatment of newly diagnosed glioblastoma. Data regarding the influence of TMZ dose density during chemoradiotherapy are currently not available. We retrospectively compared outcomes in patients receiving no TMZ, TMZ during radiotherapy on radiotherapy days only, and TMZ constantly 7 days a week.

Patients and methods

From 2002–2012, a total of 432 patients with newly diagnosed glioblastoma received radiotherapy in our department: 118 patients had radiotherapy alone, 210 had chemoradiotherapy with TMZ (75 mg/m²) daily (7/7), and 104 with TMZ only on radiotherapy days (5/7). Radiotherapy was applied to a total dose of 60 Gy.

Results

Median survival after radiotherapy alone was 9.1 months, compared to 12.6 months with 5/7-TMZ and to 15.7 months with 7/7-TMZ. The 1‑year survival rates were 33, 52, and 64%, respectively. Kaplan–Meier analysis showed a significant improvement of TMZ-7/7 vs. 5/7 (p = 0.01 by the log-rank test), while 5/7-TMZ was still superior to no TMZ at all (p = 0.02). Multivariate Cox regression showed a significant influence of TMZ regimen (p = 0.009) on hazard rate (+58% between groups) even in the presence of confounding factors age, sex, resection status, and radiotherapy dose concept.

Conclusion

Our results confirm the findings of the EORTC/NCIC trial. It seems that also a reduced TMZ scheme can at first prolong the survival of glioblastoma patients, but not as much as the daily administration.

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Oncogenic growth factor signaling mediating tumor escape from cellular immunity

Publication date: April 2017
Source:Current Opinion in Immunology, Volume 45
Author(s): Fernando Concha-Benavente, Robert L Ferris
Unrestrained growth factor signals can promote carcinogenesis, as well as other hallmarks of cancer such as immune evasion. Our understanding of the function and complex regulation of HER family of receptors has led to the development of targeted therapeutic agents that suppress tumor growth. However, these receptors also mediate escape from recognition by the host immune system. We discuss how HER family of oncogenic receptors downregulate tumor antigen presentation and upregulate suppressive membrane-bound or soluble secreted inhibitory molecules that ultimately lead to impaired cellular immunity mediated by cytotoxic T lymphocyte (CTL) recognition. Implementing this knowledge into new therapeutic strategies to enhance tumor immunogenicity may restore effector cell mediated immune clearance of tumors and clinical efficacy of tumor-targeted immunotherapy against HER receptor overexpression.



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Perceptions and Practices regarding Women's Vaginal Health following Radiation Therapy: A Survey of Radiation Oncologists Practicing in the USA

Publication date: Available online 14 February 2017
Source:Practical Radiation Oncology
Author(s): L.A. Kachnic, D.W. Bruner, M.M. Qureshi, G.A. Russo
Purpose/ObjectivesVaginal stenosis (VS) is a recognized complication of pelvic and vaginal radiation therapy (RT).Materials/MethodsA 26-item survey assessing the signs/symptoms, risk factors, diagnosis, prevention, treatment and impact of VS on women's sexual health was distributed. Descriptive statistics were calculated. Chi-square tests examined differences in categorical responses.Results233 (10.5%) completed the entire survey. Twelve%, 21%, and 68% report treating only gynecologic (GYN) tumors, only non-GYN pelvic tumors, or both, respectively. Regarding risk factors, 78% feel that VS can be caused by pelvic RT alone, 91% by vaginal brachytherapy (VB) alone, and 98% by combined pelvic RT and VB. Approximately half of respondents felt that being post-menopausal and having a hysterectomy prior to radiation therapy were risk factors for VS, while the other half felt that these were not risk factors. All respondents agree that VS is a clinical diagnosis. Reported VS symptoms include dyspareunia, vaginal pain, dryness, and/or bleeding (100%, 90%, 85% and 72%, respectively); 65% indicate all four. The most commonly recommended treatment for VS is vaginal dilator (VD) use Radiation oncologists who treat only GYN vs. non-GYN cancers are more likely to perform a vaginal exam, to distribute written instructions regarding VD use (p=0.002), to have vaginal bleeding reported after RT (p=0.001), and to refer patients to a sexual counselor (p=0.007). Most providers (73%) expressed willingness to participate in prospective research on the diagnosis and treatment of VS.ConclusionsThis is the first large-scale survey of radiation oncologists' perceptions and practices regarding VS. There is agreement among providers regarding the signs/symptoms of VS, and strategies for the prevention/treatment using vaginal dilators. Further prospective and observational research is needed. This survey shows a willingness on the part of providers to take part in prospective research regarding the diagnosis, impact, and treatment of VS on women's sexual health.



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Coronary Artery Stent Evaluation with Model-based Iterative Reconstruction at Coronary CT Angiography

Publication date: Available online 14 February 2017
Source:Academic Radiology
Author(s): Fuminari Tatsugami, Toru Higaki, Hiroaki Sakane, Wataru Fukumoto, Yoko Kaichi, Makoto Iida, Yasutaka Baba, Masao Kiguchi, Yasuki Kihara, So Tsushima, Kazuo Awai
Rationale and ObjectivesThis study aims to compare the image quality of coronary artery stent scans on computed tomography images reconstructed with forward projected model-based iterative reconstruction solution (FIRST) and adaptive iterative dose reduction 3D (AIDR 3D).Materials and MethodsCoronary computed tomography angiography scans of 23 patients with 32 coronary stents were used. The images were reconstructed with AIDR 3D and FIRST. We generated computed tomography attenuation profiles across the stents and measured the width of the edge rise distance and the edge rise slope (ERS). We also calculated the stent lumen attenuation increase ratio (SAIR) and measured visible stent lumen diameters. Two radiologists visually evaluated the image quality of the stents using a 4-point scale (1 = poor, 4 = excellent).ResultsThere was no significant difference in the edge rise distance between the two reconstruction methods (P = 0.36). The ERS on FIRST images was greater than the ERS on AIDR 3D images (325.2 HU/mm vs 224.4 HU/mm; P < 0.01). The rate of the visible stent lumen diameter compared to the true diameter on FIRST images was higher than that on AIDR 3D images (51.4% vs 47.3%, P < 0.01). The SAIR on FIRST images was lower than the SAIR on AIDR 3D images (0.19 vs 0.30, P < 0.01). The mean image quality scores for AIDR 3D and FIRST images were 3.18 and 3.63, respectively; the difference was also significant (P < 0.01).ConclusionThe image quality of coronary artery stent scans is better on FIRST than on AIDR 3D images.



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Automated Breast Density Computation in Digital Mammography and Digital Breast Tomosynthesis

Publication date: Available online 14 February 2017
Source:Academic Radiology
Author(s): Maria Castillo-García, Margarita Chevalier, Julia Garayoa, Alejandro Rodriguez-Ruiz, Diego García-Pinto, Julio Valverde
Rationale and ObjectivesThe study aimed to compare the breast density estimates from two algorithms on full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) and to analyze the clinical implications.Materials and MethodsWe selected 561 FFDM and DBT examinations from patients without breast pathologies. Two versions of a commercial software (Quantra 2D and Quantra 3D) calculated the volumetric breast density automatically in FFDM and DBT, respectively. Other parameters such as area breast density and total breast volume were evaluated. We compared the results from both algorithms using the Mann-Whitney U non-parametric test and the Spearman's rank coefficient for data correlation analysis. Mean glandular dose (MGD) was calculated following the methodology proposed by Dance et al.ResultsMeasurements with both algorithms are well correlated (r ≥ 0.77). However, there are statistically significant differences between the medians (P < 0.05) of most parameters. The volumetric and area breast density median values from FFDM are, respectively, 8% and 77% higher than DBT estimations. Both algorithms classify 35% and 55% of breasts into BIRADS (Breast Imaging-Reporting and Data System) b and c categories, respectively. There are no significant differences between the MGD calculated using the breast density from each algorithm. DBT delivers higher MGD than FFDM, with a lower difference (5%) for breasts in the BIRADS d category. MGD is, on average, 6% higher than values obtained with the breast glandularity proposed by Dance et al.ConclusionsBreast density measurements from both algorithms lead to equivalent BIRADS classification and MGD values, hence showing no difference in clinical outcomes. The median MGD values of FFDM and DBT examinations are similar for dense breasts (BIRADS d category).



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Impact of Filling Gas on Subharmonic Emissions of Phospholipid Ultrasound Contrast Agents

Publication date: Available online 14 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Emma Kanbar, Damien Fouan, Charles A. Sennoga, Alexander A. Doinikov, Ayache Bouakaz
Subharmonic signals backscattered from gas-filled lipid-shelled microbubbles have generated significant research interest because they can improve the detection and sensitivity of contrast-enhanced ultrasound imaging. However, the emission of subharmonic signals is strongly characterized by a temporal dependence, the origins of which have not been sufficiently elucidated. The features that influence subharmonic emissions need to be identified not only to better develop next-generation microbubble contrast agents, but also to develop more efficient subharmonic imaging (SHI) modes and therapeutic strategies. We examined the effect of microbubble filling gas on subharmonic emissions. Phospholipid shelled-microbubbles with different gaseous compositions such as sulfur hexafluoride (SF6), octafluoropropane (C3F8) or decafluorobutane (C4F10), nitrogen (N2)/C4F10 or air were insonated using a driving frequency of 10 MHz and peak negative pressure of 450 kPa, and their acoustic responses were tracked by monitoring both second harmonic and subharmonic emissions. Microbubbles were first acoustically characterized with their original gas and then re-characterized after substitution of the original gas with air, SF6 or C4F10. A measureable change in intensity of the subharmonic emissions with a 20- to 40-min delayed onset and increasing subharmonic emissions of the order 12–18 dB was recorded for microbubbles filled with C4F10. Substitution of C4F10 with air eliminated the earlier observed delay in subharmonic emissions. Significantly, substitution of SF6 for C4F10 successfully triggered a delay in the subharmonic emissions of the resultant agents, whereas substitution of C4F10 for SF6 eliminated the earlier observed suppression of subharmonic emissions, clearly suggesting that the type of filling gas contained in the microbubble agent influences subharmonic emissions in a time-dependent manner. Because our agents were dispersed in air-stabilized phosphate-buffered saline, these results suggest that the diffusivity of the gas from the agent to the surrounding medium is correlated with the time-dependent evolution of subharmonic emissions.



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Holistic Processing of Static and Moving Faces.

Author: Zhao, Mintao; Bulthoff, Isabelle

DOI: 10.1037/xlm0000368

Publication Date: POST AUTHOR CORRECTIONS, 13 February 2017

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Rule-Based Reasoning Is Fast and Belief-Based Reasoning Can Be Slow: Challenging Current Explanations of Belief-Bias and Base-Rate Neglect.

Author: Newman, Ian R.; Gibb, Maia; Thompson, Valerie A.

DOI: 10.1037/xlm0000372

Publication Date: POST AUTHOR CORRECTIONS, 13 February 2017

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It's Out of My Hands! Grasping Capacity May Not Influence Perceived Object Size.

Author: Collier, Elizabeth S.; Lawson, Rebecca

DOI: 10.1037/xhp0000331

Publication Date: POST AUTHOR CORRECTIONS, 13 February 2017

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Headspace single drop microextraction versus dispersive liquid-liquid microextraction using magnetic ionic liquid extraction solvents

Publication date: 15 May 2017
Source:Talanta, Volume 167
Author(s): Jiwoo An, Kira L. Rahn, Jared L. Anderson
A headspace single drop microextraction (HS-SDME) method and a dispersive liquid-liquid microextraction (DLLME) method were developed using two tetrachloromanganate ([MnCl4^2-])-based magnetic ionic liquids (MIL) as extraction solvents for the determination of twelve aromatic compounds, including four polyaromatic hydrocarbons, by reversed phase high-performance liquid chromatography (HPLC). The analytical performance of the developed HS-SDME method was compared to the DLLME approach employing the same MILs. In the HS-SDME approach, the magnetic field generated by the magnet was exploited to suspend the MIL solvent from the tip of a rod magnet. The utilization of MILs in HS-SDME resulted in a highly stable microdroplet under elevated temperatures and long extraction times, overcoming a common challenge encountered in traditional SDME approaches of droplet instability. The low UV absorbance of the [MnCl4^2-]-based MILs permitted direct analysis of the analyte enriched extraction solvent by HPLC. In HS-SDME, the effects of ionic strength of the sample solution, temperature of the extraction system, extraction time, stir rate, and headspace volume on extraction efficiencies were examined. Coefficients of determination (R²) ranged from 0.994 to 0.999 and limits of detection (LODs) varied from 0.04 to 1.0μgL⁻¹ with relative recoveries from lake water ranging from 70.2% to 109.6%. For the DLLME method, parameters including disperser solvent type and volume, ionic strength of the sample solution, mass of extraction solvent, and extraction time were studied and optimized. Coefficients of determination for the DLLME method varied from 0.997 to 0.999 with LODs ranging from 0.05 to 1.0μgL⁻¹. Relative recoveries from lake water samples ranged from 68.7% to 104.5%. Overall, the DLLME approach permitted faster extraction times and higher enrichment factors for analytes with low vapor pressure whereas the HS-SDME approach exhibited better extraction efficiencies for analytes with relatively higher vapor pressure.

Graphical abstract

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High sensitive detection of penicillin G residues in milk by surface-enhanced Raman scattering

Publication date: 15 May 2017
Source:Talanta, Volume 167
Author(s): Yongliang Chen, Xiuling Li, Ming Yang, Libin Yang, Xiaoxia Han, Xin Jiang, Bing Zhao
The antibiotic residue in animal source foods (milk, meat, etc.) is threatening people's health due to its abusing in livestock breeding more and more seriously. In this study, a simple and sensitive SERS method coupled with a two-step pretreatment process of sample was proposed for the residue detection of penicillin G (PENG) in real milk sample. It can be found that the two-step pretreatment process of sample is an essential procedure for the successful detection of PENG residue in milk, which can effectively avoid interference from other components in the sample and achieve the trace-level detection of PENG residue by SERS. Under the optimal test conditions, the limit of detection of PENG residue is 2.54×10⁻⁹mol/L (equal to 0.85μg/kg), which is lower than the standard of the European Union (4μg/kg). And, there is a good linear relationship (R²=0.9902) in the concentration range of 1.0×10⁻⁸~1.0×10⁻³mol/L. By this method, the recovery of PENG residue ranges from 76% to 97% with relative standard deviation between 4.8% and 2.1%. The proposed SERS method can be effectively applied for determination of PENG residue in milk.

Graphical abstract

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Short wave infrared chemical imaging as future tool for analysing gunshot residues patterns in targets

Publication date: 15 May 2017
Source:Talanta, Volume 167
Author(s): F.E. Ortega-Ojeda, M. Torre-Roldán, C. García-Ruiz
This work used chemical imaging in the short-wave infrared region for analysing gunshot residues (GSR) patterns in cotton fabric targets shot with conventional and non-toxic ammunition. It presents a non-destructive, non-toxic, highly visual and hiperspectral-based approach. The method was based on classical least squares regression, and was tested with the ammunition propellants and their standard components' spectra. The propellants' spectra were satisfactorily used (R² >0.966, and CorrCoef >0.982) for identifying the GSR irrespective of the type of ammunition used for the shooting. In a more versatile approach, nitrocellulose, the main component in the ammunition propellants, resulted an excellent standard for identifying GSR patterns (R²>0.842, and CorrCoef >0.908). In this case, the propellants' stabilizers (diphenilamine and centralite), and its nitrated derivatives as well as dinitrotoluene, showed also high spectral activity. Therefore, they could be recommended as complementary standards for confirming the GSR identification. These findings establish the proof of concept for a science-based evidence useful to support expert reports and final court rulings. This approach for obtaining GSR patterns can be an excellent alternative to the current and traditional chemical methods, which are based in presumptive and invasive colour tests.

Graphical abstract

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A rapid, accurate and sensitive method with the new stable isotopic tags based on microwave-assisted dispersive liquid-liquid microextraction and its application to the determination of hydroxyl UV filters in environmental water samples

Publication date: 15 May 2017
Source:Talanta, Volume 167
Author(s): Xiu Li, Guang Chen, Jianjun Liu, Yuxia Liu, Xianen Zhao, Ziping Cao, Lian Xia, Guoliang Li, Zhiwei Sun, Shijuan Zhang, Hua Wang, Jinmao You
A rapid, accurate and sensitive method, using the stable isotope labeling (SIL), microwave-assisted dispersive liquid-liquid micro extraction (MADLLME) and the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), was developed and validated for the determination of hydroxyl UV Filters in environmental water samples. A pair of new isotopic tags D0-/D3-1-methylindole-3-acetic acid (D0-/D3-MIAA) is synthesized, with which a simple yet efficient pretreatment MADLLME-SIL is developed. Under the optimized conditions (80℃, 240W, 180s), the sample pretreatment including analyte extraction, pre-concentration and isotope labeling can be finished conveniently in only 9min. D0-/D3-MIAA labeling improves the chromatographic retention by strengthening the hydrophobicity and enhances the MS response for 3–4 orders of magnitude. Excellent linearity is established by the H/D ratios of 1/10–10/1 with the correlation coefficients >0.9990. The quite low detection limits (0.54–1.79ng/L) are achieved, ensuring the trace detection. This method is successfully applied to a series of environmental water samples. The recoveries (93.2%~103.5%) are significantly improved and the analysis time is largely reduced (<15min). The excellent sensitivity, accuracy, recovery, and efficiency demonstrate this MADLLME-SIL-LC-MS/MS method a superior alternative for the analysis of UV filters in water samples.

Graphical abstract

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The Effect of Trauma on the Severity of Obsessive-Compulsive Spectrum Symptoms: A Meta-Analysis

Publication date: Available online 14 February 2017
Source:Journal of Anxiety Disorders
Author(s): Michelle L. Miller, Rebecca L. Brock
It is important to consider trauma-related sequelae in the etiology and maintenance of psychopathology, namely understudied disorders such as those belonging to the Obsessive-Compulsive Spectrum (OCS). This meta-analysis examined the association between past trauma exposure and current severity of OCS disorder symptoms. A systematic literature search was conducted with 24 (N=4,557) articles meeting inclusion criteria. A significant overall effect size was obtained (r=.20), indicating that exposure to past trauma is associated with a higher severity of OCS symptoms, with a stronger association for females (β=0.01, p<.001) but not varying as a function of relationship status. Four types of interpersonal trauma (violence, emotional abuse, sexual abuse, and neglect) were associated with OCS symptom severity (r=.19 −.24) and past trauma was significantly associated with more severe compulsions (r=.17), but not obsessions. Results suggest an important link between multiple types of past trauma exposure and OCS symptoms.



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Regulated methionine oxidation by monooxygenases

Publication date: Available online 14 February 2017
Source:Free Radical Biology and Medicine
Author(s): Bruno Manta, Vadim N. Gladyshev
Protein function can be regulated via post-translational modifications by numerous enzymatic and non-enzymatic mechanisms, including oxidation of cysteine and methionine residues. Redox-dependent regulatory mechanisms have been identified for nearly every cellular process, but the major paradigm has been that cellular components are oxidized (damaged) by reactive oxygen species (ROS) in a relatively unspecific way, and then reduced (repaired) by designated reductases. While this scheme may work with cysteine, it cannot be ascribed to other residues, such as methionine, whose reaction with ROS is too slow to be biologically relevant. However, methionine is clearly oxidized in vivo and enzymes for its stereoselective reduction are present in all three domains of life. Here, we revisit the chemistry and biology of methionine oxidation, with emphasis on its generation by enzymes from the monooxygenase family. Particular attention is placed on MICALs, a recently discovered family of proteins that harbor an unusual flavin-monooxygenase domain with an NADPH-dependent methionine sulfoxidase activity. Based on the structural and kinetic information we provide a rational framework to explain MICAL mechanism, inhibition, and regulation. Methionine residues that are targeted by MICALs are reduced back by methionine sulfoxide reductases, suggesting that reversible methionine oxidation may be a general mechanism analogous to the regulation by phosphorylation by kinases/phosphatases. The identification of new enzymes that catalyze the oxidation of methionine will open a new area of research at the forefront of redox signaling.



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CYP epoxygenase-derived H2O2 is involved in the endothelium-derived hyperpolarization (EDH) and relaxation of intrarenal arteries

Publication date: Available online 14 February 2017
Source:Free Radical Biology and Medicine
Author(s): Mercedes Muñoz, Maria Elvira López-Oliva, Estéfano Pinilla, María Pilar Martínez, Ana Sánchez, Claudia Rodríguez, Albino García-Sacristán, Medardo Hernández, Luis Rivera, Dolores Prieto
Reactive oxygen species (ROS) like hydrogen peroxide (H2O2) are involved in the in endothelium-derived hyperpolarization (EDH)-type relaxant responses of coronary and mesenteric arterioles. The role of ROS in kidney vascular function has mainly been investigated in the context of harmful ROS generation associated to kidney disease. The present study was sought to investigate whether H2O2 is involved in the endothelium–dependent relaxations of intrarenal arteries as well the possible endothelial sources of ROS generation involved in these responses. Under conditions of cyclooxygenase (COX) and nitric oxide (NO) synthase inhibition, acetylcholine (ACh) induced relaxations and stimulated H2O2 release that were reduced by catalase and by the glutathione peroxidase (GPx) mimetic ebselen in rat renal interlobar arteries, suggesting the involvement of H2O2 in the endothelium-dependent responses. ACh relaxations were also blunted by the CYP2C inhibitor sulfaphenazole and by the NADPH oxidase inhibitor apocynin. Acetylcholine stimulated both superoxide (O2^.-) and H2O2 production that were reduced by sulfaphenazole and apocynin. Expression of the antioxidant enzyme CuZn-SOD and of the H2O2 reducing enzymes catalase and GPx-1 were found in both intrarenal arteries and renal cortex. On the other hand, exogenous H2O2 relaxed renal arteries by decreasing vascular smooth muscle (VSM) intracellular calcium concentration [Ca²⁺]i and markedly enhanced endothelial KCa currents in freshly isolated renal endothelial cells. CYP2C11 and CYP2C23 epoxygenases were highly expressed in interlobar renal arteries and renal cortex, respectively, and were co-localized with eNOS in renal endothelial cells. These results demonstrate that H2O2 is involved in the EDH-type relaxant responses of renal arteries and that CYP 2C epoxygenases are physiologically relevant endothelial sources of vasodilator H2O2 in the kidney.

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Systematic Review of Measures of Impairment and Activity Limitation for Person with Upper Limb Trauma and Amputation

Publication date: Available online 14 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Linda Resnik, Matt Borgia, Ben Silver, Jill Cancio
ObjectiveStudy purposes were to 1) identify outcome measures used in studies of persons with traumatic upper limb injury and/or amputation and 2) evaluate focus, content and psychometric properties of each measure.Data SourcesSearches of PubMed and CINAHL for terms including upper extremity, function, activities of daily living, outcome assessment, amputation and traumatic injuries.Study SelectionIncluded articles had a sample of ≥10 adults with limb trauma or amputation, and were in English. Measures containing a majority of items assessing impairment of body function or activity limitation were eligible.Data ExtractionTwo hundred sixty papers containing 55 measures were included. Data on internal consistency; test-retest, inter-rater, and intra-rater reliability; content, structural, construct, concurrent, and predictive validity; responsiveness; and floor/ceiling effects were extracted and confirmed by a second investigator.Data SynthesisResultsThe mostly highly rated performance measures included 2 amputation specific measures: Activities Measure for Upper Limb Amputees, University of New Brunswick Test of Prosthetic Skill and Spontaneity, and 2 non-amputation specific measures: Box and Block Test, and modified Jebsen-Taylor Hand Function test light and heavy cans tests. Most highly rated self-report measures were DASH, Patient Rated Wrist Evaluation, QuickDASH and Hand Assessment Tool (HAT), International Osteoporosis Foundation Quality of Life Questionnaire and Patient Rated Wrist Evaluation Functional Recovery subscale. None were amputation specific.ConclusionFew performance measures were recommended for patients with limb trauma and amputation. All top rated self-report measures were suitable for use in both groups. These results will inform choice of outcome measures for these patients.



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Ultrasound-guided pulsed radiofrequency stimulation of posterior tibial nerve: A potential novel intervention for recalcitrant plantar fasciitis

Publication date: Available online 14 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Yung-Tsan Wu, Chih-Ya Chang, Yu-Ching Chou, Chun-Chang Yeh, Tsung-Ying Li, Heng-Yi Chu, Liang-Cheng Chen
ObjectiveTo evaluate the therapeutic benefit of ultrasound-guided pulsed radiofrequency (PRF) stimulation at the posterior tibial nerve (PTN) in patients with recalcitrant plantar fasciitis (PF).DesignA prospective, randomized, double-blinded, placebo-controlled trial (12-week follow-up).SettingOutpatient of local medical center settings.ParticipantsThirty-six patients with recalcitrant PF were randomized and 36 participants were included in the final data analysis.InterventionsPatients were treated with one dose of ultrasound-guided PRF stimulation at the PTN in PRF group and control group received one dose of an ultrasound-guided 0.5 cc 2% lidocaine injection at the PTN.Main Outcome MeasuresThe outcome measurements, including the visual analog scale (VAS) (first-step and overall pain), American Orthopedic Foot-Ankle Society (AOFAS) Ankle-Hindfoot scale, and ultrasonographic thickness of the plantar fascia, were evaluated 1, 4, 8, and 12 weeks after treatment.ResultsThirty-six patients (20 feet per group) completed the study. The PRF group had a significantly larger improvement in first-step pain, overall pain, and AOFAS score (all p<0.001), as well as plantar fascia thickness (p<0.05) compared to those of the control group at all observed time-points.ConclusionsThis study shows that ultrasound-guided PRF stimulation at the PTN is effective for treating recalcitrant PF. This simple, reproducible method could be a novel strategy for managing recalcitrant PF.



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Efficacy of combined ultrasound-guided steroid injection and splinting in patients with carpal tunnel syndrome: A randomized controlled trial

Publication date: Available online 14 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Jia-Chi Wang, Kwong-Kum Liao, Kon-Ping Lin, Chen-Liang Chou, Tsui-Fen Yang, Yu-Fang Huang, Kevin A. Wang, Jan-Wei Chiu
ObjectivesTo compare the effectiveness of local steroid injection plus splinting to that of local steroid injection alone using clinical and electrophysiological parameters in patients with carpal tunnel syndrome (CTS).Design; Randomized controlled study with 12 weeks of follow-up.SettingTertiary care center.ParticipantsVolunteer sample of 52 patients diagnosed with CTSClinical trial registration number: NCT02728693



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Botulinum toxin treatment for nocturnal calf cramps in patients with lumbar spinal stenosis: A randomized clinical trial

Publication date: Available online 14 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Sang Jun Park, Kyung Bong Yoon, Duck Mi Yoon, Shin Hyung Kim
ObjectivesTo evaluate the clinical effectiveness of botulinum toxin (BTX) injection into the gastrocnemius muscles in lumbar spinal stenosis (LSS) patients with frequent nocturnal calf cramps (NCCs)DesignProspective randomized clinical trialSettingOutpatient department for interventional pain management.ParticipantsFifty LSS patients with a frequency of NCCs ≥ once per week were enrolled.InterventionPatients were randomly allocated to receive either conservative treatments plus gabapentin (Group GPN) or BTX injection (Group BTX).Main outcome measuresWe assessed back/leg pain intensity, the frequency and severity of NCCs, insomnia severity, and functional disability at baseline and after 2 weeks, 1 month, and 3 months. Additionally, patient global impression of change was assessed.ResultsForty-five patients completed all assessments (Group GPN; n=21, Group BTX; n=24). Compared with Group GPN, leg pain intensity, cramp frequency and severity were significantly decreased in Group BTX at all follow-up visits (all, p<0.01). Also, insomnia significantly improved in Group BTX at 2 weeks (p=0.018) and 1 month follow-up (p=0.037). Functional disability significantly improved in Group BTX at 2 weeks follow-up (p=0.041). At the 3 month follow-up, patients in Group BTX reported higher impression of improvement for NCCs symptoms than those in Group GPN (p<0.001). A mean dose of 642.8 mg gabapentin was given daily in Group GPN, but seven patients (33.3%) reported systemic side effects. There were no serious complications related to BTX use.ConclusionsBTX treatment appears to be effective and safe for NCCs in symptomatic LSS patients receiving conservative care.



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How have evolutions in strategies for the treatment of relapsed/refractory multiple myeloma translated into improved outcomes for patients?

Publication date: Available online 14 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Pieter Sonneveld, Edwin De Wit, Philippe Moreau
Although multiple myeloma (MM) remains incurable, the introduction of novel agents has improved clinical outcomes dramatically over the past 15 years. Response rates have risen from ∼30% with single agents to up to 90% with combination therapies. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, form the foundations for treatment of relapsed and/or refractory MM (RRMM). Newer agents, such as the IMiD pomalidomide, the histone deacetylase inhibitor panobinostat and the proteasome inhibitors carfilzomib and ixazomib, as well as the monoclonal antibodies daratumumab and elotuzumab, have further improved overall response rates in these patients. Importantly, increased response rates have been observed in heavily pretreated patients. The availability of highly effective and tolerable drugs may offer alternative treatment strategies to those who are unsuitable for treatment with thalidomide, lenalidomide or bortezomib. Improving tolerability of treatment regimens and lengthening progression‐free intervals has been shown to significantly improve health-related quality of life for patients living with RRMM.



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Risk factors for malnutrition among children with cerebral palsy in Botswana

Publication date: Available online 14 February 2017
Source:Pediatric Neurology
Author(s): Allison Johnson, Claudia Gambrah-Sampaney, Esha Khurana, James Baier, Esther Baranov, Baphaleng Monokwane, David R. Bearden
BackgroundChildren with cerebral palsy in low-resource settings are at high risk of malnutrition, which further increases their risk of poor health outcomes. However, there is little published data on specific risk factors for malnutrition among children with cerebral palsy in the developing world.MethodsWe performed a case-control study among children with cerebral palsy receiving care at a tertiary care hospital in Gaborone, Botswana. Children with cerebral palsy and malnutrition were identified according to World Health Organization growth curves and compared to subjects with cerebral palsy without malnutrition. Risk factors for malnutrition were identified using multivariable logistic regression models. These risk factors were then used to generate a Malnutrition Risk Score, and Receiver Operating Characteristic (ROC) curves were used to identify optimal cutoffs to identify subjects at high risk of malnutrition.ResultsWe identified 61 children with cerebral palsy, 26 of whom (43%) met criteria for malnutrition. Non-ambulatory status (OR 13.8, 95% CI 3.8-50.1, p<0.001) and a composite measure of socioeconomic status (OR 1.6, 95% CI 1.0-2.5, p=0.03) were the strongest risk factors for malnutrition. A Malnutrition Risk Score was constructed based on these risk factors, and Receiver Operating Characteristic (ROC) curve analysis demonstrated excellent performance characteristics of this score (AUC 0.92, 95% CI 0.89-0.94).ConclusionsMalnutrition is common among children with cerebral palsy in Botswana, and a simple risk score may help identify children with the highest risk. Further studies are needed to validate this screening tool and to determine optimal nutritional interventions in this population.



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Synthesized Digital Mammography Imaging

Publication date: Available online 14 February 2017
Source:Radiologic Clinics of North America
Author(s): Phoebe E. Freer, Nicole Winkler

Teaser

Synthesized mammography (SM) is a new imaging technique similar to digital mammography constructed from an acquired digital breast tomosynthesis (DBT) examination. SM allows for widespread screening using DBT, maintaining the benefits of DBT while decreasing the radiation of DBT by nearly half. This article reviews studies evaluating SM, most of which suggest that SM may be appropriate to use clinically to replace an actual acquired conventional 2-dimensional full-field digital mammogram (FFDM) when using DBT for breast cancer screening. These results should be interpreted with caution because there are inherent differences between SM and FFDM image quality and lesion visibility and larger, more robust studies still need to be performed.


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Implementation of Whole-Breast Screening Ultrasonography

Publication date: Available online 30 January 2017
Source:Radiologic Clinics of North America
Author(s): Melissa A. Durand, Regina J. Hooley

Teaser

Whole-breast screening ultrasonography is being increasingly implemented in breast imaging centers because numerous studies have shown the benefit of supplemental screening for women with dense breasts and breast density notification laws are becoming more widespread. This article reviews the numerous considerations involved in integrating a screening ultrasonography program into a busy practice.


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Electroplating sludge derived zinc-ferrite catalyst for the efficient photo-Fenton degradation of dye

Publication date: 15 May 2017
Source:Journal of Environmental Management, Volume 193
Author(s): Zhenbang Cao, Jia Zhang, Jizhi Zhou, Xiuxiu Ruan, Dan Chen, Jianyong Liu, Qiang Liu, Guangren Qian
A zinc-dominant ferrite catalyst for efficient degradation of organic dye was prepared by the calcination of electroplating sludge (ES). Characterizations indicated that zinc ferrite (ZnFe2O4) coexisted with Fe2O3 structure was the predominant phase in the calcined electroplating sludge (CES). CES displayed a high decolorization ratio (88.3%) of methylene blue (MB) in the presence of H2O2 combined with UV irradiation. The high efficiency could be ascribed to the photocatalytic process induced by ZnFe2O4 and the photo-Fenton dye degradation by ferrous content, and a small amount of Al and Mg in the sludge might also contribute to the catalysis. Moreover, the degradation capability of dye by CES was supported by the synthetic ZnFe2O4 with different Zn to Fe molar ratio (n(Zn): n(Fe)), as 84.81%–86.83% of dye was removed with n(Zn): n(Fe) ranged from 1:0.5 to 1:3. All synthetic ferrite samples in the simulation achieved adjacent equilibrium decolorization ratio, the flexible proportioning of divalent metal ions (M²⁺) to trivalent metal ions (M³⁺) applied in the synthesis indicated that the catalyst has a high availability. Therefore, an efficacious catalyst for the degradation of dye can potentially be derived from heavy metal-containing ES, it's a novel approach for the reutilization of ES.



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Photodetector with superior functional capabilities based on monolayer WO3 developed by atomic layer deposition

Publication date: June 2017
Source:Sensors and Actuators B: Chemical, Volume 245
Author(s): Zhenyin Hai, Mohammad Karbalaei Akbari, Chenyang Xue, Hongyan Xu, Stephen Depuydt, Serge Zhuiykov
Photodetector based on monolayer of tungsten trioxide (WO3) was fabricated by atomic layer deposition (ALD) and its structure and properties were analyzed by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), ellipsometry, atomic force microscopy (AFM), transmission electron microscopy (TEM) and spectrophotometry techniques. The as-developed photodetector exhibited high sensitivity, wide-range photoresponse, extremely fast response time of ∼2.5–2.7ms and superior long-term stability over more than 250 cycles. ALD-enabled Angstrom-precision development of monolayer WO3 with thickness of ∼0.74±0.07nm was done by utilizing (^tBuN)2W(NMe2)2 as tungsten precursor and H2O as oxygen precursor, respectively, without affecting the underlying silicon substrate. The performance of monolayer WO3-based photodetector was much better than that of photodetectors based on other nanostructured WO3, monolayers and few layers of MoS2, MoSe2, GaSe and two-dimensional (2D) ZnO/ZnS nanocomposites. Its fast response speed also enables great application potential in high-frequency light-wave communications, various opto-chemical sensors, photo-switches and optoelectronic circuits.

Graphical abstract

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Ambient redox synthesis of vanadium-doped manganese dioxide nanoparticles and their enhanced zinc storage properties

Publication date: 15 May 2017
Source:Applied Surface Science, Volume 404
Author(s): Muhammad Hilmy Alfaruqi, Saiful Islam, Vinod Mathew, Jinju Song, Sungjin Kim, Duong Pham Tung, Jeonggeun Jo, Seokhun Kim, Joseph Paul Baboo, Zhiliang Xiu, Jaekook Kim
In this work, we demonstrate the first use of a V-doped MnO2 nanoparticle electrode for zinc-ion battery (ZIB) applications. The V-doped MnO2 was prepared via a simple redox reaction and the X-ray diffraction studies confirmed the formation of pure MnO2, accompanied by an anisotropic expansion of MnO2 lattice, suggesting the incorporation of V-ions into the MnO2 framework. V doping of MnO2 not only increased the specific surface area but also improved the electronic conductivity. When Zn-storage properties were tested, the V-doped MnO2 electrode registered a higher discharge capacity of 266mAhg⁻¹ compared to 213mAhg⁻¹ for the pure MnO2 electrode. On prolonged cycling, the doped electrode retained 31% higher capacity than that of the bare MnO2 electrode and thereby demonstrated superior cycling performance. This study may pave the way towards understanding the enhancement of the energy storage properties via doping in electrodes of aqueous ZIB applications and also furthers the efforts for the practical realization of a potential eco-friendly battery system.

Graphical abstract

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Structural optimization for thermoelectric properties in Cu-Bi-S pavonite compounds

Publication date: 15 May 2017
Source:Journal of Alloys and Compounds, Volume 704
Author(s): Jae-Yeol Hwang, Jun Yeon Ahn, Kyu Hyoung Lee, Sung Wng Kim
We report the enhancement of thermoelectric properties in the complex structured Cu-Bi-S pavonite compounds by optimizing the structural configuration through tuning the Bi-site occupancy, and substitutional doping at interstitial Cu sites by Zn. We verify that electronic transport properties depend on the structural deformation by the Bi site occupancy. Furthermore, we demonstrate that the modification of interstitial site ions enables selective control of thermal conductivity and intrinsically low thermal conductivity can be further suppressed by structural optimization without deteriorating electronic transport properties. We propose that understanding of crystal structure as a basic strategy permits the optimization of thermoelectric properties in the complex structures.

Graphical abstract

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Multi-approach characterization of organic sediment produced by an anaerobic digestion plant fed with pig slurry and stored for a long term in a lagoon

Publication date: 15 May 2017
Source:Journal of Hazardous Materials, Volume 330
Author(s): Anna Ricci, Luisa Massaccesi, Daniela Pezzolla, Giuseppe Corti, Alberto Agnelli, Giovanni Gigliotti
This study combined different approaches to characterize organic sediments produced by an anaerobic digestion plant feed with pig slurry, and accumulated for many years in a lagoon. The results of all analyses identified a certain homogeneity of the sediments. As a consequence of the pig diet, the sediment contained an high concentration of Zn (about 4gkg⁻¹) and Cu (about 1.2gkg⁻¹), which were mostly associated to the particles with a size ranging from 2 to 53μm. The sediment was made of large amount of organic matter, mostly cellulose and recalcitrant molecules, and 30–40% mineral fraction. XANES and XES spectroscopies indicated the presence of zinc phosphate (38%), zinc sulfide (32%), zinc carbonate (19%), and zinc oxide (11%). The presence in the sediment of forms characterized by a very scarce solubility, as also confirmed by the Zn and Cu chemical speciation, indicated a low bioavailability of these metals. However, although their low mobility, the high concentrations of Zn and Cu allowed to consider the sediment not suitable to use as a fertiliser due to the potential risk of metal interaction with the food chain.



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Intérêt de la spirométrie en médecine générale pour la motivation au sevrage tabagique. Étude pilote de faisabilité et intérêt de l’« âge pulmonaire »

Publication date: Available online 13 February 2017
Source:Revue des Maladies Respiratoires
Author(s): A. Lorenzo, F. Noël, M. Lorenzo, J. Van Den Broucke
ObjectifMesurer, chez des fumeurs non motivés au sevrage, le changement motivationnel après une spirométrie systématique au cabinet de médecine générale.Matériels et méthodeÉtude interventionnelle prospective monocentrique de type « avant-après ». Ont été inclus quel qu'était leur motif de consultation, 74 patients majeurs et fumeurs non motivés au sevrage tabagique. Les résultats spirométriques, comportant le rapport VEMS/CVF et l'âge pulmonaire, étaient commentés et remis. Neuf mois plus tard, ils étaient réévalués téléphoniquement.RésultatsCinquante-six pour cent étaient des femmes, d'en moyenne 46,5 ans, ayant fumé 26,3 paquets-années. Quatre-vingt-deux pour cent avaient un rapport VEMS/CVF normal mais 38 % un âge pulmonaire pathologique. Neuf mois après, 61,1 % ont augmenté leur motivation au sevrage. La consommation était de 10,9 cigarettes/jour, contre 13,3 cigarettes/jour à l'inclusion (p=0,0254). Augmenter sa motivation n'était pas statistiquement liée à l'âge, au sexe, aux sevrages antérieurs, au tabagisme quotidien, à la dépendance nicotinique ni à la normalité du rapport VEMS/CVF (p>0,75) mais significativement lié à la normalité ou non de l'âge pulmonaire (p<0,03).ConclusionCette étude suggère que la pratique d'une spirométrie, dans un cabinet de médecine générale, est susceptible, par la détermination de l'âge pulmonaire, de faire progresser la motivation au sevrage tabagique des fumeurs non motivés.IntroductionOur aim was to investigate whether spirometry, performed in general practitioners' offices would change non-motivated smokers' attitudes toward smoking cessation.MethodWe performed an interventional, prospective, before-after single-center study, approved by a research ethics committee. We included 74 smokers older than 18years old, who reported no intention to quit smoking, whatever they were visiting general practitioners for. We performed spirometry and gave them their results, FEV1/FVC and lung age together with a comment on it. Nine months later, we called them for another assessment.ResultsFifty-six percent were women with an average-age of 46.5, who smoked 26.3 pack-years. Eighty-two percent of them had normal FEV1/FVC but lung age was pathological among 38% of them. Nine months later, 61.1% reported an increased motivation to quit smoking. They smoked 10.9 cigarettes per day versus 13,3 at baseline (P=0.0254). Increase in motivation was not statistically related to age, gender, previous smoking cessations, daily smoking, nicotine dependence or an abnormal FEV1/VC ratio (P>0.75) but was significantly related to the presence of an abnormal lung age status (P<0.03).ConclusionThis study suggests that spirometry in general practice, combined with the determination of the lung age, may increase motivation towards smoking cessation in smokers who lack motivation.



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Intérêt de la dimension émotionnelle d’une information à destination des patients atteints d’un syndrome d’apnées obstructives du sommeil

Publication date: Available online 13 February 2017
Source:Revue des Maladies Respiratoires
Author(s): J. Bros, C. Poulet, C. Deschaux, M. Charavel
IntroductionAfin de favoriser l'adaptation au traitement par pression positive continue, un document d'information, destiné aux personnes débutant leur prise en charge, a été élaboré.MéthodesLa méthode du focus group, en suscitant une dynamique de groupe favorisant l'expression des sept participants, a permis d'identifier non seulement les informations utiles, mais aussi la manière de les transmettre.RésultatsLe focus group a permis de pointer des objectifs précis associés à la dimension émotionnelle la plus adaptée : (1) entraîner une prise de conscience, par des formulations suscitant la peur quant aux mécanismes physiologiques et aux conséquences induites par le syndrome d'apnées obstructives du sommeil, (2) permettre la reconnaissance de la symptomatologie, des facteurs de risque et de la chronicité de ce syndrome, (3) rassurer et motiver le patient au sujet du traitement par pression positive continue.ConclusionsDans le but de favoriser l'adaptation au traitement par pression positive continue en début de la prise en charge, l'association de différentes tonalités émotionnelles a été privilégiée, mêlant à la fois peur et réassurance.IntroductionTo promote adaptation to treatment with continuous positive airway pressure, an information document was developed for people starting their treatment with continuous positive airway pressure.MethodsSeven patients with obstructive sleep apnea took part in a focus group. This allowed the identification both of useful information and the best way that this information could be presented.ResultsThe key specific information objectives and the best emotional register to use were as follows: (1) develop awareness about the physiological mechanisms and consequences that can occur from obstructive sleep apnea syndrome, using formulations arousing fear, (2) enable the recognition of the symptoms, risk factors and chronicity of this syndrome, (3) reassure and motivate the patient about treatment with continuous positive airway pressure.ConclusionsTo promote adaptation to positive airway pressure in early care, combining different emotional tones is preferable, mixing both fear and reassurance.



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Chez le patient atteint de BPCO, la réduction de 50 % du tabagisme permet-elle de limiter le déclin du VEMS ?

Publication date: Available online 13 February 2017
Source:Revue des Maladies Respiratoires
Author(s): G. Peiffer, J. Perriot, M. Underner




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Anthocyanin suppresses CoCrMo particle-induced osteolysis by inhibiting IKKα/β mediated NF-κB signaling in a mouse calvarial model

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Yamin Li, Juehong Li, Bin Li, Hui Qin, Xiaochun Peng, Yaochao Zhao, Yunsu Chen
Wear particle-induced osteolysis and bone resorption have been identified as critical factors of implant failure and total joint revision, in which nuclear factor kappa B (NF-κB) signaling and chronic inflammation have been shown to play key roles. Although anthocyanin is known to have anti-inflammatory function via blocking NF-κB pathway, it is still unclear whether anthocyanin has a protective effect on particle-induced osteolysis. In the present study, we aimed to investigate the detailed effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model. One hundred and twelve male BALB/c mice were divided randomly into four groups: sham group (sham operation and injection with PBS), vehicle group (CoCrMo particle treatment and injection with PBS), low-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.1mg/g/day), and high–dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.4mg/g/day). Mice were sacrificed after two weeks, harvesting the calvariae tissue for in depth analysis by micro-CT, histomorphometry, immunohistochemical and molecular biology analysis. As expected, anthocyanin markedly inhibited CoCrMo particle–induced inflammatory infiltration and decreased bone loss in vivo. Anthocyanin also reversed the increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL)/osteoproteger (OPG) and suppressed osteoclast formation in CoCrMo particle–stimulated calvaria. Additionally, anthocyanin significantly reduced the expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the calvaria of CoCrMo-stimulated mice. Furthermore, we confirmed that anthocyanin attenuated osteolysis by blocking NF-κB pathway via inhibiting inhibitor of nuclear factor kappa-B kinase α/β (IKKα/β) phosphorylation. In conclusion, our study demonstrated that anthocyanin can protect against CoCrMo particle–induced inflammatory osteolysis via inhibiting the IKKα/β-NF-κB pathway, and have a potential therapeutic effect on the treatment of wear particle–induced osteolysis.



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Identification of triosephosphate isomerase as a novel allergen in Octopus fangsiao

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Yang Yang, Zhong-Wei Chen, Barry K. Hurlburt, Gui-Ling Li, Yong-Xia Zhang, Dan-Xia Fei, Hai-Wang Shen, Min-Jie Cao, Guang-Ming Liu
Octopus is an important mollusk in human dietary for its nutritional value, however it also causes allergic reactions in humans. Major allergens from octopus have been identified, while the knowledge of novel allergens remains poor. In the present study, a novel allergen with molecular weight of 28kDa protein was purified from octopus (Octopus fangsiao) and identified as triosephosphate isomerase (TIM) by mass spectrometry. TIM aggregated beyond 45°C, and its IgE-binding activity was affected under extreme pH conditions due to the altered secondary structure. In simulated gastric fluid digestion, TIM can be degraded into small fragments, while retaining over 80% of the IgE-binding activity. The full-length cDNA of O. fangsiao TIM (1140bp) was cloned, which encodes 247 amino acid residues, and the entire recombinant TIM was successfully expressed in Escherichia coli BL21, which showed similar immunoreactivity to the native TIM. Different intensity of cross-reactivity among TIM from related species revealed the complexity of its epitopes. Eight linear epitopes of TIM were predicted following bioinformatic analysis. Furthermore, a conformational epitope (A71G74S69D75T73F72V67) was confirmed by the phage display technology. The results revealed the physicochemical and immunological characteristics of TIM, which is significant in the development of hyposensitivity food and allergy diagnosis.



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Temporal regulation of Wnt/β-catenin signaling is important for invariant NKT cell development and terminal maturation

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Kalyani Pyaram, Jyoti Misra Sen, Cheong-Hee Chang
The Wnt/β-catenin signaling pathway plays important roles during various cellular functions including survival and proliferation of immune cells. The critical role of this pathway in conventional T cell development is established but little is known about its contributions to innate T cell development. In this study, we found that β-catenin level, an indication of the strength of Wnt/β-catenin signaling, is regulated during invariant NKT (iNKT) cell development. β-catenin levels were greatly increased during iNKT cell selection from double positive thymocytes to Stage 0 of iNKT cell development and during subsequent development to Stage 1. Thereafter, β-catenin levels decrease from Stage 2, which is essential for the terminal maturation of iNKT cells. Failure to dampen Wnt/β-catenin signaling as in mice expressing a stabilized active form of β-catenin (CATtg) resulted in increased Stage 2 and decreased Stage 3 iNKT cells. Inefficient transition from Stage 2 to 3 in CATtg iNKT cells seems to be contributed by poor expression of IL-15R (CD122) and transcription factor T-bet, both of which are necessary for terminal maturation of iNKT cells in the thymus. Consequently, IFN-γ+ iNKT cells were greatly reduced in CATtg mice. Together, our findings reveal that proper regulation of β-catenin and in turn Wnt signaling plays an important role in the terminal maturation and function of iNKT cells.



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CD47 limits antibody dependent phagocytosis against non-malignant B cells

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Sandra Gallagher, Sean Turman, Kristen Lekstrom, Susan Wilson, Ronald Herbst, Yue Wang
Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and −CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP. We show that CD47 is expressed on all B cells in mice, with the highest level on plasma cells in bone marrow and spleen. Although its expression is dispensable for B cell development in mice, CD47 on B cells limits antibody mediated phagocytosis. B cell depletion following in vivo anti-CD19 treatment is more efficient in CD47-/- mice than in wild type mice. In vitro, both naïve and activated B cells from CD47-/- mice are more sensitive to ADCP than wild type B cells. Lastly, we show in an ADCP assay that blocking CD47 can enhance anti-CD19 antibody mediated phagocytosis of wild type B cells. These results suggest that in addition to its already demonstrated benefit in cancer, targeting CD47 may be used as an adjunct in combination with B cell depletion antibodies for treatment of autoimmune diseases.



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Lactobacillus buchneri S-layer as carrier for an Ara h 2-derived peptide for peanut allergen-specific immunotherapy

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Julia Anzengruber, Merima Bublin, Eva Bönisch, Bettina Janesch, Angelika Tscheppe, Matthias L. Braun, Eva-Maria Varga, Christine Hafner, Heimo Breiteneder, Christina Schäffer
Peanut allergy is an IgE-mediated severe hypersensitivity disorder. The lack of a treatment of this potentially fatal allergy has led to intensive research on vaccine development. Here, we describe the design and initial characterization of a carrier-bound peptide derived from the most potent peanut allergen, Ara h 2, as a candidate vaccine. Based on the adjuvant capability of bacterial surface (S-) layers, a fusion protein of the S-layer protein SlpB from Lactobacillus buchneri CD034 and the Ara h 2-derived peptide AH3a42 was produced. This peptide comprised immunodominant B-cell epitopes as well as one T cell epitope. The fusion protein SlpB-AH3a42 was expressed in E. coli, purified, and tested for its IgE binding capacity as well as for its ability to activate sensitized rat basophil leukemia (RBL) cells. The capacity of Ara h 2-specific IgG rabbit-antibodies raised against SlpB-AH3a42 or Ara h 2 to inhibit IgE-binding was determined by ELISA inhibition assays using sera of peanut allergic patients sensitized to Ara h 2. IgE specific to the SlpB-AH3a42 fusion protein was detected in 69% (25 of 36) of the sera. Despite the recognition by IgE, the SlpB-AH3a42 fusion protein was unable to induce β-hexosaminidase release from sensitized RBL cells at concentrations up to 100ng per ml. The inhibition of IgE-binding to the natural allergen observed after pre-incubation of the 20 sera with rabbit anti-SlpB-AH3a42 IgG was more than 30% for four sera, more than 20% for eight sera, and below 10% for eight sera. In comparison, anti-Ara h 2 rabbit IgG antibodies inhibited binding to Ara h 2 by 48% ±13.5%. Our data provide evidence for the feasibility of this novel approach towards the development of a peanut allergen peptide-based carrier-bound vaccine. Our experiments further indicate that more than one allergen-peptide will be needed to induce a broader protection of patients allergic to Ara h 2.



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Caring for children with intellectual disabilities part 1: Experience with the population, pain-related beliefs, and care decisions

Publication date: March 2017
Source:Research in Developmental Disabilities, Volume 62
Author(s): Lara M. Genik, C. Meghan McMurtry, Lynn M. Breau
Some children with intellectual disabilities (ID): experience pain more frequently than children without ID, express their pain differently, and are incapable of providing self-reports. No research has examined disability and pain-related beliefs of respite workers (RW) and their relations to pain assessment and management decisions for children with ID.Objectives(1) compare disability and pain-related beliefs between RW and a sample with little experience in ID; (2) determine whether individuals' beliefs and personal characteristics are related to pain assessment and management decisions.ParticipantsFifty-six RW (aged: 18–67 years, Mage=33.37, 46 female) and 141 emerging adults (aged: 18–31 years, Mage=19.67, 137 female).Procedure/measuresIn an online survey, participants responded to six vignettes depicting pain in children with ID, and completed measures of pain and disability-related beliefs.Results/discussionCompared to those without experience, RW held more positive disability-related beliefs, t(192)=4.23, p<0.001. Participants' pain-related beliefs (e.g., sensitivity to pain) differed depending on severity of the child's ID and participant group. Participants' pain-related beliefs predicted care decisions. Results provide initial insight into RW pain-related beliefs about children with ID, and a basic understanding of the relations among pain beliefs, personal characteristics and pain-related decisions.



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How have evolutions in strategies for the treatment of relapsed/refractory multiple myeloma translated into improved outcomes for patients?

Publication date: Available online 14 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Pieter Sonneveld, Edwin De Wit, Philippe Moreau
Although multiple myeloma (MM) remains incurable, the introduction of novel agents has improved clinical outcomes dramatically over the past 15 years. Response rates have risen from ∼30% with single agents to up to 90% with combination therapies. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, form the foundations for treatment of relapsed and/or refractory MM (RRMM). Newer agents, such as the IMiD pomalidomide, the histone deacetylase inhibitor panobinostat and the proteasome inhibitors carfilzomib and ixazomib, as well as the monoclonal antibodies daratumumab and elotuzumab, have further improved overall response rates in these patients. Importantly, increased response rates have been observed in heavily pretreated patients. The availability of highly effective and tolerable drugs may offer alternative treatment strategies to those who are unsuitable for treatment with thalidomide, lenalidomide or bortezomib. Improving tolerability of treatment regimens and lengthening progression‐free intervals has been shown to significantly improve health-related quality of life for patients living with RRMM.



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Asparaginase pharmacology: challenges still to be faced

Abstract

Purpose

The benefits of asparaginase (ASNASE) in the treatment of ALL and NHL are indisputable and new ASNASE preparations are under clinical development to overcome limitations of the actual ASNASE therapy, especially immunogenicity. Apart from ALL and NHL further indications of ASNASE are preclinically and clinically evaluated.

Methods

We reviewed ASNASE literature and especially focused on the mechanism of action, on biomarker, which determine ASNASE sensitivity and resistance, and on ASNASE pharmacodynamics in vivo.

Results

More than 40 years after the clinical introduction of ASNASE its mechanism of action is yet not fully understood. Studies on asparagine synthetase (ASNS) as biomarker for ASNASE resistance are contradictory and complicated by methodological obstacles. The role of glutamine hydrolysis for ASNASE efficacy is still debated, other mechanisms are possibly not yet identified. In addition, individual pharmacokinetic/-dynamic relationships cannot be properly addressed because of methodological limitations.

Conclusion

More sophisticated preclinical models and suitable methods for monitoring of ASNASE pharmacodynamics are urgently needed (1) to understand the mechanism of action, (2) to establish valid biomarkers for ASNASE sensitivity and resistance, (3) to evaluate the pharmacokinetics/-dynamics of ASNASEs in individual patients, and (4) to compare the bioequivalence of clinically established, as well as new ASNASE preparations.

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Age-related reduction of dermal fibroblast size up-regulates multiple matrix metalloproteinases as observed in aged human skin in vivo

Summary

Background

Fragmentation of collagen fibrils, the major structure protein in skin, is a hallmark of dermal aging. Matrix metalloproteinases (MMPs) are largely responsible for fragmentation of collagen fibrils. However, the alteration of all known mammalian MMPs and the mechanism underlying altered expression of MMPs in chronologically aged human skin are less understood.

Objectives

To quantify gene expression of all 23 known mammalian MMPs in sun-protected young and aged human skin in vivo, and investigate the potential mechanism underlying age-related alteration of multiple MMPs.

Methods

MMPs mRNA expression levels and MMPs activity in sun-protected young and aged human skin in vivo were determined by real-time RT-PCR and in situ zymography, respectively. The relative contributions to elevated MMPs in epidermis and dermis were quantified by laser capture microdissection (LCM) coupled real-time RT-PCR. Dermal fibroblast morphology and collagen fibrils fragmentation in human skin in vivo were assessed by second harmonic generation microscopy and atomic force microscopy, respectively. In vitro cell morphology was assessed by CellTracker^® fluorescent dye and Phalloidin staining. Protein levels were determined by ProteinSimple capillary electrophoresis immunoassay.

Results

Among all 23 known mammalian MMPs, multiple MMPs are elevated in aged human skin dermis. Consistent with this finding, increased MMPs activity and collagen fibrils fragmentation were observed in aged skin dermis. As dermal fibroblasts are the major MMPs producing cells in the dermis, reduction of dermal fibroblast size, which is observed in aged human skin, contributes to elevation of age-related multiple MMPs. Reduction of fibroblast size up-regulates c-Jun/c-Fos and activates AP-1, the major regulator of multiple MMPs.

Conclusions

Combined actions of the wide variety of MMPs that are constitutively elevated in aged dermis may be involved in progressive degradation of dermal collagen fibrils. Age-related elevations of multiple MMPs are likely resulted from the reduction of fibroblast size via activation of AP-1.

This article is protected by copyright. All rights reserved.

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Detection of human parvovirus B19 DNA in 22% of 1,815 cutaneous biopsies of a wide variety of dermatologic conditions suggests viral persistence after primary infection and casts doubts on its pathogenic significance

Summary

Background

Human parvovirus B19 (B19V) has been associated with a number of dermatologic and systemic conditions, including myocarditis and autoimmune syndromes.

Objectives

To determine the frequency of B19V deoxyribonucleic acid (DNA) detection in a large dermatopathology practice, and to characterize the histopathologic patterns involved.

Methods

We selected for polymerase chain reaction (PCR) detection of B19V a total of 1,815 skin biopsies pertaining to entities allegedly related to Parvovirus B19, as well as cases suspected clinically of representing paraviral exanthemas. Immunohistochemical detection of B19V viral protein 2 (VP2) was performed in 92 PCR-positive cases.

Results

B19V DNA was found by PCR in 402 out of 1,825 biopsy specimens (22%). VP2 protein was identified by immunohistochemistry only in three instances of papular purpuric "gloves and socks" syndrome.

Conclusions

Since the virus has the capacity to persist in different tissues (including the skin) for long periods, it could represent merely an innocent bystander, so no pathogenetic significance can be inferred from the PCR positivity for B19V in the vast majority of dermatologic conditions studied.

This article is protected by copyright. All rights reserved.

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Properties and evolution of dissolved organic matter during co-composting of dairy manure and Chinese herbal residues

Abstract

Composting is an effective method in treating solid organic wastes, in which dissolved organic matter (DOM) plays an important role in transformation of organic matter and microbial activity. Therefore, an understanding of the properties and evolution of DOM during composting is crucial. In this study, DOM was studied using elemental analysis, spectroscopic analysis (UV-vis, FTIR, and pyrolysis-GC/MS), and colloidal analysis during a 120-day composting. Results showed that the content of N and O in DOM increased while C and H content declined progressively over the composting time. Aliphatic C–H stretching, aromatic C=C or C=O stretching of amide groups, and C–O stretch (carbohydrates) showed an obvious decrease, while COO– and C–N groups had a significant increase. The evolution of DOM indicated a gradual decrease of the lipid and polysaccharide fractions, whereas an increase of aromatic and nitrogenous compounds was observed. The DOM also showed a more stable status, and an accumulation of small molecular compounds occurred with composting proceeded. Taken together, these results shed a good insight into the properties and evolution of DOM during a composting process.

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Influences of chromium and cadmium on the development of black soldier fly larvae

Abstract

The black soldier fly Hermetia illucens is a good candidate for waste management. The harvested insects are rich in protein and have the potential to be used in animal feed. However, people are wary about heavy metals in waste. Therefore, it is necessary to understand how the uptake of heavy metals could affect H. illucens and where and to what extent metals are accumulated by the black soldier fly. Based on these considerations, developmental parameters were investigated in the different life stages of H. illucens fed an increasing concentration gradient of cadmium (Cd) and chromium (Cr); additionally, Cd and Cr distribution in the body parts of H. illucens at the different life stages was monitored. We found that Cd and Cr have no effects on larvae survival and eclosion rate, but they do have effects on larvae duration and pupation rate. Both Cd and Cr were transferred into larvae, prepupae, and pupae. While the concentrations of Cd in larvae and prepupae were much higher than that in their diets, the opposite case was observed with Cr. The concentrations of Cd and Cr in H. illucens decreased in later development stages. In individual larva and prepupa, Cd and Cr were mainly included in the body and not in the integument. In the pupa, the puparium contained higher Cd and Cr concentrations than the pupa body. The distribution of Cd and Cr in the different life stages and body parts may present a potential strategy for how H. illucens tolerate and remove heavy metal stress.

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Hydrothermal synthesized magnetically separable mesostructured H 2 Ti 3 O 7 /γ-Fe 2 O 3 nanocomposite for organic dye removal via adsorption and its regeneration/reuse through synergistic non-radiation driven H 2 O 2 activation

Abstract

Hydrogen titanate (H₂Ti₃O₇) nanotubes/nanosheets (HTN) are emerging class of adsorbent material which possess unique property of activating hydrogen peroxide (H₂O₂) to generate the reactive oxygen species (ROS), such as superoxide radical ions (O₂^.−) and hydroxyl radicals (·OH), effective in the decomposition of surface-adsorbed dye. However, HTN are non-magnetic which create hurdle in their effective separation from the treated aqueous solution. To overcome this issue, magnetic nanocomposites (HTNF) composed of HTN and maghemite (γ-Fe₂O₃) nanoparticles have been processed by subjecting the core–shell magnetic photocatalyst consisting of γ-Fe₂O₃/silica (SiO₂)/titania (TiO₂), having varying amounts of TiO₂ in the shell to the hydrothermal conditions. HTNF-5 magnetic nanocomposite consisting of 31 wt% H₂Ti₃O₇, typically having nanotube morphology with the highest specific surface area (133 m² g⁻¹) and pore-volume (0.22 cm³ g⁻¹), exhibits the highest capacity (74 mg g⁻¹) for the adsorption of cationic methylene blue (MB) dye from an aqueous solution involving the electrostatic attraction mechanism and pseudo-second-order kinetics. Very fast magnetic separation followed by regeneration of HTNF-5 magnetic nanocomposite has been demonstrated via non-radiation driven H₂O₂ activation. It has been ascertained for the first time that the underlying mechanism of dye decomposition involves the synergy effect between the constituents of HTNF magnetic nanocomposite.

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A Phase I/IIa Study of DHP107, a Novel Oral Paclitaxel Formulation, in Patients with Advanced Solid Tumors or Gastric Cancer

Lessons Learned

Ideally, patients should have access to an oral formulation of paclitaxel, as well as an intravenous formulation, to allow development of regimens exploring alternate schedules and to avoid reactions to Cremophor EL (BASF Corp., Ludwigshafen, Germany, https://www.basf.com).

DHP107 is a novel oral paclitaxel formulation that is a tolerable and feasible regimen for patients with gastric cancer, with data suggesting efficacy similar to that of intravenous paclitaxel.

Background.

We evaluated the maximum tolerated dose (MTD) of DHP107, a novel oral paclitaxel formulation, and the efficacy and safety of the agent in patients with advanced solid tumors.

Patients and Methods.

Phase I study: cohorts of 3–6 patients with advanced solid tumors received escalating DHP107 doses. Phase IIa study: patients with measurable advanced gastric cancer received DHP107, 200 mg/m² b.i.d., on days 1, 8, and 15 every 4 weeks. Pharmacokinetics, safety, and efficacy were analyzed.

Results.

Phase I: 17 patients received a dose-escalating regimen of DHP107, 150–250 mg/m² b.i.d. Dose-limiting toxicities were neutropenia and febrile neutropenia. The MTD (recommended dose) for phase IIa was 200 mg/m² b.i.d. Phase IIa: 11 patients with measurable advanced gastric cancer in whom first-line therapy failed received DHP107 (MTD). Three confirmed partial responses were observed. Median progression-free survival of gastric cancer patients (n = 16) treated at the MTD was 2.97 (95% confidence interval, 1.67–5.40) months (Fig. 1). The most frequent grade 3/4 adverse events were neutropenia (35.3%) and leukopenia (17.6%) at the MTD (phase I and IIa combined; n = 17).

Conclusion.

DHP107 showed good antitumor efficacy and was tolerable. The MTD (200 mg/m² b.i.d.) is recommended for use in further studies comparing DHP107 with standard intravenous paclitaxel therapy. The Oncologist 2017;22:000–000

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An International Vascular Registry Infrastructure for Medical Device Evaluation and Surveillance

Publication date: Available online 14 February 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): A. Sedrakyan, J.L. Cronenwett, M. Venermo, L. Kraiss, D. Marinac-Dabic, M. Björck




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Neck muscle fatigue differentially alters scapular and humeral kinematics during humeral elevation in subclinical neck pain participants versus healthy controls

Publication date: Available online 14 February 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Mahboobeh Zabihhosseinian, Michael W.R. Holmes, Samuel Howarth, Brad Ferguson, Bernadette Murphy
BackgroundScapular orientation is highly dependent on axioscapular muscle function. This study examined the impact of neck muscle fatigue on scapular and humeral kinematics in participants with and without subclinical neck pain (SCNP) during humeral elevation.MethodsTen SCNP and 10 control participants performed three unconstrained trials of dominant arm humeral elevation in the scapular plane to approximately 120 degrees before and after neck extensor muscle fatigue. Three-dimensional scapular and humeral kinematics were measured during the humeral elevation trials.ResultsHumeral elevation plane angle showed a significant interaction between groups (SCNP vs controls) and trial (pre- vs post-fatigue) (p=.001). Controls began the unconstrained humeral elevation task after fatigue in a more abducted position, (p=.002). Significant baseline differences in scapular rotation existed between the two groups (Posterior/Anterior tilt, p=.04; Internal/External Rotation, p=.001).DiscussionSCNP contributed to altered scapular kinematics. Neck muscle fatigue influenced humeral kinematics in controls but not the SCNP group; suggesting that altered scapular motor control in the SCNP group resulted in an impaired adaption further to the neck muscle fatigue.



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Individualized selection of beam angles and treatment isocenter in tangential breast IMRT

Publication date: Available online 14 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Joan Penninkhof, Sara Spadola, Sebastiaan Breedveld, Margreet Baaijens, Nico Lanconelli, Ben Heijmen
Purpose/objectivePropose a novel method for individualized selection of beam angles and treatment isocenter in tangential breast IMRT.Methods and MaterialsFor each patient, beam and isocenter selection starts with the fully automatic generation of a large database of IMRT plans (up to 847 in this study), each of these plans belongs to a unique combination of isocenter position, lateral beam angle, and medial beam angle. The imposed hard planning constraint on patient maximum dose may result in plans with unacceptable target dose delivery. Such plans are excluded from further analyses. Due to differences in beam set-up, database plans differ in mean doses in organs-at-risk (OARs). These mean doses are used to construct 2-dimensional graphs, showing relationships between 1) contralateral breast dose and ipsilateral lung dose, and 2) contralateral breast dose and heart dose (analyzed only for left-sided). The graphs can be used for selection of the isocenter and beam angles with the optimal, patient-specific trade-offs between the mean OAR doses. For 30 previously treated patients (15 left-sided and 15 right-sided tumors), graphs were generated considering only the clinically applied isocenter with 121 tangential beam angle pairs. For 20 of the 30 patients, 6 alternative isocenters were investigated as well.ResultsComputation time for automatic generation of 121 IMRT plans took on average 30 minutes. The generated graphs demonstrated large variations in trade-offs between conflicting OAR objectives, depending on beam angles and patient anatomy. For patients with isocenter optimization, 847 IMRT plans were considered. Adding isocenter position optimization next to beam angle optimization had a small impact on the final plan quality.ConclusionA method is proposed for individualized selection of beam angles in tangential breast IMRT. This may be especially important for patients with cardiac risk factors or an enhanced risk for development of contralateral breast cancer.

Teaser

A method for individualized selection of beam angles and treatment isocenter in tangential breast IMRT, based on graphical representations of mean OAR doses in a large database of automatically generated IMRT plans, is presented. The method may be especially useful for patients with cardiac risk factors or an enhanced risk for induction of a tumor in the contralateral breast.


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Salvage treatment options for recurrent seminoma? Expert Opinion Commentary

Publication date: Available online 14 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Peter Chung, Padraig Warde




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Development of a Quality and Safety Competency Curriculum for Radiation Oncology Residency: An International Delphi Study

Publication date: Available online 14 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jenna Adleman, Caitlin Gillan, Amanda Caissie, Carol-Anne Davis, Brian Liszewski, Andrea McNiven, Meredith Giuliani
PurposeThe purpose of this study was to develop an entry-to-practice quality and safety competency profile for radiation oncology (RO) residency.Methods and MaterialsA comprehensive list of potential quality and safety competency items was generated from public and professional resources and interprofessional focus groups. Redundant or out-of-scope items were eliminated through investigator consensus. Remaining items were subjected to an international two-round modified Delphi process involving experts in RO, radiation therapy, and medical physics. During Round One, each item was scored independently on a 9-point Likert scale indicating appropriateness for inclusion in the competency profile. Items indistinctly ranked for inclusion or exclusion were reevaluated through web-conference discussion and re-ranked in Round Two.ResultsAn initial 1,211 items were compiled from 32 international sources and distilled to 105 unique potential quality and safety competency items. Fifteen of the 50 invited experts participated in Round One: 10 radiation oncologists, four radiation therapists, and one medical physicist from 13 centres in five countries. Round One rankings resulted in 80 items included, one item excluded, and 24 items indeterminate. Two areas emerged more prominently within the latter group: change management and human factors. Web-conference with five participants resulted in nine of these 24 items edited for content or clarity. In Round Two, 12 participants rescored all indeterminate items resulting in 10 items ranked for inclusion. The final 90 enabling competency items were organized into thematic groups consisting of 18 key competencies under headings adapted from Deming's System of Profound Knowledge.ConclusionsThis quality and safety competency profile may inform minimum training standards for RO residency programs.

Teaser

The purpose of this study was to develop an entry-to-practice quality and safety competency profile for radiation oncology (RO) residency education. An international 2-round modified Delphi process was conducted with participation from 15 experts in radiation oncology representing 13 centres in five countries. Ninety of the initial 105 items were ranked for inclusion in the final competency profile. This profile may form the basis of quality and safety training standards in RO residency programs.


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Predicting patient-specific dosimetric benefits of proton therapy for skull-base tumors using a geometric knowledge-based method

Publication date: Available online 14 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): David C. Hall, Alexei V. Trofimov, Brian A. Winey, Norbert J. Liebsch, Harald Paganetti
PurposeTo predict the organ-at-risk (OAR) dose levels achievable with proton beam therapy (PBT), solely based upon the geometric arrangement of the target volume in relation to the OARs. Comparison to an alternative therapy yields a prediction of the patient-specific benefits offered by PBT. This could enable a physician at a hospital without proton capabilities to make a better-informed referral decision, or aid patient selection in model-based clinical trials.Methods and MaterialsSkull-base tumors were chosen to test the method, owing to their geometric complexity and multitude of nearby OARs. By exploiting correlations between dose and distance-to-target in existing PBT plans, models were independently trained for six types of OAR: brainstem, cochlea, optic chiasm, optic nerve, parotid gland and spinal cord. Once trained, the models could estimate the feasible dose-volume histogram and generalized equivalent uniform dose (gEUD) for OAR structures of new patients. Models were trained using 20 patients and validated with a further 21 patients. Validation was achieved by comparing the predicted gEUD to that of the actual PBT plan.ResultsThe predicted and planned gEUD were in good agreement: considering all OARs, the prediction error was +1.4 ± 5.1 Gy (mean ± SD) and Pearson's correlation coefficient was 93%. When compared to an IMRT plan, the model could classify whether an OAR structure would experience a gain with a sensitivity of 93% (95% CI: 87% – 97%) and a specificity of 63% (95% CI: 38% – 84%).ConclusionsWe trained and validated models that quickly and accurately predict the patient-specific benefits of PBT for skull-base tumors. Similar models could be developed for other tumor sites. Such models are useful when an estimation of the feasible benefits of PBT is desired, but the experience and/or resources required for treatment planning are unavailable.

Teaser

This work aims to develop models that can predict the patient-specific benefits offered by proton therapy, solely based upon a patient's geometry. A knowledge-based method trains the models upon geometric patterns observed in a set of existing proton treatment plans for skull base tumors. The models were validated yielding a Pearson's correlation coefficient of 93%; similar models could be trained for other tumor sites and be used to make better-informed referral decisions.


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Open-label study of etanercept treatment in patients with moderate to severe plaque psoriasis who lost a satisfactory response to adalimumab

Summary

Background

Some plaque psoriasis patients experience secondary failure of tumour necrosis factor inhibitor therapy.

Objectives

To evaluate efficacy, safety, and patient-reported outcomes (PROs) with etanercept in patients with secondary adalimumab failure.

Methods

This phase 4, open-label, single-arm, estimation study (NCT01543204) enrolled patients on adalimumab who had achieved static physician global assessment (sPGA) score 0/1 (clear/almost clear). Patients subsequently lost response, defined as sPGA ≥3 or loss of 50% improvement in Psoriasis Area and Severity Index (PASI 50). At baseline, patients had involved body surface area ≥10%, sPGA ≥3, and PASI ≥10. Anti-adalimumab antibodies (ADA) were measured at screening. Patients received etanercept 50mg twice weekly for 12 weeks followed by 50mg weekly. Primary endpoint was sPGA 0/1 at week 12 (intent-to-treat analysis; no hypothesis tested). Additional outcomes included rates of sPGA 0/1, PASI responses, safety, PROs of itch, pain, and flaking, Dermatology Life Quality Index (DLQI), treatment satisfaction, and Work Productivity and Activity Impairment (WPAI).

Results

Sixty-four patients enrolled; 67% had ADA. Week 12 sPGA 0/1 rates (95% confidence interval) were 39.7% (27.6%-52.8%; primary endpoint); and 45.0% (29.3%–61.5%) for ADA-positive and 35.0% (15.4%–59.2%) for ADA-negative patients. Week 12 PASI 75 response rates (95% CI) were 47.5% (31.5%–63.9%) for ADA-positive and 50.0% (27.2%–72.8%) for ADA-negative patients. No new safety signals were observed. PROs of itch, pain, and flaking consistently improved at week 12 and were maintained through week 24.

Conclusions

Psoriasis patients with secondary failure of adalimumab achieved satisfactory response to etanercept regardless of ADA status.

This article is protected by copyright. All rights reserved.

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IFNAR1 Degradation: A New Mechanism for Tumor Immune Evasion?

Publication date: 13 February 2017
Source:Cancer Cell, Volume 31, Issue 2
Author(s): Romina E. Araya, Romina S. Goldszmid
Type I interferons have been shown to play a major role in anti-cancer immunity. In this issue of Cancer Cell, Katlinski et al. describe tumor-induced degradation of type I interferon receptor IFNAR1 chain as a new immune-evasion mechanism in colorectal cancers. Stabilizing IFNAR1 inhibits tumor growth and improves immunotherapy efficacy.

Teaser

Type I interferons have been shown to play a major role in anti-cancer immunity. In this issue of Cancer Cell, Katlinski et al. describe tumor-induced degradation of type I interferon receptor IFNAR1 chain as a new immune-evasion mechanism in colorectal cancers. Stabilizing IFNAR1 inhibits tumor growth and improves immunotherapy efficacy.


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An Oncogenic Role for the Ubiquitin Ligase UBE2O by Targeting AMPK-α2 for Degradation

Publication date: 13 February 2017
Source:Cancer Cell, Volume 31, Issue 2
Author(s): D. Grahame Hardie
There has been controversy regarding the role of AMPK in cancer, some of which may be due to functional differences between isoforms. In this issue of Cancer Cell, Vila et al. report that UBE2O, a ubiquitin ligase overexpressed in some human cancers, specifically triggers the ubiquitination and degradation of AMPK-α2.

Teaser

There has been controversy regarding the role of AMPK in cancer, some of which may be due to functional differences between isoforms. In this issue of Cancer Cell, Vila et al. report that UBE2O, a ubiquitin ligase overexpressed in some human cancers, specifically triggers the ubiquitination and degradation of AMPK-α2.


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