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Πέμπτη 14 Ιουνίου 2018

Definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for advanced cervical esophageal cancer

Abstract

Background

Recently, definitive chemoradiotherapy (dCRT) has become one of the essential treatment strategies for esophageal squamous cell carcinoma (ESCC) and has been especially gaining prevalence for cervical ESCC to preserve the larynx. Our department recently introduced dCRT concomitant with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for treating advanced cervical ESCC. This study aims to assess the safety and outcomes of DCF-R in patients with advanced cervical ESCC.

Methods

We retrospectively assessed 11 patients with advanced cervical ESCC (clinical stage: II–IV, including T4b and/or M1 lymph node) who received DCF-R as the first-line treatment between December 2010 and February 2015.

Results

Our patient cohort comprised 8 males and 3 females (median age 68 years; range 54–76 years). The pretreatment clinical stage included stage II (1), stage III (7), and stage IV (3) cases [including 3 patients with T4b (2 trachea and 1 thyroid) and 3 patients with M1 lymph node]. We attained complete response (CR) in 10 patients and stable disease in 1 patient. Of 10 patients with CR, 5 experienced recurrence and 5 continued exhibiting CR. Furthermore, grade 3 or more adverse events included leucopenia (91%), neutropenia (91%), febrile neutropenia (45%), and pharyngeal pain (55%). While the 2-year overall survival rate was 72%, the 2-year recurrent-free survival rate was 64%, respectively.

Conclusions

DCF-R treatment for advanced cervical esophageal cancer could be completed by the careful administration; although a strong blood toxicity might occur, this treatment may provide the chance to obtain favorable prognosis with larynx preservation.



Effects of arsenic methylation and metabolism on the changes of arsenic-related skin lesions

Abstract

Little was known about the arsenic metabolism and arsenic methylation associated with the changes of skin lesions after reducing the arsenic in drinking water (WAs). Therefore, urinary concentrations and proportions of arsenic species were determined for recovery (RC), improvement (IC), persistent (PE), aggravation (AC), new incidence (NC), and no sign (HC) groups based on the changes of skin lesions between before (in 2004) and after (in 2017) WAs reduction. The results indicate that the urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and total arsenic (TAs) were much higher for RC and IC groups than for the other groups in 2004, while these values varied slightly among the groups in 2017. The urinary %iAs of all the groups was significantly decreased after WAs reduction. In contrast, the urinary %DMA of RC, IC, AC, and NC groups was increased. From 2004 to 2017, the PE and HC groups had lower decrease rate of %iAs and %MMA, and increase rate of %DMA, primary methylation index (PMI), and secondary methylation index (SMI) after WAs reduction. The adjusted odd ratios (ORs) showed that the RC, IC, AC, and NC groups were positively related with %iAs and %MMA and were negatively correlated with %DMA, PMI, and SMI before WAs reduction. It can be concluded that higher urinary %iAs and %MMA before WAs reduction increased the probability of skin lesions recovery and improvement, and the risks of skin lesions aggravation and incidence. Higher increase rate of urinary %DMA was positively associated with of skin lesions recovery and improvement. Moreover, higher urinary %iAs and %MMA or lower increase rate of urinary %DMA might increase the risk of skin lesions aggravation.



Time Course of Cerebral Perfusion Changes in Children with Migraine with Aura Mimicking Stroke [PEDIATRICS]

SUMMARY:

Hemiplegic migraine is a common cause of acute brain attack in pediatrics. MR imaging sequences useful in differentiating hemiplegic migraine from other entities include arterial spin-labeling, SWI, MRA, and DWI. There has been limited exploration on the simultaneous use of these sequences in pediatrics. We present 12 pediatric patients with acute hemiplegic migraine or migraine with aura who underwent MR imaging within 12 hours of symptom onset. Quantitative and qualitative analyses were performed on arterial spin-labeling; and qualitative analysis, on SWI and MRA sequences. All 12 patients had normal DWI and abnormal arterial spin-labeling findings. Furthermore, we observed a more rapid transition from hypoperfusion to rebound hyperperfusion in 3 patients compared with prior reports. These findings support the use of multimodal MR imaging to distinguish migraine with aura from stroke and the simultaneous use of these MR imaging sequences to improve understanding of perfusion changes during migraine with aura.



Prognostic Implications of Gadolinium Enhancement of Skull Base Chordomas [HEAD & NECK]

BACKGROUND AND PURPOSE:

Skull base chordomas often demonstrate variable MR imaging characteristics, and there has been limited prior research investigating the potential clinical relevance of this variability. The purpose of this retrospective study was to assess the prognostic implications of signal intensity on standard imaging techniques for the biologic behavior of skull base chordomas.

MATERIALS AND METHODS:

Medical records were retrospectively reviewed for 22 patients with pathologically confirmed skull base chordomas. Clinical data were recorded, including the degree of surgical resection, the presence or absence of radiation therapy, and time to progression/recurrence of the tumor or time without progression/recurrence of the tumor following initial treatment. Pretreatment imaging was reviewed for the presence or absence of enhancement and the T2 signal characteristics. Tumor-to-brain stem signal intensity ratios on T2, precontrast T1, and postcontrast T1 spin-echo sequences were also calculated. Statistical analysis was then performed to assess correlations between imaging characteristics and tumor progression/recurrence.

RESULTS:

Progression/recurrence of skull base chordomas was seen following surgical resection in 11 of 14 (78.6%) patients with enhancing tumors and in zero of 8 patients with nonenhancing tumors. There was a statistically significant correlation between skull base chordoma enhancement and subsequent tumor progression/recurrence (P < .001), which remained significant after controlling for differences in treatment strategy (P < .001). There was also a correlation between postcontrast T1 signal intensity (as measured by postcontrast T1 tumor-to-brain stem signal intensity ratios) and recurrence/progression (P = .02). While T2 signal intensity was higher in patients without tumor progression (median tumor-to-brain stem signal intensity ratios on T2 = 2.27) than in those with progression (median tumor-to-brain stem signal intensity ratios on T2 = 1.78), this association was not significant (P = .12).

CONCLUSIONS:

Enhancement of skull base chordomas is a risk factor for tumor progression/recurrence following surgical resection.



Zonally Magnified Oblique Multislice and Non-Zonally Magnified Oblique Multislice DWI of the Cervical Spinal Cord [SPINE]

BACKGROUND AND PURPOSE:

The zonally magnified oblique multislice EPI (ZOOM-EPI) diffusion-weighted sequence has been visually shown to provide superior MR diffusion image quality compared with the full-FOV single-shot EPI sequence (non-ZOOM-EPI) in the adult cervical spinal cord. The purpose of this study was to examine the diffusion tensor imaging indices in the normal human cervical spinal cord between ZOOMED and non-ZOOMED DTI acquisitions and determine whether DTI values are comparable between direct and indirect age-matched groups.

MATERIALS AND METHODS:

Fifty-four subjects 23–58 years of age (9 direct age-matched and 45 indirect age-matched) were scanned using a 1.5T scanner. Diffusion tensor indices including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were generated from the DTI dataset. These DTI values were calculated for both ZOOM and non-ZOOM acquisitions and compared at each intervertebral disc level. The variability of the DTI values for ZOOM and non-ZOOM sequences was measured using a coefficient of variation within direct and indirect age-matched controls.

RESULTS:

The mean diffusivity, axial diffusivity, and radial diffusivity values obtained along the cervical spinal cord in the age-matched controls showed a significant decrease using the ZOOM sequence (P = .05, P = .002, and P < .001). Mean fractional anisotropy showed a significant increase (P = .04) using the ZOOM sequence. The indirect age-matched controls showed a statistically significant increase in fractional anisotropy (P = .03) and a decrease in mean diffusivity (P = .002), axial diffusivity (P < .001), and radial diffusivity (P = .002) using the ZOOM sequence. Less variability has been shown in DTI using the ZOOM sequence compared with the non-ZOOM sequence in both direct and indirect age groups. The ZOOM sequence exhibited higher SNR (SNRZOOM = 22.84 ± 7.59) compared with the non-ZOOM sequence (SNRnon-ZOOM = 19.7 ± 7.05). However, when we used a 2-tailed t test assuming unequal variances, the ZOOM sequence did not demonstrate a statistically significant increase.

CONCLUSIONS:

ZOOM DTI acquisition methods provide superior image quality and precision over non-ZOOM techniques and are recommended over conventional full-FOV single-shot EPI DTI for clinical applications in cervical spinal cord imaging.



Detection and Characteristics of Temporal Encephaloceles in Patients with Refractory Epilepsy [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Temporal encephaloceles are increasingly visualized during neuroimaging assessment of individuals with refractory temporal lobe epilepsy, and their identification could indicate an intracranial abnormality that may be related to a potential seizure focus. Careful review by an experienced neuroradiologist may yield improved detection of TEs, and other clinical, neurophysiologic, and radiologic findings may predict their presence.

MATERIALS AND METHODS:

Data were reviewed retrospectively in patients at our institution who were presented at a multidisciplinary conference for refractory epilepsy between January 1, 2010, and December 31, 2016. Clinical, neurophysiologic, and imaging data were collected. An expert neuroradiologist reviewed the latest MR imaging of the brain in patients for whom one was available, noting the presence or absence of temporal encephaloceles as well as other associated imaging characteristics.

RESULTS:

A total of 434 patients were reviewed, 16 of whom were excluded due to unavailable or poor-quality MR imaging. Seven patients had temporal encephaloceles reported on initial imaging, while 52 patients had temporal encephaloceles identified on expert review. MR imaging findings were more often initially normal in patients with temporal encephaloceles (P < .001), and detection of temporal encephaloceles was increased in patients in whom 3T MR imaging was performed (P < .001), the T2 sampling perfection with application-optimized contrasts by using different flip angle evolutions sequence was used (P < .001), or the presence of radiologic findings suggestive of idiopathic intracranial hypertension was noted. Seizure onset by scalp electroencephalogram among patients with temporal encephaloceles was significantly more likely to be temporal compared with patients without temporal encephaloceles (P < .001). A significant correlation between intracranial electroencephalogram seizure onset and patients with temporal encephaloceles compared with patients without temporal encephaloceles was not observed, though there was a trend toward temporal-onset seizures in patients with temporal encephaloceles (P = .06).

CONCLUSIONS:

Careful review of MR imaging in patients with refractory temporal lobe epilepsy by a board-certified neuroradiologist with special attention paid to a high-resolution T2 sequence can increase the detection of subtle temporal encephaloceles, and certain clinical and neurophysiologic findings should raise the suspicion for their presence.



Contextual Radiology Reporting: A New Approach to Neuroradiology Structured Templates [PRACTICE PERSPECTIVES]

SUMMARY:

Structured reporting has many advantages over conventional narrative reporting and has been advocated for standard usage by radiologic societies and literature. Traditional structured reports though are often not tailored to the appropriate clinical situation, are generic, and can be overly constraining. Contextual reporting is an alternative method of structured reporting that is specifically related to the disease or examination indication. Herein, we create a library of 50 contextual structured reports for neuroradiologists and emphasize their clinical value over noncontextual structured reporting. These templates are located in the On-line Appendix, and a downloadable PowerScribe 360 file may be accessed at https://drive.google.com/open?id=1AlPUmfAXPzjkMFcHf7vGKF4Q-vIdpflT.



MR Imaging Features of Anaplastic Pleomorphic Xanthoastrocytoma Mimicking High-Grade Astrocytoma [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Anaplastic pleomorphic xanthoastrocytoma, which has been recently defined as a distinct entity in the 2016 World Health Organization classification, may exhibit aggressive clinical behavior and relatively worse prognosis than pleomorphic xanthoastrocytoma. This study aimed to investigate whether there were any differences in MR imaging characteristics between these 2 tumors.

MATERIALS AND METHODS:

This retrospective study included 9 patients with anaplastic pleomorphic xanthoastrocytoma and 10 patients with pleomorphic xanthoastrocytoma who underwent MR imaging before an operation. DWI was performed in 17 patients (8 with anaplastic pleomorphic xanthoastrocytoma, 9 with pleomorphic xanthoastrocytoma); and DSC-PWI, in 9 patients (5 with anaplastic pleomorphic xanthoastrocytoma, 4 with pleomorphic xanthoastrocytoma). Demographics, conventional imaging characteristics (location, size, cystic degeneration, enhancement, peritumoral edema, and leptomeningeal contact), minimum relative ADC ratio, and maximum relative CBV ratio were evaluated between the anaplastic pleomorphic xanthoastrocytoma and pleomorphic xanthoastrocytoma groups.

RESULTS:

Anaplastic pleomorphic xanthoastrocytoma was more likely to demonstrate high-grade features than pleomorphic xanthoastrocytoma, including greater maximum tumor diameter (4.7 ± 0.6 cm versus 3.1 ± 1.1 cm, P = .001), more frequent heterogeneous contrast enhancement of solid portions (88.9% versus 20.0%, P = .01), more obvious peritumoral edema (2.3 ± 0.9 cm versus 1.0 ± 0.9 cm, P = .008), lower minimum relative ADC on DWI (1.0 ± 0.2 versus 1.5 ± 0.4, P = .008), and higher maximum relative CBV on DSC-PWI (2.6 ± 0.8 versus 1.6 ± 0.2, P = .036).

CONCLUSIONS:

Anaplastic pleomorphic xanthoastrocytomas often have more aggressive MR imaging features mimicking high-grade astrocytomas than pleomorphic xanthoastrocytomas. DWI and DSC-PWI might be useful in the characterization and differentiation of anaplastic pleomorphic xanthoastrocytoma and pleomorphic xanthoastrocytoma.



Editorial Board



Table of Contents



Cutaneous squamous cell carcinoma progression during imiquimod treatment

To the Editor: We read with interest the paper by Que SKT et al regarding the management of cutaneous squamous cell carcinoma (cSCC)1 and the remarkable discussion about the field treatment with topical chemotherapy agents. Imiquimod is an immune response modifier that activates immune cells via toll-like receptor 7, initiating a cascade leading to the induction of cytokines, such as interferon alfa, interferon gamma, and interleukin 12, which promote a T helper 1 (TH1) immune response.2 The use of imiquimod for the treatment of invasive cSCC is not approved by the European Medicines Agency or Food and Drug Administration, but few reports have described its success in elderly patients and when other treatments and surgery are contraindicated.

CME examination



Reply to: “Prognostic significance of tumor budding in cutaneous squamous cell carcinoma”

To the Editor: We would like to thank Kanitakis and Karayannopoulou1 for highlighting that a key point of our article on the prognostic significance of tumor budding in cutaneous squamous cell carcinoma (cSCC) is the assessment method.2 We fully agree that a consensus method is needed because tumor budding is increasingly being recognized as a prognostic factor in several cancers.

Association of 25-hydroxyvitamin D levels and cutaneous melanoma: A nested case-control study of the Women's Health Initiative Observation Study

To the Editor: Exposure to ultraviolet radiation is an important risk factor for melanoma but is also the principal means by which the body synthesizes vitamin D in the skin. Prior studies on the association between 25-OH-D levels and melanoma occurrence and prognosis have shown conflicting results.1,2

Dermatology Calendar



CME examination



Information for Readers



Journal Based CME Instructions and Information



JAAD Case Reports Article List



Answers to CME examination



Prognostic significance of tumor budding in cutaneous squamous cell carcinoma

To the Editor: We read with interest the article by Gonzalez-Guerrero et al1 reporting the prognostic significance of tumor buds in cutaneous squamous cell carcinoma (cSCC). The results of this study confirm and complement the results of 2 similar investigations published previously on the same topic,2,3 even though the methodology of these 3 studies was not identical. In our study,2 we compared 31 aggressive cSCCs, defined as tumors with subsequent local recurrences or metastases, with 21 nonaggressive cSCCs (which had been obtained from the same group of organ-graft recipients) and counted the number of tumor buds (defined as groups of 1-5 tumor cells) on 5 adjacent microscopic hot-spot fields at the invasive tumor front.

Dermatoses caused by cultural practices

With globalization and widespread immigration, physicians increasingly encounter patients from varying backgrounds and diverse customs. Although certain cultural practices are widely performed, there is limited medical literature describing their dermatologic and systemic effects and complications. Population diversity and sharing of traditions make it increasingly important for dermatologists to understand the role of cultural practices and recognize physiologic and pathologic sequelae. In addition, dermatologists are often adjured to assess skin findings that may be mistaken for abuse.

A new cover, a new editorial board

A new cover, a new editorial board.

Answers to CME examination



Alopecia areata

To the Editor: Strazzulla et al1,2 have written instructive reviews on the clinical presentation, pathogenesis, and current treatment options for alopecia areata. In these articles, they describe and show photographs of the more common patchy subtype of the scalp and beard, as well as the less common ophiasis, androgenic-like, and diffuse subtypes. They also explain how trichoscopy and scalp biopsy are important tools in diagnosing alopecia areata. The authors mention that nail changes may be present in 10% to 20% of patients with alopecia areata and that severity of nail changes may correlate with more extensive hair loss; in addition, they list some of the more common nail changes, namely, regular pitting, longitudinal ridging, trachyonychia, and red lunulae.

July iotaderma (#293)



June iotaderma (#292)



Dermatoses caused by cultural practices

The second article in this continuing medical education series discusses cosmetic practices associated with cultural dermatoses, including hair care, traditional clothing, and skin decorations. Often, the steps individuals take to enhance their physical appearance are determined by cultural perceptions of beauty. Without awareness of cultural practices, a multitude of cutaneous dermatoses may be missed by the dermatologist. Recognition and understanding of patients' cultural backgrounds and habits will allow the practicing dermatologist to offer better counseling and treatment options while providing a more meaningful and understanding physician–patient relationship.

Simultaneous NO and SO 2 removal by aqueous persulfate activated by combined heat and Fe 2+ : experimental and kinetic mass transfer model studies

Abstract

This study evaluates the chemistry, kinetics, and mass transfer aspects of the removal of NO and SO2 simultaneously from flue gas induced by the combined heat and Fe2+ activation of aqueous persulfate. The work involves experimental studies and the development of a mathematical model utilizing a comprehensive reaction scheme for detailed process evaluation, and to validate the results of an experimental study at 30–70 °C, which demonstrated that both SO2 and Fe2+ improved NO removal, while the SO2 is almost completely removed. The model was used to correlate experimental data, predict reaction species and nitrogen-sulfur (N-S) product concentrations, to obtain new kinetic data, and to estimate mass transfer coefficient (KLa) for NO and SO2 at different temperatures. The model percent conversion results appear to fit the data remarkably well for both NO and SO2 in the temperature range of 30–70 °C. The conversions ranged from 43.2 to 76.5% and 98.9 to 98.1% for NO and SO2, respectively, in the 30–70 °C range. The model predictions at the higher temperature of 90 °C were 90.0 and 97.4% for NO and SO2, respectively. The model also predicted decrease in KLa for SO2 of 1.097 × 10−4 to 8.88 × 10−5 s−1 (30–90 °C) and decrease in KLa for NO of 4.79 × 10−2 to 3.67 × 10−2 s−1 (30–50 °C) but increase of 4.36 × 10−2 to 4.90 × 10−2 s−1 at higher temperatures (70–90 °C). This emerging sulfate-radical-based process could be applied to the treatment of flue gases from combustion sources.

Graphical abstract



Characterization of outdoor bronze monument patinas: the potentialities of near-infrared spectroscopic analysis

Abstract

The corrosion products usually found on outdoor bronzes are generated by the interaction between the metal alloy and the atmospheric pollutants. To protect the external surface of bronzes, different organic materials (natural or synthetic) can be applied, creating over time a patina consisting of a complex mixture of inorganic and organic degraded components. The correct chemical characterization of patina constituents is fundamental to define the state of conservation of a metal artwork and address proper restoration actions. In this paper, we evaluated the potentialities of near-infrared (NIR) reflectance microscopy (4000–7500 cm−1) as complementary method to mid-infrared (MIR) analyses for the characterization of bronze patinas. Although NIR spectroscopy has been already used in the field of heritage science, its application for the characterization of bronze patinas is almost unexplored. In this paper, several corrosion products usually found on the surface of outdoor bronze sculptures were synthesized, characterized, and submitted to the NIR-MIR total reflection analysis to build up a reference spectral database. We devoted particular attention to the NIR features of copper hydroxychlorides, such as atacamite and paratacamite, which have not been studied in detail up to now. A selection of organic-based formulations, commonly used by restorers to protect the bronze surface against the outdoor aggressive environment, were also considered as references. Successively, NIR-MIR reflectance microscopy was successfully employed for the analysis of patina micro-samples collected from the bronze statues of the Neptune Fountain (sixteenth century) located in Bologna. The obtained results demonstrate the ability of NIR spectroscopy to identify organic and inorganic patina constituents, even in mixtures. In addition, the study can be considered as a proof of concept for the possible future application of the technique for in situ diagnostic campaigns on bronze sculptures.



Herbicides in river water across the northeastern Italy: occurrence and spatial patterns of glyphosate, aminomethylphosphonic acid, and glufosinate ammonium

Abstract

Glyphosate and glufosinate ammonium are the active ingredients of commonly used herbicides. Active agricultural lands extend over a large part of the Veneto region (Eastern Po Valley, Italy) and glyphosate and glufosinate ammonium are widely used. Consequently, surface waters can be potentially contaminated. This study investigates the occurrence of glyphosate and glufosinate ammonium as well as aminomethylphosphonic acid (AMPA, the degradation product of glyphosate) in river water of Veneto. Eighty-six samples were collected in 2015 at multiple sampling points across the region. Samples were analyzed for the two target herbicides, AMPA as well as for other variables, including water temperature, pH, dissolved oxygen, conductivity, hardness, BOD, COD, inorganic ions, total nitrogen, total phosphorus, total suspended solids, arsenic, and lead. The average concentrations (all samples) were 0.17, 0.18, and 0.10 μg L−1 for glyphosate, AMPA, and glufosinate ammonium, respectively. The European upper tolerable level for pesticides (annual average 0.1 μg L−1) was often exceeded. Chemometric analysis was therefore applied to (i) investigate the relationships among water pollutants, (ii) detect the potential sources of water contamination, (iii) assess the effective water pollution of rivers by identifying river basins with anomalous pollution levels, and (iv) assess the spatial variability of detected sources. Factor analysis identified four factors interpreted as potential sources and processes (use of herbicides, leaching of fertilizers, urban/industrial discharges, and the biological activity on polluted or stagnant waters). A discriminant analysis revealed that the pollution from anthropogenic discharges is homogeneously present in surface water of Veneto, while biological activity and fertilizers present heterogeneous distributions. This study gives insights into the concentrations of herbicides in rivers flowing through a wide region that has heavy use of these chemicals in agriculture. The study also points out some hot-spots and suggests the future implementation of the current monitoring protocols and network.



Nerve conduction velocity as a non-destructive biomarker in the earthworm Aporrectodea caliginosa exposed to insecticides

Abstract

Earthworms are important and useful soil organisms, but in agricultural soils, they are potentially exposed to a wide variety of pesticides. Insecticides represent the highest threat to earthworms and many are neurotoxic. There is a need for a reliable, relevant, simple biomarker to assess the sub-lethal effects of neurotoxic insecticides on earthworms under laboratory or field conditions. The Aporrectodea caliginosa earthworms were exposed to 0 (control), 0.5×, 1× (normal field application rate), and 5× concentrations of a carbamate (Pirimor®) and an organophosphate (Lorsban®) insecticides. The nerve conduction velocity (NCV) of the medial giant fibers of A. caliginosa earthworm was recorded on days 0, 1, 2, 3, 4, and 7 to quantify sub-lethal neurotoxic effects. Acetylcholinesterase (AChE) enzyme activity of A. caliginosa homogenates was measured at the conclusion of the experiment. Pirimor® but not Lorsban® induced a significant decrease in NCV on days 3, 4, and 7 at 1× and 5× doses. A significant dose-dependent decrease was observed on AChE activity to Pirimor® at the doses used but not Lorsban®. A clear relationship is observed between AChE activity and NCV in the case of Pirimor®. This study showed that NCV is a sensitive biomarker that correlates well with classical biomarker measurements such as AChE enzyme activity. This technique could be used to study the impact of insecticides on earthworms and also their recovery.



The sources and dispersal of nitrate in multiple waters, constrained by multiple isotopes, in the Wudalianchi region, northeast China

Abstract

The Wudalianchi scenic area in NE China has been named an UNESCO "Global Geopark" and "Biosphere Reserve." During this investigation, the sources of nitrate and the hydrologic system through which it is dispersed were assessed using geochemical data and a multiple isotopic approach. The cold waters from the south and north springs originated from the deep subsurface. Isotopically, these waters exhibited relatively negative δD and δ18O values and nitrate in the water was substantially depleted 15N, suggesting that the mineral water was primarily derived from depth. Lakes within the Wudalianchi region were primarily composed of water from these deep mineral springs and precipitation. Chemical fertilizers were the primary source of nitrate to the Wudalianchi lakes. Groundwater was found in shallow mineral springs and wells plotted above the local meteoric water line, implying that shallow groundwater was primarily derived from precipitation. Elevated concentrations of nitrate in shallow mineral springs and well waters during the summer, autumn, and winter suggest that shallow groundwater within the Yaoquan volcanic area was also polluted by nitrate from human activities. Denitrification of shallow groundwater is slow, reducing the potential for "self-remediation". The concentration data are supported by nitrogen (N) isotope data; wells and springs exhibited N isotopic ratios between − 5‰ and + 5‰ (typical of fertilizers and precipitation) and exhibited higher oxygen (O) isotope values than water in the Wudalianchi lakes. These relationships suggest that nitrate in shallow mineral springs, wells, and lakes near the Yaoquan volcano was derived from the mixing of chemical fertilizers with local summer rainfall.



Arbuscular mycorrhizal fungi enhance antioxidant defense in the leaves and the retention of heavy metals in the roots of maize

Abstract

In this study, we investigated the effects of the arbuscular mycorrhizal fungi (AMF) Funneliformis mosseae and Diversispora spurcum on the growth, antioxidant physiology, and uptake of phosphorus (P), sulfur (S), lead (Pb), zinc (Zn), cadmium (Cd), and arsenic (As) by maize (Zea mays L.) grown in heavy metal-polluted soils though a potted plant experiment. F. mosseae significantly increased the plant chlorophyll a content, height, and biomass; decreased the H2O2 and malondialdehyde (MDA) contents; and enhanced the superoxide dismutase (SOD) and catalase (CAT) activities and the total antioxidant capacity (T-AOC) in maize leaves; this effect was not observed with D. spurcum. Both F. mosseae and D. spurcum promoted the retention of heavy metals in roots and increased the uptake of Pb, Zn, Cd, and As, and both fungi restricted heavy metal transfer, resulting in decreased Pb, Zn, and Cd contents in shoots. Therefore, the fungi reduced the translocation factors for heavy metal content (TF) and uptake (TF′) in maize. Additionally, F. mosseae promoted P and S uptake by shoots, and D. spurcum increased P and S uptake by roots. Moreover, highly significant negative correlations were found between antioxidant capacity and the H2O2, MDA, and heavy metal contents, and there was a positive correlation with the biomass of maize leaves. These results suggested that AMF alleviated plant toxicity and that this effect was closely related to antioxidant activation in the maize leaves and increased retention of heavy metals in the roots.



Economic evaluation of patient navigation programs in colorectal cancer care, a systematic review

Patient navigation has expanded as a promising approach to improve cancer care coordination and patient adherence. This paper addresses the need to identify the evidence on the economic impact of patient navig...

Variation in the RPTN gene may facilitate straight hair formation in Europeans and East Asians

Head hair shape is a distinctive feature of human appearance and shows a marked degree of variation on the world map. TCHH and EDAR, the two major hair shape genes, have been shown to influence hair structure exclusively in Europe and East Asia, respectively, indicating divergent genetic mechanisms of straight hair formation in various human populations [1–3]. However, the proportion of known heritability explained by both genes in respective populations is very small. Although genome-wide association studies have been shown to be effective in identifying genes with medium to small effect sizes, there are clear evidences that essential fraction of the overall heritability for complex traits is not properly identified using standard approaches.

Erratum: The Nail Hematoma Selfie



An empirical analysis of financial development and energy demand: establishing the role of globalization

Abstract

The rapid mode of globalization is experienced in the last few years. The acceleration in globalization expands economic activities through a share of knowledge and transfer of technology which influence energy demand. So, the objective of this empirical work is to explore the impact of financial development on energy demand incorporating globalization. The empirical finding is based on autoregressive distributed lag (ARDL) bound testing approach from 1980 to 2016 in case of China. Overall, we infer that financial development increases energy demand in China. Furthermore, the finding shows that globalization has a negative and significant impact on energy demand. The additional determinants, such as economic growth, and urbanization stimulate energy consumption. Besides, energy consumption granger cause financial development in the long-run path. Similarly, unidirectional causality is detected between globalization and energy consumption. The result gives direction to policymakers to preserve as well as to enhance efficient energy consumption and sustain economic growth in China with acceleration in globalization.



Temporal and spatial characteristics of potential energy anomaly in Lake Taihu

Abstract

In this study, water temperature and meteorological data in Lake Taihu from June 11 to July 6, 2013, are collected to calibrate and verify the unstructured grid finite-volume community ocean model (FVCOM) coupled with a heat exchange module. The spatial and temporal variations of potential energy anomalies (PEA) in the lake, simulated by the calibrated FVCOM, are analyzed to explore the stratification and de-stratification processes in water body. The temporal variation of PEA primarily follows the diurnal cycles of solar radiation, while the spatial heterogeneity of PEA is jointly determined by solar radiation and vertical shear of horizontal velocity coupled with the topography of the lake. The maxima of PEA in the lake are not greater than 4 J/m3 in the summer and even smaller along shore regions and near the Pingtaishan station. This study is helpful to improve understanding of the effect of physical processes on the algae bloom in Lake Taihu.



Toxic effects of cyhalofop-butyl on embryos of the Yellow River carp ( Cyprinus carpio var.): alters embryos hatching, development failure, mortality of embryos, and apoptosis

Abstract

As a universal environmental contaminant, the herbicide cyhalofop-butyl is considered to have infested effects on the embryonic development of aquatic species. The present study focused on an assessment of the impacts of cyhalofop-butyl on Yellow River carp embryos. It was found that cyhalofop-butyl inhibited the hatching of the embryos, and the hatching rate decreased with higher concentrations of the herbicide. The mortality rate was increased on exposure to cyhalofop-butyl and was significantly higher in the 1.6 and 2 mg/L treatment groups over 48 h. All of the embryos of the 2 mg/L treatment group died within the 48 h post-hatching stage. And the transcription of several embryos related to apoptosis was also influenced by cyhalofop-butyl exposure. Further, cyhalofop-butyl exposure leads to a series of morphological changes (pericardial edema, tail deformation, and spine deformation) in embryos, which were consistent with significant modifications in the associated genes. These results provided a scientific basis for further studies into the effects of cyhalofop-butyl on aquatic organisms.



Mineralization and cementing properties of bio-carbonate cement, bio-phosphate cement, and bio-carbonate/phosphate cement: a review

Abstract

Due to high pollution associated with traditional Portland cement and bio-carbonate cement, a new generation of cementitious material needs to be developed. Bio-barium phosphate, magnesium phosphate, and ferric phosphate are synthesized by bio-mineralization. Firstly, the substrate is hydrolyzed by alkaline phosphatase secreted via phosphate-mineralization microbes, obtaining phosphate ions. Micro- and nano-scale phosphate minerals are prepared by phosphate ions reacting with different types of metal cation. The setting time of bio-BaHPO4 has a greater effect on the strength of sand columns when a mixing precipitation process is innovatively adopted. The strength of the sand columns increases as bio-BaHPO4 content (10~50%) increases. The optimum content of bio-BaHPO4 is 60%. Porosity and permeability of the sand columns decrease as bio-BaHPO4 content (10~60%) increases. Ammonium and ammonia can effectively be synthesized to magnesium ammonium phosphate by adding K2HPO4·3H2O to Sporosarcina pasteurii liquid. Permeability, porosity, and compressive strength of the sand columns are close to CJ1, CJ1.5, and CJ2 cementation. However, the fixation ammonia ratio of CJ2 is bigger than CJ1 and CJ1.5 (The mixture solutions of Sporosarcina pasteurii and K2HPO4·3H2O (1, 1.5, and 2 mol/L) are named as CJ1, CJ1.5, and CJ2) cementation. The results show that the Sporosarcina pasteurii liquid containing K2HPO4·3H2O (2 mol/L) and the mixture solution of MgCl2 and urea (3 mol/L) cemented loose sand particles best. Two types of bio-cement are environmentally friendly and can partially or completely replace bio-carbonate cement.



An oncolytic measles virus–sensitive Group 3 medulloblastoma model in immune-competent mice

Abstract
Background
Oncolytic measles virus (MV) is effective in xenograft models of many tumor types in immune-compromised mice. However, no murine cell line exists that is tumorigenic, grows in immune-competent mice, and is killed by MV. The lack of such a model prevents an examination of the effect of the immune system on MV oncotherapy.
Methods
Cerebellar stem cells from human CD46-transgenic immunocompetent mice were transduced to express Sendai virus C-protein, murine C-Myc, and Gfi1b proteins. The resultant cells were injected into the brain of NSG mice, and a cell line, called CSCG, was prepared from the resulting tumor.
Results
CSCG cells are highly proliferative, and express stem cell markers. These cells are permissive for replication of MV and are killed by the virus in a dose- and time-dependent manner. CSCG cells form aggressive tumors that morphologically resemble medulloblastoma when injected into the brains of immune-competent mice. On the molecular level, CSCG tumors overexpress natriuretic peptide receptor 3 and gamma-aminobutyric acid type A receptor alpha 5, markers of Group 3 medulloblastoma. A single intratumoral injection of MV‒green fluorescent protein resulted in complete tumor regression and prolonged survival of animals compared with treatments with phosphate buffered saline (P = 0.0018) or heat-inactivated MV (P = 0.0027).
Conclusions
This immune-competent model provides the first platform to test therapeutic regimens of oncolytic MV for Group 3 medulloblastoma in the presence of anti-measles immunity. The strategy presented here can be used to make MV-sensitive murine models of any human tumor for which the driving mutations are known.

Descriptive survival study of nail melanoma patients treated with functional surgery versus distal amputation

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Suelen Montagner, Francisco Aparecido Belfort, Walter Belda Junior, Nilton Di Chiacchio




Prognostic significance of tumor budding in cutaneous squamous cell carcinoma

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Jean Kanitakis, Georgia Karayannopoulou




Table of Contents

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1





Information for Readers

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1





Melanoma staging: Varying precision and terminal digit clustering in Breslow thickness data is evident in a population-based study

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Marit B. Veierød, Christian M. Page, Stein Aaserud, Assia Bassarova, Kari D. Jacobsen, Per Helsing, Trude E. Robsahm
BackgroundErrors in Breslow thickness reporting can give misclassification of T category, an important classifier in melanoma staging.ObjectiveWe sought to investigate precision (number of digits) and terminal digit clustering in Breslow thickness and potential consequences for T category.MethodsAll first primary and morphologically verified invasive melanomas in Norway between 2008 and 2015 were included. A smoothing model was fitted to estimate the underlying Breslow thickness distribution without digit clustering.ResultsThickness was reported for 13,057 (97.5%) patients; the median was 1.0 mm (range, 0.09-85). It was reported as whole numbers (15.6%), to 1 decimal (78.2%) and 2 decimal places (6.2%)—thin tumors with more precision than thick tumors. Terminal digit clustering was found with marked peaks in the observed frequency distribution for terminal digits 0 and 5, and with drops around these peaks. Terminal digit clustering increased proportions of patients classified with T1 and T4 tumors and decreased proportions classified with T2 and T3.LimitationsBreslow thickness was not reported in 2.5% of cases.ConclusionsThe Norwegian recommendation of measurement to the nearest 0.1 mm was not followed. Terminal digit clustering was marked, with consequences for T category. Pathologists, clinicians, and epidemiologists should know that clustering of thickness data around T category cut points can impact melanoma staging with consequent effect on patient management and prognosis.



JAAD Case Reports Article List

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1





Journal Based CME Instructions and Information

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1





Skin in the game: Existing and upcoming physician payment models in dermatology

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Oluwatobi A. Ogbechie-Godec, Arash Mostaghimi, Vinod E. Nambudiri




Dermatoses caused by cultural practices

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Neelam A. Vashi, Nicole Patzelt, Stephen Wirya, Mayra B.C. Maymone, Pedro Zancanaro, Roopal V. Kundu
With globalization and widespread immigration, physicians increasingly encounter patients from varying backgrounds and diverse customs. Although certain cultural practices are widely performed, there is limited medical literature describing their dermatologic and systemic effects and complications. Population diversity and sharing of traditions make it increasingly important for dermatologists to understand the role of cultural practices and recognize physiologic and pathologic sequelae. In addition, dermatologists are often adjured to assess skin findings that may be mistaken for abuse. Child abuse misdiagnosis can be traumatizing to all those involved, and immigrant families with limited English proficiency may have difficulty explaining their traditional practices. The first article of this 2-part continuing medical education series begins with a review of therapeutic cultural practices, including traditional Chinese medicine, Ayurveda, acupuncture, cupping, moxibustion, and coining, and the clinically relevant complications that may occur. Therapeutic practices can cause a range of complications, including contact dermatitis, heavy metal toxicity, and severe cutaneous adverse reactions.



Editorial Board

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1





CME examination

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1





Comparative effectiveness of targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Anne M. Loos, Shanshan Liu, Celia Segel, Daniel A. Ollendorf, Steven D. Pearson, Jeffrey A. Linder
BackgroundThe comparative effectiveness of available targeted immunomodulators for moderate-to-severe psoriasis has not been evaluated.ObjectiveTo evaluate the comparative effectiveness of targeted immunomodulators for adults with moderate-to-severe plaque psoriasis.MethodsSystematic literature review of placebo-controlled and head-to-head randomized trials of 8 targeted immunomodulators that evaluated clinical benefits or harm. The primary outcome was a 75% improvement on the Psoriasis Area and Severity Index. We also conducted a network meta-analysis adjusted for placebo response to perform indirect comparisons between agents.ResultsIn the network meta-analysis, the targeted immunomodulators ordered by increasing relative risk (demonstrating greater likelihood) of achieving a 75% improvement on the Psoriasis Area and Severity Index relative to placebo were as follows: apremilast (6.2), etanercept (9.6), adalimumab (13.0), ustekinumab (14.0), secukinumab (15.4), infliximab (16.2), brodalumab (17.3), and ixekizumab (17.9). Ixekizumab, brodalumab, and infliximab were all statistically superior to ustekinumab, adalimumab, etanercept, and apremilast; results were similar to those of head-to-head studies where data were available.LimitationsMuch of the evidence is short-term (covering 10-16 weeks); limited direct comparisons.ConclusionsThe interleukin 17A inhibitors are more effective in achieving clearance than ustekinumab, and they are generally more effective than etanercept, adalimumab, and apremilast.



Answers to CME examination

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1





Dermatoses caused by cultural practices

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Neelam A. Vashi, Nicole Patzelt, Stephen Wirya, Mayra B.C. Maymone, Roopal V. Kundu
The second article in this continuing medical education series discusses cosmetic practices associated with cultural dermatoses, including hair care, traditional clothing, and skin decorations. Often, the steps individuals take to enhance their physical appearance are determined by cultural perceptions of beauty. Without awareness of cultural practices, a multitude of cutaneous dermatoses may be missed by the dermatologist. Recognition and understanding of patients' cultural backgrounds and habits will allow the practicing dermatologist to offer better counseling and treatment options while providing a more meaningful and understanding physician–patient relationship.



Atopic dermatitis is not a risk factor for keratoconus: A population-based cohort study

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Hyun Sun Jeon, Mira Choi, Seong Jun Byun, Leejee H. Suh, Joon Young Hyon, Kyu Hyung Park, Sang Jun Park




CME examination

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1





Low conversion rate of QuantiFERON-TB Gold screening tests in patients treated with tumor necrosis factor inhibitors: A retrospective cohort study identifying an important practice gap

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Jina Chung, Adam B. Aronson, Rithu Srikantha, Scott A. Vogelgesang, Karolyn A. Wanat




Answers to CME examination

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1





Simple mixing technique of triamcinolone acetonide solution by air bubble movement

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Mohammed I. AlJasser




A new cover, a new editorial board

Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Dirk M. Elston




Ultraviolet radiation-mediated development of cutaneous melanoma: An update

Publication date: Available online 14 June 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Gabriella Emri, György Paragh, Ágnes Tósaki, Eszter Janka, Sándor Kollár, Csaba Hegedűs, Emese Gellén, Irén Horkay, Gábor Koncz, Éva Remenyik
Ultraviolet (UV) light is absorbed by nucleic acids, proteins or other endogenous chromophores, such as porphyrins, flavins and melanin, triggering biological processes in skin cells. Both UV-induced mutations in melanocytes and changes in the immune microenvironment are understood to play a role in the development of cutaneous melanoma. The degree of UV-induced stress and the protection against this stress are influenced by both intracellular and intercellular molecular interactions. The present review summarizes the known major molecular biological changes induced by UV light in the skin that play a role in melanoma initiation and promotion. Nevertheless, cutaneous melanoma is not a homogenous disease, and the interaction of variable environmental exposure and different genetic susceptibility and other host factors lead to the formation of melanomas with different biological behavior and clinical characteristics. This review highlights the challenges in the understanding of how UV radiation contributes to the formation of cutaneous melanoma, and reviews the new results of photobiology and their link to tumor genetics and tumor immunology with potential implications on melanoma prevention and therapeutic strategies. The information presented here is expected to add clarity to ongoing research efforts in this field to aid the development of novel strategies to prevent and treat melanoma.



Article 8 - how to successfully navigate the all-day interview



SecA inhibitors as potential antimicrobial agents: differential actions on SecA-only and SecA-SecYEG protein-conducting channels

Abstract
Sec-dependent protein translocation is an essential process in bacteria. SecA is a key component of the translocation machinery and has multiple domains that interact with various ligands. SecA acts as an ATPase motor to drive the precursor protein/peptide through the SecYEG protein translocation channels. As SecA is unique to bacteria and there is no mammalian counterpart, it is an ideal target for the development of new antimicrobials. Several reviews detail the assays for ATPase and protein translocation, as well as the search for SecA inhibitors. Recent studies have shown that, in addition to the SecA-SecYEG translocation channels, there are SecA-only channels in the lipid bilayers, which function independently from the SecYEG machinery. This mini-review focuses on recent advances on the newly developed SecA inhibitors that allow the evaluation of their potential as antimicrobial agents, as well as a fundamental understanding of mechanisms of SecA function(s). These SecA inhibitors abrogate the effects of efflux pumps in both Gram-positive and Gram-negative bacteria. We also discuss recent findings that SecA binds to ribosomes and nascent peptides, which suggest other roles of SecA. A model for the multiple roles of SecA is presented.

Bioplastic reservoir of diverse bacterial communities revealed along altitude gradient of Pangi-Chamba trans-Himalayan region

Abstract
Himalaya hosts a unique environment for microbial ecology. The present study aimed to explore the bioplastic producing bacterial communities along altitude gradient of Pangi-Chamba trans-Himalayan (PCH) region. A total of four hundred eleven bacteria were isolated and seventy characterized at the molecular level for potential polyhydroxyalkanoates (PHA) producers. The most abundant phylum for PHA synthesis was Proteobacteria (73%), followed by Actinobacteria (11%), Firmicutes (10%), and Bacteroidetes (6%). However, at the genus level, Pseudomonas and Janthinobacterium were dominantly reported. Also, the ability to synthesize PHA was reported for the first time for few genera such as Collimonas, Pseudarthrobacter, and Paenarthrobacter. Phylogenetic analysis of partial 16S rDNA and phaC genes revealed conservation in phaC and possibility of horizontal gene transfer among distant taxa. Furthermore, GCMS also confirmed the ability of potential bacterial isolates to synthesize PHA. In fact, we found that PHA positive bacteria are dominant in the high altitude of Himalaya, suggesting the vital role of PHA in bacterial adaptation and survival. Together, these findings had revealed the rich bacterial diversity and genetic machinery for PHA synthesis which does have potential for further utilization in the commercial applications.

Distribution of Staphylococcus species in dairy cows, workers, and shared farm environments

Abstract
Dairy farming involves frequent contact among animals, workers and farm environments. To explore the Staphylococcus spp. diversity that occurs on dairy farms, a pilot study sampled dairy workers, cows, and the farm environments from five farms, two organic and three conventional farms, in Washington State. Samples were taken from the nares and hands of consenting workers (n = 24), udders and nares of selected cows (n = 25) and representative environmental surfaces (n = 96) from each farm. To increase diversity of the Staphylococcus spp. characterized, five distinct colonies were selected from each sample for identification with 16S analysis. A total of 198 staphylococci were characterized representing 19 different Staphylococcus spp. The diversity of species ranged from 9–15 Staphylococcus spp./farm with no difference between conventional and organic farms. S. haemolyticus [n = 60 isolates] was the most common species and was isolated from all farms and from cows, humans, and environmental samples. Whole genome sequencing of selected S. haemolyticus found no genetically related isolates among human, animal, and environmental samples within the same farm. S. epidermidis, S. saprophyticus, S. sciuri and S. xylosus were also found in ≥ 1 farms from human, animal, and environmental samples.

Autotransporter MisL of Salmonella enterica serotype Typhimurium facilitates bacterial aggregation and biofilm formation

Abstract
Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important food-borne zoonotic pathogen that causes increased morbidity and mortality worldwide. The autotransporter (AT) proteins are a large and diverse family of extracellular proteins, many of which contribute to the pathogenicity of Gram-negative bacteria. The S. Typhimurium AT protein MisL mediates intestinal colonization in mice. Bioinformatics analyses indicated that MisL clusters with ATs involved in bacterial biofilm formation, aggregation and adherence. In this study, we found that the misL overexpression increased S. Typhimurium biofilm formation. In addition, the misL deletion reduced bacterial adherence and invasion abilities on HeLa cells, but did not affect the bacterial virulence. Similarly, MisL expression in Escherichia coli strain promoted bacterial biofilm formation as well as adhesion and invasion capacities. However, the misL overexpression had no influence on the bacterial aggregation excepting for AAEC189Δflu, a strain lacking type I fimbriae. Moreover, we demonstrated that immunization with recombinant MisL protein stimulated the production of high IgG antibody titers, which conferred modest protection against S. Typhimurium infection. This study illustrates the novel biological functions and immunoprotective effects of MisL in S. Typhimurium.

YebC controls virulence by activating T3SS gene expression in the pathogen Edwardsiella piscicida

Abstract
Edwardsiella piscicida is an infectious Gram-negative bacterium that causes great losses to the aquaculture industry worldwide. Based on pattern analysis of conditional essentiality (PACE), a new method for transposon insertion sequencing (Tn-seq) data analysis, we investigated the genome-wide genetic requirements during the dynamic process of infection and colonization in turbot in this study. As a result, disruption of ETAE_1437 was discovered to lead to substantially reduced colonization, which was similar to the in vivo dynamic patterns of the mutants of T3SS or T6SS. Bioinformatics analysis indicated that ETAE_1437 is a YebC/PmpR family regulator. Moreover, we found that ETAE_1437 not only regulated quorum sensing by directly binding to the edwR promoter region but also activated T3SS expression by directly binding to the promoter region of the T3SS gene ETAE_0873. In addition, ETAE_1437 mutants exhibited substantial colonization defects and significantly decreased virulence in turbot. Overall, this study identified ETAE_1437 as a novel virulence regulator in E. piscicida and enriched our understanding of the pathogenesis of E. piscicida in fish. We thus reannotated ETAE_1437 as YebC.

Pleural mesothelioma: is the surgeon still there?

Abstract
MPM is a rare malignancy with some unique characteristics. Tumor biology is aggressive and prognosis is poor. Despite more knowledge on histology, tumor biology and staging, there is still a relevant discrepancy between clinical and pathologic staging resulting in difficult prediction of prognosis and treatment outcome, making treatment allocation more challenging than in most other malignancies.After years of nihilism in the late eighties, a period of activism started evaluating different treatment protocols combined with research driven mainly by academic centers; at the time, selection was based on histology and stage only. This period was important to gain knowledge about the disease. However, the interpretation of data was difficult since selection criteria and definitions varied substantially. Not surprisingly, until now there is no common agreement on best treatment even among specialists. Hence, a review of our current concepts is indicated and personalized treatment should become applicable in the future.Surgery was and still is an issue of debate. In principle, surgery is an effective approach as it allows macroscopic complete elimination of a tumor, which is relatively resistant to medical treatment. It helps to set the clock back and other therapies that have also just a limited effect can be applied sequentially before or after surgery. Furthermore, to date best long-term outcome is reported from surgical series in combination with other modalities.However, part of the community consider surgery associated with too high morbidity and mortality when balanced to the limited life expectancy. This criticism is understandable, since poor results after surgery are reported. The present article will review the indication for surgery and discuss the different procedures available for macroscopic complete resection– such as lung-preserving (extended) pleurectomy/decortication as well as extrapleural pneumonectomy to illustrate that "The surgeon is still there!".

Adherence to geriatric assessment-based recommendations in older patients with cancer: a multicenter prospective cohort study in Belgium

Abstract
Background
In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this study was to investigate the adherence to geriatric recommendations and subsequent actions undertaken in older patients with cancer.
Patient and methods
A prospective Belgian multicenter (N=22) cohort study included patients ≥70 years with a malignant tumor upon oncologic treatment decision. Patients with an abnormal result on the geriatric screening (G8 ≤14/17) underwent GA. Geriatric recommendations were formulated based on GA results. At follow-up the adherence to geriatric recommendations was documented including a description of actions undertaken.
Results
From 11-2012 till 2-2015, G8 screening was performed in 8451 patients, of which 5838 patients had an abnormal result. Geriatric recommendations data were available for 5631 patients. Geriatric recommendations were made for 4459 patients. Geriatric interventions data were available for 4167 patients. A total of 12384 geriatric recommendations were made. At least one different geriatric recommendation was implemented in 2874 patients. A dietician, social worker and geriatrician intervened most frequently for problems detected on the nutritional, social and functional domain. A total of 7569 actions were undertaken for a total of 5725 geriatric interventions, most frequently nutritional support and supplements, extended home care and psychological support.
Conclusions
This large scale Belgian study focuses on the adherence to geriatric recommendations and subsequent actions undertaken and contributes to the optimal management of older patients with cancer. We identified the domains for which geriatric recommendations are most frequently made and adhered to, and which referrals to other health care workers and facilities are frequently applied in the multidisciplinary approach of older patients with cancer.

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer

Abstract
Background
Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non–small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs.
Design
Randomized trials of EGFR-directed mAbs cetuximab and necitumumab in combination with chemotherapy, immunotherapy, or anti-angiogenic therapy in patients with advanced NSCLC, including SqCLC, were searched in the literature. Results of associations of potential biomarkers and outcomes were summarized.ResultsData from phase III clinical trials indicate that patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein (H-score of ≥ 200) and/or gene copy numbers of EGFR (e.g., ≥40% cells with ≥4 EGFR copies as detected by fluorescence in situ hybridization; gene amplification in ≥ 10% of analyzed cells) derive greater therapeutic benefits from EGFR-directed mAbs. Biomarker data are limited for EGFR mAbs used in combination with immunotherapy and are absent when used in combination with anti-angiogenic agents.
Conclusions
Therapy with EGFR-directed mAbs in combination with chemotherapy is associated with greater clinical benefits in patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein and/or have increased EGFR gene copy number. These data support validating the role of these as biomarkers to identify those patients who derive the greatest clinical benefit from EGFR mAb therapy. However, data on biomarkers for EGFR-directed mAbs combined with immunotherapy or anti-angiogenic agents remain limited.

Surrogate Endpoints in Lymphoma



Tumor-treating fields: time for demystification



Biomarker assessment of the CBCSG006 trial: A randomized phase III trial of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer

Abstract
Background
CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy.
Patients and methods
Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect patter plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided.
Results
Median progression-free survival was 7.73 (95% CI 6.46-9.00) months for GP arm and 6.07 (95% CI 5.32-6.83) months for GT arm (P = 0.005). No significant difference in overall survival was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher ORR and longer PFS in GP than GT arm (71.9% vs. 38.7%, P = 0.008; 10.37 vs. 4.30 months, P = 0.011). There was no significant interaction between gBRCA1/2 status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP than GT arm (83.3% vs. 37.5%, p = 0.086; 8.90 vs. 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks.
Conclusions
GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients.
Trial registration
ClinicalTrials.gov, NCT01287624

Where are virtues?

Abstract

This paper argues that the question, 'where are virtues?' demands a response from virtue theorists. Despite the polarizing nature of debates about the relevance of empirical work in psychology for virtue theory, I first show that there is widespread agreement about the underlying structure of virtue. Namely, that virtues are comprised of cognitive and affective processes. Next, I show that there are well-developed arguments that cognitive processes can extend beyond the agent. Then, I show that there are similarly well-developed arguments that affective processes can extend beyond the agent. I then introduce three cases to establish that these cognitive and affective processes are relevantly similar to the cognitive and affective processes countenanced by plausible theories of virtue. Finally, I conclude that virtue theorists must abandon default internalism, the (often implicit) view that the cognitive and affective processes comprising virtues are internal to the agent.



Phenotypes of Thyroid Eye Disease

Purpose: To describe a new classification system of thyroid eye disease (TED) based on the phenotypic features (clinical and radiologic) of the disease. Methods: Clinical features, photographic, and orbital imaging of TED patients were considered in relation to their natural history and treatment response in the experience of the author. Phenotypically distinct categories of patients were identified and described. Results: Six phenotypes of TED are observed: 1) congestive (active inflammatory), 2) "white eye" expansion, 3) "hydraulic" apex, 4) "white eye" apex, 5) cicatricial active, and 6) cicatricial passive. Conclusions: The observable characteristics of TED are determined by the underlying pathophysiology of the disease. TED is heterogeneous in its underlying pathogenesis, clinical manifestations, and response to medical and surgical treatment modalities. Several previous categorizations of the clinical appearance of TED exist, but they are dichotomous and underrepresent the heterogeneity of the disease. The authors present clinical and radiologic features of 6 different classes or phenotypes of TED and their response to different treatments. Accepted for publication April 11, 2018. Patient consents were obtained and are on file with the authors. Presented at the 4th International Thyroid Eye Disease Society Symposium on June 24, 2016 in London, United Kingdom. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Jimmy M. Uddin, M.D., F.R.C. Ophth., Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, United Kingdom. E-mail: infouddin@me.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Primary Extracranial Meningioma of the Lacrimal Sac Fossa

Primary extracranial meningioma is a rare tumor, unlike its common intracranial counterpart. Infrequently found in the head and neck region, it can cause local or neurologic symptoms depending on its location and interaction with cranial nerves. While uncommon, it is an important diagnosis to have on the differential of periorbital lesions as surgical removal and prognosis are generally good. The authors present the first report of a patient with primary extracranial meningioma originating in the lacrimal sac fossa. Accepted for publication April 20, 2018. The authors do not have any proprietary interests in the materials described in the article. The manuscript has not, and will not be, submitted in a different publication. All coauthors have read, participated, and approved the final constructed manuscript. Address correspondence and reprint requests to Bryan Sires, M.D., Ph.D., 625 4th Avenue, Suite 301, Kirkland, WA 98033. E-mail: bssires@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

The Columbia Thyroid Eye Disease-Compressive Optic Neuropathy Formula

Purpose: Diagnosing thyroid eye disease–compressive optic neuropathy (TED–CON) is challenging, particularly in cases lacking a relative afferent pupillary defect. Large case series of TED–CON patients and accessible diagnostic tools are lacking in the current literature. This study aims to create a mathematical formula that accurately predicts the presence or absence of CON based on the most salient clinical measures of optic neuropathy. Methods: A retrospective case series compares 108 patients (216 orbits) with either unilateral or bilateral TED–CON and 41 age-matched patients (82 orbits) with noncompressive TED. Utilizing clinical variables assessing optic nerve function and/or risk of compressive disease, and with the aid of generalized linear regression modeling, the authors create a mathematical formula that weighs the relative contribution of each clinical variable in the overall prediction of CON. Results: Data from 213 orbits in 110 patients derived the formula: y = −0.69 + 2.58 × (afferent pupillary defect) − 0.31 × (summed limitation of ductions) − 0.2 × (mean deviation on Humphrey visual field testing) − 0.02 × (% color plates). This accurately predicted the presence of CON (y > 0) versus non-CON (y

Dacryoendoscopy in a Case of Unexplained Hemolacria

No abstract available

Imaging Investigation of Thyroid Eye Disease

Introduction: Thyroid eye disease (TED), is a term referring to the extrathyroidal manifestation of Grave's disease, a disorder which is currently the most common cause of hyperthyroidism and is characterised by underlying autoimmunity. The pathogenic course of the disease can be broadly classified into two stages, an early inflammatory and a late fibrotic stage. These stages are reflected in clinical severity and activity classifications, such as Clinical Activity Score and Class 0: No signs or symptoms, 1: Only signs, no symptoms (e. g. lid retraction), 2: Soft tissue involvement, 3: Proptosis, 4: Extraocular muscle involvement, 5: Corneal involvement, 6: Sight loss (NOSPECS). Classifications based on the latter, have important implications in treatment decisions since patients in the early active stage of the disease are more likely to respond to anti-inflammatory and immunosuppressive therapies, whereas patients in the late fibrotic stage require different therapeutic approaches, including rehabilitative surgery. Methods: We reviewed cases of TED investigated with CT and Magnetic Resonance Imaging (MRI) in our department. We assessed the findings of imaging studies and their role in the clinical investigation of patients with TED as well as in the differential diagnosis from other disorders. Results: Imaging has a significant role in the investigation of TED, however a consensus on the use of different imaging modalities in the course of disease has yet to be reached. Nevertheless, imaging and specifically CT and MRI can have a vital role in the initial diagnosis of clinically atypical presentation of TED, in surgical planning, as well as in the differential diagnosis from other orbital disorders. Conclusion: In this review, we attempt to present current trends in imaging investigation of TED. Rather than focusing on the findings of each imaging modality separately, we present the two main imaging modalities focusing on CT and MRI, in the context of pathogenic stages of the disease. Accepted for publication April 4, 2018. The authors have no financial or conflict of interest to disclose. Address correspondence and reprint requests to Loizos C. Siakallis, M.D., M.Res, M.sc, Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom. E-mail: loizos.siakallis@nhs.net © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Surgical Treatment of Diplopia in Graves Orbitopathy Patients

Purpose: To review the authors' current understanding of motility dysfunction in patients with thyroid eye disease and to summarize appropriate evaluation and available management options. Methods: Data were retrieved from a systematic search of the literature. Results: Diplopia is one of the most disabling symptoms for Graves orbitopathy patients. It occurs in moderate-to-severe Graves orbitopathy stages and does not respond well to available anti-inflammatory treatment. Inflammation of extraocular muscles induces relatively rapid fibrotic and degenerative changes, which lead to scarring and loss of elasticity with preserved contractility. Inferior and medial rectus muscles are most often involved, which results in horizontal or vertical misalignment or both, and sometimes cyclotorsion. Impaired motility can also be caused by entrapment after orbital decompression. The aim of surgical correction is to restore/enlarge the field of binocular single vision and alleviate abnormal head posture. The basis for successful treatment is dependent on the identification of the involved muscles combined with the correct assessment of motility, misalignment, and binocular single vision. Conclusions: Due to increased muscle tightness, recessions are the first choice of surgical procedures. Dosing is the most difficult part of the surgery. Several techniques are described: deviation-correction with preoperative determination of the dose, duction-correction either by active or passive intraoperative evaluation of ductions, and the application of adjustable sutures. Achievable success rates are comparable among these techniques but are dependent on the surgeon's experience. Cyclotorsion and misalignment after decompression and combined horizontal and vertical misalignments are more challenging to correct. Those types of deviations need special solutions like surgery on the oblique muscles and the usage of implants. The field of binocular single vision is the main outcome criteria for success, and the quantification may differ for research questions, study designs, and clinical purposes. Accepted for publication April 11, 2018. All authors report that there are no financial disclosures. Address correspondence and reprint requests to Anja K. Eckstein, M.D., EUGOGO Center Essen, Clinic for Ophthalmology, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany. E-mail anja.eckstein@uk-essen.de © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

String Technique for Anterior Orbital Fish Hook Removal

Removing fish hooks is a common procedure performed by many emergency department providers. There are several techniques that are commonly employed to aid in successful removal. However, when a fish hook becomes embedded within the orbit, there are limited options as to avoid damaging vital surrounding structures. The authors report the removal of a fish hook within the anterior orbit using the string technique in a 25-year-old patient. The procedure was performed under general anesthesia with the aid of size 5 polyglactin suture wrapped around the hook. The procedure itself took less than 10 seconds and was successful in swiftly and safely removing the hook without damaging surrounding orbital structures. The patient recovered well without any permanent sequelae. Accepted for publication April 24, 2018. Supported by the Research to Prevent Blindness, New York, NY. The authors have no financial or conflicts of interest to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.op-rs.com.). Address correspondence and reprint requests to David F. Patterson, M.D., Department of Ophthalmology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, U.S.A. E-mail: david.f.patterson@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

The Multisystem Effects of Simulated Agricultural Whole Body Vibration on Acute Sensorimotor, Physical, and Cognitive Performance

Abstract
Background
Exposure to whole body vibration (WBV) is common in construction, agriculture, mining, and transportation. There is strong epidemiological evidence linking WBV with adverse health outcomes in the long-term, including low back pain. Fortunately, WBV exposure guidelines to prevent long-term musculoskeletal disorders and discomfort exist. In the shorter-term, it has been speculated that occupational levels of WBV may lead to increased risk of vehicle accidents and falls during egress; however, the acute effects of different vibration intensities remain poorly understood and it is uncertain whether established standards protect the worker from injurious short-term effects.
Objective
The aim of this study was to investigate the acute sensorimotor, physical, and cognitive effects of occupationally-relevant, simulated whole body vibration (WBV) at levels equivalent to international standard guideline thresholds for long-term discomfort and musculoskeletal disorder risk.
Method
Eighteen participants were recruited to perform four, 60-min conditions: (i) Control—no vibration, (ii) Low vibration—equivalent to the exposure action value, (iii) Shock—transient impacts at 1-min intervals superimposed on the Low condition, and (iv) High vibration—equivalent to the exposure limit value. Whole body vibration was simulated using data based on field-collected accelerations experienced by rural workers while operating an all-terrain vehicle. This vibration signal was manipulated to achieve required intensities for each condition and simulated with a 6 degree-of-freedom hexapod platform. Before and after each condition, we collected: rating of perceived body discomfort, rating of perceived headache, postural sway, blink frequency, King-Devick test, and psychomotor vigilance task. Pre- and post-condition data in each condition were submitted to either a paired t-test (parametric) or Wilcoxon signed-rank test (non-parametric). To determine differences between conditions, each condition's post-condition data was normalized to its pre-condition value and entered as the dependent variable in a repeated measures analysis of variance.
Results
All conditions, including Control, led to increased upper body discomfort when compared to pre-exposure baseline. The Low condition led to increased discomfort in seven body locations, headache (91% increase from baseline; t = −2.44, P = 0.03), and postural imbalance (53% increase from baseline; t = −2.88, P = 0.01), but the effect on cognitive functioning was less clear. Shock condition led to whole body discomfort, specifically at nine upper body and lower body locations. The High condition led to increased whole body discomfort at all 10 body locations, headache (154% increase from baseline; t = −2.91, P = 0.01), postural imbalance (61% increase from baseline; t = −2.57, P = 0.02), and decrements in vigilance (mean reaction time: 6% increase from baseline, t = −3.27, P = 0.005; Number of lapses: 100% increase from baseline, S = −42.5, P = 0.002).
Conclusion
Although the number of pre-post condition effects increased with higher vibration intensity, these effects were not significantly different from sitting without vibration. Therefore, current guideline thresholds might not protect the worker from acute WBV effects. However, further research is needed to discern these effects from other sources of WBV. Based on this study, future WBV interventions and action controls should not only address vibration reduction, but also consider potential effects from prolonged sitting.

Anti‐nuclear antibodies in patients with breast cancer

Clinical &Experimental Immunology, EarlyView.


Pemphigus et herpès : enquête multicentrique et revue de la littérature

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Publication date: Available online 14 June 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): M. Merlant, V. Seta, P. Bernard, S. Fourati, J.-F. Meritet, P. Wolkenstein, N. Dupin, P. Joly, O. Chosidow, S. Ingen-Housz-Oro
IntroductionLa surinfection herpétique (SH) est une complication connue mais peu étudiée du pemphigus.ObjectifÉvaluer la fréquence et les circonstances de survenue des SH au cours du pemphigus.MéthodesÉtude rétrospective multicentrique incluant les cas de SH parmi les pemphigus nouvellement diagnostiqués entre 2008 et 2016. Les données cliniques, virologiques, immunologiques et thérapeutiques ont été colligées. Une revue de la littérature sur pemphigus et herpès a été effectuée.RésultatsParmi les 191 pemphigus, un prélèvement herpétique a été pratiqué chez 11 à 71 % des malades selon les centres. Ainsi, une SH a été démontrée chez 24 (12 femmes, âge médian 58 ans), soit une fréquence de SH de 0 à 42 % des patients prélevés selon les centres. Le pemphigus était un pemphigus vulgaire dans 21 cas et le site atteint était muqueux chez 19 malades. La SH était trouvée au moment du diagnostic de pemphigus dans 15 cas. La technique identifiant le virus était une PCR dans 23 des 24 cas (HSV1 dans 22 cas). Dix malades ont reçu par la suite un traitement antiviral préventif. Le suivi médian était de 36 mois (0–89 mois). Treize des 24 malades ont totalisé 23 rechutes de pemphigus. Un prélèvement herpétique a été réalisé lors de 19 rechutes, positif dans 6 cas (31,5 %).ConclusionNotre étude montre une variabilité de fréquence de la SH au cours du pemphigus, reflétant des pratiques de prélèvements différant selon les centres (systématique ou seulement si forte suspicion clinique). L'intérêt pronostique d'un dépistage systématique sur l'évolution du pemphigus reste à démontrer par une étude prospective.BackgroundAlthough herpes superinfection is a well-known complication of pemphigus, it has not been widely investigated.AimTo investigate the frequency and features of herpes infection in patients with ongoing pemphigus.Patients and methodsWe carried out a multicenter retrospective study between 2008 and 2016 in patients with newly diagnosed pemphigus presenting active herpes infection. Clinical, virological, immunological and therapeutic data were collated. We performed a literature review for pemphigus and herpes.ResultsAmong the 191 pemphigus patients, screening for herpes (PCR or culture) was carried out in 11 to 71 % of subjects, depending on the center in question. Twenty-four patients (12 women, mean age 58 years) presented at least one episode of herpes infection. The frequency of positivity ranged from 0 to 42 % by center. Twenty-one cases consisted of pemphigus vulgaris and infection occurred at a mucosal site in 19 patients. Herpes infection was identified at the time of diagnosis in 15 patients and 17 patients received no specific treatment for their pemphigus. The virus was identified using PCR in 23 cases. Ten patients subsequently received prophylactic treatment for herpes. The mean duration of follow-up was 36 months (0–89 months). Thirteen of the 24 patients had 23 relapses of pemphigus; PCR testing for herpes was performed 19 times and was positive in 6 cases (31.5 %).ConclusionOur study showed wide variation in the incidence of herpes superinfection in patients with pemphigus, reflecting the different screening approach at each center (being performed either routinely or only in the event of strong suspicion). The prognostic value of routine screening for herpes in patients with active pemphigus lesions remains to be demonstrated by further prospective investigations.



Vitiligo sous inhibiteur de checkpoint

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Publication date: Available online 14 June 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): M. Amini-Adle, S. Dalle