Solvent-promoted Catalyst-free N-Formylation of Amines Using Carbon Dioxide under Ambient Conditions

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC01234E, Communication

Hui Lv, Qi Xing, Chengtao yue, Zi Qiang Lei, fuwei li
An unprecedented catalyst-free formylation of amines with CO2 and hydrosilanes was developed. Solvent plays a vital role in promoting the interaction of amines with hydrosilanes and subsequent CO2 insertion, thus...
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Onwettig advies van de HRHB belet herstelvordering niet

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The Panama Papers and the International Battle Against Tax Havens: Lessons for the EU

The collaborative publication of the Panama Papers in the first week of April revealed in an unprecdented level tax evasion via the Panamanian lawyer's office Mossack Fonseca - this article examines lessons for the EU.

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Wie niet weg is, is gezien: ondersteuningsstrategieën van praktijkwerkers

Deze bijdrage rapporteert over een recente studie die kadert binnen het Vlaams Armoedesteunpunt (VLAS) en ontwikkeld werd vanuit de Vakgroep Sociaal Werk en Sociale Pedagogiek (UGent). We bevroegen praktijkwerkers die als ondersteunend werden aangeduid door ouders met jonge kinderen in armoede. Via open diepte-interviews gingen we daarbij na hoe deze ondersteuningspraktijken ontwikkeld worden in het samenspel tussen strategieën van frontliniewerkers en condities op organisatorisch, inter-organisatorisch en overheidsniveau.

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What families in poverty consider supportive: welfare strategies of parents with young children in relation to (child and family) social work

In current European Welfare states, Child and Family Social Work has been assigned a pivotal role in constructing a route out of (child) poverty. The direction, processes and outcomes of these interventions are, however, rarely negotiated with the families involved. Based on a retrospective biographical research with parents of young children who experienced financial difficulties over time, this paper therefore seeks to uncover and understand how parents give meaning to welfare which strategies they accordingly develop and how these perspectives and welfare strategies interact with Child and Family Social Work interventions. We aim to acquire knowledge about how interventions are constructed, interpreted and being used as potentially supportive levers in realizing the well-being of parents and children in poverty situations and explore how they may influence families' routes out of poverty. Drawing on Lister's analytical framework of agency within the bounds of structural constraints, our research provides insights in the essentially complex, multi-layered and paradoxical nature of support and suggests that support cannot simply be perceived as synonymous to mobility out of poverty.

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Film & NotFilm: Becketts bijdrage aan de filmgeschiedenis

Het 22 minuten durende Film (1965) was Samuel Becketts (1906-1989) enige filmavontuur. De Ierse auteur en Nobelprijswinnaar bedacht de film, schreef het scenario en hield nauw toezicht over de productie én over regisseur Alan Schneider. In overeenstemming met de expliciet zelfreflexieve titel, opent Film met een extreme close-up van een menselijk oog. Het thema van de film is onmiddellijk geïntroduceerd: het zal gaan over kijken en bekeken worden, kortom, over cinema. Tegelijk introduceert het openingsbeeld een van de twee hoofdpersonages in de film, E of het oog, meestal verpersoonlijkt door de camera. De andere hoofdpersoon is O, het object waarnaar E op zoek is. O tracht voortdurend aan de blik van E, en dus van de camera, te ontsnappen, waardoor we O enkel vanop de rug zien. Het is opmerkelijk dat de toen 68-jarige grootmeester van de stille slapstickfilm Buster Keaton de rol van O speelt. De belangrijkste eigenschap van the great stone face, Keatons stoïcijnse gezichtsuitdrukking, is immers niet zichtbaar tot het einde van de film. Deze stilistische keuze onderstreept het centrale belang van de blik, en de poging om hieraan te ontsnappen. Beckett kiest er ook bewust voor om zich louter te richten op de visuele dimensie. Een soundtrack is volledig afwezig, met één uitzondering aan het begin van de film, waarbij een vrouw een vinger voor haar lippen houdt en 'Sst!' zegt. De Latijnse uitdrukking esse est percipi (zijn is waargenomen worden), waarover de 18de-eeuwse Ierse filosoof George Berkeley contempleerde, vormde dan ook een belangrijke leidraad voor Beckett. In een interview met filmhistoricus Kevin Brownlow verklaarde Beckett dat 'Iemand die wil ophouden te bestaan, moet ophouden te worden waargenomen.' De hele film vormt een reflectie over dit idee. Hoewel Beckett zelf zijn film grotendeels als een mislukking beschouwde, tracht het UCLA Film and Television Archive via een voortreffelijke 4K restauratie de opmerkelijke kwaliteiten van Film opnieuw onder de aandacht te brengen. Tegelijk realiseerde restaurateur Ross Lipman NotFilm. Deze documentaire biedt een grondige en bijzonder boeiende reconstructie van de totstandkoming van Film. Erg opzienbarend is de herontdekking van de verloren gewaande beelden van de eerste scène van de film zoals Beckett die oorspronkelijk geconcipieerd had. Ook de teruggevonden audio-opnames van de productievergaderingen zijn van groot historisch belang. Aangezien er slechts een paar minuten audio- en video-opnames van Beckett bestaan, bieden deze opnames een uniek inzicht in Becketts creatieve proces. Behalve een uitmuntende filmhistorische documentaire is NotFilm echter ook een audiovisueel essay over Film en diens filosofische implicaties. Lipman neemt hierbij regelmatig interessante stellingen in, bijvoorbeeld wanneer hij erop wijst dat Film in wezen een achtervolgingsfilm is. Op andere momenten lijkt Lipman in zijn zoektocht naar sterke stellingen iets te veel nuance te verliezen, zoals wanneer hij stelt dat Beckett zijn 'dubbelganger' vond in Keaton. Lipmans argumenten zijn echter steeds intrigerend en nodigen uit tot een diepere reflectie over Film, precies zoals het een essay betaamt.

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Reliability of the quantitative assessment of peripheral blood perfusion by laser speckle contrast analysis in a systemic sclerosis cohort

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An EULAR Study Group pilot study on reliability of simple capillaroscopic definitions to describe capillary morphology in rheumatic diseases

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Structure and expression of nuclear genes encoding polypeptides of the photosynthetic apparatus

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Use of chimeric genes to study light-inducible gene expression and chloroplast import of the small subunit of ribulose-1,5-bisphosphate carboxylase

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Transfer and regulation of expression of chimeric genes in plants

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Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation

2016-04-15T01-37-38Z
Source: Journal of Intercultural Ethnopharmacology
Sadia Saleem Rao, Rahila Najam.
Aim Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw-edema model of inflammation using plethysmometer. Methodology For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally, group 2 and 3 were treated with young and mature coconut water respectively at 4ml/100g dose orally. Group 4 was treated with standard drug (ibuprofen) at 400mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. Results Results revealed that both coconut waters possess significant anti-inflammatory activity (p


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In vitro antimicrobial activity of five essential oils on multi-drug resistant Gram-negative clinical isolates

2016-04-15T01-37-38Z
Source: Journal of Intercultural Ethnopharmacology
Hercules Sakkas, Panagiota Gousia, Vangelis Economou, Vassilios Sakkas, Stefanos Petsios, Chrissanthy Papadopoulou.
Aim/background: The emergence of drug-resistant pathogens has drawn attention on medicinal plants for potential antimicrobial properties. The objective of the present study was the investigation of the antimicrobial activity of five plant essential oils on multi-drug resistant Gram-negative bacteria. Material and Methods: Basil, Chamomile Blue, Origanum, Thyme and Tea Tree oil were tested against clinical isolates of Acinetobacter baumannii (n=6), Escherichia coli (n=4), Klebsiella pneumoniae (n=7) and Pseudomonas aeruginosa (n=5) using the broth macrodilution method. Results: The tested essential oils produced variable antibacterial effect, while Chamomile blue oil demonstrated no antibacterial activity. Origanum, Thyme and Basil oils were ineffective on P. aeruginosa isolates. The MIC and MBC values ranged from 0.12 -1.50% (v/v) for Tea Tree oil, 0.25-4% (v/v) for Origanum and Thyme oil, 0.50->4% for Basil oil and >4% for Chamomile Blue oil. Compared to literature data on reference strains the reported MIC values were different by 2SD, denoting less successful antimicrobial activity against multi-drug resistant isolates. Conclusions: The antimicrobial activities of the essential oils are influenced by the strain origin (wild, reference, drug sensitive or resistant) and it should be taken into consideration whenever investigating the plants potential for developing new antimicrobials.


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The scaling of postcranial muscles in cats (Felidae) II: hindlimb and lumbosacral muscles

Abstract

In quadrupeds the musculature of the hindlimbs is expected to be responsible for generating most of the propulsive locomotory forces, as well as contributing to body support by generating vertical forces. In supporting the body, postural changes from crouched to upright limbs are often associated with an increase of body mass in terrestrial tetrapods. However, felids do not change their crouched limb posture despite undergoing a 300-fold size increase between the smallest and largest extant species. Here, we test how changes in the muscle architecture (masses and lengths of components of the muscle-tendon units) of the hindlimbs and lumbosacral region are related to body mass, to assess whether there are muscular compensations for the maintenance of a crouched limb posture at larger body sizes. We use regression and principal component analyses to detect allometries in muscle architecture, with and without phylogenetic correction. Of the muscle lengths that scale allometrically, all scale with negative allometry (i.e. relative shortening with increasing body mass), whereas all tendon lengths scale isometrically. Only two muscles' belly masses and two tendons' masses scale with positive allometry (i.e. relatively more massive with increasing body mass). Of the muscles that scale allometrically for physiological cross-sectional area, all scale positively (i.e. relatively greater area with increasing body mass). These muscles are mostly linked to control of hip and thigh movements. When the architecture data are phylogenetically corrected, there are few significant results, and only the strongest signals remain. None of the vertebral muscles scaled significantly differently from isometry. Principal component analysis and manovas showed that neither body size nor locomotor mode separate the felid species in morphospace. Our results support the inference that, despite some positively allometric trends in muscle areas related to thigh movement, larger cats have relatively weaker hindlimb and lumbosacral muscles in general. This decrease in power may be reflected in relative decreases in running speeds and is consistent with prevailing evidence that behavioural changes may be the primary mode of compensation for a consistently crouched limb posture in larger cats.

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MoV Reagents in Organic Synthesis (Eur. J. Org. Chem. 11/2016)

The cover picture shows three racing cars representing Mo^V, ^IIII and Fe^III reagents in the oxidative aryl–aryl coupling reaction with the molybdenum(V) car up in front as the most versatile and powerful reagent. A variety of products that can easily be synthesized by molybdenum(V)-mediated coupling reactions are arranged along the race circuit to underline the impressive possibilities of molybdenum(V) reagents in those reactions. In addition to five- to eight-membered ring systems and their heterocyclic analogues like carbazoles, intermolecular reactions leading to very valuable iodinated biarlys can also be carried out by Mo^V reagents. Details are presented in the Microreview by M. Schubert and S. R. Waldvogel on p. 1921 ff.

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Spotlights on our sister journals: Eur. J. Org. Chem. 11/2016

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Adjuvant Pelvic Radiation Therapy+/-Vaginal Brachytherapy in Patients With High-risk Stage I or Stage II Uterine Papillary Serous, Clear Cell, and High-grade Endometrioid Carcinoma.

Purpose: Radiation therapy (RT) for stages I-II uterine papillary serous carcinoma (UPSC), clear cell (CC), and high-grade endometrioid (HGE) carcinoma present a treatment challenge. Regimens include external beam radiotherapy (EBRT) with or without brachytherapy. We examine the use of these radiation modalities in these endometrial cancers (EC) with respect to cause-specific survival (CSS). Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with AJCC stages I-II UPSC, CC, or HGE cancer treated with hysterectomy and RT between 1998 and 2008. Patients who did not receive adjuvant RT or received brachytherapy alone were excluded. CSS was evaluated by the Kaplan-Meier survival analysis and the log-rank test was used to compare CSS. Multivariate analysis was performed using the Cox proportional hazards regression model. Adjusted hazard ratios (HR) were calculated for risk of EC death. Results: There were 1653 patients included in this analysis. The overall 100-month CSS for the entire cohort was 81.0%. The 100-month CSS was 85.3% for EBRT alone and 86.5% for EBRT+brachytherapy (P=0.72). Stage IC/IIA/IIB patients had a greater risk of EC death compared with stage IA/IB patients (adjusted HR=2.39; P

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Management of Skin Reactions During Cetuximab Treatment in Association With Chemotherapy or Radiotherapy: Update of the Italian Expert Recommendations.

Objectives: Cetuximab was shown in phase III clinical trials to improve chemotherapy efficacy in patients with advanced colorectal and head-neck cancer. Appropriate management of skin reactions associated with epidermal growth factor receptor inhibitor therapy is necessary to allow adequate drug compliance and to improve patient quality of life and outcomes. Methods: The RAND/UCLA Appropriateness Method was used by a group of experts to produce new Italian recommendations on the management of skin reactions in this setting. Statements were generated on the basis of an updated systematic review of the literature and rated twice by a panel of 38 expert physicians. A meeting of the panel was held after the first rating session. Results: Skin reactions included acneiformic rash, skin dryness (xerosis), pruritus, paronychia, hair abnormalities, mucositis, and increased growth of eyelashes or facial hair. Updates of the previous recommendations on the prevention and treatment of each type of reaction were proposed. Conclusions: This updated Expert Opinion focuses on how to assess and correctly grade skin reactions according to the latest National Cancer Institute Common Terminology Criteria for Adverse Events and on how to manage these adverse events in clinical practice. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Sarcomatous and Desmoplastic Mesotheliomas

The separation of sarcomatous and desmoplastic mesotheliomas from benign organizing pleuritis can be morphologically very difficult. Deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) testing appears to be a reliable marker of malignancy in mesothelial proliferations, and more recently it has been reported that, in this setting, loss of BAP1 by immunohistochemistry is only seen in malignant mesotheliomas. To determine how useful these tests are with sarcomatous and desmoplastic mesotheliomas, we examined 20 such tumors. Loss of BAP1 was seen in 3/20 (15%) and deletion of p16 by FISH was seen in 16/20 (80%) cases. Loss of one or the other marker was observed in 17/20 (85%). We also examined 13 sarcomatoid carcinomas, an important differential diagnosis of sarcomatoid mesotheliomas, and found that BAP1 was never lost, but p16 was deleted in 3/11 (27%). We conclude that: (1) BAP1 immunohistochemistry is relatively insensitive in the context of sarcomatous and desmoplastic mesotheliomas, but as a matter of time and cost efficiency may nonetheless be a useful first approach to the problem; (2) deletion of p16 by FISH is considerably more sensitive, but there remain a proportion of cases in which p16 is not deleted; (3) a small improvement in sensitivity can be achieved by using both markers; (4) in the context of a spindle cell malignant tumor in the pleura or peritoneum, which morphologically might be a metastatic sarcomatoid carcinoma or a mesothelioma, the finding of BAP1 loss favors mesothelioma, but p16 FISH cannot be used to separate sarcomatous mesotheliomas from sarcomatoid carcinomas.

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Neuroendocrine Carcinoma of the Endometrium: A Clinicopathologic Study of 25 Cases

Neuroendocrine carcinoma (NECa) of the endometrium is an uncommon tumor. In this study, we present the clinicopathologic features of 25 such cases. The patients ranged in age from 37 to 87 years (median, 57 y) and most commonly presented with vaginal bleeding. The tumors were either pure NECa (10) or mixed with other histotypes (15), most commonly endometrioid carcinoma. The NECas were large cell type (15), small cell type (4), or a mixture of both (6). NECa was underrecognized in 89% of referral/consultation cases. All tumors were positive for ≥1 neuroendocrine marker (chromogranin, synaptophysin, CD56). Additional immunohistochemical (IHC) studies were obtained in 18 cases, with positive results as follows: keratin cocktail (17), diffuse p16 (6), PAX-8 (6), CD117 (6), and TTF-1 (1). Mismatch-repair protein expression by IHC was abnormal in 8 of 18 cases (6 MLH1/PMS2 loss; 1 MSH2/MSH6 loss; 1 MSH6 loss). According to FIGO staging, cases were distributed as follows: I (6), II (2), III (10), and IV (7). All patients underwent surgical treatment, and 20 patients received adjuvant therapy. Twelve patients died of disease (mean survival 12.3 mo). Eleven patients were alive 5 to 134 months after diagnosis, including 7 who achieved a 5-year survival (3 stage I; 4 stage III). In summary, most of our endometrial NECas were large cell type, mixed with other histotypes, and underrecognized. These tumors tend to be PAX-8 negative and may be associated with microsatellite instability. The recognition of NECa may have an impact on the treatment of the patients affected by this disease. Although NECa usually has an aggressive behavior, 28% of our patients survived at least 5 years.

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Prognostic Factors of Hepatosplenic T-cell Lymphoma: Clinicopathologic Study of 28 Cases

Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis, and there is no standard of care. We evaluated 28 HSTCL patients to determine factors that may be associated with outcome. There were 19 men and 9 women with a median age of 32.5 years. Most patients had massive splenomegaly, and bone marrow showed sinusoidal involvement by lymphoma. The HSTCL cells expressed γδ T-cell receptor (TCR) in 20 (74%), αβ TCR in 5 (19%), and neither in 2 (7%) patients (1 case not assessed). Conventional cytogenetics and/or fluorescence in situ hybridization analysis in 24 patients at diagnosis showed isochromosome 7q (i7q) in 10 (42%) and trisomy 8 in 8 (33%) patients. Median overall survival (OS) and event-free survival (EFS) were each 28.3 months. Serum bilirubin level ≥1.5 mg/dL, αβ TCR expression, and trisomy 8 each correlated significantly with shorter OS and EFS. Patients with HSTCL received a variety of chemotherapy regimens with no regimen better than any other. However, patients who underwent stem cell transplant showed longer survival (OS: hazard ratio 0.3, P=0.09; EFS: hazard ratio 0.2, P=0.034). In conclusion, although HSTCL patients have a poor prognosis overall, the data presented support the novel suggestions that HSTCL patients can be stratified into 2 prognostic groups, with an elevated serum bilirubin level, αβ TCR expression, and trisomy 8 identifying a poorer prognostic group. In addition, the outcomes of this patient cohort suggest that stem cell transplantation has value for the treatment of patients with HSTCL.

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Primary Pseudomyogenic Hemangioendothelioma of Bone

Pseudomyogenic hemangioendothelioma (PMH) is a well-recognized neoplasm that usually arises in the soft tissue; concurrent bone involvement occurs in 24% of cases. PMH of bone without soft tissue involvement is rare. We describe the clinicopathologic findings of 10 such cases, the largest series reported to date. The study included 9 male and 1 female patient; their ages ranged from 12 to 74 years (mean 36.7 y). All patients had multiple tumors with a distinct regional distribution: 45% restricted to the lower extremity; 25% to the spine and pelvis; and 15% to the upper extremity. On imaging studies the tumors were well circumscribed and lytic. The neoplasms were composed of spindled cells arranged in intersecting fascicles with scattered epithelioid cells; epithelioid cells predominated in 3 cases. The neoplastic cells contained abundant densely eosinophilic cytoplasm and vesicular nuclei. There was limited cytologic atypia and necrosis, few mitoses (0 to 2/10 high-power fields), and inconspicuous stroma. Unique findings included abundant intratumoral reactive woven bone and hemorrhage with numerous osteoclast-like giant cells. Immunohistochemically, most tumors were positive for keratin, ERG, and CD31; CD34 was negative. The balanced t(7:19)(q22;13) translocation was documented in 3 cases. Follow-up is limited, but no patient developed documented visceral dissemination, and all have stable or progressive osseous disease. PMH exclusively involving bone is rare. It is multicentric, often involves the lower extremity, and has unusual morphology. The differential diagnosis includes epithelioid vascular neoplasms, giant cell tumor, bone forming neoplasms, and metastatic carcinoma. Because of its rarity, unusual presentation, and morphology, accurate diagnosis can be challenging.

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Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases

Several morphologic features have been reported to be predictive of abnormal expression of mismatch repair (MMR) proteins in endometrial and colon carcinomas. Although it is known that abnormal MMR expression is increased in frequency in ovarian endometrioid and clear cell carcinomas, no such histologic correlation has been identified. We reviewed 109 unselected ovarian clear cell carcinomas for specific tumor characteristics (architecture, nuclear atypia, signet ring cells, stromal hyalinization, background precursor) and inflammatory response (peritumoral lymphocytes found along the leading edge of the tumor, intratumoral stromal inflammation found within the tumor, percentage of plasma cells in the intratumoral stromal inflammation, tumor-infiltrating lymphocytes) and performed immunohistochemistry for all 4 MMR proteins. Abnormal MMR expression was identified in 6% of tumors and included MSH2/MSH6 (3), MLH1/PMS2 (1), MSH6 (1), and PMS2 (1). These patients had a mean age of 40 (range, 31 to 48) years, which contrasted with a mean of 53.2 (range, 28 to 82) years for the overall cohort. One had a concurrent diagnosis of endometrial carcinoma, whereas another had a family history of endometrial carcinoma. None had a personal/family history of colonic carcinoma. Tumors with diffuse intratumoral stromal inflammation and peritumoral lymphocytes were more frequently associated with MMR loss on univariate analysis (P

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Fumarate Hydratase–deficient Uterine Leiomyomas Occur in Both the Syndromic and Sporadic Settings

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome secondary to germline fumarate hydratase (FH) mutation presents with cutaneous and uterine leiomyomas, and a distinctive aggressive renal carcinoma. Identification of HLRCC patients presenting first with uterine leiomyomas may allow early intervention for renal carcinoma. We reviewed the morphology and immunohistochemical (IHC) findings in patients with uterine leiomyomas and confirmed or presumed HLRCC. IHC was also performed on a tissue microarray of unselected uterine leiomyomas and leiomyosarcomas. FH-deficient leiomyomas underwent Sanger and massively parallel sequencing on formalin-fixed paraffin-embedded tissue. All 5 patients with HLRCC had at least 1 FH-deficient leiomyoma: defined as completely negative FH staining with positive internal controls. One percent (12/1152) of unselected uterine leiomyomas but 0 of 88 leiomyosarcomas were FH deficient. FH-deficient leiomyoma patients were younger (42.7 vs. 48.8 y, P=0.024) and commonly demonstrated a distinctive hemangiopericytomatous vasculature. Other features reported to be associated with FH-deficient leiomyomas (hypercellularity, nuclear atypia, inclusion-like nucleoli, stromal edema) were inconstantly present. Somatic FH mutations were identified in 6 of 10 informative unselected FH-deficient leiomyomas. None of these mutations were found in the germline. We conclude that, while the great majority of patients with HLRCC will have FH-deficient leiomyomas, 1% of all uterine leiomyomas are FH deficient usually due to somatic inactivation. Although IHC screening for FH may have a role in confirming patients at high risk for hereditary disease before genetic testing, prospective identification of FH-deficient leiomyomas is of limited clinical benefit in screening unselected patients because of the relatively high incidence of somatic mutations.

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Improving Selection Criteria for ALK Inhibitor Therapy in Non–Small Cell Lung Cancer: A Pooled-Data Analysis on Diagnostic Operating Characteristics of Immunohistochemistry

Lung cancer is often diagnosed by molecular markers for prediction and treatment. To date, the golden standard for detection of anaplastic lymphoma kinase (ALK) rearrangements is fluorescence in situ hybridization (FISH). We performed a pooled-data analysis on the diagnostic operating characteristics of immunohistochemistry (IHC) assay on non–small cell lung cancer (NSCLC). We searched Embase, Pubmed, and Springer databases. The results of IHC were evaluated using a modified H-score. We used a 2-level bivariate meta-analysis following a random effect model to summarize sensitivity and specificity and fit hierarchical summary receiver-operating characteristic curves. We also performed sensitivity analysis using different antibodies to investigate potential heterogeneity. Twelve studies consisting of a total of 3754 NSCLC specimens were analyzed. When we defined 1+/2+/3+, 2+/3+, and 3+ as ALK positive, we found the sensitivities to be 99% (95% confidence interval [CI], 97%-100%), 86% (95% CI, 73%-93%), and 56% (95% CI, 36%-74%) and the specificities to be 98% (95% CI, 95%-99%), 99% (95% CI, 99%-100%), and 100% (95% CI, 100%-100%), respectively. We demonstrated that when defining 3+ as positive and 0 as negative the sensitivity was 99% and specificity was 100%. In our sensitivity analysis, we found the sensitivity of D5F3 and 5A4 antibodies to be much higher than that of ALK1. We concluded that IHC scores 0 and 3+ were nearly 100% concordant with FISH-negative and FISH-positive status, respectively. However, IHC scores 1+ and 2+ might require further confirmatory testing by FISH assay. IHC assay using D5F3 and 5A4 antibodies reliably detected NSCLC with ALK rearrangement and may be useful as a screening method to identify these tumors.

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Clinicopathologic Characteristics of Hepatocellular Carcinoma With Reactive Ductule-like Components, a Subset of Liver Cancer Currently Classified as Combined Hepatocellular-Cholangiocarcinoma With Stem-Cell Features, Typical Subtype

The aim of this study was to elucidate the clinicopathologic characteristics of hepatocellular carcinoma with reactive ductule-like components (HCC-RD), corresponding to combined hepatocellular-cholangiocarcinoma (CHC) with stem cell features, typical subtype. Retrospective clinicopathologic analysis was performed on HCCs surgically treated at the University of Tokyo Hospital between 1995 and 2013. RD components were defined as neoplastic ductular structures composed of small "stem/progenitor-like" cells. There were 46 HCC-RDs, comprising about 3% of all HCCs. Thirty-eight cases of CHC, classical type (classical CHC), were identified during the study period. When compared with conventional HCC, HCC-RD was characterized by younger patient age (P=0.016), higher frequency of female patients (P

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Barrett’s Esophagus: A Comprehensive and Contemporary Review for Pathologists

This review provides a summary of our current understanding of, and the controversies surrounding, the diagnosis, pathogenesis, histopathology, and molecular biology of Barrett's esophagus (BE) and associated neoplasia. BE is defined as columnar metaplasia of the esophagus. There is worldwide controversy regarding the diagnostic criteria of BE, mainly with regard to the requirement to histologically identify goblet cells in biopsies. Patients with BE are at increased risk for adenocarcinoma, which develops in a metaplasia-dysplasia-carcinoma sequence. Surveillance of patients with BE relies heavily on the presence and grade of dysplasia. However, there are significant pathologic limitations and diagnostic variability in evaluating dysplasia, particularly with regard to the more recently recognized unconventional variants. Identification of non–morphology-based biomarkers may help risk stratification of BE patients, and this is a subject of ongoing research. Because of recent achievements in endoscopic therapy, there has been a major shift in the treatment of BE patients with dysplasia or intramucosal cancer away from esophagectomy and toward endoscopic mucosal resection and ablation. The pathologic issues related to treatment and its complications are also discussed in this review article.

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IgG Subclass Staining in Routine Renal Biopsy Material

Immunofluorescence staining plays a vital role in nephropathology, but the panel of antibodies used has not changed for decades. Further classification of immunoglobulin (Ig)G-containing immune-type deposits with IgG subclass staining (IgG1, IgG2, IgG3, and IgG4) has been shown to be of diagnostic utility in glomerular diseases, but their value in the evaluation of renal biopsies has not been addressed systematically in large renal biopsy material. Between January 2007 and June 2014, using direct immunofluorescence, we stained every renal biopsy for the IgG subclasses if there was moderate to prominent glomerular IgG staining and/or IgG-predominant or IgG-codominant glomerular staining. The total number of biopsies stained was 1084, which included 367 cases of membranous glomerulonephritis, 307 cases of lupus nephritis, 74 cases of fibrillary glomerulonephritis, 53 cases of proliferative glomerulonephritis with monoclonal IgG deposits, and 25 cases of antiglomerular basement membrane disease, among others. We found that monoclonality of IgG deposits cannot always be reliably determined on the basis of kappa and lambda light chain staining alone, particularly if concomitant (frequently nonspecific) IgM staining is present. In IgG heavy and heavy and light chain deposition disease (3 cases), subclass staining is very helpful, and in proliferative glomerulonephritis with monoclonal IgG deposits subclass staining is necessary. IgG subclass staining is useful in differentiating primary from secondary membranous glomerulonephritis. In proliferative glomerulonephritis with polyclonal IgG deposition, IgG1 dominance/codominance with concomitant IgG3 and IgG2 but weak or absent IgG4 staining favors an underlying autoimmune disease. IgG subclass staining is a very useful diagnostic method in a selected cohort of renal biopsies, particularly in biopsies with glomerulonephritis with monoclonal IgG deposits.

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Biphasic Squamoid Alveolar Renal Cell Carcinoma: A Distinctive Subtype of Papillary Renal Cell Carcinoma?

Biphasic squamoid alveolar renal cell carcinoma (BSARCC) has been recently described as a distinct neoplasm. Twenty-one cases from 12 institutions were analyzed using routine histology, immunohistochemistry, array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization. Tumors were removed from 11 male and 10 female patients, whose age ranged from 53 to 79 years. The size of tumors ranged from 1.5 to 16 cm. Follow-up information was available for 14 patients (range, 1 to 96 mo), and metastatic spread was found in 5 cases. All tumors comprised 2 cell populations arranged in organoid structures: small, low-grade neoplastic cells with scant cytoplasm usually lining the inside of alveolar structures, and larger squamoid cells with more prominent cytoplasm and larger vesicular nuclei arranged in compact nests. In 9/21 tumors there was a visible transition from such solid and alveolar areas into papillary components. Areas composed of large squamoid cells comprised 10% to 80% of total tumor volume. Emperipolesis was present in all (21/21) tumors. Immunohistochemically, all cases were positive for cytokeratin 7, EMA, vimentin, and cyclin D1. aCGH (confirmed by fluorescence in situ hybridization) in 5 analyzable cases revealed multiple numerical chromosomal changes including gains of chromosomes 7 and 17 in all cases. These changes were further disclosed in 6 additional cases, which were unsuitable for aCGH. We conclude that tumors show a morphologic spectrum ranging from RCC with papillary architecture and large squamoid cells to fully developed BSARCC. Emperipolesis in squamoid cells was a constant finding. All BSARCCs expressed CK7, EMA, vimentin, and cyclin D1. Antibody to cyclin D1 showed a unique and previously not recognized pattern of immunohistochemical staining. Multiple chromosomal aberrations were identified in all analyzable cases including gains of chromosomes 7 and 17, indicating that they are akin to papillary RCC. Some BSARCCs were clinically aggressive, but their prognosis could not be predicted from currently available data. Present microscopic, immunohistochemical, and molecular genetic data strongly support the view that BSARCC is a distinctive and peculiar morphologic variant of papillary RCC.

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Ovarian Low-grade Serous Carcinoma: A Clinicopathologic Study of 33 Cases With Primary Surgery Performed at a Single Institution

Ovarian low-grade serous carcinoma (LGSC) is an entity with distinct pathologic and clinical features. The number of studies on this type of tumor is limited. In this article, we present our experience with 33 cases of ovarian LGSC with primary surgical treatment at our institution. For comparison, a cohort of ovarian high-grade serous carcinoma (HGSC) was also studied. Clinical information was obtained from the patients' charts or from the treating physicians. Hematoxylin and eosin slides were reviewed of 28 available LGSCs, and the following parameters were recorded: presence/absence of a serous borderline tumor (SBT), presence/absence of micropapillary/cribriform pattern (MP/CP), architectural pattern in the invasive component, and presence/absence of desmoplasia or fibrosis. The incidence of ovarian LGSC was 4.7%. LGSC patients ranged in age from 19 to 79 years (mean, 52 y), with 21.2% younger than 40 years. HGSC patients ranged in age from 38 to 90 years (mean, 62 y), with 1.6% younger than 40 years. LGSCs were staged as follows: stage I (2), stage III (23), and stage IV (8). Twenty-eight of 33 LGSC cases had concurrent SBT, with this component accounting for >50% of the neoplasm in 15 cases. In addition, MP/CP was noted in 19 cases. Invasion patterns included micropapillae (93%), cribriform nests (74%), elongated papillae (26%), glandular (44.4%), medium-sized papillae (33.3%), solid nests (22.2%), macropapillae (19%), and single cells (19%). In addition, desmoplasia (44.4%) and fibrosis (37%) were noted. Follow-up data ranging from 13 to 195 months (median 61.2 mo) were available on 30/33 LGSC patients: 18 (60%) were dead of disease; 1 (3.3%) was dead of other cause; 5 (16.7%) were alive with disease; and 6 (20%) had no evidence of disease. Follow-up data from 1 to 169 months (median 48 mo) were available on 185 HGSC patients: 132 (71.4%) were dead of disease; 3 (1.6%) were dead of other cause; 21 (11.4%) were alive with disease; and 29 (15.7%) had no evidence of disease. Ovarian LGSC is rare with a predilection for younger patients relative to HGSC. Most LGSC cases are associated with SBT with an MP/CP, and their invasive component usually contains a micropapillary pattern. Most patients with ovarian LGSC present with advanced-stage disease and have a short-term survival advantage over patients with HGSC (estimated 5 y survival: 62.3% vs. 43.9%). However, over a prolonged period of time, this survival advantage decreases (estimated 10 y survival: 21.2% vs. 22.7%).

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BSEP and MDR3: Useful Immunohistochemical Markers to Discriminate Hepatocellular Carcinomas From Intrahepatic Cholangiocarcinomas and Hepatoid Carcinomas

We herein examined the immunohistochemical expression of 2 hepatocyte-specific transporters (bile salt export pump [BSEP] and multidrug-resistance protein 3 [MDR3]) in hepatocellular carcinomas (HCCs, n=54), intrahepatic cholangiocarcinomas (n=34), combined hepatocellular and cholangiocarcinomas (n=23), and hepatoid carcinomas originated from extrahepatic organs (n=27) to compare their diagnostic values with those of arginase-1 (ARG1) and hepatocyte paraffin-1 (HepPar-1). BSEP was expressed in 91% of HCCs and MDR3 in 83%. Although their sensitivities were slightly lower than those of ARG1 (96%) and HepPar-1 (93%), the 2 transporters appeared to be more specific for HCCs. ARG1 and HepPar-1 were expressed in intrahepatic cholangiocarcinomas (9% and 6%) and hepatoid carcinomas (22% and 44%, respectively), whereas BSEP and MDR3 were entirely negative in these neoplasms, except for 1 case of BSEP-positive hepatoid carcinoma of the esophagus. The highly specific expression of BSEP and MDR3 in hepatocytes was recapitulated in additional examinations of combined hepatocellular and cholangiocarcinomas, in which the expression of the transporters was restricted to morphologically hepatocellular areas. In contrast, ARG1 and HepPar-1 were also variably positive in areas of biliary or indeterminate differentiation. We also applied BSEP and MDR3 immunohistochemistry to 8 biopsy cases of poorly differentiated primary liver cancer, in which the original diagnosis was not conclusive. The diagnosis of HCC was retrospectively suggested in 2 cases expressing both BSEP and MDR3. In conclusion, given the highly specific expression of BSEP and MDR3 in HCCs, immunohistochemistry for these transporters will be useful not only for determining hepatocellular differentiation in primary liver cancers but also for discriminating HCCs from hepatoid carcinomas.

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A Detailed Immunohistochemical Analysis of a Large Series of Cervical and Vaginal Gastric-type Adenocarcinomas

Adenocarcinomas exhibiting gastric differentiation represent a recently described and uncommon subtype of non–human papillomavirus (HPV)-related cervical adenocarcinoma. They comprise a spectrum from a well-differentiated variant (adenoma malignum/mucinous variant of minimal deviation adenocarcinoma) to a more poorly differentiated overtly malignant form, generally referred to as gastric-type adenocarcinoma. Rarely, such tumors have also been described as primary vaginal neoplasms. Gastric-type adenocarcinomas exhibit considerable morphologic overlap with adenocarcinomas originating outside the female genital tract, especially mucinous adenocarcinomas arising in the pancreas and biliary tract. Moreover, they often metastasize to unusual sites, such as the ovary and peritoneum/omentum, where they can be mistaken for metastatic adenocarcinomas from other, nongynecologic sites. There is little information regarding the immunophenotype of gastric-type adenocarcinomas, and knowledge of this is important to aid in the distinction from other adenocarcinomas. In this study, we undertook a detailed immunohistochemical analysis of a large series of cervical (n=45) and vaginal (n=2) gastric-type adenocarcinomas. Markers included were cytokeratin (CK)7, CK20, CDX2, carcinoembryonic antigen, CA125, CA19.9, p16, estrogen receptor, progesterone receptor, MUC6, PAX8, PAX2, p53, hepatocyte nuclear factor 1 beta, carbonic anhydrase IX, human epidermal receptor 2 (HER2), and mismatch repair (MMR) proteins. All markers were classified as negative, focal (

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Epithelioid Schwannomas: An Analysis of 58 Cases Including Atypical Variants

The histologic features and outcome of 58 cases of epithelioid schwannoma were studied to determine the significance of atypical histologic features. Cases were retrieved from personal consultation files from 1999 to 2013. Patients (31 male and 26 female patients) ranged in age from 14 to 80 years (median, 38 y). Two patients had schwannomatosis 1. Tumors developed in the dermis/subcutis (n=56) or muscle (n=2) of the upper extremity (34.5%), lower extremity (34.5%), thorax/abdomen/back (18%), and less common anatomic locations including the scalp, neck, lip, and breast. They ranged in size from 0.25 to 4.5 cm (median, 2.0 cm). Typically circumscribed and surrounded by a perineurium, they comprised single or small groups of epithelioid schwann cells with a moderate amphophilic cytoplasm and occasional nuclear pseudoinclusions. Stroma varied from myxoid to hyalinized, often with thick-walled vessels (55 cases). Mitotic rate ranged from 0 to 9 mitoses/10 high-power field (HPF) (2.37 mm2) in the most active areas (mean, 2 to 3 mitoses/10 HPFs). Thirteen cases (22%) were "atypical," defined by a high mitotic rate (≥3 mitoses per 10 HPFs) and nuclear size variation (≥3:1). All (56/56) expressed S100 protein; type IV collagen invested groups or individual cells (16/17). Melanoma markers were negative, except for melan A (1 case). Follow-up in 39 patients (median, 78 mo; range, 6 to 174 mo) indicated that 31 (79%) were alive without disease (including 9/13 atypical cases; median, 78 mo), 7 (18%) were alive with unknown status, and 1 patient had died of unrelated causes. One tumor recurred, but none metastasized. Epithelioid schwannomas, even those with atypical features, are benign and do not constitute a histologic continuum with epithelioid malignant peripheral nerve sheath tumors, which typically occur in deep soft tissues and have more anaplastic features.

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Recurrent CIC Gene Abnormalities in Angiosarcomas: A Molecular Study of 120 Cases With Concurrent Investigation of PLCG1, KDR, MYC, and FLT4 Gene Alterations

Angiosarcoma (AS) is a rare sarcoma subtype showing considerable clinicopathologic and genetic heterogeneity. Most radiation-induced AS show MYC gene amplifications, with a subset of cases harboring KDR, PTPRB, and PLCG1 mutations. Despite recent advances, the genetic abnormalities of most primary AS remain undefined. Whole-transcriptome sequencing was initiated in 2 index cases of primary soft tissue AS with epithelioid morphology occurring in young adults for novel gene discovery. The candidate abnormalities were validated and then screened by targeted sequencing and fluorescence in situ hybridization in a large cohort of 120 well-characterized AS cases. Findings were subsequently correlated with the status of KDR, PLCG1, MYC, and FLT4 gene abnormalities. The clinicopathologic relevance and prognostic significance of these genetic changes were analyzed by statistical methods. Concurrent CIC mutations and CIC rearrangements were identified in both index cases, with a CIC-LEUTX fusion detected in 1 case. Upon screening, an additional visceral AS in a young adult had a complex CIC rearrangement, whereas 6 others harbored only CIC mutations. All 3 CIC-rearranged AS cases lacked vasoformation and had a solid growth of round, epithelioid to rhabdoid cells, showing immunoreactivity for CD31 and Ets-related gene and sharing a transcriptional signature with other round cell sarcomas, including CIC-rearranged tumors. Overall, CIC abnormalities occurred in 9% (9/98) of cases, affecting younger patients with primary AS, with an inferior disease-free survival. In contrast, PLCG1 and KDR mutations occurred in both primary and secondary AS cases, accounting for 9.5% and 7%, respectively, with a predilection for breast and bone/viscera location, regardless of MYC status. MYC amplification was present in most secondary AS related to breast cancer (91%) compared with other causes (25%) or primary AS (7%). FLT4-amplified AS lacked PLCG1/KDR mutations, occurring predominantly in MYC-amplified population, and showed poor prognosis.

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Frequent BRAF V600E Mutations in Metanephric Stromal Tumor

No abstract available

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Six-week treatment of axial spondyloarthritis patients with an optimal dose of nonsteroidal antiinflammatory drugs: early response to treatment in signal intensity on magnetic resonance imaging of the sacroiliac joints

Objective. To evaluate the early effect of full-dose nonsteroidal antiinflammatory drugs (NSAIDs) on the extent and intensity of bone marrow edema of the sacroiliac (SI) joints on magnetic resonance imaging (MRI) in axial spondyloarthritis (SpA). Methods. A single-center, 6-week study of a cohort of consecutive patients with clinically suspected axial SpA was conducted. A total of 117 patients were screened. Forty patients who were diagnosed as having axial SpA and had presented with a positive MRI of the SI joints as defined by the Assessment of SpondyloArthritis international Society (ASAS) criteria were considered for a followup MRI after 6 weeks of an optimal dose of NSAIDs. Twenty patients completed the study. Disease activity was monitored by determining the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score every 2 weeks and the Bath Ankylosing Spondylitis Functional Index score at baseline and week 6. NSAID intake was assessed by the ASAS NSAID index. Primary end points were improvement in bone marrow edema of the SI joints on MRI and BASDAI response at week 6. Results. Approximately one-third of eligible patients newly diagnosed as having axial SpA were unable to continue the full-dose NSAID schedule. The median NSAID index was 97% in patients who completed the study. There was a reduction of 1.1 units (10.5%) in mean Spondyloarthritis Research Consortium of Canada (SPARCC) scores at week 6 in comparison to baseline (P=0.032). Overall, only 30% of the patients (6 of 20) had a minimal clinically important difference of 2.5 in SPARCC score. However, 80% of the patients displayed high-intensity lesions on STIR images at baseline, which decreased significantly at week 6 (P=0.011). There was a significant decrease in the relative intensity of the region of interest (P=0.007) and a mean decrease of 0.6 in the BASDAI score per 2 weeks of therapy (P=0.001). Only 29.4% of the patients met the BASDAI criteria for 50% improvement (BASDAI50) at week 6. Conclusion. Our findings indicate a high level of dropout among patients receiving full-dose NSAID therapy in daily practice. In those who tolerated NSAID therapy, there was no clinically relevant decrease in SPARCC scores and low BASDAI50 response. However, we found a decrease in signal intensity of bone marrow edema of the SI joints as an early response to 6 weeks of optimal NSAID therapy in patients newly presenting with axial SpA.

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Resistin is a predictor of asthma risk and resistin: adiponectin ratio is a negative predictor of lung function in asthma

Abstract

Background

Adipokines, such as resistin and adiponectin, modify inflammation and may contribute to increased asthma risk and severity in obese people.

Objective

To examine plasma resistin and resistin: adiponectin ratio: (1) in asthmatics compared to healthy controls, (2) according to asthma severity, obesity and gender (3) following weight loss in obese asthmatics.

Methods

In a cross-sectional observational study of asthmatic adults (n=96) and healthy controls (n=46), plasma resistin and adiponectin were measured. In a separate intervention study, obese asthmatic adults (n=27) completed a 10-week weight-loss intervention and plasma resistin and adiponectin concentrations were analysed.

Results

Plasma resistin and resistin: adiponectin ratio were higher in asthma compared to controls and were higher again in subjects with a severe versus mild to moderate asthma pattern. Amongst asthmatic subjects, resistin was not modified by gender or obesity, while adiponectin was lower in males and obese subjects. As a result, resistin: adiponectin ratio was higher in obese males, non-obese males and obese females, compared to non-obese females. In a logistic regression model, plasma resistin concentration was a predictor of asthma risk. In a multiple linear regression model, plasma resistin: adiponectin ratio was a negative predictor of FEV₁ in asthma. Following weight loss, neither resistin, adiponectin nor resistin: adiponectin ratio were changed. However, the change (Δ) in %body fat was associated with Δ resistin: adiponectin ratio. Post intervention Δ resistin was negatively correlated with both ΔFRC and ΔRV.

Conclusion and clinical relevance

This study demonstrates that resistin and resistin: adiponectin ratio are higher in asthma and are higher again in subjects who have more severe disease. Resistin: adiponectin ratio is highest in obese male asthmatics. As resistin is a predictor of asthma risk and resistin:adiponectin is a predictor of FEV₁ in asthma, these adipokines may be contributing to the obese-asthma phenotype, thus providing a potential therapeutic target for obese asthma.

This article is protected by copyright. All rights reserved.

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Human bronchial and parenchymal fibroblasts display differences in basal inflammatory phenotype and response to IL-17A

Abstract

Background

Chronic inflammation, typified by increased expression of IL-17A, together with airway and parenchymal remodeling are features of chronic lung diseases. Emerging evidence suggests that phenotypic heterogeneity of repair and inflammatory capacities of fibroblasts may contribute to the differential structural changes observed in different regions of the lung.

Objective

To investigate phenotypic differences in parenchymal and bronchial fibroblasts, either in terms of inflammation and remodeling or the ability of these fibroblasts to respond to IL-17A.

Methods

Four groups of primary fibroblasts were used: normal human bronchial fibroblast (NHBF), normal human parenchymal fibroblast (NHPF), COPD human bronchial fibroblast (CHBF) and COPD human parenchymal fibroblast (CHPF). Cytokine and extracellular matrix (ECM) expression were measured at baseline and after stimulation with IL-17A. Actinomycin D was used to measure cytokine mRNA stability.

Results

At baseline, we observed higher protein production of IL-6 in NHPF than NHBF, but higher levels of IL-8 and GRO-α in NHBF. IL-17A induced a higher expression of GRO-α (CXCL1) and IL-6 in NHPF than in NHBF, and a higher level of IL-8 expression in NHBF. IL-17A treatment decreased the mRNA stability of IL-6 in NHBF when compared with NHPF. CHPF expressed higher protein levels of fibronectin, collagen-I and collagen-III than CHBF, NHBF and NHPF. IL-17A increased fibronectin and collagen-III protein only in NHPF and collagen-III protein production in CHBF and CHPF.

Conclusions and Clinical Relevance

These findings provide insight into the inflammatory and remodeling processes that may be related to the phenotypic heterogeneity of fibroblasts from airway and parenchymal regions and in their response to IL-17A.

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CIC-DUX4 Fusion-Positive Round Cell Sarcomas of soft tissue and bone: a single institution morphologic and molecular analysis of 7 cases

Abstract

Aims

Round cell sarcomas lacking specific translocations represent a diagnostic challenge. The aim of this study is to describe seven cases of CIC-DUX4 positive sarcomas, including the first reported example arising primarily in bone.

Methods and results

Patients ranged in age from 15 to 44 years (median: 33). Six cases arose from the soft tissues and one from the iliac bone. Morphologically, all cases showed an undifferentiated round cell population with greater atypia and pleomorphism than Ewing sarcoma. Immunohistochemically, all tumours showed focal and weak positivity for CD99 and 5/7 displayed nuclear and/or cytoplasmic positivity for WT1. Five patients had lung metastases at presentation. All patients received chemotherapy according to Ewing sarcoma protocols. All but one patient (the one with a bone tumour) died of disease after a mean of 14.5 months from the diagnosis (range: 8-20 months).

Conclusions

Our series confirms that CIC-DUX4 positive sarcomas are aggressive tumours with an adverse prognosis and with clinical, histological, and genetic differences compared to Ewing sarcoma. The best therapeutic approach needs to be investigated.

This article is protected by copyright. All rights reserved.

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Salivary duct carcinoma with rhabdoid features: a salivary counterpart against pleomorphic lobular carcinoma of the breast

Abstract

Aim

We analyzed the clinicopathologic features and immunohistochemical characteristics of 9 cases of salivary duct carcinoma (SDC) with rhabdoid features (SDCRF), representing a new, extremely rare type of salivary gland malignancy.

Methods and results

We analyzed 2511 cases of salivary gland tumors, clinicopathologically and immunohistochemically. The incidence of SDCRF was 0.4%. Eight patients were male. Age ranged from 36–85 years (mean, 61 years). SDC arose from the parotid glands and submandibular gland in 6 and 3 cases, respectively. Seven cases appeared as a carcinoma component of carcinoma ex pleomorphic adenoma (CXPA) cases. Six patients died from disease. Histologically, diffuse proliferation of non-coherent large ovoid or polygonal carcinoma cells with eosinophilic cytoplasm and eccentric nuclei were observed in all cases; such cytological characteristics were defined as "rhabdoid features." Immunohistochemically, all cases were positive for cytokeratin, gross cystic disease fluid protein-15, androgen receptor, and SMARCB1; 7 cases were positive for Her-2, whereas two cases were positive for epidermal growth factor receptor. However, all cases were negative for vimentin and myoepithelial markers. Eight cases showed no or aberrant expression of E-cadherin and β-catenin. The results suggest SDCRF is an extremely rare subtype of SDC, not sarcomatoid variant SDC. SDCRF is histologically unique and is positive for SDC markers but negative for vimentin, unlike rhabdoid type carcinomas arising from other organs.

Conclusions

The morphogenesis of SDCRF is related to no or aberrant expression of cell–cell adhesion molecules. Therefore, SDCRF could be a salivary counterpart to pleomorphic lobular breast carcinoma.

This article is protected by copyright. All rights reserved.

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Toxicity assessment of four insecticides with different modes of action on pupae and adults of Eriopis connexa (Coleoptera: Coccinellidae), a relevant predator of the Neotropical Region

Abstract

Pesticides can be toxic to nontarget organisms including the natural enemies of agricultural pests, thus reducing the biodiversity of agroecosystems. The lethal and sublethal effects of four insecticides with different modes of action—pyriproxyfen, teflubenzuron, acetamiprid, and cypermethrin—were evaluated on pupae and adults of Eriopis connexa, an effective predator in horticultural crops. Pupal survival was reduced by pyriproxyfen (26 %) and cypermethrin (41 %). Malformations in adults emerged from treated pupae were observed after acetamiprid (82.7 and 100 % for 100 and 200 mg a.i./l, respectively), pyriproxyfen (48.6 %), and cypermethrin (13.3 %) treatments. A longer mean oviposition time was also observed in adults emerged from pupae treated with cypermethrin. Moreover, the latter insecticide as well as teflubenzuron did not reduce reproductive parameters, whereas females emerged from pyriproxyfen-treated pupae were not be able to lay eggs even when females showed large abdomens. Upon exposure of adults, survival was reduced to approximately 90 % by acetamiprid, but no reduction occurred with pyriproxyfen, teflubenzuron, or cypermethrin though the fecundity at fifth oviposition time of the female survivors was reduced. Pyriproxyfen decreased the hatching at all the oviposition times tested, whereas fertility was reduced in the fourth and fifth ovipositions by teflubenzuron and in the first and third ovipositions by cypermethrin. In conclusion, all four insecticides tested exhibited lethal or sublethal effects, or both, on E. connexa. The neurotoxic insecticides were more harmful than the insect-growth regulators, and pupae were more susceptible than adults. The toxicity of insecticides on the conservation of predators in agroecosystems of the Neotropical Region is discussed.

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A Fe 3 O 4 /FeAl 2 O 4 composite coating via plasma electrolytic oxidation on Q235 carbon steel for Fenton-like degradation of phenol

Abstract

The Fe₃O₄/FeAl₂O₄ composite coatings were successfully fabricated on Q235 carbon steel by plasma electrolytic oxidation technique and used to degrade phenol by Fenton-like system. XRD, SEM, and XPS indicated that Fe₃O₄ and FeAl₂O₄ composite coating had a hierarchical porous structure. The effects of various parameters such as pH, phenol concentration, and H₂O₂ dosage on catalytic activity were investigated. The results indicated that with increasing of pH and phenol content, the phenol degradation efficiency was reduced significantly. However, the degradation rate was improved with the addition of H₂O₂, but dropped with further increasing of H₂O₂. Moreover, 100 % removal efficiency with 35 mg/L phenol was obtained within 60 min at 303 K and pH 4.0 with 6.0 mmol/L H₂O₂ on 6-cm² iron oxide coating. The degradation process consisted of induction period and rapid degradation period; both of them followed pseudo-first-order reaction. Hydroxyl radicals were the mainly oxidizing species during phenol degradation by using n-butanol as hydroxyl radical scavenger. Based on Fe leaching and the reaction kinetics, a possible phenol degradation mechanism was proposed. The catalyst exhibited excellent stability.

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Environmental application of nanotechnology: air, soil, and water

Abstract

Global deterioration of water, soil, and atmosphere by the release of toxic chemicals from the ongoing anthropogenic activities is becoming a serious problem throughout the world. This poses numerous issues relevant to ecosystem and human health that intensify the application challenges of conventional treatment technologies. Therefore, this review sheds the light on the recent progresses in nanotechnology and its vital role to encompass the imperative demand to monitor and treat the emerging hazardous wastes with lower cost, less energy, as well as higher efficiency. Essentially, the key aspects of this account are to briefly outline the advantages of nanotechnology over conventional treatment technologies and to relevantly highlight the treatment applications of some nanomaterials (e.g., carbon-based nanoparticles, antibacterial nanoparticles, and metal oxide nanoparticles) in the following environments: (1) air (treatment of greenhouse gases, volatile organic compounds, and bioaerosols via adsorption, photocatalytic degradation, thermal decomposition, and air filtration processes), (2) soil (application of nanomaterials as amendment agents for phytoremediation processes and utilization of stabilizers to enhance their performance), and (3) water (removal of organic pollutants, heavy metals, pathogens through adsorption, membrane processes, photocatalysis, and disinfection processes).

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Managing the drinking water catchment areas: the French agricultural cooperatives feed back

Abstract

The quality of raw water is problematic in France, largely polluted by nitrates and pesticides (Mueller and Helsel, Nutrients in the nation's waters—too much of a good thing? Geological Survey (U.S.), 1996; European Environment Agency, European waters—assessment of status and pressures, 2012).

This type of pollution, even though not always due to agriculture (example of the catchment of Ambleville, county 95, France where the nitrate pollution is mainly due to sewers (2012)), has been largely related to the agricultural practices (Sci Total Environ 407:6034–6043, 2009).

Taking note of this observation, and instead of letting it paralyze their actions, the agricultural cooperatives decided with Agrosolutions to act directly on the field with their subscribers to change the agricultural practices impacting the water and the environment.

This article shows how the French agricultural cooperatives transformed the awareness of the raw water quality problem into an opportunity for the development and implementation of more precise and responsible practices, to protect their environment. They measure in order to pilot, co-construct and build the best action plans possible according to the three pillars of environment, economy and agronomy.

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Ultrasound based AOP for emerging pollutants: from degradation to mechanism

Abstract

Ultrasound is known to degrade organic compounds by pyrolysis and by the reaction of free radicals. In this work, sonolytic degradation of an identified water pollutant, coomassie brilliant blue (CBB), has been carried out in pure water as well as in river water. In the case of pure water, 90 % degradation was obtained after 30 min of sonication (350 kHz frequency, 60 W power), whereas in river water, the same efficiency was achieved only after 90 min. The degradation was also performed in the presence of varying concentration of (10–100 mg L⁻¹) inorganic ions such as chloride, sulfate, nitrate, bicarbonate, and carbonate ions which were detected in the river water sample. Higher concentration of chloride enhanced the degradation due to the salting out mechanism. The enhancement of degradation in the presence of nitrate is mainly due to the change in the surface potential at the interface of the cavitating bubble. Bicarbonate ion and carbonate ion enhanced the degradation due to the involvement of carbonate radicals. A possible degradation mechanism is proposed based on the product profile determined by LC-Q-ToF-MS. The low efficiency of degradation in river water compared to that in pure water is likely due to the increased rate of bubble dissolution or escape of bubbles (degassing effect), and the scavenging of ^•OH by the organic content (high chemical oxygen demand (COD)).

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Peclet number analysis of cross-flow in porous gas diffusion layer of polymer electrolyte membrane fuel cell (PEMFC)

Abstract

Adoption of hydrogen economy by means of using hydrogen fuel cells is one possible solution for energy crisis and climate change issues. Polymer electrolyte membrane (PEM) fuel cell, which is an important type of fuel cells, suffers from the problem of water management. Cross-flow is induced in some flow field designs to enhance the water removal. The presence of cross-flow in the serpentine and interdigitated flow fields makes them more effective in proper distribution of the reactants on the reaction layer and evacuation of water from the reaction layer than diffusion-based conventional parallel flow fields. However, too much of cross-flow leads to flow maldistribution in the channels, higher pressure drop, and membrane dehydration. In this study, an attempt has been made to quantify the amount of cross-flow required for effective distribution of reactants and removal of water in the gas diffusion layer. Unit cells containing two adjacent channels with gas diffusion layer (GDL) and catalyst layer at the bottom have been considered for the parallel, interdigitated, and serpentine flow patterns. Computational fluid dynamics-based simulations are carried out to study the reactant transport in under-the-rib area with cross-flow in the GDL. A new criterion based on the Peclet number is presented as a quantitative measure of cross-flow in the GDL. The study shows that a cross-flow Peclet number of the order of 2 is required for effective removal of water from the GDL. Estimates show that this much of cross-flow is not usually produced in the U-bends of Serpentine flow fields, making these areas prone to flooding.

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Lethal and sub-lethal effects of elevated CO 2 concentrations on marine benthic invertebrates and fish

Abstract

Concern about leakage of carbon dioxide (CO₂) from deep-sea storage in geological reservoirs is increasing because of its possible adverse effects on marine organisms locally or at nearby coastal areas both in sediment and water column. In the present study, we examined how elevated CO₂ affects various intertidal epibenthic (benthic copepod), intertidal endobenthic (Manila clam and Venus clam), sub-tidal benthic (brittle starfish), and free-living (marine medaka) organisms in areas expected to be impacted by leakage. Acute lethal and sub-lethal effects were detected in the adult stage of all test organisms exposed to varying concentrations of CO₂, due to the associated decline in pH (8.3 to 5.2) during 96-h exposure. However, intertidal organisms (such as benthic copepods and clams) showed remarkable resistance to elevated CO₂, with the Venus clam being the most tolerant (LpH₅₀ = 5.45). Sub-tidal species (such as brittle starfish [LpH₅₀ = 6.16] and marine medaka [LpH₅₀ = 5.91]) were more sensitive to elevated CO₂ compared to intertidal species, possibly because they have fewer defensive capabilities. Of note, the exposure duration might regulate the degree of acute sub-lethal effects, as evidenced by the Venus clam, which showed a time-dependent effect to elevated CO₂. Finally, copper was chosen as a model toxic element to find out the synergistic or antagonistic effects between ocean acidification and metal pollution. Combination of CO₂ and Cu exposure enhances the adverse effects to organisms, generally supporting a synergistic effect scenario. Overall, the significant variation in the degree to which CO₂ adversely affected organisms (viz., working range and strength) was clearly observed, supporting the general concept of species-dependent effects of elevated CO₂.

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Absence of effects of different types of detergents on the cholinesterasic activity and histological markers of mosquitofish ( Gambusia holbrooki ) after a sub-lethal chronic exposure

Abstract

The release of anthropogenic compounds into the aquatic environment has been a particular concern, since some of these substances exhibit biologic activity of different types in non-target species. Among anthropogenic compounds present in the aquatic compartment, detergents are commonly found and may be responsible for physiological modifications in exposed organisms. The impairment of key physiological functions, such as neurotransmission, and tissue damage in some important organs, has been used to assess the effects of several classes of xenobiotics, including detergents, in aquatic organisms. The present study intended to assess the effect of three types of detersive compounds (sodium dodecylsulfate (SDS), benzalkonium chloride (BZC), and Triton X-100 (TX100)) in the acetylcholinesterase activity (AChE) and tissue damage (gills and liver) of Gambusia holbrooki after a chronic exposure to realistic levels of these compounds. SDS, BZC, and TX100 did not cause any significant alteration in AChE. Furthermore, no specific gross morphological changes were also observed in the gills and liver of the exposed individuals. It is possible to conclude that, under ecologically relevant conditions of exposure, both tissue damage and cholinesterasic impairment are not toxicological pathways affected by detergents in G. holbrooki.

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Waste load equilibrium allocation: a soft path for coping with deteriorating water systems

Abstract

Waste load allocation is always regarded as another efficient approach comparing with the technology-based approach to improve the water quality. This paper proposes a bi-level multi-objective optimization model for optimally allocating the waste load of a river basin incorporating some concerns (i) the allocation equity from the regional authority, (ii) maximal benefits from the subareas along the river, and (iii) the Stackelberg-Nash-Cournot equilibrium strategy between the upper and lower decision makers. Especially, a novel Gini coefficient for measuring the load allocation equity is defined by considering the economic level and waste water quantity. The applicability and effectiveness of the proposed model is demonstrated through a practical case based on the Tuojiang River, which is a typical basin with diversified industrial waste discharges in western China. Some operational suggestions are developed to assist the decision makers' cope with deteriorating water systems.

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Factorial Kriging analysis and sources of heavy metals in soils of different land-use types in the Yangtze River Delta of Eastern China

Abstract

The objectives of this study are to analyse the pollution status and spatial correlation of soil heavy metals and identify natural and anthropogenic sources of these heavy metals at different spatial scales. Two hundred and twenty-four soil samples (0–20 cm) were collected and analysed for eight heavy metals (Cd, Hg, As, Cu, Pb, Cr, Zn and Ni) in soils of different land-use types in the Yangtze River Delta of Eastern China. The multivariate methods and factorial Kriging analysis were used to achieve the research objectives. The results indicated that the human and natural effects of different land-use types on the contents of soil heavy metals were different. The Cd, Hg, Cu, Pb and Zn in soils of industrial area were affected by human activities, and the pollution level of these heavy metals in this area was moderate. The Pb in soils of traffic area was affected by human activities, and eight heavy metals in soils of residential area and farmland area were affected by natural factor. The ecological risk status of eight heavy metals in soils of the whole study area was light. The heavy metals in soils showed three spatial scales (nugget effect, short range and long range). At the nugget effect and short range scales, the Cd, Hg, Cu, Pb and Zn in soils were affected by human and natural factors. At three spatial scales, the As, Cr and Ni in soils were affected by soil parent materials.

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