Synchronous bilateral Warthin's tumours of the parotid glands: a case report

Warthin's tumour is the most frequent monomorphic adenoma of the major salivary glands, representing about 2-15% of all parotid tumours. Most of the multifocal Warthin's tumours are unilateral, whereas bilateral Warthin's tumours are far less common; bilateral Warthin's tumours are metachronous with few synchronous cases having been described in the literature. The Authors present an interesting case of simultaneously occurring bilateral Warthin's tumours growing in the parotid glands

The deep equatorial ocean circulation in wind-forced numerical solutions

We perform eddy-resolving and high-vertical-resolution numerical simulations of the circulation in an idealized equatorial Atlantic Ocean in order to explore the formation of the deep equatorial circulation (DEC) in this basin. Unlike in previous studies, the deep equatorial intraseasonal variability (DEIV) that is believed to be the source of the DEC is generated internally by instabilities of the upper ocean currents. Two main simulations are discussed: Solution 1, configured with a rectangular basin and with wind forcing that is zonally and temporally uniform; and Solution 2, with realistic coastlines and with an annual cycle of wind forcing varying zonally. Somewhat surprisingly, Solution 1 produces the more realistic DEC: The large-vertical-scale currents (Equatorial Intermediate Currents or EICs) are found over a large zonal portion of the basin, and the small-vertical-scale equatorial currents (Equatorial Deep Jets or EDJs) form low-frequency, quasi-resonant, baroclinic equatorial basin modes with phase propagating mostly downward, consistent with observations. We demonstrate that both types of currents arise from the rectification of DEIV, consistent with previous theories. We also find that the EDJs contribute to maintaining the EICs, suggesting that the nonlinear energy transfer is more complex than previously thought. In Solution 2, the DEC is unrealistically weak and less spatially coherent than in the first simulation probably because of its weaker DEIV. Using intermediate solutions, we find that the main reason for this weaker DEIV is the use of realistic coastlines in Solution 2. It remains to be determined, what needs to be modified or included to obtain a realistic DEC in the more realistic configuration

On the width of the equatorial deep jets

The equatorial deep jets (EDJ) are a striking feature of the equatorial ocean circulation. In the Atlantic Ocean, the EDJ are associated with a vertical scale of between 300 and 700 m, a time scale of roughly 4.5 years and upward energy propagation to the surface. It has been found that the meridional width of the EDJ is roughly 1.5 times larger than expected based on their vertical scale. Here we use a shallow water model for a high order baroclinic vertical normal mode to argue that mixing of momentum along isopycnals can explain the enhanced width. A lateral eddy viscosity of 300 m2 s−1 10 is found to be sufficient to account for the width implied by observations

Influence of rainfall on E. coli concentrations in clams: results of collaboration between competent health authority and producers’ association in the Province of Fermo (Italy)

The Area Vasta di Fermo (the competent health authority of the Marche Region), in collaboration with the local Producers’ Association conducted a series of studies on the presence of E. coli as an indicator of faecal contamination in the environment, in shellfish and in fishery waters, and on the factors that can affect their presence. These studies, carried out from 2008 to 2011, included an assessment of the currents along the coast, of the precipitations, and data from the monitoring of E. coli on shellfish harvested in the collection areas were examined. The results showed that in most cases, small concentrations of microorganisms in shellfish corresponded to little or no precipitations, while an increase in the levels of E. coli was preceded by more or less abundant rainfalls. The conclusions suggest that it is advisable to carry out a more detailed risk analysis which should take into account the above-mentioned factors. Furthermore, monitoring alone based on the determination of indicator organisms, especially when carried out as a single analysis or with a small number of E. coli determinations, does not provide a satisfactory indication of safety. The regional surveillance plans should be applied timely and rigorously, together with on-site investigations aimed at identifying changes that can affect the presence of E. coli in shellfish. Food business operators themselves could implement good manufacturing practices to verify whether the microbiological parameters are within the prescribed limits after rainfalls, especially if heavy

Hodgkin's lymphoma: The pathologist's viewpoint

Despite its well known histological and clinical features, Hodgkin's lymphoma (HL) has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics, histogenesis, and possible mechanisms of lymphomagenesis. There is complete consensus on the B cell derivation of the tumour in most cases, and on the relevance of Epstein-Barr virus infection and defective cytokinesis in at least a proportion of patients. The REAL/WHO classification recognises a basic distinction between lymphocyte predominance HL (LP-HL) and classic HL (CHL), reflecting the differences in clinical presentation and behaviour, morphology, phenotype, and molecular features. CHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, with mixed cellularity, and lymphocyte depleted. The borders between CHL and anaplastic large cell lymphoma have become sharper, whereas those between LP-HL and T cell rich B cell lymphoma remain ill defined. Treatments adjusted to the pathobiological characteristics of the tumour in at risk patients have been proposed and are on the way to being applied

New somatic TERT promoter variants enhance the Telomerase activity in Glioblastoma

The catalytic activity of human Telomerase Reverse Transcriptase (TERT) compensates for the loss of telomere length, eroded during each cell cycle, to ensure a correct division of stem and germinal cells. In human tumors, ectopic TERT reactivation, most frequently due to hotspot mutations in the promoter region (TERTp), i.e. c.1-124 C > T, c.1-146 C > T, confers a proliferative advantage to neoplastic cells. In gliomas, TERTp mutations (TERTpmut) mainly occur in oligodendroglioma and glioblastoma. We screened, for TERTp hotspot mutations, 301 adult patients with gliomas and identified heterozygous mutations in 239 cases: 94% of oligodendroglioma, 85% of glioblastoma, and 37.5% of diffuse/anaplastic astrocytoma. Besides the recurrent c.1-124 C > T and c.1-146 C > T, two cases of glioblastoma harbored novel somatic TERTp variants, which consisted of a tandem duplications of 22 nucleotides, i.e. a TERTp c.1-100_1-79dup and TERTp c.1-110_1-89, both located downstream c.1-124 C > T and c.1-146 C > T. In silico analysis predicted the formation of 119 and 108 new transcription factor's recognition sites for TERTp c.1-100_1-79dup and TERTp c.1-110_1-89, respectively. TERTp duplications (TERTpdup) mainly affected the binding capacity of two transcription factors' families, i.e. the members of the E-twenty-six and the Specificity Protein/Krüppel-Like Factor groups. In fact, these new TERTpdup significantly enhanced the E-twenty-six transcription factors' binding capacity, which is also typically increased by the two c.1-124 C > T/c.1-146 C > T hotspot TERTpmut. On the other hand, they were distinguished by enhanced affinity for the Krüppel proteins. The luciferase assay confirmed that TERTpdup behaved as gain-of-function mutations causing a 2,3-2,5 fold increase of TERT transcription. The present study provides new insights into TERTp mutational spectrum occurring in central nervous system tumors, with the identification of new recurrent somatic gain-of-function mutations, occurring in 0.8% of glioblastoma IDH-wildtype

Short-term variability in euphotic zone biogeochemistry and primary productivity at Station ALOHA : a case study of summer 2012

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 29 (2015): 1145–1164, doi:10.1002/2015GB005141.Time-series observations are critical to understand the structure, function, and dynamics of marine ecosystems. The Hawaii Ocean Time-series program has maintained near-monthly sampling at Station ALOHA (22°45′N, 158°00′W) in the oligotrophic North Pacific Subtropical Gyre (NPSG) since 1988 and has identified ecosystem variability over seasonal to interannual timescales. To further extend the temporal resolution of these near-monthly time-series observations, an extensive field campaign was conducted during July–September 2012 at Station ALOHA with near-daily sampling of upper water-column biogeochemistry, phytoplankton abundance, and activity. The resulting data set provided biogeochemical measurements at high temporal resolution and documents two important events at Station ALOHA: (1) a prolonged period of low productivity when net community production in the mixed layer shifted to a net heterotrophic state and (2) detection of a distinct sea-surface salinity minimum feature which was prominent in the upper water column (0–50 m) for a period of approximately 30 days. The shipboard observations during July–September 2012 were supplemented with in situ measurements provided by Seagliders, profiling floats, and remote satellite observations that together revealed the extent of the low productivity and the sea-surface salinity minimum feature in the NPSG.NOAA Climate Observation Division; National Science Foundation (NSF) Center for Microbial Oceanography: Research and Education (C-MORE) Grant Numbers: EF0424599, OCE-1153656, OCE-1260164; Gordon and Betty Moore Foundation Marine Microbiology Investigator2016-02-1

Novel NPM1 exon 5 mutations and gene fusions leading to aberrant cytoplasmic nucleophosmin in AML

Nucleophosmin (NPM1) mutations in acute myeloid leukemia (AML) affect exon 12, but also sporadically affect exons 9 and 11, causing changes at the protein C-terminal end (tryptophan loss, nuclear export signal [NES] motif creation) that lead to aberrant cytoplasmic NPM1 (NPM1c+), detectable by immunohistochemistry. Combining immunohistochemistry and molecular analyses in 929 patients with AML, we found non–exon 12 NPM1 mutations in 5 (1.3%) of 387 NPM1c+ cases. Besides mutations in exons 9 (n = 1) and 11 (n = 1), novel exon 5 mutations were discovered (n = 3). Another exon 5 mutation was identified in an additional 141 patients with AML selected for wild-type NPM1 exon 12. Three NPM1 rearrangements (NPM1/RPP30, NPM1/SETBP1, NPM1/CCDC28A) were detected and characterized among 13 979 AML samples screened by cytogenetic/fluorescence in situ hybridization and RNA sequencing. Functional studies demonstrated that in AML cases, new NPM1 proteins harbored an efficient extra NES, either newly created or already present in the fusion partner, ensuring its cytoplasmic accumulation. Our findings support NPM1 cytoplasmic relocation as critical for leukemogenesis and reinforce the role of immunohistochemistry in predicting AML-associated NPM1 genetic lesions. This study highlights the need to develop new assays for molecular diagnosis and monitoring of NPM1-mutated AML

What do we have to know about PD-L1 expression in prostate cancer? A systematic literature review. part 4: Experimental treatments in pre-clinical studies (cell lines and mouse models)

In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating the effects of various treatments (alone or combined) may discover how to overcome the immunotherapyresistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) to delineate the landscape of pre-clinical studies (including cell lines and mouse models) that tested treatments with effects on PD-L1 signaling in PC. NF-kB, MEK, JAK, or STAT inhibitors on human/mouse, primary/metastatic PC-cell lines variably down-modulated PD-L1-expression, reducing chemoresistance and tumor cell migration. If PC-cells were co-cultured with NK, CD8+ Tcells or CAR-T cells, the immune cell cytotoxicity increased when PD-L1 was downregulated (opposite effects for PD-L1 upregulation). In mouse models, radiotherapy, CDK4/6-inhibitors, and RB deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs may reduce PD-L1 expression. In some PC experimental models, blocking only the PD-1/PD-L1 pathway had limited efficacy in reducing the tumor growth. Anti-tumor effects could be increased by combining the PD-1/PD-L1 blockade with other approaches (inhibitors of tyrosine kinase, PI3K/mTOR or JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223)

What do we have to know about PD-L1 expression in prostate cancer? A systematic literature review. Part 3: PD-L1, intracellular signaling pathways and tumor microenvironment

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells