Natural history and clinical outcome of differentiated thyroid carcinoma: a retrospective analysis of 1503 patients treated at a single institution

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Dimethylsulphide (DMS) emissions from the West Pacific Ocean: a potential marine source for the stratospheric sulphur layer

Sea surface and atmospheric measurements of dimethylsulphide (DMS) were performed during the TransBrom cruise in the western Pacific Ocean between Japan and Australia in October 2009. Air–sea DMS fluxes were computed between 0 and 30 μmol m−2 d−1, which are in agreement with those computed by the current climatology, and peak emissions of marine DMS into the atmosphere were found during the occurrence of tropical storm systems. Atmospheric variability in DMS, however, did not follow that of the computed fluxes and was more related to atmospheric transport processes. The computed emissions were used as input fields for the Lagrangian dispersion model FLEXPART, which was set up with actual meteorological fields from ERA-Interim data and different chemical lifetimes of DMS. A comparison with aircraft in situ data from the adjacent HIPPO2 campaign revealed an overall good agreement between modelled versus observed DMS profiles over the tropical western Pacific Ocean. Based on observed DMS emissions and meteorological fields along the cruise track, the model projected that up to 30 g S per month in the form of DMS, emitted from an area of 6 × 104 m2, can be transported above 17 km. This surprisingly large DMS entrainment into the stratosphere is disproportionate to the regional extent of the area of emissions and mainly due to the high convective activity in this region as simulated by the transport model. Thus, if DMS can cross the tropical tropopause layer (TTL), we suggest that the considerably larger area of the tropical western Pacific Ocean can be a source of sulphur to the stratosphere, which has not been considered as yet

Chemistry and antigerminative activity of essential oils and monoterpenoids from Mediterranean plants

The Mediterranean flora is characterized by the abundance of aromatic plants. The feature differentiating these plants from all others, in spite of the fact that they belong to many different families, is the production of chemically related secondary compounds, the low molecular weight and volatile isoprenoids. This remarkable presence of aromatic species is important in determining the allelopathic potential within this ecosystem. Such plants make a significant contribution to phryganic Mediterranean ecosystems both in terms of species number and biomass. Thus, the essential oils play an important role in this ecological context. Mediating various processes in the frame of an ecosystem, they become indirectly beneficial to the plants, considering their involvement in processes of adaptative character in Mediterranean ecosystem . For this reason, our research group carried out a series of studies on the possible allelopathic properties of aromatic plants that, being rich in active principles, are considered a primary source of potential allelochemicals.The focus of this overview is direct to have an overall idea about the chemistry and antigerminative activity of essential oils of some Mediterranean aromatic plants and their main constituent

Modelling marine emissions and atmospheric distributions of halocarbons and dimethyl sulfide: the influence of prescribed water concentration vs. prescribed emissions

Marine-produced short-lived trace gases such as dibromomethane (CH2Br2), bromoform (CHBr3), methyliodide (CH3I) and dimethyl sulfide (DMS) significantly impact tropospheric and stratospheric chemistry. Describing their marine emissions in atmospheric chemistry models as accurately as possible is necessary to quantify their impact on ozone depletion and Earth's radiative budget. So far, marine emissions of trace gases have mainly been prescribed from emission climatologies, thus lacking the interaction between the actual state of the atmosphere and the ocean. Here we present simulations with the chemistry climate model EMAC (ECHAM5/MESSy Atmospheric Chemistry) with online calculation of emissions based on surface water concentrations, in contrast to directly prescribed emissions. Considering the actual state of the model atmosphere results in a concentration gradient consistent with model real-time conditions at the ocean surface and in the atmosphere, which determine the direction and magnitude of the computed flux. This method has a number of conceptual and practical benefits, as the modelled emission can respond consistently to changes in sea surface temperature, surface wind speed, sea ice cover and especially atmospheric mixing ratio. This online calculation could enhance, dampen or even invert the fluxes (i.e. deposition instead of emissions) of very short-lived substances (VSLS). We show that differences between prescribing emissions and prescribing concentrations (−28 % for CH2Br2 to +11 % for CHBr3) result mainly from consideration of the actual, time-varying state of the atmosphere. The absolute magnitude of the differences depends mainly on the surface ocean saturation of each particular gas. Comparison to observations from aircraft, ships and ground stations reveals that computing the air–sea flux interactively leads in most of the cases to more accurate atmospheric mixing ratios in the model compared to the computation from prescribed emissions. Calculating emissions online also enables effective testing of different air–sea transfer velocity (k) parameterizations, which was performed here for eight different parameterizations. The testing of these different k values is of special interest for DMS, as recently published parameterizations derived by direct flux measurements using eddy covariance measurements suggest decreasing k values at high wind speeds or a linear relationship with wind speed. Implementing these parameterizations reduces discrepancies in modelled DMS atmospheric mixing ratios and observations by a factor of 1.5 compared to parameterizations with a quadratic or cubic relationship to wind spee

Regulatory T-cells in chronic lymphocytic leukemia: actor or innocent bystander?

Abstract: Regulatory T (Treg) cells are now under extensive investigation in chronic lymphocytic leukemia (CLL). This small subset of T-cells has been, in fact, considered to be involved in the pathogenesis and progression of CLL. However, whether Treg dysregulation in CLL plays a key role or it rather represents a simple epiphenomenon is still matter of debate. In the former case, Treg cells could be appealing for targeting therapies. Finally, Treg cells have also been proposed as a prognostic indicator of the disease clinical course

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs

Modelling marine emissions and atmospheric distributions of halocarbons and dimethyl sulfide: The influence of prescribed water concentration vs. prescribed emissions

Marine-produced short-lived trace gases such as dibromomethane (CH$_{2}$Br$_{2}$), bromoform (CHBr$_{3}$), methyliodide (CH$_{3}$I) and dimethyl sulfide (DMS) significantly impact tropospheric and stratospheric chemistry. Describing their marine emissions in atmospheric chemistry models as accurately as possible is necessary to quantify their impact on ozone depletion and Earth’s radiative budget. So far, marine emissions of trace gases have mainly been prescribed from emission climatologies, thus lacking the interaction between the actual state of the atmosphere and the ocean. Here we present simulations with the chemistry climate model EMAC (ECHAM5/MESSy Atmospheric Chemistry) with online calculation of emissions based on surface water concentrations, in contrast to directly prescribed emissions. Considering the actual state of the model atmosphere results in a concentration gradient consistent with model realtime conditions at the ocean surface and in the atmosphere, which determine the direction and magnitude of the computed flux. This method has a number of conceptual and practical benefits, as the modelled emission can respond consistently to changes in sea surface temperature, surface wind speed, sea ice cover and especially atmospheric mixing ratio. This online calculation could enhance, dampen or even invert the fluxes (i.e. deposition instead of emissions) of very short-lived substances (VSLS). We show that differences between prescribing emissions and prescribing concentrations (-28%for CH$_{2}$Br$_{2}$ to +11%for CHBr$_{3}$) result mainly from consideration of the actual, time-varying state of the atmosphere. The absolute magnitude of the differences depends mainly on the surface ocean saturation of each particular gas. Comparison to observations from aircraft, ships and ground stations reveals that computing the air–sea flux interactively leads in most of the cases to more accurate atmospheric mixing ratios in the model compared to the computation from prescribed emissions. Calculating emissions online also enables effective testing of different air–sea transfer velocity (k) parameterizations, which was performed here for eight different parameterizations. The testing of these different k values is of special interest for DMS, as recently published parameterizations derived by direct flux measurements using eddy covariance measurements suggest decreasing k values at high wind speeds or a linear relationship with wind speed. Implementing these parameterizations reduces discrepancies in modelled DMS atmospheric mixing ratios and observations by a factor of 1.5 compared to parameterizations with a quadratic or cubic relationship to wind speed

A globally applicable PCR-based detection and discrimination of BK and JC polyomaviruses

BKV and JCV belong to the Polyomaviridae family and are opportunistic agents associated with complications in immunocompromised individuals. Although a single screening assay for both viruses would be convenient, the diversity of BKV and JCV serotypes and genotypes is a methodological challenge. In this paper, we developed a PCR method able to detect and segregate BKV and JCV, despite these genetic discrepancies. A duplex semi-nested PCR (duplex snPCR) was designed to target a conserved region (639nt-1516nt) within the VP2 gene. In the first PCR, a primer set common to all BKV and JCV serotypes/ genotypes was used, followed by a semi-nested PCR with internal primers for BKV and JCV segregation. The limit of detection of the duplex snPCR was as low as 10 copies of BKV or JCV plasmids/µL. Specific products were observed when JCV and BKV plasmids were mixed in the same reaction. In field sample testing, the duplex snPCR detected and distinguished both viruses in different biological samples. Results were confirmed by Sanger’s sequencing. The geographical complexity of BKV and JCV serotypes and genotypes imposes limits to a simple and universal method that could detect each virus. However, we describe here a sensitive and reliable PCR technique for BKV and JCV diagnosis that overcomes these limitations and could be universally applied

A novel real-time PCR assay for quantitative detection of Campylobacter fetus based on ribosomal sequences

Background: Campylobacter fetus is a pathogen of major concern for animal and human health. The species shows a great intraspecific variation, with three subspecies: C. fetus subsp. fetus, C. fetus subsp. venerealis, and C. fetus subsp. testudinum. Campylobacter fetus fetus affects a broad range of hosts and induces abortion in sheep and cows. Campylobacter fetus venerealis is restricted to cattle and causes the endemic disease bovine genital campylobacteriosis, which triggers reproductive problems and is responsible for major economic losses. Campylobacter fetus testudinum has been proposed recently based on genetically divergent strains isolated from reptiles and humans. Both C. fetus fetus and C. fetus testudinum are opportunistic pathogens for immune-compromised humans. Biochemical tests remain as the gold standard for identifying C. fetus but the fastidious growing requirements and the lack of reliability and reproducibility of some biochemical tests motivated the development of molecular diagnostic tools. These methods have been successfully tested on bovine isolates but fail to detect some genetically divergent strains isolated from other hosts. The aim of the present study was to develop a highly specific molecular assay to identify and quantify C. fetus strains. Results: We developed a highly sensitive real-time PCR assay that targets a unique region of the 16S rRNA gene. This assay successfully detected all C. fetus strains, including those that were negative for the cstA gene-based assay used as a standard for molecular C. fetus identification. The assay showed high specificity and absence of cross-reactivity with other bacterial species. The analytical testing of the assay was determined using a standard curve. The assay demonstrated a wide dynamic range between 102 and 107 genome copies per reaction, and a good reproducibility with small intra- and inter-assay variability. Conclusions: The possibility to characterize samples in a rapid, sensitive and reproducible way makes this assay a good option to establish a new standard in molecular identification and quantification of C. fetus species