Metastatic gallbladder adenocarcinoma with signet-ring cells: A case report

<p>Abstract</p> <p>Introduction</p> <p>Signet-ring cell carcinoma is a rare and aggressive variant of mucinous adenocarcinoma. Only a few cases of gallbladder adenocarcinoma with signet-ring cells have been reported and because of this there is a lack of knowledge about the behavior and biology of this pathology.</p> <p>Case presentation</p> <p>We present the case of a 63-year-old Arab man with gallbladder signet-ring cell adenocarcinoma. He had an elective cholecystectomy and refused chemotherapy. Two months later, a small hepatic metastatic nodule was found, and nine months later he presented with multiple metastases in the liver, lymphatic nodes, both pleuras, peritoneum and subcutaneous tissue.</p> <p>Conclusion</p> <p>The proliferation of signet-ring cells in a gallbladder adenocarcinoma worsens the prognosis of an already adverse neoplasm. New lines of treatment in chemotherapy, such as cisplatin, or new biological therapy, such as monoclonal antibody c-myc oncogene, should be encouraged to improve the survival and life quality of these oncologic patients.</p

Effect of propofol and etomidate on normoxic and chronically hypoxic pulmonary artery

BACKGROUND: Chronic alveolar hypoxia results in sustained arterial constriction, and increase in pulmonary vascular resistance leading to pulmonary artery hypertension (PAHT). The aim of this study was to investigate the effect of propofol and etomidate on pulmonary artery (PA) reactivity in chronically hypoxic (CH) rats, a model of pulmonary arterial hypertension (PAHT), in normoxic animals, and human PA. METHODS: CH rats were maintained 14 days at 380 mmHg pressure in a hypobaric chamber. Human tissue was retrieved from histological lung pieces from patients undergoing resection for carcinoma. Cumulative concentrations of anaesthetics were tested on isolated vascular rings precontracted with phenylephrine (PHE) or 100 mM KCl. Statistical comparisons were done by ANOVA, followed, when needed, by Student t tests with Bonferroni correction as post-hoc tests. RESULTS: In normoxic rat PA, maximal relaxation (R(max)) induced by etomidate and propofol was 101.3 ± 0.8% and 94.0 ± 2.3%, respectively, in KCl-precontracted rings, and 63.3 ± 9.7% and 46.1 ± 9.1%, respectively, in PHE-precontracted rings (n = 7). In KCl-precontracted human PA, R(max )was 84.7 ± 8.6 % and 66.5 ± 11.8%, for etomidate and propofol, respectively, and 154.2 ± 22.4 % and 51.6 ± 15.1 %, respectively, in PHE-precontracted human PA (n = 7). In CH rat PA, the relaxant effect of both anaesthetics was increased in PHE-precontracted and, for etomidate only, in KCl-precontracted PA. In aorta, CH induced no change in the relaxant effect of anaesthetics. CONCLUSION: Propofol and etomidate have relaxant properties in PA from human and normoxic rat. The relaxant effect is specifically accentuated in PA from CH rat, mainly via an effect on the pharmacomechanical coupling. Etomidate appears to be more efficient than propofol at identical concentration, but, taking into account clinical concentrations, etomidate is less potent than propofol, which effect was in the range of clinical doses. Although these findings provide experimental support for the preferential use of etomidate for haemodynamic stability in patients suffering from PAHT, the clinical relevance of the observations requires further investigation

RECCAP2 Future Component: Consistency and Potential for Regional Assessment to Constrain Global Projections

This is the final version. Available from Wiley via the DOI in this record. Data Availability Statement: All CMIP6 model output datasets analyzed during this study are available online at https://esgf-node.llnl.gov/search/cmip6/ and code required to reproduce figures is available at https://github.com/ChrisJones-MOHC/RECCAP2Future_2023 (ChrisJones-MOHC, 2023) and Zenodo at https://doi.org/10.5281/zenodo.8420250.Projections of future carbon sinks and stocks are important because they show how the world's ecosystems will respond to elevated CO2 and changes in climate. Moreover, they are crucial to inform policy decisions around emissions reductions to stay within the global warming levels identified by the Paris Agreement. However, Earth System Models from the 6th Coupled Model Intercomparison Project (CMIP6) show substantial spread in future projections—especially of the terrestrial carbon cycle, leading to a large uncertainty in our knowledge of any remaining carbon budget (RCB). Here we evaluate the global terrestrial carbon cycle projections on a region‐by‐region basis and compare the global models with regional assessments made by the REgional Carbon Cycle Assessment and Processes, Phase 2 activity. Results show that for each region, the CMIP6 multi‐model mean is generally consistent with the regional assessment, but substantial cross‐model spread exists. Nonetheless, all models perform well in some regions and no region is without some well performing models. This gives confidence that the CMIP6 models can be used to look at future changes in carbon stocks on a regional basis with appropriate model assessment and benchmarking. We find that most regions of the world remain cumulative net sources of CO2 between now and 2100 when considering the balance of fossil‐fuels and natural sinks, even under aggressive mitigation scenarios. This paper identifies strengths and weaknesses for each model in terms of its performance over a particular region including how process representation might impact those results and sets the agenda for applying stricter constraints at regional scales to reduce the uncertainty in global projections.European Union’s Horizon 2020European Union’s Horizon 2020European Union’s Horizon 2020Joint UK BEIS/Defra Met Office Hadley Centre Climate ProgrammeCarbonWatch-NZ Endeavour Research ProgrammeSão Paulo Research FoundationSão Paulo Research FoundationSão Paulo Research FoundationNational Science FoundationAndrew Carnegie Fellow ProgramCNPqKorea Ministry of EnvironmentNatural Environment Research Council (NERC)Natural Environment Research Council (NERC)National Environmental Science Progra

An Sp1/Sp3 Binding Polymorphism Confers Methylation Protection

Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is known about the causes of this hypermethylation. We identified RIL as a frequent methylation target in cancer. In search for factors that influence RIL hypermethylation, we found a 12-bp polymorphic sequence around its transcription start site that creates a long allele. Pyrosequencing of homozygous tumors revealed a 2.1-fold higher methylation for the short alleles (P<0.001). Bisulfite sequencing of cancers heterozygous for RIL showed that the short alleles are 3.1-fold more methylated than the long (P<0.001). The comparison of expression levels between unmethylated long and short EBV-transformed cell lines showed no difference in expression in vivo. Electrophorectic mobility shift assay showed that the inserted region of the long allele binds Sp1 and Sp3 transcription factors, a binding that is absent in the short allele. Transient transfection of RIL allele-specific transgenes showed no effects of the additional Sp1 site on transcription early on. However, stable transfection of methylation-seeded constructs showed gradually decreasing transcription levels from the short allele with eventual spreading of de novo methylation. In contrast, the long allele showed stable levels of expression over time as measured by luciferase and ∼2–3-fold lower levels of methylation by bisulfite sequencing (P<0.001), suggesting that the polymorphic Sp1 site protects against time-dependent silencing. Our finding demonstrates that, in some genes, hypermethylation in cancer is dictated by protein-DNA interactions at the promoters and provides a novel mechanism by which genetic polymorphisms can influence an epigenetic state

DNA Methylation Profiles of Primary Colorectal Carcinoma and Matched Liver Metastasis

BACKGROUND: The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear. METHODS: We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM) in three paired primary and metastatic cancers. RESULTS: Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively) (P<.05). When paired primary and metastatic tumors were compared, only MGMT methylation was significantly higher in metastatic cancers (27.4% vs. 13.4%, P = .013), and this difference was due to an increase in methylation density rather than frequency in the majority of cases. MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic samples. The numbers of differentially hypermethylated genes in the liver metastases increased with increasing time between resection of the primary and resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12 paired samples showed that most of these increases were not conserved, and could be explained by differences in methylation density rather than frequency. CONCLUSIONS: Most DNA methylation differences between primary CRCs and matched liver metastasis are due to random variation and an increase in DNA methylation density rather than de-novo inactivation and silencing. Thus, DNA methylation changes occur for the most part before progression to liver metastasis

Desempenho agronômico do feijoeiro com doses de nitrogênio em semeadura e cobertura

Práticas de manejo adequadas e o aumento das doses de nitrogênio têm propiciado incrementos substanciais na produção de grãos do feijoeiro comum; no entanto, em cultivos de inverno e irrigado existem poucos estudos relatando a interferência do uso de doses de N em semeadura e cobertura na produção de grãos. O estudo teve o objetivo de avaliar o efeito da adição de doses crescentes de nitrogênio em semeadura e cobertura no desempenho agronômico do feijoeiro irrigado no período de inverno no Norte do Estado de Minas Gerais. Para tanto, utilizou-se o esquema fatorial 4 x 4 consistindo de quatro doses idênticas de nitrogênio em semeadura e cobertura (0, 40, 80 e 120 kg ha-1). O delineamento estatístico utilizado foi em blocos casualizados com três repetições. Foram avaliadas as características: estande inicial, estande final, número de grãos por vagem, vagem por planta, peso médio de 100 grãos e rendimento de grãos. Não se obteve diferença significativa (p > 0,05) entre doses de N em semeadura e/ou coberta para o número de grãos por vagem nem para o peso de 100 grãos. Considerando apenas a adição de N em semeadura, o número de vagens por planta e o rendimento de grãos se elevaram com o incremento da dose de N até 120 kg ha-1. Apesar da interdependência das doses de N em semeadura e cobertura, acréscimos no rendimento de grãos foram obtidos apenas com a adição de doses de N na semeadura

Soil physical attributes in chemigated banana plantation with wastewater

The feasibility of using sewage wastewater as a water and nutrient source for plants is an alternative to harness agricultural natural resource, observing its influence on the organic matter dynamics and soil energy. Our objective here was to evaluate the effects of applying different doses of effluent from a sewage treatment plant, in Janaúba – MG, Brazil, over the physical attributes of a soil grown with “Prata Anã” banana. From soil sample collection at depths of 0-20, 20-40, and 40-60 cm, we determined the following soil properties: soil density, total porosity, macroporosity, microporosity, organic matter, clay dispersed in water and stability of soil aggregate. The experimental design was in randomized blocks with four repetitions. Wastewater raising doses promoted increase in suspended solids, contributing to macroporosity reduction at 20-40 and 40-60 cm depths; as well as a reduction in organic matter within 0-20 cm layer. Clay dispersal was observed in the depths of 0-20 cm, being derived from an increase in sodium content. Concurrently, there was a reduction of soil aggregate stability.A utilização de água residuária proveniente do tratamento de esgoto, como fonte hídrica e nutricional para as plantas, é uma alternativa para racionalizar o aproveitamento do recurso natural na agricultura, observando-se sua influência sobre a dinâmica da matéria e da energia no solo. O objetivo deste trabalho foi avaliar os efeitos da aplicação de diferentes doses de efluente da estação de tratamento de esgoto de Janaúba - MG, sobre os atributos físicos de um solo cultivado com banana ‘Prata-Anã’. A partir da coleta de amostras de solo, nas profundidades de 0-20; 20-40 e 40-60 cm, foram avaliados os seguintes atributos: densidade do solo, porosidade total, macroporosidade, microporosidade, matéria orgânica, argila dispersa em água e a estabilidade de agregados do solo. O delineamento experimental foi o em blocos casualizados, com quatro repetições. O aumento das doses de água residuária sanitária tratada no solo promove: a) Incremento nos sólidos suspensos aportados ao solo, o que contribui para a redução da macroporosidade nas profundidades de 20-40 e 40-60 cm do solo; b) Redução da matéria orgânica na profundidade de 0-20 cm do solo; c) Aumento do aporte de sódio, o que determina a dispersão de argilas na profundidade de 0-20 cm, e d) Redução da estabilidade de agregados do solo