AS VIOLAÇÕES DE DIREITOS HUMANOS PELA INDÚSTRIA EXTRATIVISTA

O presente artigo procura alertar, por meio de revisão bibliográfia, para os efeitosnegativos que a exploração da atividade extrativista provoca nos direitos humanos.Para tanto, esclarece as origens e o que é a indústria extrativista; explora as violaçõespossíveis por meio de alguns exemplos e indica como a comunidade internacionalbusca enfrentar o problema. Reconhece que algumas medidas já foram tomadas,a partir da preocupação com o meio ambiente, mas conclui que em um regimecapitalista se faz necessária a elaboração de um instrumento vinculante para diminuirsensivelmente a ocorrência de violações.Palavras-Chave: Indústria extrativista. direitos humanos. responsabilidade.ABSTRACTThis article seeks to alert, through a bibliographical review, to the negative effects thatexploitation of the extractive activity causes on human rights. To do so, it clarifis theorigins and what the extractive industry is; explores the possible violations throughsome examples and indicates how the international community seeks to address theproblem. It acknowledges that some measures have already been taken, based onconcern for the environment, but concludes that in a capitalist regime it is necessaryto draw up a binding instrument to signifiantly reduce the occurrence of violations.Keywords: Extractive industry. human rights. responsibility

Identification of a Twelve-microRNA Signature with Prognostic Value in Stage II Microsatellite Stable Colon Cancer

Simple Summary Colorectal cancer (CRC) is one of the most prevalent cancers, and approximately a quarter of patients diagnosed at stage II exhibit a significant risk of recurrence. In this study, we successfully identified a microRNA (miRNA) signature allowing the recognition of patients at high recurrence risk. The validity of these findings has been confirmed through an entirely separate group of patients diagnosed with stage II microsatellite stability (MSS) colon adenocarcinoma (COAD). Most of the miRNAs present in the signature have demonstrated prognostic relevance in various other cancer types. Upon examining their gene targets, we discovered that some of these miRNAs are intricately involved in pivotal pathways of cancer progression. We aimed to identify and validate a set of miRNAs that could serve as a prognostic signature useful to determine the recurrence risk for patients with COAD. Small RNAs from tumors of 100 stage II, untreated, MSS colon cancer patients were sequenced for the discovery step. For this purpose, we built an miRNA score using an elastic net Cox regression model based on the disease-free survival status. Patients were grouped into high or low recurrence risk categories based on the median value of the score. We then validated these results in an independent sample of stage II microsatellite stable tumor tissues, with a hazard ratio of 3.24, (CI95% = 1.05-10.0) and a 10-year area under the receiver operating characteristic curve of 0.67. Functional analysis of the miRNAs present in the signature identified key pathways in cancer progression. In conclusion, the proposed signature of 12 miRNAs can contribute to improving the prediction of disease relapse in patients with stage II MSS colorectal cancer, and might be useful in deciding which patients may benefit from adjuvant chemotherapy

Fears and beliefs of people living with rheumatoid arthritis : a systematic literature review

Objective: To assess the main fears and beliefs of people with rheumatoid arthritis (RA) and their effect on treatment outcomes; Methods: A systematic literature review was conducted in Pubmed/Medline; original articles published up to May 2017, reporting fears and/or beliefs of adult patients with RA were analyzed. Fears and beliefs were collected by two independent researchers and grouped into categories. Results: Among 474 references identified, 84 were analyzed, corresponding to 24,336 RA patients. Fears were reported in 38.4% of the articles (N = 32/84): most studies described fears related to pharmacological therapy (50.0%, N = 16/32) and fear of disability (28.1%, N = 9/32). Beliefs were reported in 88.0% of articles (N = 74/84) and were found to moderate the patient-perceived impact of RA in 44.6% (N = 33/74), mainly the emotional impact (18.9%, N = 14/74); measures of function, quality of life, fatigue and pain were also found to be affected by patients’ beliefs in 8.1% (N = 6/74), 6.8% (N = 5/74), 2.7% (N = 2/74) and 2.7% (N = 2/74) of the articles, respectively. Beliefs about therapy were linked to adherence in 17.6% of articles (N = 13/74) and beliefs about cause of RA predicted coping patterns in 12.2% of publications (N = 9/74). Only 9.5% (N = 8/84) of articles reported fears and/or beliefs of patients living outside Europe and North America: there was only one work which recruited patients in Latin America and no article included patients from Africa. Conclusion: In RA, patients’ beliefs are linked to impact of disease and non-adherence. Further research is needed on fears/ beliefs of patients living outside Europe and North America

Colon-specific eQTL analysis to inform on functional SNPs

BACKGROUND: Genome-wide association studies on colorectal cancer have identified more than 60 susceptibility loci, but for most of them there is no clear knowledge of functionality or the underlying gene responsible for the risk modification. Expression quantitative trail loci (eQTL) may provide functional information for such single nucleotide polymorphisms (SNPs). METHODS: We have performed detailed eQTL analysis specific for colon tissue on a series of 97 colon tumours, their paired adjacent normal mucosa and 47 colon mucosa samples donated by healthy individuals. R package MatrixEQTL was used to search for genome-wide cis-eQTL and trans-eQTL fitting linear models adjusted for age, gender and tissue type to rank transformed expression data. RESULTS: The cis-eQTL analyses has revealed 29,073 SNP-gene associations with permutation-adjusted P-values < 0.01. These correspond to 363 unique genes. The trans-eQTL analysis identified 10,665 significant SNP-gene associations, most of them in the same chromosome, further than 1 Mb of the gene. We provide a web tool to search for specific SNPs or genes. The tool calculates Pearson or Spearman correlation, and allows to select tissue type for analysis. Data and plots can be exported. CONCLUSIONS: This resource should be useful to prioritise SNPs for further functional studies and to identify relevant genes behind identified loci

Lung metastases share common immune features regardless of primary tumor origin

Background: Only certain disseminated cells are able to grow in secondary organs to create a metastatic tumor. Under the hypothesis that the immune microenvironment of the host tissue may play an important role in this process, we have categorized metastatic samples based on their immune features. Methods: Gene expression data of metastatic samples (n=374) from four secondary sites (brain, bone, liver and lung) were used to characterize samples based on their immune and stromal infiltration using gene signatures and cell quantification tools. A clustering analysis was done that separated metastatic samples into three different immune categories: high, medium and low. Results: Significant differences were found between the immune profiles of samples metastasizing in distinct organs. Metastases in lung showed a higher immunogenic score than metastases in brain, liver or bone, regardless of their primary site of origin. Also, they preferentially clustered in the high immune group. Samples in this cluster exhibited a clear inflammatory phenotype, higher levels of immune infiltrate, overexpression of programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) pathways and upregulation of genes predicting clinical response to programmed cell death protein 1 (PD-1) blockade (T-cell inflammatory signature). A decision tree algorithm was used to select CD74 as a biomarker that identify samples belonging to this high-immune subtype of metastases, having specificity of 0.96 and sensitivity of 1. Conclusions: We have found a group of lung-enriched metastases showing an inflammatory phenotype susceptible to be treated with immunotherapy

Community-based screening enhances hepatitis B virus linkage to care among West African migrants in Spain

Hepatitis B virus; Community approach; Screening programsVirus de l'hepatitis B; Abordatge comunitari; Programes de deteccióVirus de la hepatitis B; Abordaje comunitario; Programas de detecciónBackground: Chronic infection with HBV is responsible for >50% of all hepatocellular cancer cases globally and disproportionately affects sub-Saharan African (sSA) countries. Migration from these countries to Europe has increased substantially in recent years, posing unique challenges to health systems. The aim of this study was to carry out a community-based intervention to increase HBV screening, vaccination, and linkage to care among sSA migrants in Catalonia, Spain. Methods:This was a prospective cohort study. Participants ≥18 years were offered community-based HBV screening between 20/11/20 and 21/01/22. Rapid HBV testing and blood sample collection utilizing plasma separation cards were carried out and linkage to care was offered to all participants. HBV vaccination and post-test counseling were performed at a second visit in the community. The main outcome was the odds of those with current HBV infection being successfully linked to hepatology. Rates of completing the care cascade of this model were analyzed. Results: In the present study, 444 people undergo screening, with 50.6% of participants showing evidence of past or current HBV infection, including an HBsAg prevalence of 9.2%. Migrants with current HBV infection exhibit 5.2 times higher odds of successful linkage to care compared to those in need of post-test counseling or vaccination. The study achieves a successful linkage to care rate of 72% for all participants, with specialist appointments arranged within 15.5 days.Conclusions:This community-based HBV screening program provides evidence of a successful model for identifying and providing care, including vaccination, to west African migrants at high risk of HBV infection who may otherwise not engage in care.Antecedents: La infecció crònica pel VHB és responsable del >50% de tots els casos de càncer hepatocel·lular a nivell mundial i afecta desproporcionadament els països de l'Àfrica subsahariana (SAS). La migració d'aquests països a Europa ha augmentat substancialment en els últims anys, plantejant reptes únics per als sistemes de salut. L'objectiu d'aquest estudi va ser dur a terme una intervenció basada en la comunitat per augmentar la detecció del VHB, la vacunació i la vinculació amb l'atenció entre els migrants de SSA a Catalunya, Espanya. Mètodes: Es tractava d'un estudi de cohort prospectiu. Als participants ≥18 anys se'ls va oferir un cribratge comunitari del VHB entre el 20/11/20 i el 21/01/22. Es van dur a terme proves ràpides de VHB i recollida de mostres de sang mitjançant targetes de separació de plasma i es va oferir vinculació a l'atenció a tots els participants. La vacunació contra el VHB i l'assessorament post-test es van realitzar en una segona visita a la comunitat. El resultat principal van ser les probabilitats que les persones amb infecció actual pel VHB estiguin vinculades amb èxit a l'hepatologia. Es van analitzar les taxes de completar la cascada assistencial d'aquest model. Resultats: En el present estudi, 444 persones se sotmeten a cribratge, amb el 50.6% dels participants que mostren evidència d'infecció passada o actual pel VHB, inclosa una prevalença de VHB del 9.2%. Els migrants amb infecció actual pel VHB presenten 5,2 vegades més probabilitats d'èxit en l'atenció en comparació amb aquells que necessiten assessorament o vacunació post-prova. L'estudi aconsegueix una taxa de vinculació reeixida a l'atenció del 72% per a tots els participants, amb cites amb especialistes concertades en un termini de 15,5 dies. Conclusions: Aquest programa de cribratge del VHB basat en la comunitat proporciona proves d'un model reeixit per identificar i proporcionar atenció, inclosa la vacunació, als migrants de l'Àfrica occidental amb alt risc d'infecció pel VHB que d'altra manera podrien no dedicar-se a l'atenció.C.A.P., J.V.L. and Lv.S. acknowledge support to ISGlobal from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and from the Government of Catalonia through the “CERCA Program”. C.A.P. acknowledges support from the Secretaria d’Universitats i Recerca de la Generalitat de Catalunya and the European Social Fund as an AGAUR-funded PhD fellow. E.M. thanks the CERCA Program/Generalitat de Catalunya for their support to the Germans Trias i Pujol Research Institute (IGTP). This study was carried out by ISGlobal with competitive funding through the Gilead Sciences global HBV-CARE program (IN-ES-988–5799)

Acute tubulointerstitial nephritis induced by checkpoint inhibitors versus classical acute tubulointerstitial nephritis : are they the same disease?

The incidence of acute tubulointerstitial nephritis (ATIN) related to drugs has dramatically increased over recent years. A new subtype of ATIN, apparently different from classical drug-related ATIN, has emerged that has been related to the administration of immune checkpoint inhibitors (ICIs). We investigated these differences between ICI-related ATIN (ICI ATIN) and non-ICI-related ATIN in terms of clinical features, response to treatment with steroids and the evolution of kidney function. A total of 47 patients diagnosed with ATIN from two centres were recruited. Of these, 13 patients presented with ATIN during ICI treatment and 34 were diagnosed with ATIN attributed to other drugs. The main demographic, clinical and analytical variables such as gender, age and current medication were recorded. The type of malignancy, oncological treatment, ICI dose and presence of extrarenal immune-related adverse events were also reviewed. Renal biopsy diagnosis, time to drug withdrawal and ATIN-specific treatment, as well as laboratory data during follow-up, were also studied. Patients diagnosed with ICI ATIN presented with lower creatinine (ICI ATIN 3.8 ± 1.03 versus classical ATIN 5.98 ± 4.15 mg/dL, P = 0.007) at diagnosis and higher urinary leucocyte counts (ICI ATIN 263.2 ± 418.04 versus classical ATIN 133.55 ± 284.62, P = 0.048) compared with patients with non-ICI-related ATIN. Time from initiation of the culprit drug to ATIN diagnosis was longer in patients with ICI ATIN than in those with classical ATIN (197.07 ± 184.99 versus 114.4 ± 352.16 days, P = 0.006). In addition, during follow-up, the slope of decreasing creatinine over time was lower for ICI ATIN compared with non-ICI-related ATIN. In this study, we analysed differences between ICI ATIN and classical ATIN. We found that patients with ICI ATIN presented with a larger latency period after culprit drug initiation, milder acute kidney injury and slower creatinine amelioration compared with those with classical ATIN. These results may, in part, be ascribed to potential differences in the pathological mechanisms involved in ATIN development, suggesting that ICI and classical ATIN may be different diseases with similar renal histologies

Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer

Background: A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient's gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response. Methods: A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software). Results: Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue. Conclusions: The systems-level approach provides new insights into the micro-ecology of colorectal tumorogenesis. Disrupting this intricate molecular network of cell-cell communication and pro-inflammatory microenvironment could be a therapeutic target in CRC patient

Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response

Telomeres are repetitive sequences (TTAGGG) located at the end of chromosomes. Telomeres progressively shorten with each cell replication cycle, ultimately leading to chromosomal instability and loss of cell viability. Telomere length anomaly appears to be one of the earliest and most prevalent genetic alterations in malignant transformation. Here we aim to estimate telomere length from whole-exome sequencing data in colon tumors and normal colonic mucosa, and to analyze the potential association of telomere length with clinical factors and gene expression in colon cancer. Reads containing at least five repetitions of the telomere sequence (TTAGGG) were extracted from the raw sequences of 42 adjacent normal-tumor paired samples. The number of reads from the tumor sample was normalized to build the Tumor Telomere Length Ratio (TTLR), considered an estimation of telomere length change in the tumor compared to the paired normal tissue. We evaluated the associations between TTLR and clinical factors, gene expression and copy number (CN) aberrations measured in the same tumor samples. Colon tumors showed significantly shorter telomeres than their paired normal samples. No significant association was observed between TTLR and gender, age, tumor location, prognosis, stromal infiltration or molecular subtypes. The functional gene set enrichment analysis showed pathways related to immune response significantly associated with TLLR. By extracting a relative measure of telomere length from whole-exome sequencing data, we have assessed that colon tumor cells predominantly shorten telomeres, and this alteration is associated with expression changes in genes related to immune response and inflammation in tumor cells