War exposure and post-traumatic stress as predictors of portuguese colonial war veterans’ physical health

The relationship between war exposure and PTSD has been largely investigated but the impact of the combat experience on physical health has only recently merited attention. The authors investigated the relationship between war exposure, psychological and physical health among 350 Portuguese colonial war veterans. The role of current PTSD symptoms as a mediator of these relationships was also investigated. The results showed that 39% of the veterans met criteria for current PTSD diagnosis and psychological distress was present in half of the sample. Pain, fatigue and sleep problems were the most reported physical symptoms and mental health and gastro-intestinal problems, the most reported illnesses. Combat exposure variables were significant predictors of current health. The results indicated that veterans with higher exposure to war trauma maintained higher current levels of psychological distress and presented more physical health problems and physical symptoms than those less exposed. Mediation analyses showed that current PTSD was a full mediator of the relationship between war exposure and physical health outcomes.The authors wish to thank the Fundação para a Ciência e Tecnologia, grant POCTI (POCTI/ESP/39515/2000), for financing this project. The authors are also grateful for the collaboration of the Associação Portuguesa de Veteranos de Guerra and their aid with the data collection

Pseudomonadota in the oral cavity: a glimpse into the environment-human nexus

The phylum Pseudomonadota is amongst the most represented in the environment, with a comparatively lower prevalence in the human oral cavity. The ubiquity of Pseudomonadota and the fact that the oral cavity is the most likely entry portal of bacteria from external sources underlie the need to better understand its occurrence in the interface environment-humans. Yet, the relevance oral Pseudomonadota is largely underexplored in the scientific literature, a gap that this review aims at addressing by making, for the first time, an overview of the diversity and ecology of Pseudomonadota in the oral cavity. The screening of scientific literature and human microbiome databases unveiled 1328 reports of Pseudomonadota in the oral cavity. Most of these belonged to the classes Beta- and Gammaproteobacteria, mainly to the families Neisseriaceae, Campylobacteriaceae, and Pasteurelaceae. Others also regularly reported include genera such as Enterobacter, Klebsiella, Acinetobacter, Escherichia, Burkholderia, or Citrobacter, whose members have high potential to acquire virulence and antibiotic resistance genes. This review provides evidence that clinically relevant environmental Pseudomonadota may colonize humans via oral cavity. The need for further investigation about Pseudomonadota at the environment-oral cavity interface and their role as vectors potentially involved in virulence and antibiotic resistance transmission is demonstrated. Key points: • Neisseriaceae, Campylobacteriaceae, and Pasteurelaceae are part of the core oral microbiome • Enterobacteriaceae, Acinetobacter, or Burkholderia are frequent in the oral microbiome • Gut dysbiosis may be associated with colonization by ubiquitous oral Pseudomonadota.info:eu-repo/semantics/publishedVersio

A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malaria

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Two malaria parasite species, Plasmodium falciparum (Pf) and P. vivax (Pv) are responsible for most of the disease burden caused by malaria. Vaccine development against this disease has focused mainly on Pf. Whole-sporozoite (WSp) vaccination, targeting pre-erythrocytic (PE) parasite stages, is a promising strategy for immunization against malaria and several PfWSp-based vaccine candidates are currently undergoing clinical evaluation. In contrast, no WSp candidates have been developed for Pv, mainly due to constraints in the production of Pv sporozoites in the laboratory. Recently, we developed a novel approach for WSp vaccination against Pf based on the use of transgenic rodent P. berghei (Pb) sporozoites expressing immunogens of this human-infective parasite. We showed that this platform can be used to deliver PE Pf antigens, eliciting both targeted humoral responses and cross-species cellular immune responses against Pf. Here we explored this WSp platform for the delivery of Pv antigens. As the Pv circumsporozoite protein (CSP) is a leading vaccine candidate antigen, we generated a transgenic Pb parasite, PbviVac, that, in addition to its endogenous PbCSP, expresses PvCSP under the control of a strictly PE promoter. Immunofluorescence microscopy analyses confirmed that both the PbCSP and the PvCSP antigens are expressed in PbviVac sporozoites and liver stages and that PbviVac sporozoite infectivity of hepatic cells is similar to that of its wild-type Pb counterpart. Immunization of mice with PbviVac sporozoites elicits the production of anti-PvCSP antibodies that efficiently recognize and bind to Pv sporozoites. Our results warrant further development and evaluation of PbviVac as a surrogate for WSp vaccination against Pv malaria.A.D. and J.C.S. were supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (U19AI110820 and R01AI141900). A.M.M. acknowledges Fundação para a Ciência e Tecnologia, Portugal (FCT) for Grant PTDC-BBB-BMD-2695-2014. M.P. acknowledges the “la Caixa” Foundation for Grant HR21-848, the GSK OpenLab Foundation for grant TC269, and FCT for grant PTDC-SAU-INF-29550-2017. D.M. acknowledges FCT for grant SFRH/BD/144817/2019.info:eu-repo/semantics/publishedVersio

Telephone-based psychological crisis intervention: the Portuguese experience with COVID-19

Published online: 07 Jun 2020Portugal is one of the European countries that implemented early protective measures in the context of the COVID-19 pandemic. Portugal declared a state of emergency on 18 March, and a set of regional and national preventive public health measures was progressively implemented. Studies on the psychological impact of pandemics show evidence of the negative impact on mental health. Of particular concern are individuals with previous fragility (e.g. personal, family or occupational) and those undergoing life transitions. In this paper, we present a telephone-based psychological crisis intervention that was implemented to provide brief, appropriate, and timely psychological help. This intervention follows standard models of crisis intervention and is structured in five phases and five different intervention modules to take into account the impact of the pandemic on the mental health of specific risk groups. With these support services, we hope to help our community better cope with the immediate impact of the pandemic and to contribute to preventing serious mental health problems in the medium and long term.This study was partially conducted at the Psychology Research Centre (PSI/01662), University of Minho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education (UID/PSI/01662/2019), through the national funds (PIDDAC). We acknowledge Associação de Psicologia da Universidade do Minho (APsi-UMinho) and APsiUMinho collaborators for supporting the telephone-based psychological crisis intervention: Ana Daniela Silva, Ana Isabel Gonçalves, Ana Rita Pereira, Andreia Milhazes, Ângela Ferreira, Alexandra Vieira, Célia Sampaio, Carina Magalhães, Cátia Braga, Delfina Fernandes, Dulce Lopes, Dulce Pinto, Inês Castro, Inês Marques, Gabriela Santana, Joana Andrade, Joana Coutinho, Joana Guimarães, Joana Soares, Joana Teixeira, Joana Torres, João Batista, João Tiago Oliveira, Mariana Leite, Marta Sousa, Patrícia Mendes, Sara Lima, Soraia Mesquita, Teresa Castanho. We would like to thanks P5 and affiliated Psychologists: Liliana Amorim, and Inês Fernandes. We gratefully acknowledge OutSystems for the financial support through OutSystems COVID-19 Community Response Program

THOR is a targetable epigenetic biomarker with clinical implications in breast cancer

Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of death among women worldwide. Early BC is potentially curable, but the mortality rates still observed among BC patients demon‑ strate the urgent need of novel and more efective diagnostic and therapeutic options. Limitless self-renewal is a hallmark of cancer, governed by telomere maintenance. In around 95% of BC cases, this process is achieved by telom‑ erase reactivation through upregulation of the human telomerase reverse transcriptase (hTERT). The hypermethylation of a specifc region within the hTERT promoter, termed TERT hypermethylated oncological region (THOR) has been associated with increased hTERT expression in cancer. However, its biological role and clinical potential in BC have never been studied to the best of our knowledge. Therefore, we aimed to investigate the role of THOR as a biomarker and explore the functional impact of THOR methylation status in hTERT upregulation in BC.info:eu-repo/semantics/publishedVersio

Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers.

INTRODUCTION: Cis-acting regulatory single nucleotide polymorphisms (SNPs) at specific loci may modulate penetrance of germline mutations at the same loci by introducing different levels of expression of the wild-type allele. We have previously reported that BRCA2 shows differential allelic expression and we hypothesize that the known variable penetrance of BRCA2 mutations might be associated with this mechanism. METHODS: We combined haplotype analysis and differential allelic expression of BRCA2 in breast tissue to identify expression haplotypes and candidate cis-regulatory variants. These candidate variants underwent selection based on in silico predictions for regulatory potential and disruption of transcription factor binding, and were functionally analyzed in vitro and in vivo in normal and breast cancer cell lines. SNPs tagging the expression haplotypes were correlated with the total expression of several genes in breast tissue measured by Taqman and microarray technologies. The effect of the expression haplotypes on breast cancer risk in BRCA2 mutation carriers was investigated in 2,754 carriers. RESULTS: We identified common haplotypes associated with differences in the levels of BRCA2 expression in human breast cells. We characterized three cis-regulatory SNPs located at the promoter and two intronic regulatory elements which affect the binding of the transcription factors C/EBPα, HMGA1, D-binding protein (DBP) and ZF5. We showed that the expression haplotypes also correlated with changes in the expression of other genes in normal breast. Furthermore, there was suggestive evidence that the minor allele of SNP rs4942440, which is associated with higher BRCA2 expression, is also associated with a reduced risk of breast cancer (per-allele hazard ratio (HR) = 0.85, 95% confidence interval (CI) = 0.72 to 1.00, P-trend = 0.048). CONCLUSIONS: Our work provides further insights into the role of cis-regulatory variation in the penetrance of disease-causing mutations. We identified small-effect genetic variants associated with allelic expression differences in BRCA2 which could possibly affect the risk in mutation carriers through altering expression levels of the wild-type allele.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Bark anatomy, chemical composition and ethanol-water extract composition of Anadenanthera peregrina and Anadenanthera colubrina

The bark of Anadenanthera peregrina (L.) Speg and Anadenanthera colubrina (Vell.) Brenan were characterized in relation to anatomical and chemical features. The barks were similar and included a thin conducting phloem, a largely dilated and sclerified non-conducting phloem, and a rhyridome with periderms with thin phellem interspersed by cortical tissues. Only small differences between species were observed that cannot be used alone for taxonomic purposes. The summative chemical composition of A. peregrina and A. colubrina was respectively: 8.2% and 7.7% ash; 28.8% and 29.3% extractives; 2.4% and 2.6% suberin; and 18.9% lignin. The monosaccharide composition showed the predominance of glucose (on average 82% of total neutral sugars) and of xylose (9%). The ethanol-water extracts of A. peregrina and A. colubrina barks included a high content of phenolics, respectively: total phenolics 583 and 682 mg GAE/g extract; 148 and 445 mg CE/g extract; tannins 587 and 98 mg CE/g extract. The antioxidant activity was 238 and 269 mg Trolox/g extract. The barks of the Anadenanthera species are a potential source of polar extractives that will represent an important valorization and therefore contribute to improve the overall economic potential and sustainability of A. peregrina and A. colubrinainfo:eu-repo/semantics/publishedVersio

Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma

The historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK-MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8+ T cells with reduced immunosuppressive regulatory T (Treg) cells, while late MYC acquisition in slow progressors was associated with lower CD8+ T cell infiltration and more abundant Treg cells. Single-cell transcriptomics and functional assays defined a high ratio of CD8+ T cells versus Treg cells as a predictor of response to immune checkpoint blockade (ICB). In clinical series, high CD8+ T/Treg cell ratios underlie early progression in untreated smoldering MM, and correlated with early relapse in newly diagnosed patients with MM under Len/Dex therapy. In ICB-refractory MM models, increasing CD8+ T cell cytotoxicity or depleting Treg cells reversed immunotherapy resistance and yielded prolonged MM control. Our experimental models enable the correlation of MM genetic and immunological traits with preclinical therapy responses, which may inform the next-generation immunotherapy trials

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands