Heparan sulfate glycosaminoglycans: (un)expected allies in cancer clinical management

In an era when cancer glycobiology research is exponentially growing, we are witnessing a progressive translation of the major scientific findings to the clinical practice with the overarching aim of improving cancer patients’ management. Many mechanistic cell biology studies have demonstrated that heparan sulfate (HS) glycosaminoglycans are key molecules responsible for several molecular and biochemical processes, impacting extracellular matrix properties and cellular functions. HS can interact with a myriad of different ligands, and therefore, hold a pleiotropic role in regulating the activity of important cellular receptors and downstream signalling pathways. The aberrant expression of HS glycan chains in tumours determines main malignant features, such as cancer cell proliferation, angiogenesis, invasion and metastasis. In this review, we devote particular attention to HS biological activities, its expression profile and modulation in cancer. Moreover, we highlight HS clinical potential to improve both diagnosis and prognosis of cancer, either as HS-based biomarkers or as therapeutic targets.This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and by the grant POCI-01-0145-FEDER-028489 (to A.M.). J.P. and C.M. are funded by FCT PhD scholarships SFRH/BD/137319/2018 and 2020.06412.BD, respectively. The APC was funded by FCT grant POCI-01-0145-FEDER-028489. The authors acknowledge the support of the COST Action CA18103 INNOGLY

High Quality Long-Term CD4+ and CD8+ Effector Memory Populations Stimulated by DNA-LACK/MVA-LACK Regimen in Leishmania major BALB/c Model of Infection

Heterologous vaccination based on priming with a plasmid DNA vector and boosting with an attenuated vaccinia virus MVA recombinant, with both vectors expressing the Leishmania infantum LACK antigen (DNA-LACK and MVA-LACK), has shown efficacy conferring protection in murine and canine models against cutaneus and visceral leishmaniasis, but the immune parameters of protection remain ill defined. Here we performed by flow cytometry an in depth analysis of the T cell populations induced in BALB/c mice during the vaccination protocol DNA-LACK/MVA-LACK, as well as after challenge with L. major parasites. In the adaptive response, there is a polyfunctional CD4+ and CD8+ T cell activation against LACK antigen. At the memory phase the heterologous vaccination induces high quality LACK-specific long-term CD4+ and CD8+ effector memory cells. After parasite challenge, there is a moderate boosting of LACK-specific CD4+ and CD8+ T cells. Anti-vector responses were largely CD8+-mediated. The immune parameters induced against LACK and triggered by the combined vaccination DNA/MVA protocol, like polyfunctionality of CD4+ and CD8+ T cells with an effector phenotype, could be relevant in protection against leishmaniasis

Serious fungal infections in Portugal

There is a lack of knowledge on the epidemiology of fungal infections worldwide because there are no reporting obligations. The aim of this study was to estimate the burden of fungal disease in Portugal as part of a global fungal burden project. Most published epidemiology papers reporting fungal infection rates from Portugal were identified. Where no data existed, specific populations at risk and fungal infection frequencies in those populations were used in order to estimate national incidence or prevalence, depending on the condition. An estimated 1,510,391 persons develop a skin or nail fungal infection each year. The second most common fungal infection in Portugal is recurrent vulvovaginal candidiasis, with an estimated 150,700 women (15-50 years of age) suffering from it every year. In human immunodeficiency virus (HIV)-infected people, oral or oesophageal candidiasis rates were estimated to be 19.5 and 16.8/100,000, respectively. Candidaemia affects 2.19/100,000 patients, in a total of 231 cases nationally. Invasive aspergillosis is less common than in other countries as chronic obstructive pulmonary disease (COPD) is uncommon in Portugal, a total of 240 cases annually. The estimated prevalence of chronic pulmonary aspergillosis after tuberculosis (TB) is 194 cases, whereas its prevalence for all underlying pulmonary conditions was 776 patients. Asthma is common (10% in adults) and we estimate 16,614 and 12,600 people with severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis, respectively. Sixty-five patients develop Pneumocystis pneumonia in acquired immune deficiency syndrome (AIDS) and 13 develop cryptococcosis. Overall, we estimate a total number of 1,695,514 fungal infections starting each year in Portugal.info:eu-repo/semantics/publishedVersio

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.info:eu-repo/semantics/publishedVersio

Impacto de un programa intervención em alunos del segundo ciclo

O objetivo do presente estudo consistiuem avaliar um programa de intervenção junto a alunos do 2º ciclo de escolaridade nas seguintes dimensões: tomada de decisão, conhecimentos sobre sexualidade, competências sociais, assertividade e autoconceito. Metodologia: Participaram 145 alunos, distribuídos pelos grupos controle e experimental. Os instrumentos utilizados foram: TCU Decision-Making; Questionário de Conhecimentos sobre Sexualidade; Assertion Self-Statement Test- Revised; Questionário de Competências Sociais; Piers-Harris Children’s Self-Concept Scale. Os resultados revelaram diferenças no pós-teste entre os grupos ao nível da sexualidade. Verificaram-se diferenças do pré-teste para o pós-teste no grupo experimental nos níveis da sexualidade, da assertividade e das competências sociais. No grupo experimental encontraram-se associações positivas entre tomada de decisão, competências sociais e assertividade, bem como entre sexualidade, competências sociais e autoconceito, no pós-teste. Os preditores da assertividade no pós-teste foram tomada de decisão, sexualidade e competências sociais. Como conclusão, os resultados enfatizam a importância de intervenção junto a adolescentes, particularmente na tomada de decisão, na sexualidade e nas competências sociais. Palavras-chave: Habilidades sociais, sexualidade, autoconceito.In this study we evaluate an intervention program in the following dimensions: Decision Making, Knowledge on Sexuality, Social Skills, Assertiveness and Self-Concept with students in 5th and 6th grade. Methodology: 145 students participated in the study divided by control and experimental group. The instruments used were: Decision-Making TCU, Knowledge on Sexuality Questionnaire; Assertion Self-Statement Test-Revised;Social Skills Questionnaire, and Piers-Harris Children's Self- Concept Scale. The results indicate differences at post-test between the groups on knowledge regarding sexuality. There were also differences from pre-test to post-test in the experimental group on knowledge on sexuality, assertiveness and social skills. Positive associations among decision making, social skills and assertiveness were found as well as among knowledge on sexuality, social skills and self-concept, in the experimental group, in the pos-test. Finally, the predictors of assertiveness regarding health behaviors, in the pos-test were: decision making, knowledge regarding sexuality and social skills. The results emphasize the importance of intervention for adolescents in terms of health promotion particularly in decision making, sexuality and social skills.El objetivo del presente estudio fue evaluar un programa de intervención con alumnos del 2º ciclo de escolaridad en las siguientes dimensiones: Toma de Decisión, Conocimientos sobre Sexualidad, Habilidades Sociales, Asertividad y Autoconcepto. Metodología: Participaron 145 alumnos, distribuidos en grupo control y experimental. Los instrumentos utilizados fueron: TCU Decision-Making; Cuestionario de Conocimientos sobre Sexualidad; AssertionSelf-Statement Test-Revised; Cuestionario de Habilidades Sociais; Piers-Harris Children'sSelf-Concept Scale. Los resultados mostraron diferencias en el post-test entre los grupos en cuanto a la sexualidad. Se verificaron diferencias del pre-test para el post-teste en el grupo experimental, cuanto a sexualidad, asertividad y habilidades sociales. Se encontraron asociaciones positivas entre toma de decisión, habilidades sociales y asertividad, así como entre sexualidad,habilidades sociales yautoconcepto, en el post-test en el grupo experimental. Los predictores de la asertividad en el post-test fueron toma de decisión, sexualidad y habilidades sociales. Los resultados destacan la importancia de la intervención con adolescentes particularmente en la toma de decisiones, sexualidad y habilidades sociales.(undefined

Can parasites adapt to pollutants? A multigenerational experiment with a Daphnia x Metschnikowia model system exposed to the fungicide tebuconazole

There is increasing evidence about negative effects of fungicides on non-target organisms, including parasitic species, which are key elements in food webs. Previous experiments showed that environmentally relevant concentrations of fungicide tebuconazole are toxic to the microparasite Metschnikowia bicuspidata, a yeast species that infects the planktonic crustacean Daphnia spp. However, due to their short-term nature, this and other experimental studies were not able to test if parasites could potentially adapt to these contaminants. Here, we tested if M. bicuspidata parasite can adapt to tebuconazole selective pressure. Infected D. magna lineages were reared under control conditions (no tebuconazole) and environmentally realistic tebuconazole concentrations, for four generations, and their performance was compared in a follow-up reciprocal assay. Additionally, we assessed whether the observed effects were transient (phenotypic) or permanent (genetic), by reassessing parasite fitness after the removal of selective pressure. Parasite fitness was negatively affected throughout the multigenerational exposure to the fungicide: prevalence of infection and spore load decreased, whereas host longevity increased, in comparison to control (naive) parasite lineages. In a follow-up reciprocal assay, tebuconazole-conditioned (TEB) lineages performed worse than naive parasite lineages, both in treatments without and with tebuconazole, confirming the cumulative negative effect of tebuconazole. The underperformance of TEB lineages was rapidly reversed after removing the influence of the selective pressure (tebuconazole), demonstrating that the costs of prolonged exposure to tebuconazole were phenotypic and transient. The microparasitic yeast M. bicuspidata did not reveal potential for rapid evolution to an anthropogenic selective pressure; instead, the long-term exposure to tebuconazole was hazardous to this non-target species. These findings highlight the potential environmental risks of azole fungicides on non-target parasit- This work was supported by the European Regional Development Fund (programmes COMPETE2020 and PT2020) and by National Funds (Portuguese Science Foundation - FCT, I.P.), through the strategic programmes UID/AMB/50017/2013 and UID/BIA/04050/2019 (POCI-01-0145-FEDER-007569), as well as by the research projects FunG-Eye (POCI-01-0145-FEDER-029505) and EcoAgriFood (NORTE-01-0145-FEDER-000009). Part of the work presented here was developed during the PhD of Ana P. Cuco, who was supported by FCT (PhD grant SFRH/BD/81661/2011). JW was supported by Beethoven Life-1 grant from the German Science Foundation and Polish National Science Center (WO 1587/9-1). Nelson Abrantes is the recipient of an individual postdoctoral research contract (CEECIND/01653/2017)

Enhancing sampling design in mist-net bat surveys by accounting for sample size optimization

The advantages of mist-netting, the main technique used in Neotropical bat community studies to date, include logistical implementation, standardization and sampling representativeness. Nonetheless, study designs still have to deal with issues of detectability related to how different species behave and use the environment. Yet there is considerable sampling heterogeneity across available studies in the literature. Here, we approach the problem of sample size optimization. We evaluated the common sense hypothesis that the first six hours comprise the period of peak night activity for several species, thereby resulting in a representative sample for the whole night. To this end, we combined re-sampling techniques, species accumulation curves, threshold analysis, and community concordance of species compositional data, and applied them to datasets of three different Neotropical biomes (Amazonia, Atlantic Forest and Cerrado). We show that the strategy of restricting sampling to only six hours of the night frequently results in incomplete sampling representation of the entire bat community investigated. From a quantitative standpoint, results corroborated the existence of a major Sample Area effect in all datasets, although for the Amazonia dataset the six-hour strategy was significantly less species-rich after extrapolation, and for the Cerrado dataset it was more efficient. From the qualitative standpoint, however, results demonstrated that, for all three datasets, the identity of species that are effectively sampled will be inherently impacted by choices of sub-sampling schedule. We also propose an alternative six-hour sampling strategy (at the beginning and the end of a sample night) which performed better when resampling Amazonian and Atlantic Forest datasets on bat assemblages. Given the observed magnitude of our results, we propose that sample representativeness has to be carefully weighed against study objectives, and recommend that the trade-off between logistical constraints and additional sampling performance should be carefully evaluated

Assessment of the genetic risks of a metallic alloy used in medical implants

The use of artificial implants provides a palliative or permanent solution for individuals who have lost some bodily function through disease, an accident or natural wear. This functional loss can be compensated for by the use of medical devices produced from special biomaterials. Titanium alloy (Ti-6Al-4V) is a well-established primary metallic biomaterial for orthopedic implants, but the toxicity of the chemical components of this alloy has become an issue of concern. In this work, we used the MTT assay and micronucleus assay to examine the cytotoxicity and genotoxicity, respectively, of an extract obtained from this alloy. The MTT assay indicated that the mitochondrial activity and cell viability of CHO-K1 cells were unaffected by exposure to the extract. However, the micronucleus assay revealed DNA damage and an increase in micronucleus frequency at all of the concentrations tested. These results show that ions released from Ti-6Al-4V alloy can cause DNA and nuclear damage and reinforce the importance of assessing the safety of metallic medical devices constructed from biomaterials