National Institute of Health Dr. Ricardo Jorge
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Mental Health of Healthcare Professionals: Two Years of the COVID-19 Pandemic in Portugal
Get PDF(This article belongs to the Special Issue The Psychological Impacts of the COVID-19 Pandemic on Different At-Risk Population Groups)The COVID-19 pandemic increased psychosocial risk factors among healthcare professionals (HCPs). Objective: To characterize Portuguese HCPs mental health (MH), estimate anxiety, depression, post-traumatic stress disorder (PTSD) and burnout symptoms, and identify risk/protective
factors. A cross-sectional online survey and a longitudinal assessment were conducted in 2020 (T0)
and 2021 (T1). Sociodemographic and occupational variables, COVID-19-related experiences and protective behavior data were collected from a non-probabilistic sample of HCPs in Portugal. Symptoms
of anxiety, depression, PTSD, burnout and resilience were assessed using the Portuguese versions
of the Generalized Anxiety Disorder Scale (GAD-7), the Patient Health Questionnaire (PHQ-9), the
Post-traumatic Stress Disorder Checklist (PCL-5), the Shirom–Melamed Burnout Measure (MBSM)
and the Connor–Davidson Resilience Scale (CD-RISC-10), respectively. Risk and protective factors
were identified through simple and multiple logistic regression models. Overall, 2027 participants
answered the survey in T0 and 1843 in T1. The percentage of moderate-to-severe symptoms decreased
from T0 to T1; however, a considerable proportion of HCPs reported symptoms of distress in both
years. Being a woman, working in a COVID-19-treatment frontline position and work–life balance
increased the odds of distress. High resilience, good social/family support, and hobbies/lifestyle
maintenance were found to be protective factors. Globally, our results show that performing as a
HCP during the pandemic may result in long-term effects on MH.Part of this research was funded by Fundação para a Ciência e a Tecnologia (FCT), under
the project SM-COVID19 (Saúde Mental em Tempos de Pandemia COVID-19 | Mental Health during
the COVID-19 Pandemic); grant Ref. 279_596885124.info:eu-repo/semantics/publishedVersio
Pathogenic Escherichia coli, Salmonella spp. and Campylobacter spp. in two Natural Conservation Centers of Wildlife in Portugal: genotypic and phenotypic characterization
Get PDFA coexistência entre humanos e animais selvagens pode aumentar o risco de transmissão direta de agentes patogénicos zoonóticos emergentes ou reemergentes para humanos. Este trabalho teve como objetivo avaliar a ocorrência de três importantes agentes patogénicos de origem alimentar em animais selvagens de dois centros de conservação da vida selvagem, em Portugal. Para tal, foram testadas 132 amostras fecais para a presen- ça de Escherichia coli (E. coli produtora de toxina Shiga (STEC) e não pro- dutora de toxina Shiga (não-STEC)), Salmonella spp. e Campylobacter spp.. Foi realizada a caracterização genotípica (pesquisa de genes de vi- rulência, pesquisa de genes de resistência a antimicrobianos (AMR), se- quenciação total do genoma (WGS)) e fenotípica (serotipagem e perfis de AMR) de todos os isolados de interesse.
No geral, 62 amostras testaram positivo para pelo menos uma das espé- cies analisadas: 27,3% para STEC, 11,4% para não-STEC, 3,0% para Sal- monella spp. e 6,8% para Campylobacter spp. Foi detetada resistência a antimicrobianos em quatro isolados de E. coli e no único isolado de Cam- pylobacter coli. A análise de WGS revelou que 57,7% (30/52) das E. coli patogénicas integram agrupamentos genéticos de isolados fortemente relacionados (muitas vezes envolvendo diferentes espécies de animais), indicando a existência de circulação e transmissão de diferentes estirpes patogénicas de E. coli nas áreas estudadas.
Estes resultados apoiam a ideia de que a saúde dos seres humanos, dos animais e dos ecossistemas são interdependentes, reforçando a importân- cia de uma abordagem One Health (Uma Só Saúde) para melhor monitori- zar e controlar as ameaças em saúde públicaHuman–wildlife coexistence may increase the potential risk of direct transmission of emergent or re-emergent zoonotic pathogens to humans. Intending to assess the occurrence of three important foodborne pathogens in wild animals of two wildlife conservation centers in Portugal. We investigated 132 fecal samples for the presence of pathogenic E. coli (Shiga toxin-producing E. coli (STEC) and non-STEC), Salmonella spp. and Campylobacter spp.. Genotypic characterization (search for virulence and antimicrobial resistance (AMR) genes, Whole-Genome Sequencing (WGS)), as well as phenotypic characterization (serotyping and AMR profiles) of all isolates of interest were performed.
Overall, 62 samples tested positive for at least one of these species: 27.3% for STEC, 11.4% for non-STEC, 3.0% for Salmonella spp. and 6.8% for Campylobacter spp. AMR was detected in four E. coli isolates and in the only Campylobacter coli isolated in this study. WGS analysis revealed that 57.7% (30/52) of pathogenic E. coli integrated genetic clusters of highly closely related isolates (often involving different animal species), supporting the circulation and transmission of different pathogenic E. coli strains in the studied areas.
These results support the idea that the health of humans, animals and ecosystems are interconnected, reinforcing the importance of a One Health approach to better monitor and control public health threats.info:eu-repo/semantics/publishedVersio
Participação de Adolescentes com Paralisia Cerebral no Desporto
No full textA participação no desporto propicia o desenvolvimento de competências
motoras, cognitivas e socioemocionais, impactando positivamente na
saúde, na qualidade de vida e na participação de crianças e jovens. Para
os adolescentes com paralisia cerebral (PC), o envolvimento nestas
atividades pode promover interações positivas com pares, com e sem
deficiência, em contexto desportivo. OBJETIVO
Analisar a participação no desporto de adolescentes com PC na coorte
nacional de nascimento 2001-2003, residentes da Área Metropolitana de
Lisboa e do Alto Minho, avaliados pelo Programa de Vigilância Nacional
da Paralisia Cerebral (PVNPC). RESULTADOS 51 (44,3%) reportaram participação
em atividades desportivas. Identificamos correlação significativa entre
a participação no desporto e uma maior funcionalidade motora global
(r=.244; p=0.002), motricidade fina (r=.249; p=0.009), nível cognitivo
(r=.222; p=0.02) e de expressão (r=.240; p=0.01). CONCLUSÃO
No intuito de potenciar a inclusão e participação de adolescentes com
PC, professores de educação física e treinadores devem considerar
a adaptação das atividades no planeamento e promoção da prática
desportiva. Embora não incluídos neste estudo, as atitudes e
condicionantes físicas do contexto devem ser monitorizadas, por forma
a minimizar barreiras à participação desta população em atividades
desportivas.info:eu-repo/semantics/publishedVersio
Firefighters' sleep quality: results of a study in The Northeast of Portugal
No full textThe aim of this study was to evaluate and describe the overall sleep quality of firefighters. Application of the Portuguese version of the Pittsburgh Sleep Quality Index (PSQI) to firefighters, from the Northeast of Portugal, who accepted to participate in the study. Data collected between June 2021 and July 2022. The PSQI global score classified participants as 36,9% of participants as poor sleepers, although 73,9% of firefighters reported a subjective quality of sleep of “very good” or “good”, with 9,1% recording a “bad” quality of sleep. In particular, among the 273 total of participants, 35,8% of firefighter’s assumed sleeping more than 7 hours, whilst 59,7% have a sleep efficiency of 85%. Nevertheless, 7% of individuals stated difficulties staying awake on some occasions, and/or some degree of unwillingness to carry out daily activities, in addition, 26 participants (9,5% of the cohort) stated ever took medicine to help them sleep over the past month. Results revealed a global PSQI score ranged from 0 to 19, being higher scores indicative of worse quality of sleep. The mean score was 4.6 and the median score was 4, being scores >5 considered as a significant sleep disturbance.
The analytical results of this study reveal the presence of concerns related to the quality of sleep in firefighters, although they have a contrary perception, which can compromise their health and well-being. Thus, it is necessary to develop more research and appropriate interventions to optimize firefighters' sleep and reduce subsequent risks.This work was supported by the Portuguese Foundation for Science and Technology (FCT) through the project PCIF/SSO/0017/2018 and for financial support through national funds FCT/MCTES (PIDDAC) to CIMO (UIDB/00690/2020 and UIDP/00690/2020) and SusTEC (LA/P/0007/2020).N/
Comparison of Multi-locus Genotypes Detected in Aspergillus fumigatus Isolated from COVID Associated Pulmonary Aspergillosis (CAPA) and from Other Clinical and Environmental Sources
Get PDF(This article belongs to the Special Issue Biology, Immunology, Epidemiology, and Therapy of Fungal Infections: A Themed Issue Dedicated to Professor David A. Stevens)Background: Aspergillus fumigatus is a saprophytic fungus, ubiquitous in the environment and responsible for causing infections, some of them severe invasive infections. The high morbidity and mortality, together with the increasing burden of triazole-resistant isolates and the emergence of new risk groups, namely COVID-19 patients, have raised a crescent awareness of the need to better comprehend the dynamics of this fungus. The understanding of the epidemiology of this fungus, especially of CAPA isolates, allows a better understanding of the interactions of the fungus in the environment and the human body.
Methods: In the present study, the M3 markers of the STRAf assay were used as a robust typing technique to understand the connection between CAPA isolates and isolates from different sources (environmental and clinical-human and animal).
Results: Of 100 viable isolates that were analyzed, 85 genotypes were found, 77 of which were unique. Some isolates from different sources presented the same genotype. Microsatellite genotypes obtained from A. fumigatus isolates from COVID+ patients were all unique, not being found in any other isolates of the present study or even in other isolates deposited in a worldwide database; these same isolates were heterogeneously distributed among the other isolates.
Conclusions: Isolates from CAPA patients revealed high heterogeneity of multi-locus genotypes. A genotype more commonly associated with COVID-19 infections does not appear to exist.info:eu-repo/semantics/publishedVersio
Occurrence of Multidrug-Resistant Bacteria Resulting from the Selective Pressure of Antibiotics: A Comprehensive Analysis of ESBL K. pneumoniae and MRSP Isolated in a Dog with Rhinorrhea
Get PDF(This article belongs to the Special Issue Antimicrobial Use in Companion Animals)Because of public health concerns, much greater scrutiny is now placed on antibiotic use in pets, especially for antimicrobial agents that have human analogs. Therefore, this study aimed to characterize the phenotypic and genotypic profiles of multidrug-resistant bacteria isolated from nasal swabs samples taken from a one-year-old male Serra da Estrela dog with rhinorrhea that was treated with amikacin. An extended-spectrum β-lactamases (ESBL) Klebsiella pneumoniae was isolated in the first sample taken from the left nasal cavity of the dog. Seven days later, methicillin-resistant (MRSP) Staphylococcus pseudintermedius was also isolated. Nevertheless, no alterations to the therapeutic protocol were performed. Once the inhibitory action of the antibiotic disappeared, the competitive advantage of the amikacin-resistant MRSP was lost, and only commensal flora was observed on both nasal cavities. The genotypic profile of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae revealed the same characteristics and close relation to other strains, mainly from Estonia, Slovakia and Romania. Regarding MRSP isolates, although resistance to aminoglycosides was present in the first MRSP, the second isolate carried aac(6')-aph(2″), which enhanced its resistance to amikacin. However, the veterinary action was focused on the treatment of the primary agent (ESBL K. pneumoniae), and the antibiotic applied was according to its phenotypic profile, which may have led to the resolution of the infectious process. Therefore, this study highlights the importance of targeted therapy, proper clinical practice and laboratory-hospital communication to safeguard animal, human and environmental health.Simple Summary: Antimicrobial resistance (AMR) poses a major threat to human and animal health. One of the causes underlying the emergence of increasingly resistant strains is antibiotic selective pressure. This study aimed to evaluate the impact of treatment with amikacin on an extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolated in a dog with rhinorrhea. In the middle of the treatment, methicillin-resistant Staphylococcus pseudintermedius (MRSP) was isolated from the left nasal cavity of the dog. At the end of the treatment, K. pneumoniae was not recovered from nasal swab samples, while MRSP displayed phenotypical and genotypical changes. Six weeks after the end of the treatment, only commensal flora was observed in both nasal cavities. These results warn of the effects of antibiotic pressure, which can lead to the emergence of multidrug-resistant strains either by directly promoting the enrichment of bacteria with resistance to multiple antimicrobial agents or via the subsequent acquisition of resistance genes. Therefore, adapting clinical practice to this new reality is crucial to limit the selection and spread of multi-resistant bacteria among pets, humans and the environment.info:eu-repo/semantics/publishedVersio
Comparative Effectiveness of COVID-19 Vaccines in Preventing Infections and Disease Progression from SARS-CoV-2 Omicron BA.5 and BA.2, Portugal
Get PDFAuthor affiliations: Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal (I. Kislaya, V. Borges, C. Matias Dias, S. Duarte, L. Coelho, R. Ferreira, J. Isidro, M. Pinto, D. Sobral, A. Nunes, D. Santos, L. Vieira, J.P. Gomes, B. Nunes, A. Machado).We estimated comparative primary and booster vaccine effectiveness (VE) of SARS-CoV-2 Omicron BA.5 and BA.2 lineages against infection and disease progression. During April-June 2022, we implemented a case-case and cohort study and classified lineages using whole-genome sequencing or spike gene target failure. For the case-case study, we estimated the adjusted odds ratios (aORs) of vaccination using a logistic regression. For the cohort study, we estimated VE against disease progression using a penalized logistic regression. We observed no reduced VE for primary (aOR 1.07 [95% CI 0.93-1.23]) or booster (aOR 0.96 [95% CI 0.84-1.09]) vaccination against BA.5 infection. Among BA.5 case-patients, booster VE against progression to hospitalization was lower than that among BA.2 case-patients (VE 77% [95% CI 49%-90%] vs. VE 93% [95% CI 86%-97%]). Although booster vaccination is less effective against BA.5 than against BA.2, it offers substantial protection against progression from BA.5 infection to severe disease.The acquisition of sequencing equipment and reagents used
in this study by the Instituto Nacional de Saúde Doutor
Ricardo Jorge was partially funded by the HERA project
(grant no. 2021/PHF/23776) supported by the European
Commission through the European Centre for Disease
Control, and also partially funded by the GenomePT
project (grant no. POCI-01-0145-FEDER-022184), supported
by COMPETE 2020–Operational Programme for
Competitiveness and Internationalisation, Lisboa Portugal Regional Operational Programme, Algarve
Portugal Regional Operational, under the Portugal 2020
Partnership Agreement, through the European Regional
Development Fund, and by the Portuguese Science and
Technology Foundation. Algarve Biomedical Center
Laboratory received public funding through the Project
ALG-D2-2021-06 Variants Screen in Southern Portugal–
Monitoring Variants of Concern in Southern Portugal and
the Portuguese Science and Technology Foundation
national support through the Comprehensive Health
Research Center (grant no. UIDP/04923/2020)info:eu-repo/semantics/publishedVersio
Distribution and Clinical Significance of HPV16 Variants in Head and Neck Squamous Cell Carcinomas: Data from a Portuguese Cohort and Systematic Review
No full textReviewIntroduction: Genomic variants of the human papillomavirus type 16 (HPV16) are thought to play differential roles in the susceptibility to head and neck squamous cell carcinomas (HNSCC) and its biological behaviour. This study aimed to establish the prevalence of HPV16 variants in an HNSCC cohort and associate them with clinical pathological characteristics and patient survival.
Methods: We retrieved samples and clinical data from 68 HNSCC patients. DNA samples were available from tumour biopsy at the time of the primary diagnosis. Targeted next-generation sequencing was used to obtain whole-genome sequences, and variants were established based on phylogenetic classification.
Results: 74% of samples clustered in lineage A, 5.7% in lineage B, 2.9% in lineage C, and 17.1% in lineage D. Comparative genome analysis revealed 243 single nucleotide variations. Of these, one hundred were previously reported, according to our systematic review. No significant associations with clinical pathological variables or patient survival were observed. The E6 amino acid variations E31G, L83V, and D25E and E7 N29S, associated with cervical cancer, were not observed, except for N29S in a single patient.
Conclusion: These results provide a comprehensive genomic map of HPV16 in HSNCC, highlighting tissue-specific characteristics which will help design tailored therapies for cancer patients.This study was financially supported by the Virology Laboratory Pathology Department from the
Portuguese Oncology Institute of Lisboa IUIC/1168, with contributions by the GenomePT project
(POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for
Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme
(Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the
PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF),
and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/acceptedVersio
Multiple non contiguous copy gains and a terminal loss in 8q24 identified in a fetus with cleft palate and lip
No full textObjectives:
Chromosomal microarray analysis (CMA) is the recommended genetic test in pregnancies with ultrasound abnormalities but in some cases karyotype may still be needed to clarify the underlying mechanism of complex rearrangements.
Here we report the case of a fetus from a healthy 24-year-old G1P0 woman, with a low risk for common aneuploidies in the 1st trimester prenatal screening but referred for CMA at 17+6 weeks of gestation due to cleft palate and lip in the 1st trimester ultrasound.
Method:
After a normal result in the rapid aneuploidy diagnostic test we performed CMA using ThermoFisher Cytoscan™ 750K. Our reporting resolution includes gains and losses larger than 35 Kb, considered clinically relevant for the course of the pregnancy.
In this case further tests were done to assess recurrence risk and a possible chromosomal rearrangement: CMA and karyotype on the parents and karyotype on the fetus.
Results:
The CMA profile revealed a female fetus with three non-contiguous interstitial copy gains and a terminal loss in the long arm of chromosome 8 (8q24), as follows:
- x4 copy gain at 8q24.12q24.13 with 585 Kb
- x2 copy neutral region with 1.5 Mb
- x4 copy gain at 8q24.13 with 2.9 Mb
- x2 copy neutral region with 1.2 Mb
- x3 copy gain at 8q24.21q24.23 with 17.8 Mb
- x1 terminal loss at 8q24.3 with 130 Kb
The fetal karyotype showed, in one of the chromosomes 8, an abnormal pattern in the long arm with a larger relative size. After parental studies the reported copy number variants were shown to be de novo.
Conclusions.
Most of the cases reported in the literature with gains along 8q result from a rearrangement involving another chromosome making it challenging to assess a genotype-phenotype correlation (PMID: 34265769; PMID: 31141803; PMID: 34794751).
The few cases of individuals reported with isolated gains in the 8q24 have been described as having different features, depending on the size of the gain, and those may include facial dysmorphysms, clef lip and palate, developmental delay, among others (PMID: 25506438; PMID: 11484205; PMID: 33316910; UNIQUE - rarechromo.org: duplications of 8q).
Recently a fetus with multiple congenital abnormalities, including clef palate, was reported having a similar imbalance, and although the parents decided to keep the pregnancy the baby died soon after birth given the extension of the congenital abnormalities (PMID: 30638476).
The CMA results in our case explained the clef palate and lip identified in the fetus and, after genetic counseling, the parents opted to terminate the pregnancy.
Although the identified non-contiguous gains and the terminal loss may suggest a mechanism of chromothripsis/chromoanagenesis for the arising of this abnormal chromosome 8, no further studies were performed after determining that the parents had a normal result and therefore a low recurrence risk for future pregnancies.N/
A tradução não-canónica da proteína UPF1 (up-frameshift 1) e a sua relevância na tumorigénese do cancro colorretal
Get PDFDissertação de Mestrado em Biologia Molecular e Genética, apresentada à Faculdade de Ciências da Universidade de Lisboa, 2023.Dissertação orientada por: Doutora Rafaela Lacerda Santos (INSA) e Doutora Luísa Maria Ferreira Romão Loison (INSA e FCUL).Trabalho prático desenvolvido no Laboratório de Oncobiologia e Vias de Sinalização do Departamento de Genética Humana do INSA.A iniciação da tradução é o passo limitante da síntese proteica. Em condições de stresse, a tradução canónica é inibida e a tradução de transcritos específicos é mantida por mecanismos alternativos, como os que envolvem IRES (internal ribosome entry site). A UPF1 (up-frameshift 1) contribui para a tumorigénese no cancro colorretal (CRC, colorectal cancer). Anteriormente neste laboratório verificouse que a região 5'UTR (5’untranslated region) do transcrito de UPF1 apresenta atividade IRES e que esta é mantida em condições de stresse. Assim, esta tese teve como objetivo aferir como a tradução da UPF1 mediada por IRES pode contribuir para a progressão do CRC. As análises in silico realizadas através da plataforma Xena, para medir a variação dos níveis de expressão do transcrito e da proteína entre diferentes tipos de cancro e entre tecidos normais e cancerígenos do cólon, mostraram que a expressão de mRNA e proteína é superior nos tecidos de CRC do que noutros tipos de cancro e também em comparação com os tecidos normais do cólon, sugerindo que a expressão da UPF1 é superior quando esta contribui para a tumorigénese. Adicionalmente, a análise da expressão endógena da UPF1 em células epiteliais cultivadas da mucosa normal do cólon humano (NCM460) e em linhas celulares correspondentes a diferentes estádios de desenvolvimento de CRC (HT29, HCT116 e SW480), expostas a 1 μM de tapsigargina (que induz o stresse do retículo endoplasmático e, portanto, inibe a tradução canónica), revelou que a expressão da UPF1 é mantida em condições nas quais a tradução canónica é inibida, sugerindo que ocorre tradução mediada por IRES e que esta permite a manutenção dos níveis de UPF1 nessas condições. Concluindo, a tradução mediada por IRES contribui para a síntese da UPF1 em tecidos de CRC, o que, por sua vez, contribui para a progressão deste tipo de cancro.Translation initiation is the rate-limiting step of protein synthesis. In stress conditions, canonical
translation is inhibited, and the translation of specific transcripts is maintained by alternative
mechanisms, such as those involving IRES (internal ribosome entry sites). UPF1 (up-frameshift 1)
contributes to tumorigenesis in colorectal cancer (CRC), and it was previously shown in our lab that its
5' untranslated region (5’UTR) has IRES activity which is maintained in stress conditions. Thus, the
general aim of this thesis was to understand whether and how UPF1 IRES-mediated translation
contributes to the progression of CRC. In silico analyses through the Xena platform to measure
variations in mRNA and protein expression among different types of cancer, and between normal and
carcinogenic colon tissues, has shown that mRNA and protein expression is higher in CRC tissues than
in other cancers and also higher than in normal colon tissues, suggesting that UPF1 expression is higher
when UPF1 contributes to tumorigenesis. Accordingly, the analysis of UPF1 endogenous expression in
cultivated epithelial cells of the normal human colon mucosa (NCM460), and in cell lines corresponding
to different CRC developmental stages (HT29, HCT116 and SW480), exposed to 1 μM of thapsigargin,
which induces endoplasmic reticulum stress and hence inhibits canonical translation, revealed that UPF1
expression is maintained in conditions in which canonical translation is inhibited. These results suggest
that the IRES-mediated translation allows the maintenance of endogenous UPF1 levels in these
conditions. In conclusion, IRES-mediated translation contributes to the synthesis of UPF1 in CRC
tissues, which in turn contributes to the progression of this type of cancer.Work supported by INSA and UIDB/04046/2020 (DOI: 10.54499/UIDB/04046/2020 ) and UIDP/04046/2020 (DOI: 10.54499/UIDP/04046/2020) Centre grants from FCT, Portugal (to BioISI).N/