literature review and a Portuguese case-study

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2022, Universidade de Lisboa, Faculdade de Farmácia.Contextualização. A vacinação é a maneira mais eficaz de prevenir infeções graves por influenza, especialmente naqueles que pertencem a grupos de risco. Contudo, as taxas de vacinação mantêm-se abaixo das metas desejadas. Para combater esta problemática, os farmacêuticos têm ganhado o poder legal de praticar o ato de vacinação em diversos países, incluindo Portugal. Objetivos. Avaliar o papel do farmacêutico enquanto prestador do serviço de vacinação contra a gripe sazonal, do ponto de vista internacional e nacional. Adicionalmente, pretendeu-se determinar o impacto da extensão do programa de vacinação contra a gripe sazonal do Serviço Nacional de Saúde às farmácias comunitárias de Loures. Métodos. Foi realizada uma revisão abrangente da literatura. Todos os artigos que correspondessem aos critérios de inclusão foram considerados. Para o segundo capítulo, dados relativos às práticas portuguesas de vacinação foram reunidos e analisados, a fim de se caraterizar o serviço de vacinação nas farmácias. Por fim, um caso de estudo foi apresentado. Uma metodologia antes e depois foi usada para avaliar o impacto do projeto na cobertura vacinal e no número de inoculações. Outros resultados foram considerados: a caraterização sociodemográfica dos indivíduos vacinados, a sua satisfação, tempos de espera e tempo e meios de transporte usados na deslocação à farmácia. Resultados. Um total de 36 artigos científicos foi incluído na revisão. Os farmacêuticos demonstraram ser um recurso valioso enquanto prestadores do serviço de vacinação contra a gripe sazonal, uma vez que aumentam o acesso e a satisfação dos utentes, enquanto aliviam a pressão de trabalho das unidades de saúde primárias. A primeira campanha de vacinação nas farmácias foi implementada em 2008. Dez anos depois, em Loures, as mesmas condições de vacinação oferecidas nos centros de saúde foram aplicadas às farmácias, resultando num total de 17 308 vacinas SNS administradas e em satisfação e grau de acesso elevados. Conclusões. Os farmacêuticos têm potencial para melhorar o serviço de vacinação em diversas vertentes. No futuro, devem continuar a ser considerados e encorajados a fazer parte desse processo. A extensão da iniciativa de Loures a todo o país deve ser considerada.Background. Vaccination is the most effective way to prevent serious influenza infection, especially in those at-risk. However, flu vaccination rates among the world remain below the desired targets. To overcome this problem, pharmacists have becoming flu vaccine immunisers in several countries, including Portugal. Aims. To evaluate the pharmacist´s role in flu immunisation as vaccine providers, both from an international and national perspectives. Furthermore, to determine the impact of extending the NHS flu vaccination programme to Loures community pharmacies. Methods. A scoping review following the framework proposed by Arksey and O’Malley and the PRISMA-ScR instructions was conducted. All the articles that met the inclusion criteria were considered. For the second chapter, data regarding Portuguese flu vaccination practices were gathered and analysed to characterise the Portuguese pharmacy-based service over the years. A case-study from Loures was further presented. A before-and-after methodology was used to evaluate the impact of the project in the flu immunisation coverage and in the number of inoculations. Other outcomes measures were considered: the sociodemographic characteristics of the vaccinated population, satisfaction and waiting time concerning the service, and time and means of transport to get the vaccine at the pharmacy. Results. A final number of 36 studies were included in the scoping review. Pharmacists have shown to be a valuable resource in the flu vaccination process as immunisers. They increase the accessibility and the satisfaction of the immunisation service, while realising workload from the primary healthcare facilities. In Portugal, the first flu immunisation campaign in CPs was implemented in 2008. Ten years later, in Loures, the same flu vaccination conditions of the GPs were offered in the CPs. As a result, a total of 17 308 NHS flu vaccinations were administered in pharmacies, and overall satisfaction and accessibility were high. Conclusions. Pharmacists have the potential to improve the vaccination service in numerous ways. In the future, they should continue to be considered and encouraged to take part on the flu vaccination process as flu vaccine providers. Moreover, the extension of the Loures initiative to the national level should be considered

Antibioterapia em associação com Epigalocatequina-3 galato (EGCG) é uma alternativa eficaz para infeções causadas por Staphylococcus aureusresistente à meticilina?

H&TRC authors gratefully acknowledge the FCT/MCTES national support through the UIDB/05608/2020 and UIDP/05608/2020. The authors acknowledge the institutional support given by Escola Superior de Tecnologia da Saúde de Lisboa – Instituto Politécnico de Lisboa.ABSTRACT - Antimicrobial resistance of human pathogens such as Methicillin-Resistant Staphylococcus aureus (MRSA), is globally defined as a major public health concern. Currently, several new therapeutic approaches are being developed with the aim find an alternative to treat these infections, including the use of natural compounds with epigenetic modulation potential such as green tea catechins. In green tea, Epigallocatechin-3 gallate (EGCG) is the most abundant and medically relevant catechin, with anti-inflammatory, antioxidant, anti-carcinogenic, and antimicrobial properties as well as synergistic effects reported for several antibiotics. The search for new therapeutic alternatives has led to the development of studies regarding the EGCG effect in S. aureus virulence factors and transcriptional modulation. Several studies, including from our research group, have demonstrated that EGCG exposure is able to affect the bacteria transcriptional pattern in numerous genes. Transcriptional effects were reported in genes implicated in toxin production, such as hly, which encodes for an alpha-haemolysin-precursor and hlgA, hlgB, the gamma haemolysin subunits A and B, respectively, in the epigenetic modulator orfx (a staphylococci methyltransferase) and in genes involved in resistance responses (spdC and WalKR). Moreover, increasing evidence has demonstrated potential correlations between epigenetic modulation and the expression of virulence factors including haemolysins. It is clear that EGCG should be considered as a new compound for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms even in divergent phenotypic resistance strains.RESUMO - A resistência antimicrobiana de patógenos humanos, como Staphylococcus aureus resistente à meticilina (MRSA), é globalmente definida como uma grande preocupação de saúde pública. Atualmente, várias novas abordagens terapêuticas estão a ser desenvolvidas com o objetivo de encontrar uma alternativa para tratar essas infeções, incluindo o uso de compostos naturais com potencial de modulação epigenética, como as catequinas do chá verde. No chá verde, a Epigalocatequina-3 galato (EGCG) é a catequina mais abundante e clinicamente relevante, com propriedades anti-inflamatórias, antioxidantes, anticancerígenas e antimicrobianas, bem como efeitos sinérgicos relatados para vários antibióticos. A busca por novas alternativas terapêuticas tem levado ao desenvolvimento de estudos sobre o efeito do EGCG em fatores de virulência e modulação transcricional de S. aureus. Vários estudos, inclusive do nosso grupo de investigação, demonstraram que a exposição ao EGCG é capaz de afetar o padrão transcricional da bactéria em vários genes. Efeitos de transcrição foram relatados em genes implicados na produção de toxinas, como hly, que codifica para um precursor da alfa-hemolisina e hlgA, hlgB, as subunidades A e B da gama-hemolisina, respetivamente, no modulador epigenético orfx (um estafilococo metiltransferase) e em genes envolvidos em respostas de resistência (spdC e WalKR). Além disso, evidências crescentes demonstraram correlações potenciais entre a modulação epigenética e a expressão de fatores de virulência, incluindo hemolisinas. Assim, o EGCG deve ser considerado como um novo composto para tratamento antimicrobiano e/ou adjuvante terapêutico contra microrganismos resistentes a antibióticos, mesmo em estirpes com fenótipos de resistência divergentes.info:eu-repo/semantics/publishedVersio

EDCs mixture effects in human cell lines

Endocrine disrupting chemicals (EDCs) are exogenous agents commonly employed in a wide variety of consumer products and indoor/outdoor applications. Human exposure to these compounds either by environmental and/or occupational sources is omnipresent, persistent and occurs in complex mixtures which, therefore, can origin a mixed “body burden” of contaminants. Extensive research in human cell lines, particularly from sex hormone-responsive tissues, show that EDCs can simultaneously and differentially trigger specific signaling pathways, predominantly associated to estrogen receptors. Evidence demonstrates that EDCs endorse distinct cellular responses in different cell lines, however, most of the studies have focused exclusively in the independent action of the tested compounds whereas information regarding EDCs mixtures effects is still scared. We performed a revision of the state of the art in PubMed focused on studies that evaluate EDCs mixture effects. Based on published data a review of the utilized EDCs, tested doses, studied cell lines and observed effects of co-exposure studies are presented. Although the independent action of chemicals is still considered the main principle of EDCs mixture toxicity, the evidence demonstrates that some effects cannot be predicted when analyzing single compounds independently and thus it is undoubtedly that the daily doses of each compound are not the only one that can be taken into consideration. There is an emergent concern that the current toxicological assessment based in a chemical-by-chemical approach may not be adequately protected in the context of EDCs mixtures and that recognizing potential aggregate and cumulative exposures are crucial for an adequate risk assessment.info:eu-repo/semantics/publishedVersio

EDCs mixtures: a stealthy hazard for human health ?

ReviewEndocrine disrupting chemicals (EDCs) are exogenous chemicals that may occur naturally (e.g., phytoestrogens), while others are industrial substances and plasticizers commonly utilized worldwide to which human exposure, particularly at low-doses, is omnipresent, persistent and occurs in complex mixtures. EDCs can interfere with/or mimic estrogenic hormones and, consequently, can simultaneously trigger diverse signaling pathways which result in diverse and divergent biological responses. Additionally, EDCs can also bioaccumulate in lipid compartments of the organism forming a mixed “body burden” of contaminants. Although the independent action of chemicals has been considered the main principle in EDCs mixture toxicity, recent studies have demonstrated that numerous effects cannot be predicted when analyzing single compounds independently. Co-exposure to these agents, particularly in critical windows of exposure, may induce hazardous health effects potentially associated with a complex “body burden” of different origins. Here, we performed an exhaustive review of the available literature regarding EDCs mixtures exposure, toxicity mechanisms and effects, particularly at the most vulnerable human life stages. Although the assessment of potential risks to human health due to exposure to EDCs mixtures is a major topic for consumer safety, information regarding effective mixtures effects is still scarceinfo:eu-repo/semantics/publishedVersio

MRSA colonization in workers from different occupational environments: a one health approach perspective

Projeto “Occupational exposure of ambulance drivers to bioburden” (IPL/2020/BIOAmbuDrivers_ESTeSL).Projeto “Bacterial Bioburden assessment in the context of occupational exposure and animal health of swine productions” (IPL/2016/BBIOR-Health).FCT_UIDB/05608/2020. FCT_UIDP/05608/2020.Staphylococcus aureus and particularly methicillin-resistant S. aureus (MRSA) infections are currently associated with extremely high morbidity and mortality rates worldwide. The global escalation in the development of antibiotic-resistant human pathogens and S. aureus's ability in developing new clones with the capacity to invade community settings leads to an urgent need to develop accurate and efficient assessments of S. aureus colonization in occupational settings, particularly those with increased risk of human and animal colonization and food contamination. Here we present cross-sectional studies with the aim to assemble crucial information regarding MRSA prevalence in workers from five different Portuguese occupational environments (bakeries, swineries (humans and animals), ambulance crews, veterinary clinics, and healthcare facilities). Our data demonstrated a high prevalence of S. aureus asymptomatic carriers among bakery workers (40%; 75% MSSA and 25% MRSA), swinery workers (54%; 8% MSSA and 46% MRSA), firefighters (48.5%; 24% MSSA and 21% MRSA) and healthcare workers (Study 1: 42.2%; 18.4% MSSA and 23.7% MRSA, Study 2: 43.3% MRSA). S. aureus prevalence in veterinary staff was 7.1% (MSSA), lower than the results obtained in control groups (33.3% S. aureus; MRSA 4% to 10%). The present study sustains the urge to develop an accurate and efficient assessment of S. aureus human and animal colonization, particularly in high-risk occupational settings, with proper guidelines and validated procedures in order to avoid potential hazardous health outcomes associated with bioaerosol exposure and associated infectious diseases.info:eu-repo/semantics/publishedVersio

A epigenética das infeções nosocomiais

Definição de epigenética: “adaptação estrutural de regiões de cromossomas que permitem registar, sinalizar ou perpetuar estados de actividade alterados”. A epigenética permite a diferenciação celular em células de tecidos com a mesma informação genética através da alteração hereditária de expressão de genes ou fenótipos que não envolvem alterações na sequência de DNA.info:eu-repo/semantics/publishedVersio

Plasma versus serum analysis by FTIR spectroscopy to capture the human physiological state

Fourier Transform InfraRed spectroscopy of serum and plasma has been highly explored for medical diagnosis, due to its general simplicity, and high sensitivity and specificity. To evaluate the plasma and serum molecular fingerprint, as obtained by FTIR spectroscopy, to acquire the system metabolic state, serum and plasma spectra were compared to characterize the metabolic state of 30 human volunteers, between 90 days of consumption of green tea extract rich in Epigallocatechin-3-gallate (EGCG). Both plasma and serum spectra enabled the high impact of EGCG consumption on the biofluid spectra to be observed, as analyzed by the spectra principal component analysis, hierarchical-cluster analysis, and univariate data analysis. Plasma spectra resulted in the prediction of EGCG consumption with a slightly higher specificity, accuracy, and precision, also pointing to a higher number of significant spectral bands that were different between the 90 days period. Despite this, the lipid regions of the serum spectra were more affected by EGCG consumption than the corresponding plasma spectra. Therefore, in general, if no specific compound analysis is highlighted, plasma is in general the advised biofluid to capture by FTIR spectroscopy the general metabolic state. If the lipid content of the biofluid is relevant, serum spectra could present some advantages over plasma spectra.The present work was conducted at H&TRCHealth & Technology Research Center, Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa, and in the Engineering and Health Laboratory, that resulted from a collaboration protocol established between Universidade Católica Portuguesa and Instituto Politécnico de Lisboa.info:eu-repo/semantics/publishedVersio

Green tea epigallocatechin-3-gallate (EGCG) oxidative stress and DNA damage

Epigallocatechin-3-gallate (EGCG) antioxidant properties have been demonstrated however, increasing evidence indicates that EGCG produces reactive oxygen species. The aim of this study was to evaluate the effect of EGCG intake during 90 days in hematological cardiovascular risk factors, vitamins A and E, DNA damage, and oxidative damage in human blood. Peripheral blood from 30 healthy individuals (10 males and 20 females; 18 – 45 years), was collected at time 0 (T0) and time 90 (T90). During 90 days, participants ingested capsules of green tea extract (225mg EGCG) daily. Hematological cardiovascular risk factors including lipid profile and liver function parameters were assessed using colorimetric methods. Vitamins A and E in serum were quantified by HPLC and analysis of DNA damage and oxidative damage was performed by comet assay. Our results showed that lipid profile and liver function parameters are not affected by EGCG and serum levels of vitamin E increased, but not vitamin A. An increase in DNA damage and DNA oxidative damage after 90 days of EGCG consumption was also reported. The results suggest that EGCG can induce DNA damage, possibly due to ROS induction, with an associated increase of the antioxidant vitamin E, however without alteration of hematological cardiovascular risk factors.info:eu-repo/semantics/publishedVersio

Síndrome da angustia respiratória aguda e proteinose alveolar congênita

Pulmonary surfactant is a substance composed of a lipoprotein complex that is essential to pulmonary function. Pulmonary surfactant proteins play an important role in the structure, function, and metabolism of surfactant; 4 specific surfactant proteins have been identified: surfactant proteins-A, surfactant proteins-B, surfactant proteins-C, and surfactant proteins-D. Clinical, epidemiological, and biochemical evidence suggests that the etiology of respiratory distress syndrome is multifactorial with a significant genetic component. There are reports about polymorphisms and mutations on the surfactant protein genes, especially surfactant proteins-B, that may be associated with respiratory distress syndrome, acute respiratory distress syndrome, and congenital alveolar proteinosis. Individual differences regarding respiratory distress syndrome and acute respiratory distress syndrome as well as patient response to therapy might reflect phenotypic diversity due to genetic variation, in part. The study of the differences between the allelic variants of the surfactant protein genes can contribute to the understanding of individual susceptibility to the development of several pulmonary diseases. The identification of the polymorphisms and mutations that are indeed important for the pathogenesis of the diseases related to surfactant protein dysfunction, leading to the possibility of genotyping individuals at increased risk, constitutes a new research field. In the future, findings in these endeavors may enable more effective genetic counseling as well as the development of prophylactic and therapeutic strategies that would provide a real impact on the management of newborns with respiratory distress syndrome and other pulmonary diseases.O surfactante pulmonar é uma substância composta por um complexo lipoprotéico essencial para a função pulmonar normal. As proteínas do surfactante têm importante papel na estrutura, função e metabolismo do surfactante. São descritas quatro proteínas específicas denominadas surfactante pulmonar-A, surfactante pulmonar-B, surfactante pulmonar-C e surfactante pulmonar-D. Evidências clínicas, epidemiológicas e bioquímicas sugerem que a etiologia da síndrome do desconforto respiratório é multifatorial com um componente genético significativo. Existem na literatura algumas descrições sobre a presença de polimorfismos e mutações em genes dos componentes do surfactante, particularmente no gene da surfactante pulmonar-B, os quais parecem estar associados à síndrome do desconforto respiratório, síndrome da angustia respiratória aguda e proteinose alveolar congênita. Diferenças individuais relacionadas à síndrome do desconforto respiratórioe síndrome da angustia respiratória aguda e à resposta dos pacientes ao tratamento podem refletir diversidade fenotípica, devido, parcialmente, à variação genética. O estudo das diferenças entre as variantes alélicas dos genes das proteínas do surfactante pode ajudar na compreensão das variabilidades individuais na susceptibilidade ao desenvolvimento de várias doenças pulmonares. A determinação de quais polimorfismos e mutações são, de fato, importantes na patogênese das doenças relacionadas à disfunção das proteínas do surfactante e a possibilidade da realização da genotipagem em indivíduos de alto risco constitui um novo campo de pesquisa, que pode permitir, futuramente, um aconselhamento genético mais efetivo, resultando no desenvolvimento de estratégias profiláticas e terapêuticas que representem um impacto real no manejo dos recém-nascidos portadores da síndrome do desconforto respiratório e outras patologias pulmonares

Assessment of staphylococcus aureus colonization in bakery workers: a case study

Introduction - The World Health Organization (WHO) describes antimicrobial resistance in human pathogens as a global health challenge. In the context of food handlers, although human colonization with bacteria such as s. aureus is associated high risk to transfer the infection to others, or contaminate foods and food surfaces during handling, information regarding bacteria bioburden is still scarce. Considering that s. aureus is a cause of staphylococcal food poisoning (SFP), resultant from ingestion of staphylococcal enterotoxins present in food, is one of the most prevalent foodborne intoxications in the world, with fatality rates particularly concerning for children and the elderly and that foodstuff contamination by colonized food handlers represent a major risk for SFP, the assessment of colonization of these workers is crucial. Aim of study - Considering that food contamination by colonized food handlers represent a major risk for SFP, here we aim to assess s. aureus colonization prevalence of both sensible and resistant strains in a bakery as a case study.info:eu-repo/semantics/publishedVersio