Development of a buccal in vitro permeation method - exploring aQbD implementation.

The buccal mucosa is arising within the pharmaceutical landscape as an attractive option for local and systemic drug delivery, mostly due to its high vascularization, inherent permeability and robustness. Still, one of the major challenges in bringing oromucosal preparations to market remains the accurate evaluation of permeability. During pre-clinical drug development, in vitro permeation assessment is essential, and methodologies, based on the selection of a proper membrane in a diffusion cell, have become appealing alternatives to the conventional cell-based models. The development of such methods is being constrained by the number of variables - related to study conditions, setup and formulation - that need to be optimized to accurately estimate buccal permeation. The gap of knowledge over the mentioned variables may lead to long costly developments and poorly accurate methods, especially if the empirical analytical approach is used. In this paper, a systematic risk-based analytical quality by design approach was applied to the development of a buccal in vitro permeation method, ensuring that all sources of variability affecting permeation process were identified, explained and managed by appropriate measures. Researchers are guided through a step by step model, successfully demonstrating with experimental data the impact of critical variables on method's performance.

[Adaptation of the Standardized Patient Evaluation of Eye Dryness Questionnaire to European Portuguese (SPEED-Vp) in a Non-Clinical Sample]. / Adaptação do Questionário Standardized Patient Evaluation of Eye Dryness para Português (SPEED-Vp) numa População Não Clínica.

INTRODUCTION: The aim of this study was to translate and adapt the Standardized Patient Evaluation of Eye Dryness questionnaire to European Portuguese, as well as assess the psychometric performance of the translated version, including repeatability and agreement. MATERIAL AND METHODS: The original Standardized Patient Evaluation of Eye Dryness - SPEED questionnaire was translated and adapted to the Portuguese cultural context by following a scientifically valid methodology commonly used in the process of adapting tools to other cultures and languages. The questionnaire resulting from the translation into the new language was subject to a pre-test where the comments of the participants were written and considered for the final version of the questionnaire. For the scale validation of the final version of the translated questionnaire, 89 subjects from a non-clinical population, aged 18 to 84 years, were asked to answer the questionnaire (61% were women). One week later, the same questionnaire was repeated by 63 subjects. The internal reliability of the questionnaire was analyzed by Cronbach's alpha, temporal stability by test-retest, and analysis of agreement between measures by the Bland-Altman method. RESULTS: The internal consistency of the translated questionnaire, SPEED-vP was high (α = 0.871) and all questionnaire items contributed to an increase in this index. This consistency was also confirmed to be high in the retest (α = 0.856) and when the sample was stratified by age and sex. The SPEED-complete questionnaire also showed high consistency (α = 0.88). The repeatability of the instrument was high (ICC 0.933; 95% CI: 0.899 and 0.960) and the Bland-Altman plot revealed good agreement between measures. CONCLUSION: The Standardized Patient Evaluation of Eye Dryness in Portuguese (SPEED-vP) showed good psychometric properties for the Portuguese population. Therefore, the translated version of the SPEED-vP questionnaire could be used to quantitatively measure the presence of dry eye symptoms in the Portuguese population.

Introdução: O objetivo deste estudo foi traduzir e adaptar o questionário de avaliação padronizada do paciente com secura ocular para a língua portuguesa, bem como avaliar o desempenho psicométrico da escala da versão traduzida, incluindo a sua repetibilidade e concordância entre medidas. Material e Métodos: O questionário original Standardized Patient Evaluation of Eye Dryness ­ SPEED foi traduzido e adaptado à cultura portuguesa, seguindo uma metodologia cientificamente válida e habitualmente utilizada no processo de adaptação de ferramentas a outras culturas e línguas. O questionário resultante da tradução para a nova língua foi sujeito a um pré-teste onde se registaram os comentários dos participantes e estes foram considerados para a versão final do questionário. Para a validação da escala da versão final do questionário traduzido participaram 89 indivíduos de uma população não clínica, com idades compreendidas entre os 18 e os 84 anos, dos quais 61% eram mulheres. Uma semana depois, o mesmo questionário foi preenchido pela segunda vez por 63 indivíduos. A confiabilidade interna do questionário foi analisada pelo alfa de Cronbach, a estabilidade temporal pelo teste-reteste e a análise da concordância entre medidas pelo método Bland-Altman. Resultados: A consistência interna do questionário traduzido, SPEED-vP, foi alta (α = 0,871) e todos os itens do questionário contribuíram para um aumento deste índice. Esta consistência confirmou-se também alta no reteste (α = 0,856) e quando a amostra foi estratificada por idades e por sexo. O questionário SPEED-completo também apresentou alta consistência (α = 0,88). A repetibilidade do instrumento foi alta (ICC 0,933; 95% IC: 0,899 e 0,960) e o gráfico de Bland-Altman revela boa concordância entre medidas. Conclusão: O questionário Standardized Patient Evaluation of Eye Dryness, na língua portuguesa (SPEED-vP) demonstrou boas propriedades psicométricas na população portuguesa. Consequentemente, a versão traduzida do questionário SPEED poderá ser usada para medir quantitativamente a presença de sintomas de olho seco, na população portuguesa.

Eye discomfort at close work in Portuguese university students: A comparative analysis between the pre-COVID and confinement period.

BACKGROUND: Many individuals experience visual symptoms associated with near work. The level of discomfort appears to increase with the amount of digital screen use. OBJECTIVE: To study the eye discomfort with near tasks in university students in the pre-COVID period and in the period of confinement due to the pandemic. METHODS: Two independent samples of students, aged between 18 and 35 years, were used to assess symptomatic behaviour with the Convergence Insufficiency Symptom Survey (CISS) questionnaire. In the pre-COVID period the sample had 342 participants, 64.6% females and in the COVID period 322 students participated, 71.4% females. The study of differences was carried out by the Mann-Whitney U test. The interpretation of the statistical inference was performed for a significance level≤0.05. RESULTS: There was an increase in the number of symptomatic cases in the COVID period without statistical evidence of differences in the frequency of symptoms reported in the two periods. The dimensions "somatic sensations" and "cognitive performance" were the typology of symptoms that most contributed to visual complaints with near vision. There was a significantly different symptomatic behaviour between genders in the period of confinement (p = 0.001), worsening in females and improving in males. CONCLUSION: These findings suggest that females and males exposed to digital environments, over time, may exhibit different symptomatic behaviour. Our results suggest that boys adapt more quickly than girls. Factors that predispose to these changes, aetiology and potential intervention actions still need further study.

Clinical, economical and safety impact of ferric carboxymaltose use in Patient Blood Management programme in Portuguese National Health Service hospitals.

Ferric carboxymaltose (FCM) can be used in Patient Blood Management (PBM) to promote the optimization of preoperative haemoglobin (Hb), which aims to minimise the use of allogeneic blood components and improve clinical outcomes, with better cost-effectiveness. This was an observational study conducted in a retrospective and multicentre cohort with adults from elective orthopaedic, cardiac and colorectal surgeries, treated according to local standards of PBM with allogeneic blood product transfusions (ABTs) on demand and with FCM to correct iron deficiency with or without anaemia. In this work, only the first pillar of the PBM model issue by Directorate-General for Health (DGS) was evaluated, which involves optimising Hb in the preoperative period with iron treatment if it's necessary/indicated. Before the implementation of PBM in Portugal, most patients did not undergo preoperative laboratory evaluation with blood count and iron kinetics. Therefore, the existence of Iron Deficiency Anaemia (IDA) or Iron Deficiency (ID) without anaemia was not early detected, and there was no possibility of treating these patients with iron in order to optimise their Hb and/or iron stores. Those patients ended up being treated with ABTs on demand. A total of 405 patients from seven hospitals were included; 108 (26.7%) underwent FCM preoperatively and 197 (48.6%) were transfused with ABTs on demand. In the FCM preoperative cohort, there was an increase in patients with normal preoperative Hb, from 14.4 to 45.7%, before and after FCM, respectively, a decrease from 31.7 to 9.6% in moderate anaemia and no cases of severe anaemia after FCM administration, while 7.7% of patients were severely anaemic before FCM treatment. There were significant differences (p < 0.001) before and after correction of preoperative anaemia and/or iron deficiency with FCM in Hb, serum ferritin and transferrin saturation rate (TS). In the ABT group, there were significant differences between pre- and postoperative Hb levels (p < 0.001). Hb values tended to decrease, with 44.1% of patients moving from mild anaemia before transfusion to moderate anaemia in the postoperative period. Concerning the length of hospital stay, the group administered with ABTs had a longer hospital stay (p < 0.001). Regarding the clinical outcomes of nosocomial infection and mortality, there was no evidence that the rate of infection or mortality differed in each group (p = 0.075 and p = 0.243, respectively). However, there were fewer nosocomial infections in the FCM group (11.9% versus 21.2%) and mortality was higher in the transfusion group (21.2% versus 4.2%). Economic analysis showed that FCM could reduce allogenic blood products consumption and the associated costs. The economic impact of using FCM was around 19%. The preoperative Hb value improved when FMC was used. Patients who received ABTs appeared to have a longer hospital stay. The FCM group reported fewer infections during hospitalisation. The economic results showed savings of around €1000 for each patient with FCM administration. The use of FCM as part of the PBM program had a positive impact on patients' outcomes and on economic results. However, it will be essential to perform studies with a larger sample to obtain more robust and specific results.

[Dabigatran Reversal: A Practical Approach]. / Reversão do Dabigatrano: Abordagem Prática.

Dabigatran is a direct oral anticoagulant used to prevent stroke and systemic embolism in patients with atrial fibrillation. In situations that require the urgent reversal of its anticoagulant activity, such as in the case of severe bleeding that is life-threatening; urgent/ emergent surgery or invasive procedures with significant bleeding risk; and the need for thrombolysis in a patient with ischemic stroke, several measures can be taken, including the use of its specific reversal agent, idarucizumab. Based on the guidelines for the use of reversal agents for oral anticoagulants, and on the clinical experience of reversal of dabigatran, a practical guide is presented for use in clinical situations where reversal of dabigatran anticoagulation is required, including the use of idarucizumab. The adoption of this type of guideline contributes to therapeutic optimization and, consequently, greater reversal efficiency and a better resource management.

O dabigatrano é um anticoagulante oral direto utilizado na prevenção do acidente vascular cerebral (AVC) e embolia sistémica em doentes com fibrilhação auricular. Em situações que implicam a reversão urgente da sua atividade anticoagulante, como em caso de hemorragia grave com risco de vida; cirurgia ou manobra invasiva urgente/ emergente com risco hemorrágico significativo; e necessidade de trombólise em doente com AVC isquémico, podem ser adotadas diversas medidas, nomeadamente o recurso ao seu agente de reversão específico, o idarucizumab. Com base nas orientações de utilização dos agentes de reversão dos anticoagulantes orais e na experiência clínica de reversão do dabigatrano, apresenta-se um guia prático de atuação em situações urgentes de necessidade de reversão da anticoagulação do dabigatrano, incluindo a utilização de idarucizumab. A adoção deste tipo de protocolos contribui para a otimização terapêutica e, consequentemente, uma reversão mais eficaz e uma melhor gestão dos recursos.

[Anemia in Chronic Kidney Disease: The State of the Art]. / Anemia da Doença Renal Crónica: O Estado da Arte.

The aging of the population has led to an increased prevalence of chronic diseases such as chronic kidney disease. Anemia is one of the most frequent complications of chronic kidney disease, with an impact not only on the quality of life but also on the patient's prognosis and associated costs. Knowledge in this therapeutic area has increased significantly: from the appearance of recombinant erythropoietin in 1989, through the use of increasing doses of parenteral iron and, more recently, to new molecules such as hypoxia-inducible factor inhibitors. The aim of this article is to present a pragmatic review of the state of the art in the epidemiology, pathophysiology, diagnosis and treatment of anemia associated with chronic kidney disease.

O envelhecimento populacional tem-se traduzido no aumento de prevalência de doenças crónicas como a doença renal crónica. A anemia é uma das complicações mais frequentes da doença renal crónica, com impacto não só na qualidade de vida como no prognóstico do doente e nos custos associados. O conhecimento nesta área terapêutica tem aumentado de forma significativa: desde o aparecimento da eritropoietina recombinante em 1989, passando pelo uso de doses crescentes de ferro parentérico e, mais recentemente, a novas moléculas como os inibidores do hypoxia-inducible factor. Os autores pretendem rever, de uma forma pragmática, o estado da arte da anemia associada à doença renal crónica, desde a epidemiologia, à fisiopatologia, ao diagnóstico e ao tratamento.

Oromucosal products - Market landscape and innovative technologies: A review.

Strategies that rely on oral mucosal administration have increased in the last decade and oromucosal products are paving the way to overcome specific challenges, namely improving drug bioavailability when compared with the conventional oral route, due to a reduction of the hepatic first-pass metabolism and pre-systemic degradation. Overall, the advantages of these products make oromucosal route of administration attractive for the development of value-added medicines, which can address more properly the unmet medical needs of specific patients. Generally, such products have an easy and convenient administration since they do not require water for ingestion, which may be particularly relevant for geriatric and pediatric groups, or non-cooperative patients. Usually, the development of these products aims to provide a faster onset of action, critical for acute or emergency treatments. Although oriented to achieve better therapeutic outcomes, today's drug development is primarily focused on patient-centered care, meaning that patients' specific characteristics/needs are an important driving force behind product-development efforts. In accordance, pharmaceutical innovation can rely not only on new drug substances but also on re-formulation of already approved ones or alternative routes of administration, enhancing patient convenience, treatment efficacy and/or safety. Throughout this review, the oromucosal drug products, approved in the last decade, and a retrospective analysis of their critical quality attributes and specifications will be described. Furthermore, trends and opportunities of the latest technologies in this field, as well as the number of ongoing clinical studies, will be presented and discussed.

Improving Awareness about Patient Blood Management in Portugal: A Call for Action Arising from a Delphi Panel.

INTRODUCTION: Anaemia and iron deficiency are associated with increased mortality and poor surgical outcomes. Consensus in their definitions is expected to optimize their management, which is encompassed by patient blood management, providing patient-centred care while improving patient safety and clinical outcomes. Patient blood management implementation is even more relevant in contingency times and faces barriers due to lack of standardization, among others. The aim is to establish a consensus on these diagnoses and implement patient blood management principles in clinical practice in Portugal. MATERIAL AND METHODS: Eight experts in Transfusion Medicine, Haematology, Anaesthesiology, Internal Medicine, and Obstetrics/Gynaecology were assembled; a focus group was conducted, defining 33 statements. A Delphi panel was conducted, with experts from the clinical specialities named above as well as from General Surgery, Urology, and Orthopaedics. RESULTS: The Delphi panel's rounds had 70 (Round 1) and 46 (Round 2) respondents. Specialists were consensual in only two statements, on the existence of a preoperative patient blood management consultation for candidates to elective surgeries in which the use of blood derivatives is anticipated and, on the importance of the correction of postoperative anaemia and iron deficiency. Of the remaining 31 statements, 27 reached high agreement or disagreement by the respondents. CONCLUSION: Consensus was reached in only two (6%) of the 33 statements. There was a consensual agreement on the relevance of establishing patient blood management as the standard of care and of valuing preoperative and postoperative patient blood management interventions. Nevertheless, our results point to the lack of awareness regarding patient blood management principles - which could result in better postoperative outcomes, shorter hospitalizations, reduced costs and increased availability of beds. Training and literacy initiatives could help further implement patient blood management standards in Portuguese hospitals.

Introdução: A anemia e ferropenia estão associadas a um aumento da mortalidade e a piores resultados no período pós-operatório. Consensualizar as suas definições permitirá otimizar a sua gestão. O patient blood management engloba essa gestão, com relevo acrescido em situações de contingência, focado nos cuidados centrados no doente e na melhoria da segurança e dos outcomes. As barreiras à implementação de princípios patient blood management prendem-se, entre outras, com falta de padronização. Pretende--se estabelecer um consenso sobre estes diagnósticos e implementação de patient blood management na prática clínica em Portugal. Material e Métodos: Foram reunidos oito especialistas em Imuno-hemoterapia, Hematologia Clínica, Anestesiologia, Medicina Interna e Obstetrícia/ Ginecologia. Foi realizado um focus group, onde foram definidas 33 afirmações. Além disso, foi realizado um painel Delphi, com especialistas das áreas mencionadas acima, assim como de Cirurgia Geral, Urologia e Ortopedia. Resultados: As duas rondas do painel Delphi tiveram, respetivamente, 70 e 46 respondedores. Estes foram consensuais em apenas duas afirmações, na existência de consulta pré-operatória de patient blood management para os candidatos a cirurgias eletivas em que se antecipa o uso de hemoderivados e, na importância da correção da anemia e ferropenia pós-operatórias. Das 31 afirmações restantes, 27 atingiram alta concordância ou discordância pelos respondentes. Conclusão: Foi alcançado consenso em apenas duas (6%) das 33 afirmações. Houve consenso sobre a relevância de estabelecer o patient blood management como standard of care e a valorização das intervenções de patient blood management pré e pós-operatórias. No entanto, os resultados indiciam falta de consciencialização sobre os princípios de patient blood management ­ que poderiam levar a melhores resultados pós-operatórios, com redução do tempo de hospitalização e dos custos e maior disponibilidade de camas. Iniciativas de formação e literacia poderiam ajudar a uma melhor implementação dos princípios de patient blood management nos hospitais portugueses.

Effects of Innovation, Total Quality Management, and Internationalization on Organizational Performance of Higher Education Institutions.

The aim of this research is to analyze the effects of innovation strategies, Total Quality Management (TQM) dimensions, and internationalization strategies that Higher Education Institutions (HEIs) might adopt, and their effects on their organizational performance. Due to globalization and the constant changes and demands that have taken place today, HEIs are forced to seek new quality assurance instruments in higher education, to ensure greater competitiveness in the markets and their survival. To examine the association between the independent variables, namely, TQM dimensions, innovation strategies, and internationalization strategies with the dependent variable, that is organizational performance of HEIs, we have chosen to use multiple linear regression analysis. A nine-predictor multiple linear regression model was proposed. The nine predictor variables are Communication, Involvement/teacher empowerment, Development/Teacher training, Continuous improvement, Leadership/Administration's Commitment, Data analysis/Measurement of results, Focus on students, Innovation Strategies, and Internationalization strategy. We conclude that some TQM variables have a significant association with the organizational performance of HEIs, namely, Involvement/teacher empowerment, and Development/teacher training. On the other hand, also the Innovation strategies and Internationalization strategy have a significant association with the organizational performance of HEIs. This research is of enormous importance for the study of HEIs, considering their role in the development of any country and its impact on society as creators of knowledge and science. Since these institutions increasingly must deal with extremely competitive market environments, knowledge of the factors that can assist in increasing the organizational performance of HEIs is of great relevance.

ATLANTIC ANTS: a data set of ants in Atlantic Forests of South America.

Ants, an ecologically successful and numerically dominant group of animals, play key ecological roles as soil engineers, predators, nutrient recyclers, and regulators of plant growth and reproduction in most terrestrial ecosystems. Further, ants are widely used as bioindicators of the ecological impact of land use. We gathered information of ant species in the Atlantic Forest of South America. The ATLANTIC ANTS data set, which is part of the ATLANTIC SERIES data papers, is a compilation of ant records from collections (18,713 records), unpublished data (29,651 records), and published sources (106,910 records; 1,059 references), including papers, theses, dissertations, and book chapters published from 1886 to 2020. In total, the data set contains 153,818 ant records from 7,636 study locations in the Atlantic Forest, representing 10 subfamilies, 99 genera, 1,114 ant species identified with updated taxonomic certainty, and 2,235 morphospecies codes. Our data set reflects the heterogeneity in ant records, which include ants sampled at the beginning of the taxonomic history of myrmecology (the 19th and 20th centuries) and more recent ant surveys designed to address specific questions in ecology and biology. The data set can be used by researchers to develop strategies to deal with different macroecological and region-wide questions, focusing on assemblages, species occurrences, and distribution patterns. Furthermore, the data can be used to assess the consequences of changes in land use in the Atlantic Forest on different ecological processes. No copyright restrictions apply to the use of this data set, but we request that authors cite this data paper when using these data in publications or teaching events.

Ants associated with fronds of the tropical bracken fern Pteridium esculentum subsp. arachnoideum / Formigas associadas às frondes da samambaia Pteridium esculentum subsp. arachnoideum

Abstract: Pteridium is a cosmopolitan genus of ferns that possess nectaries on its fronds (fern leaves), thereby attracting ants. Foliar (or extrafloral) nectaries are nectar-producing glands that are not related to pollination, but rather attract ants and other arthropods. Foliar nectaries are found in 101 fern species, belonging to 11 genera and six families. The aim of the study is to characterize the community of ants that visit the fronds of Pteridium esculentum subsp. arachnoideum, as well as daily and seasonal ant abundance in different frond development stages. The study was conducted in the Atlantic Forest of Rio de Janeiro state, Brazil. Bimonthly collections were established, where 30 expanding fronds and 30 fully expanded fronds were randomly marked. In each 1-hour shift starting at 8:30 am and ending at 5:30 pm, the fronds were observed for the presence of ants. Thirty three ant species were recorded on the Pteridium esculentum subsp. arachnoideum fronds, distributed into six subfamilies and 13 genera. The most abundant species were Solenopsis sp.1 and Ectatomma tuberculatum. Eight ant species were observed foraging the nectaries of tropical bracken fern fronds. Ectatomma tuberculatum has been observed feeding on the nectaries and patrolling the fronds. Ant activity peak was on mid-day during the rainy season. The tropical bracken fern Pteridium esculentum subsp. arachnoideum has a rich (the highest recorded until now on Pteridium species) and diverse ant community on its fronds, mainly on the expanding fronds. The presence of generalist predatory ants (Ectatomma tuberculatum and Solenopsis sp.1) during the entire study period suggests a positive interaction between ants and Pteridium esculentum subsp. arachnoideum.

Resumo: Pteridium é um gênero cosmopolita de samambaias que possui nectários em suas frondes (folhas de samambaias), atraindo formigas. Nectários foliares (ou extraflorais) são glândulas produtoras de néctar que não estão relacionadas com a polinização, mas podem atrair formigas e outros artrópodes. Nectários foliares já foram registrados em 101 espécies de samambaias, pertencentes a 11 gêneros e seis famílias. O objetivo do estudo é caracterizar a comunidade de formigas que visitam as frondes de Pteridium esculentum subsp. arachnoideum, bem como a abundância diária e sazonal das formigas em diferentes estágios foliares. O estudo foi realizado na Mata Atlântica do estado do Rio de Janeiro, Brasil. Foram estabelecidas coletas bimestrais, onde foram marcadas aleatoriamente 30 frondes em expansão e 30 frondes totalmente expandidas. Em cada turno de 1 hora com início às 8h30 e término às 17h30, as frondes marcadas foram observadas quanto à presença de formigas. Trinta e três espécies de formigas foram registradas nas frondes do Pteridium esculentum subsp. arachnoideum, distribuídas em seis subfamílias e 13 gêneros. As espécies mais abundantes foram Solenopsis sp.1 e Ectatomma tuberculatum. Foram registradas oito espécies de formigas forrageando os nectários foliares da samambaia. Ectatomma tuberculatum foi observada se alimentando nos nectários e patrulhando as frondes. As formigas tiveram o pico de atividade ao meio-dia e na estação chuvosa. A samambaia tropical Pteridium esculentum subsp. arachnoideum tem uma elevada riqueza (a maior já registrada até o momento para espécies de Pteridium) e diversidade de formigas em suas frondes, com maior frequência nas frondes não totalmente expandidas. A presença de formigas predadoras generalistas (Ectatomma tuberculatum e Solenopsis sp.1) durante todo o período de estudo sugere uma interação positiva entre as formigas e Pteridium esculentum subsp. arachnoideum.

Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia.

Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of therapy. Thus, multi-aspect imaging of both tumor apoptosis and oxygenation in vivo would be of enormous value for the effective evaluation of therapy response. Herein, we demonstrate the capability of a hybrid imaging modality known as multispectral optoacoustic tomography (MSOT) to provide high-resolution, simultaneous imaging of tumor apoptosis and oxygenation, based on both the exogenous contrast of an apoptosis-targeting dye and the endogenous contrast of hemoglobin. MSOT imaging was applied on mice bearing orthotopic 4T1 breast tumors before and following treatment with doxorubicin. Apoptosis was monitored over time by imaging the distribution of xPLORE-APOFL750©, a highly sensitive poly-caspase binding apoptotic probe, within the tumors. Oxygenation was monitored by tracking the distribution of oxy- and deoxygenated hemoglobin within the same tumor areas. Doxorubicin treatment induced an increase in apoptosis-depending optoacoustic signal of xPLORE-APOFL750© at 24 h after treatment. Furthermore, our results showed spatial correspondence between xPLORE-APO750© and deoxygenated hemoglobin. In vivo apoptotic status of the tumor tissue was independently verified by ex vivo fluorescence analysis. Overall, our results provide a rationale for the use of MSOT as an effective tool for simultaneously investigating various aspects of tumor pathophysiology and potential effects of therapeutic regimes based on both endogenous and exogenous molecular contrasts.

Correction to the article "Viscoelastic Tests in the Evaluation of Haemostatic Disorders in SARS-CoV-2 Infection", Published on Acta Med Port 2021 Jan;34(1):35-46.

On page 36, in the fifth sentence of right-side column, where it reads: "Direct thrombin inhibitors (DTI) (argatroban, bivalirrubin) are used in COVID-19 infected patients with significantly lower antithrombin levels,24 or if heparin induced thrombocytopenia (HIT) occurs."It should read: "Direct thrombin inhibitors (DTI) (argatroban, bivalirudin) are used in COVID-19 infected patients with significantly lower antithrombin levels,24 or if heparin induced thrombocytopenia (HIT) occurs."Article published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/14784.

Viscoelastic Tests in the Evaluation of Haemostasis Disturbances in SARS-CoV2 Infection.

COVID-19 associated coagulopathy is a dysfunction of severe SARS-CoV-2 infection, characterized by significantly increased fibrinogen, D-dimer and C reactive protein and normal to near-normal prothrombin time, activated partial thromboplastin time and platelet count. Hypercoagulopathy and hypofibrinolysis coexist and are detected by viscoelastic tests. These features, when associated with immobilization and intrinsic risk factors (age, obesity, comorbidities, drugs) of the patient, can trigger thromboembolic events, despite thromboprophylaxis. The lungs are the first and most severely damaged organ. To date, most patients have exhibited hypercoagulability on viscoelastic tests not detected by standard coagulation tests. A high rate of thrombotic events was reported, suggesting that it should be considered as a cause of clinical deterioration in intensive care and potentially other clinical settings. In advanced stage, COVID-19 associated coagulopathy, fibrinogen and platelet count can decrease significantly, depending on the severity of clinical status resembling consumptive coagulopathy. In this stage, bleeding events can occur, especially if the patient is under extracorporeal membrane oxygenation (ECMO). Viscoelastic tests are very useful tools to assess hypercoagulability and hypofibrinolysis (not detectable by standard coagulation tests) in critically ill SARS-CoV-2 patients with COVID-19 associated coagulopathy and look like very promising tools for anticoagulation management. However, further research needs to be carried out to determine whether abnormal viscoelastic tests alone or in combination with other clinical or laboratory findings can identify patients at increased thrombotic risk. Clinical trials to evaluate hypercoagulability using viscoelastic tests and the need for personalized dosage of anticoagulation in SARS-CoV-2 patientsare quickly emerging.

A coagulopatia associada à COVID-19 é uma disfunção associada à infeção SARS-CoV-2 grave, caraterizada por aumento significativo do fibrinogénio, D-dímeros e Proteína C reativa, e por valores normais/muito pouco alterados do tempo de protrombina, tempo de tromboplastina parcial ativado, e número de plaquetas. A hipercoagulabilidade e a hipofibrinólise coexistem e são detetadas por testes viscoelásticos. Quando associadas à imobilização e aos fatores de risco intrínsecos do doente (idade, obesidade, comorbilidades, drogas) potenciam eventos tromboembólicos, apesar da tromboprofilaxia. Os pulmões são o órgão inicialmente e mais gravemente afetado. Até à data, a maioria dos doentes apresentou hipercoagulabilidade nos testes viscoelásticos, não detetada pelos testes de coagulação de rotina, e foi reportada uma elevada taxa de eventos trombóticos, sugerindo que esta deveria ser considerada uma das causas de deterioração clínica, não só em cuidados intensivos. Na coagulopatia associada à COVID-19 avançada, o número de plaquetas e o fibrinogénio podem diminuir significativamente, dependendo da gravidade clínica da infeção, assemelhando-se o quadro a uma coagulopatia de consumo. Nesta fase pode haver hemorragia, especialmente se o doente estiver sob extracorporeal membrane oxygenation. Os testes viscoelásticos afiguram-se muito úteis para avaliar a hipercoagulabilidade e a hipofibrinólise em doentes críticos SARS-CoV-2 com coagulopatia associada à COVID-19, parecendo também promissores para a gestão da anticoagulação. No entanto, é necessária mais investigação para determinar se testes viscoelásticos alterados, individualmente ou quando combinadoscom outros resultados clínicos/laboratoriais, podem identificar os doentes com risco trombótico acrescido. Estão a emergir rapidamente ensaios clínicos para avaliação da hipercoagulabilidade por testes viscoelásticos e da necessidade de personalização da anticoagulação em doentes SARS-CoV-2.

Screening for Anemia and Iron Deficiency in the Adult Portuguese Population.

Anemia and iron deficiency (ID) can impair quality of life and socioeconomic development. We evaluated the prevalence of anemia and ID in the adult Portuguese population in real-life contexts by gender, age, and pregnancy status. We performed a cross-sectional screening in adult individuals in mainland Portugal from 2013 to 2017. Participants completed a survey about demographics and signs or symptoms compatible with anemia, and ID and hemoglobin and ferritin concentrations were determined by point-of-care tests. We estimated and compared prevalence ratios (PR) of anemia and ID using Poisson regression with robust variance and the Wald chi-square test. We collected data from 11,030 individuals (26% men, 64% nonpregnant women, and 10% pregnant women). We found anemia in 51.8% (95% CI 50.1-53.4%) of nonpregnant women in fertile age, 46.6% (95% CI 44.7-48.6%) of nonpregnant women >51 years, 38.2% (95% CI 35.4-41.1%) of pregnant women, and 33.3% (95% CI 31.6-35.1%) of men. The prevalence of ID was 72.9% (95% CI 71.4-74.4%) in nonpregnant women in fertile age, 50.5% (95% CI 48.5-52.4%) in nonpregnant women >51 years, 94.8% (95% CI 93.3-96.0%) in pregnant women, and 28.9% (95% CI 27.3-30.6%) in men. We found significant associations between the prevalence of anemia or ID and nonpregnant women (PR: 1.50, 95% CI 1.42-1.59 or PR: 2.21, 95% CI 2.09-2.35, respectively), manifestation of signs or symptoms (PR: 1.19, 95% CI 1.53-1.23 or PR: 1.22, 95% CI 1.18-1.26), pregnant women (PR: 0.74, 95% CI 0.68-0.80 or PR: 1.30, 95% CI 1.27-1.33), and nonpregnant women ≤51 years (PR: 1.11, 95% CI 1.06-1.17 or PR: 1.42, 95% CI 1.36-1.48). In conclusion, anemia and ID represent moderate to severe public health problems, particularly among women in fertile age and in 3rd trimester, of pregnancy emphasizing the need to raise the public and health professionals' awareness of these problems and their prevention, diagnosis, and treatment.

Interventional Algorithm in Gastrointestinal Bleeding-An Expert Consensus Multimodal Approach Based on a Multidisciplinary Team.

The approach to the patient with gastrointestinal bleeding (GIB) can be very complex. A multidisciplinary panel of physicians with expertise in Gastroenterology, Anesthesiology, and Transfusion Medicine worked together to provide the best knowledge and guide clinical practitioners in the real setting of health institutions, characterized by disparate availability of human and technical resources. The authors propose a global and personalized approach according to different clinical scenarios to improve the outcomes of patients with GIB, for whom the reduction of inappropriate transfusions is crucial. The goal of this document is to provide clear and objective guidance through interventional algorithms toward a goal-directed approach according to the clinical situation and supported by the latest available scientific data on GIB management in different settings.

Factor structure of the convergence insufficiency symptom survey questionnaire.

The purpose of this study is to analyze the factorial structure of the Convergence Insufficiency Symptom Survey questionnaire with 15 items, in order to identify latent dimensions that can contribute to a more focused implementation. The questionnaire was self-administered in paper by 183 university students, in the age span of 18 to 30. Both Kaiser-Meyer-Olkin measure and Bartlett's sphericity test were performed to ensure the validity of the factorization. In order to analyze the principal components, factors which obtained eigenvalues greater than 1 were chosen. The extraction of factors was performed after computing a Promax rotation and a Kaiser criterion. In each extracted factor, the internal consistency was used to prove its reliability. Bartlett's sphericity test was statistically significant (p <0.001), and the Both Kaiser-Meyer-Olkin test was 0.89, confirming the factorization of this instrument. Exploratory factor analysis followed by a Promax rotation and scree plots graphic, extracted three factors that explained 62.1% of the total variance. The composition of each factor suggests the following meanings: Factor 1 (somatic sensation) includes 8 of 15 items; Factor 2 (impaired vision) includes 3 of 15 items; Factor 3 (cognitive performance) includes 4 of 15 items. Cronbach's alpha coefficient demonstrated good internal consistency (α> 0.75) in three dimensions. The multivariate statistical analysis of the Convergence Insufficiency Symptom Survey revealed a three-factor structure, so new forms of questionnaire analysis can be designed in order to obtain gains in the management of a symptomatic patient, using 3 subscores, one for each factor, instead of a total score. The factorial structure of the questionnaire can be used with a high level of confidence in future investigations, which aim to assess which dimensions are most affected in each type of visual changes and develop more targeted therapeutic performances.

Portal Vein Thrombosis Secondary to Occult Polycythemia Vera.

Portal vein thrombosis (PVT) is an uncommon finding in patients without cirrhosis. The underlying x\aetiology is challenging and the condition has a wide differential diagnosis. We present a case of PVT in an anaemic patient with chronic iron and folic acid deficiency masking underlying polycythemia vera (PV). Only a careful review of the patient's clinical history allowed the identification of a short period of laboratory erythrocytosis, 6 months before the clinical onset of PVT, while the patient was on iron and folic acid supplementation. The finding raised clinical suspicion of PV previously masked by iron deficiency anaemia. Subsequent investigation confirmed the presence of the JAK2 V617F mutation and, ultimately, showed that the patient met all diagnostic criteria for PV. Myeloproliferative disorders (MPD) are associated with systemic prothrombotic states. PV is distinguished clinically from other MPD by the presence of increased red blood cell mass. Moreover, patients with abnormal haematocrit values in the pre-JAK2 V617F era may have had occult or latent PV. Diagnosis confirmation requires a combination of major and minor criteria to capture occasional cases of occult PV. This case emphasizes the importance of always considering MPD in the aetiological investigation of PVT, even in patients who apparently do not fulfil the diagnostic criteria. LEARNING POINTS: We describe a rare gastroenterological presentation of a haematological condition, which provided an unexpected diagnosis.Myeloproliferative disorders should always be considered in the investigation of portal vein thrombosis.

Early Warning of Suspected Doping from Biological Passport Based on Multivariate Trends.

The indirect identification of doping in sports can be performed by assessing athletes' hematological perturbations from the analysis of blood collected on different occasions. Because prosecution for doping based on this information requires expensive and time-consuming interpretation of blood analysis results by various expert hematologists, mathematical data screening is performed to decide which cases should be forwarded to hematologists. The current Bayesian and univariate screening of data does not process the multivariate trends of blood parameters or take the time interval between samplings into account. This work presents a computational tool that overcomes these limitations by calculating a single score, the hematological perturbation index (HPIx), for which a threshold is defined above which hematologists should be asked to assess the athlete's biological passport. The doping detection from this index, normalized for days difference between samplings based on 3, 4 or 5 consecutive samplings, is associated with true positive result rates (TP) not below 98% and false positive result rates (FP) less than 0.9%. Therefore, this tool can be useful as an early warning system of hematological perturbations to decide which athletes should be more closely monitored and which biological passports should be forwarded to hematologists for medical interpretation of data.

New Lectins from Mediterranean Flora. Activity against HT29 Colon Cancer Cells.

Experiments conducted in vitro and in vivo, as well as some preclinical trials for cancer therapeutics, support the antineoplastic properties of lectins. A screening of antitumoral activity on HT29 colon cancer cells, based on polypeptide characterization and specific lectin binding to HT29 cells membrane receptors, was performed in order to assess the bioactivities present in four Mediterranean plant species: Juniperus oxycedrus subsp. oxycedrus, Juniperus oxycedrus subsp. badia, Arbutus unedo and Corema album. Total leaf proteins from each species were evaluated with respect to cell viability and inhibitory activities on HT29 cells (cell migration, matrix metalloproteinase -MMP proteolytic activities). A discussion is presented on a possible mechanism justifying the specific binding of lectins to HT29 cell receptors. All species revealed the presence of proteins with affinity to HT29 cell glycosylated receptors, possibly explaining the differential antitumor activity exhibited by the two most promising species, Juniperus oxycedrus subsp. badia and Arbutus unedo.