Three-dimensional lung parenchyma model for studies of Aspergillus fumigatus infection and antifungal treatment.

Aim: This work aims to standardize the three-dimensional hydroxyethyl-alginate-gelatin (HAG) scaffold as a model to evaluate Aspergillus fumigatus biofilm and antifungal treatments. Methods: The scaffold was characterized by physical, rheological and microscopic analyses; the antibiofilm action was evaluated by determination of cfu and metabolic activity. Results: The scaffold was non-toxic showing stability in aqueous media, swelling capacity, elasticity and had homogeneously distributed pores averaging 190 µm. The A. fumigatus biofilm established itself very well on the scaffold and treatment with amphotericin B and voriconazole reduced viable cells and metabolic activity. Conclusion: The HAG scaffold proved to be a model to mimic lung parenchyma, suitable for establishing a 3D biofilm culture of A. fumigatus and evaluating the efficacy of antifungals.

[Box: see text].

Tubeless field anaesthesia for surgical removal of an aspirated endoscopy capsule.

Capsule endoscopy is a safe, minimally invasive procedure used to investigate gastrointestinal bleeding of unknown origin that persists or recurs after a negative initial endoscopy. The most common adverse effects of capsule endoscopy include abdominal pain, nausea and vomiting. Capsule pulmonary aspiration, although a rare complication, has been reported in the literature. Most reported cases resolve without further medical intervention. In these cases, the capsule is either expelled by coughing, or it re-enters the oropharynx and is then swallowed. In a small number of cases, the capsule remains in the lung, unable to be expectorated. This requires prompt diagnosis and emergency bronchoscopic removal under general anaesthesia. Due to the smooth, rounded surfaces of the capsule, it may be difficult to grasp, and consequently extraction may be technically challenging. The existing literature contains limited documentation on anaesthetic and surgical approaches for managing an aspirated endoscopy capsule. In this case report, we present the management of an aspirated endoscopy capsule in a district general hospital, in which thoracic surgery was not available. Local resources were used to manage this potentially life-threatening complication without patient transfer. In our case, we provided a tubeless field to optimise surgical access. This facilitated the successful surgical extraction of the endoscopy capsule from the left main bronchus.

The effect of TB patient delay on loss to follow-up in Portugal.

BACKGROUND: Early identification of TB cases, followed by treatment to completion, are essential for controlling and preventing the disease. Previous studies have found some factors associated with both loss to follow-up (LTFU) and patient delay. We aim to build a causal model to investigate the association between TB patient delay and LTFU.METHODS: Pulmonary TB cases were identified using the national surveillance system in Portugal between 2008 and 2017. A directed acyclic graph was used to identify the minimal set of variables to adjust for when studying the association between delay (exposure) and LTFU (outcome). Crude and adjusted hazard were estimated using Cox regression.RESULTS: Nearly 4% of the patients did not follow up treatment. There was no association between patient delay and LTFU, even after adjustment with the minimal set of covariates. Factors associated with a higher risk of LTFU were being younger, being unemployed, living in urban areas, having HIV and the abuse of alcohol and drugs.CONCLUSION: Patient delay was not associated with LTFU, while social conditions were. Future research should investigate the underlying reasons why patients discontinue TB treatment and use these findings to develop targeted interventions that can support patients in completing their treatment regimen.

T-type Ca2+ channels and their relationship with pre-neoplastic and neoplastic lesions in the human breast.

The expression of T-type voltage-dependent Ca2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ. These results suggest a possible involvement of CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.

Lung cancer survival and sex-specific patterns in Portugal: A population-based analysis.

INTRODUCTION: In Portugal, lung cancer (LC) is the first cause of cancer-related death and of death and disability combined. This study aims to analyze the overall survival (OS) and relative survival (RS) of patients diagnosed with LC in 2009-2011 by socio-demographic and tumor characteristics, and analyze sex-specific patterns. METHODS: We estimated 5-year OS using the Kaplan-Meier method and 5-year net survival through the RS framework. Cox regression modeling was used to determine the hazard ratio (HR) of death associated with each independent variable. FINDINGS: For the 11,523 cases analyzed, median 5-year OS was 264 days (95% confidence interval [CI]: 254.8-273.2), the cumulative OS was 13.6% and RS was 15.1%. Males had a lower median survival (237 days; 95% CI: 228.2-245.7) compared to females (416 days; 95% CI: 384.4-447.6) (p < 0.0001) and lower 5-year RS proportions (12.1% vs. 24.9%). RS progressively decreased with age (41.7% for age-group <40 to 7.2% for ≥80) and stage (66.6% for stage I to 2.4% for stage IV). As predictors of decreased survival, we identified male gender, increasing age >50, histologic types (squamous cell carcinoma, non-small cell lung cancer not otherwise specified, other unspecified and small cell lung cancer), and increasing stage. Compared to women, the risk of death in men was 37.7% higher (HR = 1.386; 95% CI: 1.295-1.484). CONCLUSIONS: The differences between OS and RS were small, reflecting the high lethality of LC. Male gender and older age are factors related to poor prognosis. Histology also plays a role in survival prognosis and varies with gender, but the factor related to the worst survival is stage. Although the study reflects data from a decade ago, and major changes occurred in diagnosis, staging and treatment, particularly for advanced disease, as LC mortality is strongly correlated with late stage diagnosis, all efforts should be made to secure early diagnosis and improve survival prospects.

T-type Ca2+ channels and their relationship with pre-neoplastic and neoplastic lesions in the human breast

The expression of T-type voltage-dependent Ca2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ. These results suggest a possible involvement of CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.

Non-adherence to COVID-19 lockdown: who are they? A cross-sectional study in Portugal.

OBJECTIVES: The SARS-CoV-2 virus has spread worldwide, leading governments to implement mitigation measures. Understanding the reluctance to adhere to non-pharmacological interventions might help promote adherence to these measures. This study aimed to identify factors associated with non-adherence to the first lockdown in Portugal. STUDY DESIGN: Cross-sectional study. METHODS: This study used data from a Portuguese community-based survey entitled 'COVID-19 Barometer: Social Opinion'. Data were collected on risk perception, health status and social experiences using a snowball sampling technique. The event of interest corresponded to participants who reported not staying home during the lockdown period, serving as a proxy for non-adherence to lockdown. Logistic regression was used to identify factors associated with non-adherence to the first lockdown. RESULTS: Responses from 133,601 individual questionnaires that were completed during the first week of the first lockdown in 2020 were analysed. A minority of participants (5.6%) reported non-adherence to lockdown (i.e. leaving home for reasons other than essential situations). Working in the workplace was the factor with the strongest association of non-adherence to the lockdown. Several other factors were also associated with non-adherence to the first lockdown; namely, being a man, being a student, having a low level of education, having a low income, living alone or with a high-infection-risk professional (e.g. doctor, nurse, pharmaceutical, health technician, firefighter, police officer, military, essential services worker), perceiving the risk of getting COVID-19 to be high, not having social support in case of infection, feeling agitated, sad or anxious every day, and considering the preventive measures to be unimportant or inadequate. CONCLUSIONS: Non-adherence to lockdown was associated with socio-economic, trust and perception factors. Future research should investigate the mechanisms underlying these associations to help identify the population groups who are most at risk of non-adherence.

Ecological factors associated with areas of high tuberculosis diagnosis delay.

OBJECTIVE: We aimed to identify areas of high tuberculosis (TB) diagnosis delay in mainland Portugal in 2017 and ecological factors associated with these areas. STUDY DESIGN: This was an ecological study. METHODS: We considered all notified pulmonary TB cases from the Portuguese National Tuberculosis Surveillance System in mainland Portugal. Diagnostic delays were calculated at the municipality level. Demographic variables, proxies for TB awareness, health services capacity indicators, and socio-economic variables were included and extracted from official databases, such as Statistics Portugal, Ministeries, Foreigners and Border Services. We used spatial analysis to identify areas of high delay in 2017 and logistic generalised additive models to identify ecological factors associated with the identified cluster. RESULTS: We identified an area of high delay in 2017 in the South region of the country. Overall, municipalities with a smaller population density, smaller proportion of unemployed, fewer health centres and higher old-age dependency ratio, proportion of men, TB incidence, proportion of immigrants and high school dropout had a higher probability of belonging in a high delay area. CONCLUSION: The role of primary health care in TB diagnosis should be further explored. Interventions should address factors interplaying at the local and individual levels. Policies influencing social and health conditions, leading to changes in individual behaviour, can lead to sustained improvements over time.

Toughening robocast chitosan/biphasic calcium phosphate composite scaffolds with silk fibroin: Tuning printable inks and scaffold structure for bone regeneration.

The present work aims the production of composite bioceramic scaffolds by robocasting suppressing sintering as post printing process. To achieve this purpose, extrudable ink compositions containing a high concentration of bioceramic powders (hydroxyapatite and ß-tricalcium phosphate) embedded in aqueous polymeric solutions of chitosan and silk fibroin were fine-tuned. Polymeric solutions of chitosan/silk fibroin with different ratios were tested, maintaining the total amount of bioceramic solids at 30 vol%. The inks were characterized by rheological studies in viscometry and oscillatory modes, being the printable ones selected to produce scaffolds with different macropore sizes (300 µm and 500 µm). The scaffolds were characterized by mechanical properties (dry and wet conditions) and morphological features, as well as its degradability. In vitro studies were also evaluated in the scaffolds that presented the best structural performance. The addition of 2 wt% silk fibroin to a 5 wt% chitosan matrix allows to significantly improve the mechanical performance of the printed composite scaffolds, reflected in high values for Young's modulus and maximum compressive strength. This trend was continued in wet scaffolds with a concomitant reduction of mechanical properties. Regarding degradability, the scaffolds in general presented a weight loss in the range of 14-18% after 28 days incubation in HEPES solution at two different pH values at 37 °C, with an associated release of calcium and phosphorus ions. The scaffold with 300 µm porosity comprising the both polymers in its composition presented the less rate degradation when compared to the scaffolds with similar porosity and containing only chitosan as base matrix. Moreover, the combined natural polymers gave rise to a significant increase in the metabolic activity of human osteoblasts grown on the scaffolds with both macropore' size, being in line with the full cellular filling of their surfaces, demonstrated by SEM and confocal imaging. The advances presented in this work are a promising path in the ink's development for extrusion-based additive manufacturing techniques and subsequent biomaterials, encompassing suitable physical and chemical characteristics with high potential to be used as bone substitutes.

Teaching young consumers in Europe: a multicentre qualitative needs assessment with educators on food hygiene and food safety.

AIM: Foodborne illnesses have a significant global burden and can be life-threatening, with higher risk in vulnerable groups such as children. SafeConsume is an EU-funded, transdisciplinary project aiming to improve consumers' food safety behaviour. Developing educational resources on food safety for use in schools has potential to improve teaching of our young consumers. The aim of this study was to explore school educators' attitudes, behaviours and knowledge towards food hygiene, safety and education. METHODS: Focus groups and interviews in England, France, Portugal and Hungary explored educator knowledge, skills, intentions and beliefs around educating young people (11-18 years) about food safety. Data were analysed using NVivo and emerging themes were applied to the Theoretical Domains Framework. RESULTS: A total of 48 educators participated. Knowledge, confidence and skills to teach food safety to young people varied depending on background and training. Educators reported they had a role to teach food safety to young people, were positive about delivering education and optimistic they could improve students' food safety behaviour. Barriers to teaching included lack of national curriculum coverage, limited time and money, and lack of facilities. Educators reported that social influences (family, celebrity chefs, public health campaigns and social media) were important opportunities to improve young peoples' awareness of food safety and consequences of foodborne illness. CONCLUSION: Educator food safety expertise varied; training could help to optimise educator knowledge, confidence and skills. Ministries of Health and Education need encouragement to get food safety incorporated further into school curricula across Europe, so schools will be motivated to prioritise these topics.

Prospective international validation of the predisposition, infection, response and organ dysfunction (PIRO) clinical staging system among intensive care and general ward patients.

BACKGROUND: Stratifying patients with sepsis was the basis of the predisposition, infection, response and organ dysfunction (PIRO) concept, an attempt to resolve the heterogeneity in treatment response. The purpose of this study is to perform an independent validation of the PIRO staging system in an international cohort and explore its utility in the identification of patients in whom time to antibiotic treatment is particularly important. METHODS: Prospective international cohort study, conducted over a 6-month period in five Portuguese hospitals and one Australian institution. All consecutive adult patients admitted to selected wards or the intensive care, with infections that met the CDC criteria for lower respiratory tract, urinary, intra-abdominal and bloodstream infections were included. RESULTS: There were 1638 patients included in the study. Patients who died in hospital presented with a higher PIRO score (10 ± 3 vs 8 ± 4, p < 0.001). The observed mortality was 3%, 15%, 24% and 34% in stage I, II, III and IV, respectively, which was within the predicted intervals of the original model, except for stage IV patients that presented a lower mortality. The hospital survival rate was 84%. The application of the PIRO staging system to the validation cohort resulted in a positive predictive value of 97% for stage I, 91% for stage II, 85% for stage III and 66% for stage IV. The area under the receiver operating characteristics curve (AUROC) was 0.75 for the all cohort and 0.70 if only patients with bacteremia were considered. Patients in stage III and IV who did not have antibiotic therapy administered within the desired time frame had higher mortality rate than those who have timely administration of antibiotic. CONCLUSIONS: To our knowledge, this is the first external validation of this PIRO staging system and it performed well on different patient wards within the hospital and in different types of hospitals. Future studies could apply the PIRO system to decision-making about specific therapeutic interventions and enrollment in clinical trials based on disease stage.

Patient and healthcare delays in critical and non-critical pulmonary tuberculosis incidence areas in Portugal: are there differences?

OBJECTIVES: To characterize patient, healthcare, and total delay in diagnosing pulmonary tuberculosis (PTB) in critical (higher PTB incidence) and non-critical (lower PTB incidence) areas and their determinants considering clinical and sociodemographic factors. STUDY DESIGN: Retrospective cohort study. METHODS: Data was retrieved from the Portuguese National Tuberculosis Surveillance System (SVIG-TB). Were included in the study all active PTB patients (n = 11,762) notified between 2008 and 2017. Spatial analysis was used to define critical and non-critical areas. Kaplan-Meier estimator, logrank test, and Cox regression were conducted, stratified by area. RESULTS: PTB cases in critical areas (n = 6594, 56.1%) presented longer patient median delay (41 vs 31days), shorter healthcare median delay (7 vs 10 days), and longer total median delay (63 vs 61days) t.han non-critical areas. Patient and total delay increased in both areas over time, while healthcare delay only increased in non-critical areas. Icn both areas, being from a high TB incidence country and alcohol abuse were associated with longer patient delays. Being female, older age, and oncologic diseases were associated with longer healthcare delays. Respiratory diseases were only associated with a longer healthcare delay in non-critical areas. Being female, older, and from a high TB incidence country were associated with a longer total delay in both areas. CONCLUSIONS: Patient delay was significantly longer in critical areas, and healthcare delay was significantly longer in non-critical areas. Several factors associated with longer delays have been identified, most of which are shared by critical and non-critical areas. Differences in patient and healthcare delay, for example, by sex, age, or country of birth, highlight the need for targeted public health interventions to help reduce these differences.

Early Cerebrovascular Ultrasonography as a Predictor of Hemorrhagic Transformation After Thrombectomy.

OBJECTIVES: To determine the predictive value of early transcranial color-coded sonography (TCCS) for intracranial hemorrhage (ICH) in patients with large artery occlusion (LAO) stroke of carotid circulation, who were submitted to endovascular therapy (EVT) with successful reperfusion. MATERIALS AND METHODS: Retrospective study evaluating a cohort of consecutive stroke patients with LAO of the carotid circulation that were recanalyzed with EVT. We measured angle-corrected peak systolic velocities, end-diastolic velocities and mean flow velocities (PSV, EDV and MFV) of the symptomatic and asymptomatic middle cerebral artery (MCA). The ratio between MFV of the symptomatic MCA and MFV of the asymptomatic MCA (MCA-Ra) was calculated. Parenchymal hematoma in the 24 hours control CT was considered as ICH. Univariate associations and multivariate analyses were used to identify early independent predictors for ICH among TCCS findings. RESULTS: We included 234 patients, mean age 72.5 (SD 12.6) years, 52.1% male. The mean time between recanalization and TCCS was 12.3 hours (range 3-22). Patients who developed postinterventional ICH showed a higher MCA-Ra (1.02 ± 0.26 vs 1.16 ± 0,21, p = 0.036). In multivariate analysis, only higher MCA-Ra remained independently associated with postinterventional ICH (OR: 6.778, 95%CI: 1.152-39.892, p = 0.034). A value of MCA-Ra ≥ 1,05 was associated with ICH, showing a sensitivity of 81.3% and a specificity of 65.9%; the AUC based of the ROC analysis was 0.688 (95% CI 0.570-0.806). CONCLUSION: TCCS performed within the first 24 hours after stroke onset can help to predict hemorrhagic transformation in patients with LAO.

A influência de variáveis contextuais e situacionais na classificação de árbitros de futebol de elite / La influencia de las variables contextuales y situacionales en la clasificación de los árbitros de fútbol de élite / The influence of contextual and situational variables on the classification of elite soccer referees

OBJETIVO: Este estudo teve como objetivo avaliar a relação entre a classificação de árbitros de futebol de elite e variáveis contextuais e situacionais que caraterizam os jogos arbitrados no decorrer de uma época. Para tal, foi realizada uma regressão ordinal com função Link Logit entre a classificação final e variáveis contextuais e situacionais. As variáveis contextuais revelaram um efeito significativo sobre a classificação final, não se verificando efeitos significativos das variáveis situacionais, sobre a classificação dos árbitros no final da época desportiva. Na globalidade o modelo revelou-se estatisticamente significativo. A probabilidade de obtenção de melhor classificação final dos árbitros aumenta 54.2% com o aumento do número de jogos realizados na I Liga e aumenta 24.8% com aumento do número de jogos equilibrados. Diminui 61.2% com jogos realizados sem equipas Top 3. Os resultados reforçam a influência significativa que os fatores contextuais têm sobre a classificação e avaliação de um árbitro no final da época desportiva

OBJETIVO: Este trabajo tuvo como objetivo evaluar la relación entre la clasificación de árbitros de fútbol de élite y las variables contextuales y situacionales que caracterizan los juegos de árbitrados durante la temporada desportiva. Para ello se realizó una regresión ordinal con función Link Logit entre la clasificación final y las variables contextuales y situacionales. Las variables contextuales tuvieron un efecto significativo en la clasificación final, sin efectos significativos de las variables situacionales, en la clasificación de los árbitros al final de la temporada deportiva. En general, el modelo se ai revelado como estadísticamente significativo. La probabilidad de obtener una mejor clasificación final de los árbitros aumenta 54,2% con el incremento del número de partidos julgados en La Liga, y 24,8% con el incremento del número de partidos equilibrados. Disminuye 61,2% con partidos jugados sin equipos Top 3. Los resultados refuerzan la influencia significativa que los factores contextuales tienen en la clasificación y evaluación de un árbitro al final de la temporada deportiva

OBJECTIVE: This study aimed to evaluate the relationship between the classification of elite soccer referees and the contextual and situational variables that characterize the matches refereed during a sports season. So, an ordinal regression with Link Logit function was carried out between the final classification and the contextual and situational variables. The contextual variables revealed a significant effect on the final classification, with no significant effects of the situational variables, on the classification of referees at the end of the sports season. In general, the model proved to be statistically significant. The probability of obtaining a better final referees classification increases 54.2% with the increase in the number of games played in the I League and 24.8% with the increase in the number of balanced games. Decreases 61.2% with games played without Top 3 teams. The results reinforce the significant influence that contextual factors have on the classification and assessment of a referee at the end of the sports season

REALMS study: real-world effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis in Portugal.

BACKGROUND: Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal. METHODS: Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected. RESULTS: Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study. CONCLUSIONS: Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.

Growth kinetics of Myceliophthora thermophila M.7·7 in solid-state cultivation.

AIMS: This work aimed to estimate the growth of Myceliophthora thermophila M.7·7 in solid-state cultivation (SSC) through quantification of N-acetyl-d-glucosamine (NAG) and enzyme activity. METHODS AND RESULTS: The fungus was cultivated in sugarcane bagasse and wheat bran. A consistent statistical analysis was done to assess the reliability of experimental data. Logistic model equation was fitted to experimental data and growth parameters were estimated. The results showed strong influence of the sample size on NAG and a minimum recommended sample size was identified. Scanning electron microscopy (SEM) was used to identify the strategy of substrate colonization. Wheat bran was attacked firstly, while sugarcane bagasse was consumed after wheat bran depletion. The biomass growth was poorly estimated by secretion kinetics of α-amylase, endoglucanase, protease and xylanase, but enzyme kinetics were important for understanding substrate colonization. CONCLUSIONS: In conclusion, the NAG concentration was strongly affected by the sample size and sampling procedure. The strategy of fungal colonization on the substrates was well characterized through SEM analysis. The colonization strategy has direct influence on the kinetic parameters of the logistic model. Myceliophthora thermophila has a well-defined dynamic of enzyme secretion to degrade the substrate, although the kinetics of enzyme secretion has shown not adequate to characterize the kinetics of fungal growth. SIGNIFICANCE AND IMPACT OF THE STUDY: The paper provides reliable growth kinetic parameters in the SSC of the cellulase producer fungus M. thermophila M.7·7, as well as a robust analysis on three indirect methods (NAG, enzymes and SEM) for estimation of fungal development.

Targeted nanostructured lipid carriers for doxorubicin oral delivery.

The treatment with anticancer drugs remains a challenge, as available drugs still entail the risk of deleterious off-target effects. The present study describes folic acid conjugated nanostructured lipid carriers (NLCs) as an effective doxorubicin delivery approach targeted to breast cancer cells. Two distinct NLCs formulations were designed and optimized leading to an encapsulation efficiency over than 65%. Cytotoxic and targeting potential of NLCs were studied in vitro, using MDA-MB-231 cell line. Results showed an enhanced cellular uptake of conjugated NLCs. In vitro release studies, mimicking the path in the body after oral administration, show that all formulations would reach the tumor microenvironment bearing 50% of the encapsulated doxorubicin. Moreover, NLCs demonstrated storage stability at 25 °C for at least 42 days. Overall, results revealed that the developed NLCs enable the possibility of oral administration and are a promising approach for the targeted delivery of doxorubicin to breast cancer cells.

Healthy immigrant effect in non-European Union immigrants in Portugal: after a decade of (non-)integration!

OBJECTIVES: The aim of the study was to characterise the existence of the healthy immigrant effect (HIE; better health initially, worsening with an increase in the length of residence) in a big city from a Western European country, particularly in a non-European Union immigrant population. STUDY DESIGN: This is a cross-sectional study. METHODS: We used data from the National Health Survey 2014 to compare the health status of the immigrant and Portuguese populations with different lengths of residence. After descriptive statistics, binary logistic regressions models, with adjusted levels and 95% confidence intervals, were used. RESULTS: Immigrants were healthier than the Portuguese population (<10 years: odds ratio [OR] = 0.07; 95% confidence interval [CI] = [0.01; 0.51]; ≥10 years: OR = 0.62; 95% CI = [0.19; 2.03]), but had an increased likelihood of suffering from chronic diseases and risk behaviours with the increase in their length of stay in Portugal. After living in Portugal for more than 10 years, the immigrants showed no statistical difference in the main health indicators. CONCLUSIONS: There was a tendency for the health status of immigrants to deteriorate over 10 years of residence in Portugal. To better understand the reasons behind the HIE, specific and tailored studies must be developed.