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The timely identification of cohort participants at higher risk for attrition is important to earlier interventions and efficient use of research resources. Machine learning may have advantages over the conventional approaches to improve discrimination by analysing complex interactions among predictors. We developed predictive models of attrition applying a conventional regression model and different machine learning methods. A total of 542 very preterm (< 32 gestational weeks) infants born in Portugal as part of the European Effective Perinatal Intensive Care in Europe (EPICE) cohort were included. We tested a model with a fixed number of predictors (Baseline) and a second with a dynamic number of variables added from each follow-up (Incremental). Eight classification methods were applied: AdaBoost, Artificial Neural Networks, Functional Trees, J48, J48Consolidated, K-Nearest Neighbours, Random Forest and Logistic Regression. Performance was compared using AUC- PR (Area Under the Curve—Precision Recall), Accuracy, Sensitivity and F-measure. Attrition at the four follow-ups were, respectively: 16%, 25%, 13% and 17%. Both models demonstrated good predictive performance, AUC-PR ranging between 69 and 94.1 in Baseline and from 72.5 to 97.1 in Incremental model. Of the whole set of methods, Random Forest presented the best performance at all follow-ups [AUC-PR 1 : 94.1 (2.0); AUC-PR 2 : 91.2 (1.2); AUC-PR 3 : 97.1 (1.0); AUC-PR 4 : 96.5 (1.7)]. Logistic Regression performed well below Random Forest. The top-ranked predictors were common for both models in all follow-ups: birthweight, gestational age, maternal age, and length of hospital stay. Random Forest presented the highest capacity for prediction and provided interpretable predictors. Researchers involved in cohorts can benefit from our robust models to prepare for and prevent loss to follow-up by directing efforts toward individuals at higher risk.

Background Exclusive breastfeeding is the optimal infant nutrition, providing infants immunoprotection against many diseases including SARS-CoV-2 infection. Restrictions during the COVID-19 pandemic may have negatively affected breastfeeding practices in maternity care facilities. The aims of the study were to examine exclusive breastfeeding rates at discharge over time and to identify factors associated with exclusive breastfeeding during the pandemic. Methods A cross-sectional survey was conducted among mothers who gave birth in a maternity care facility in the World Health Organization (WHO) European Region countries during the COVID-19 pandemic. The socio-ecological model was employed to examine intrapersonal, interpersonal, organizational, and community/society factors associated with maternal report of exclusive breastfeeding at the time of discharge. Results There were 26,709 participating mothers from 17 European Region countries who were included in the analysis. Among the mothers, 72.4% ( n  = 19,350) exclusively breastfed and 27.6% ( n  = 7,359) did not exclusively breastfeed at discharge. There was an overall decline in exclusive breastfeeding rates over time ( p  = 0.015) with a significantly lower rate following the publication of the WHO breastfeeding guidelines on 23 June 2020 (AOR 0.88; 95% CI 0.82, 0.94). Factors significantly associated with exclusive breastfeeding outcomes in the logistic regression analysis included maternal age, parity, education, health insurance, mode of birth, inadequate breastfeeding support, lack of early breastfeeding initiation, lack of full rooming-in, birth attendant, perceived healthcare professionalism and attention, facility room cleanliness, timing of birth, and location of birth. Conclusions Results from the study indicate the decline in exclusive breastfeeding rates in the WHO European Region during the COVID-19 pandemic. Using the socio-ecological model to identify factors associated with breastfeeding outcomes facilitates an integrated and holistic approach to address breastfeeding needs among women across the region. These findings demonstrate the need to augment breastfeeding support and to protect exclusive breastfeeding among mother-infant dyads, in an effort to reverse the declining exclusive breastfeeding rates. The study highlights the need to educate mothers and their families about the importance of exclusive breastfeeding, reduce maternal-infant separation, increase professional breastfeeding support, and follow evidence-based practice guidelines to promote breastfeeding in a comprehensive and multi-level manner. Trial registration number Clinical Trials NCT04847336.

In a cohort of children born very preterm (VPT), we investigated the association between breast milk feeding (BMF) initiation and its duration on cognitive development at 2 years of corrected age. Data were obtained from the Effective Perinatal Intensive Care in Europe population‐based prospective cohort of children born <32 weeks of gestation, in 11 European countries, in 2011–2012. The study sample included 4323 children. Nonverbal cognitive ability was measured applying the Parental Report of Children's Abilities, except for France where the problem‐solving domain of the Ages & Stages Questionnaire was used. Verbal cognition was based on the number of words the child could say. To determine the association between BMF (mother's own milk) and nonverbal and verbal cognition (outcome categorized as optimal and suboptimal), adjusted risk ratios (aRRs) were estimated fitting Poisson regression models, with inverse probability weights to account for nonresponse bias. Overall, 16% and 11% of the children presented suboptimal nonverbal and verbal cognition, respectively. Never BMF was associated with a significantly increased risk for suboptimal nonverbal (aRR = 1.29, 95% confidence interval [CI] = 1.09–1.53) and verbal (aRR = 1.45, 95% CI = 1.09–1.92) cognitive development compared with those ever breastfed, after adjustment for perinatal and sociodemographic characteristics. Compared with children breastfed 6 months or more, children with shorter BMF duration exhibited a statistically nonsignificant elevated aRR. VPT children fed with breast milk had both improved nonverbal and verbal cognitive development at 2 years in comparison with never breastfed, independently of perinatal and sociodemographic characteristics. This study encourages targeted interventions to promote BMF among these vulnerable children. In a European cohort of children born very preterm, we investigated the association between breast milk initiation and its duration on cognitive development at 2 years of corrected age. We found that never‐breastfed children faced a higher risk of having suboptimal nonverbal and verbal cognition at 2 years of corrected age when compared with those who were breastfed, independently of perinatal and sociodemographic characteristics. Key messages In a European cohort of children born very preterm, 16% and 11% presented suboptimal nonverbal and verbal cognitive development, respectively. Never‐breastfed children faced a higher risk of having suboptimal nonverbal and verbal cognition at 2 years of corrected age when compared with those who were breastfed, independently of perinatal and sociodemographic characteristics. Breastfeeding support is a modifiable factor regardless of perinatal and sociodemographic characteristics, which reinforces the importance of specifically targeted interventions to protect, promote and support breast milk feeding in neonatal intensive care units and after discharge.

Preterm birth is a global health concern. Its adverse consequences may persist throughout the life course, exerting a potentially heavy burden on families, health systems, and societies. In high-income countries, the first children who benefited from improved care are now adults entering middle age. However, there is a clear gap in the knowledge regarding the long-term outcomes of individuals born preterm. This study aimed to assess the feasibility of recruiting and following up an e-cohort of adults born preterm worldwide and provide estimations of participation, characteristics of participants, the acceptability of questions, and the quality of data collected. We implemented a prospective, open, observational, and international e-cohort pilot study (Health of Adult People Born Preterm-an e-Cohort Pilot Study [HAPP-e]). Inclusion criteria were being an adult (aged ≥18 years), born preterm (<37 weeks of gestation), having internet access and an email address, and understanding at least 1 of the available languages. A large, multifaceted, and multilingual communication strategy was established. Between December 2019 and June 2021, inclusion and repeated data collection were performed using a secured web platform. We provided descriptive statistics regarding participation in the e-cohort, namely, the number of persons who registered on the platform, signed the consent form, initiated and completed the baseline questionnaire, and initiated and completed the follow-up questionnaire. We also described the main characteristics of the HAPP-e participants and provided an assessment of the quality of the data and the acceptability of sensitive questions. As of December 31, 2020, a total of 1004 persons had registered on the platform, leading to 527 accounts with a confirmed email and 333 signed consent forms. A total of 333 participants initiated the baseline questionnaire. All participants were invited to follow-up, and 35.7% (119/333) consented to participate, of whom 97.5% (116/119) initiated the follow-up questionnaire. Completion rates were very high both at baseline (296/333, 88.9%) and at follow-up (112/116, 96.6%). This sample of adults born preterm in 34 countries covered a wide range of sociodemographic and health characteristics. The gestational age at birth ranged from 23+6 to 36+6 weeks (median 32, IQR 29-35 weeks). Only 2.1% (7/333) of the participants had previously participated in a cohort of individuals born preterm. Women (252/333, 75.7%) and highly educated participants (235/327, 71.9%) were also overrepresented. Good quality data were collected thanks to validation controls implemented on the web platform. The acceptability of potentially sensitive questions was excellent, as very few participants chose the \"I prefer not to say\" option when available. Although we identified room for improvement in specific procedures, this pilot study confirmed the great potential for recruiting a large and diverse sample of adults born preterm worldwide, thereby advancing research on adults born preterm.

Caffeine is a bioactive compound worldwide consumed with effect into the brain. Part of its action in reducing incidence or delaying Alzheimer’s and Parkinson’s diseases symptoms in human is credited to the adenosine receptors properties. However, the impact of caffeine consumption during aging on survival of brain cells remains debatable. This work, we investigated the effect of low-dose of caffeine on the ectonucleotidase activities, adenosine receptors content, and paying particular attention to its pro-survival effect during aging. Male young adult and aged Swiss mice drank water or caffeine (0.3 g/L) ad libitum for 4 weeks. The results showed that long-term caffeine treatment did not unchanged ATP, ADP or AMP hydrolysis in hippocampus when compared to the mice drank water. Nevertheless, the ATP/ADP hydrolysis ratio was higher in young adult (3:1) compared to the aged (1:1) animals regardless of treatment. The content of A1 receptors did not change in any groups of mice, but the content of A2A receptors was reduced in hippocampus of mice that consumed caffeine. Moreover, the cell viability results indicated that aged mice not only had increased pyknotic neurons in the hippocampus but also had reduced damage after caffeine treatment. Overall, these findings indicate a potential neuroprotective effect of caffeine during aging through the adenosinergic system.

Alheira is a naturally fermented meat sausage traditionally made in the Portuguese region of Trás-os-Montes. Lactic acid bacteria (LAB) are the dominant microorganisms in alheira and can endow it with various technological properties. This study aimed (1) to characterize technological features and in vitro antimicrobial activity of LAB isolated from alheira, and (2) to reveal associations between such phenotypic characteristics and the isolates species identified through amplification and sequencing of the 16S ribosomal gene. Sixty-two LAB isolates were identified and Enterococcus (E.) faecium corresponded to 32.3% of isolates, followed by Leuconostoc (L.) mesenteroides (19.4%) and Latilactobacillus (Lb.) sakei (17.7%), aligning with previous research on traditional Portuguese fermented meat sausages. The phenotypic analysis of LAB isolates indicated diverse acidification capacities, proteolytic activities, and inhibitory effects against foodborne pathogens Listeria (L.) monocytogenes, Salmonella (S.) Typhimurium and Staphylococcus (S.) aureus. Overall, lactobacilli displayed high inhibition activity against the pathogens S. aureus, L. monocytogenes, and S. Typhimurium. Although the mechanisms for the inhibition of pathogen growth need to be further elucidated, these findings enhance our understanding of LAB diversity and functionality in alheira sausages, contributing to product safety and quality.

Objective Scientific scrutiny has proved the safety and benefits of caffeine to treat apnoea of prematurity (AOP). However, there is no consensus on the effects of this treatment on sleep, especially considering the key role of adenosine and early brain development for sleep maturation. We systematically reviewed studies with sleep as a primary and/or secondary outcome or any mention of sleep parameters in the context of caffeine treatment for AOP. Methods We performed a systematic search of PubMed, Web of Science and the Virtual Health Library from inception to 7 September 2022 to identify studies investigating the short- and long-term effects of caffeine to treat AOP on sleep parameters. We used the PIC strategy considering preterm infants as the Population, caffeine for apnoea as the Intervention and no or other intervention other than caffeine as the Comparison. We registered the protocol on PROSPERO (CRD42021282536). Results Of 4019 studies, we deemed 20, including randomised controlled trials and follow-up and observational studies, to be eligible for our systematic review. The analysed sleep parameters, the evaluation phase and the instruments for sleep assessment varied considerably among the studies. The main findings can be summarised as follows: (i) most of the eligible studies in this systematic review indicate that caffeine used to treat AOP seems to have no effect on key sleep parameters and (ii) the effects on sleep when caffeine is administered earlier, at higher doses or for longer periods than the most common protocol have not been investigated. There is a possible correlation between the caffeine concentration and period of exposure and negative sleep quality, but the sleep assessment protocols used in the included studies did not have high-quality standards and could not provide good evidence. Conclusions and implications Sleep quality is an important determinant of health, and better investments in research with adequate sleep assessment tools are necessary to guarantee the ideal management of children who were born preterm.

Background Maternal country of birth has been associated with perinatal health outcomes but less is known regarding breastfeeding practices in contemporary European settings. This study investigated effect of maternal country of birth on breastfeeding initiation and duration by comparing native Portuguese and migrant mothers. Methods We analyzed data of 7065 children of the Generation XXI (GXXI) birth cohort recruited at birth (2005–06) and followed-up 4 years later. Logistic regression was used to assess the effect of maternal country of birth on breastfeeding initiation. Kaplan-Meier estimate was used to compare breastfeeding duration by maternal country of birth and length of residence by migrant mothers in Portugal. Results Breastfeeding initiation and the type of breastfeeding practice were similar for native Portuguese and migrant mothers. The migrants had significantly higher median duration in months of any breastfeeding (Odds Ratio [OR] 6.0, 95% Confidence Interval [CI] 5.4,6.6) and exclusive breastfeeding (OR 4.0, 95% CI 3.8,4.2) than native Portuguese mothers (OR 4.0, 95% CI 3.8,4.2 and OR 3.0, 95% CI 2.9,3.0). Migrant mothers who resided in Portugal for either ≤5 years (OR 5.0, 95% CI 3.9,6.1 and OR 4.0, 95% CI 3.8,4.2) or >  5 years (OR 6.0, 95% CI 5.5,6.5 and OR 4.0, 95% CI 3.7,4.3) years had similar duration of any breastfeeding or exclusive breastfeeding, in both cases higher than the native Portuguese mothers. No significant differences were found when world regions were compared. Conclusions Maternal country of birth does not influence breastfeeding initiation and type of feeding practice. However, migrant mothers have longer breastfeeding duration of either exclusive or any breastfeeding, which was not changed by length of residence in Portugal.

The aim of this study is to prepare and characterize simvastatin-loaded nanoemulsions (SIM-LN) as well as evaluate their physicochemical properties and toxicity. The SIM-LN were prepared, their characteristics evaluated for 30 days, and after that, the SIM-LN toxicity was evaluated using Vero cell culture and the model of . The prepared SIM-LN had an average droplet size of 139 ± 22 nm, with high encapsulation rate (>98.4%). The storage at room temperature proved to be the most optimal condition. Toxicity assays demonstrated no toxicity. It was demonstrated that the surfactants used as emulsifiers optimized the properties without side effects, because no toxicity was measured in preliminary tests.

Rodrigues discusses and introduces to an international audience Manuela Bacelar and her groundbreaking work in the field of Portuguese picturebooks. Bacelar was one of the precursors of and the most emblematic voice in Portugal's picturebook segment. Rather than telling a story, Bacelar's picturebooks set up a sort of game with the reader, where both text and illustrations mutually complete each other and where all elements combine and act in the construction of meaning, allowing room for ambiguity by encouraging anticipation and prediction in more attentive and curious readers. Bacelar strives to challenge both her younger and older readers. She reworks and renews ancestral works through her subversion and the consequent recourse to reinterpretative processes such as humor, parody, satire, and irony, demonstrating aesthetic and intertextual virtuosity. Bacelar's work brings the reader closer to names and works of the Western cultural tradition and offers allegorical visions of a broad set of symbols, images, and myths.