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  • Detection of Patients at Risk of Multidrug-Resistant Enterobacteriaceae Infection Using Graph Neural Networks: A Retrospective Study
    Publication . Gouareb, Racha; Bornet, Alban; Proios, Dimitrios; Pereira, Sónia Gonçalves; Teodoro, Douglas
    Background: While Enterobacteriaceae bacteria are commonly found in the healthy human gut, their colonization of other body parts can potentially evolve into serious infections and health threats. We investigate a graph-based machine learning model to predict risks of inpatient colonization by multidrug-resistant (MDR) Enterobacteriaceae. Methods: Colonization prediction was defined as a binary task, where the goal is to predict whether a patient is colonized by MDR Enterobacteriaceae in an undesirable body part during their hospital stay. To capture topological features, interactions among patients and healthcare workers were modeled using a graph structure, where patients are described by nodes and their interactions are described by edges. Then, a graph neural network (GNN) model was trained to learn colonization patterns from the patient network enriched with clinical and spatiotemporal features. Results: The GNN model achieves performance between 0.91 and 0.96 area under the receiver operating characteristic curve (AUROC) when trained in inductive and transductive settings, respectively, up to 8% above a logistic regression baseline (0.88). Comparing network topologies, the configuration considering ward-related edges (0.91 inductive, 0.96 transductive) outperforms the configurations considering caregiver-related edges (0.88, 0.89) and both types of edges (0.90, 0.94). For the top 3 most prevalent MDR Enterobacteriaceae, the AUROC varies from 0.94 for Citrobacter freundii up to 0.98 for Enterobacter cloacae using the best-performing GNN model. Conclusion: Topological features via graph modeling improve the performance of machine learning models for Enterobacteriaceae colonization prediction. GNNs could be used to support infection prevention and control programs to detect patients at risk of colonization by MDR Enterobacteriaceae and other bacteria families.
  • Modulation of gut microbiota by diet and probiotics: potential approaches to prevent gestational diabetes mellitus
    Publication . Cruz, Marisa Carreira; Azinheiro, Sarah; Pereira, Sónia Gonçalves
    Gestational diabetes mellitus (GDM) is a rising global health problem that affects approximately 6% of pregnant women. Lifestyle interventions, particularly diet, and exercise are the first-line treatment, followed by pharmacotherapy, but with associated side effects to both mother and offspring. Modulation of gut microbiota may help prevent or manage GDM. Some gut bacterial groups associated with GDM are also associated with inflammatory biomarkers and gut dysbiosis. Available literature reports that low-glycaemic index diet reduces maternal fasting and 2-hour postprandial glucose and maintains a beneficial gut bacterial composition. Pre- and probiotics can aid GDM therapy by modulating gut microbiota to eubiotic status and improving glucose metabolism. Probiotics as adjuvant GDM therapy should consider bacterial strains, dosage, and treatment duration. Limitations in their use require further studies to develop specific probioticbased GDM supplement therapy that impacts glycaemic control and inflammatory status by reducing fasting plasma glucose, insulin resistance, and improving lipid profiles of pregnant women.
  • Bacteria: Potential Make-or-Break Determinants of Celiac Disease
    Publication . Roque, Ana; Pereira, Sónia Gonçalves
    Celiac disease is an autoimmune disease triggered by dietary gluten in genetically susceptible individuals that primarily affects the small intestinal mucosa. The sole treatment is a gluten-free diet that places a social and economic burden on patients and fails, in some, to lead to symptomatic or mucosal healing. Thus, an alternative treatment has long been sought after. Clinical studies on celiac disease have shown an association between the presence of certain microbes and disease outcomes. However, the mechanisms that underlie the effects of microbes in celiac disease remain unclear. Recent studies have employed disease models that have provided insights into disease mechanisms possibly mediated by bacteria in celiac disease. Here, we have reviewed the bacteria and related mechanisms identified so far that might protect from or incite the development of celiac disease. Evidence indicates bacteria play a role in celiac disease and it is worth continuing to explore this, particularly since few studies, to the best of our knowledge, have focused on establishing a mechanistic link between bacteria and celiac disease. Uncovering host–microbe interactions and their influence on host responses to gluten may enable the discovery of pathogenic targets and development of new therapeutic or preventive approaches.
  • Multidrug resistance assessment of indoor air in Portuguese long-term and acute healthcare settings
    Publication . Santos-Marques, C.; Teixeira, C.; Pinheiro, R.; Brück, W. M.; Pereira, Sónia Gonçalves; dos Santos Marques, Catarina; Silva Teixeira, Camila; Pinheiro, Rafael; Gonçalves Pereira, Sónia
    Background: Knowledge about air as a pool of pathogens and multidrug resistance (MDR) in healthcare units apart from hospitals is scarce. Aim: To investigate these features in a Portuguese long-term healthcare unit (LTHU) and a central hospital (CH). Methods: Air samples were collected and their microbial load (bacteria and fungi) determined. Bacterial isolates were randomly selected for further characterization, particularly identification by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, antimicrobial susceptibility testing, and polymerase chain reaction screening of extended-spectrum b-lactamases, carbapenemase genes and mecA gene, with RAPD profile assessment of positive results of the latter. Findings: A total of 192 samples were collected (LTHU: 86; CH: 106). LTHU showed a statistically significantly higher bacterial load. CH bacteria and fungi loads in inpatient sites were statistically significantly lower than in outpatients or non-patient sites. A total of 164 bacterial isolates were identified (MALDI-TOF: 78; presumptively: 86), the majority belonging to Staphylococcus genus (LTHU: 42; CH: 57). The highest antimicrobial resistance rate was to erythromycin and vancomycin the least, in both settings. Eighteen isolates (11%) were classified as MDR (LTHU: 9; CH: 9), with 7 MDR Staphylococcus isolates (LTHU: 4; CH: 3) presenting mecA. Nine non-MDR Staphylococcus (LTHU: 5; CH: 4) also presented mecA. Conclusion: The current study highlights that healthcare unit indoor air can be an important pool of MDR pathogens and antimicrobial resistance genes. Also, LTHUs appear to have poorer air quality than hospitals, as well as supportive areas compared to curative care areas. This may suggest possible yet unknown routes of infection that need to be explored.
  • Patterns of Medication Management and Associated Medical and Clinical Features among Home-Dwelling Older Adults: A Cross-Sectional Study in Central Portugal
    Publication . Dixe, Maria dos Anjos; Pinho, Joana; Pereira, Filipa; Verloo, Henk; Meyer-Massetti, Carla; Pereira, Sónia Gonçalves
    Ageing is frequently associated with multimorbidity and polypharmacy. The present study aimed to identify the current medication management patterns and the profiles of homedwelling older adults and to find any association with their conditions, including frailty and cognitive impairment. Within the scope of this cross-sectional study, 112 older adults living in the community were assessed via face-to-face structured interviews. Frailty, cognitive status, medication management and clinical and sociodemographic variables were evaluated. Descriptive and inferential statistics were calculated. The mean participant age was 76.6 ± 7.1 years, 53.6% of participants were women, and 40.2% of participants lived alone. More than half were classified as having frailty (58.9%), almost one-fifth (19.6%) presented with a moderate cognitive impairment had more than one disease, and 60.7% were polymedicated. No associations were found between polymedication and medication self-management, the use of over-the-counter medications, living alone, having a poor understanding of pharmacological therapy and/or pathology, or having more than one prescriber. Self-management was associated with age, the number of medications, frailty and cognitive status. Binary logistic regressions showed that cognitive impairment had statistically significant differences with medication management, having a poor understanding of pharmacological therapy and/or pathology, having one prescriber and the use of medications not prescribed by physicians. Interventions to prevent medication-related problems in home-dwelling older adults are recommended.
  • An Intervention Program to Reduce Medication-Related Problems Among Polymedicated Home-Dwelling Older Adults (OptiMed): Protocol for a Pre-Post, Multisite, Pilot, and Feasibility Study
    Publication . Pereira, Filipa; Dixe, Maria dos Anjos; Pereira, Sónia Gonçalves; Meyer-Massetti, Carla; Verloo, Henk
    Background: Effective medication management is one of the essential preconditions for enabling polymedicated home-dwelling older adults with multiple chronic conditions to remain at home and preserve their quality of life and autonomy. Lack of effective medication management predisposes older adults to medication-related problems (MRPs) and adverse health outcomes, which can lead to the degradation of a patient’s acute clinical condition, physical and cognitive decline, exacerbation of chronic medical conditions, and avoidable health care costs. Nonetheless, it has been shown that MRPs can be prevented or reduced by using well-coordinated, patient-centered, interprofessional primary care interventions. Objective: This study aimed to explore the feasibility and acceptability of an evidence-based, multicomponent, interprofessional intervention program supported by informal caregivers to decrease MRPs among polymedicated home-dwelling older adults with multiple chronic conditions. Methods: This quasi-experimental, pre-post, multisite pilot, and feasibility study will use an open-label design, with participants knowing the study’s objectives and relevant information, and it will take place in primary health care settings in Portugal and Switzerland. The research population will comprise 30 polymedicated, home-dwelling adults, aged ≥65 years at risk of MRPs and receiving community-based health care, along with their informal caregivers and health care professionals. Results: Before a projected full-scale study, this pilot and feasibility study will focus on recruiting and ensuring the active collaboration of its participants and on the feasibility of expanding this evidence-based, multicomponent, interprofessional intervention program throughout both study regions. This study will also be essential to projected follow-up research programs on informal caregivers’ multiple roles, enhancing their coordination tasks and their own needs. Results are expected at the end of 2024. Conclusions: Designing, establishing, and exploring the feasibility and acceptability of an intervention program to reduce the risks of MRPs among home-dwelling older adults is an underinvestigated issue. Doing so in collaboration with all the different actors involved in that population’s medication management and recording the first effects of the intervention will make this pilot and feasibility study’s findings very valuable as home care becomes an ever more common solution. Trial Registration: Swiss National Clinical Trials Portal 000004654; https://tinyurl.com/mr3yz8t4
  • The role of pseudocereals in celiac disease: reducing nutritional deficiencies to improve well-being and health
    Publication . Caeiro, Carolina; Pragosa, Caroline; Carreira Cruz, Marisa; Pereira, Cidália; Pereira, Sónia Gonçalves
    Celiac disease or gluten-dependent enteropathy is a chronic autoimmune pathology triggered by dietary gluten in genetic predisposed individuals, mediated by transglutaminase 2 IgA autoantibodies and associated with a deteriorating immune and inflammatory response. ,is leads to intestinal villous atrophy, impairing the intestinal mucosa structure and function of secretion, digestion, and absorption. ,e result is macro- and micronutrient deficiency, including fat soluble vitamins and minerals, and a consequent nutritional status depletion. A lifelong gluten-free diet is the only available treatment for celiac patients in order to assure normal intestinal mucosa and remission of gastrointestinal symptoms. However, a gluten-free diet can itself cause other nutritional deficiencies due to its restrictive nature regarding gluten-containing cereals. A group of gluten-free cereals, known as pseudocereals, is increasingly recognized as valuable options for gluten-free diets due to their high nutritional value. Amaranth, quinoa, millet, and buckwheat are examples of gluten-free nutrient-dense grains that can be used as alternatives to the conventional gluten-containing grains and improve the variety and nutritional quality of the celiac diet. Current work reviews the nutritional pitfalls of a gluten-free diet and analyses how pseudocereals can contribute to revert those deficiencies and optimize the nutritional value of this mandatory diet for the celiac population.
  • Dietary patterns drive loss of fiber-foraging species in the celiac disease patients gut microbiota compared to first-degree relatives
    Publication . Roque, Ana; Zanker, Joyce; Brígido, Sara; Tomaz, Maria Beatriz; Gonçalves, André; Barbeiro, Sandra; Benítez-Páez, Alfonso; Pereira, Sónia Gonçalves
    Background Celiac disease is an autoimmune disorder triggered by dietary gluten in genetically predisposed indi‑viduals that primarily afects the small intestine. Studies have reported diferentially abundant bacterial taxa in the gut microbiota of celiac patients compared with non-celiac controls. However, fndings across studies have inconsisten‑cies and no microbial signature of celiac disease has been defned so far. Results Here, we showed, by comparing celiac patients with their non-celiac 1st-degree relatives, that bacterial com‑munities of related individuals have similar species occurrence and abundance compared with non-relatives, regard‑less the disease status. We also found in celiac patients a loss of bacterial species associated with fber degradation,and host metabolic and immune modulation, as ruminiclostridia, ruminococci, Prevotella, and Akkermansia muciniphila species. We demonstrated that the diferential abundance of bacterial species correlates to diferent dietary pat‑terns observed between the two groups. For instance, Ruminiclostridium siraeum, Ruminococcus bicirculans, and Bacteroides plebeious, recognized as fber-degraders, appear more abundant in non-celiac 1st-degree relatives, which havea vegetable consumption pattern higher than celiac patients. Pattern of servings per day also suggests a possible link between these species’ abundance and daily calorie intake. Conclusions Overall, we evidenced that a kinship approach could be valuable in unveiling potential celiac disease microbial traits, as well as the signifcance of dietary factors in shaping microbial profles and their infuence on dis‑ease development and progression. Our results pave the way for designing and adopting novel dietary strategies based on gluten-free fber-enriched ingredients to improve disease management and patients’ quality of life.
  • How have covid-19 prevention measures affected professionals working at nursing homes?
    Publication . Santos-Marques, Catarina; Mangas, Catarina; Marques, Tânia; Gil, Ana Paula; Ramalho, Nelson; Pereira, Sónia Gonçalves
  • Celiac disease gut microbiome studies in the third millennium: reviewing the findings and gaps of available literature
    Publication . Luz, Vanessa C. C.; Pereira, Sónia Gonçalves
    Celiac disease is an autoimmune enteropathy caused by the ingestion of minute amounts of gluten in a subset of genetically predisposed individuals. Its onset occurs at different ages and with variable symptoms. The gut microbiome may contribute to this variability. This review aims to provide an overview of the available research on celiac disease gut microbiome and identify the knowledge gap that could guide future studies. Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews (PRISMA-ScR), four electronic databases were searched for literature from January 2000 to July 2023 addressing celiac disease gut microbiome characterization using next-generation sequencing (NGS) approaches. From the 489 publications retrieved, 48 publications were selected and analyzed, focusing on sample characterization (patients, controls, and tissues) and methodologies used for NGS microbiome analysis and characterization. The majority of the selected publications regarded children and adults, and four were randomized clinical trials. The number of participants per study greatly varied and was typically low. Feces were the most frequently tested sample matrix, and duodenal samples were analyzed in one-third of the studies. Incomplete and diverse information on the methodological approaches and gut microbiome results was broadly observed. While similar trends regarding the relative abundance of some phyla, such as Pseudomonadota (former Proteobacteria), were detected in some studies, others contradicted those results. The observed high variability of technical approaches and possibly low power and sample sizes may prevent reaching a consensus on celiac disease gut microbiome composition. Standardization of research protocols to allow reproducibility and comparability is required, as interdisciplinary collaborations to further data analysis, interpretation, and, more importantly, health outcome prediction or improvement.