Bacteria: Potential Make-or-Break Determinants of Celiac Disease.

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.

Patterns of Medication Management and Associated Medical and Clinical Features among Home-Dwelling Older Adults: A Cross-Sectional Study in Central Portugal.

Ageing is frequently associated with multimorbidity and polypharmacy. The present study aimed to identify the current medication management patterns and the profiles of home-dwelling 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.

Detection of Patients at Risk of Multidrug-Resistant Enterobacteriaceae Infection Using Graph Neural Networks: A Retrospective Study.

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.

Insights into the mechanisms of Cronobacter sakazakii virulence.

Cronobacter species have adapted to survive harsh conditions, particularly in the food manufacture environment, and can cause life-threatening infections in susceptible hosts. These opportunistic pathogens employ a multitude of mechanisms to aid their virulence throughout three key stages: environmental persistence, infection strategy, and systemic persistence in the human host. Environmental persistence is aided by the formation of biofilms, development of subpopulations, and high tolerance to environmental stressors. Successful infection in the human host involves several mechanisms such as protein secretion, motility, quorum sensing, colonisation, and translocation. Survival inside the host is achieved via competitive acquisition and utilization of minerals and metabolites respectively, coupled with host immune system evasion and antimicrobial resistance (AMR) mechanisms. Across the globe, Cronobacter sakazakii is associated with often fatal systemic infections in populations including neonates, infants, the elderly and the immunocompromised. By providing insight into the mechanisms of virulence utilised by this pathogen across these three stages, this review identifies current gaps in the literature. Further research into these virulence mechanisms is required to inform novel mitigation measures to improve global food safety with regards to this food-borne pathogen.

The Role of Pseudocereals in Celiac Disease: Reducing Nutritional Deficiencies to Improve Well-Being and Health.

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. This leads to intestinal villous atrophy, impairing the intestinal mucosa structure and function of secretion, digestion, and absorption. The 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.

Studies of antimicrobial resistance in rare mycobacteria from a nosocomial environment.

BACKGROUND: Nontuberculous mycobacteria (NTM) are ubiquitous in nature and recognized agents of opportunistic infection, which is often aggravated by their intrinsic resistance to antimicrobials, poorly defined therapeutic strategies and by the lack of new drugs. However, evaluation of their prevalence in anthropogenic environments and the associated antimicrobial resistance profiles have been neglected. In this work, we sought to determine minimal inhibitory concentrations of 25 antimicrobials against 5 NTM isolates recovered from a tertiary-care hospital surfaces. Antimicrobial susceptibilities of 5 other Corynebacterineae isolated from the same hospital were also determined for their potential clinical relevance. RESULTS: Our phylogenetic study with each of the NTM isolates confirm they belong to Mycobacterium obuense, Mycobacterium mucogenicum and Mycobacterium paragordonae species, the latter initially misidentified as strains of M. gordonae, a species frequently isolated from patients with NTM disease in Portugal. In contrast to other strains, the M. obuense and M. mucogenicum examined here were resistant to several of the CLSI-recommended drugs, suggestive of multidrug-resistant profiles. Surprisingly, M. obuense was susceptible to vancomycin. Their genomes were sequenced allowing detection of gene erm (erythromycin resistance methylase) in M. obuense, explaining its resistance to clarithromycin. Remarkably, and unlike other strains of the genus, the Corynebacterium isolates were highly resistant to penicillin, ciprofloxacin and linezolid. CONCLUSIONS: This study highlights the importance of implementing effective measures to screen, accurately identify and control viable NTM and closely related bacteria in hospital settings. Our report on the occurrence of rare NTM species with antibiotic susceptibility profiles that are distinct from those of the corresponding Type strains, along with unexpected resistance mechanisms detected seem to suggest that resistance may be more common than previously thought and also a potential threat to frail and otherwise vulnerable inpatients.

Multidrug and extensive drug resistance in Pseudomonas aeruginosa clinical isolates from a Portuguese central hospital: 10-year survey.

Multidrug-resistant (MDR) Pseudomonas aeruginosa isolates are increasing worldwide and greatly limit therapeutic options, particularly when considering extensively drug-resistant (XDR) or pandrug-resistant isolates. The resistance profile of P. aeruginosa isolates from a Portuguese central hospital was surveyed during 10 years (n=3,778). About 39.9% were classified as MDR and 2.9% as XDR. Statistical analysis (Mann-Whitney test and regression modeling) revealed a decrease in total MDR rates over time but an increase in XDR rates. This suggests a tendency for higher proportions of XDR isolates in the future, which is of great concern. Isolates of nosocomial origin presented similar results to total population but, when analyzing them according to the different wards of origin, it was still observed a trend of increase in MDR rates in some wards, particularly pneumology, neurology, and neurosurgery. Similar analysis considering the nosocomial specimen source revealed a negative trend of evolution in MDR rates of respiratory origin and a positive trend over time in XDR rates of isolates collected from urine. Regarding the association of antibiotic resistance to MDR and XDR profiles, it was observed a negative relation over time between imipenem resistance and MDR and gentamicin resistance and XDR, suggesting that resistance to these antibiotics may predict the absence of MDR or XDR in P. aeruginosa isolates, respectively. Similar studies in other European hospitals should be performed to give further information to physicians, important for their empirical antibiotherapy regimens.

Prevalence and molecular epidemiology of imipenem-resistant Pseudomonas aeruginosa carrying metallo-beta-lactamases from two central hospitals in Portugal.

Metallo-beta-lactamases (MBLs) can confer broad-spectrum beta-lactam resistance, including carbapenems. The aim of this work was to document the occurrence of MBLs in 122 imipenem-resistant Pseudomonas aeruginosa isolates collected in two Portuguese central hospitals, to determine their antimicrobial susceptibility, and to observe if there were intra- and interhospital epidemic spread. About 20.5% of these isolates presented blaVIM-2, which was found to be widespread in both hospitals. Clonal diversity was observed within hospitals, and no interhospital spread was observed. Ten of the blaVIM-2-positive isolates (44%), from both hospitals, presented one or two class 1 integrons. Two of those contained a VIM-2 gene, one from each hospital, which is indicative for the possibility of MBL gene transfer. No interhospital spread of integrons was observed. Regular screening and surveillance is needed to prevent spread of this worrisome resistance determinant.