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.

Genomic reconstruction of the SARS-CoV-2 epidemic across England from September 2020 to May 2021

The evolution of the SARS-CoV-2 pandemic continuously produces new variants, which warrant timely epidemiological characterisation. Here we use the dense genomic surveillance generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of sub-epidemics that peaked in the early autumn of 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. Alpha grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed Alpha and eliminated nearly all other lineages in early 2021. However, a series of variants (mostly containing the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. Accounting for sustained introductions, however, indicates that their transmissibility is unlikely to have exceeded that of Alpha. Finally, B.1.617.2/Delta was repeatedly introduced to England and grew rapidly in the early summer of 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on June 26.

Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data

The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution.

Is poor quality sleep present in older adults with worse social and health status? / Se presenta sueño de mala calidad en adultos mayores con peor nivel social y de salud? / Sono de má qualidade está presente em idosos com pior nível social e de saúde?

ABSTRACT Objective: to analyze the relationship among sleep and sociodemographic aspects, health, frailty, performance in activities of daily living, cognitive performance and depressive symptoms of older residents in the community. Method: a cross-sectional, quantitative study was conducted with 81 older adults residents in the area covered by a Family Health Unit in the city of São Carlos (SP), Brazil. Data collection occurred in 2019, through the application of the following instruments: questionnaire for socioeconomic and health characterization of the older adult, Pittsburgh Sleep Quality Index, Frailty Phenotype proposed by Linda Fried, Mini Mental State Examination, Geriatric Depression Scale, Katz Index and Lawton Scale. Participants were divided into comparative groups according to sleep quality scores. Fisher's exact and Pearson's χ2 were used. A significance level of 5% was adopted. Results: 50.6% of the older adults had poor quality sleep (n=41), followed by 33.3% of older adults with good quality sleep (n=27) and 16.1% had sleep disorders (n=13). There was a relationship between sleep quality and sex (p=0.008), work status (p=0.001), self-assessment of health (p=0.013), falls (p=0.034), pain (p=0.012), frailty level (p=0.026) and the slow gait criterion (p<0.001). Conclusion: there was a higher prevalence of poor quality sleep and sleep disorders in older patients, who do not work outside the home, who evaluated their health as regular or poor, who suffered falls in the last year and who complained of pain, frailty and slow gait.

RESUMEN Objetivo: analizar la relación entre sueño y aspectos sociodemográficos, salud, fragilidad, desempeño en actividades de la vida diaria, desempeño cognitivo y síntomas depresivos en adultos mayores residentes en comunidad. Método: estudio transversal, cuantitativo, realizado con 81 adultos mayores residentes en el área de cobertura de una Unidad de Salud de la Familia en la ciudad de São Carlos (SP), Brasil. La recolección de datos se llevó a cabo en 2019, mediante la aplicación de los siguientes instrumentos: cuestionario para la caracterización socioeconómica y de salud del adulto mayor, Índice de Calidad del Sueño de Pittsburgh, Fenotipo de Fragilidad propuesto por Linda Fried, Mini Examen del Estado Mental, Escala de Depresión Geriatríca, Índice de Katz y Escala de Lawton. Los participantes se dividieron en grupos comparativos según las puntuaciones de calidad del sueño. Se utilizaron la exacta de Fisher y la χ2 de Pearson. Se adoptó un nivel de significancia del 5%. Resultados: el 50,6% de los adultos mayores tenía mala calidad del sueño (n=41), seguido por el 33,3% de los ancianos con buena calidad de sueño (n=27) y el 16,1% con trastornos del sueño (n=13). Hubo relación entre la calidad del sueño y el género (p=0,008), situación laboral (p=0,001), salud autoevaluada (p=0,013), caída (p=0,034), dolor (p=0,012), nivel de fragilidad (p=0,026) y el criterio de lentitud de la marcha (p <0,001). Conclusión: hubo una mayor prevalencia de sueño de mala calidad y trastornos del sueño en mujeresmayores, que no trabajan fuera del hogar, que calificaron su salud como regular o mala, que sufrieron caídas en el último año, que se quejaron de dolor, frágil y lentitud de la marcha.

RESUMO Objetivo: analisar a relação entre sono e aspectos sociodemográficos, de saúde, fragilidade, desempenho em atividades de vida diária, desempenho cognitivo e sintomas depressivos de idosos residentes na comunidade. Método: estudo transversal, quantitativo, realizado com 81 idosos residentes na área de abrangência de uma Unidade de Saúde da Família do município de São Carlos (SP), Brasil. A coleta de dados ocorreu em 2019, mediante a aplicação dos seguintes instrumentos: questionário para caracterização socioeconômica e de saúde do idoso, Índice de Qualidade do Sono de Pittsburgh, Fenótipo de Fragilidade proposto por Linda Fried, Mini Exame do Estado Mental, Escala de Depressão Geriátrica, Índice de Katz e Escala de Lawton. Os participantes foram divididos em grupos comparativos segundo os escores de qualidade do sono. Foram utilizados Exato de Fisher e χ2 de Pearson. Adotou-se nível de significância de 5%. Resultados: 50,6% dos idosos apresentaram sono de má qualidade (n=41), seguidos de 33,3% de idosos com sono de boa qualidade (n=27) e 16,1% com distúrbios do sono (n=13). Houve relação entre qualidade do sono e sexo (p=0,008), situação laboral (p=0,001), autoavaliação de saúde (p=0,013), queda (p=0,034), dor (p=0,012), nível de fragilidade (p=0,026) e o critério lentidão da marcha (p<0,001). Conclusão: houve maior prevalência de sono de má qualidade e de distúrbios do sono em mulheres idosas, que não trabalham fora de casa, que avaliaram a sua saúde como regular ou ruim, que sofreram quedas no último ano, que se queixaram de dor, frágeis e com lentidão da marcha.

Patterns of within-host genetic diversity in SARS-CoV-2

Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1,181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within and between host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.

MAJORA: Continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance

Genomic epidemiology has become an increasingly common tool for epidemic response. Recent technological advances have made it possible to sequence genomes rapidly enough to inform outbreak response, and cheaply enough to justify dense sampling of even large epidemics. With increased availability of sequencing it is possible for agile networks of sequencing facilities to collaborate on the sequencing and analysis of epidemic genomic data. In response to the ongoing SARS-CoV-2 pandemic in the United Kingdom, the COVID-19 Genomics UK (COG-UK) consortium was formed with the aim of rapidly sequencing SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of Majora, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network. The system was designed and implemented pragmatically to stand up capacity rapidly in a pandemic caused by a novel virus. This approach has underpinned the success of COG-UK, which has rapidly become the leading contributor of SARS-CoV-2 genomes to international databases and has generated over 60,000 sequences to date.

COVID-19 infection dynamics in care homes in the East of England: a retrospective genomic epidemiology study

COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1,167 residents from 337 care homes were identified from a dataset of 6,600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns - outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population. Impact statementSARS-CoV-2 can spread efficiently within care homes causing COVID-19 outbreaks among residents, who are at increased risk of severe disease, emphasising the importance of stringent infection control in this 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.

A temporal analysis of the relationships between social stress, humoral immune response and glutathione-related antioxidant defenses.

The exposure to different kinds of stress impacts on the reactive oxygen species production with potential risk to the integrity of the tissues. Psychological or biological stress is responsible for a significant increase in the oxidative stress markers and also for activation of the antioxidant defense system. In this study, we analyzed the relationships between social stress, humoral immune response and glutathione-related antioxidant defenses. Groups of male Swiss mice were subjected to different lengths of social stress exposure (social confrontation) which varied from 1 up to 13 days. As a biological stressor, 10(9) sheep red blood cells (SRBC)/mL were injected by intraperitoneal route. As controls, animals not subjected to social stress and/or injected with vehicle solution were used. The serum samples and the cerebral cortex were collected at 4 h, 3, 5, 7, 9, 11, and 13 days after the end of social confrontation. The results indicated that the antioxidant enzymes activities were affected by psychological as well as by biological stressor. These alterations were dependent on the timing of stress exposure which resulted in a positive or in a negative correlation between the antibody titres to SRBC and antioxidant enzymes. We also discuss the possible role of SRBC injection in the modulation of the effects of psychosocial stress on antioxidant metabolism.

Género e VIH: a vulnerabilidade da mulher nos países em desenvolvimento

Trabalho apresentado no 4º Congresso Virtual de HIV/AIDS, 2003, Portugal. Analisa a vulnerabilidade da mulher à infecção pelo HIV/AIDS e as causas, entre elas, fatores culturais associados às relações de poder e gênero e apresenta orientações para intevenções e políticas de Saúde Pública.

Long-term consequences of social stress on corticosterone and IL-1beta levels in endotoxin-challenged rats.

Social stress has strong and long-lasting effects on autonomic nervous, neuroendocrine and behavioural functioning. The functionality of the immune system is profoundly influenced by autonomic nervous and neuroendocrine activities. Changes in sympathetic-adrenal and hypothalamic-pituitary-adrenocortical (HPA) axis activities as observed during and after social defeat, therefore, probably represent an important factor in the modulation of the immune response. In the present study, the impact of social defeat stress on the responsiveness of the immune system was studied by the presentation of a systemic inflammatory challenge through the injection of the bacterial endotoxin lipopolysaccharide (LPS). Male Wistar rats were subjected twice to social defeat 7 days apart. One week after the second defeat, they were injected with LPS in a low (150 microg/kg; DLPS). Another group of defeated rats was injected with saline. Control, nondefeated rats also received the immune challenges. Previously defeated rats responded to the high dose of LPS with a deficient corticosterone (CORT) response resulting in an aggravated interleukin-1beta (IL-1beta) response 4 h after LPS injection. Furthermore, the experiments indicated that mortality rates after LPS administration were high in previously defeated rats, whereas mortality was absent in nondefeated rats. The results indicate that social stress has long-lasting effects on the functioning of the immune system and that it can seriously compromise the effectiveness of the adrenocortical response in containing some immunological defense mechanisms.