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Introduction: Adults with Post-COVID-19 Condition (PCC) may show cognitive impairments in attention, processing speed, memory, and executive function. Multimodal programs that combine cognitive training, physical activity and emotional tasks, such as mindfulness-based interventions (MBIs), may offer a suitable alternative for improving PCC treatments. Immersive Virtual Reality (IVR) is a promising technology that can enhance traditional cognitive training, physical activity, and MBIs. The use of IVR technology may increase engagement with these interventions and potentially enhance the individual benefits of cognitive training, exercise and MBIs. The current study evaluated the impact of a multimodal IVR intervention, comparing this with a usual care intervention (control group), in order to assess changes in cognition and mental health in adults with PCC. We also aimed to assess user experience factors such as enjoyment, perceived improvement, and fatigue following each multimodal IVR session within the experimental group. Method: Thirty-one participants with PCC symptoms were assigned to either the experimental group (IVR, n = 15) or the control group (usual care intervention, n = 16) in a quasi-experimental design study. The multimodal IVR intervention consisted of MBI, cognitive training and physical exercise and was delivered in a 60-min group session with 5 participants, twice a week, for 8 weeks (16 sessions in total). Measures of global cognition, attention, processing speed, verbal episodic memory and subjective memory complaints (primary measures), and depressive and anxiety symptoms and fatigue (secondary measures) were assessed at baseline and also after 8 weeks (post-intervention). Results: Mixed between-group (group) and within-group (pre-post assessments) ANOVAs revealed significant group*time interactions in global cognition, simple attention, processing speed, memory and depressive symptoms, with large effect sizes (p < 0.05; partial η2 > 0.14). There was also a marginally significant group*time interaction for executive function (p = 0.05). Follow-up analyses comparing pre-and post-intervention outcomes for each group separately showed that the experimental group significantly improved in global cognition, processing speed, memory and depressive symptoms, while the control group showed no significant pre-post changes. Friedman tests showed a significant main effect of time (χ2(2) = 6.609, p = 0.04), with a gradual increase in enjoyment from the first, to the mid, and then to the final session. In addition, perceived improvement scores remained high throughout the intervention, and patient-reported fatigue levels did not fluctuate significantly throughout the intervention. Conclusion: To our knowledge, no previous research has combined cognitive training, physical exercise and MBI using an IVR paradigm in adults with PCC. Despite their inherent limitations, our findings mark a pioneering step toward improving cognition and mental health outcomes in PCC through the innovative use of new technology and multimodal approaches. This first study should be accompanied by more extensive, randomized clinical trials aimed at further exploring and refining these interventions.
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BACKGROUND: Spanish primary care services are managed differently by each region's authorities. Catalonia started its services provision and design nearly two decades before other Spanish regions and developed nurses' roles and task shifting in primary care. PURPOSE: This work identifies differences in the Europe PRICOV-19 study answers between Catalonia and those submitted from the rest of Spain regarding how primary care teams (PCT) were organised during the SARS-CoV-2-2019 pandemic, how tasks and roles changed, and the pandemic's impact on the care providers. Initially, we computed bivariate relationships and tested using contingency association and unpaired Wilcoxon. ANALYSIS: Still, we estimated multiple linear regressions controlling with a list of individual and GP practice characteristics and clustering standard errors at the kind of location. RESULTS: Main statistically significant differences were found in the adaptation to the new tasks, the ability to solve most health problems, and specific accessibilities to primary care. In Catalonia, satisfaction with the adaptation to the new tasks was higher (41.9% satisfied and 30.2% neutral) than in the rest of Spain (50.9% dissatisfaction). Also, GPs in Catalonia reported to a greater extent than the rest of Spain that chronic patients were listed for extensive follow-up. These differences may be related to Catalonia's strategy for empowering primary care professionals other than family doctors. CONCLUSIONS: Considering future pandemics, demographic ageing, and professional shortages, we point out the potential benefits of these changes in PCT organisations and the need to review the centres's design.
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Background: This research project aims to build a Machine Learning algorithm (ML) to predict first-time ADHD diagnosis, given that it is the most frequent mental disorder for the non-adult population. Methods: We used a stacked model combining 4 ML approaches to predict the presence of ADHD. The dataset contains data from population health care administrative registers in Catalonia comprising 1,225,406 non-adult individuals for 2013-2017, linked to socioeconomic characteristics and dispensed drug consumption. We defined a measure of proper ADHD diagnoses based on medical factors. Results: We obtained an AUC of 79.6% with the stacked model. Significant variables that explain the ADHD presence are the dispersion across patients' visits to healthcare providers; the number of visits, diagnoses related to other mental disorders and drug consumption; age, and sex. Conclusions: ML techniques can help predict ADHD early diagnosis using administrative registers. We must continuously investigate the potential use of ADHD early detection strategies and intervention in the health system.
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Biosourced and biodegradable plastics offer a promising solution to reduce environmental impacts of plastics for specific applications. Here, we report a novel bacterium named Alteromonas plasticoclasticus MED1 isolated from the marine plastisphere that forms biofilms on foils of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). Experiments of degradation halo, plastic matrix weight loss, bacterial oxygen consumption and heterotrophic biosynthetic activity showed that the bacterial isolate MED1 is able to degrade PHBV and to use it as carbon and energy source. The likely entire metabolic pathway specifically expressed by this bacterium grown on PHBV matrices was shown by further genomic and transcriptomic analysis. In addition to a gene coding for a probable secreted depolymerase, a gene cluster was located that encodes characteristic enzymes involved in the complete depolymerization of PHBV, the transport of oligomers, and in the conversion of the monomers into intermediates of central carbon metabolism. The transcriptomic experiments showed the activation of the glyoxylate shunt during PHBV degradation, setting the isocitrate dehydrogenase activity as regulated branching point of the carbon flow entering the tricarboxylic acid cycle. Our study also shows the potential of exploring the natural plastisphere to discover new bacteria with promising metabolic capabilities.
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Bactérias , Poliésteres , Bactérias/genética , Bactérias/metabolismo , Hidroxibutiratos , Biopolímeros , Carbono/metabolismoRESUMO
Context: The American College of Radiology Thyroid Image Reporting and Data System (ACR TI-RADS) was developed to predict malignancy risk in thyroid nodules using ultrasound features. TI-RADS was derived from a database of patients already selected for fine-needle aspiration (FNA), raising uncertainty about applicability to unselected patients. Objective: We aimed to assess the effect of ACR TI-RADS reporting in unselected patients presenting for thyroid ultrasound in a real-world setting. Methods: Records for all patients presenting for thyroid ultrasonography in Canterbury, New Zealand, were reviewed across two 18-month periods, prior to and after implementation of TI-RADS reporting. Patient outcomes were compared between the 2 periods. Malignancy rates were calculated for nodules 10 mm or larger with a definitive FNA or histology result. Results: A total of 1210 nodules were identified in 582 patients prior to implementation of TI-RADS; 1253 nodules were identified in 625 patients after implementation of TI-RADS. TI-RADS category was associated with malignancy rate (0% in TR1 and TR2, 3% in TR3, 5% in TR4, 12% in TR5; P = .02); however, 63% of nodules were graded TR3 or TR4, for which malignancy rate did not meaningfully differ from baseline risk. After implementation of TI-RADS there was a small reduction in the proportion of patients proceeding to FNA (49% vs 60%; P < .01) or surgery (14% vs 18%; P < .05), with no difference in cancer diagnoses (3% vs 4%, not significant). Conclusion: TI-RADS category is associated with malignancy rate and may alter clinical decision-making in a minority of patients; however, it is nondiscriminatory in the majority of nodules. In this study of unselected patients, nodules classified as TR5 and thus considered "highly suspicious" for cancer had only a modest risk of malignancy.
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AIMS: Using machine learning algorithms and administrative data, we aimed to predict the risk of being diagnosed with several diabetes-related complications after one-, two- and three-year post-diabetes diagnosis. METHODS: We used longitudinal data from administrative registers of 610,019 individuals in Catalonia with a diagnosis of diabetes and checked the presence of several complications after diabetes onset from 2013 to 2017: hypertension, renal failure, myocardial infarction, cardiovascular disease, retinopathy, congestive heart failure, cerebrovascular disease, peripheral vascular disease and stroke. Four different machine learning (ML) algorithms (logistic regression (LR), Decision tree (DT), Random Forest (RF), and Extreme Gradient Boosting (XGB)) will be used to assess their prediction performance and to evaluate the prediction accuracy of complications changes over the period considered. RESULTS: 610,019 people with diabetes were included. After three years since diabetes diagnosis, the area under the curve values ranged from 60% (retinopathy) to 69% (congestive heart failure), whereas accuracy rates varied between 60% (retinopathy) to 75% (hypertension). RF was the most relevant technique for hypertension, myocardial and retinopathy, and LR for the rest of the comorbidities. The Shapley additive explanations values showed that age was associated with an elevated risk for all diabetes-related complications except retinopathy. Gender, other comorbidities, co-payment levels and age were the most relevant factors for comorbidity diagnosis prediction. CONCLUSIONS: Our ML models allow for the identification of individuals newly diagnosed with diabetes who are at increased risk of developing diabetes-related complications. The prediction performance varied across complications but within acceptable ranges as prediction tools.
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Complicações do Diabetes , Diabetes Mellitus , Insuficiência Cardíaca , Hipertensão , Infarto do Miocárdio , Doenças Retinianas , Humanos , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/epidemiologia , Algoritmos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Aprendizado de MáquinaRESUMO
During the emergence of new host-microbe symbioses, microbial fitness results from the ability to complete the different steps of symbiotic life cycles, where each step imposes specific selective pressures. However, the relative contribution of these different selective pressures to the adaptive trajectories of microbial symbionts is still poorly known. Here, we characterized the dynamics of phenotypic adaptation to a simplified symbiotic life cycle during the experimental evolution of a plant pathogenic bacterium into a legume symbiont. We observed that fast adaptation was predominantly explained by improved competitiveness for host entry, which outweighed adaptation to within-host proliferation. Whole-population sequencing of bacteria at regular time intervals along this evolution experiment revealed the continuous accumulation of new mutations (fuelled by a transient hypermutagenesis phase occurring at each cycle before host entry, a phenomenon described in previous work) and sequential sweeps of cohorts of mutations with similar temporal trajectories. The identification of adaptive mutations within the fixed mutational cohorts showed that several adaptive mutations can co-occur in the same cohort. Moreover, all adaptive mutations improved competitiveness for host entry, while only a subset of those also improved within-host proliferation. Computer simulations predict that this effect emerges from the presence of a strong selective bottleneck at host entry occurring before within-host proliferation and just after the hypermutagenesis phase in the rhizosphere. Together, these results show how selective bottlenecks can alter the relative influence of selective pressures acting during bacterial adaptation to multistep infection processes.
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Fabaceae , Fabaceae/genética , Bactérias/genética , Adaptação Fisiológica , Mutação , Aclimatação , Simbiose/genéticaRESUMO
Large-scale genome sequencing and the increasingly massive use of high-throughput approaches produce a vast amount of new information that completely transforms our understanding of thousands of microbial species occurring in our environment. However, despite the development of powerful bioinformatics approaches, full interpretation of the content of these genomes remains a difficult task. To address this challenge, the MicroScope platform has been developed. It is an integrated Web platform for management, annotation, comparative analysis, and visualization of microbial genomes ( https://mage.genoscope.cns.fr/microscope ). Launched in 2005, the platform has been under continuous development and provides analyzes for complete and ongoing genome projects together with metabolic network reconstruction and transcriptomic experiments allowing users to improve the understanding of gene functions. MicroScope platform is widely used by microbiologists from academia and industry all around the world for collaborative studies and expert annotation. It enables collaborative work in a rich comparative genomic context and improves community-based curation efforts. Here, we describe the protocol to follow for the integration and analysis of transcriptomics data in the Microscope platform. The chapter reviews each key step from the experimental design to the analysis and interpretation of the experiment data and results. The integration of transcriptomics data gives a dynamic view of the genome by allowing the users to improve the understanding of gene functions by interpreting them in the light of regulatory cell processes. Moreover, they can also contribute to the refinement of genome annotation through the discovery of new genes and help to fill metabolic gaps.
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Software , Transcriptoma , Genômica/métodos , Biologia Computacional/métodos , Genoma Microbiano , Bases de Dados Genéticas , Anotação de Sequência MolecularRESUMO
PURPOSE: Knee arthrodesis is an established procedure for limb salvage in cases of recurrent infection, total knee arthroplasty soft tissue defect, poor bone stock or a deficient extensor mechanism. Surgical options include compression plate, external fixator and arthrodesis nail. Different types of nail exist: long fusion nail, short modular nail and bridging nail. This study presents the results on knee arthrodesis using different types of intramedullary nails. The aim is to assess if a specific type of nail has a better fusion rate, clinical outcome and lower complication rate. METHODS: A mono-centric retrospective study of 48 knees arthrodesis was performed between 2000 and 2018. 15 T2™ Arthrodesis Nail, 6 OsteoBridge® Knee Arthrodesis and 27 Wichita® fusion nail were used. The mean clinic and radiological follow-up was 9.8 ± 3.8 years (2.6-18 years). RESULTS: Fusion rate was 89.6%. Time to fusion was 6.9 months. Mean Parker score was 6.9/9 points. Visual Analogic Scale was 1.9. The Wichita® fusion nail showed better results in terms of fusion, time to fusion and clinical outcome measured by Parker score and VAS but without statistical significance. The early revision rate was 10.4% and 20.8% presented a late complication requiring a surgery, due to nonunion or infection. 93.3% of infection was cured. Two patients live with a fistula (4.2%) and 1 was amputated (2.1%). CONCLUSION: Although burdened by a big complication rate, knee arthrodesis with an intramedullary nail provides satisfactory results and is a good alternative to above-knee-amputation. The Wichita® fusion nail shows a tendency to better results compared to the two other nails. LEVEL OF EVIDENCE: Case series, level IV.
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Artroplastia do Joelho , Infecções Relacionadas à Prótese , Humanos , Estudos Retrospectivos , Pinos Ortopédicos/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Joelho/cirurgia , Reoperação/métodos , Artrodese/efeitos adversos , Artrodese/métodos , Resultado do Tratamento , Infecções Relacionadas à Prótese/cirurgia , Infecções Relacionadas à Prótese/etiologiaRESUMO
Metformin is one of the most prescribed antidiabetic agents worldwide and is also considered for other therapeutic applications including cancer and endocrine disorders. It is largely unmetabolized by human enzymes and its presence in the environment has raised concern, with reported toxic effects on aquatic life and potentially also on humans. We report on the isolation and characterisation of strain MD1, an aerobic methylotrophic bacterium growing with metformin as its sole carbon, nitrogen and energy source. Strain MD1 degrades metformin into dimethylamine used for growth, and guanylurea as a side-product. Sequence analysis of its fully assembled genome showed its affiliation to Aminobacter niigataensis. Differential proteomics and transcriptomics, as well as mini-transposon mutagenesis of the strain, point to genes and proteins essential for growth with metformin and potentially associated with hydrolytic C-N cleavage of metformin or with cellular transport of metformin and guanylurea. The obtained results suggest the recent evolution of the growth-supporting capacity of strain MD1 to degrade metformin. Our results identify candidate proteins of the enzymatic system for metformin transformation in strain MD1 and will inform future research on the fate of metformin and its degradation products in the environment and in humans.
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Dichloromethane (DCM, methylene chloride) is a toxic halogenated volatile organic compound massively used for industrial applications, and consequently often detected in the environment as a major pollutant. DCM biotransformation suggests a sustainable decontamination strategy of polluted sites. Among methylotrophic bacteria able to use DCM as a sole source of carbon and energy for growth, Methylorubrum extorquens DM4 is a longstanding reference strain. Here, the primary 5'-ends of transcripts were obtained using a differential RNA-seq (dRNA-seq) approach to provide the first transcription start site (TSS) genome-wide landscape of a methylotroph using DCM or methanol. In total, 7231 putative TSSs were annotated and classified with respect to their localization to coding sequences (CDSs). TSSs on the opposite strand of CDS (antisense TSS) account for 31% of all identified TSSs. One-third of the detected TSSs were located at a distance to the start codon inferior to 250 nt (average of 84 nt) with 7% of leaderless mRNA. Taken together, the global TSS map for bacterial growth using DCM or methanol will facilitate future studies in which transcriptional regulation is crucial, and efficient DCM removal at polluted sites is limited by regulatory processes.
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Bacteria adapt to utilize the nutrients available in their environment through a sophisticated metabolic system composed of highly specialized enzymes. Although these enzymes can metabolize molecules other than those for which they evolved, their efficiency toward promiscuous substrates is considered too low to be of physiological relevance. Herein, we investigated the possibility that these promiscuous enzymes are actually efficient enough at metabolizing secondary substrates to modify the phenotype of the cell. For example, in the bacterium Acinetobacter baylyi ADP1 (ADP1), panD (coding for l-aspartate decarboxylase) encodes the only protein known to catalyze the synthesis of ß-alanine, an obligate intermediate in CoA synthesis. However, we show that the ADP1 ΔpanD mutant could also form this molecule through an unknown metabolic pathway arising from promiscuous enzymes and grow as efficiently as the wildtype strain. Using metabolomic analyses, we identified 1,3-diaminopropane and 3-aminopropanal as intermediates in this novel pathway. We also conducted activity screening and enzyme kinetics to elucidate candidate enzymes involved in this pathway, including 2,4-diaminobutyrate aminotransferase (Dat) and 2,4-diaminobutyrate decarboxylase (Ddc) and validated this pathway in vivo by analyzing the phenotype of mutant bacterial strains. Finally, we experimentally demonstrate that this novel metabolic route is not restricted to ADP1. We propose that the occurrence of conserved genes in hundreds of genomes across many phyla suggests that this previously undescribed pathway is widespread in prokaryotes.
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Acinetobacter , Vias Biossintéticas , Acinetobacter/genética , Acinetobacter/metabolismo , Escherichia coli/metabolismo , Redes e Vias Metabólicas , Transaminases/genética , Transaminases/metabolismo , beta-Alanina/metabolismoRESUMO
The reductive glycine pathway was described as the most energetically favorable synthetic route of aerobic formate assimilation. Here we report the successful implementation of formatotrophy in Escherichia coli by means of a stepwise adaptive evolution strategy. Medium swap and turbidostat regimes of continuous culture were applied to force the channeling of carbon flux through the synthetic pathway to pyruvate establishing growth on formate and CO2 as sole carbon sources. Labeling with 13C-formate proved the assimilation of the C1 substrate via the pathway metabolites. Genetic analysis of intermediate isolates revealed a mutational path followed throughout the adaptation process. Mutations were detected affecting the copy number (gene ftfL) or the coding sequence (genes folD and lpd) of genes which specify enzymes implicated in the three steps forming glycine from formate and CO2, the central metabolite of the synthetic pathway. The mutation R191S present in methylene-tetrahydrofolate dehydrogenase/cyclohydrolase (FolD) abolishes the inhibition of cyclohydrolase activity by the substrate formyl-tetrahydrofolate. The mutation R273H in lipoamide dehydrogenase (Lpd) alters substrate affinities as well as kinetics at physiological substrate concentrations likely favoring a reactional shift towards lipoamide reduction. In addition, genetic reconstructions proved the necessity of all three mutations for formate assimilation by the adapted cells. The largely unpredictable nature of these changes demonstrates the usefulness of the evolutionary approach enabling the selection of adaptive mutations crucial for pathway engineering of biotechnological model organisms.
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Dióxido de Carbono , Escherichia coli , Biocatálise , Dióxido de Carbono/metabolismo , Escherichia coli/metabolismo , Formiatos/metabolismo , Glicina/metabolismoRESUMO
The electroencephalogram (EEG) can be analyzed in its raw form for characteristic drug-induced patterns of change or summarized using mathematical parameters as a processed electroencephalogram (pEEG). In this article we aim to summarize the contemporary literature pertaining to the commonly available pEEG monitors including the effects of commonly used anesthetic drugs on the EEG and pEEG parameters, pEEG monitor pitfalls, and the clinical implications of pEEG monitoring for anesthesia, pediatrics, and intensive care.
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Anestesia , Anestesiologia , Criança , Cuidados Críticos , Eletroencefalografia , Humanos , Monitorização FisiológicaRESUMO
The nicotinamide cofactor specificity of enzymes plays a key role in regulating metabolic processes and attaining cellular homeostasis. Multiple studies have used enzyme engineering tools or a directed evolution approach to switch the cofactor preference of specific oxidoreductases. However, whole-cell adaptation toward the emergence of novel cofactor regeneration routes has not been previously explored. To address this challenge, we used an Escherichia coli NADPH-auxotrophic strain. We continuously cultivated this strain under selective conditions. After 500 to 1,100 generations of adaptive evolution using different carbon sources, we isolated several strains capable of growing without an external NADPH source. Most isolated strains were found to harbor a mutated NAD+-dependent malic enzyme (MaeA). A single mutation in MaeA was found to switch cofactor specificity while lowering enzyme activity. Most mutated MaeA variants also harbored a second mutation that restored the catalytic efficiency of the enzyme. Remarkably, the best MaeA variants identified this way displayed overall superior kinetics relative to the wild-type variant with NAD+. In other evolved strains, the dihydrolipoamide dehydrogenase (Lpd) was mutated to accept NADP+, thus enabling the pyruvate dehydrogenase and 2-ketoglutarate dehydrogenase complexes to regenerate NADPH. Interestingly, no other central metabolism oxidoreductase seems to evolve toward reducing NADP+, which we attribute to several biochemical constraints, including unfavorable thermodynamics. This study demonstrates the potential and biochemical limits of evolving oxidoreductases within the cellular context toward changing cofactor specificity, further showing that long-term adaptive evolution can optimize enzyme activity beyond what is achievable via rational design or directed evolution using small libraries. IMPORTANCE In the cell, NAD(H) and NADP(H) cofactors have different functions. The former mainly accepts electrons from catabolic reactions and carries them to respiration, while the latter provides reducing power for anabolism. Correspondingly, the ratio of the reduced to the oxidized form differs for NAD+ (low) and NADP+ (high), reflecting their distinct roles. We challenged the flexibility of E. coli's central metabolism in multiple adaptive evolution experiments using an NADPH-auxotrophic strain. We found several mutations in two enzymes, changing the cofactor preference of malic enzyme and dihydrolipoamide dehydrogenase. Upon deletion of their corresponding genes we performed additional evolution experiments which did not lead to the emergence of any additional mutants. We attribute this restricted number of mutational targets to intrinsic thermodynamic barriers; the high ratio of NADPH to NADP+ limits metabolic redox reactions that can regenerate NADPH, mainly by mass action constraints.
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Coenzimas/metabolismo , Escherichia coli/enzimologia , Escherichia coli/metabolismo , Evolução Molecular , NADP/metabolismo , Oxirredutases/metabolismo , Carbono/metabolismo , Coenzimas/genética , Escherichia coli/genética , Proteínas de Escherichia coli , Cinética , Malato Desidrogenase/metabolismo , NAD/metabolismo , Oxirredutases/genéticaRESUMO
It is unclear what the effects of taxes on sugar sweetened beverages (SSBs) are on consumer behaviour and which consumers may be affected the most. We evaluate the effect of the SSB tax introduced in Catalonia (but not in the rest of Spain) in May 2017 using loyalty card data of monthly purchases by 884,843 households from May 2016 to April 2018. Using a Difference-in-Differences approach, we study the SSB tax effect on the purchased quantity of beverages and sugar. Our results suggest a reduction in purchases of taxed beverages and a small increase in purchases of untaxed beverages. Households have substituted taxed beverages with their lower sugar (untaxed) counterparts. This has led to a 2.2% overall reduction in sugar purchases from beverages. Our study implies that although sin taxes moderately change consumer behaviour, a combination of different policies would be required to tackle obesity.
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Comércio , Bebidas Adoçadas com Açúcar , Bebidas , Humanos , Espanha , ImpostosRESUMO
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the strain of coronavirus that causes coronavirus disease 2019 (COVID-19) can cause serious illness in some people resulting in admission to intensive care units (ICU) and frequently, ventilatory support for acute respiratory failure. Evaluating ICU care, and what is effective in improving outcomes for these patients is critical. Care bundles, a small set of evidence-based interventions, delivered together consistently, may improve patient outcomes. To identify the extent of the available evidence on the use of care bundles in patients with COVID-19 in the ICU, the World Health Organization (WHO) commissioned a scoping review to inform WHO guideline discussions. This review does not assess the effectiveness of the findings, assess risk of bias, or assess the certainty of the evidence (GRADE). As this review was commissioned to inform guideline discussions, it was done rapidly over a three-week period from 26 October to 18 November 2020. OBJECTIVES: To identify and describe the available evidence on the use of care bundles in the ICU for patients with COVID-19 or related conditions (acute respiratory distress syndrome (ARDS) viral pneumonia or pneumonitis), or both. In carrying out the review the focus was on characterising the evidence base and not evaluating the effectiveness or safety of the care bundles or their component parts. SEARCH METHODS: We searched MEDLINE, Embase, the Cochrane Library (CENTRAL and the Cochrane COVID-19 Study Register) and the WHO International Clinical Trials Registry Platform on 26 October 2020. SELECTION CRITERIA: Studies of all designs that reported on patients who are critically ill with COVID-19, ARDS, viral pneumonia or pneumonitis, in the ICU setting, where a care bundle was implemented in providing care, were eligible for inclusion. One review author (VS) screened all records on title and abstract. A second review author (DR) checked 20% of excluded and included records; agreement was 99.4% and 100% respectively on exclude/include decisions. Two review authors (VS and DR) independently screened all records at full-text level. VS and DR resolved any disagreements through discussion and consensus, or referral to a third review author (AN) as required. DATA COLLECTION AND ANALYSIS: One review author (VS) extracted the data and a second review author (DR) checked 20% of this for accuracy. As the review was not designed to synthesise effectiveness data, assess risk of bias, or characterise the certainty of the evidence (GRADE), we mapped the extracted data and presented them in tabular format based on the patient condition; that is patients with confirmed or suspected COVID-19, patients with ARDS, patients with any influenza or viral pneumonia, patients with severe respiratory failure, and patients with mixed conditions. We have also provided a narrative summary of the findings from the included studies. MAIN RESULTS: We included 21 studies and identified three ongoing studies. The studies were of variable designs and included a systematic review of standardised approaches to caring for critically ill patients in ICU, including but not exclusive to care bundles (1 study), a randomised trial (1 study), prospective and retrospective cohort studies (4 studies), before and after studies (7 studies), observational quality improvement reports (4 studies), case series/case reports (3 studies) and audit (1 study). The studies were conducted in eight countries, most commonly China (5 studies) and the USA (4 studies), were published between 1999 and 2020, and involved over 2000 participants in total. Studies categorised participant conditions patients with confirmed or suspected COVID-19 (7 studies), patients with ARDS (7 studies), patients with another influenza or viral pneumonia (5 studies), patients with severe respiratory failure (1 study), and patients with mixed conditions (1 study). The care bundles described in the studies involved multiple diverse practices. Guidance on ventilator settings (10 studies), restrictive fluid management (8 studies), sedation (7 studies) and prone positioning (7 studies) were identified most frequently, while only one study mentioned chest X-ray. None of the included studies reported the prespecified outcomes ICU-acquired weakness (muscle wasting, weight loss) and users' experience adapting care bundles. Of the remaining prespecified outcomes, 14 studies reported death in ICU, nine reported days of ventilation (or ventilator-free days), nine reported length of stay in ICU in days, five reported death in hospital, three reported length of stay in hospital in days, and three reported adherence to the bundle. AUTHORS' CONCLUSIONS: This scoping review has identified 21 studies on care bundle use in critically ill patients in ICU with COVID-19, ARDS, viral influenza or pneumonia and severe respiratory failure. The data for patients with COVID-19 specifically are limited, derived mainly from observational quality improvement or clinical experiential accounts. Research is required, urgently, to further assess care bundle use and optimal components of these bundles in this patient cohort. The care bundles described were also varied, with guidance on ventilator settings described in 10 care bundles, while chest X-ray was part mentioned in one care bundle in one study only. None of the studies identified in this scoping review measured users' experience of adapting care bundles. Optimising care bundle implementation requires that the components of the care bundle are collectively and consistently applied. Data on challenges, barriers and facilitators to implementation are needed. A formal synthesis of the outcome data presented in this review and a critical appraisal of the evidence is required by a subsequent effectiveness review. This subsequent review should further explore effect estimates across the included studies.
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COVID-19/terapia , Cuidados Críticos , Pacotes de Assistência ao Paciente/métodos , SARS-CoV-2 , COVID-19/complicações , COVID-19/epidemiologia , Humanos , Influenza Humana/terapia , Unidades de Terapia Intensiva , Pandemias , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório/terapia , Insuficiência Respiratória/terapia , Resultado do TratamentoRESUMO
Thiomonas bacteria are ubiquitous at acid mine drainage sites and play key roles in the remediation of water at these locations by oxidizing arsenite to arsenate, favouring the sorption of arsenic by iron oxides and their coprecipitation. Understanding the adaptive capacities of these bacteria is crucial to revealing how they persist and remain active in such extreme conditions. Interestingly, it was previously observed that after exposure to arsenite, when grown in a biofilm, some strains of Thiomonas bacteria develop variants that are more resistant to arsenic. Here, we identified the mechanisms involved in the emergence of such variants in biofilms. We found that the percentage of variants generated increased in the presence of high concentrations of arsenite (5.33 mM), especially in the detached cells after growth under biofilm-forming conditions. Analysis of gene expression in the parent strain CB2 revealed that genes involved in DNA repair were upregulated in the conditions where variants were observed. Finally, we assessed the phenotypes and genomes of the subsequent variants generated to evaluate the number of mutations compared to the parent strain. We determined that multiple point mutations accumulated after exposure to arsenite when cells were grown under biofilm conditions. Some of these mutations were found in what is referred to as ICE19, a genomic island (GI) carrying arsenic-resistance genes, also harbouring characteristics of an integrative and conjugative element (ICE). The mutations likely favoured the excision and duplication of this GI. This research aids in understanding how Thiomonas bacteria adapt to highly toxic environments, and, more generally, provides a window to bacterial genome evolution in extreme environments.
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Arsenitos/metabolismo , Biofilmes/crescimento & desenvolvimento , Burkholderiales , Genoma Bacteriano/genética , Adaptação Fisiológica/genética , Arseniatos/metabolismo , Arsênio/metabolismo , Burkholderiales/genética , Burkholderiales/crescimento & desenvolvimento , Burkholderiales/metabolismo , Reparo do DNA/genética , Elementos de DNA Transponíveis/genética , Evolução Molecular , Perfilação da Expressão Gênica , Variação Genética/genética , Ilhas Genômicas/genética , Mineração , Sequenciamento Completo do GenomaRESUMO
Large-scale genome sequencing and the increasingly massive use of high-throughput approaches produce a vast amount of new information that completely transforms our understanding of thousands of microbial species. However, despite the development of powerful bioinformatics approaches, full interpretation of the content of these genomes remains a difficult task. Launched in 2005, the MicroScope platform (https://www.genoscope.cns.fr/agc/microscope) has been under continuous development and provides analysis for prokaryotic genome projects together with metabolic network reconstruction and post-genomic experiments allowing users to improve the understanding of gene functions. Here we present new improvements of the MicroScope user interface for genome selection, navigation and expert gene annotation. Automatic functional annotation procedures of the platform have also been updated and we added several new tools for the functional annotation of genes and genomic regions. We finally focus on new tools and pipeline developed to perform comparative analyses on hundreds of genomes based on pangenome graphs. To date, MicroScope contains data for >11 800 microbial genomes, part of which are manually curated and maintained by microbiologists (>4500 personal accounts in September 2019). The platform enables collaborative work in a rich comparative genomic context and improves community-based curation efforts.
Assuntos
Genes Arqueais , Genes Bacterianos , Genômica/métodos , Anotação de Sequência Molecular/métodos , Software , Bases de Dados Genéticas , Redes e Vias MetabólicasRESUMO
Brochothrix thermosphacta is one of the main spoilers in food, responsible for meat and seafood spoilage through the production of malodorous volatile organic compounds. The molecules produced by this bacterium depend on the substrate (meat or seafood) and the storage conditions such as gas mixtures used in the packaging. It seems also that the spoilage potential is strain dependent as production of diacetyl and acetoin, two molecules responsible for seafood spoilage, varies with strains. Therefore, this suggests the involvement of different metabolic functions depending on both food substrate and strain capacities. In this study, we selected two strains with different abilities to produce diacetyl and acetoin and compared their behavior after grown in beef or cooked peeled shrimp juices. We determined the genes upregulated by both strains depending on the growth substrate and those that were specifically upregulated in only one strain. The genes upregulated by both strains in meat or in shrimp juice revealed the importance of the substrate for inducing specific metabolic pathways. The examination of genes that were specifically upregulated in only one of the two strains revealed strain features associated to specific substrates and also strain-specific regulations of metabolic pathways putatively leading to different levels of spoilage molecule production. This shows that the spoilage potential of B. thermosphacta depends on nutrients provided by food substrate and on metabolic activity potential that each strain possesses.