Lessons learned from urgent computing in Europe: Tackling the COVID-19 pandemic.

PRACE (Partnership for Advanced Computing in Europe), an international not-for-profit association that brings together the five largest European supercomputing centers and involves 26 European countries, has allocated more than half a billion core hours to computer simulations to fight the COVID-19 pandemic. Alongside experiments, these simulations are a pillar of research to assess the risks of different scenarios and investigate mitigation strategies. While the world deals with the subsequent waves of the pandemic, we present a reflection on the use of urgent supercomputing for global societal challenges and crisis management.

The Chlamydia trachomatis IncM Protein Interferes with Host Cell Cytokinesis, Centrosome Positioning, and Golgi Distribution and Contributes to the Stability of the Pathogen-Containing Vacuole.

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes ocular and urogenital infections in humans. The ability of C. trachomatis to grow intracellularly in a pathogen-containing vacuole (known as an inclusion) depends on chlamydial effector proteins transported into the host cell by a type III secretion system. Among these effectors, several inclusion membrane proteins (Incs) insert in the vacuolar membrane. Here, we show that human cell lines infected by a C. trachomatis strain deficient for Inc CT288/CTL0540 (renamed IncM) displayed less multinucleation than when infected by IncM-producing strains (wild type or complemented). This indicated that IncM is involved in the ability of Chlamydia to inhibit host cell cytokinesis. The capacity of IncM to induce multinucleation in infected cells was shown to be conserved among its chlamydial homologues and appeared to require its two larger regions predicted to be exposed to the host cell cytosol. C. trachomatis-infected cells also displayed IncM-dependent defects in centrosome positioning, Golgi distribution around the inclusion, and morphology and stability of the inclusion. The altered morphology of inclusions containing IncM-deficient C. trachomatis was further affected by depolymerization of host cell microtubules. This was not observed after depolymerization of microfilaments, and inclusions containing wild-type C. trachomatis did not alter their morphology upon depolymerization of microtubules. Overall, these findings suggest that IncM may exert its effector function by acting directly or indirectly on host cell microtubules.

FODMAPs, inflammatory bowel disease and gut microbiota: updated overview on the current evidence.

PURPOSE: Based on the fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) hypothesis, the low-FODMAP diet has been suggested as a potential therapeutic approach for inflammatory bowel disease (IBD) with promising results on disease management. However, this diet implies a specific broad food restriction, which potentially increases the risk of nutritional deficiencies and may aggravate gut microbiota dysbiosis of IBD patients. The aim of the present study is to review the effect of individual FODMAPs on the human gut microbiota. In addition, this narrative review provides an updated overview of the use of the low-FODMAP diet in IBD, namely the implementation, advantages, limitations, and the impact on the gut microbiota. METHODS: The literature search strategy was applied to PubMed and Web of Science using relevant keywords, IBD, FODMAPs, Fructose, Lactose, Polyols, FOS, GOS, low-FODMAP diet and gut microbiota. RESULTS: Current data suggest that the low-FODMAP diet may effectively improve clinical outcomes in the management of IBD and ensure better quality of life for IBD patients. However, there is evidence highlighting some issues of concern, particularly the adequacy of the diet and the impact on the gut microbiota. The various FODMAP types differently modulate the gut microbiota. CONCLUSION: IBD management should be achieved with the least possible dietary restriction to avoid detrimental consequences, particularly on nutritional adequacy and gut microbiota. Thus, it is important to individualize and monitor the nutrition intervention. Further studies are required to better characterize the relationship between diet, the gut microbiota, and IBD to support the generalization of this approach for clinical practice in IBD therapy and management.

Development of an international Core Outcome Set (COS) for best care for the dying person: study protocol.

BACKGROUND: In contrast to typical measures employed to assess outcomes in healthcare such as mortality or recovery rates, it is difficult to define which specific outcomes of care are the most important in caring for dying individuals. Despite a variety of tools employed to assess different dimensions of palliative care, there is no consensus on a set of core outcomes to be measured in the last days of life. In order to optimise decision making in clinical practice and comparability of interventional studies, we aim to identify and propose a set of core outcomes for the care of the dying person. METHODS: Following the COMET initiative approach, the proposed study will proceed through four stages to develop a set of core outcomes: In stage 1, a systematic review of the literature will identify outcomes measured in existing peer reviewed literature, as well as outcomes derived through qualitative studies. Grey literature, will also be included. Stage 2 will allow for the identification and determination of patient and proxy defined outcomes of care at the end of life via quantitative and qualitative methods at an international level. In stage 3, from a list of salient outcomes identified through stages 1 and 2, international experts, family members, patients, and patient advocates will be asked to score the importance of the preselected outcomes through a Delphi process. Stage 4 consists of a face-to-face consensus meeting of international experts and patient/family representatives in order to define, endorse, and propose the final Core Outcomes Set. DISCUSSION: Core Outcome Sets aim at promoting uniform assessment of care outcomes in clinical practice as well as research. If consistently employed, a robust set of core outcomes for the end of life, and specifically for the dying phase, defined by relevant stakeholders, can ultimately be translated into best care for the dying person. Patient care will be improved by allowing clinicians to choose effective and meaningful treatments, and research impact will be improved by employing internationally agreed clinically relevant endpoints and enabling accurate comparison between studies in systematic reviews and/or in meta-analyses.

Evidences and perspectives in the utilization of CLNA isomers as bioactive compounds in foods.

Conjugated alpha linolenic acid (CLNA) isomers are promising lipids owing to their similarities with conjugated linoleic acid (CLA) but exerting their bioactivity at lower doses; some isomers also belong to omega 3 family. This review aims to summarize the state of the art about the utilization of CLNA as a functional ingredient. Indeed, in vitro and in vivo studies reported that CLNA exerted anticancer, anti-inflammatory, anti-obese, and antioxidant activities. However, CLNA has not been tested in humans. These compounds are naturally present in meat and milk fat from ruminants but the highest concentrations are found in vegetable oils. Their incorporation in foodstuffs is one of the most effective strategies to elaborate CLNA-enriched products together with the microbiological production. Lactobacilli, propionibacteria, and bifidobacteria strains have been assayed to produce CLNA isomers but at the current moment there are not high CLNA concentration products elaborated using these strains. Furthermore, it is known that CLNA isomers are highly prone to oxidation when compared with linoleic acid and CLA, but the possible effects of elaboration and storage on high CLNA productsare unknown.The utilization of CLNA as a functional compound still remains a challenge and requires more research to address all of its technological and bioactivity aspects.

Habitual dietary intake is associated with stool microbiota composition in monozygotic twins.

The impact of diet on the gut microbiota has usually been assessed by subjecting people to the same controlled diet and thereafter following the shifts in the microbiota. In the present study, we used habitual dietary intake, clinical data, quantitative polymerase chain reaction, and denaturing gradient gel electrophoresis (DGGE) to characterize the stool microbiota of Finnish monozygotic twins. The effect of diet on the numbers of bacteria was described through a hierarchical linear mixed model that included the twin individuals, stratified by body mass index, and their families as random effects. The abundance and diversity of the bacterial groups studied did not differ between normal-weight, overweight, and obese individuals with the techniques used. Intakes of energy, monounsaturated fatty acids, n3 polyunsaturated fatty acids (PUFAs), n6 PUFAs, and soluble fiber had significant associations with the stool bacterial numbers (e.g., increased energy intake was associated with reduced numbers of Bacteroides spp.). In addition, co-twins with identical energy intake had more similar numbers and DGGE-profile diversities of Bacteroides spp. than did the co-twins with different intake. Moreover, the co-twins who ingested the same amounts of saturated fatty acids had very similar DGGE profiles of Bacteroides spp., whereas the co-twins with similar consumption of fiber had a very low bifidobacterial DGGE-profile similarity. In conclusion, our findings confirm that the diet plays an important role in the modulation of the stool microbiota, in particular Bacteroides spp. and bifidobacteria.

Toward Redox-Free Reverse Electrodialysis with Carbon-Based Slurry Electrodes.

Clean and renewable salinity gradient energy can be harvested using reverse electrodialysis (RED). The electrode system is an essential part to convert ionic current into electrical current. In this study, a typical 0.10 × 0.10 m2 RED stack with a cross-flow configuration was used to test carbon-based slurry electrodes (CSEs) to replace the usual redox solutions, like hexacyanoferrate, to enhance the RED process' sustainability, stability, and economic value. Six different slurry compositions comprising activated carbon, carbon black, and graphite powder were tested. The CSE characteristics were systematically studied by measuring viscosity, electrode compartment pressure drop, maximum current density, stability, and performance of power density and energy efficiency. Using a single membrane configuration, the CSE ran continuously for 17 days with a stable output. The application of CSEs for RED, with artificial seawater and river water, using mixing activated carbon and carbon black at a total concentration of 20 wt %, resulted in the best performance with a net power density of 0.7 W·m-2. Moreover, higher current densities up to 350 A·m-2 were tested for ED and shown to be feasible until 150 A·m-2. CSEs show promising versatility for different application modes.

INFLAMMATORY BOWEL DISEASE AND SARCOPENIA: A FOCUS ON MUSCLE STRENGTH - NARRATIVE REVIEW.

•Muscle strength decline is a crucial factor for the course of sarcopenia in inflammatory bowel disease (IBD) patients. •There is a need to discuss the association between IBD and sarcopenia focusing not only on changes of muscle mass, but also on muscle strength. •A narrative review was conducted in order to present the set of factors with impact in both muscle strength and IBD. •Inflammation, reduced nutrient intake and malabsorption, changes in body composition and gut microbiota dysbiosis are most likely the main factors with impact on muscle strength in IBD patients. Inflammation, changes in nutrient absorption and gut dysbiosis are common conditions in patients with inflammatory bowel disease. These factors may lead to variations in macro- and micronutrients and, particularly, to an imbalance of protein metabolism, loss of muscle mass and development of sarcopenia. This narrative review aims to present the set of factors with impact in muscle strength and physical performance that may potentially mediate the relation between inflammatory bowel disease and sarcopenia. Studies that associated changes in muscle strength, sarcopenia and inflammatory bowel disease were selected through a literature search in databases Medline, Pubmed and Scielo using relevant keywords: muscle strength, physical performance, sarcopenia and inflammatory bowel disease. Chronic inflammation is currently reported as a determinant factor in the development of muscle atrophy in inflammatory bowel disease. In addition, strength decline in inflammatory bowel disease patients may be also influenced by changes in body composition and by gut dysbiosis. Measures of muscle strength and physical performance should be considered in the initial identification of sarcopenia, particularly in patients with inflammatory bowel disease, for a timely intervention can be provided. Presence of proinflammatory cytokines, high adiposity, malabsorption and consequent deficits of macro and micronutrients, loss of muscle mass, and gut dysbiosis may be the main factors with impact in muscle strength, that probably mediate the relation between inflammatory bowel disease and sarcopenia.

Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts.

There is growing evidence supporting the role of fibroblasts in all stages of atherosclerosis, from the initial phase to fibrous cap and plaque formation. In the arterial wall, as with macrophages and vascular smooth muscle cells, fibroblasts are exposed to a myriad of LDL lipids, including the lipid species formed during the oxidation of their polyunsaturated fatty acids of cholesteryl esters (PUFA-CEs). Recently, our group identified the final oxidation products of the PUFA-CEs, cholesteryl hemiesters (ChE), in tissues from cardiovascular disease patients. Cholesteryl hemiazelate (ChA), the most prevalent lipid of this family, is sufficient to impact lysosome function in macrophages and vascular smooth muscle cells, with consequences for their homeostasis. Here, we show that the lysosomal compartment of ChA-treated fibroblasts also becomes dysfunctional. Indeed, fibroblasts exposed to ChA exhibited a perinuclear accumulation of enlarged lysosomes full of neutral lipids. However, this outcome did not trigger de novo lysosome biogenesis, and only the lysosomal transcription factor E3 (TFE3) was slightly transcriptionally upregulated. As a consequence, autophagy was inhibited, probably via mTORC1 activation, culminating in fibroblasts' apoptosis. Our findings suggest that the impairment of lysosome function and autophagy and the induction of apoptosis in fibroblasts may represent an additional mechanism by which ChA can contribute to the progression of atherosclerosis.

Improving Pharmacists' Awareness of Inadequate Antibiotic Use for URTIs through an Educational Intervention: A Pilot Study.

The inadequate use of antibiotics led to the development of multi-resistant bacteria that are now causing millions of deaths worldwide. Since most antibiotics are prescribed/dispensed to treat respiratory tract infections, it is important to raise awareness among health professionals to optimize antibiotic use, especially within the primary care context. Thus, this pilot study aimed to evaluate pharmacists' feedback about the eHealthResp platform, composed by an online course and a mobile application (app) to help in the management of upper respiratory tract infections (URTIs). Ten community pharmacists were invited to participate in this study, exploring the contents of the eHealthResp platforms and answering a content validation questionnaire composed by eight qualitative and thirty-five quantitative questions about the online course and mobile app. The eHealthResp platform is a comprehensive, consistent, and high-quality e-learning tool. Median scores of 5.00 were attributed to the course contents' and clinical cases' adequacy and correction. Most qualitative feedback was about completeness and objectivity of the course, and its usefulness for clinical practice. This study showed that eHealthResp has great potential as an e-health tool for the management of URTIs' symptoms, which may ultimately aid in reducing inappropriate antibiotic use.