IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals

Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We perform an observational study to investigate seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5-79 years). Seropositivity for SARS-CoV-2 Spike glycoprotein aligns with PCR results that confirm the previous infection. Anti-Spike IgG/IgM titers remain high 60 days post-infection and do not strongly associate with symptoms, except for fever. We analyze PBMCs from a subset of seropositive and seronegative adults. TLR7 agonist-activation reveals an increased population of IL-6+TNF-IL-1β+ monocytes, while SARS-CoV-2 peptide stimulation elicits IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlates with CD4+ T cell activation in PBMCs from convalescent subjects and is likely due to T cell-mediated effects on IL-33-producing cells. IL-33 is associated with pulmonary infection and chronic diseases like asthma and COPD, but its role in COVID-19 is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid (BALF) from patients with mild to severe COVID-19 reveals a population of IL-33-producing cells that increases with the disease. Together these findings show that IL-33 production is linked to SARS-CoV-2 infection and warrant further investigation of IL-33 in COVID-19 pathogenesis and immunity

Walking on common ground: a cross-disciplinary scoping review on the clinical utility of digital mobility outcomes

Physical mobility is essential to health, and patients often rate it as a high-priority clinical outcome. Digital mobility outcomes (DMOs), such as real-world gait speed or step count, show promise as clinical measures in many medical conditions. However, current research is nascent and fragmented by discipline. This scoping review maps existing evidence on the clinical utility of DMOs, identifying commonalities across traditional disciplinary divides. In November 2019, 11 databases were searched for records investigating the validity and responsiveness of 34 DMOs in four diverse medical conditions (Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease, hip fracture). Searches yielded 19,672 unique records. After screening, 855 records representing 775 studies were included and charted in systematic maps. Studies frequently investigated gait speed (70.4% of studies), step length (30.7%), cadence (21.4%), and daily step count (20.7%). They studied differences between healthy and pathological gait (36.4%), associations between DMOs and clinical measures (48.8%) or outcomes (4.3%), and responsiveness to interventions (26.8%). Gait speed, step length, cadence, step time and step count exhibited consistent evidence of validity and responsiveness in multiple conditions, although the evidence was inconsistent or lacking for other DMOs. If DMOs are to be adopted as mainstream tools, further work is needed to establish their predictive validity, responsiveness, and ecological validity. Cross-disciplinary efforts to align methodology and validate DMOs may facilitate their adoption into clinical practice

Walking on common ground: a cross-disciplinary scoping review on the clinical utility of digital mobility outcomes

Physical mobility is essential to health, and patients often rate it as a high-priority clinical outcome. Digital mobility outcomes (DMOs), such as real-world gait speed or step count, show promise as clinical measures in many medical conditions. However, current research is nascent and fragmented by discipline. This scoping review maps existing evidence on the clinical utility of DMOs, identifying commonalities across traditional disciplinary divides. In November 2019, 11 databases were searched for records investigating the validity and responsiveness of 34 DMOs in four diverse medical conditions (Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease, hip fracture). Searches yielded 19,672 unique records. After screening, 855 records representing 775 studies were included and charted in systematic maps. Studies frequently investigated gait speed (70.4% of studies), step length (30.7%), cadence (21.4%), and daily step count (20.7%). They studied differences between healthy and pathological gait (36.4%), associations between DMOs and clinical measures (48.8%) or outcomes (4.3%), and responsiveness to interventions (26.8%). Gait speed, step length, cadence, step time and step count exhibited consistent evidence of validity and responsiveness in multiple conditions, although the evidence was inconsistent or lacking for other DMOs. If DMOs are to be adopted as mainstream tools, further work is needed to establish their predictive validity, responsiveness, and ecological validity. Cross-disciplinary efforts to align methodology and validate DMOs may facilitate their adoption into clinical practice

Genome Analysis of the Meat Starter Culture Bacterium Staphylococcus carnosus TM300▿ †

The Staphylococcus carnosus genome has the highest GC content of all sequenced staphylococcal genomes, with 34.6%, and therefore represents a species that is set apart from S. aureus, S. epidermidis, S. saprophyticus, and S. haemolyticus. With only 2.56 Mbp, the genome belongs to a family of smaller staphylococcal genomes, and the ori and ter regions are asymmetrically arranged with the replichores I (1.05 Mbp) and II (1.5 Mbp). The events leading up to this asymmetry probably occurred not that long ago in evolution, as there was not enough time to approach the natural tendency of a physical balance. Unlike the genomes of pathogenic species, the TM300 genome does not contain mobile elements such as plasmids, insertion sequences, transposons, or STAR elements; also, the number of repeat sequences is markedly decreased, suggesting a comparatively high stability of the genome. While most S. aureus genomes contain several prophages and genomic islands, the TM300 genome contains only one prophage, ΦTM300, and one genomic island, νSCA1, which is characterized by a mosaic structure mainly composed of species-specific genes. Most of the metabolic core pathways are present in the genome. Some open reading frames are truncated, which reflects the nutrient-rich environment of the meat starter culture, making some functions dispensable. The genome is well equipped with all functions necessary for the starter culture, such as nitrate/nitrite reduction, various sugar degradation pathways, two catalases, and nine osmoprotection systems. The genome lacks most of the toxins typical of S. aureus as well as genes involved in biofilm formation, underscoring the nonpathogenic status

Predicting advanced balance ability and mobility with an instrumented timed up and go test

Extensive test batteries are often needed to obtain a comprehensive picture of a person\u2019s functional status. Many test batteries are not suitable for active and healthy adults due to ceiling effects, or require a lot of space, time, and training. The Community Balance and Mobility Scale (CBMS) is considered a gold standard for this population, but the test is complex, as well as time-and resource intensive. There is a strong need for a faster, yet sensitive and robust test of physical function in seniors. We sought to investigate whether an instrumented Timed Up and Go (iTUG) could predict the CBMS score in 60 outpatients and healthy community-dwelling seniors, where features of the iTUG were predictive, and how the prediction of CBMS with the iTUG compared to standard clinical tests. A partial least squares regression analysis was used to identify latent components explaining variation in CBMS total score. The model with iTUG features was able to predict the CBMS total score with an accuracy of 85.2% (84.9\u201385.5%), while standard clinical tests predicted 82.5% (82.2\u201382.8%) of the score. These findings suggest that a fast and easily administered iTUG could be used to predict CBMS score, providing a valuable tool for research and clinical care

ParSeq: searching motifs with structural and biochemical properties

Summary: Searches for variable motifs such as proteinbinding sites or promoter regions are more complex than the search for casual motifs. For example, in amino acid sequences comparing motifs alone mostly proves to be insufficient to detect regions that represent proteins with a special function, because the function depends on biochemical properties of individual amino acids (such as polarity or hydrophobicity) . Pure string matching programs are not able to find these motifs; hence, we developed ParSeq, a program that combines the search for motifs with certain structural properties, the verification of biochemical properties, an approximate search mechanism and a stepwise creation of the motif description by allowing to search on previously obtained results

The association of basic and challenging motor capacity with mobility performance and falls in young seniors

Background: Understanding the association between motor capacity (MC) (what people can do in a standardized environment), mobility performance (MP) (what people actually do in real-life) and falls is important for early detection of and counteracting on functional decline, particularly in the rapidly growing population of young seniors. Therefore, this study aims to 1) explore the association between MC and MP, and between MC and falls, and 2) investigate whether challenging MC measures are better associated with MP and falls than basic MC measures. Methods: Basic (habitual gait speed, Timed Up-and-Go) and challenging (fast gait speed, Community Balance & Mobility Scale) MC measures were performed in 169 young seniors (61\u201370 years). MP was assessed using one-week sensor-monitoring including time being sedentary, light active, and at least moderately active. Falls in the previous six months were reported. Associations and discriminative ability were calculated using correlation, regression and receiver operating curve analysis. Results: Mean age was 66.4 (SD 2.4) years (50.6 % women). Small to moderate associations (r = 0.06 120.31; p < .001\u2013.461) were found between MC, MP and falls. Challenging MC measures showed closer associations with MP and falls (r = 0.10 120.31; p < .001\u2013.461) compared to basic (r = 0.06 120.22; p = .012\u2013.181), remained significant in three out of four regression models explaining 2.5\u20138.6 % of the variance, and showed highest discriminative ability (area under the curve = 0.59 120.70) in all analyses. Conclusions: Challenging MC measures are closer associated with mobility performance and falls as compared to basic MC measures in young seniors. This indicates the importance of applying challenging motor capacity assessments in young seniors. On the same note, small to moderate associations imply a need for an assessment of both MC and MP in order to capture the best possible MC and the actual daily-life MP in young seniors