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Abstract Background The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion, disrupts immune equilibrium, and potentially triggers diseases including various human leucocyte antigen (HLA)-B27-associated autoinflammatory and autoimmune diseases such as inflammatory bowel disease (IBD) and spondyloarthropathy (SpA). This study assesses compositional and functional alterations of the GM in patients with HLA-B27-associated non-infectious anterior uveitis (AU) compared to healthy controls. Methods The gut metagenomes of 20 patients with HLA-B27-associated non-infectious AU, 21 age- and sex-matched HLA-B27-negative controls, and 6 HLA-B27-positive healthy controls without a history of AU were sequenced using the Illumina NovaSeq 6000 platform for whole metagenome shotgun sequencing. To identify taxonomic and functional features with significantly different relative abundances between groups and to identify associations with clinical metadata, the multivariate association by linear models (MaAsLin) R package was applied. Results Significantly higher levels of the Eubacterium ramulus species were found in HLA-B27-negative controls (p = 0.0085, Mann-Whitney U-test). No significant differences in microbial composition were observed at all other taxonomic levels. Functionally, the lipid IVA biosynthesis pathway was upregulated in patients (p

Aging is associated with an increased risk of fragility fractures at the hip, resulting from a loss of bone mass. While this loss is typically reported as a decreased mean areal bone mineral density (aBMD) in the proximal femur or the femoral neck, its evolution is spatially inhomogeneous, which might also contribute to the increased risk of fractures. Yet, little is known about the evolution of BMD distribution and cortical thickness with age in the proximal femur. We propose a 3D spatio-temporal atlas of the proximal femur to identify regions with high BMD losses and cortical thinning. The atlas is based on 532 post-mortem QCT scans from donors aged 20 to 94, including 179 female subjects. A point cloud with anatomically corresponding positions was defined for each femur based on a personalized coordinate system. The evolution of BMD and cortical thickness was computed as a multiple linear regression with age and BMI, for female and male subjects separately. The average BMD decrease with age was significant in all subregions for both sexes but higher in females. High BMD losses were observed in the superior and middle neck regions, in the medial part of the head, and in the trochanteric trabecular bone. BMD was well preserved in the inferior neck and, for males, in cortical regions. In both sexes, the cortical thickness decreased significantly in the superior and posterior neck cortex and increased significantly in the inferior neck. Higher BMI was associated with increased BMD in the inferior neck and medial shaft cortex, as well as with increased cortical thickness in all neck and shaft regions for both sexes. The spatio-temporal atlas showed the evolution of BMD distribution and cortical thickness in the proximal femur, with high losses in typical fracture locations, such as the femoral neck and pertrochanteric regions.

Abstract Background Fragility fractures in older adults are often caused by fall events. The estimation of an expected fall rate might improve the identification of individuals at risk of fragility fractures and improve fracture prediction. Methods A combined analysis of three previously developed fall rate models using individual participant data (n = 1850) was conducted using the methodology of a two-stage meta-analysis to derive an overall model. These previously developed models included the fall history as a predictor recorded as the number of experienced falls within 12 months, treated as a factor variable with the levels 0, 1, 2, 3, 4 and ≥ 5 falls. In the first stage, negative binomial regression models for every cohort were fit. In the second stage, the coefficients were compared and used to derive overall coefficients with a random effect meta-analysis. Additionally, external validation was performed by applying the three data sets to the models derived in the first stage. Results The coefficient estimates for the prior number of falls were consistent among the three studies. Higgin’s I 2 as heterogeneity measure ranged from 0 to 55.39%. The overall coefficient estimates indicated that the expected fall rate increases with an increasing number of previous falls. External model validation revealed that the prediction errors for the data sets were independent of the model to which they were applied. Conclusion This analysis suggests that the fall history treated as a factor variable is a robust predictor of estimating future falls among different cohorts.

Despite the dominant role of bone mass in osteoporotic fractures, aging bone tissue properties must be thoroughly understood to improve osteoporosis management. In this context, collagen content and integrity are considered important factors, although limited research has been conducted on the tensile behavior of demineralized compact bone in relation to its porosity and elastic properties in the native mineralized state. Therefore, this study aims (i) at examining the age-dependency of mineralized bone and collagen micromechanical properties; (ii) to test whether, and if so to which extent, collagen properties contribute to mineralized bone mechanical properties.Two cylindrical cortical bone samples from fresh frozen human anatomic donor material were extracted from 80 proximal diaphyseal sections from a cohort of 24 female and 19 male donors (57 to 96 years at death). One sample per section was tested in uniaxial tension under hydrated conditions. First, the native sample was tested elastically (0.25 % strain), and after demineralization, up to failure. Morphology and composition of the second specimen was assessed using micro-computed tomography, Raman spectroscopy, and gravimetric methods. Simple and multiple linear regression were employed to relate morphological, compositional, and mechanical variables with age and sex.Macro-tensile properties revealed that only elastic modulus of native samples was age dependent whereas apparent elastic modulus was sex dependent (p

High-resolution peripheral quantitative computed tomography (HR-pQCT) based micro-finite element (μFE) analysis allows accurate prediction of stiffness and ultimate load of standardised (∼1 cm) distal radius and tibia sections. An alternative homogenized finite element method (hFE) was recently validated to compute the ultimate load of larger (∼2 cm) distal radius sections that include Colles' fracture sites. Since the mechanical integrity of the weight-bearing distal tibia is gaining clinical interest, it has been shown that the same properties can be used to predict the strength of both distal segments of the radius and the tibia. Despite the capacity of hFE to predict structural properties of distal segments of the radius and the tibia, the limitations of such homogenization scheme remain unclear. Therefore, the objective of this study is to build a complete mechanical data set of the compressive behavior of distal segments of the tibia and to compare quantitatively the structural properties with the hFE predictions. As a further aim, it is intended to verify whether hFE is also able to capture the post-yield strain localisation or fracture zones in such a bone section, despite the absence of strain softening in the constitutive model.Twenty-five fresh-frozen distal parts of tibias of human donors were used in this study. Sections were cut corresponding to an in-house triple-stack protocol HR-pQCT scan, lapped, and scanned using micro computed tomography (μCT). The sections were tested in compression until failure, unloaded and scanned again in μCT. Volumetric bone mineral density (vBMD) and bone mineral content (BMC) were correlated to compression test results. hFE analysis was performed in order to compare computational predictions (stiffness, yield load and plastic deformation field pattern) with the compressive experiment. Namely, strain localization was assessed based on digital volume correlation (DVC) results and qualitatively compared to hFE predictions by comparing mid-slices patterns.Bone mineral content (BMC) showed a good correlation with stiffness (R2 = 0.92) and yield (R2 = 0.88). Structural parameters also showed good agreement between the experiment and hFE for both stiffness (R2 = 0.96, slope = 1.05 with 95 % CI [0.97, 1.14]) and yield (R2 = 0.95, slope = 1.04 [0.94, 1.13]). The qualitative comparison between hFE and DVC strain localization patterns allowed the classification of the samples into 3 categories: bad (15 sections), semi (8), and good agreement (2).The good correlations between BMC or hFE and experiment for structural parameters were similar to those obtained previously for the distal part of the radius. The failure zones determined by hFE corresponded to registration only in 8 % of the cases. We attribute these discrepancies to local elastic/plastic buckling effects that are not captured by the continuum-based FE approach exempt from strain softening. A way to improve strain localization hFE prediction would be to use longer distal segments with intact cortical shells, as done for the radius. To conclude, the used hFE scheme captures the elastic and yield response of the tibia sections reliably but not the subsequent failure process.

Child obesity is a growing global issue. Preventing early development of overweight and obesity requires identifying reliable risk factors for high body mass index (BMI) in children. Child eating behavior might be an important and malleable risk factor that can be reliably assessed with the parent-report Child Eating Behavior Questionnaire (CEBQ). Using a hierarchical dataset (children nested within child care centers) from a representative cohort of Swiss preschool children, we tested whether eating behavior, assessed with a 7-factor solution of the CEBQ, and BMI at baseline predicted the outcome BMI after 1 year, controlling for socioeconomic status (n = 555; 47% female; mean age = 3.9 years, range: 2.2–6.6; mean BMI = 16 kg/m2, range: 11.2–23; mean age- and sex-corrected z-transformed BMI, zBMI = 0.4, range −4 to +4.7). The statistical model explained 65.2% of zBMI at follow-up. Baseline zBMI was a strong positive predictor, uniquely explaining 48.8% of outcome variance. A linear combination of all CEBQ scales, taken together, explained 10.7% of outcome variance. Due to their intercorrelations, uniquely explained variance by any individual scale was of negligible clinical relevance. Only food responsiveness was a significant predictor, when accounting for all other predictors and covariates in the model, and uniquely explained only 0.4% of outcome variance. Altogether, our results confirm, extend, and refine previous research on eating behavior and zBMI in preschool children, by adjusting for covariates, accounting for intercorrelations between predictors, partitioning explained outcome variance, and providing standardized beta estimates. Our findings show the importance of carefully examining the contribution of predictors in multiple regression models for clinically relevant outcomes.

Background The need to maintain physical and social distance between people and the stay-at-home recommendation/order to contain the spread of COVID-19 have raised concerns about the possible increase in loneliness. However, few studies have analyzed trends or changes in loneliness in samples of young adults. The present study aimed to explore the prevalence of loneliness and its change during the COVID-19 pandemic. Participants and procedure This is a repeated cross-sectional study analyzing data collected through six online surveys between April 2020 and March 2021 from 5,669 university students in Switzerland. Logistic regression models were used to examine trends in loneliness and associations between loneliness, well-being, life at home, COVID-19 symptoms and tests. Results Loneliness decreased between April 2020 and May-June 2020. In contrast, loneliness was higher in December 2020, January and March 2021 compared to April 2020. Loneliness was associated with younger age, studying architecture, design and civil engineering or engineering, enjoying time spent with family/partner, experiencing tensions and conflicts at home, boredom, feeling locked up and subjective well-being and current health. Conclusions Our findings highlight an increase in loneliness during the second wave of the COVID-19 pandemic, although a seasonality effect cannot be excluded. Public health systems and educational institutions need to monitor the effects of social distancing measures and reduced social contact on students’ loneliness and well-being.

Abstract Proper disinfection and inactivation of highly pathogenic viruses is an essential component of public health and prevention. Depending on environment, surfaces, and type of contaminant, various methods of disinfection must be both efficient and available. To test both established and novel chemical disinfectants against risk group 4 viruses in our maximum containment facility, we developed a standardized protocol and assessed the chemical inactivation of the two Ebola virus variants Mayinga and Makona suspended in two different biological soil loads. Standard chemical disinfectants ethanol and sodium hypochlorite completely inactivate both Ebola variants after 30 s in suspension at 70% and 0.5% v/v, respectively, concentrations recommended for disinfection by the World Health Organization. Additionally, peracetic acid is also inactivating at 0.2% v/v under the same conditions. Continued vigilance and optimization of current disinfection protocols is extremely important due to the continuous presence of Ebola virus on the African continent and increased zoonotic spillover of novel viral pathogens. Furthermore, to facilitate general pandemic preparedness, the establishment and sharing of standardized protocols is very important as it allows for rapid testing and evaluation of novel pathogens and chemical disinfectants.

Although glaucoma is a leading cause of irreversible blindness worldwide, its pathogenesis is incompletely understood, and intraocular pressure (IOP) is the only modifiable risk factor to target the disease. Several associations between the gut microbiome and glaucoma, including the IOP, have been suggested. There is growing evidence that interactions between microbes on the ocular surface, termed the ocular surface microbiome (OSM), and tear proteins, collectively called the tear proteome, may also play a role in ocular diseases such as glaucoma. This study aimed to find characteristic features of the OSM and tear proteins in patients with glaucoma. The whole-metagenome shotgun sequencing of 32 conjunctival swabs identified Actinobacteria, Firmicutes, and Proteobacteria as the dominant phyla in the cohort. The species Corynebacterium mastitidis was only found in healthy controls, and their conjunctival microbiomes may be enriched in genes of the phospholipase pathway compared to glaucoma patients. Despite these minor differences in the OSM, patients showed an enrichment of many tear proteins associated with the immune system compared to controls. In contrast to the OSM, this emphasizes the role of the proteome, with a potential involvement of immunological processes in glaucoma. These findings may contribute to the design of new therapeutic approaches targeting glaucoma and other associated diseases.

Background: Cardiovascular phantoms for patient education, pre-operative planning, surgical training, haemodynamic simulation, and device testing may help improve patient care. However, currently used materials may have different mechanical properties compared to biological tissue.Methods/Aim: The aim of this study was to investigate the mechanical properties of 3D-printing and silicone materials in comparison to biological cardiovascular tissues. Uniaxial cyclic tension testing was performed using dumbbell samples from porcine tissue (aorta, pulmonary artery, right and left ventricle). Flexible testing materials included 15 silicone (mixtures) and three 3D-printing materials. The modulus of elasticity was calculated for different deformation ranges.Results: The modulus of elasticity (0%–60%) for the aorta ranged from 0.16 to 0.18 N/mm2, for the pulmonary artery from 0.07 to 0.09 N/mm2, and for the right ventricle as well as the left ventricle short-axis from 0.1 to 0.16 N/mm2. For silicones the range of modulus of elasticity was 0.02–1.16 N/mm2, and for the 3D-printed materials from 0.85 to 1.02 N/mm2. The stress-strain curves of all tissues showed a non-linear behaviour in the cyclic tensile testing, with a distinct toe region, followed by exponential strain hardening behaviour towards the peak elongation. The vessel samples showed a more linear behaviour comparted to myocardial samples. The silicones and 3D printing materials exhibited near-linearity at higher strain ranges, with a decrease in stiffness following the initial deformation. All samples showed a deviation between the loading and unloading curves (hysteresis), and a reduction in peak force over the first few cycles (adaptation effect) at constant deformation.Conclusion: The modulus of elasticity of silicone mixtures is more in agreement to porcine cardiovascular tissues than 3D-printed materials. All synthetic materials showed an almost linear behaviour in the mechanical testing compared to the non-linear behaviour of the biological tissues, probably due to fibre recruitment mechanism in the latter.

Abstract Osteogenesis imperfecta (OI) is a genetic, collagen‐related bone disease that increases the incidence of bone fractures. Still, the origin of this brittle mechanical behavior remains unclear. The extracellular matrix (ECM) of OI bone exhibits a higher degree of bone mineralization (DBM), whereas compressive mechanical properties at the ECM level do not appear to be inferior to healthy bone. However, it is unknown if collagen defects alter ECM tensile properties. This study aims to quantify the tensile properties of healthy and OI bone ECM. In three transiliac biopsies (healthy n = 1, OI type I n = 1, OI type III n = 1), 23 microtensile specimens (gauge dimensions 10 × 5 × 2 μm3) were manufactured and loaded quasi‐statically under tension in vacuum condition. The resulting loading modulus and ultimate strength were extracted. Interestingly, tensile properties in OI bone ECM were not inferior compared to controls. All specimens revealed a brittle failure behavior. Fracture surfaces were graded according to their mineralized collagen fibers (MCF) orientation into axial, mixed, and transversal fracture surface types (FST). Furthermore, tissue mineral density (TMD) of the biopsy cortices was extracted from micro–computed tomogra[hy (μCT) images. Both FST and TMD are significant factors to predict loading modulus and ultimate strength with an adjusted R2 of 0.556 (p = 2.65e−05) and 0.46 (p = 2.2e−04), respectively. The influence of MCF orientation and DBM on the mechanical properties of the neighboring ECM was further verified with quantitative polarized Raman spectroscopy (qPRS) and site‐matched nanoindentation. MCF orientation and DBM were extracted from the qPRS spectrum, and a second mechanical model was developed to predict the indentation modulus with MCF orientation and DBM (R2 = 67.4%, p = 7.73e−07). The tensile mechanical properties of the cortical bone ECM of two OI iliac crest biopsies are not lower than the one from a healthy and are primarily dependent on MCF orientation and DBM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Abstract Background Around a third of adults aged 65 and older fall every year, resulting in unintentional injuries in 30% of the cases. Fractures are a frequent consequence of falls, primarily caused in individuals with decreased bone strength who are unable to cushion their falls. Accordingly, an individual’s number of experienced falls has a direct influence on fracture risk. The aim of this study was the development of a statistical model to predict future fall rates using personalized risk predictors. Methods In the prospective cohort GERICO, several fall risk factor variables were collected in community-dwelling older adults at two time-points four years apart (T1 and T2). Participants were asked how many falls they experienced during 12 months prior to the examinations. Rate ratios for the number of reported falls at T2 were computed for age, sex, reported fall number at T1, physical performance tests, physical activity level, comorbidity and medication number with negative binomial regression models. Results The analysis included 604 participants (male: 122, female: 482) with a median age of 67.90 years at T1. The mean number of falls per person was 1.04 and 0.70 at T1 and T2. The number of reported falls at T1 as a factor variable was the strongest risk factor with an unadjusted rate ratio [RR] of 2.60 for 3 falls (95% confidence interval [CI] 1.54 to 4.37), RR of 2.63 (95% CI 1.06 to 6.54) for 4 falls, and RR of 10.19 (95% CI 6.25 to 16.60) for 5 and more falls, when compared to 0 falls. The cross-validated prediction error was comparable for the global model including all candidate variables and the univariable model including prior fall numbers at T1 as the only predictor. Conclusion In the GERICO cohort, the prior fall number as single predictor information for a personalized fall rate is as good as when including further available fall risk factors. Specifically, individuals who have experienced three and more falls are expected to fall multiple times again. Trial registration ISRCTN11865958, 13/07/2016, retrospectively registered.

Abstract Background During the 2020/2021 winter, the labour market was under the impact of the COVID-19 pandemic. Changes in socioeconomic resources during this period could have influenced individual mental health. This association may have been mitigated or exacerbated by subjective risk perceptions, such as perceived risk of getting infected with SARS-CoV-2 or perception of the national economic situation. Therefore, we aimed to determine if changes in financial resources and employment situation during and after the second COVID-19 wave were prospectively associated with depression, anxiety and stress, and whether perceptions of the national economic situation and of the risk of getting infected modified this association. Methods One thousand seven hundred fifty nine participants from a nation-wide population-based eCohort in Switzerland were followed between November 2020 and September 2021. Financial resources and employment status were assessed twice (Nov2020–Mar2021, May–Jul 2021). Mental health was assessed after the second measurement of financial resources and employment status, using the Depression, Anxiety and Stress Scale (DASS-21). We modelled DASS-21 scores with linear regression, adjusting for demographics, health status, social relationships and changes in workload, and tested interactions with subjective risk perceptions. Results We observed scores above thresholds for normal levels for 16% (95%CI = 15–18) of participants for depression, 8% (95%CI = 7–10) for anxiety, and 10% (95%CI = 9–12) for stress. Compared to continuously comfortable or sufficient financial resources, continuously precarious or insufficient resources were associated with worse scores for all outcomes. Increased financial resources were associated with higher anxiety. In the working-age group, shifting from full to part-time employment was associated with higher stress and anxiety. Perceiving the Swiss economic situation as worrisome was associated with higher anxiety in participants who lost financial resources or had continuously precarious or insufficient resources. Conclusion This study confirms the association of economic stressors and mental health during the COVID-19 pandemic and highlights the exacerbating role of subjective risk perception on this association.

Abstract Background Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in childhood. In Switzerland, the complex diagnosis and treatment are being carried out by adolescent−/child psychiatrists, and pediatricians. Guidelines recommend a multimodal therapy for patients with ADHD. However, it has been questioned whether health professionals follow this approach or favor drug therapy. This study aims to provide insights into the practice of pediatricians in Switzerland regarding diagnosis and treatment of ADHD and their perceptions of these processes. Method An online survey (self-report) about current practices of diagnosis and management as well as challenges regarding ADHD was distributed to office-based pediatricians in Switzerland. One hundred fifty-one pediatricians participated. Results show that therapy options were almost always discussed with parents and older children. Exchange with parents (81%) and level of child’s suffering (97%) were central when selecting therapy options. Results Therapies about which pediatricians informed most often were: pharmacological therapy, psychotherapy, and multimodal therapy. Challenges voiced were the subjectivity of diagnostic criteria and dependence on third parties, low availability of psychotherapy, and a rather negative public attitude towards ADHD. Needs that were expressed were further education for all professionals, support for coordination with specialists and schools as well as improvement of information on ADHD. Conclusions Pediatricians do consider a multimodal approach when treating ADHD and take the families` and children’s opinions into account. Improvements of the availability of child and youth psychotherapy, the strengthening of the interprofessional cooperation with therapists and schools, and efforts to increase public knowledge about ADHD are proposed.

PurposeThe low microbial abundance on the ocular surface results in challenges in the characterization of its microbiome. The purpose of this study was to reveal factors introducing bias in the pipeline from sample collection to data analysis of low-abundant microbiomes.MethodsLower conjunctiva and lower lid swabs were collected from six participants using either standard cotton or flocked nylon swabs. Microbial DNA was isolated with two different kits (with or without prior host DNA depletion and mechanical lysis), followed by whole-metagenome shotgun sequencing with a high sequencing depth set at 60 million reads per sample. The relative microbial compositions were generated using the two different tools MetaPhlan3 and Kraken2.ResultsThe total amount of extracted DNA was increased by using nylon flocked swabs on the lower conjunctiva. In total, 269 microbial species were detected. The most abundant bacterial phyla were Actinobacteria, Firmicutes and Proteobacteria. Depending on the DNA extraction kit and tool used for profiling, the microbial composition and the relative abundance of viruses varied.ConclusionThe microbial composition on the ocular surface is not dependent on the swab type, but on the DNA extraction method and profiling tool. These factors have to be considered in further studies about the ocular surface microbiome and other sparsely colonized microbiomes in order to improve data reproducibility. Understanding challenges and biases in the characterization of the ocular surface microbiome may set the basis for microbiome-altering interventions for treatment of ocular surface associated diseases.

Virginie G Peter,1 Sophia C Morandi,1,2 Elio L Herzog,1– 3 Martin S Zinkernagel,1,2 Denise C Zysset-Burri1,2 1Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 2Department for BioMedical Research, University of Bern, Bern, Switzerland; 3Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, SwitzerlandCorrespondence: Virginie G Peter, Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 15, Bern, 3010, Switzerland, Email virginie.peter@insel.chAbstract: While pathogens of the eye have been studied for a very long time, the existence of resident microbes on the surface of healthy eyes has gained interest only recently. It appears that commensal microbes are a normal feature of the healthy eye, whose role and properties are currently the subject of extensive research. This review provides an overview of studies that have used 16s rRNA gene sequencing and whole metagenome shotgun sequencing to characterize microbial communities associated with the healthy ocular surface from kingdom to genus level. Bacteria are the primary colonizers of the healthy ocular surface, with three predominant phyla: Proteobacteria, Actinobacteria, and Firmicutes, regardless of the host, environment, and method used. Refining the microbial classification to the genus level reveals a highly variable distribution from one individual and study to another. Factors accounting for this variability are intriguing - it is currently unknown to what extent this is attributable to the individuals and their environment and how much is artifactual. Clearly, it is technically challenging to accurately describe the microorganisms of the ocular surface because their abundance is relatively low, thus, permitting substantial contaminations. More research is needed, including better experimental standards to prevent biases, and the exploration of the ocular surface microbiome’s role in a spectrum of healthy to pathological states. Outcomes from such research include the opportunity for therapeutic interventions targeting the microbiome.Keywords: ocular surface, ocular surface microbiome, 16s rRNA gene sequencing, whole metagenome shotgun sequencing

Abstract Background Eating behavior represents individual appetitive traits which are related to the individual’s regulation of food intake. Eating behavior develops at an early age. There is some evidence that parenting styles might impact on the child’s eating behavior. The aim of this study was to investigate the relationship of different dimensions of positive and negative parenting styles with the child’s eating behavior at a critical age period of the child’s early development. Methods Parents of 511 preschool children (aged 2–6 years) completed the Children Eating Behavior Questionnaire and the Alabama Parenting Questionnaire. Results Analyses revealed that different dimensions of negative parenting styles were associated with eating behavior of the child. In details, inconsistent parenting showed a consistent association with eating behavior of a child (i.e. higher emotional eating, higher food responsiveness, higher food fussiness, higher satiety responsiveness and more enjoyment of food), whereas corporal punishment was associated with more emotional overeating and more food responsiveness but less satiety responsiveness. Further, powerful implementation was related to higher food responsiveness and less enjoyment of food and low monitoring was associated with higher emotional overeating and more slowness in eating. There was no such consistent association of positive parenting and eating behavior. Conclusions More negative parenting styles were associated with eating behavior which is more often related to potential weight problems in a long term, whereas positive parenting did not show such a consistent relationship with eating behavior. Negative parenting should be in the focus of prevention and treatment of eating behavior problems in young children. Trial registration: ISRCTN41045021 (06/05/2014).

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naïve OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1-/- and Rgs1+/+ T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1+/+ T cells outnumbered the co-transferred OT-I Rgs1-/- T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1-/- T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1+/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1-/- TRM cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8+ T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens.

Introduction: Osteoporosis is currently diagnosed based on areal bone mineral density (aBMD) computed from 2D DXA scans. However, aBMD is a limited surrogate for femoral strength since it does not account for 3D bone geometry and density distribution. QCT scans combined with finite element (FE) analysis can deliver improved femoral strength predictions. However, non-negligible radiation dose and high costs prevent a systematic usage of this technique for screening purposes. As an alternative, the 3D-Shaper software (3D-Shaper Medical, Spain) reconstructs the 3D shape and density distribution of the femur from 2D DXA scans. This approach could deliver a more accurate estimation of femoral strength than aBMD by using FE analysis on the reconstructed 3D DXA.Methods: Here we present the first independent evaluation of the software, using a dataset of 77 ex vivo femora. We extend a prior evaluation by including the density distribution differences, the spatial correlation of density values and an FE analysis. Yet, cortical thickness is left out of this evaluation, since the cortex is not resolved in our FE models.Results: We found an average surface distance of 1.16 mm between 3D DXA and QCT images, which shows a good reconstruction of the bone geometry. Although BMD values obtained from 3D DXA and QCT correlated well (r2 = 0.92), the 3D DXA BMD were systematically lower. The average BMD difference amounted to 64 mg/cm3, more than one-third of the 3D DXA BMD. Furthermore, the low correlation (r2 = 0.48) between density values of both images indicates a limited reconstruction of the 3D density distribution. FE results were in good agreement between QCT and 3D DXA images, with a high coefficient of determination (r2 = 0.88). However, this correlation was not statistically different from a direct prediction by aBMD. Moreover, we found differences in the fracture patterns between the two image types. QCT-based FE analysis resulted mostly in femoral neck fractures and 3D DXA-based FE in subcapital or pertrochanteric fractures.Discussion: In conclusion, 3D-Shaper generates an altered BMD distribution compared to QCT but, after careful density calibration, shows an interesting potential for deriving a standardized femoral strength from a DXA scan.

Although dry eye disease (DED) is one of the most common ocular surface diseases worldwide, its pathogenesis is incompletely understood, and treatment options are limited. There is growing evidence that complex interactions between the ocular surface microbiome (OSM) and tear fluid constituents, potentially leading to inflammatory processes, are associated with ocular surface diseases such as DED. In this study, we aimed to find unique compositional and functional features of the OSM associated with human and microbial tear proteins in patients with DED. Applying whole-metagenome shotgun sequencing of forty lid and conjunctival swabs, we identified 229 taxa, with Actinobacteria and Proteobacteria being the most abundant phyla and Propionibacterium acnes the dominating species in the cohort. When DED patients were compared to controls, the species Corynebacterium tuberculostearicum was more abundant in conjunctival samples, whereas the family Propionibacteriaceae was more abundant in lid samples. Functional analysis showed that genes of L-lysine biosynthesis, tetrapyrrole biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis, and the super pathway of L-threonine biosynthesis were enriched in conjunctival samples of controls. The relative abundances of Acinetobacter johnsonii correlated with seven human tear proteins, including mucin-16. The three most abundant microbial tear proteins were the chaperone protein DnaK, the arsenical resistance protein ArsH, and helicase. Compositional and functional features of the OSM and the tear proteome are altered in patients with DED. Ultimately, this may help to design novel interventional therapeutics to target DED.

At preschool age, motor skills and cognitive functions are regularly examined at well-child visits. Although reliable screening depends on the stability of the assessed developmental domains, little is known about the stability of motor and cognitive performance in preschool children. The aim of the present study was to investigate how stable motor skills and cognitive functioning are in the preschool years and whether they can predict their own and respective outcome 1 year later. 509 children were examined (46.4% female; M = 3.9 years; SD = 0.6; range 3.0-6.0 years) from the Swiss Preschoolers' Health Study (SPLASHY) at baseline and 1 year later. A Latent Variable Cross-lagged Panel Model revealed that both motor skills and cognitive functioning are highly stable in the preschool age (0.65/0.67). Cross-lagged coefficients were smaller (0.37/0.22). However, as the cross-lagged paths did not differ significantly from each other, no reliable conclusions for the prediction of motor skills and cognitive functions may be drawn. We conclude that cognitive functioning and motor skills are highly stable already in the preschool years. Although small cross-lagged predictive values were found, motor skills and cognitive functions may not to be reliable predictors of their respective outcomes. Future studies should test cross-lagged predictive effects in clinical samples, where the effects might be larger.

Young children's eating behavior is crucial for any further development of healthy eating. Early eating behavior are often assessed through parental report. The Children's Eating Behaviour Questionnaire (CEBQ) is a widely used parental questionnaire that has been validated in families of different gender, age and cultural background. Research has shown that the 8-factor structure has some inconsistencies and sample characteristics such as age, gender, and culture can influence the results. To which extent such sample characteristics might influence results within a multi-lingual culture has not been investigated so far. Therefore, the aim of the study was to evaluate the factor structure of the CEBQ among 511 preschool children of the French and German parts of Switzerland, aged 2 to 6 years (Mean 3.85 years; SD 0.69). Confirmatory Factor Analysis showed a modified structure of the original questionnaire, with a 7-factor structure providing a reasonable fit to the data (TLI = 0.954, CFI = 0.952, RMSEA = 0.063 and SRMR = 0.067). The subscale 'Desire to drink' was removed, and a few items moved to other subscales as they loaded higher on a different subscale compared to the original model. Reliabilities based on the coefficient omega were acceptable to satisfying across the seven factors, ranging from 0.66 to 0.90. There were no significant gender or age differences, but French speaking children showed higher levels of 'Satiety responsiveness' and lower 'Enjoyment of food' than German speaking children. Yet, these effects were small. The German and French CEBQ are valid and reliable versions of the original CEBQ and can be used in a multicultural context.

Abstract Background Motor deficiencies are observed in a large number of children with ADHD. Especially fine motor impairments can lead to academic underachievement, low self-esteem and frustration in affected children. Despite these far-reaching consequences, fine motor deficiencies have remained widely undertreated in the ADHD population. The aim of this review was to systematically map the evidence on existing training programs for remediating fine motor impairments in children with ADHD and to assess their effectiveness. Methods The scoping review followed the PRISMA-ScR guidelines. In March 2020, PsycINFO, MEDLINE (PubMed), Web of Science, Google Scholar and The Cochrane Database of Systematic Reviews were searched for evidence. The eligibility criteria and the data charting process followed the PICO framework, complemented by study design. The investigated population included children with a formal ADHD diagnosis (either subtype) or elevated ADHD symptoms aged between 4 and 12 years, both on and off medication. All training interventions aiming at improving fine motor skills, having a fine motor component or fine motor improvements as a secondary outcome were assessed for eligibility; no comparators were specified. Results Twelve articles were included in the final report, comprising observational and experimental studies as well as a review. Both offline and online or virtual training interventions were reported, often accompanied by physical activity and supplemented by training sessions at home. The training programs varied in length and intensity, but generally comprised several weeks and single or multiple training sessions per week. All interventions including more than one session were effective in the treatment of fine motor deficiencies in children with ADHD and had a wide range of additional positive outcomes. The effects could be maintained at follow-up. Conclusions Fine motor training in children with ADHD can be very effective and multiple approaches including specific fine motor and cognitive training components, some kind of physical activity, feedback mechanisms, or multimodal treatments can be successful. Training programs need to be tailored to the specific characteristics of the ADHD population. A mHealth approach using serious games could be promising in this context due to its strong motivational components.

Background: Olecranon osteotomies are frequently used to expose distal humeral intraarticular fractures. The step-cut olecranon osteotomy (SCOOT) is an augmented version of the oblique olecranon osteotomy, which has recently been evaluated biomechanically with tension band wiring (TBW) fixation. However, complications with TBW are common. In this study, we, therefore, compared the mean load to failure of TBW with compression screws for SCOOT fixation. We hypothesized a higher load to failure for the compression screw group. Methods: We performed a SCOOT on 36 Sawbones. Eighteen were fixed with TBW, and another 18 with two compression screws. The humeroulnar joint was simulated using an established test setup, which allows the application of triceps traction force through a tendon model to the ulna, while the humeroulnar joint is in a fixed position. Eight models of each fixation group were tested at 20°, and eight at 70° of flexion by isometrical loading until failure, which was defined as either a complete fracture or gap formation of more than 2 mm at the osteotomy site. Results: At 20° of flexion, mean load to failure was similar between the TBW group (1360 ± 238 N) and the compression screw group (1401 ± 261 N) (P = .88). Also, at 70° of flexion, the mean load to failure was similar between the TBW group (1398 ± 215 N) and the compression screw group (1614 ± 427 N) (P = .28). Conclusions: SCOOTs fixed with TBW and compression screws showed similar loads to failure. A SCOOT fixed with compression screws might be a valuable alternative for surgeons when treating intraarticular distal humeral fractures. However, future in vivo studies are necessary to confirm our results in a clinical setting.

Background: A third of adults aged 65 years and older fall every year, and falls are a common cause of unintentional injuries. Accurate identification of people at risk of falling is an important step in the implementation of preventive strategies.Objective: Our aim was to investigate the association of fall risk factors with number of reported falls in terms of incidence rate ratios and to develop a fall rate prediction model.Methods: In the randomized controlled trial Swiss CHEF, multiple fall risk variables were assessed in community-dwelling older adults at baseline examination, including age, sex, body mass index, fear of falling, number of falls during the prior 12 months, scores on several physical performance tests, comorbidities, and quality of life. Over the following 6 months, interventions were administered in the form of three home-based exercise programs. Participants were subsequently followed up for another 6 months. Falls were reported prospectively using monthly calendars. Incidence rate ratios were derived via negative binomial regression models. Variable selection for the prediction model was conducted using backward elimination and the least absolute shrinkage and selection operator method; the model with the smallest prediction error was then identified.Results: Associations with the number of reported falls were found for number of prior falls, fear of falling, balance and gait deficits, and quality of life. The final model was derived via backward elimination, and the predictors included were prior number of falls and a measure of fear of falling.Outcome: Number of prior falls and fear of falling can be used as predictors in a personalized fall rate estimate for community-dwelling older adults. Recurrent fallers having experienced four or more falls are especially at risk of falling again.

Today, we are facing rapid aging of the world population, which increases the incidence of hip fractures. The gold standard of bone strength assessment in the laboratory is micro-computed finite element analysis (μFEA) based on micro-computed tomography (μCT) images. In clinics, the standard method to assess bone fracture risk is based on areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA). In addition, homogenized finite element analysis (hFEA) constructed from quantitative computed tomography reconstructions (QCT) predicts clinical bone strength more accurately than DXA. Despite considerable evidence of degradation of bone material properties with age, in the past fifty years of finite element analysis to predict bone strength, bone material parameters remained independent of age. This study aims to assess the influence of age on apparent modulus, yield stress, and strength predictions of the human femoral neck made by laboratory-available bone volume fraction (BV/TV) and μFEA; and by clinically available DXA and hFEA. Using an inverse method, we test the hypothesis that FEA material parameters are independent of age. Eighty-six human femora were scanned with DXA (aBMD) and with QCT. The femoral necks were extracted and scanned at 16 μm resolution with μCT. The grayscale images were downscaled to 32 μm and 65 μm for linear and non-linear analyses, respectively, and segmented. The μFE solver ParOSolNL (non-linear) and a standard hFEA method were applied to the neck sections with the same material properties for all samples to compute apparent modulus, yield stress, and strength. Laboratory-available BV/TV was a good predictor of apparent modulus (R2 = 0.76), almost as good as μFEA (R2 = 0.79). However, yield stress and strength were better predicted by μFEA (R2 = 0.92, R2 = 0.86, resp.) than BV/TV (R2 = 0.76, R2 = 0.76, resp.). For clinically available variables, prediction of apparent modulus was better with hFEA than aBMD (R2 = 0.67, R2 = 0.58, resp.). hFEA outperformed aBMD for predictions of yield stress (R2 = 0.63 vs R2 = 0.34 for female and R2 = 0.55 for male) and strength (R2 = 0.48 vs R2 = 0.33 for female and R2 = 0.15 for male). The inclusion of age did not improve the multiple linear models for apparent modulus, yield stress, and strength. The resolution of the μFE meshes seems to account for most morphological changes induced by aging. The errors between the simulation and the experiment for apparent modulus, yield stress, and strength were age-independent, suggesting no rationale for correcting tissue material parameters in the current FE analysis of the aging femoral neck.

Abstract Background The onset of walking is thought to be an indicator of early development. However, evidence is mixed and clear data on this relationship at preschool age is missing. The study aimed at investigating if walking onset and motor and cognitive development in preschool children are related. Methods A total of 555 children (mean age 3.86 years) of the Swiss Preschoolers’ Health Study SPLASHY were tested twice at their childcare center (at baseline and one year later). Motor skills and cognitive skills were assessed by standardized testing procedures and parents were asked to provide information on walking onset of their child. Results Late onset of walking was related to poorer motor skills (fine motor skills, static and dynamic balance (all p

Vertebrae containing osteolytic and osteosclerotic bone metastases undergo pathologic vertebral fracture (PVF) when the lesioned vertebrae fail to carry daily loads. We hypothesize that task-specific spinal loading patterns amplify the risk of PVF, with a higher degree of risk in osteolytic than in osteosclerotic vertebrae. To test this hypothesis, we obtained clinical CT images of 11 cadaveric spines with bone metastases, estimated the individual vertebral strength from the CT data, and created spine-specific musculoskeletal models from the CT data. We established a musculoskeletal model for each spine to compute vertebral loading for natural standing, natural standing + weights, forward flexion + weights, and lateral bending + weights and derived the individual vertebral load-to-strength ratio (LSR). For each activity, we compared the metastatic spines’ predicted LSRs with the normative LSRs generated from a population-based sample of 250 men and women of comparable ages. Bone metastases classification significantly affected the CT-estimated vertebral strength (Kruskal–Wallis, p < 0.0001). Post-test analysis showed that the estimated vertebral strength of osteosclerotic and mixed metastases vertebrae was significantly higher than that of osteolytic vertebrae (p = 0.0016 and p = 0.0003) or vertebrae without radiographic evidence of bone metastasis (p = 0.0010 and p = 0.0003). Compared with the median (50%) LSRs of the normative dataset, osteolytic vertebrae had higher median (50%) LSRs under natural standing (p = 0.0375), natural standing + weights (p = 0.0118), and lateral bending + weights (p = 0.0111). Surprisingly, vertebrae showing minimal radiographic evidence of bone metastasis presented significantly higher median (50%) LSRs under natural standing (p < 0.0001) and lateral bending + weights (p = 0.0009) than the normative dataset. Osteosclerotic vertebrae had lower median (50%) LSRs under natural standing (p < 0.0001), natural standing + weights (p = 0.0005), forward flexion + weights (p < 0.0001), and lateral bending + weights (p = 0.0002), a trend shared by vertebrae with mixed lesions. This study is the first to apply musculoskeletal modeling to estimate individual vertebral loading in pathologic spines and highlights the role of task-specific loading in augmenting PVF risk associated with specific bone metastatic types. Our finding of high LSRs in vertebrae without radiologically observed bone metastasis highlights that patients with metastatic spine disease could be at an increased risk of vertebral fractures even at levels where lesions have not been identified radiologically.

Abstract Background The opportunistic pathogen Naegleria fowleri establishes infection in the human brain, killing almost invariably within 2 weeks. The amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing direct tissue damage and massive inflammation. The cellular basis distinguishing N. fowleri from other Naegleria species, which are all non-pathogenic, is not known. Yet, with the geographic range of N. fowleri advancing, potentially due to climate change, understanding how this pathogen invades and kills is both important and timely. Results Here, we report an -omics approach to understanding N. fowleri biology and infection at the system level. We sequenced two new strains of N. fowleri and performed a transcriptomic analysis of low- versus high-pathogenicity N. fowleri cultured in a mouse infection model. Comparative analysis provides an in-depth assessment of encoded protein complement between strains, finding high conservation. Molecular evolutionary analyses of multiple diverse cellular systems demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in free-living N. gruberi. From transcriptomics, neither stress responses nor traits conferred from lateral gene transfer are suggested as critical for pathogenicity. By contrast, cellular systems such as proteases, lysosomal machinery, and motility, together with metabolic reprogramming and novel N. fowleri proteins, are all implicated in facilitating pathogenicity within the host. Upregulation in mouse-passaged N. fowleri of genes associated with glutamate metabolism and ammonia transport suggests adaptation to available carbon sources in the central nervous system. Conclusions In-depth analysis of Naegleria genomes and transcriptomes provides a model of cellular systems involved in opportunistic pathogenicity, uncovering new angles to understanding the biology of a rare but highly fatal pathogen.

Abstract Bone is an intriguingly complex material. It combines high strength, toughness and lightweight via an elaborate hierarchical structure. This structure results from a biologically driven self-assembly and self-organisation, and leads to different deformation mechanisms along the length scales. Characterising multiscale bone mechanics is fundamental to better understand these mechanisms including changes due to bone-related diseases. It also guides us in the design of new bio-inspired materials. A key-gap in understanding bone’s behaviour exists for its fundamental mechanical unit, the mineralised collagen fibre, a composite of organic collagen molecules and inorganic mineral nanocrystals. Here, we report an experimentally informed statistical elasto-plastic model to explain the fibre behaviour including the nanoscale interplay and load transfer with its main mechanical components. We utilise data from synchrotron nanoscale imaging, and combined micropillar compression and synchrotron X-ray scattering to develop the model. We see that a 10-15% micro- and nanomechanical heterogeneity in mechanical properties is essential to promote the ductile microscale behaviour preventing an abrupt overall failure even when individual fibrils have failed. We see that mineral particles take up 45% of strain compared to collagen molecules while interfibrillar shearing seems to enable the ductile post-yield behaviour. Our results suggest that a change in mineralisation and fibril-to-matrix interaction leads to different mechanical properties among mineralised tissues. Our model operates at crystalline-, molecular- and continuum-levels and sheds light on the micro- and nanoscale deformation of fibril-matrix reinforced composites.

Low back pain is often due to degeneration of the intervertebral discs (IVD). It is one of the most common age- and work-related problems in today’s society. Current treatments are not able to efficiently restore the full function of the IVD. Therefore, the aim of the present work was to reconstruct the two parts of the intervertebral disc—the annulus fibrosus (AF) and the nucleus pulposus (NP)—in such a way that the natural structural features were mimicked by a textile design. Silk was selected as the biomaterial for realization of a textile IVD because of its cytocompatibility, biodegradability, high strength, stiffness, and toughness, both in tension and compression. Therefore, an embroidered structure made of silk yarn was developed that reproduces the alternating fiber structure of +30° and −30° fiber orientation found in the AF and mimics its lamellar structure. The developed embroidered ribbons showed a tensile strength that corresponded to that of the natural AF. Fiber additive manufacturing with 1 mm silk staple fibers was used to replicate the fiber network of the NP and generate an open porous textile 3D structure that may serve as a reinforcement structure for the gel-like NP.

Summary: Fractures to the keel bone is one of the greatest problems facing the laying hen industry. With most severe effects observed in non-cage housing, frequencies are expected to dramatically increase as the industry continues transitioning away from battery cages. Incidences within commercial systems are well documented, where the main cause is believed to be high egg production and the associated need for calcium drawing on endogenous reserves (i.e., bone) leaving bone weakened and prone to fracture. The current work sought to characterize various bone mineral and biomechanical properties of 5 distinct purebred or crossbred laying hen lines (3 commercial: Bovans Brown, Dekalb White, and Institut de Sélection Animale Dual Brown; 2 non-commercial: Experimental Brown and Experimental White), following previous work that demonstrated differences in susceptibility to keel fracture using an ex vivo impact testing apparatus. The keel was then removed to undergo analysis by computer tomography; the humerus and tibia were also removed for biomechanical testing. The keel bone mineral density and moment of area correlated moderately with hen weight and susceptibility to fracture. The biomechanical properties of the tibia, but not the humerus, showed a strong relationship with hen weight. One commercial genetic line (Dekalb White) with a high susceptibility to fracture exhibited a mean tibia strength below the value expected from its mean weight. Our results suggest that for the purebred or crossbred lines other than Dekalb White, rather than properties of bone, lower mean weight may imply higher levels of activity, higher risk of collisions, and lower soft tissue protection that reflect greater susceptibility to keel fracture.

ObjectivesYoung adults have been overly affected by the containment measures against COVID-19 and, consequently, worsening in mental health and change in health behavior have been reported. Because the life phase of emerging adulthood is crucial for developing health behaviors, this study aims to examine increase in alcohol consumption, single and multiple binge drinking, and associated factors in students during lockdown and post-lockdown periods.MethodsA prospective open cohort study design with nine survey time points between April 2020 and June 2021 was conducted. The present study uses pooled data from the first survey T0 (3 April to 14 April) and follow-ups at T1 (30 April to 11 May 2020) and T2 (28 May to 8 June 2020). Students from all faculties of the Zurich University of Applied Sciences (ZHAW) (N = 12'431) were invited. Of the 1,300 students who participated at baseline and in at least one follow-up, 1,278 (98.3%) completed the questionnaires, final net sample size was 947. Generalized Estimating Equations (GEE) models were used to investigate the factors associated with increases in alcohol consumption based on number of occasions/last 30 days; drinks/week, and binge drinking at T0, and respective changes at T1 and T2 (increases, decreases, no change).ResultsOverall, 20% of Swiss university students reported an increased alcohol consumption and 26% engaged in binge drinking. Number of drinks at baseline was associated with a higher probability of increased alcohol consumption, as well as engaging in single and multiple binge drinking events. Higher anxiety scores were associated with a higher probability to increase the alcohol consumption and engaging at least once in binge drinking. Additional factors associated with any binge drinking were male gender, younger age and not living with parents. Higher perceived social support was only associated with engaging in heavy binge drinking.ConclusionsA substantial number of students developed a more risky health behavior regarding alcohol consumption. It is important to identify at risk students and design target prevention including factors such as age, gender and social norms. Further, health behavior and determinants of health behaviors of students should be carefully monitored during the further course of the pandemic.