Antibiotics in early life associate with specific gut microbiota signatures in a prospective longitudinal infant cohort

BACKGROUND The effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota. METHODS Antibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians' discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home. RESULTS One hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions. CONCLUSIONS Antibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.Peer reviewe

Urban green space and mental health among people living alone: The mediating roles of relational and collective restoration in an 18-country sample

This is the final version. Available on open access from Elsevier via the DOI in this record. Rates of living alone, especially in more urbanised areas, are increasing across many industrialised countries, with associated increases in feelings of loneliness and poorer mental health. Recent studies have suggested that access to nature (e.g. parks and green spaces) can reduce the stressors associated with loneliness, partly through providing opportunities to nurture personal relationships (relational restoration) and engage in normative community activities (collective restoration). Such associations might vary across different household compositions and socio-demographic or geographical characteristics, but these have not been thoroughly tested. Using data collected across 18 countries/territories in 2017-2018, we grouped urban respondents into those living alone (n = 2062) and those living with a partner (n = 6218). Using multigroup path modelling, we tested whether the associations between neighbourhood greenspace coverage (1-km-buffer from home) and mental health are sequentially mediated by: (a) visits to greenspace; and subsequently (b) relationship and/or community satisfaction, as operationalisations of relational and collective restoration, respectively. We also tested whether any indirect associations varied among subgroups of respondents living alone. Analyses showed that visiting green space was associated with greater mental well-being and marginally lower odds of using anxiety/depression medication use indirectly, mediated via both relationship and community satisfaction. These indirect associations were equally strong among respondents living alone and those living with a partner. Neighbourhood green space was, additionally, associated with more visits among respondents living with a partner, whereas among those living alone, this was sensitive to the green space metric. Within subgroups of people living alone, few overall differences were found. Some indirect pathways were, nevertheless, stronger in males, under 60-year-olds, those with no financial strain, and residents in warmer climates. In conclusion, supporting those living alone, as well as those living with a partner, to more frequently access their local greenspaces could help improve mental health via promoting relational and collective restoration.Academy of FinlandTHL foundatio

Selective laser melting–enabled electrospinning: Introducing complexity within electrospun membranes

Additive manufacturing technologies enable the creation of very precise and well-defined structures that can mimic hierarchical features of natural tissues. In this article, we describe the development of a manufacturing technology platform to produce innovative biodegradable membranes that are enhanced with controlled microenvironments produced via a combination of selective laser melting techniques and conventional electrospinning. This work underpins the manufacture of a new generation of biomaterial devices that have significant potential for use as both basic research tools and components of therapeutic implants. The membranes were successfully manufactured and a total of three microenvironment designs (niches) were chosen for thorough characterisation. Scanning electron microscopy analysis demonstrated differences in fibre diameters within different areas of the niche structures as well as differences in fibre density. We also showed the potential of using the microfabricated membranes for supporting mesenchymal stromal cell culture and proliferation. We demonstrated that mesenchymal stromal cells grow and populate the membranes penetrating within the niche-like structures. These findings demonstrate the creation of a very versatile tool that can be used in a variety of tissue regeneration applications including bone healing

1H-NMR-Based Metabolomic Profiling of CSF in Early Amyotrophic Lateral Sclerosis

Background: Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to analyze the CSF of patients with ALS by 1 H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS. Methodology: CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional 1 H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses. Principal Findings: Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites reveale

Results from an 18 country cross-sectional study examining experiences of nature for people with common mental health disorders

This is the final version. Available on open access from Nature Research via the DOI in this recordExposure to natural environments is associated with a lower risk of common mental health disorders (CMDs), such as depression and anxiety, but we know little about nature-related motivations, practices and experiences of those already experiencing CMDs. We used data from an 18-country survey to explore these issues (n = 18,838), taking self-reported doctor-prescribed medication for depression and/or anxiety as an indicator of a CMD (n = 2698, 14%). Intrinsic motivation for visiting nature was high for all, though slightly lower for those with CMDs. Most individuals with a CMD reported visiting nature ≥ once a week. Although perceived social pressure to visit nature was associated with higher visit likelihood, it was also associated with lower intrinsic motivation, lower visit happiness and higher visit anxiety. Individuals with CMDs seem to be using nature for self-management, but ‘green prescription’ programmes need to be sensitive, and avoid undermining intrinsic motivation and nature-based experiences.European Union Horizon 202

A family based tailored counselling to increase non-exercise physical activity in adults with a sedentary job and physical activity in their young children: design and methods of a year-long randomized controlled trial

Background. Epidemiological evidence suggests that decrease in sedentary behaviour is beneficial for health. This family based randomized controlled trial examines whether face-to-face delivered counselling is effective in reducing sedentary time and improving health in adults and increasing moderate-to-vigorous activities in children. Methods. The families are randomized after balancing socioeconomic and environmental factors in the Jyväskylä region, Finland. Inclusion criteria are: healthy men and women with children 3-8 years old, and having an occupation where they self-reportedly sit more than 50% of their work time and children in all-day day-care in kindergarten or in the first grade in primary school. Exclusion criteria are: body mass index > 35 kg/m2, self-reported chronic, long-term diseases, families with pregnant mother at baseline and children with disorders delaying motor development. From both adults and children accelerometer data is collected five times a year in one week periods. In addition, fasting blood samples for whole blood count and serum metabonomics, and diurnal heart rate variability for 3 days are assessed at baseline, 3, 6, 9, and 12 months follow-up from adults. Quadriceps and hamstring muscle activities providing detailed information on muscle inactivity will be used to realize the maximum potential effect of the intervention. Fundamental motor skills from children and body composition from adults will be measured at baseline, and at 6 and 12 months follow-up. Questionnaires of family-influence-model, health and physical activity, and dietary records are assessed. After the baseline measurements the intervention group will receive tailored counselling targeted to decrease sitting time by focusing on commute and work time. The counselling regarding leisure time is especially targeted to encourage toward family physical activities such as visiting playgrounds and non-built environments, where children can get diversified stimulation for play and practice fundamental of motor skills. The counselling will be reinforced during the first 6 months followed by a 6-month maintenance period. Discussion. If shown to be effective, this unique family based intervention to improve lifestyle behaviours in both adults and children can provide translational model for community use. This study can also provide knowledge whether the lifestyle changes are transformed into relevant biomarkers and self-reported health. Trial registration number. ISRCTN: ISRCTN28668090peerReviewe

Metabolic Profiling Reveals Distinct Variations Linked to Nicotine Consumption in Humans — First Results from the KORA Study

Exposure to nicotine during smoking causes a multitude of metabolic changes that are poorly understood. We quantified and analyzed 198 metabolites in 283 serum samples from the human cohort KORA (Cooperative Health Research in the Region of Augsburg). Multivariate analysis of metabolic profiles revealed that the group of smokers could be clearly differentiated from the groups of former smokers and non-smokers. Moreover, 23 lipid metabolites were identified as nicotine-dependent biomarkers. The levels of these biomarkers are all up-regulated in smokers compared to those in former and non-smokers, except for three acyl-alkyl-phosphatidylcholines (e.g. plasmalogens). Consistently significant results were further found for the ratios of plasmalogens to diacyl-phosphatidylcolines, which are reduced in smokers and regulated by the enzyme alkylglycerone phosphate synthase (alkyl-DHAP) in both ether lipid and glycerophospholipid pathways. Notably, our metabolite profiles are consistent with the strong down-regulation of the gene for alkyl-DHAP (AGPS) in smokers that has been found in a study analyzing gene expression in human lung tissues. Our data suggest that smoking is associated with plasmalogen-deficiency disorders, caused by reduced or lack of activity of the peroxisomal enzyme alkyl-DHAP. Our findings provide new insight into the pathophysiology of smoking addiction. Activation of the enzyme alkyl-DHAP by small molecules may provide novel routes for therapy

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention