Influence of the Available Surface Area and Cell Elasticity on Bacterial Adhesion Forces on Highly Ordered Silicon Nanopillars

[Image: see text] Initial bacterial adhesion to solid surfaces is influenced by a multitude of different factors, e.g., roughness and stiffness, topography on the micro- and nanolevel, as well as chemical composition and wettability. Understanding the specific influences and possible interactive effects of all of these factors individually could lead to guidance on bacterial adhesion and prevention of unfavorable consequences like medically relevant biofilm formation. On this way, the aim of the present study was to identify the specific influence of the available surface area on the adhesion of clinically relevant bacterial strains with different membrane properties: Gram-positive Staphylococcus aureus and Gram-negative Aggregatibacter actinomycetemcomitans. As model surfaces, silicon nanopillar specimens with different spacings were fabricated using electron beam lithography and cryo-based reactive ion etching techniques. Characterization by scanning electron microscopy and contact angle measurement revealed almost defect-free highly ordered nanotopographies only varying in the available surface area. Bacterial adhesion forces to these specimens were quantified by means of single-cell force spectroscopy exploiting an atomic force microscope connected to a microfluidic setup (FluidFM). The nanotopographical features reduced bacterial adhesion strength by reducing the available surface area. In addition, the strain-specific interaction in detail depended on the bacterial cell’s elasticity and deformability as well. Analyzed by confocal laser scanning microscopy, the obtained results on bacterial adhesion forces could be linked to the subsequent biofilm formation on the different topographies. By combining two cutting-edge technologies, it could be demonstrated that the overall bacterial adhesion strength is influenced by both the simple physical interaction with the underlying nanotopography and its available surface area as well as the deformability of the cell

Linking geological and infrastructural requirements for large-scale underground hydrogen storage in Germany

Hydrogen storage might be key to the success of the hydrogen economy, and hence the energy transition in Germany. One option for cost-effective storage of large quantities of hydrogen is the geological subsurface. However, previous experience with underground hydrogen storage is restricted to salt caverns, which are limited in size and space. In contrast, pore storage facilities in aquifers -and/or depleted hydrocarbon reservoirs- could play a vital role in meeting base load needs due to their wide availability and large storage capacity, but experiences are limited to past operations with hydrogen-bearing town gas. To overcome this barrier, here we investigate hydrogen storage in porous storage systems in a two-step process: 1) First, we investigate positive and cautionary indicators for safe operations of hydrogen storage in pore storage systems. 2) Second, we estimate hydrogen storage capacities of pore storage systems in (current and decommissioned) underground natural gas storage systems and saline aquifers. Our systematic review highlights that optimal storage conditions in terms of energy content and hydrogen quality are found in sandstone reservoirs in absence of carbonate and iron bearing accessory minerals at a depth of approx. 1,100 m and a temperature of at least 40°C. Porosity and permeability of the reservoir formation should be at least 20% and 5 × 10−13 m2 (∼500 mD), respectively. In addition, the pH of the brine should fall below 6 and the salinity should exceed 100 mg/L. Based on these estimates, the total hydrogen storage capacity in underground natural gas storages is estimated to be up to 8 billion cubic meters or (0.72 Mt at STP) corresponding to 29 TWh of energy equivalent of hydrogen. Saline aquifers may offer additional storage capacities of 81.6–691.8 Mt of hydrogen, which amounts to 3.2 to 27.3 PWh of energy equivalent of hydrogen, the majority of which is located in the North German basin. Pore storage systems could therefore become a crucial element of the future German hydrogen infrastructure, especially in regions with large industrial hydrogen (storage) demand and likely hydrogen imports via pipelines and ships

What do children understand? Communicating health behavior in a European multicenter study

Background: Diet and physical activity are important factors in the prevention of childhood overweight. This article stresses the importance of effective communication for health behavior. Methods: Transcription, description and analysis of standardized focus group discussions (FGD) in seven European countries using standardized questioning routes. Results: Parents are well informed about health-related topics for children, but seem to have difficulties understanding their role in promoting healthy behavior. They mentioned health-related rules, but our results show limited communication between parents and children, and no follow-up of rules. Consequently, children do not understand rules about good health and do not follow them. Conclusion: Effective and sustainable intervention programs should focus on educational methods and, using parental role modeling, facilitate parents' comprehension of their key role in setting rules and controlling them in order to communicate good health behavior to their children

Validation of an apoptosis assay for extracorporeal photopheresis

Objectives This validation study investigated a flow cytometric apoptosis assay according to good manufacturing practice (GMP). Background Extracorporeal photopheresis (ECP) is a treatment for various immunological diseases and cutaneous T‐cell lymphomas. It is based on the induction of apoptosis by 8‐methoxypsoralene and ultraviolet A light. The quantification of apoptosis is therefore essential for ECP improvements. However, despite numerous publications on apoptosis, validated technical details are lacking. Methods and materials Mononuclear cells were collected by apheresis and treated by ECP or camptothecin. Samples taken before and after ECP were cultured for 24, 48 and 72 h and analysed for apoptosis and viability of T cells and monocytes by flow cytometry with Annexin V and 7‐AAD staining. Accuracy of the assay, intra‐ and inter‐assay precision and the pre‐analytical and analytical stability of the analytes were the investigated parameters. Results Our data indicate that the median intra‐ and inter‐assay precision coefficient of variation for T cells was 3.86% and 4.80%, respectively. Pre‐analytical stability of T cells and monocytes was ensured during short‐term storage for up to 2 h on ice. After staining, analytical stability was limited to 30 min, likely because of ongoing apoptosis and loss of monocytes due to plastic adhesion. Conclusion The results of this validation study show that the assay is GMP‐compliant and that its reliability, accuracy and precision are acceptable. While pre‐analytical stability of the cells was compatible with on‐site procedures, our analytical stability data indicate that this assay is not suited for batch mode analysis of ECP products

Efficacy, safety and quality of life in a multicenter, randomized, placebo-controlled trial of low-dose peanut oral immunotherapy in children with peanut allergy

BACKGROUND: Only 2 small placebo-controlled trials on peanut oral immunotherapy (OIT) have been published. OBJECTIVE: We examined the efficacy, safety, immunologic parameters, quality of life (QOL), and burden of treatment (BOT) of low-dose peanut OIT in a multicenter, double-blind, randomized placebo-controlled trial. METHODS: A total of 62 children aged 3 to 17 years with IgE-mediated, challenge-proven peanut allergy were randomized (1:1) to receive peanut OIT with a maintenance dose of 125 to 250 mg peanut protein or placebo. The primary outcome was the proportion of children tolerating 300 mg or more peanut protein at oral food challenge (OFC) after 16 months of OIT. We measured the occurrence of adverse events (AEs), immunologic changes, and QOL before and after OIT and BOT during OIT. RESULTS: Twenty-three of 31 (74.2%) children of the active group tolerated at least 300 mg peanut protein at final OFC compared with 5 of 31 (16.1%) in the placebo group (P < .001). Thirteen of 31 (41.9%) children of the active versus 1 of 31 (3.2%) of the placebo group tolerated the highest dose of 4.5 g peanut protein at final OFC (P < .001). There was no significant difference between the groups in the occurrence of AE-related dropouts or in the number, severity, and treatment of objective AEs. In the peanut-OIT group, we noted a significant reduction in peanut-specific IL-4, IL-5, IL-10, and IL-2 production by PBMCs compared with the placebo group, as well as a significant increase in peanut-specific IgG4 levels and a significant improvement in QOL; 86% of children evaluated the BOT positively. DISCUSSION: Low-dose OIT is a promising, effective, and safe treatment option for peanut-allergic children, leading to improvement in QOL, a low BOT, and immunologic changes showing tolerance development

Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis

Background: Bone Morphogenetic Protein (BMP)-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. Methods: BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT)-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8) expression was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-b induced epithelial-to-mesenchymal transition (EMT), expression of TGF-b receptor type I (TGF-bRI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-a induced apoptosis of proximal tubular cells. Results: BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml) were able to reverse TNF-a-induced apoptosis and TGF-b-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-bRI. In addition, BMP-7 was able to reverse TGF-b-induced phosphorylation of Smad 2. Conclusions: The findings suggest a protective role for BMP-7 by counteracting the TGF-b and TNF-a-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease

Birth Order, Caesarean Section, or Daycare Attendance in Relation to Child- and Adult-Onset Type 1 Diabetes: Results from the German National Cohort

Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to “only-children”, HRs for second- or later-born individuals were 0.70 (95% CI = 0.50–0.96) and 0.65 (95% CI = 0.45–0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults’ T1D risk assessment for early detection

Identification and Characterization of Human Observational Studies in Nutritional Epidemiology on Gut Microbiomics for Joint Data Analysis

In any research field, data access and data integration are major challenges that even large, well-established consortia face. Although data sharing initiatives are increasing, joint data analyses on nutrition and microbiomics in health and disease are still scarce. We aimed to identify observational studies with data on nutrition and gut microbiome composition from the Intestinal Microbiomics (INTIMIC) Knowledge Platform following the findable, accessible, interoperable, and reusable (FAIR) principles. An adapted template from the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) consortium was used to collect microbiome-specific information and other related factors. In total, 23 studies (17 longitudinal and 6 cross-sectional) were identified from Italy (7), Germany (6), Netherlands (3), Spain (2), Belgium (1), and France (1) or multiple countries (3). Of these, 21 studies collected information on both dietary intake (24 h dietary recall, food frequency questionnaire (FFQ), or Food Records) and gut microbiome. All studies collected stool samples. The most often used sequencing platform was Illumina MiSeq, and the preferred hypervariable regions of the 16S rRNA gene were V3-V4 or V4. The combination of datasets will allow for sufficiently powered investigations to increase the knowledge and understanding of the relationship between food and gut microbiome in health and disease