An optimized, robust and reproducible protocol to generate well-differentiated primary nasal epithelial models from extremely premature infants

Extremely premature infants are prone to severe respiratory infections, and the mechanisms underlying this exceptional susceptibility are largely unknown. Nasal epithelial cells (NEC) represent the first-line of defense and adult-derived ALI cell culture models show promising results in mimicking in vivo physiology. Therefore, the aim of this study was to develop a robust and reliable protocol for generating well-differentiated cell culture models from NECs of extremely premature infants. Nasal brushing was performed in 13 extremely premature infants at term corrected age and in 11 healthy adult controls to obtain NECs for differentiation at air-liquid interface (ALI). Differentiation was verified using imaging and functional analysis. Successful isolation and differentiation was achieved for 5 (38.5%) preterm and 5 (45.5%) adult samples. Preterm and adult ALI-cultures both showed well-differentiated morphology and ciliary function, however, preterm cultures required significantly longer cultivation times for acquiring full differentiation (44 +/- 3.92 vs. 23 +/- 1.83 days; p <0.0001). Moreover, we observed that recent respiratory support may impair successful NECs isolation. Herewithin, we describe a safe, reliable and reproducible method to generate well-differentiated ALI-models from NECs of extremely premature infants. These models provide a valuable foundation for further studies regarding immunological and inflammatory responses and respiratory disorders in extremely premature infants.Peer reviewe

Shotgun lipidomics of liver and brain tissue of Alzheimer's disease model mice treated with acitretin

Alzheimer’s disease (AD) is a very frequent neurodegenerative disorder characterized by an accumulation of amyloid-β (Aβ). Acitretin, a retinoid-derivative and approved treatment for Psoriasis vulgaris, increases non-amyloidogenic Amyloid-Precursor-Protein-(APP)-processing, prevents Aβ-production and elicits cognitive improvement in AD mouse models. As an unintended side effect, acitretin could result in hyperlipidemia. Here, we analyzed the impact of acitretin on the lipidome in brain and liver tissue in the 5xFAD mouse-model. In line with literature, triglycerides were increased in liver accompanied by increased PCaa, plasmalogens and acyl-carnitines, whereas SM-species were decreased. In brain, these effects were partially enhanced or similar but also inverted. While for SM and plasmalogens similar effects were found, PCaa, TAG and acyl-carnitines showed an inverse effect in both tissues. Our findings emphasize, that potential pharmaceuticals to treat AD should be carefully monitored with respect to lipid-homeostasis because APP-processing itself modulates lipid-metabolism and medication might result in further and unexpected changes. Moreover, deducing effects of brain lipid-homeostasis from results obtained for other tissues should be considered cautiously. With respect to acitretin, the increase in brain plasmalogens might display a further positive probability in AD-treatment, while other results, such as decreased SM, indicate the need of medical surveillance for treated patients

Social capital and dental pain in Brazilian northeast: a multilevel cross-sectional study.

<p>Abstract</p> <p>Background</p> <p>There is limited evidence on possible associations between social determinants and dental pain. This study investigated the relationship of neighborhood and individual social capital with dental pain in adolescents, adults and the elderly.</p> <p>Methods</p> <p>A population-based multilevel study was conducted involving 624 subjects from 3 age groups: 15–19, 35–44 and 65–74 years. They were randomly selected from 30 census tracts in three cities in the State of Paraíba, Brazil. A two-stage cluster sampling was used considering census tracts and households as sampling units. The outcome of study was the presence of dental pain in the last 6 months. Information on dental pain, demographic, socio-economic, health-related behaviors, use of dental services, self-perceived oral health and social capital measures was collected through interviews. Participants underwent a clinical examination for assessment of dental caries. Neighborhood social capital was evaluated using aggregated measures of social trust, social control, empowerment, political efficacy and neighborhood safety. Individual social capital assessment included bonding and bridging social capital. Multilevel logistic regression was used to test the relationship of neighborhood and individual social capital with dental pain after sequential adjustment for covariates.</p> <p>Results</p> <p>Individuals living in neighborhoods with high social capital were 52% less likely to report dental pain than those living in neighborhoods with low social capital (OR = 0.48, 95% CI = 0.27-0.85). Bonding social capital (positive interaction) was independently associated with dental pain (OR = 0.88, 95% CI = 0.80-0.91). Last dental visit, self-perceived oral health and number of decayed teeth were also significantly associated with dental pain.</p> <p>Conclusions</p> <p>Our findings suggest that contextual and individual social capital are independently associated with dental pain.</p