Smoking, DNA Methylation, and Lung Function: a Mendelian Randomization Analysis to Investigate Causal Pathways.

Whether smoking-associated DNA methylation has a causal effect on lung function has not been thoroughly evaluated. We first investigated the causal effects of 474 smoking-associated CpGs on forced expiratory volume in 1 s (FEV1) in UK Biobank (n = 321,047) by using two-sample Mendelian randomization (MR) and then replicated this investigation in the SpiroMeta Consortium (n = 79,055). Second, we used two-step MR to investigate whether DNA methylation mediates the effect of smoking on FEV1. Lastly, we evaluated the presence of horizontal pleiotropy and assessed whether there is any evidence for shared causal genetic variants between lung function, DNA methylation, and gene expression by using a multiple-trait colocalization ("moloc") framework. We found evidence of a possible causal effect for DNA methylation on FEV1 at 18 CpGs (p < 1.2 × 10-4). Replication analysis supported a causal effect at three CpGs (cg21201401 [LIME1 and ZGPAT], cg19758448 [PGAP3], and cg12616487 [EML3 and AHNAK] [p < 0.0028]). DNA methylation did not clearly mediate the effect of smoking on FEV1, although DNA methylation at some sites might influence lung function via effects on smoking. By using "moloc", we found evidence of shared causal variants between lung function, gene expression, and DNA methylation. These findings highlight potential therapeutic targets for improving lung function and possibly smoking cessation, although larger, tissue-specific datasets are required to confirm these results.

Innovative Biomarkers for Obesity and Type 1 Diabetes Based on Bifidobacterium and Metabolomic Profiling.

The role of Bifidobacterium species and microbial metabolites such as short-chain fatty acids (SCFAs) and human milk oligosaccharides in controlling intestinal inflammation and the pathogenesis of obesity and type 1 diabetes (T1D) has been largely studied in recent years. This paper discusses the discovery of signature biomarkers for obesity and T1D based on data from a novel test for profiling several Bifidobacterium species, combined with metabolomic analysis. Through the NUTRISHIELD clinical study, a total of 98 children were recruited: 40 healthy controls, 40 type 1 diabetics, and 18 obese children. Bifidobacterium profiles were assessed in stool samples through an innovative test allowing high taxonomic resolution and precise quantification, while SCFAs and branched amino acids were measured in urine samples through gas chromatography-mass spectrometry (GC-MS). KIDMED questionnaires were used to evaluate the children's dietary habits and correlate them with the Bifidobacterium and metabolomic profiles. We found that B. longum subs. infantis and B. breve were higher in individuals with obesity, while B. bifidum and B. longum subs. longum were lower compared to healthy individuals. In individuals with T1D, alterations were found at the metabolic level, with an overall increase in the level of the most measured metabolites. The high taxonomic resolution of the Bifidobacterium test used meant strong correlations between the concentrations of valine and isoleucine, and the relative abundance of some Bifidobacterium species such as B. longum subs. infantis, B. breve, and B. bifidum could be observed.

Forces between oil drops in polymer-surfactant systems: Linking direct force measurements to microfluidic observations.

HYPOTHESIS: Linking atomic force microscopy and microfluidics opens up the possibility of probing adhesive interactions between drops in a high-throughput context. A microfluidic device designed to form, and subsequently break-up, chains of drops, where the drop break-up is sensitive to the underlying surface forces between drops, not hydrodynamic drainage forces, would play a key role in developing this link. EXPERIMENTS: Both techniques have been used to quantify the forces between oil drops in the presence of complexes formed with anionic surfactant, sodium dodecylsulphate, and neutral, water soluble polymer, poly(vinylpyrrolidone). Measurement and modelling of the interaction forces between both rigid and deformable surfaces demonstrated that the attraction between the drops is due to depletion forces, whereas the repulsive force is a combination of electrical double layer and steric forces, indicating complexes exist both in the bulk and at the drop interface. FINDINGS: The interaction behaviour between the force measurements and the microfluidic observations showed a strong correlation, where the observed adhesion between drops in the microfluidics is sensitive to the drop deformation and Laplace pressure. Correlation between the two techniques provides insight into the surface forces between drops in flowing systems and has potential utility in the formulation of emulsions.

Feasibility Testing of an Emergency Department Screening Tool To Identify Older Adults Appropriate for Palliative Care Consultation.

BACKGROUND: Seriously ill older adults in the emergency department (ED) may benefit from palliative care referral, yet little is known about how to identify these patients. OBJECTIVES: To assess the performance and determine the acceptability of a content-validated palliative care screening tool. DESIGN: We surveyed Emergency Medicine (EM) attending physicians at the end of their shifts using the screening tool and asked them to retrospectively apply it to all patients ≥65 years whom they had cared for. We conducted the survey for three consecutive weeks in October 2015. SETTING/SUBJECTS: EM attending physicians at an urban, university-affiliated ED. MEASUREMENT: Patient characteristics, acceptability rating, and time per patient screened. RESULTS: We approached 38 attending physicians to apply the screening tool for 69 eligible shifts. Physicians agreed to participate during 55 shifts (80%) and screened 207 patients. On 14 shifts (20%), physicians declined to participate. Mean age of the screened patients was 75 years, 51% were male, and 45% had at least one life-limiting illness. Overall, 67 patients (32%) screened positive for palliative care needs. Seventy percent of physicians (n = 33) found the screening tool acceptable to use and the average time of completion was 1.8 minutes per patient screened. CONCLUSION: A rapid screen of older adults for palliative care needs was acceptable to a majority of EM physicians and identified a significant number of patients who may benefit from palliative care referral. Further research is needed to improve acceptability and determine the appropriate care pathway for patients with palliative care needs.