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The gut microbiome is known to play a significant role in human health but its role in aging remains unclear. The objective of this study was to compare the gut microbiome composition between young adult and geriatric nonhuman primates (marmosets) as a model of human health and disease. Stool samples were collected from geriatric (8+ years) and young adult males (2-5 years). Stool 16s rRNA V4 sequences were amplified and sequenced on the Illumina MiSeq platform. Sequences were clustered into operational taxonomic units and classified via mothur's Bayesian classifier referenced against the Greengenes database. A total of 10 young adult and 10 geriatric marmosets were included. Geriatric marmosets had a lower mean Shannon diversity compared to young marmosets (3.15 vs. 3.46; p=0.0191). Geriatric marmosets had a significantly higher mean abundance of Proteobacteria (0.22 vs. 0.09; p=0.0233) and lower abundance of Firmicutes (0.15 vs. 0.19; p=0.0032) compared to young marmosets. Geriatric marmosets had a significantly higher abundance of Succinivibrionaceae (0.16 vs. 0.01; p=0.0191) and lower abundance of Porphyromonadaceae (0.07 vs. 0.11; p=0.0494). In summary, geriatric marmosets had significantly altered microbiome diversity and composition compared to young adult marmosets. Further studies are needed to test microbiome-targeted therapies to improve healthspan and lifespan.

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV1) despite many years of heavy smoking. We hypothesised that these “resistant smokers” may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re-sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the “resistant smokers” and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.34×10−4) in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial epithelium may affect growth of cilia or the extent of damage caused by tobacco smoke.

Silicon samples containing narrow boron markers were depth profiled using normally incident 0.25-1 keV O 2 + ion beams in combination with secondary ion mass spectrometry (SIMS). The profiles revealed significant deviations from ideal delta distributions, either as tails or shoulders. All tracer profiles exhibited the well-known apparent shift towards the surface, which is due to the initial decrease in erosion rate. The peak positions, z , showed a much more pronounced non-linear energy-dependent shift than the centroids, hzi, up to a factor of 2 stronger. To evaluate the form of measured profiles, a reduced shape parameter is defined as 1 = hzi − z . For ideal deltas, this parameter can be calculated using the analytical resolution function (rf) after Dowsett et al. Depending on the orientation and magnitude of the tracer distortions, the measured values of 1 differed from 1 rf by up to 0.8 nm. This difference is attributed to the fact that the 'weight' of the distortions gives rise to a corresponding change of hzi. The results imply that (relative) marker locations are determined more safely from z than from hzi.

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Developing a TOC program similar to this pilot program requires several resources including time, collaboration, and support from the management team. Pharmacy is well positioned to complete an accurate medication review and conduct postdischarge telephone calls to address medication-related issues. By providing these services, patients will receive continuity of care and positively impact emergency room visitation rates and hospital readmission rates.

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