<Emphasis Type="Italic">Chlamydia pneumoniae</Emphasis> aggravates vein graft intimal hyperplasia in a rat model

Background  

Along with angioplasty, autologus vein grafts are commonly used for artery bypass grafting in patients with advanced arterial stenosis and drug-resistant angina pectoris. Although initially a successful procedure, long-term functionality is limited due to proliferation and migration of smooth muscle cells. Like in atherosclerosis, common chronic infections caused by viruses and bacteria may contribute to this process of vein graft failure. Here we investigated the possible role of Chlamydia pneumoniae (Cpn) in the pathogenesis of venous graft failure in an experimental animal model. In 2 groups (n = 10 rats/group), an epigastric vein-to-common femoral artery interposition graft was placed. Immediately thereafter, rats were infected with Cpn (5*10⁸ IFU) or injected with control solutions. Rats were sacrificed three weeks after surgery and the grafts were harvested for morphometrical and immunohistochemical analysis.     

Multivariable association discovery in population-scale meta-omics studies

It is challenging to associate features such as human health outcomes, diet, environmental conditions, or other metadata to microbial community measurements, due in part to their quantitative properties. Microbiome multi-omics are typically noisy, sparse (zero-inflated), high-dimensional, extremely non-normal, and often in the form of count or compositional measurements. Here we introduce an optimized combination of novel and established methodology to assess multivariable association of microbial community features with complex metadata in population-scale observational studies. Our approach, MaAsLin 2 (Microbiome Multivariable Associations with Linear Models), uses generalized linear and mixed models to accommodate a wide variety of modern epidemiological studies, including cross-sectional and longitudinal designs, as well as a variety of data types (e.g., counts and relative abundances) with or without covariates and repeated measurements. To construct this method, we conducted a large-scale evaluation of a broad range of scenarios under which straightforward identification of meta-omics associations can be challenging. These simulation studies reveal that MaAsLin 2’s linear model preserves statistical power in the presence of repeated measures and multiple covariates, while accounting for the nuances of meta-omics features and controlling false discovery. We also applied MaAsLin 2 to a microbial multi-omics dataset from the Integrative Human Microbiome (HMP2) project which, in addition to reproducing established results, revealed a unique, integrated landscape of inflammatory bowel diseases (IBD) across multiple time points and omics profiles.     

Metagenomic microbial community profiling using unique clade-specific marker genes

Metagenomic shotgun sequencing data can identify microbes populating a microbial community and their proportions, but existing taxonomic profiling methods are inefficient for increasingly large data sets. We present an approach that uses clade-specific marker genes to unambiguously assign reads to microbial clades more accurately and >50× faster than current approaches. We validated our metagenomic phylogenetic analysis tool, MetaPhlAn, on terabases of short reads and provide the largest metagenomic profiling to date of the human gut. It can be accessed at http://huttenhower.sph.harvard.edu/metaphlan/.     

Postmortem absorption of lead by the skeleton

In a study of bones recovered from lead coffins at two sites in the United Kingdom, the lead concentration was so high that postmortem absorption seemed the most likely explanation. Electron probe analysis showed that in one bone from a lead coffin, the lead was concentrated on the surfaces of the bone, as would be expected if absorption had occurred after death. It is suggested that in any further study of the lead content of bones from archaeological sites, steps must be taken to assess environmental lead levels and if these are unusually high, the results of the analyses should be viewed with suspicion.     

Studies on Inhibition of Intestinal Absorption of Radioactive Strontium: I. Prevention of Absorption from Ligated Intestinal Segments

A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, permitting the calcium to be available to the body. Studies were carried out in vivo by injection of Sr⁸⁹ and Ca⁴⁵ in the presence of inert carrier into ligated intestinal segments in rats, and the amount of absorption was measured by standard monitoring techniques. The pattern of absorption of both ions is very similar but the rate of absorption is different. It was found that the polyelectrolyte, sodium alginate, obtained from brown algae (Phaeophyceae), injected simultaneously with radiostrontium effectively reduces the absortion of Sr⁸⁹ from all segments of the intestine by as much as 50-80% of the control values. No significant reduction in absorption of Ca⁴⁵ was observed in equivalent concentrations. The reduction in blood levels of Sr⁸⁹ and in bone uptake corresponded to the absorption pattern. The difference in the effect on strontium and calcium absorption may be due to differences in the binding capacity of sodium alginate from the two metal ions under the conditions present in vivo.     

Some implications of a constant fiber stress hypothesis in the diastolic left ventricle

A thick-wall incompressible, elastic sphere was used as a model for the diastolic rat left ventricle. A model for myocardial nonhomogeneity was derived assuming that fiber (circumferential) stress was independent of position in the ventricular wall. The theoretical implications of the resulting constitutive relations together with the spherical model were analyzed in the context of large deformation elasticity theory. It was found that muscle stiffness at a given level of uniaxial stress increased monotonically from the endocardium to the epicardium. In addition, fiber stress was found to be essentially a linear function of transmural pressure above a pressure of 6 g/cm². It was also shown theoretically that neglecting the nonhomogeneity of the myocardium resulted in a state of stress which differed significantly from that predicted by the nonhomogeneous model. For example, at a transmural pressure of 14 g/cm², fiber stress in the nonhomogenous model was equal to 17 g/cm² while fiber stress in the homogeneous model varied between 100 g/cm² at the endocardial surface and 2 g/cm² at the epicardial surface. The change in muscle stiffness with position which characterized the nonhomogeneous model also tended to linearize the highly curvilinear radial stress distribution predicted by the homogeneous model at a given transmural pressure.