Ancient Clostridium DNA and variants of tetanus neurotoxins associated with human archaeological remains.

The analysis of microbial genomes from human archaeological samples offers a historic snapshot of ancient pathogens and provides insights into the origins of modern infectious diseases. Here, we analyze metagenomic datasets from 38 human archaeological samples and identify bacterial genomic sequences related to modern-day Clostridium tetani, which produces the tetanus neurotoxin (TeNT) and causes the disease tetanus. These genomic assemblies had varying levels of completeness, and a subset of them displayed hallmarks of ancient DNA damage. Phylogenetic analyses revealed known C. tetani clades as well as potentially new Clostridium lineages closely related to C. tetani. The genomic assemblies encode 13 TeNT variants with unique substitution profiles, including a subgroup of TeNT variants found exclusively in ancient samples from South America. We experimentally tested a TeNT variant selected from an ancient Chilean mummy sample and found that it induced tetanus muscle paralysis in mice, with potency comparable to modern TeNT. Thus, our ancient DNA analysis identifies DNA from neurotoxigenic C. tetani in archaeological human samples, and a novel variant of TeNT that can cause disease in mammals.

Loaded and unloaded timed stair tests as tools for assessing advanced functional mobility in people with stroke.

BACKGROUND: The Timed Stair Test (TST) was originally designed to measure advanced functional mobility in patients who have undergone a total hip replacement. Its psychometric properties have not been examined systematically in people with stroke. AIM: The aims of this study were to: 1) determine the intra-rater reliability of TST under loaded and unloaded condition; 2) identify the minimal detectable changes (MDCs) in TST completion times; 3) investigate the concurrent validity between TST completion times and stroke-specific outcome measures; and 4) determine the cut-off TST completion time to differentiate the performance between people with stroke and healthy older adults. DESIGN: Cross-sectional study. SETTING: A university-based rehabilitation center. POPULATION: Ninety-four people with stroke and 34 healthy older adults. METHODS: TSTs were conducted under loaded and unloaded conditions. Two trials of the TST for each of the two conditions were performed on the same day. The Fugl-Meyer Assessment of Lower Extremity (FMA-LE), lower-limb muscle strength test assessed by a hand held dynamometer, Berg Balance Scale (BBS), Limit of Stability (LOS) Test, Timed Up and Go (TUG) Test, and the Cantonese version of the Community Integration Measure (CIM) were also used to assess the subjects. RESULTS: Excellent intra-rater reliability was demonstrated for TST completion times under loaded (intraclass correlation coefficient [ICC2,1]=0.991) and unloaded (ICC2,1=0.985) conditions. The MDCs in TST completion times were 6.55 seconds and 7.25 seconds under loaded and unloaded conditions, respectively. FMA-LE scores, mean strength of the affected-side dorsiflexors and plantar flexors, BBS scores, and LOS movement velocity and maximum excursion scores demonstrated fair to excellent negative correlations with TST completion times under both loaded (r=-0.314 to -0.786) and unloaded (r=-0.296 to -0.794) conditions. TUG results demonstrated good to excellent positive correlations with TST completion times under both loaded (r=0.875, P<0.001) and unloaded (r=0.872, P<0.001) conditions. The TST completion times of 26.3 seconds and 23.4 seconds under loaded and unloaded conditions, respectively, differentiated between people with stroke and healthy older adults. CONCLUSIONS: The TST is a reliable clinical tool for evaluating advanced functional mobility in people with stroke. CLINICAL REHABILITATION IMPACT: TST is a fast and simple test that does not require sophisticated equipment, making it suitable for busy hospital and rehabilitation settings.