Automatic Radar-Based Step Length Measurement in the Home for Older Adults Living with Frailty.

With an aging population, numerous assistive and monitoring technologies are under development to enable older adults to age in place. To facilitate aging in place, predicting risk factors such as falls and hospitalization and providing early interventions are important. Much of the work on ambient monitoring for risk prediction has centered on gait speed analysis, utilizing privacy-preserving sensors like radar. Despite compelling evidence that monitoring step length in addition to gait speed is crucial for predicting risk, radar-based methods have not explored step length measurement in the home. Furthermore, laboratory experiments on step length measurement using radars are limited to proof-of-concept studies with few healthy subjects. To address this gap, a radar-based step length measurement system for the home is proposed based on detection and tracking using a radar point cloud followed by Doppler speed profiling of the torso to obtain step lengths in the home. The proposed method was evaluated in a clinical environment involving 35 frail older adults to establish its validity. Additionally, the method was assessed in people's homes, with 21 frail older adults who had participated in the clinical assessment. The proposed radar-based step length measurement method was compared to the gold-standard Zeno Walkway Gait Analysis System, revealing a 4.5 cm/8.3% error in a clinical setting. Furthermore, it exhibited excellent reliability (ICC(2,k) = 0.91, 95% CI 0.82 to 0.96) in uncontrolled home settings. The method also proved accurate in uncontrolled home settings, as indicated by a strong consistency (ICC(3,k) = 0.81 (95% CI 0.53 to 0.92)) between home measurements and in-clinic assessments.

Differences in TCDD-elicited gene expression profiles in human HepG2, mouse Hepa1c1c7 and rat H4IIE hepatoma cells.

BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that elicits a broad spectrum of toxic effects in a species-specific manner. Current risk assessment practices routinely extrapolate results from in vivo and in vitro rodent models to assess human risk. In order to further investigate the species-specific responses elicited by TCDD, temporal gene expression responses in human HepG2, mouse Hepa1c1c7 and rat H4IIE cells were compared. RESULTS: Microarray analysis identified a core set of conserved gene expression responses across species consistent with the role of AhR in mediating adaptive metabolic responses. However, significant species-specific as well as species-divergent responses were identified. Computational analysis of the regulatory regions of species-specific and -divergent responses suggests that dioxin response elements (DREs) are involved. These results are consistent with in vivo rat vs. mouse species-specific differential gene expression, and more comprehensive comparative DRE searches. CONCLUSIONS: Comparative analysis of human HepG2, mouse Hepa1c1c7 and rat H4IIE TCDD-elicited gene expression responses is consistent with in vivo rat-mouse comparative gene expression studies, and more comprehensive comparative DRE searches, suggesting that AhR-mediated gene expression is species-specific.

Automated dose-response analysis and comparative toxicogenomic evaluation of the hepatic effects elicited by TCDD, TCDF, and PCB126 in C57BL/6 mice.

The toxic equivalency factor (TEF) approach recommended by the World Health Organization is used to quantify dioxin-like exposure concentrations for mixtures of polychlorinated dibenzo-dioxins, -furans, and polychlorinated biphenyls (PCBs), including 2,3,7,8-tetrachlorodibenzofuran (TCDF) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Whole-genome microarrays were used to evaluate the hepatic gene expression potency of TCDF and PCB126 relative to TCDD with complementary histopathology, tissue level analysis, and ethoxyresorufin-O-deethylase (EROD) assay results. Immature ovariectomized C57BL/6 mice were gavaged with 0.001, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, 100, and 300 µg/kg TCDD and TEF-adjusted doses (TEF for TCDF and PCB126 is 0.1) of TCDF or PCB126 (1, 3, 10, 30, 100, 300, 1000, and 3000 µg/kg of TCDF or PCB126) or sesame oil vehicle and sacrificed 24 h post dose. In general, TCDD, TCDF, and PCB126 tissue levels, as well as histopathological effects, were comparable when comparing TEF-adjusted doses. Automated dose-response modeling (ToxResponse Modeler) of the microarray data identified 210 TCDF and 40 PCB126 genes that exhibited sigmoidal dose-response curves with comparable slopes when compared with TCDD. These similar responses were used to calculate a median TCDF gene expression relative potency (REP) of 0.06 and a median PCB126 gene expression REP of 0.02. REPs of 0.02 were also calculated for EROD induction for both compounds. Collectively, these data suggest that differences in the ability of the liganded aryl hydrocarbon receptor:AhR nuclear translocator complex to elicit differential hepatic gene expression, in addition to pharmacokinetic differences between ligands, influence their potency in immature ovariectomized C57BL/6 mice.

Alternatively spliced caspase-6B isoform inhibits the activation of caspase-6A.

Caspase-6 (Casp6) is activated early in Alzheimer disease and involved in axonal degeneration, but the regulation of Casp6 activity has not been explored. Several alternatively spliced forms of caspases act as inhibitors of caspase activation. The CASP6 gene generates an alternatively spliced transcript known as CASP6ß in addition to the CASP6α that encodes pro-Casp6a. Here, we show that the CASP6ß transcript and the pro-Casp6b protein are present in many cell lines, in primary human neurons, and in human brains. Unlike most other alternatively spliced caspase transcripts, pro-Casp6b contains a catalytic site. However, purified pro-Casp6b did not have caspase activity, nor did it inhibit already activated Casp6a. Pro-Casp6b prevented the proteolytic activation of pro-Casp6a in vitro and in cells. Pro-Casp6b interacts directly with pro-Casp6a. This work shows that pro-Casp6b is an inhibitor of pro-Casp6a activation. These results imply that pro-Casp6b could negatively regulate pro-Casp6a activation in neurons and prevent Casp6a-mediated axonal degeneration.