Description, Reliability and Validation of a Novel Ground-Reaction-Force-Triggered Protocol for Simulation of Tripping Perturbations During Gait

Tripping is a common cause of falls across different age populations particularly in older adults. Concerns regarding the validity of simulated-fall research protocols reside in the current literature. The purpose of this study was to develop a novel treadmill-based tripping protocol that allowed researchers to deliver unanticipated tripping perturbations during walking with a high level of timing precision. The protocol utilized a side-by-side split-belt treadmill instrumented with force platforms. Treadmill belt acceleration profiles (two levels of perturbation severity: small perturbation vs large perturbation) were delivered unilaterally when the tripped leg bore 20% of the body weight during early stance. Peak trunk flexion angle during trip recovery was the primary variable used to represent the fall recovery response and likelihood of falls. Test-retest reliability of the fall responses was examined in a group of 10 young participants; validity was examined through differentiation of the fall responses between young and older adults (age 20.9 vs. 57.1 years, n=10 per group). We found that the perturbations were precisely delivered during the early stance phase (10-45 ms after initial contact). Moreover, this protocol elicited excellent reliability of recovery responses during both perturbation severities (ICC=0.944 and 0.911). Older adults exhibited significantly greater peak trunk flexion angle than young adults (p=0.035), indicating the current protocol was valid in differentiating individuals with different levels of fall risks. This novel protocol addressed some of the issues of previous simulated-fall protocols and may be useful as a tool for future fall research and clinical intervention

Quadruple mutation GCAC1809-1812TTCT acts as a biomarker in healthy European HBV carriers

Many mutation analyses of the HBV genome have been performed in the search for new prognostic markers. However, the Kozak sequence preceding precore was covered only infrequently in these analyses. In this study, the HBV core promoter/precore region was sequenced in serum samples from European inactive HBV carriers. Quadruple mutation GCAC1809-1812TTCT was found with a high prevalence of 42% in the Kozak sequence preceding precore among all HBV genotypes. GCAC1809-1812TTCT was strongly associated with coexistence of basal core promoter (BCP) double mutation A1762T/G1764A and lower HBV DNA levels. In vitro GCAC1809-1812TTCT lead to drastically diminished synthesis of pregenomic RNA (pgRNA), precore mRNA, core, HBsAg, and HBeAg. Calculation of the pgRNA secondary structure suggests a destabilization of the pgRNA structure by A1762T/G1764A that was compensated by GCAC1809-1812TTCT. In 125 patients with HBV-related cirrhosis, GCAC1809-1812TTCT was not detected. While a strong association of GCAC1809-1812TTCT with inactive carrier status was observed, BCP double mutation was strongly correlated with cirrhosis, but this was only observed in absence of GCAC1809-1812TTCT. In conclusion, our data reveal that GCAC1809-1812TTCT is highly prevalent in inactive carriers and acts as a compensatory mutation for BCP double mutation. GCAC1809-1812TTCT seems to be a biomarker of good prognosis in HBV infection