Consequences of lower extremity and trunk muscle fatigue on balance and functional tasks in older people: A systematic literature review

<p>Abstract</p> <p>Background</p> <p>Muscle fatigue reduces muscle strength and balance control in young people. It is not clear whether fatigue resistance seen in older persons leads to different effects. In order to understand whether muscle fatigue may increase fall risk in older persons, a systematic literature review aimed to summarize knowledge on the effects of lower extremity and trunk muscle fatigue on balance and functional tasks in older people was performed.</p> <p>Methods</p> <p>Studies were identified with searches of the PUBMED and SCOPUS data bases.</p> <p>Papers describing effects of lower extremity or trunk muscle fatigue protocols on balance or functional tasks in older people were included. Studies were compared with regards to study population characteristics, fatigue protocol, and balance and functional task outcomes.</p> <p>Results</p> <p>Seven out of 266 studies met the inclusion criteria. Primary findings were: fatigue via resistance exercises to lower limb and trunk muscles induces postural instability during quiet standing; induced hip, knee and ankle muscle fatigue impairs functional reach, reduces the speed and power of sit-to-stand repetitions, and produces less stable and more variable walking patterns; effects of age on degree of fatigue and rate of recovery from fatigue are inconsistent across studies, with these disparities likely due to differences in the fatigue protocols, study populations and outcome measures.</p> <p>Conclusion</p> <p>Taken together, the findings suggest that balance and functional task performance are impaired with fatigue. Future studies should assess whether fatigue is related to increased risk of falling and whether exercise interventions may decrease fatigue effects.</p

Interaction among apoptosis-associated sequence variants and joint effects on aggressive prostate cancer

<p>Abstract</p> <p>Background</p> <p>Molecular and epidemiological evidence demonstrate that altered gene expression and single nucleotide polymorphisms in the apoptotic pathway are linked to many cancers. Yet, few studies emphasize the interaction of variant apoptotic genes and their joint modifying effects on prostate cancer (PCA) outcomes. An exhaustive assessment of all the possible two-, three- and four-way gene-gene interactions is computationally burdensome. This statistical conundrum stems from the prohibitive amount of data needed to account for multiple hypothesis testing.</p> <p>Methods</p> <p>To address this issue, we systematically prioritized and evaluated individual effects and complex interactions among 172 apoptotic SNPs in relation to PCA risk and aggressive disease (i.e., Gleason score ≥ 7 and tumor stages III/IV). Single and joint modifying effects on PCA outcomes among European-American men were analyzed using statistical epistasis networks coupled with multi-factor dimensionality reduction (SEN-guided MDR). The case-control study design included 1,175 incident PCA cases and 1,111 controls from the prostate, lung, colo-rectal, and ovarian (PLCO) cancer screening trial. Moreover, a subset analysis of PCA cases consisted of 688 aggressive and 488 non-aggressive PCA cases. SNP profiles were obtained using the NCI Cancer Genetic Markers of Susceptibility (CGEMS) data portal. Main effects were assessed using logistic regression (LR) models. Prior to modeling interactions, SEN was used to pre-process our genetic data. SEN used network science to reduce our analysis from > 36 million to < 13,000 SNP interactions. Interactions were visualized, evaluated, and validated using entropy-based MDR. All parametric and non-parametric models were adjusted for age, family history of PCA, and multiple hypothesis testing.</p> <p>Results</p> <p>Following LR modeling, eleven and thirteen sequence variants were associated with PCA risk and aggressive disease, respectively. However, none of these markers remained significant after we adjusted for multiple comparisons. Nevertheless, we detected a modest synergistic interaction between <it>AKT3 rs2125230-PRKCQ rs571715 </it>and disease aggressiveness using SEN-guided MDR (p = 0.011).</p> <p>Conclusions</p> <p>In summary, entropy-based SEN-guided MDR facilitated the logical prioritization and evaluation of apoptotic SNPs in relation to aggressive PCA. The suggestive interaction between <it>AKT3-PRKCQ </it>and aggressive PCA requires further validation using independent observational studies.</p

AAV ancestral reconstruction library enables selection of broadly infectious viral variants

Adeno-associated virus (AAV) vectors have achieved clinical efficacy in treating several diseases. Enhanced vectors are required to extend these landmark successes to other indications, however, and protein engineering approaches may provide the necessary vector improvements to address such unmet medical needs. To generate new capsid variants with potentially enhanced infectious properties, and to gain insights into AAV’s evolutionary history, we computationally designed and experimentally constructed a putative ancestral AAV library. Combinatorial variations at 32 amino acid sites were introduced to account for uncertainty in their identities. We then analyzed the evolutionary flexibility of these residues, the majority of which have not been previously studied, by subjecting the library to iterative selection on a representative cell line panel. The resulting variants exhibited transduction efficiencies comparable to the most efficient extant serotypes, and in general ancestral libraries were broadly infectious across the cell line panel, indicating that they favored promiscuity over specificity. Interestingly, putative ancestral AAVs were more thermostable than modern serotypes and did not utilize sialic acids, galactose, or heparan sulfate proteoglycans for cellular entry. Finally, variants mediated 19–31 fold higher gene expression in muscle compared to AAV1, a clinically utilized serotype for muscle delivery, highlighting their promise for gene therapy

The Effects of Performance Fatigability on Postural Control and Rehabilitation in the Older Patient

Fatigue is common in older adults and has a significant effect on quality of life. Despite the high prevalence of fatigue in older individuals, several aspects are poorly understood. It is important to differentiate subjective fatigue complaints from fatigability of motor performance because the two are independent constructs with potentially distinct consequences on mobility. Performance fatigability is the magnitude of change in a performance criterion over a given time of task performance. Performance fatigability is a compulsory element of any strength training program, yet strength training is an important component of rehabilitation programs for older adults. The consequences of fatigability for older adults suggest that acute exercise of various types may result in acute impairments in postural control. The effects of performance fatigability on postural control in older adults are evaluated here to aid the rehabilitation clinician in making recommendations for evaluation of fall risks and exercise prescription