Surface, but Not Age, Impacts Lower Limb Joint Work during Walking and Stair Ascent

Older adults often suffer an accidental fall when navigating challenging surfaces during common locomotor tasks, such as walking and ascending stairs. This study examined the effect of slick and uneven surfaces on lower limb joint work in older and younger adults while walking and ascending stairs. Fifteen young (18–25 years) and 12 older (\u3e65 years) adults had stance phase positive limb and joint work quantified during walking and stair ascent tasks on a normal, slick, and uneven surface, which was then submitted to a two-way mixed model ANOVA for analysis. The stair ascent required greater limb, and hip, knee, and ankle work than walking (all p \u3c 0.001), with participants producing greater hip and knee work during both the walk and stair ascent (both p \u3c 0.001). Surface, but not age, impacted positive limb work. Participants increased limb (p \u3c 0.001), hip (p = 0.010), and knee (p \u3c 0.001) positive work when walking over the challenging surfaces, and increased hip (p = 0.015), knee (p \u3c 0.001), and ankle (p = 0.010) work when ascending stairs with challenging surfaces. Traversing a challenging surface during both walking and stair ascent tasks required greater work production from the large proximal hip and knee musculature, which may increase the likelihood of an accidental fall in older adults

Surface, but Not Age Impact Lower Limb Joint Work During Walk and Stair Ascent

During common locomotor activates, such as walk or stair negotiation, older adults exhibit unfavorable lower limb biomechanical changes, including diminished joint torque and power, and proximal mechanical work redistribution that may increase their fall risk. To investigate age-related differences in lower limb work, twelve young (18 to 25 years) and 12 older (\u3e 65 years) adults performed a walk and stair ascent task on a normal, slick, and uneven surface. For each walk and stair ascent trial, synchronous 3D marker trajectories and GRF data were collected. Stance phase positive limb and joint work, and relative joint work were submitted to statistical analysis. Ascending stairs required more positive work than the walk, particularly from the knee, which may increase fall risk. Yet, both walking and ascending stairs over a challenging surface required more, proximally distributed work

Surface, but Not Age Impact Lower Limb Joint Work During Walk and Stair Ascent

During common locomotor activates, such as walk or stair negotiation, older adults exhibit unfavorable lower limb biomechanical changes, including diminished joint torque and power, and proximal mechanical work redistribution that may increase their fall risk. Twelve young (18 to 25 years) and 12 older (\u3e 65 years) adults performed a walk and stair ascent task on a normal, slick, and uneven surface. For each walk and stair ascent trial, synchronous 3D marker trajectories and GRF data were collected. Stance phase positive limb and joint work, and relative joint work were submitted to statistical analysis. Ascending stairs required more positive work than the walk, particularly from the knee, which may increase fall risk. Yet, both walking and ascending stairs over a challenging surface required more, proximally distributed work

Surface, but Not Age Impacts Lower Limb Joint Work During Stair Ascent

Introduction: Age-related loss in lower limb strength, particularly at the ankle, may impair older adults (over 65 years of age) mobility, and result in biomechanical deficits compared to their younger counterparts. Older adults tend to walk slower with shorter steps and exhibit diminished ankle joint kinetics (i.e., moment, power and work). Although the compromised ankle function leads older adults to produce smaller ankle joint torques and power output, reducing forces to propel the center of mass forward, it is unclear if they redistributed, or increase hip or knee work to safely walk, particularly when challenged with an uneven or slick surface. Objective: To compare positive lower limb work for young and older adults when walking over challenging surfaces, and determine whether redistributed power output. Methods: Twenty-eight (16 young, 18 to 25 years and 12 older, over 65 years) adults had positive work in the lower limb quantified when walking a self-selected speed over three surfaces (normal, uneven, and slick). Total limb, hip, knee and ankle positive work, and relative effort (% of total) at each joint were submitted to RM ANOVA to test main effect and interaction between surface (normal, uneven, and slick) and age (young and older adults). Results: Surface, but not age impact positive lower limb work. Surface impacted total limb (p=0.000), hip (p=0.007) and knee (p=0.001) positive work. The limb and knee produced more positive work on the uneven compared normal (

Insulin-like growth factors and cancer: no role in screening. Evidence from the BUPA study and meta-analysis of prospective epidemiological studies

Insulin-like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), and insulin-like growth factor binding protein-3 (IGFBP-3) were measured in frozen serum samples from 1051 men with cancer and 3142 controls in a nested case–control study from the British United Provident Association (BUPA) study cohort and associations with 14 cancers were examined, including prostate, colorectal, and lung. A meta-analysis of studies on these three cancer sites was also conducted. In the meta-analysis the odds ratio between the highest quartile IGF-1 group and the lowest quartile group was 1.31 (95% confidence interval (CI): 1.03–1.67) for prostate, 1.37 (1.05–1.78) for colorectal and 1.02 (0.80–1.31) for lung cancer, and for IGF-2 it was 0.72 (0.36–1.44) for prostate and 1.95 (1.26–3.00) for colorectal cancer. Results from the BUPA study were consistent with the estimates from the other studies. There were no statistically significant associations with IGFBP-3 and any of the cancer sites considered. Our results suggest that IGF-1, IGF-2, and IGFBP-3 measurements have no value in cancer screening, although IGF-1 and IGF-2 may be of aetiological significance in relation to colorectal and prostate cancer

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

Local Translation in Primary Afferent Fibers Regulates Nociception

Recent studies have demonstrated the importance of local protein synthesis for neuronal plasticity. In particular, local mRNA translation through the mammalian target of rapamycin (mTOR) has been shown to play a key role in regulating dendrite excitability and modulating long-term synaptic plasticity associated with learning and memory. There is also increased evidence to suggest that intact adult mammalian axons have a functional requirement for local protein synthesis in vivo. Here we show that the translational machinery is present in some myelinated sensory fibers and that active mTOR-dependent pathways participate in maintaining the sensitivity of a subpopulation of fast-conducting nociceptors in vivo. Phosphorylated mTOR together with other downstream components of the translational machinery were localized to a subset of myelinated sensory fibers in rat cutaneous tissue. We then showed with electromyographic studies that the mTOR inhibitor rapamycin reduced the sensitivity of a population of myelinated nociceptors known to be important for the increased mechanical sensitivity that follows injury. Behavioural studies confirmed that local treatment with rapamycin significantly attenuated persistent pain that follows tissue injury, but not acute pain. Specifically, we found that rapamycin blunted the heightened response to mechanical stimulation that develops around a site of injury and reduced the long-term mechanical hypersensitivity that follows partial peripheral nerve damage - a widely used model of chronic pain. Our results show that the sensitivity of a subset of sensory fibers is maintained by ongoing mTOR-mediated local protein synthesis and uncover a novel target for the control of long-term pain states

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy