Project description:Chronic low back pain (CLBP) is associated with postural control impairments and is highly prevalent in elderly people. The objective of this study is to verify whether anticipatory postural adjustments (APAs) and compensatory postural adjustments (CPAs) are affected by CLBP in elderly people by assessing their postural control during a self-initiated perturbation paradigm induced by rapid upper arm movement when pointing to a target. The participants' lower limb muscle onset and center of pressure (COP) displacements were assessed prior to perturbation and throughout the entire movement. T0 moment (i.e., the beginning of the movement) was defined as the anterior deltoid (DEL) onset, and all parameters were calculated with respect to it. The rectus femoris (RT), semitendinosus (ST), and soleous (SOL) showed delayed onset in the CLBP group compared with the control group: RF (control: - 0.094 ± 0.017 s; CLBP: - 0.026 ± 0.012 s, t = 12, p < 0.0001); ST (control: - 0.093 ± 0.013 s; CLBP: - 0.018 ± 0.019 s, t = 12, p < 0.0001); and SOL (control: - 0.086 ± 0.018 s; CLBP: - 0.029 ± 0.015 s, t = 8.98, p < 0.0001). In addition, COP displacement was delayed in the CLBP group (control: - 0.035 ± 0.021 s; CLBP: - 0.015 ± 0.009 s, t = 3; p = 0.003) and presented a smaller amplitude during APA COPAPA [control: 0.444 cm (0.187; 0.648); CLBP: 0.228 cm (0.096; 0.310), U = 53, p = 0.012]. The CLBP group required a longer time to reach the maximum displacement after the perturbation (control: 0.211 ± 0.047 s; CLBP 0.296 ± 0.078 s, t = 3.582, p = 0.0013). This indicates that CLBP elderly patients have impairments to recover their postural control and less efficient anticipatory adjustments during the compensatory phase. Our results suggest that people with CLBP have altered feedforward hip and ankle muscle control, as shown from the SOL, ST, and RT muscle onset. This study is the first study in the field of aging that investigates the postural adjustments of an elderly population with CLBP. Clinical assessment of this population should consider postural stability as part of a rehabilitation program.

Project description:This is a pilot study. We are trying to detect potential salivary biomarkers in mice with a pancreatic tumor. Global gene expression profiling has shown great promise in high-throughput biomarker discovery for early disease detection in body fluids such as saliva, which is accessible, cost-effective, and non-invasive. However, this goal has not been fully realized because saliva, like many clinical samples, contains partially fragmented and degraded RNAs that are difficult to amplify and detect with prevailing technologies. Here, using nanogram scale salivary RNA as a proof-of-principle example, we describe our progress with a novel poly-A tail independent mRNA amplification strategy combined with the Affymetrix GeneChip Exon arrays. We defined a Salivary Exon Core Transcriptome (SECT) with highly similar expression profiles in healthy individuals verified by quantitative PCR. Informatics analysis of SECT provided important mechanistic insight to their potential origin and function. Finally we demonstrated the diagnostic potential of true exon level expression profiling approach with salivary exon biomarkers that accurately discriminated gender in healthy individuals. Recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected upon the development of systemic diseases such as pancreatic cancer, breast cancer, lung cancer and ovarian cancer. However, the utility of salivary biomarkers for the detection of systemic diseases has been undermined due to the absence of biological and mechanistic rationale why distal diseases from the oral cavity would lead to the development of discriminatory biomarkers in saliva. Here, we examine the hypothesis that pancreatic tumor-derived exosomes are mechanistically involved in the development of pancreatic cancer-discriminatory salivary transcriptomic biomarkers. We first developed a pancreatic cancer mouse model that yielded discriminatory salivary biomarkers by implanting the mouse pancreatic cancer cell line Pan02 into the pancreas of the syngeneic host C57BL/6. The role of pancreatic cancer-derived exosomes in the development of discriminatory salivary biomarkers was then tested by engineered a Pan02 cell line that is suppressed for exosome biogenesis, implanted into the C56BL/6 mouse and examine if the discriminatory salivary biomarker profile was ablated or disrupted. Suppression of exosome biogenesis results in the ablation of discriminatory salivary biomarker development. This study supports that tumor-derived exosomes provide a mechanism in the development of discriminatory biomarkers in saliva and distal systemic diseases. We analyzed saliva from 6 healthy mice and 6 mice with a pancreatic tumor using the Affymetrix Mouse Exon Genome 430 2.0 platform. Array data was processed by dChip. No techinical replicates were performed.

Project description:This is a pilot study. We are trying to detect potential salivary biomarkers in mice with a pancreatic tumor. Global gene expression profiling has shown great promise in high-throughput biomarker discovery for early disease detection in body fluids such as saliva, which is accessible, cost-effective, and non-invasive. However, this goal has not been fully realized because saliva, like many clinical samples, contains partially fragmented and degraded RNAs that are difficult to amplify and detect with prevailing technologies. Here, using nanogram scale salivary RNA as a proof-of-principle example, we describe our progress with a novel poly-A tail independent mRNA amplification strategy combined with the Affymetrix GeneChip Exon arrays. We defined a Salivary Exon Core Transcriptome (SECT) with highly similar expression profiles in healthy individuals verified by quantitative PCR. Informatics analysis of SECT provided important mechanistic insight to their potential origin and function. Finally we demonstrated the diagnostic potential of true exon level expression profiling approach with salivary exon biomarkers that accurately discriminated gender in healthy individuals. Recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected upon the development of systemic diseases such as pancreatic cancer, breast cancer, lung cancer and ovarian cancer. However, the utility of salivary biomarkers for the detection of systemic diseases has been undermined due to the absence of biological and mechanistic rationale why distal diseases from the oral cavity would lead to the development of discriminatory biomarkers in saliva. Here, we examine the hypothesis that pancreatic tumor-derived exosomes are mechanistically involved in the development of pancreatic cancer-discriminatory salivary transcriptomic biomarkers. We first developed a pancreatic cancer mouse model that yielded discriminatory salivary biomarkers by implanting the mouse pancreatic cancer cell line Pan02 into the pancreas of the syngeneic host C57BL/6. The role of pancreatic cancer-derived exosomes in the development of discriminatory salivary biomarkers was then tested by engineered a Pan02 cell line that is suppressed for exosome biogenesis, implanted into the C56BL/6 mouse and examine if the discriminatory salivary biomarker profile was ablated or disrupted. Suppression of exosome biogenesis results in the ablation of discriminatory salivary biomarker development. This study supports that tumor-derived exosomes provide a mechanism in the development of discriminatory biomarkers in saliva and distal systemic diseases.

Project description:BackgroundPhysical function and exercise capacity decline with age and are a major source of disability in older people. Recent evidence suggests a potential role for the renin-angiotensin system in modulating muscle function. We sought to examine the effect of the angiotensin-converting-enzyme (ACE) inhibitor perindopril on physical function in elderly people with functional impairment who had no heart failure or left ventricular systolic dysfunction.MethodsIn this double-blind randomized controlled trial, participants aged 65 years and older who had problems with mobility or functional impairment were randomly assigned to receive either perindopril or placebo for 20 weeks. The primary outcome was the change in the 6-minute walking distance over the 20 weeks. Secondary outcomes were changes in muscle function, daily activity levels, self-reported function and health-related quality of life.ResultsA total of 130 participants were enrolled in the study (mean age 78.7, standard deviation 7.7 years); 95 completed the trial. At 20 weeks, the mean 6-minute walking distance was significantly improved in the perindopril group relative to the placebo group (mean between-group difference 31.4 m, 95% confidence interval [CI] 10.8 to 51.9 m; p = 0.003). There was a significant impact on health-related quality of life: although the mean score for part 1 of the EQ-5D questionnaire deteriorated over time in the placebo group, quality of life was maintained in the perindopril group, for a between-group difference of 0.09 (p = 0.046). There were no significant differences between the 2 groups in the other outcomes.InterpretationUse of the ACE inhibitor perindopril improved exercise capacity in functionally impaired elderly people who had no heart failure and maintained health-related quality of life. The degree of improvement was equivalent to that reported after 6 months of exercise training. (International Standard Randomised Controlled Trial Register no. ISRCTN67679521).

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Correlation between biomarkers of pain in saliva and PAINAD scale in elderly people with cognitive impairment and inability to communicate: descriptive study protocol.

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Correlation between biomarkers of pain in saliva and PAINAD scale in elderly people with cognitive impairment and inability to communicate: descriptive study protocol.

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