Impact of Stretching Exercises on Work-Related Musculoskeletal Disorders: A Systematic Review

Objective: This study aims to compile the latest information concerning workplace stretching regimens and to give a panoramic view of their effectiveness in reducing work-related Musculoskeletal disorders (MSDs). Methods: Searching MEDLINE, Embase, CINAHL, PEDro, Web of Science, Scopus, Google Scholar, SPORTDiscus and PubMed databases from 2010 to 2022 found 723 eligible studies, based on predefined inclusion criteria. Results: In the review, 14 included studies recruited subjects aged 18 years, with males (n=813), females (n=5141), and some research did not identify gender (n=3). The included studies were of both high (n=6) and low quality (n=8). Seven studies revealed stretching exercises to be an effective and safe non-pharmacological intervention for MSDs, and one study included an active control group observed better improvement in the treatment group. Four trials showed a significant effect from stretching exercises as a stand-alone treatment. Three studies revealed that stretching exercises had a meaningful and major effect on MSDs complaints, while two studies reported no significant results when utilizing Anti-fatigue mats in addition to stretching. Conclusion: The current study indicated that stretching exercises are a crucial and useful technique for preventing and treating pain and function in Work-related MSDs affecting the neck, shoulder, back, etc. Workplace/ergonomic changes can enhance the results of stretching exercises

Proteome-based plasma biomarkers for Alzheimer's disease

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and α-2-macroglobulin (α- 2M). Using semi-quantitative immunoblotting, the elevation of CFH and α- 2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as α- 2M may be a specific markers of this illness. © 2006 The Author(s).link_to_subscribed_fulltex

Receptor-Associated Protein (RAP) Plays a Central Role in Modulating Aβ Deposition in APP/PS1 Transgenic Mice

BACKGROUND: Receptor associated protein (RAP) functions in the endoplasmic reticulum (ER) to assist in the maturation of several membrane receptor proteins, including low density lipoprotein receptor-related protein (LRP) and lipoprotein receptor 11 (SorLA/LR11). Previous studies in cell and mouse model systems have demonstrated that these proteins play roles in the metabolism of the amyloid precursor protein (APP), including processes involved in the generation, catabolism and deposition of beta-amyloid (Abeta) peptides. METHODOLOGY/PRINCIPAL FINDINGS: Mice transgenic for mutant APPswe and mutant presenilin 1 (PS1dE9) were mated to mice with homozygous deletion of RAP. Unexpectedly, mice that were homozygous null for RAP and transgenic for APPswe/PS1dE9 showed high post-natal mortality, necessitating a shift in focus to examine the levels of amyloid deposition in APPswe/PS1dE9 that were hemizygous null for RAP. Immunoblot analysis confirmed 50% reductions in the levels of RAP with modest reductions in the levels of proteins dependent upon RAP for maturation [LRP trend towards a 20% reduction ; SorLA/LR11 statistically significant 15% reduction (p<0.05)]. Changes in the levels of these proteins in the brains of [APPswe/PS1dE9](+/-)/RAP(+/-) mice correlated with 30-40% increases in amyloid deposition by 9 months of age. CONCLUSIONS/SIGNIFICANCE: Partial reductions in the ER chaperone RAP enhance amyloid deposition in the APPswe/PS1dE9 model of Alzheimer amyloidosis. Partial reductions in RAP also affect the maturation of LRP and SorLA/LR11, which are each involved in several different aspects of APP processing and Abeta catabolism. Together, these findings suggest a central role for RAP in Alzheimer amyloidogenesis

Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice

As impaired insulin signalling (IIS) is a risk factor for Alzheimer's disease we crossed mice (Tg2576) over-expressing human amyloid precursor protein (APP), with insulin receptor substrate 2 null (Irs2(-/-)) mice which develop insulin resistance. The resulting Tg2576/Irs2(-/-) animals had increased tau phosphorylation but a paradoxical amelioration of Abeta pathology. An increase of the Abeta binding protein transthyretin suggests that increased clearance of Abeta underlies the reduction in plaques. Increased tau phosphorylation correlated with reduced tau-phosphatase PP2A, despite an inhibition of the tau-kinase glycogen synthase kinase-3. Our findings demonstrate that disruption of IIS in Tg2576 mice has divergent effects on pathological processes-a reduction in aggregated Abeta but an increase in tau phosphorylation. However, as these effects are accompanied by improvement in behavioural deficits, our findings suggest a novel protective effect of disrupting IRS2 signalling in AD which may be a useful therapeutic strategy for this condition

p68/DdX5 supports β-Catenin &amp; RNAP II during androgen receptor mediated transcription in prostate cancer

The DEAD box RNA helicase p68 (Ddx5) is an important androgen receptor (AR) transcriptional co-activator in prostate cancer (PCa) and is over-expressed in late stage disease. β-Catenin is a multifunctional protein with important structural and signalling functions which is up-regulated in PCa and similar to p68, interacts with the AR to co-activate expression of AR target genes. Importantly, p68 forms complexes with nuclear β-Catenin and promotes gene transcription in colon cancer indicating a functional interplay between these two proteins in cancer progression. In this study, we explore the relationship of p68 and β-Catenin in PCa to assess their potential co-operation in AR-dependent gene expression, which may be of importance in the development of castrate resistant prostate cancer (CRPCa). We use immunoprecipitation to demonstrate a novel interaction between p68 and β-Catenin in the nucleus of PCa cells, which is androgen dependent in LNCaP cells but androgen independent in a hormone refractory derivative of the same cell line (representative of the CRPCa disease type). Enhanced AR activity is seen in androgen-dependent luciferase reporter assays upon transient co-transfection of p68 and β-Catenin as an additive effect, and p68-depleted Chromatin-Immunoprecipitation (ChIP) showed a decrease in the recruitment of the AR and β-Catenin to androgen responsive promoter regions. In addition, we found p68 immunoprecipitated with the processive and non-processive form of RNA polymerase II (RNAP II) and show p68 recruited to elongating regions of the AR mediated PSA gene, suggesting a role for p68 in facilitating RNAP II transcription of AR mediated genes. These results suggest p68 is important in facilitating β-Catenin and AR transcriptional activity in PCa cells

A Factor Graph Nested Effects Model To Identify Networks from Genetic Perturbations

Complex phenotypes such as the transformation of a normal population of cells into cancerous tissue result from a series of molecular triggers gone awry. We describe a method that searches for a genetic network consistent with expression changes observed under the knock-down of a set of genes that share a common role in the cell, such as a disease phenotype. The method extends the Nested Effects Model of Markowetz et al. (2005) by using a probabilistic factor graph to search for a network representing interactions among these silenced genes. The method also expands the network by attaching new genes at specific downstream points, providing candidates for subsequent perturbations to further characterize the pathway. We investigated an extension provided by the factor graph approach in which the model distinguishes between inhibitory and stimulatory interactions. We found that the extension yielded significant improvements in recovering the structure of simulated and Saccharomyces cerevisae networks. We applied the approach to discover a signaling network among genes involved in a human colon cancer cell invasiveness pathway. The method predicts several genes with new roles in the invasiveness process. We knocked down two genes identified by our approach and found that both knock-downs produce loss of invasive potential in a colon cancer cell line. Nested effects models may be a powerful tool for inferring regulatory connections and genes that operate in normal and disease-related processes

Use of Catheter Lock Solutions in Patients Receiving Home Parenteral Nutrition: A Systematic Review and Individual-Patient Data Meta-Analysis

BACKGROUND: Use of catheter lock solutions (CLSs) as a strategy to prevent catheter-related bloodstream infections (CRBSIs) has been evaluated in recent clinical trials. Our aim was to identify the most effective CLS formulation in patients receiving home parenteral nutrition (HPN). METHODS: We conducted a systematic review and individual-patient data meta-analysis (IPDMA). Prospective randomized clinical trials in adult HPN patients using CLS were identified from PubMed, EMBASE, Web of Science, CINAHL, Cochrane library, and ClinicalTrials.gov. Primary outcome was the number of CRBSIs per 1000 catheter days for each CLS. Other outcomes included time to CRBSI and identification of patients with a higher risk for CRBSIs. RESULTS: In total, 1107 studies were screened for eligibility, of which three studies comprising 162 HPN patients and 45,695 catheter days were included in the IPDMA. CRBSI rates were significantly decreased in patients using taurolidine (rate 0.13; 95% confidence interval [CI], 0.05-0.32) when compared with saline (rate 0.74; 95% CI, 0.31-1.74; P = .002) or heparin (rate 2.01; 95% CI, 1.03-3.91; P < .001). The cumulative proportion of CRBSI-free patients using taurolidine, saline, and heparin after 1 year was 88%, 56%, and 14%, respectively. Three risk factors for CRBSIs were identified: type of CLS, intestinal dysmotility as underlying condition, and use of central venous catheters. CONCLUSIONS: Taurolidine was the most effective CLS formulation in HPN patients for the prevention of CRBSIs. We suggest discussing with patients the benefits and risks when starting taurolidine, especially in patients who are considered to have a higher risk for CRBSIs

Revision 1; date: 06.16.04

FAST WAVELET ESTIMATION OF WEAK BIOSIGNALS Wavelet based signal processing has become commonplace in the signal processing community over the past decade and wavelet based software tools and integrated circuits are now commercially available. One of the most important applications of wavelets is in removal of noise from signals, called denoising, accomplished by thresholding wavelet coefficients in order to separate signal from noise. Substantial work in this area was summarized by Donoho and colleagues at Stanford University, who developed a variety of algorithms for conventional denoising. However, conventional denoising fails for signals with low signal-to-noise ratio (SNR). Electrical signals acquired from the human body, called biosignals, commonly have below 0 dB SNR. Synchronous linear averaging of a large number of acquired data frames is universally used to increase the SNR of weak biosignals. A novel wavelet-based estimator is presented for fast estimation of such signals. The new estimation algorithm provides a faster rate of convergence to the underlying signal than linear averaging. The algorithm is implemented for processing of auditory brainstem response (ABR) and of auditory middle latency evoke