What is the role body sway deviation and body sway velocity play in postural stability in older adults?

This cross sectional study focused on how Postural Stability (PS) indicators: body sway deviation (BSD) and body sway velocity (BSV), change with age and their association with levels of social and physical activity. Observational study: 80 older adults (aged: 60-96) were purposefully recruited from two sources: the University of the Third Age (TAU) (n = 35) and a residential care home (CH) (n = 45). Differences in the indicators of PS, approximated through Centre of Pressure (COP) measurements, were assessed by the Romberg Stance Test (Test A) subsequently repeated on 10 cm foam surface (Test B), using a Kistler Dynamometric Platform. The RCH Group was older, had higher BMI and was less socially and physically active, showed more body sway in all indicators compared to TAU group. For all participants body sway velocity (BSV) was significantly correlated with age. The strength of correlation of body sway deviation (BSD) with age was also significant but not as strong. The findings indicate in line with previous studies that deterioration in BSV is associated with poor PS more than deterioration in BSD

Multimodal Pain Management in Extremely Low Birth Weight Neonates after Major Abdominal Surgery

Limited data are available in the literature on multimodal pain management in extremely low birth weight (ELBW) neonates. This chapter aimed to summarize current knowledge about the effects of analgesics and sedatives (paracetamol, opioids, benzodiazepines and anaesthetics) on postoperative pain management (≤ 48 hours after surgery). The primary endpoints of postoperative pain management were searched using validated pain assessment instruments, such as pain intensity, excessive sedation, drug consumption or adequate rescue medication. The secondary endpoints are the safety parameters of the drugs used, while the determinants of short/long-term outcome (duration of mechanical ventilation, intraventricular haemorrhage—IVH, periventricular leukomalacia—PVL, postnatal growth restriction, stage of chronic lung disease—CLD or neurodevelopmental outcome according to the Bayley-II Scale of Infant Development at 18–24 months or developmental equivalents at early-school age) were assessed as tertiary endpoints. Additionally, one of the most important key elements of clinical science is known as clinical research study validation, including specific tools and techniques within the validation processes. This chapter focuses on postoperative multimodal pain management, including the implementation of pain assessment tools and analgesic and sedative dosing regimens needed to achieve the efficacy and safety goals of an optimal pain profile in ELBW neonates; only proven non-pharmacological procedures are not included

What is the role body sway deviation and body sway velocity play in postural stability in older adults?

Summary: This cross sectional study focused on how Postural Stability (PS) indicators: body sway deviation (BSD) and body sway velocity (BSV), change with age and their association with levels of social and physical activity. Observational study: 80 older adults (aged: 60–96) were purposefully recruited from two sources: the University of the Third Age (TAU) (n = 35) and a residential care home (CH) (n = 45). Differences in the indicators of PS, approximated through Centre of Pressure (COP) measurements, were assessed by the Romberg Stance Test (Test A) subsequently repeated on 10 cm foam surface (Test B), using a Kistler® Dynamometric Platform. The RCH Group was older, had higher BMI and was less socially and physically active, showed more body sway in all indicators compared to TAU group. For all participants body sway velocity (BSV) was significantly correlated with age. The strength of correlation of body sway deviation (BSD) with age was also significant but not as strong. The findings indicate in line with previous studies that deterioration in BSV is associated with poor PS more than deterioration in BSD

High prevalence of anti-C1q antibodies in biopsy-proven active lupus nephritis

Background. Anti-C1q antibodies (anti-C1q) have been shown to correlate positively with systemic lupus erythematosus (SLE) nephritis. Several clinical studies indicated a high negative predictive value, suggesting that active lupus nephritis is rarely seen in patients with no anti-C1q. However, the true prevalence of anti-C1q at the time of active lupus nephritis has not been well established. The aim of this study was to determine prospectively the prevalence of anti-C1q in proven active lupus nephritis at the time of the renal biopsy. Methods. In this prospective multi-centre study, we investigated adult SLE patients undergoing renal biopsy for suspected active lupus nephritis. Serum samples were taken at the time of the biopsy and analysed for the presence of anti-C1q in a standardized way. The activity of lupus nephritis was classified according to the renal histology. Biopsies were also analysed for the presence of glomerular IgG, C1q and C3 deposition. Results. A total of 38 patients fulfilling at least 4/11 American College of Rheumatology (ACR) criteria for the diagnosis of SLE were included. Out of this, 36 patients had proliferative (class II, III or IV) and two had class V lupus nephritis. All but one patient with proliferative lupus nephritis were positive for anti-C1q (97.2%) compared with the 35% of control SLE patients with inactive lupus nephritis and 25% of SLE patients without lupus nephritis ever. All patients were positive for glomerular C1q (36/36) and 37/38 patients had glomerular IgG deposits. Anti-C1q strongly decreased during successful treatment. Conclusions. Anti-C1q have a very high prevalence in biopsy-proven active lupus nephritis, thus a negative test result almost excludes active nephritis. The data support the hypothesis of a pathogenic role of anti-C1q in lupus nephriti

High prevalence of anti-C1q antibodies in biopsy-proven active lupus nephritis

BACKGROUND: Anti-C1q antibodies (anti-C1q) have been shown to correlate positively with systemic lupus erythematosus (SLE) nephritis. Several clinical studies indicated a high negative predictive value, suggesting that active lupus nephritis is rarely seen in patients with no anti-C1q. However, the true prevalence of anti-C1q at the time of active lupus nephritis has not been well established. The aim of this study was to determine prospectively the prevalence of anti-C1q in proven active lupus nephritis at the time of the renal biopsy. METHODS: In this prospective multi-centre study, we investigated adult SLE patients undergoing renal biopsy for suspected active lupus nephritis. Serum samples were taken at the time of the biopsy and analysed for the presence of anti-C1q in a standardized way. The activity of lupus nephritis was classified according to the renal histology. Biopsies were also analysed for the presence of glomerular IgG, C1q and C3 deposition. RESULTS: A total of 38 patients fulfilling at least 4/11 American College of Rheumatology (ACR) criteria for the diagnosis of SLE were included. Out of this, 36 patients had proliferative (class II, III or IV) and two had class V lupus nephritis. All but one patient with proliferative lupus nephritis were positive for anti-C1q (97.2%) compared with the 35% of control SLE patients with inactive lupus nephritis and 25% of SLE patients without lupus nephritis ever. All patients were positive for glomerular C1q (36/36) and 37/38 patients had glomerular IgG deposits. Anti-C1q strongly decreased during successful treatment. CONCLUSIONS: Anti-C1q have a very high prevalence in biopsy-proven active lupus nephritis, thus a negative test result almost excludes active nephritis. The data support the hypothesis of a pathogenic role of anti-C1q in lupus nephritis

NRF2 Activation Restores Disease Related Metabolic Deficiencies in Olfactory Neurosphere-Derived Cells from Patients with Sporadic Parkinson's Disease

Extent: 14p.Background: Without appropriate cellular models the etiology of idiopathic Parkinson’s disease remains unknown. We recently reported a novel patient-derived cellular model generated from biopsies of the olfactory mucosa (termed olfactory neurosphere-derived (hONS) cells) which express functional and genetic differences in a disease-specific manner. Transcriptomic analysis of Patient and Control hONS cells identified the NRF2 transcription factor signalling pathway as the most differentially expressed in Parkinson’s disease. Results: We tested the robustness of our initial findings by including additional cell lines and confirmed that hONS cells from Patients had 20% reductions in reduced glutathione levels and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium, inner salt] metabolism compared to cultures from healthy Control donors. We also confirmed that Patient hONS cells are in a state of oxidative stress due to higher production of H2O2 than Control cultures. siRNA-mediated ablation of NRF2 in Control donor cells decreased both total glutathione content and MTS metabolism to levels detected in cells from Parkinson’s Disease patients. Conversely, and more importantly, we showed that activation of the NRF2 pathway in Parkinson’s disease hONS cultures restored glutathione levels and MTS metabolism to Control levels. Paradoxically, transcriptomic analysis after NRF2 pathway activation revealed an increased number of differentially expressed mRNAs within the NRF2 pathway in L-SUL treated Patient-derived hONS cells compared to L-SUL treated Controls, even though their metabolism was restored to normal. We also identified differential expression of the PI3K/AKT signalling pathway, but only post-treatment. Conclusions: Our results confirmed NRF2 as a potential therapeutic target for Parkinson’s disease and provided the first demonstration that NRF2 function was inducible in Patient-derived cells from donors with uniquely varied genetic backgrounds. However, our results also demonstrated that the response of PD patient-derived cells was not co-ordinated in the same way as in Control cells. This may be an important factor when developing new therapeutics.Anthony L. Cook, Alejandra M. Vitale, Sugandha Ravishankar, Nicholas Matigian, Greg T. Sutherland, Jiangou Shan, Ratneswary Sutharsan, Chris Perry, Peter A. Silburn, George D. Mellick, Murray L. Whitelaw, Christine A. Wells, Alan Mackay-Sim and Stephen A. Woo

A Systems Biology Approach Reveals the Role of a Novel Methyltransferase in Response to Chemical Stress and Lipid Homeostasis

Using small molecule probes to understand gene function is an attractive approach that allows functional characterization of genes that are dispensable in standard laboratory conditions and provides insight into the mode of action of these compounds. Using chemogenomic assays we previously identified yeast Crg1, an uncharacterized SAM-dependent methyltransferase, as a novel interactor of the protein phosphatase inhibitor cantharidin. In this study we used a combinatorial approach that exploits contemporary high-throughput techniques available in Saccharomyces cerevisiae combined with rigorous biological follow-up to characterize the interaction of Crg1 with cantharidin. Biochemical analysis of this enzyme followed by a systematic analysis of the interactome and lipidome of CRG1 mutants revealed that Crg1, a stress-responsive SAM-dependent methyltransferase, methylates cantharidin in vitro. Chemogenomic assays uncovered that lipid-related processes are essential for cantharidin resistance in cells sensitized by deletion of the CRG1 gene. Lipidome-wide analysis of mutants further showed that cantharidin induces alterations in glycerophospholipid and sphingolipid abundance in a Crg1-dependent manner. We propose that Crg1 is a small molecule methyltransferase important for maintaining lipid homeostasis in response to drug perturbation. This approach demonstrates the value of combining chemical genomics with other systems-based methods for characterizing proteins and elucidating previously unknown mechanisms of action of small molecule inhibitors