Specific premature epigenetic aging of cartilage in osteoarthritis

Osteoarthritis (OA) is a disease affecting multiple tissues of the joints in the elderly, but most notably articular cartilage. Premature biological aging has been described in this tissue and in blood cells, suggesting a systemic component of premature aging in the pathogenesis of OA. Here, we have explored epigenetic aging in OA at the local (cartilage and bone) and systemic (blood) levels. Two DNA methylation age‐measures (DmAM) were used: the multi‐tissue age estimator for cartilage and bone; and a blood‐specific biomarker for blood. Differences in DmAM between OA patients and controls showed an accelerated aging of 3.7 years in articular cartilage (95 % CI = 1.1 to 6.3, P = 0.008) of OA patients. By contrast, no difference in epigenetic aging was observed in bone (0.04 years; 95 % CI = ‐1.8 to 1.9, P = 0.3) and in blood (‐0.6 years; 95 % CI = ‐1.5 to 0.3, P = 0.2) between OA patients and controls. Therefore, premature epigenetic aging according to DNA methylation changes was specific of OA cartilage, adding further evidence and insight on premature aging of cartilage as a component of OA pathogenesis that reflects damage and vulnerability

Radiographic knee osteoarthritis in ex-elite table tennis players

<p>Abstract</p> <p>Background</p> <p>Table tennis involves adoption of the semi-flexed knee and asymmetrical torsional trunk movements creating rotational torques on the knee joint which may predispose players to osteoarthritis (OA) of the knee. This study aims to compare radiographic signs of knee OA and associated functional levels in ex-elite male table tennis players and control subjects.</p> <p>Methods</p> <p>Study participants were 22 ex-elite male table tennis players (mean age 56.64 ± 5.17 years) with 10 years of involvement at the professional level and 22 non-athletic males (mean age 55.63 ± 4.08 years) recruited from the general population. A set of three radiographs taken from each knee were evaluated by an experienced radiologist using the Kellgren and Lawrence (KL) scale (0-4) to determine radiographic levels of OA severity. The intercondylar distance was taken as a measure of lower limb angulation. Participants also completed the pain, stiffness, and physical function categories of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) 3.1 questionnaire.</p> <p>Results</p> <p>The results showed 78.3% of the ex-elite table tennis players and 36.3% of controls had varying signs of radiographic knee OA with a significant difference in the prevalence levels of definite radiographic OA (KL scale > 2) found between the two groups (<it>P </it>≤ 0.001). Based on the WOMAC scores, 68.2% of the ex-elite table tennis players reported symptoms of knee pain compared with 27.3% of the controls (<it>p </it>= 0.02) though no significant differences were identified in the mean physical function or stiffness scores between the two groups. In terms of knee alignment, 73.7% of the ex-elite athletes and 32% of the control group had signs of altered lower limb alignment (genu varum) (<it>p </it>= 0.01). Statistical differences were found in subjects categorized as having radiographic signs of OA and altered lower limb alignment (<it>p </it>= 0.03).</p> <p>Conclusions</p> <p>Ex-elite table tennis players were found to have increased levels of radiological signs of OA in the knee joint though this did not transpire through to altered levels of physical disability or knee stiffness in these players when compared with subjects from the general population suggesting that function in these players is not severely impacted upon.</p

MFA11 (MFA 2011)

Catalogue of a culminating student exhibition held at the Mildred Lane Kemper Art Museum, May 6-Aug. 1, 2011. Content includes Introduction / Buzz Spector -- Patricia Olynyk -- Marshall N. Klimasewiski -- John Talbott Allen -- Meghan Bean -- Shira Berkowitz / Maggie Stanley Majors -- Darrick Byers, Bryce Olen Robinson -- Jisun Choi -- Zlatko Ćosić -- James R. Daniels -- Kara Daving -- Andrea Degener -- Kristin Fleischmann / Randi Shapiro -- William Frank / Lawrence Ypil -- Nicholas Kania -- Katherine McCullough -- Jordan McGirk / Aditi Machado -- Zachary Miller -- Esther Murphy / Maggie Stanley Majors -- Kathryn Neale -- Christopher Ottinger / Melissa Olson -- Maia Palmer -- Nicole Petrescu / Melissa Olson -- Lauren Pressler / Randi Shapiro -- Whitney Sage / Aliya A. Reich -- Donna Smith.https://openscholarship.wustl.edu/books/1005/thumbnail.jp

Learning behaviours in the workplace: The role of high-quality interpersonal relationships and psychological safety

Organizational learning is an important means for improving performance. Learning is a process, that is, often relational in the sense of relying on interactions between people to determine what needs improving and how to do it. This study addresses the question of how the quality of work relationships facilitates learning behaviours in organizations through the ways it contributes to psychological safety. Data collected from 212 part-time students who hold full-time jobs in organizations operating in a wide variety of industries show that capacities of high-quality relationships (measured at time 1) are positively associated with psychological safety, which, in turn, are related to higher levels of learning behaviours (measured at time 2). The results also show that experiences of high-quality relationships (measured at time 1) are both directly and indirectly (through psychological safety) associated with learning behaviours (measured at time 2). These findings shed light on the importance of quality relationships in the workplace for cultivating and developing perceptions of psychological safety and ultimately learning behaviours in organizations. Copyright © 2008 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61533/1/932_ftp.pd

Compensatory Motor Neuron Response to Chromatolysis in the Murine hSOD1(G93A) Model of Amyotrophic Lateral Sclerosis

We investigated neuronal self-defense mechanisms in a murine model of amyotrophic lateral sclerosis (ALS), the transgenic hSOD1(G93A), during both the asymptomatic and symptomatic stages. This is an experimental model of endoplasmic reticulum (ER) stress with severe chromatolysis. As a compensatory response to translation inhibition, chromatolytic neurons tended to reorganize the protein synthesis machinery at the perinuclear region, preferentially at nuclear infolding domains enriched in nuclear pores. This organization could facilitate nucleo-cytoplasmic traffic of RNAs and proteins at translation sites. By electron microscopy analysis, we observed that the active euchromatin pattern and the reticulated nucleolar configuration of control motor neurons were preserved in ALS chromatolytic neurons. Moreover the 5'-fluorouridine (5'-FU) transcription assay, at the ultrastructural level, revealed high incorporation of the RNA precursor 5'-FU into nascent RNA. Immunogold particles of 5'-FU incorporation were distributed throughout the euchromatin and on the dense fibrillar component of the nucleolus in both control and ALS motor neurons. The high rate of rRNA transcription in ALS motor neurons could maintain ribosome biogenesis under conditions of severe dysfunction of proteostasis. Collectively, the perinuclear reorganization of protein synthesis machinery, the predominant euchromatin architecture, and the active nucleolar transcription could represent compensatory mechanisms in ALS motor neurons in response to the disturbance of ER proteostasis. In this scenario, epigenetic activation of chromatin and nucleolar transcription could have important therapeutic implications for neuroprotection in ALS and other neurodegenerative diseases. Although histone deacetylase inhibitors are currently used as therapeutic agents, we raise the untapped potential of the nucleolar transcription of ribosomal genes as an exciting new target for the therapy of some neurodegenerative diseases

Efficacy and Safety of a New 20% Immunoglobulin Preparation for Subcutaneous Administration, IgPro20, in Patients With Primary Immunodeficiency

Subcutaneous human IgG (SCIG) therapy in primary immunodeficiency (PID) offers sustained IgG levels throughout the dosing cycle and fewer adverse events (AEs) compared to intravenous immunoglobulin (IVIG). A phase I study showed good local tolerability of IgPro20, a new 20% liquid SCIG stabilized with L-proline. A prospective, open-label, multicenter, single-arm, phase III study evaluated the efficacy and safety of IgPro20 in patients with PID over 15 months. Forty-nine patients (5–72 years) previously treated with IVIG received weekly subcutaneous infusions of IgPro20. The mean serum IgG level was 12.5 g/L. No serious bacterial infections were reported. There were 96 nonserious infections (rate 2.76/patient per year). The rate of days missed from work/school was 2.06/patient per year, and the rate of hospitalization was 0.2/patient per year. Ninety-nine percent of AEs were mild or moderate. No serious, IgPro20-related AEs were reported. IgPro20 effectively protected patients with PID against infections and maintained serum IgG levels without causing unexpected AEs