The associations of leg lean mass with foot pain, posture and function in the Framingham foot study

Background: Foot disorders are common in older adults and associated with impaired lower extremity function. Reduced muscle mass may play a role in the etiology of foot disorders and consequent poor function. Methods: We examined the association of leg lean mass with foot pain, posture and function among 1,795 individuals (mean age 67 years) from the population-based Framingham Foot Study (2002–2008). Pain was assessed via questionnaire, and a pressure mat classified foot posture (arch: high, low, referent) during standing and function (pronation, supination, referent) during gait. Leg lean mass was measured by whole body dual energy x-ray absorptiometry. Results: In age- and body mass index-adjusted logistic (pain) and multinomial logistic (posture, function) regression models, a 1-standard deviation increase in leg lean mass was associated with lower odds of foot pain (OR = 0.76, 95% CI: 0.68, 0.86) and pronation (OR = 0.76, 95% CI: 0.67, 0.85), and higher odds of supination (OR = 1.17, 95% CI: 1.04, 1.31). Adjustment for sex attenuated these associations. Higher leg lean mass was associated with lower odds of high arch, even after adjustment for sex (OR = 0.73, 95% CI: 0.60, 0.89). Conclusions: Though not related to foot pain or function, reduced leg lean mass was associated with extreme foot posture in older adults. Loss of muscle mass with aging may thus play a role in the etiology of functional impairment due to foot disorders

Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells

Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor. The Lgr5-expressing cells differentiate into hair cells in high yield. From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction. The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity. Targeting supporting cells capable of proliferation and cochlear hair cell replacement could lead to the discovery of hearing loss treatments.United States. National Institutes of Health (DE-013023)United States. National Institutes of Health (DC-007174)United States. National Institutes of Health (DC-013909)United States. National Institutes of Health (RR-00168

Immunologic aspects of the nephrotic syndrome

The nephrotic syndrome is a clinical entity characterized by proteinuria, hypoalbuminemia, edema and hyperlipidemia. All the features of this syndrome are ultimately related to increased permeability of the glomerular capillary to protein. A specific disease entity in its mildest form may result in mild proteinuria insufficient to cause hypoalbuminemia and the other physiological manifestations of the nephrotic syndrome; the same disease in another patient or at another time in the same patient may cause marked proteinuria and the nephrotic state. The principal difference between proteinuria alone and that associated with the nephrotic syndrome in any specific disease would therefore appear to be quantitative, although it is likely that other factors play a role

Characterization of Patients With Axial Spondyloarthritis by Enthesitis Presence: Data from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: To compare the characteristics of patients with axial spondyloarthritis (axSpA) who had enthesitis versus those without enthesitis. METHODS: This study included adult patients with axSpA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry (March 2013 to August 2018). Enthesitis was assessed at enrollment via the Spondyloarthritis Research Consortium of Canada Enthesitis Index. Characteristics were compared between patients with and without enthesitis using t tests or Wilcoxon rank-sum tests for continuous variables and χ RESULTS: Of 477 patients with axSpA, 121 (25.4%) had enthesitis (mean, 3.9 sites) at enrollment. Higher proportions of patients with enthesitis were female and had nonradiographic axSpA than those without enthesitis (both P \u3c 0.05). Additionally, higher proportions of patients with enthesitis had prior biologic (38.8% vs 27.2%) and conventional synthetic disease-modifying antirheumatic drug (csDMARD; 24.8% vs 13.3%) use and were currently receiving a combination of biologics and csDMARDs (28.6% vs 18.1%) than those without enthesitis. Patients with enthesitis had worse disease activity (tender and swollen joint counts, physician global assessment, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondylitis Functional Index), spinal mobility, and quality of life (pain, fatigue, Health Assessment Questionnaire, and EuroQol visual analog scale scores); greater work impairment; and had a history of depression and fibromyalgia than those without enthesitis (all P \u3c 0.05). CONCLUSION: In this US-based real-world study, enthesitis in patients with axSpA was associated with worse disease activity and quality of life than those with no enthesitis

Experts\u27 Advice to Information Systems Doctoral Students

This paper summarizes the results of a panel discussion offering advice to doctoral students in advancing through their programs and getting a start on their career. The panel was held at the 2003 Annual Conference of the Southern Association for Information Systems, and panelists included five senior MIS faculty members who, combined, have chaired over 80 dissertations. Topics included choosing a dissertation topic, dealing with the dissertation committee, completing the dissertation, the job hunt, marketability, building a publication record, and advice for new faculty

Essential role for proteinase-activated receptor-2 in arthritis

Using physiological, pharmacological, and gene disruption approaches, we demonstrate that proteinase-activated receptor-2 (PAR-2) plays a pivotal role in mediating chronic inflammation. Using an adjuvant monoarthritis model of chronic inflammation, joint swelling was substantially inhibited in PAR-2-deficient mice, being reduced by more than fourfold compared with wild-type mice, with virtually no histological evidence of joint damage. Mice heterozygous for PAR-2 gene disruption showed an intermediate phenotype. PAR-2 expression, normally limited to endothelial cells in small arterioles, was substantially upregulated 2 weeks after induction of inflammation, both in synovium and in other periarticular tissues. PAR-2 agonists showed potent proinflammatory effects as intra-articular injection of ASKH95, a novel synthetic PAR-2 agonist, induced prolonged joint swelling and synovial hyperemia. Given the absence of the chronic inflammatory response in the PAR-2-deficient mice, our findings demonstrate a key role for PAR-2 in mediating chronic inflammation, thereby identifying a novel and important therapeutic target for the management of chronic inflammatory diseases such as rheumatoid arthritis

Phase distribution, composition and disorder in Y2(Hf,Sn)2O7 ceramics : insights from solid-state NMR spectroscopy and first-principles calculations

The authors would like to thank the ERC (EU FP7 Consolidator Grant 614290 “‘EXONMR’”), and EPSRC for support for SS and ASG (EP/L005581/1). SEA would like to thank the Royal Society and Wolfson Foundation for a merit award. We acknowledge support from the Collaborative Computational Project on NMR Crystallography CCP-NC funded by EPSRC (EP/M022501/1).A NMR crystallographic approach, combining 89Y, 119Sn and 17O NMR spectroscopy with X-ray diffraction and first-principles calculations has been used investigate the number and type of phases present, and the local structure and disorder in Y2Hf2–xSnxO7 ceramics. Although a phase change is predicted with increasing Hf content, NMR spectra clearly show the presence of a significant two-phase region, with a Sn-rich pyrochlore and relatively Hf-rich defect fluorite phase co-existing for much of the compositional series. A single-phase pyrochlore is found only for the Sn end member, and a single defect fluorite phase only for x = 0 to 0.2. A solid-solution limit of ~10% is seen for the substitution of Hf into Y2Sn2O7, although no evidence is seen for any cation ordering or antisite disorder in this phase. In the defect fluorite phase there is preferential ordering of oxygen vacancies around Sn, which is only ever seen in a six-coordinate environment. The remaining vacancies are more likely to be associated with Hf than with Y, although this distinction is less apparent at higher Sn concentrations. To acquire 17O NMR spectra samples were post-synthetically exchanged with 17O2(g), although high temperatures (> 900 ºC) were required to ensure uniform enrichment of different chemical species. although these 17O NMR spectra confirm the formation of mixed-metal materials and the presence of two phases, more quantitative analysis is hindered by the overlap of signals from pyrochlore and defect fluorite phases. In all cases, DFT calculations play a vital role in the interpretation and assignment of the NMR spectra, and in understanding the local structure and disorder in these complex multi-phase materials.PostprintPostprintPeer reviewe

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

<b>Background</b> Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. <p></p> <b>Methods</b> 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. <p></p> <b>Results</b> People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. <p></p> <b>Conclusion</b> People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

Biomechanical Measures of Neuromuscular Control and Valgus Loading of the Knee Predict Anterior Cruciate Ligament Injury Risk in Female Athletes

Background: Female athletes participating in high-risk sports suffer anterior cruciate ligament injury at a 4- to 6-fold greater rate than do male athletes. Hypothesis: Prescreened female athletes with subsequent anterior cruciate ligament injury will demonstrate decreased neuromuscular control and increased valgus joint loading, predicting anterior cruciate ligament injury risk. Study Design: Cohort study; Level of evidence, 2. Methods: There were 205 female athletes in the high-risk sports of soccer, basketball, and volleyball prospectively measured for neuromuscular control using 3-dimensional kinematics (joint angles) and joint loads using kinetics (joint moments) during a jump-landing task. Analysis of variance as well as linear and logistic regression were used to isolate predictors of risk in athletes who subsequently ruptured the anterior cruciate ligament. Results: Nine athletes had a confirmed anterior cruciate ligament rupture; these 9 had significantly different knee posture and loading compared to the 196 who did not have anterior cruciate ligament rupture. Knee abduction angle (P \u3c .05) at landing was 8° greater in anterior cruciate ligament–injured than in uninjured athletes. Anterior cruciate ligament–injured athletes had a 2.5 times greater knee abduction moment (P \u3c .001) and 20% higher ground reaction force (P \u3c .05), whereas stance time was 16% shorter; hence, increased motion, force, and moments occurred more quickly. Knee abduction moment predicted anterior cruciate ligament injury status with 73% specificity and 78% sensitivity; dynamic valgus measures showed a predictive r 2 of 0.88. Conclusion: Knee motion and knee loading during a landing task are predictors of anterior cruciate ligament injury risk in female athletes. Clinical Relevance: Female athletes with increased dynamic valgus and high abduction loads are at increased risk of anterior cruciate ligament injury. The methods developed may be used to monitor neuromuscular control of the knee joint and may help develop simpler measures of neuromuscular control that can be used to direct female athletes to more effective, targeted interventions