Defining Optimal Self-Management in Osteoarthritis: Racial Differences in a Population-Based Sample

The aim of this study was to examine optimal self-management in osteoarthritis and its association with patient-reported outcomes. We recruited a population-based sample of Medicare beneficiaries (n = 551) residing in Allegheny County, PA, USA and elicited an expanded set of self-management behaviors using open-ended inquiry. We defined optimal self-management according to clinical recommendations, including use of hot compresses on affected joints, alteration of activity, and exercise. Only 20% practiced optimal self-management as defined by two or more of these criteria. Optimal and suboptimal self-managers did not differ in sociodemographic features. Both white and African–Americans who practiced optimal self-management reported significantly less pain, but the benefit was greatest in severe disease for whites and for mild-moderate disease among African–Americans. This backdrop of naturally occurring self-management behaviors may be important to recognize in planning programs that seek to bolster self-management skills.     

Cor triatriatum sinistrum. Diagnostic features on cross sectional echocardiography

M mode and cross sectional echocardiography was carried out in three cases of cor triatriatum sinistrum (two infants and one adult). In two cases a peculiar double arch appearance, not previously reported, was found. All three cases were referred for surgery without cardiac catheterisation, and the diagnosis proved to be correct. The characteristic echocardiographic feature of cor triatriatum is an intra-atrial membrane detected in multiple planes of examination, curving anteroinferiorly and inserting some distance away from the mitral valve ring, proximal to the left atrial appendage. Superiorly the membrane runs parallel to, and a short distance behind, the aortic root creating a superior recess of the distal left atrial chamber. These features differentiate cor triatriatum from a supravalvar mitral ring. During diastole the membrane moves forward towards the mitral valve funnel. This, together with the arching appearance of the membrane on four chamber views and the more superior position of the membrane, makes it possible to distinguish cor triatriatum from total anomalous pulmonary venous drainage to the coronary sinus. From a review of past experience at the Brompton Hospital of the diagnostic accuracy of cardiac catheterisation in this condition, it is concluded that cross sectional echocardiography is superior to angiography as a technique for diagnosing cor triatriatum.     

Recognition of left coronary artery fistula to the left and right ventricles by contrast echocardiography

A coronary-cameral fistula was inspected clinically by two-dimensional and pulsed Doppler ultrasound. At cardiac catheterization a fistulous connection between the left coronary artery and the right ventricle was observed. Contrast echocardiography using agitated saline solution injected into the aortic catheter clearly showed the passage of microcavitations into the left and the right ventricles confirming the connection of the fistula to both chambers. Contrast echocardiography is a valuable technique that can help define the site of drainage of coronary artery fistulas.     

Inhibitory Effects of Incomplete Freund's Adjuvant on Experimental Autoimmune Encephalomyelitis

Freund's incomplete adjuvant (IFA), an aqueous/oil emulsion that is widely used in combination with antigenic proteins and peptides to induce tolerance, is considered to be immunologically inert. However, sporadic reports indicate that IFA may itself have inhibitory properties on induction of adjuvant induced arthritis and spontaneous diabetes. In the current study, the effects of IFA/saline were evaluated on the induction of experimental autoimmune encephalomyelitis (EAE) in three different strains of mice. IFA/saline given i.p. in two doses of >100 &#117 &#119 l 10 &#117 days apart were found to inhibit EAE induction to varying degrees in all three strains of mice in a dose dependent fashion. The IFA/saline injections inhibited both mitogen and antigen-induced T cell proliferation, induced elevated secretion of IFN- &#110 and IL-10 by neuroantigen specific T cells, and reduced expression of cytokines, chemokines, and chemokine receptors of CNS-infiltrating mononuclear cells. These data demonstrate for the first time a direct inhibitory effect of IFA/saline on EAE, and re-emphasize the need to properly control experiments using IFA to induce antigen-specific tolerance.     

The relationship between smartphone use and subjective musculoskeletal symptoms and university students

[Purpose] The purpose of this study was to investigate the use of smartphones by university students in selected areas, their musculoskeletal symptoms, and the associated hazard ratio. [Subjects and Methods] This involved the completion of a self-administered questionnaire by dental hygiene students in Seoul, Gyeonggido, and Gyeongsangbukdo. The 292 completed copies of the questionnaire were then analyzed. [Results] The most painful body regions after the use of smartphones were found to be the shoulders and neck. In the musculoskeletal system, back pain was found to have a positive correlation with the size of the smartphone’s liquid crystal display (LCD) screen, and pain in legs and feet were found to have a negative correlation with the length of time that the smartphone was used. As a result, it was revealed that the use of a smartphone was correlated with musculoskeletal symptoms. [Conclusion] Therefore, in today’s environment, where the use of smartphones is on the rise, it is necessary to improve the ways that they are used and to develop a preventive program to alleviate the symptoms of musculoskeletal damage.Key words: Smartphone, Musculoskeletal symptoms, Prevent     

The life cycle of the steroidogenic acute regulatory (StAR) protein: from transcription through proteolysis

The Steroidogenic Acute Regulatory (StAR) protein is a mitochondrial protein required for the transport of cholesterol substrate to the P450scc enzyme located in the inner mitochondrial membranes of steroid producing cells. This study suggests that the acute regulation of the rodent StAR gene in the ovary is mediated by two factors, C/EBPbeta and GATA-4. Once translated, the StAR precursor protein is either imported into the mitochondria, or it is rapidly degraded in the cytosol. We predicted that in order to perpetuate StAR activity cycles, imported StAR should turn over rapidly to avoid a potentially harmful accumulation of the protein in sub-mitochondrial compartments. Pulse-chase experiments in metabolically labeled cells showed that: (a) the turnover rate of mature mitochondrial StAR protein (30 kDa) is much faster (t(1/2) = 4-5 h) than that of other mitochondrial proteins; (b) dissipation of the inner membrane potential (-delta psi) by carbonyl cyanide m-chlorophenylhydrazone (mCCCP) accelerates the mitochondrial degradation of StAR; (c) unexpectedly, the mitochondrial degradation of StAR is inhibited by MG132 and lactacystin, but not by epoxomicin. Furthermore, StAR degradation becomes inhibitor-resistant two hours after import. Therefore, these studies suggest a bi-phasic route of StAR turnover in the mitochondria. Shortly after import, StAR is degraded by inhibitor-sensitive protease(s) (phase I), whereas at later times, StAR turnover proceeds to completion through an MG132-resistant proteolytic activity (phase II). Collectively, this study defines StAR as a unique protein that can authentically be used to probe multiple proteolytic activities in mammalian mitochondria.     

Induction of ppp(A2''p)nA-dependent RNase in murine JLS-V9R cells during growth inhibition.

We recently reported that interferon induces the synthesis of ppp(A2'p)nA(n = 2 to greater than or equal to 4) (2-5A)-dependent RNase in the murine cell line JLS-V9R. These cells normally contain very low levels of the nuclease; after interferon treatment, however, they develop levels approaching those found in murine L or Ehrlich ascites tumor cells. Here, we report a similar increase in the nuclease levels in JLS-V9R cells during the transition from the subconfluent actively growing state to the confluent stationary phase. Levels of 2-5A synthetase increased in parallel with the nuclease. The induced levels of both the nuclease and synthetase returned to low basal amounts after trypsinization, dilution, and culturing of the cells at subconfluent densities. The addition of anti-murine interferon (alpha + beta) antibodies to the medium did not affect the induction of the nuclease nor could any interferon be detected in the culture supernatants as determined by the lack of antiviral activity. The increase in the enzymes was not, therefore, due to the spontaneous production of interferon. The induction of the nuclease during confluency preceded an inhibition of [3H]-thymidine incorporation by the cells into DNA. The regulation of the 2-5A-dependent RNase in JLS-V9R cells may, therefore, be related to the control of cell growth.     

Lupus-associated causal mutation in neutrophil cytosolic factor 2 (NCF2) brings unique insights to the structure and function of NADPH oxidase

Systemic lupus erythematosus (SLE), the prototypic systemic autoimmune disease, is a debilitating multisystem autoimmune disorder characterized by chronic inflammation and extensive immune dysregulation in multiple organ systems, resulting in significant morbidity and mortality. Here, we present a multidisciplinary approach resulting in the identification of neutrophil cytosolic factor 2 (NCF2) as an important risk factor for SLE and the detailed characterization of its causal variant. We show that NCF2 is strongly associated with increased SLE risk in two independent populations: childhood-onset SLE and adult-onset SLE. The association between NCF2 and SLE can be attributed to a single nonsynonymous coding mutation in exon 12, the effect of which is the substitution of histidine-389 with glutamine (H389Q) in the PB1 domain of the NCF2 protein, with glutamine being the risk allele. Computational modeling suggests that the NCF2 H389Q mutation reduces the binding efficiency of NCF2 with the guanine nucleotide exchange factor Vav1. The model predicts that NCF2/H389 residue interacts with Vav1 residues E509, N510, E556, and G559 in the ZF domain of Vav1. Furthermore, replacing H389 with Q results in 1.5 kcal/mol weaker binding. To examine the effect of the NCF2 H389Q mutation on NADPH oxidase function, site-specific mutations at the 389 position in NCF2 were tested. Results show that an H389Q mutation causes a twofold decrease in reactive oxygen species production induced by the activation of the Vav-dependent Fcγ receptor-elicited NADPH oxidase activity. Our study completes the chain of evidence from genetic association to specific molecular function.