Expression and diagnostic utility of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

Background: Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous group of arthritis occurring in children. Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been recently included in the revised diagnostic criteria for adult onset rheumatoid arthritis. Its diagnostic value in JIA is still debatable. Objective: The study is aimed to investigate the expression and diagnostic utility of anti-CCP antibodies in pediatric JIA in relationship to its various clinical phenotypes. Methods: Forty children and adolescents (13 males, 27 females) with JIA as well as 35 healthy children were enrolled in this cross-sectional study. Serum anti-CCP antibodies were determined by enzymatic immunoassay and its expression was statistically correlated to clinical, laboratory, and radiological data of the patients. Results: Anti-CCP antibodies were positive in 8 (20%) patients while not expressed in the control group. Seven out of the 8 positive cases (87.5%) had polyarticular JIA and only one patient (12.5%) had the oligoarticular onset variety. A significant positive correlation was elicited between the anti-CCP antibody levels and the number of tender joints (r= 0.39), swollen joints (0.68) and disease duration (r = 0.59). Radiographic erosive arthritis was found in 8 patients with positive anti-CCP antibodies; 7 of whom (87.5%) suffered the polyarticular subtype and only one patient (12.5%) had the oligoarticular subtype. All the rheumatoid factor (RF) seropositive patients had positive anti-CCP antibody as well as radiographic erosive arthritis. The overall anti-CCP antibody diagnostic value in our series showed a sensitivity and specificity of 20% and 100% respectively and the positive and negative predictive values were 100%, and 52.2%, respectively. Conclusion: Anti-CCP antibodies have a low sensitivity but high specificity in patients with JIA with a significant relationship to clinical and radiologic severity especially in RF seropositive cases. It may thus have a diagnostic and/or prognostic utility in severe polyarticular onset disease.Keywords: Anti-cyclic citrullinated peptide antibodies; Juvenile idiopathic arthritis; children

Array algorithms for H^2 and H^∞ estimation

Currently, the preferred method for implementing H^2 estimation algorithms is what is called the array form, and includes two main families: square-root array algorithms, that are typically more stable than conventional ones, and fast array algorithms, which, when the system is time-invariant, typically offer an order of magnitude reduction in the computational effort. Using our recent observation that H^∞ filtering coincides with Kalman filtering in Krein space, in this chapter we develop array algorithms for H^∞ filtering. These can be regarded as natural generalizations of their H^2 counterparts, and involve propagating the indefinite square roots of the quantities of interest. The H^∞ square-root and fast array algorithms both have the interesting feature that one does not need to explicitly check for the positivity conditions required for the existence of H^∞ filters. These conditions are built into the algorithms themselves so that an H^∞ estimator of the desired level exists if, and only if, the algorithms can be executed. However, since H^∞ square-root algorithms predominantly use J-unitary transformations, rather than the unitary transformations required in the H^2 case, further investigation is needed to determine the numerical behavior of such algorithms

Using a Non-Image-Based Medium-Throughput Assay for Screening Compounds Targeting N-myristoylation in Intracellular Leishmania Amastigotes

We have refined a medium-throughput assay to screen hit compounds for activity against N-myristoylation in intracellular amastigotes of Leishmania donovani. Using clinically-relevant stages of wild type parasites and an Alamar blue-based detection method, parasite survival following drug treatment of infected macrophages is monitored after macrophage lysis and transformation of freed amastigotes into replicative extracellular promastigotes. The latter transformation step is essential to amplify the signal for determination of parasite burden, a factor dependent on equivalent proliferation rate between samples. Validation of the assay has been achieved using the anti-leishmanial gold standard drugs, amphotericin B and miltefosine, with EC50 values correlating well with published values. This assay has been used, in parallel with enzyme activity data and direct assay on isolated extracellular amastigotes, to test lead-like and hit-like inhibitors of Leishmania Nmyristoyl transferase (NMT). These were derived both from validated in vivo inhibitors of Trypanosoma brucei NMT and a recent high-throughput screen against L. donovani NMT. Despite being a potent inhibitor of L. donovani NMT, the activity of the lead T. brucei NMT inhibitor (DDD85646) against L. donovani amastigotes is relatively poor. Encouragingly, analogues of DDD85646 show improved translation of enzyme to cellular activity. In testing the high-throughput L. donovani hits, we observed macrophage cytotoxicity with compounds from two of the four NMT-selective series identified, while all four series displayed low enzyme to cellular translation, also seen here with the T. brucei NMT inhibitors. Improvements in potency and physicochemical properties will be required to deliver attractive lead-like Leishmania NMT inhibitors

A Brain-Computer Interface Based Attention Training Program for Treating Attention Deficit Hyperactivity Disorder

10.1371/journal.pone.0046692PLoS ONE710

The clinical utility of the continuous performance test and objective measures of activity for diagnosing and monitoring ADHD in children: a systematic review

Attention deficit hyperactivity disorder (ADHD) is typically diagnosed using clinical observation and subjective informant reports. Once children commence ADHD medication, robust monitoring is required to detect partial or non-responses. The extent to which neuropsychological continuous performance tests (CPTs) and objective measures of activity can clinically aid the assessment and titration process in ADHD is not fully understood. This review describes the current evidence base for the use of CPTs and objectively measured activity to support the diagnostic procedure and medication management for children with ADHD. Four databases (PsycINFO, Medline, Allied and Complementary Medicine (AMED) and PsycARTICLES) were systematically searched to understand the current evidence base for: (1) the use of CPTs to aid clinical assessment of ADHD; (2) the use of CPTs to aid medication management; (3) the clinical utility of objective measures of activity in ADHD. Sixty relevant articles were identified. The search revealed six commercially available CPTs that had been reported on for their clinical use. There were mixed findings with regard to the use of CPTs to assess and manage medication, with contrasting evidence on their ability to support clinical decision making. There was a strong evidence base for the use of objective measures of activity to aid ADHD/non-ADHD group differentiation, which appears sensitive to medication effects and would also benefit from further research on their clinical utility. The findings suggest that combining CPTs and an objective measure of activity may be particularly useful as a clinical tool and worthy of further pursuit

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Fractional modeling dynamics of HIV and CD4+ T-cells during primary infection

In this paper, we introduce fractional-order into a model of HIV-1 infection of CD4+ T cells. We study the effect of the changing the average number of viral particles N with different sets of initial conditions on the dynamics of the presented model. Generalized Euler method (GEM) will be used to find a numerical solution of the HIV-1 infection fractional order model

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Patterns of hepatocellular carcinoma incidence in Egypt from a population-based cancer registry

Hepatocellular carcinoma (HCC) is increasing worldwide, and is frequently attributed to rising rates of hepatitis C virus infection and interactions between viral and environmental risk factors. Because of Egypt's unique risk factor profile, we analyzed data from the Gharbiah Population-Based Cancer Registry for the period 1999–2003 to characterize demographic and geographic patterns of cases in this province. Methods:  We calculated age- and sex-specific and age- and sex-standardized HCC incidence rates for the eight districts in Gharbiah. We also compared rates from Gharbiah with the USA (US Surveillance Epidemiology and End Results [SEER] database). Results:  The analysis revealed a higher incidence in males than in females, significant geographic variations among districts, and a higher incidence in Gharbiah than that reported by SEER. Conclusion:  The findings of this study document the heterogeneous distribution of HCC at regional and international levels. This population-based registry offers the opportunity for careful representative studies of various etiologies, particularly infectious and/or environmental factors that may contribute to risk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75374/1/j.1872-034X.2007.00299.x.pd