Oligoclonal bands predict multiple sclerosis in children with optic neuritis

We retrospectively evaluated predictors of conversion to multiple sclerosis (MS) in 357 children with isolated optic neuritis (ON) as a first demyelinating event who had a median follow‐up of 4.0 years. Multiple Cox proportional‐hazards regressions revealed abnormal cranial magnet resonance imaging (cMRI; hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.39–10.39, p < 0.001), presence of cerebrospinal fluid immunoglobulin G oligoclonal bands (OCB; HR = 3.69, 95% CI = 2.32–5.86, p < 0.001), and age (HR = 1.08 per year of age, 95% CI = 1.02–1.13, p = 0.003) as independent predictors of conversion, whereas sex and laterality (unilateral vs bilateral) had no influence. Combined cMRI and OCB positivity indicated a 26.84‐fold higher HR for developing MS compared to double negativity (95% CI = 12.26−58.74, p < 0.001). Accordingly, cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON. Ann Neurol 2015;77:1076–1082     

The Eurotransplant Donor Risk Index in Liver Transplantation: ET‐DRI

Recently we validated the donor risk index (DRI) as conducted by Feng et al. for the Eurotransplant region. Although this scoring system is a valid tool for scoring donor liver quality, for allocation purposes a scoring system tailored for the Eurotransplant region may be more appropriate. Objective of our study was to investigate various donor and transplant risk factors and design a risk model for the Eurotransplant region. This study is a database analysis of all 5939 liver transplantations from deceased donors into adult recipients from the 1st of January 2003 until the 31st of December 2007 in Eurotransplant. Data were analyzed with Kaplan–Meier and Cox regression models. From 5723 patients follow‐up data were available with a mean of 2.5 years. After multivariate analysis the DRI (p < 0.0001), latest lab GGT (p = 0.005) and rescue allocation (p = 0.007) remained significant. These factors were used to create the Eurotransplant Donor Risk Index (ET‐DRI). Concordance‐index calculation shows this ET‐DRI to have high predictive value for outcome after liver transplantation. Therefore, we advise the use of this ET‐DRI for risk indication and possibly for allocation purposes within the Eurotrans‐plant region.     

Chronic infection with hepatitis B viruses and antiviral drug evaluation in uPA mice after liver repopulation with tupaia hepatocytes

BACKGROUND/AIMS: Transplantation of primary human hepatocytes and establishment of hepatitis B virus (HBV) infection in immunodeficient urokinase plasminogen activator (uPA) transgenic mice was shown. However, the availability of usable primary human hepatocytes is very limited. Therefore, alternative and more accessible sources of hepatocytes permissive for HBV infection are highly desirable. Here we investigated the potential of primary hepatocytes from the tree shrew Tupaia belangeri that were shown to be susceptible to HBV infection. METHODS: Freshly isolated or cryopreserved primary tupaia hepatocytes were transplantated via intrasplenic injection into immunodeficient uPA/RAG-2 mice. Engrafted mice were then infected with HBV and woolly monkey (WM)-HBV positive sera. RESULTS: Extensive proliferation of xenografted cells was demonstrated by the stable production of tupaia alpha1-antitrypsin in serum and liver of transplanted mice. Quantitative PCR assays demonstrated the presence of circulating viral particles as well as intracellular viral DNA, including covalently closed circular (ccc) DNA, in transplanted mice. Viral infection could be serially passaged in mice. Furthermore, viral replication was strongly inhibited by treating mice with adefovir dipivoxil. CONCLUSIONS: uPA mice repopulated with tupaia hepatocytes represent a useful and more accessible model for HBV infection studies, including the evaluation of antiviral therapy and cccDNA.     

Risk Factors for Disease in a Homeless Population

Risk factors of smoking, drug and alcohol abuse, obesity, and sedentary lifestyle were related to health problems of clients at a walk-in clinic for the homeless. The sample of 1252 clients was predominately male (91.4%) and multiethnic, with a majority (65%) age 18 to 40 years. Data on diagnoses of health-related conditions were collected from clinic charts, coded into ICD categories, analyzed for relationships of risk factors to health problems, and compared with categories of diagnoses in a matched national sample of ambulatory care visits. Findings indicate that a larger proportion of homeless suffered from health problems in 24 of 27 diagnostic categories than the nonhomeless. Most prevalent were respiratory, dermal conditions, injuries, and digestive problems, in that order. Risk factors of alcohol abuse, smoking, sedentary lifestyle, drug abuse, and obesity were predictive of health problems in 18 of the categories analyzed. The findings suggest that immediate interventions such as education and rehabilitation to reduce risk factors, and provision of facilities for personal hygiene and cleaning of clothing could reduce some of the health-related conditions in this population while longer-term solutions of housing and employment are sought. The analysis model developed here appears to be a useful way of comparing relative effects of risk factors as a basis for establishing priorities for interventions.     

Handwriting difficulties in primary school children: a search for underlying mechanisms.

OBJECTIVE: This study investigated the contribution of perceptual-motor dysfunction and cognitive planning problems to the quality or speed of handwriting in children with handwriting problems (HWP). METHOD: Twenty-nine children with HWP and 20 classroom peers attending regular schools (grade 2 and grade 3) were tested with regard to visual perception, visual-motor integration, fine motor coordination, and cognitive planning abilities. RESULTS: The HWP group scored significantly lower on visual perception, visual-motor integration, fine motor coordination, and cognitive planning in comparison with classroom controls. Regression analyses showed that visual-motor integration was the only significant predictor for quality of handwriting in the HWP group, whereas fine motor coordination (i.e., unimanual dexterity) was the only significant predictor of quality of handwriting in the control group. CONCLUSIONS: Results suggest that two different mechanisms underlie the quality of handwriting in children with and without handwriting problems. Poor quality of handwriting of children with HWP seems particularly related to a deficiency in visual-motor integration.     

Quantitative structure-activity analysis of acetylcholinesterase inhibition by oxono and thiono analogues of organophosphorus compounds.

A comparison of the bimolecular rate constants (ki) for inhibition of electric eel acetylcholinesterase (AChE) by the oxono (i.e., P=O) and thiono (i.e., P=S) analogues of parathion, methylparathion, leptophos, fonofos, sarin, and soman revealed that the oxono/thiono ratios of ki values varied from 14 for soman to 1240 for parathion. Analysis of the relative importance of the dissociation equilibrium constant and the phosphorylation rate constant in producing this variation in ki values indicated that the oxono analogues and the phosphorylation rate constant values that varied in a narrow range from 8- to 14-fold greater than their thiono counterparts, while the oxono/thiono ratios for dissociation constants varied widely from 1 for soman to 82 for fonofos. The lower affinities of thiono analogues for AChE probably resulted from differences in the hydrophobic binding of oxono and thiono analogues to the active site of AChE, inasmuch as the hydrophobicities (i.e., octanol/water partition coefficients) of thiono organophosphorus compounds were much greater than the hydrophobicities of their oxono analogues. Quantitative structure--activity analysis indicated that the hydrophobic effects of oxono and thiono moieties correlated with log ki for AChE inhibition to a greater extent (r2 = 0.79) than their electronic effects (r2 less than or equal to 0.48). These observations suggest that the differences in hydrophobicity of oxono and thiono analogues of organophosphorus compounds may be as important as their electronic differences in determining their effectiveness as AChE inhibitors.