Diagnostic Accuracy of Anti-CN1A on the Diagnosis of Inclusion Body Myositis. A Hierarchical Bivariate and Bayesian Meta-analysis.

ABSTRACT: Sporadic inclusion body myositis (IBM) is an acquired muscle disease and the most common idiopathic inflammatory myopathy over the age of 50. It is characterized by male predominance, with a prevalence rate between 1 and 71 cases per million, reaching 139 cases per million over the age of 50 globally. The diagnosis of IBM is based on clinical presentation and muscle biopsy findings. However, there is increasing evidence for the role of genetics and serum biomarkers in supporting a diagnosis. Antibodies against the cytosolic 5'-nucleotidase 1A (Anti-CN1A), an enzyme catalyzing the conversion of adenosine monophosphate into adenosine and phosphate and is abundant in skeletal muscle, has been reported to be present in IBM and could be of crucial significance in the diagnosis of the disease. In this study, we investigated the diagnostic accuracy of anti-CN1A antibodies for sporadic IBM in comparison with other inflammatory myopathies, autoimmune disorders, motor neurone disease, using a hierarchical bivariate approach, and a Bayesian model taking into account the variable prevalence. The results of the present analysis show that anti-CN1A antibodies have moderate sensitivity, and despite having high specificity, they are not useful biomarkers for the diagnosis of IBM, polymyositis or dermatomyositis, other autoimmune conditions, or neuromuscular disorders. Neither the hierarchical bivariate nor the Bayesian analysis showed any significant usefulness of anti-CN1A antibodies in the diagnosis of IBM.

A meta-analysis on RT-QuIC for the diagnosis of sporadic CJD.

Creutzfeld-Jakob disease (CJD) is a fatal neurodegenerative disease which belongs to the family of transmissible spongiform encephalopathies (TSEs), or prion diseases. Historically, CJD diagnosis has been based on the combination of clinical features and in vivo markers, including CSF protein assays, MRI and EEG changes. Brain-derived CSF proteins, such as 14-3-3, t-tau and p-tau have been largely used to support the diagnosis of probable CJD, although with certain limitations concerning sensitivity and specificity of these tests. More recently, a new method for the pre-mortem diagnosis of sporadic CJD has been developed, based on the ability of PrPsc to induce the polymerization of protease-sensitive recombinant PrP (PrPsen) into amyloid fibrils, and is known as Real-Time Quaking- Induced Conversion (RT-QuIC) assay allows the detection of > 1 fg of PrPsc in diluted CJD brain homogenate and a variety of biological tissues and fluids. In the present study, we did a meta-analysis on the liability of RT-QuIC method in the diagnosis of sporadic CJD, in comparison to 14-3-3 and Tau protein. Twelve studies were finally included in the statistical analysis which showed that RT-QuIC has a very high specificity and comparable sensitivity to 14-3-3 protein and Tau protein in the CSF, and hence can be used as a reliable biomarker for the diagnosis of sporadic CJD.

Sodium valproate-induced Fanconi type proximal renal tubular acidosis.

We present a case series of three patients with sodium valproate-induced Fanconi's syndrome, with ages ranging from 5 years to 12 years. The most important diagnostic features of this syndrome include hypophosphataemia, glycosuria and proteinuria, which are also noted in our series. Furthermore, also added is that clinical fractures representing an underlying osteopaenia may provide an opportunity for early intervention as it raises the suspicion of Fanconi's syndrome. Previous case reports suggest there is a subpopulation of individuals who are at risk of developing this condition. These individuals share similar characteristics, including being non-ambulatory, developmentally delayed and/or tube fed. Withdrawing sodium valproate therapy is the ultimate treatment for valproate-induced Fanconi's syndrome and from previous case series, normalised renal function occurs in approximately 6 months. Often, supplement support is also required for deranged electrolyte balance.

The effects of sodium valproate on the renal function of children with epilepsy.

Sodium valproate is one of the most commonly used drugs to treat epilepsy. However, there is growing evidence that valproate can cause renal tubular injury in children, and there are increasing reports of valproate-induced Fanconi's syndrome where the renal tubules lose their ability to reabsorb electrolytes, urea, glucose and protein. In this review article we attempt to bring together all of the studies conducted to date on the effects of valproate on renal function in epileptic children. The research is generally considered in two themes; the first comprises studies which indicate subclinical tubular injury measured by renal enzymes such as N-acetyl-ß-D-glucosaminidase (NAG), and the second comprises clinical reports where Fanconi's syndrome has occurred. This article goes on to analyse the current data and draws on recurring patterns to suggest that a specific subpopulation of severely disabled epileptic children may benefit hugely from the close monitoring of enzymes which are indicative of renal tubular injury, particularly NAG or in the very least periodical urinalysis.

Taking a historical turn: possible points of connection between social pyschology and history.

The article confronts methodological differences between (and among) social psychologists and historians about how far the social psychologist should be interested only in contemporary or very recent history and how far general conclusions can be drawn about human behaviour across time and space. The article suggests that social psychology need not be present-centric and might take different forms of a 'historical turn'. In turn, it is suggested, historians can benefit from approaches developed by social psychologists. Seven possible points of connection with the discipline of history are put forward in the hope of fostering future collaborations. These are: the nature of modernity; collective memory and the uses of the past; political discourse and ideologies; partisanship; the public sphere; stereotypes; and languages and images. Indeed, just as they can encourage closer collaboration between historians and social psychologists, these themes might also open a wider inter-disciplinary discussion with anthropologists, sociologists, literary scholars, art historians and scholars of political discourse.

Characteristic features of stem cells in glioblastomas: from cellular biology to genetics.

Glioblastoma is the most common type of primary brain tumor in adults and is among the most lethal and least successfully treated solid tumors. Recently, research into the area of stem cells in brain tumors has gained momentum. However, due to the relatively new and novel hypothesis that a subpopulation of cancer cells in each malignancy has the potential for tumor initiation and repopulation, the data in this area of research are still in its infancy. This review article is aimed at attempting to bring together research carried out so far in order to build an understanding of glioblastoma stem cells (GSCs). Initially, we consider GSCs at a morphological and cellular level, and then discuss important cell markers, signaling pathways and genetics. Furthermore, we highlight the difficulties associated with what some of the evidence indicates and what collectively the studies contribute to further defining the interpretation of GSCs.