Genetic and Epigenomic Modifiers of Diabetic Neuropathy

Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.     

Engineering a Web site

The World Wide Web (WWW) is famous for weaving far-flung fans with like interests into true communities. It also puts a spin all its own on product and information delivery. Nowhere is this more apparent than in a global industry such as electrical and electronic engineering. The Web is still unmatched in its ability to receive and distribute information and software, and to encourage interaction and collaboration. These strengths stem from the Web's combination of many of the best features of existing media-audio, video, text, and graphics-to which it adds some unique new talents, such as the ability to manipulate information through software. Most corporations acknowledge the opportunities the Web presents. The paper presents some guidelines on how best to start turning them to advantage     

Modulated Hebb-Oja learning Rule-a method for principal subspace analysis

This paper presents analysis of the recently proposed modulated Hebb-Oja (MHO) method that performs linear mapping to a lower-dimensional subspace. Principal component subspace is the method that will be analyzed. Comparing to some other well-known methods for yielding principal component subspace (e.g., Oja's Subspace Learning Algorithm), the proposed method has one feature that could be seen as desirable from the biological point of view-synaptic efficacy learning rule does not need the explicit information about the value of the other efficacies to make individual efficacy modification. Also, the simplicity of the "neural circuits" that perform global computations and a fact that their number does not depend on the number of input and output neurons, could be seen as good features of the proposed method.     

Placebo-induced conversion reaction: A neurobehavioral and EEG study of hysterical aphasia, seizure, and coma.

A patient in her mid-20's with an alleged idiosyncratic reaction to phenytoin (Dilantin) was studied by an objective double-dissociation method. Under carefully monitored conditions an iv saline placebo was administered. A variety of dose-dependent pseudoneurologic symptoms developed, including hysterical aphasia, pseudoseizures, and profound unresponsiveness. Optokinetic nystagmus, the visual threat reflex, corneal reflex, the auditory startle response, and responses to deep pain were completely lost. Despite the dramatic nature of symptoms, however, the EEG remained normal, and S responded to cues she overheard concerning her "drug" level. Later, no reactions occurred when, thinking it was something else, S actually received phenytoin. Hysterical aphasias and the implications for afferent theories of conversion reactions are discussed. A speculative model that pertains to dissociative phenomena (e.g., hidden-observer effect, selective awareness, and amnesia) and the controlled aspect of consciousness is suggested. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Symptomatic and functional outcome of surgical treatment of cervical dystonia

OBJECTIVES: Previous studies of surgical treatment for cervical dystonia have reported highly variable rates of postoperative symptomatic benefit and morbidity. Little is known about functional improvement and long term results. This study evaluates the symptomatic and functional outcome of surgical treatment of cervical dystonia in a consecutive series of 46 patients. METHODS: The most affected muscles were selected for denervation after clinical examination and confirmation by four channel EMG studies. Surgical treatment, aiming at selective elimination of pathological activity while preserving normal motor function and avoiding side effects, was achieved by using a broad scope of techniques including intradural denervation, extradural denervation, and myotomy. Rather than carrying out standard operations, the treatment was tailored to the needs of the patient according to the individual pattern of dystonic activity. Long term benefit was assessed with a global outcome score, and a modified Toronto western spasmodic torticollis rating scale (TWSTRS) in those 34 patients who were available for a recent follow up evaluation. RESULTS: The 46 patients underwent a total of 70 procedures with intradural approaches in 33 instances, extradural approaches in 21, and muscle sections (singly or combined) in 22 instances. Transient mild postoperative side effects occurred in 10% of the procedures. The mean duration of long term follow up was 6.5 years. The global outcome was rated as excellent in nine patients (21%), as marked in 12 (27%), as moderate in nine (21%), as mild in nine (21%), and as no improvement in five (11%). A persistent side effect consisting of mild difficulty with balance was noted in one case. There were highly significant changes of the preoperative and postoperative mean values for almost all TWSTRS subscores for severity of cervical dystonia, functional disability, and pain. Patients with excellent outcome underwent a higher number of surgical procedures on average than those patients who achieved no benefit. CONCLUSIONS: Surgical treatment tailored to the specific pattern of dystonic activity in the individual patient is a valuable alternative in the long term management of cervical dystonia.     

Adaptive nonlinear output feedback tracking with a partialhigh-gain observer and backstepping

An adaptive output feedback controller for nonlinear systems with nonlinearities depending on the first r (1⩽r⩽n) derivatives of the output is proposed. The derivatives are estimated with a partial state high-gain observer, and the remaining states are handled using a backstepping method. Compared with methods based on full state high-gain observer, this approach improves robustness with respect to measurement noise and avoids overparametrization. Semiglobal tracking is proven under the assumption that the regressor is persistently exciting     

Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS), neurodegenerative motor neuron disorder is characterized as multisystem disease with important contribution of genetic factors. The etiopahogenesis of ALS is not fully elucidate, but the dominant theory at present relates to RNA processing, as well as protein aggregation and miss-folding, oxidative stress, glutamate excitotoxicity, inflammation and epigenetic dysregulation. Additionally, as mitochondria plays a leading role in cellular homeostasis maintenance, a rising amount of evidence indicates mitochondrial dysfunction as a substantial contributor to disease onset and progression. The aim of this review is to summarize most relevant findings that link genetic factors in ALS pathogenesis with different mechanisms with mitochondrial involvement (respiratory chain, OXPHOS control, calcium buffering, axonal transport, inflammation, mitophagy, etc.). We highlight the importance of a widening perspective for better understanding overlapping pathophysiological pathways in ALS and neurodegeneration in general. Finally, current and potentially novel therapies, especially gene specific therapies, targeting mitochondrial dysfunction are discussed briefly.     

Design of a new nozzle for direct current plasma guns with improved spraying parameters

A new design is proposed for direct current plasma spray gas-shroud attachments. It has curvilinearly shaped internal walls aimed toward elimination of the cold air entrainment, recorded for commercially available conical designs of the shrouded nozzle. The curvilinear nozzle design was tested; it proved to be capable of withstanding high plasma temperatures and enabled satisfactory particle injection. Parallel measurements with an enthalpy probe were performed on the jet emerging from two different nozzles. Also, corresponding calculations were made to predict the plasma flow parameters and the particle parameters. Adequate spray tests were performed by spraying iron-aluminum and MCrAlY coatings onto stainless steel substrates. Coating analyses were performed, and coating qualities, such as microstructure, open porosity, and adhesion strength, were determined. The results indicate that the coatings sprayed with a curvilinear nozzle exhibited lower porosity, higher adhesion strength, and an enhanced microstructure.