Encefalopatías espongiformes transmisibles. Bases moleculares, diagnóstico y perspectivas terapéuticas

Las encefalopatías espongiformes transmisibles constituyen un grupo de enfermedades neurodegenerativas que estánasociadas a la presencia en el tejido nervioso de agregados insolubles constituidos por una isoforma anómala de unaproteína denominada prión. Esta isoforma se produce por un cambio conformacional en una molécula que puedetransmitirse a otras proteínas priónicas normales. Las proteínas modificadas pierden su actividad biológica, desencadenándosela muerte de las neuronas por apoptosis. Los cambios conformacionales de los priones que derivan enenfermedad pueden deberse a la existencia de mutaciones que disminuyan la estabilidad de las formas celulares.Existe susceptibilidad genética, por tanto, a padecer tipos hereditarios de la enfermedad o adquiridos por infeccióncon isoformas priónicas anormales. En la actualidad se están perfeccionando métodos sensibles de diagnósticobasados en la detección de las isoformas anormales de la proteína priónica. Todavía no existen tratamientos curativospara estas enfermedades aunque se están diseñando métodos terapéuticos que bloqueen los cambios conformacionalesque conducen a la precipitación de la proteína priónica

Transmissible spongiform encephalopathies: molecular biology, diagnosis and therapeutic approaches

Las encefalopatías espongiformes transmisibles constituyen un grupo de enfermedades neurodegenerativas que están asociadas a la presencia en el tejido nervioso de agregados insolubles constituidos por una isoforma anómala de una proteína denominada prión. Esta isoforma se produce por un cambio conformacional en una molécula que puede transmitirse a otras proteínas priónicas normales. Las proteínas modificadas pierden su actividad biológica, desencadenándose la muerte de las neuronas por apoptosis. Los cambios conformacionales de los priones que derivan en enfermedad pueden deberse a la existencia de mutaciones que disminuyan la estabilidad de las formas celulares. Existe susceptibilidad genética, por tanto, a padecer tipos hereditarios de la enfermedad o adquiridos por infección con isoformas priónicas anormales. En la actualidad se están perfeccionando métodos sensibles de diagnóstico basados en la detección de las isoformas anormales de la proteína priónica. Todavía no existen tratamientos curativos para estas enfermedades aunque se están diseñando métodos terapéuticos que bloqueen los cambios conformacionales que conducen a la precipitación de la proteína priónica.Transmissible spongiform encephalopaties constitute a group of neurodegenerative diseases associated to the presence in nervous tissue of insoluble aggregates originated by an anomalous isoform of a protein called prion. This isoform is produced by a conformational change in a molecule which is transmitted to normal prion proteins. Modified proteins loose their biological activity, provoking apoptotic death of neurons. Conformational changes of prions occasioning the illness can be due to the existence of mutations diminishing the stability of cellular forms. There is genetic susceptibility for suffering any type of the illness, either hereditary or acquired by infection with abnormal prion isoforms. New sensitive diagnostic methods are presently being developed, based on detection of abnormal isoforms of prion protein. There are no curative treatments for these illnesses, although new therapeutic strategies based on the blockage of conformational changes driving to protein precipitation are being designed

Development of a compact and low-cost weather station for renewable energy applications

This paper describes the development of a weather station integrating several sensors which allows the measurement and data storage of the following environmental parameters: solar irradiance, temperature, humidity, wind speed, and wind direction. The collected data is later transferred to a mobile device, where it is stored in a database and processed in order to be visualized and analyzed by the user. For such purpose, a dedicated mobile app was developed and presented along the paper. The weather station also integrates small solar photovoltaic modules of three different technologies: polycrystalline, monocrystalline and amorphous silicon. Based on that, the weather station also collects information that may be employed to help the user in determining the most suitable solar photovoltaic technology for installation in a particular location. The developed system uses a Bluetooth Low Energy (BLE) wireless network to transfer the data to the mobile device when the user approaches the weather station. The system operation was validated through experimental tests that encompass all the main developed features, from the data acquisition in the weather station, to the visualization in the mobile device.- (undefined

Mobile ad hoc network testbed using mobile robot technology

MANET (Mobile Ad Hoc Network) researchers have shown increased interest in using mobile robot technology for their testbed platforms. Thus, the main motivation of this paper is to review various robot-based MANET testbeds that have been developed in previously reported research. Additionally, suggestions to heighten mobility mechanisms by using mobile robots to be more practical, easy and inexpensive are also included in this paper, as we unveils ToMRobot, a low-cost MANET robot created from an ordinary remote control car that is capable of performing a real system MANET testbed with the addition of only a few low-cost electronic components. Despite greatly reduced costs, the ToMRobot does not sacrifice any of the necessary MANET basic structures and will still be easily customizable and upgradeable through the use of open hardware technology like Cubieboard2 and Arduino, as its robot controller. This paper will also include guidelines to enable technically limited MANET researchers to design and develop the ToMRobot. It is hoped that this paper achieves its two pronged objectives namely (i) to facilitate other MANET researchers by providing them with a source of reference that eases their decision making for selecting the best and most suitable MANET mobile robots for real mobility in their MANET testbeds (ii) to provide MANET researchers with a prospect of building their own MANET robots that can be applied in their own MANET testbed in the future

Parkinsonism secondary to metastatic lesions within the central nervous system: a case report

<p>Abstract</p> <p>Introduction</p> <p>Colorectal cancer is one of the most common human diseases worldwide, and metastases are detected in approximately 20% of patients at diagnosis. Brain metastases occur in only 4% of cases, however, and usually present with hemiparesis or other motor or sensory symptoms. There have been only a few reports of parkinsonism secondary to a brain tumor-related mass effect.</p> <p>Case presentation</p> <p>We present an unusual case of parkinsonism secondary to multiple brain metastases. A 57-year-old Caucasian man had recently been diagnosed with primary carcinoma of the colon and had multiple metastases in the lungs and liver. He subsequently developed bilateral symmetrical parkinsonism, and multiple brain tumors were detected by computed tomography scanning. The condition of our patient deteriorated rapidly, and he became akinetic and dependent for all activities of daily living. He was followed up and treated at home by our palliative care unit team and died two weeks after the onset of his neurologic symptoms.</p> <p>Conclusion</p> <p>Although primary and secondary brain tumors are uncommon causes of parkinsonism, their clinical presentation may resemble that of idiopathic Parkinson's disease. An awareness of this rare differential diagnosis is therefore important in ensuring early diagnosis and treatment, thus improving prognosis and quality of life. A rapid progression in neurologic symptoms was observed in our patient, and clinicians should be alert to this atypical presentation of secondary parkinsonism.</p

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report

BACKGROUND: Since tacrolimus ointment was approved by the U.S. Food and Drug Administration (FDA) as a promising treatment for atopic dermatitis, it has been approved in more than 30 additional countries, including numerous European Union member nations. Moreover, in the current clinical routine the use of this drug is no longer restricted to the approved indication, but has been extended to a wide variety of inflammatory skin diseases including some with the potential of malignant transformation. So far, the side-effects reported from the topical use of tacrolimus have been relatively minor (e.g. burning, pruritus, erythema). Recently, however, the FDA reviewed the safety of topical tacrolimus, which resulted in a warning that the use of calcineurin inhibitors may be associated with an increased risk of cancer. CASE PRESENTATION: Oral lichen planus (OLP) was diagnosed in a 56-year-old women in February 1999. After several ineffective local and systemic therapeutic measures an off-label treatment of this recalcitrant condition using Tacrolimus 0.1% ointment was initiated in May 2002. After a few weeks of treatment most of the lesions ameliorated, with the exception of the plaques on the sides of the tongue. Nevertheless, the patient became free of symptoms which, however, reoccurred once tacrolimus was weaned, as a consequence treatment was maintained. In April 2005, the plaques on the left side of the tongue appeared increasingly compact and a biopsy specimen confirmed the suspected diagnosis of an oral squamous cell carcinoma. CONCLUSION: The suspected causal relationship between topical use of tacrolimus and the development of a squamous cell carcinoma prompted us to test the notion that the carcinogenicity of tacrolimus may go beyond mere immune suppression. To this end, tacrolimus has been shown to have an impact on cancer signalling pathways such as the MAPK and the p53 pathway. In the given case, we were able to demonstrate that these pathways had also been altered subsequent to tacrolimus therapy

Changes in liver mitochondrial plasticity induced by brain tumor

BACKGROUND: Accumulating data suggest that liver is a major target organ of systemic effects observed in the presence of a cancer. In this study, we investigated the consequences of the presence of chemically induced brain tumors in rats on biophysical parameters accounting for the dynamics of water in liver mitochondria. METHODS: Tumors of the central nervous system were induced by intraveinous administration of ethylnitrosourea (ENU) to pregnant females on the 19th day of gestation. The mitochondrial crude fraction was isolated from the liver of each animal and the dynamic parameters of total water and its macromolecule-associated fraction (structured water, H(2)Ost) were calculated from Nuclear Magnetic Resonance (NMR) measurements. RESULTS: The presence of a malignant brain tumor induced a loss of water structural order that implicated changes in the physical properties of the hydration shells of liver mitochondria macromolecules. This feature was linked to an increase in the membrane cholesterol content, a way to limit water penetration into the bilayer and then to reduce membrane permeability. As expected, these alterations in mitochondrial plasticity affected ionic exchanges and led to abnormal features of mitochondrial biogenesis and caspase activation. CONCLUSION: This study enlightens the sensitivity of the structured water phase in the liver mitochondria machinery to external conditions such as tumor development at a distant site. The profound metabolic and functional changes led to abnormal features of ion transport, mitochondrial biogenesis and caspase activation