Controversias con los medicamentos sintomáticos de acción lenta para la Osteoartritis (SYSADOAs)

La osteoartritis es una enfermedad de patogenia compleja y etiología multifactorial, clínicamente se caracteriza por su naturaleza heterogénea con expresiones fenotípicas distintas. El diagnóstico clásicamente se ha establecido en base a la combinación de las características clínicas y los hallazgos radiológicos compatibles con cambios degenerativos en la articulación afectada. Entre los medicamentos disponibles para el manejo de la osteoartritis se cuenta con los analgésicos de acción rápida (Ej. Paracetamol, antiinflamatorios no esteroideos); los medicamentos sintomáticos de acción lenta (denominados SYSADOAs por sus siglas en inglés: Symptomatic Slow-Acting Drugs for Osteoarthritis); y finalmente se considera un tercer grupo, los medicamentos modificadores de la enfermedad (denominados también DMOA por sus siglas en inglés: “Disease modifying OA drugsâ€), pero como grupo es inexistente, porque ningún medicamento ha demostrado el potencial para remodelar o renovar la estructura de la articulación afectada. Se reconoce que algunos de los SYSADOA podrían tener también efecto estructural.Se ha propuesto que un SYSADOA, debe de cumplir cuatro objetivos: Proporcionar alivio de los síntomas, disminuir el requerimiento de medicación sintomática concomitante (analgésicos, AINEs, etc.), prevenir el daño estructural y evitar (o retardar) el requerimiento de cirugía de reemplazo articular. Diferentes estudios clínicos y metanálisis encuentran evidencia que apoya la eficacia sobre el control del dolor de los SYSADOAs, pero con una heterogeneidad importante.El propósito de este artículo es revisar las razones por las cuales existe discrepancia sobre la eficacia sintomática de los SYSADOAs, entre las cuales se encuentran la baja calidad metodológica de algunos estudios clínicos, las características y la naturaleza de la molécula específicamente empleada, las variaciones en la molécula original, el estatus de registro (medicamentos de venta libre o bajo prescripción), el procesamiento y la fuente de financiación de los estudios clínicos entre otros.La osteoartritis es una enfermedad de patogenia compleja y etiología multifactorial, clínicamente se caracteriza por su naturaleza heterogénea con expresiones fenotípicas distintas. El diagnóstico clásicamente se ha establecido en base a la combinación de las características clínicas y los hallazgos radiológicos compatibles con cambios degenerativos en la articulación afectada. Entre los medicamentos disponibles para el manejo de la osteoartritis se cuenta con los analgésicos de acción rápida (Ej. Paracetamol, antiinflamatorios no esteroideos); los medicamentos sintomáticos de acción lenta (denominados SYSADOAs por sus siglas en inglés: Symptomatic Slow-Acting Drugs for Osteoarthritis); y finalmente se considera un tercer grupo, los medicamentos modificadores de la enfermedad (denominados también DMOA por sus siglas en inglés: “Disease modifying OA drugsâ€), pero como grupo es inexistente, porque ningún medicamento ha demostrado el potencial para remodelar o renovar la estructura de la articulación afectada. Se reconoce que algunos de los SYSADOA podrían tener también efecto estructural.Se ha propuesto que un SYSADOA, debe de cumplir cuatro objetivos: Proporcionar alivio de los síntomas, disminuir el requerimiento de medicación sintomática concomitante (analgésicos, AINEs, etc.), prevenir el daño estructural y evitar (o retardar) el requerimiento de cirugía de reemplazo articular. Diferentes estudios clínicos y metanálisis encuentran evidencia que apoya la eficacia sobre el control del dolor de los SYSADOAs, pero con una heterogeneidad importante.El propósito de este artículo es revisar las razones por las cuales existe discrepancia sobre la eficacia sintomática de los SYSADOAs, entre las cuales se encuentran la baja calidad metodológica de algunos estudios clínicos, las características y la naturaleza de la molécula específicamente empleada, las variaciones en la molécula original, el estatus de registro (medicamentos de venta libre o bajo prescripción), el procesamiento y la fuente de financiación de los estudios clínicos entre otros

GSLC architecture for sequence detectors using spatial diversity

The role of advanced front-ends including spatial diversity, has been considered as an independent part of peak-distortion equalizers, Wiener and Viterbi equalizers. This involves that the optimum processing to remove point or distributed sources, together with inner and outer intersymbol interference is analyzed independently at the beamformer and at the equalizer stages. Recently, based on extensions of the works performed with forward equalizers and optimal combining in communications systems with spatial diversity, several solutions to the joint design of sequence detectors and spatial combiners have been reported. All these solutions have in common the principle that the optimum design holds the constraint of matching the spatial response of the combiner to the DIR (Desired Impulse Response) of the sequence detector. This work enhances the matched DIR concept with the Generalized Sidelobe Canceller architecture; proving that, for stationary Intersymbol Interference (ISI) for the desired user, the GLSC represents a suitable spatial processing. The GSLC allows continuous updating of the combiner either in order to reject late arrivals and co-channel interferers, without requiring the presence of training sequence or to maximize the effective SNR.Peer ReviewedPostprint (published version

Joint beamforming and Viterbi equalizer in wireless communications

The presence of a sequence detector in the baseline architecture for base stations for mobile communications has become a standard. Also the use of coding allows the baseband detector to work at very low signal to noise ratios. When spatial diversity is included in the front-end, the joint design of the beamformer, matched filter and the desired impulse response DIR of the Viterbi equalizer VE is mandatory. This work describes the joint design of these stages when the matched DIR response has priority in the maximization of the signal to noise plus interferences ratio at the input of the VE.Peer ReviewedPostprint (published version

Optimal array combiner for sequence detectors

The use of spatial diversity at the receiver front-end together with a sequence detector implies a joint design problem of the spatial combiner and the sequence detector impulse response. This joint design is usually faced under the constraint that the impulse response of the sequence detector is matched to the channel plus combiner response. This procedure maximizes the signal to noise ratio at the input of the detector but does not guarantee that the so-called effective signal to noise ratio is maximized. This work presents a procedure that, starting from the matched criteria, faces directly the maximization of the effective signal to noise ratio, yet preserving all the features of the spatial processor in terms of co-channel and high order intersymbol interference rejection.Peer ReviewedPostprint (published version

Joint array combining and MLSE for single-user receivers in multipath Gaussian multiuser channels

The well-known structure of an array combiner along with a maximum likelihood sequence estimator (MLSE) receiver is the basis for the derivation of a space-time processor presenting good properties in terms of co-channel and intersymbol interference rejection. The use of spatial diversity at the receiver front-end together with a scalar MLSE implies a joint design of the spatial combiner and the impulse response for the sequence detector. This is faced using the MMSE criterion under the constraint that the desired user signal power is not cancelled, yielding an impulse response for the sequence detector that is matched to the channel and combiner response. The procedure maximizes the signal-to-noise ratio at the input of the detector and exhibits excellent performance in realistic multipath channels.Peer Reviewe

Software Radio para antenas inteligentes en comunicaciones personales multistandard

Peer ReviewedPostprint (published version

Spatial processing for frequency diversity schemes

A novel technique to obtain optimum blind spatial processing for frequency diversity spread spectrum (FDSS) communication systems is introduced. The sufficient statistics for a linear combiner, which prove ineffective due to the interferers frequency characteristics, are modified to yield improved detection under partial jamming in the spectral domain. Robustness to partial time jamming is achieved by extending the notion of replicas over the frequency axis to a repetition over the time variable. Analysis and simulations are provided, showing the advantages of using FDSS with spatial diversity to combat the interference when it is confined to a narrow frequency band or short time interval relative to the desired signal extent in either domain.Peer Reviewe

Post-veraison sunlight exposure induces MYB-mediated transcriptional regulation of anthocyanin and flavonol synthesis in berry skins of Vitis vinifera

Anthocyanins, flavan-3-ols, and flavonols are the three major classes of flavonoid compounds found in grape berry tissues. Several viticultural practices increase flavonoid content in the fruit, but the underlying genetic mechanisms responsible for these changes have not been completely deciphered. The impact of post-veraison sunlight exposure on anthocyanin and flavonol accumulation in grape berry skin and its relation to the expression of different transcriptional regulators known to be involved in flavonoid synthesis was studied. Treatments consisting of removing or moving aside the basal leaves which shade berry clusters were applied. Shading did not affect sugar accumulation or gene expression of HEXOSE TRANSPORTER 1, although in the leaf removal treatment, these events were retarded during the first weeks of ripening. Flavonols were the most drastically reduced flavonoids following shading and leaf removal treatments, related to the reduced expression of FLAVONOL SYNTHASE 4 and its putative transcriptional regulator MYB12. Anthocyanin accumulation and the expression of CHS2, LDOX, OMT, UFGT, MYBA1, and MYB5a genes were also affected. Other regulatory genes were less affected or not affected at all by these treatments. Non-transcriptional control mechanisms for flavonoid synthesis are also suggested, especially during the initial stages of ripening. Although berries from the leaf removal treatment received more light than shaded fruits, malvidin-3-glucoside and total flavonol content was reduced compared with the treatment without leaf removal. This work reveals that flavonol-related gene expression responds rapidly to field changes in light levels, as shown by the treatment in which shaded fruits were exposed to light in the late stages of ripening. Taken together, this study establishes MYB-specific responsiveness for the effect of sun exposure and sugar transport on flavonoid synthesis

The Test Your Memory cognitive screening tool: sociodemographic and cardiometabolic risk correlates in a population-based study of older British men.

OBJECTIVE: This study aimed to examine the association of Test Your Memory (TYM)-defined cognitive impairment groups with known sociodemographic and cardiometabolic correlates of cognitive impairment in a population-based study of older adults. METHODS: Participants were members of the British Regional Heart Study, a cohort across 24 British towns initiated in 1978-1980. Data stemmed from 1570 British men examined in 2010-2012, aged 71-92 years. Sociodemographic and cardiometabolic factors were compared between participants defined as having TYM scores in the normal cognitive ageing, mild cognitive impairment (MCI) and severe cognitive impairment (SCI) groups, defined as ≥46 (45 if ≥80 years of age), ≥33 and <33, respectively. RESULTS: Among 1570 men, 636 (41%) were classified in the MCI and 133 (8%) in the SCI groups. Compared with participants in the normal cognitive ageing category, individuals with SCI were characterized primarily by lower socio-economic position (odds ratio (OR) = 6.15, 95% confidence interval (CI) 4.00-9.46), slower average walking speed (OR = 3.36, 95% CI 2.21-5.10), mobility problems (OR = 4.61, 95% CI 3.04-6.97), poorer self-reported overall health (OR = 2.63, 95% CI 1.79-3.87), obesity (OR = 2.59, 95% CI 1.72-3.91) and impaired lung function (OR = 2.25, 95% CI 1.47-3.45). A similar albeit slightly weaker pattern was observed for participants with MCI. CONCLUSION: Sociodemographic and lifestyle factors as well as adiposity measures, lung function and poor overall health are associated with cognitive impairments in late life. The correlates of cognitive abilities in the MCI and SCI groups, as defined by the TYM, resemble the risk profile for MCI and Alzheimer's disease outlined in current epidemiological models. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons, Ltd

Stability of DON and OTA during the breadmaking process and determination of process and performance criteria

The fate of deoxynivalenol (DON) and ochratoxin A (OTA) during the breadmaking process was studied. In particular, toxin content was analysed in mixed baking ingredients before kneading, after fermentation and proofing, and finally after baking. Fermentation and proofing were carried out at 30 C for 1 h, while baking was performed at different temperature levels (from 170 to 210 C) and baking times from 45 to 135 min, in a full factorial design. DON increased from unkneaded mix to fermented dough, and decreased due to baking; this trend depended on the initial concentration of DON in the flour. The level in the bread was significantly lower than in the initial mix of ingredients. In contrast, deoxynivalenol-3-glucoside (DON-3-G) content increased both during kneading and fermentation, and also during baking. Moreover, the results confirmed the high stability of OTA as no significant change in its content could be observed as a result of the breadmaking process. As conclusion, the design of bakery product processes may help to control DON in final products, because although quite stable, its levels can be reduced to some extent. However, high levels of DON-3-G were released during baking, and this point should be further investigated. Mycotoxins have been always considered as stable compounds; however, in depth knowledge of the processing steps that may lead to some reduction (although limited) and those which can stimulate their release from conjugated forms, will definitely help in their control in finished foodstuffs.The authors are grateful to the Spanish government (projects AGL2010-22182-C04-04 and AGL2011-24862) for the financial support. A. Vidal thanks the Spanish Government (Ministry of Education) for the pre-doctoral grant. H. Morales is grateful to the Portuguese Government. (Ministerio da Ciecia, Tecnologia e Ensino Superior; FCT Fundacao para a Ciencia e a Tecnologia) Grant ref. SFRH/BPD/38011/2007