Tactile Sensing for Mechatronics: A State of the Art Survey

Lee M.H. and Nicholls H.R., Tactile Sensing for Mechatronics: A State of the Art Survey, Mechatronics, 9, Jan 1999, pp1-31.

Comparação quantitativa dos andares médio e inferiores da face na AGIHF

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

Novos sistemas terapêuticos de administração transcutânea

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice.

Nicotinic acid is one of the most effective agents for both lowering triglycerides and raising HDL. However, the side effect of cutaneous flushing severely limits patient compliance. As nicotinic acid stimulates the GPCR GPR109A and Gi/Go proteins, here we dissected the roles of G proteins and the adaptor proteins, beta-arrestins, in nicotinic acid-induced signaling and physiological responses. In a human cell line-based signaling assay, nicotinic acid stimulation led to pertussis toxin-sensitive lowering of cAMP, recruitment of beta-arrestins to the cell membrane, an activating conformational change in beta-arrestin, and beta-arrestin-dependent signaling to ERK MAPK. In addition, we found that nicotinic acid promoted the binding of beta-arrestin1 to activated cytosolic phospholipase A2 as well as beta-arrestin1-dependent activation of cytosolic phospholipase A2 and release of arachidonate, the precursor of prostaglandin D2 and the vasodilator responsible for the flushing response. Moreover, beta-arrestin1-null mice displayed reduced cutaneous flushing in response to nicotinic acid, although the improvement in serum free fatty acid levels was similar to that observed in wild-type mice. These data suggest that the adverse side effect of cutaneous flushing is mediated by beta-arrestin1, but lowering of serum free fatty acid levels is not. Furthermore, G protein-biased ligands that activate GPR109A in a beta-arrestin-independent fashion may represent an improved therapeutic option for the treatment of dyslipidemia.

Implant healing in experimental animal models of diabetes.

Diabetes mellitus is becoming increasingly prevalent worldwide. Additionally, there is an increasing number of patients receiving implantable devices such as glucose sensors and orthopedic implants. Thus, it is likely that the number of diabetic patients receiving these devices will also increase. Even though implantable medical devices are considered biocompatible by the Food and Drug Administration, the adverse tissue healing that occurs adjacent to these foreign objects is a leading cause of their failure. This foreign body response leads to fibrosis, encapsulation of the device, and a reduction or cessation of device performance. A second adverse event is microbial infection of implanted devices, which can lead to persistent local and systemic infections and also exacerbates the fibrotic response. Nearly half of all nosocomial infections are associated with the presence of an indwelling medical device. Events associated with both the foreign body response and implant infection can necessitate device removal and may lead to amputation, which is associated with significant morbidity and cost. Diabetes mellitus is generally indicated as a risk factor for the infection of a variety of implants such as prosthetic joints, pacemakers, implantable cardioverter defibrillators, penile implants, and urinary catheters. Implant infection rates in diabetic patients vary depending upon the implant and the microorganism, however, for example, diabetes was found to be a significant variable associated with a nearly 7.2% infection rate for implantable cardioverter defibrillators by the microorganism Candida albicans. While research has elucidated many of the altered mechanisms of diabetic cutaneous wound healing, the internal healing adjacent to indwelling medical devices in a diabetic model has rarely been studied. Understanding this healing process is crucial to facilitating improved device design. The purpose of this article is to summarize the physiologic factors that influence wound healing and infection in diabetic patients, to review research concerning diabetes and biomedical implants and device infection, and to critically analyze which diabetic animal model might be advantageous for assessing internal healing adjacent to implanted devices.

Component-wise gradient boosting and false discovery control in survival analysis with high-dimensional covariates.

MOTIVATION: Technological advances that allow routine identification of high-dimensional risk factors have led to high demand for statistical techniques that enable full utilization of these rich sources of information for genetics studies. Variable selection for censored outcome data as well as control of false discoveries (i.e. inclusion of irrelevant variables) in the presence of high-dimensional predictors present serious challenges. This article develops a computationally feasible method based on boosting and stability selection. Specifically, we modified the component-wise gradient boosting to improve the computational feasibility and introduced random permutation in stability selection for controlling false discoveries. RESULTS: We have proposed a high-dimensional variable selection method by incorporating stability selection to control false discovery. Comparisons between the proposed method and the commonly used univariate and Lasso approaches for variable selection reveal that the proposed method yields fewer false discoveries. The proposed method is applied to study the associations of 2339 common single-nucleotide polymorphisms (SNPs) with overall survival among cutaneous melanoma (CM) patients. The results have confirmed that BRCA2 pathway SNPs are likely to be associated with overall survival, as reported by previous literature. Moreover, we have identified several new Fanconi anemia (FA) pathway SNPs that are likely to modulate survival of CM patients. AVAILABILITY AND IMPLEMENTATION: The related source code and documents are freely available at https://sites.google.com/site/bestumich/issues. CONTACT: yili@umich.edu.

Induction of apoptosis in host cells: a survival mechanism for Leishmania parasites?

Leishmania parasites invade host macrophages, causing infections that are either limited to skin or spread to internal organs. In this study, 3 species causing cutaneous leishmaniasis, L. major, L. aethiopica and L. tropica, were tested for their ability to interfere with apoptosis in host macrophages in 2 different lines of human monocyte-derived macrophages (cell lines THP-1 and U937) and the results confirmed in peripheral blood mononuclear cells (PBMC). All 3 species induced early apoptosis 48 h after infection (expression of phosphatidyl serine on the outer membrane). There were significant increases in the percentage of apoptotic cells both for U937 and PBMC following infection with each of the 3 species. Early apoptotic events were confirmed by mitochondrial membrane permeabilization detection and caspase activation 48 and 72 h after infection. Moreover, the percentage of infected THP-1 and U937 macrophages increased significantly (up to 100%) following treatment with an apoptosis inducer. Since phosphatidyl serine externalization on apoptosing cells acts as a signal for engulfment by macrophages, induction of apoptosis in the parasitized cells could actively participate in spreading the infection. In summary, parasite-containing apoptotic bodies with intact membranes could be released and phagocytosed by uninfected macrophages.

Variaciones termométricas en la planta del pie y piernas valorada en corredores antes y después de correr 30 km

La termometría es una técnica no invasiva que permite cuantificar los cambios en la temperatura cutánea y evaluarla de forma cuantitativa. El aumento significativo de la temperatura puede indicar la existencia de patología. Se ha demostrado que la actividad muscular induce procesos de transferencia de calor entre los músculos y las capas superficiales de tejido. En este estudio queremos cuantificar los cambios de temperatura que se producen en los músculos del pie y miembro inferior tras una carrera de 30 km, para ello hemos utilizado una cámara termográfica de alta resolución. Contamos con la colaboración voluntaria de 32 sujetos sanos a los que procedimos a tomar fotografías de la planta del pie, parte anterior de la pierna, parte posterior de la pierna, parte anterior del muslo y parte posterior del muslo en dos etapas, primero antes de la carrera y segunda toma después de la carrera de 30 km, de esta manera pudimos valorar si había o no variación de temperatura en las zonas seleccionadas. Tras el análisis de los datos obtenidos encontramos significativas variaciones térmicas en Talón, cabeza primer metatarsiano, cabeza segundo metatarsiano, cabeza tercer metatarsiano, cabeza cuarto metatarsiano, cabeza quinto metatarsiano, apófisis estiloides quinto metatarsiano, arco longitudinal interno, maléolo interno, maléolo externo, peroneo lateral largo, vasto interno, vasto externo, recto femoral, tensor de la fascia lata, inserción cuádriceps, gemelo interno, tendón de Aquiles y Biceps femoral.

Los diferentes tipos de láser y sus aplicaciones en podología

Los diferentes tipos de láseres, sobre todo el láser de diodo, irrumpen en la terapéutica podológica para proporcionar una alternativa más de tratamiento en muchas patologías que son el día a día de las consultas. El buen manejo y el conocimiento de sus características son requisitos imprescindibles para no tener efectos secundarios indeseados y poder llevar a cabo tratamientos poco dolorosos, minimizando el tiempo total, y muchas veces proporcionando una solución a diversas patologías.

Stability of 5-aminolevulinic acid in novel non-aqueous gel and patch-type systems intended for topical application.

Aminolevulinic acid (ALA) stability within topical formulations intended for photodynamic therapy (PDT) is poor due to dimerisation to pyrazine-2,5-dipropionic acid (PY). Most strategies to improve stability use low pH vehicles, which can cause cutaneous irritancy. To overcome this problem, a novel approach is investigated that uses a non-aqueous vehicle to retard proton-induced charge separation across the 4-carbonyl group on ALA and lessen nucleophilic attack that leads to condensation dimerisation. Bioadhesive anhydrous vehicles based on methylvinylether-maleic anhydride copolymer patches and poly(ethyleneglycol) or glycerol thickened poly(acrylic acid) gels were formulated. ALA stability fell below pharmaceutically acceptable levels after 6 months, with bioadhesive patches stored at 5°C demonstrating the best stability by maintaining 86.2% of their original loading. Glycerol-based gels maintained 40.2% in similar conditions. However, ALA loss did not correspond to expected increases in PY, indicating the presence of another degradative process that prevented dimerisation. Nuclear magnetic resonance (NMR) analysis was inconclusive in respect of the mechanism observed in the patch system, but showed clearly that an esterification reaction involving ALA and both glycerol and poly(ethyleneglycol) was occurring. This was especially marked in the glycerol gels, where only 2.21% of the total expected PY was detected after 204 days at 5°C. Non-specific esterase hydrolysis demonstrated that ALA was recoverable from the gel systems, further supporting esterified binding within the gel matrices. It is conceivable that skin esterases could duplicate this finding upon topical application of the gel and convert these derivatives back to ALA in situ, provided skin penetration is not affected adversely.

Transient receptor potential melastatin 8 (TRPM8) channel involvement in the regulation of vascular tone

The transient receptor potential melastatin 8 (TRPM8) channel has been characterized as a cold and menthol receptor expressed in a subpopulation of sensory neurons but was recently identified in other tissues, including the respiratory tract, urinary system, and vasculature. Thus TRPM8 may play multiple functional roles, likely to be in a tissue- and activation state-dependent manner. We examined the TRPM8 channel presence in large arteries from rats and the functional consequences of their activation. We also aimed to examine whether these channels contribute to control of conscious human skin blood flow. TRPM8 mRNA and protein were detected in rat tail, femoral and mesenteric arteries, and thoracic aorta. This was confirmed in single isolated vascular myocytes by immunocytochemistry. Isometric contraction studies on endothelium-denuded relaxed rat vessels found small contractions on application of the TRPM8-specific agonist menthol (300 microM). However, both menthol and another agonist icilin (50 microM) caused relaxation of vessels precontracted with KCl (60 mM) or the alpha-adrenoceptor agonist phenylephrine (2 microM) and a reduction in sympathetic nerve-mediated contraction. These effects were antagonized by bromoenol lactone treatment, suggesting the involvement of Ca(2+)-independent phospholipase A(2) activation in TRPM8-mediated vasodilatation. In thoracic aorta with intact endothelium, menthol-induced inhibition of KCl-induced contraction was enhanced. This was unaltered by preincubation with either N(omega)-nitro-l-arginine methyl ester (l-NAME; 100 nM), a nitric oxide synthase inhibitor, or the ACh receptor antagonist atropine (1 microM). Application of menthol (3% solution, topical application) to skin caused increased blood flow in conscious humans, as measured by laser Doppler fluximetry. Vasodilatation was markedly reduced or abolished by prior application of l-NAME (passive application, 10 mM) or atropine (iontophoretic application, 100 nM, 30 s at 70 microA). We conclude that TRPM8 channels are present in rat artery vascular smooth muscle and on activation cause vasoconstriction or vasodilatation, dependent on previous vasomotor tone. TRPM8 channels may also contribute to human cutaneous vasculature control, likely with the involvement of additional neuronal mechanisms.

Response of vulval lichen sclerosus and squamous hyperplasia to photodynamic treatment using sustained topical delivery of aminolevulinic acid from a novel bioadhesive patch system

This study evaluated the clinical and histopathological responses of vulval lichen sclerosus (LS) and squamous hyperplasia (SH) to photodynamic therapy (PDT). A novel bioadhesive patch containing aminolevulinic acid (ALA) at a dose of (38 mg/cm(2)) was used to treat 10 patients before irradiation with light of 630 nm. Clinical, histopathological and pathological responses to treatment were assessed at 6 weeks post-treatment. After 17 cycles of PDT, six patients reported significant symptomatic relief and no cutaneous photosensitivity. Histopathological differences were not demonstrated, but statistically significant induction of apoptosis was seen. It can be concluded that ALA-PDT patch-based formulation is pragmatic and primarily offers symptomatic management of vulval LS and SH.

Priming of CD8+ and CD4+ T Cells in Experimental Leishmaniasis Is Initiated by Different Dendritic Cell Subtypes

The biological role of Langerin(+) dendritic cells (DCs) such as Langerhans cells and a subset of dermal DCs (dDCs) in adaptive immunity against cutaneous pathogens remains enigmatic. Thus, we analyzed the impact of Langerin(+) DCs in adaptive T cell-mediated immunity toward Leishmania major parasites in a Lang-DTR mouse model that allows conditional diphtheria toxin (DT)-induced ablation of The biological role of Langerin+ dendritic cells (DCs) such as Langerhans cells and a subset of dermal DCs (dDCs) in adaptive immunity against cutaneous pathogens remains enigmatic. Thus, we analyzed the impact of Langerin+ DCs in adaptive T cell-mediated immunity toward Leishmania major parasites in a Lang-DTR mouse model that allows conditional diphtheria toxin (DT)-induced ablation of Langerin+ DCs in vivo. For the first time, infection experiments with DT-treated Lang-DTR mice revealed that proliferation of L. major-specific CD8+ T cells is significantly reduced during the early phase of the immune response following depletion of Langerin+ DCs. Consequently, the total number of activated CD8+ T cells within the draining lymph node and at the site of infection is diminished. Furthermore, we show that the impaired CD8+ T cell response is due to the absence of Langerin+ dDCs and not Langerhans cells. Nevertheless, the CD4+ T cell response is not altered and the infection is cleared as effectively in DT-treated Lang-DTR mice as in control mice. This clearly demonstrates that Langerin+ DCs are, in general, dispensable for an efficient adaptive immune response against L. major parasites. Thus, we propose a novel concept that, in the experimental model of leishmaniasis, priming of CD4+ T cells is mediated by Langerin− dDCs, whereas Langerin+ dDCs are involved in early priming of CD8+ T cells.