Endothelial, but not smooth muscle, peroxisome proliferator-activated receptor β/δ regulates vascular permeability and anaphylaxis.

BACKGROUND: Remodeling of quiescent vessels with increases in permeability, vasodilatation, and edema are hallmarks of inflammatory disorders. Factors involved in this type of remodeling represent potential therapeutic targets. OBJECTIVES: We investigated whether the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) β/δ, a regulator of metabolism, fibrosis, and skin homeostasis, is involved in regulation of this type of remodeling. METHODS: Wild-type and various Pparb/d mutant mice were used to monitor dermal acute vascular hyperpermeability (AVH) and passive systemic anaphylaxis-induced hypothermia and edema. PPARβ/δ-dependent kinase activation and remodeling of endothelial cell-cell junctions were addressed by using human endothelial cells. RESULTS: AVH and dilatation of dermal microvessels stimulated by vascular endothelial growth factor A, histamine, and thrombin are severely compromised in PPARβ/δ-deficient mice. Selective deletion of the Pparb/d-encoding gene in endothelial cells in vivo similarly limits dermal AVH and vasodilatation, providing evidence that endothelial PPARβ/δ is the major player in regulating acute dermal microvessel remodeling. Furthermore, endothelial PPARβ/δ regulatory functions are not restricted to the skin vasculature because its deletion in the endothelium, but not in smooth muscle cells, also leads to reduced systemic anaphylaxis, the most severe form of allergic reaction, in which an acute vascular response plays a key role. PPARβ/δ-dependent AVH activation likely involves the activation of mitogen-activated protein kinase and Akt pathways and leads to downstream destabilization of endothelial cell-cell junctions. CONCLUSION: These results unveil not only a novel function of PPARβ/δ as a direct regulator of acute vessel permeability and dilatation but also provide evidence that antagonizing PPARβ/δ represents an important strategy to consider for moderating diseases with altered endothelial integrity, such as acute inflammatory and allergic disorders.

Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure.

Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

Cambio climático y diversidad de la flora vascular en las montañas tabulares de Guayana.

Una de las posibles consecuencias del calentamiento global es la extinción de especies de alta montaña por migración ascendente de las condiciones ambientales y pérdida de hábitat, fenómeno que, por el momento, ha sido considerado únicamente en montañas templadas y boreales. Este trabajo analiza la misma situación en montañas tropicales y estima el grado de amenaza de la flora vascular de las cimas de las montañas neotropicales de Guayana, al norte de Sudamérica. Del estudio basado en una muestra de 83 especies, entre aproximadamente el 8 y el 33% de las mismas se encuentran en peligro de extinguirse debido a la desaparición de su hábitat. La mayoría de estas especies son endémicas de Guayana, por lo que su desaparición afectaría a la biodiversidad global.

Statistical mechanics of multi-edge networks

Statistical properties of binary complex networks are well understood and recently many attempts have been made to extend this knowledge to weighted ones. There are, however, subtle yet important considerations to be made regarding the nature of the weights used in this generalization. Weights can be either continuous or discrete magnitudes, and in the latter case, they can additionally have undistinguishable or distinguishable nature. This fact has not been addressed in the literature insofar and has deep implications on the network statistics. In this work we face this problem introducing multiedge networks as graphs where multiple (distinguishable) connections between nodes are considered. We develop a statistical mechanics framework where it is possible to get information about the most relevant observables given a large spectrum of linear and nonlinear constraints including those depending both on the number of multiedges per link and their binary projection. The latter case is particularly interesting as we show that binary projections can be understood from multiedge processes. The implications of these results are important as many real-agent-based problems mapped onto graphs require this treatment for a proper characterization of their collective behavior.

Use of the Flixene vascular access graft as an early cannulation solution.

OBJECTIVE: The primary end points of this study were safety and efficacy of early cannulation of the Flixene graft (Maquet-Atrium Medical, Hudson, NH). Secondary end points were complications and patency. METHODS: This is a prospective single-center nonrandomized study. Study data included patient characteristics; history of vascular access; operative technique; interval between implantation and initial cannulation; complications; and patency at 1 month, 3 months, and every 6 months. Patency rates were estimated by the Kaplan-Meier method. RESULTS: Between January 2011 and September 2013, a total of 46 Flixene grafts were implanted in 44 patients (27 men) with a mean age of 63 years. The implantation site was the upper arm in 67% of cases, the forearm in 11%, and the thigh in 22%. Seven grafts were never cannulated during the study period. Of the remaining 39 grafts, 32 (82%) were successfully cannulated within the first week after implantation, including 16 (41%) on the first day. The median interval from implantation to initial cannulation was 2 days (interquartile range, 1-3 days). The median follow-up was 223.5 days (interquartile range, 97-600 days). Five hematomas occurred, but only one required surgical revision. Primary assisted and secondary patency rates were 65% and 86%, respectively, at 6 months and 56% and 86%, respectively, at 1 year. CONCLUSIONS: This study suggests that cannulation of the Flixene graft within 1 week after implantation is safe and effective. Early cannulation avoids or shortens the need for a temporary catheter. One-year patency rates appeared to be comparable to those achieved with conventional grafts, but long-term follow-up and randomized controlled studies will be needed to confirm this finding.

Estudo clínico e videofluoroscópico da disfagia na fase subaguda do acidente vascular encefálico

OBJETIVO: Correlacionar, em pacientes portadores de acidente vascular encefálico (AVE) na fase subaguda, as alterações clínicas da deglutição com as observadas na videofluoroscopia. MATERIAIS E MÉTODOS: De 37 portadores de AVE subagudo confirmado por exame de imagem, 26 pacientes de ambos os sexos, com idade média de 59,69 anos, foram avaliados clínica e videofluoroscopicamente. Consideramos como variáveis para pareamento estatístico os parâmetros clínicos indicativos de penetração/aspiração e sua confirmação na videofluoroscopia. RESULTADOS: Identificamos disfagia em 19 (73%) dos 26 pacientes que fizeram videofluoroscopia; dez (38,46%) apresentaram penetração/aspiração de líquidos. Os dados resultantes mostraram não existir correlação (p < 0,05) entre a presença de disfagia e/ou disartria e a presença de penetração/aspiração de líquidos na videofluoroscopia. Houve correlação entre a presença de penetração/aspiração de líquidos observados na videofluoroscopia com os seguintes parâmetros clínicos: estado dos dentes (p = 0,047), mobilidade (p = 0,019) e sensibilidade da face (p = 0,039) e mobilidade da língua (p = 0,012). CONCLUSÃO: Não foi possível definir a presença de penetração/aspiração de líquidos nas vias aéreas por dados epidemiológicos do AVE. A existência de mau estado de preservação dos dentes, alterações na mobilidade da face e da língua e na sensibilidade da face mostrou risco aumentado de penetração/aspiração para líquidos. Permanece importante a indicação da videofluoroscopia para melhor avaliação dos quadros de disfagia após AVE.

Angiografia por ressonância magnética: aspectos técnicos de um método de estudo vascular não-invasivo

As primeiras técnicas de angiografia por ressonância magnética (angio-RM) utilizavam seqüências sensíveis ao fluxo sanguíneo para estabelecimento do contraste vascular. Há três técnicas fundamentadas neste princípio: contraste de fase ("phase-contrast"), TOF ("time-of-flight") e as técnicas de sangue escuro ("black blood"). Estas seqüências, de aquisição demorada, são mais suscetíveis a artefatos de movimento, perda de sinal em áreas de estenoses ou turbilhonamento de fluxo, e apresentam ainda baixa sensibilidade à detecção do fluxo lento. O uso do contraste paramagnético para estudos angiográficos pela ressonância magnética ofereceu um método simples, rápido e de excelente detalhamento vascular, baseando o contraste da imagem no realce do sinal vascular em oposição à supressão dos demais tecidos. Metodologias modernas que priorizam a obtenção do espaço k central, responsável pelo contraste da imagem, e o aperfeiçoamento das técnicas de planejamento do intervalo temporal para aquisição dos dados foram fatores fundamentais para o aprimoramento técnico da angio-RM. O papel atual da angio-RM como ferramenta diagnóstica merece destaque na avaliação de anomalias anatômicas, estenoses, oclusões e complicações vasculares pós-cirúrgicas, principalmente nos casos de transplantes de órgãos. Suas principais vantagens estão na não utilização do contraste iodado ou radiação ionizante, rapidez e fácil execução, mínima invasividade e possibilidade de avaliar complementarmente o parênquima de órgãos adjacentes de interesse diagnóstico.

Energetics and mechanics of walking in patients with chronic low back pain and healthy matched controls.

PURPOSE: Walking in patients with chronic low back pain (cLBP) is characterized by motor control adaptations as a protective strategy against further injury or pain. The purpose of this study was to compare the preferred walking speed, the biomechanical and the energetic parameters of walking at different speeds between patients with cLBP and healthy men individually matched for age, body mass and height. METHODS: Energy cost of walking was assessed with a breath-by-breath gas analyser; mechanical and spatiotemporal parameters of walking were computed using two inertial sensors equipped with a triaxial accelerometer and gyroscope and compared in 13 men with cLBP and 13 control men (CTR) during treadmill walking at standard (0.83, 1.11, 1.38, 1.67 m s(-1)) and preferred (PWS) speeds. Low back pain intensity (visual analogue scale, cLBP only) and perceived exertion (Borg scale) were assessed at each walking speed. RESULTS: PWS was slower in cLBP [1.17 (SD = 0.13) m s(-1)] than in CTR group [1.33 (SD = 0.11) m s(-1); P = 0.002]. No significant difference was observed between groups in mechanical work (P ≥ 0.44), spatiotemporal parameters (P ≥ 0.16) and energy cost of walking (P ≥ 0.36). At the end of the treadmill protocol, perceived exertion was significantly higher in cLBP [11.7 (SD = 2.4)] than in CTR group [9.9 (SD = 1.1); P = 0.01]. Pain intensity did not significantly increase over time (P = 0.21). CONCLUSIONS: These results do not support the hypothesis of a less efficient walking pattern in patients with cLBP and imply that high walking speeds are well tolerated by patients with moderately disabling cLBP.