Oral aspirin for treating venous leg ulcers

Background Venous leg ulcers (VLUs) or varicose ulcers are the final stage of chronic venous insufficiency (CVI), and are the most common type of leg ulcer. The development of VLUs on ankles and lower legs can occur spontaneously or after minor trauma. The ulcers are often painful and exudative, healing is often protracted and recurrence is common. This cycle of healing and recurrence has a considerable impact on the health and quality of life of individuals, and healthcare and socioeconomic costs. VLUs are a common and costly problem worldwideprevalence is estimated to be between 1.65% to 1.74% in the western world and is more common in adults aged 65 years and older. The main treatment for a VLU is a firm compression bandage. Compression assists by reducing venous hypertension, enhancing venous return and reducing peripheral oedema. However, studies show that it only has moderate effects on healing, with up to 50% of VLUs unhealed after two years of compression. Non-adherence may be the principal cause of these poor results, but presence of inflammation in people with CVI may be another factor, so a treatment that suppresses inflammation (healing ulcers more quickly) and reduces the frequency of ulcer recurrence (thereby prolonging time between recurrent episodes) would be an invaluable intervention to complement compression treatments. Oral aspirin may have a significant impact on VLU clinical practice worldwide. Evidence for the effectiveness of aspirin on ulcer healing and recurrence in high quality RCTs is currently lacking. Objectives To assess the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. Search methods In May 2015 we searched: The Cochrane Wounds Specialised RegisterThe Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library)Ovid MEDLINEOvid MEDLINE (In-Process & Other Non-Indexed Citations)Ovid EMBASE and EBSCO CINAHL. Additional searches were made in trial registers and reference lists of relevant publications for published or ongoing trials. There were no language or publication date restrictions. Selection criteria We included randomised controlled trials (RCTs) that compared oral aspirin with placebo or no drug intervention (in the presence or absence of compression therapy) for treating people with venous leg ulcers. Our main outcomes were time to complete ulcer healing, rate of change in the area of the ulcer, proportion of ulcers healed in the trial period, major bleeding, pain, mortality, adverse events and ulcer recurrence (time for recurrence and proportion of recurrence). Data collection and analysis Two review authors independently selected studies for inclusion, extracted data, assessed the risk of bias of each included trial and assessed overall quality of evidence for the main outcomes in the 'Summary of findings' table. Main results The electronic search located 62 studies. We included two RCTs of oral aspirin (300 mg/daily) given in addition to compression compared with compression and placebo, or compression alone. To date, the impact of aspirin on VLUs has been examined by only two randomised clinical trials, both with a small number of participants. The first RCT was conducted in the United Kingdom (n=20) and reported that daily administration of aspirin (300mg) in addition to compression bandages increased both the rate of healing, and the number of participants healed when compared to placebo in addition to compression bandaging over a four month period. Thirty-eight per cent of the participants given aspirin reported complete healing compared with 0% in the placebo group. Improvement (assessed by reduction in wound size) occurred in 52% of the participants taking aspirin compared with 26% in those taking placebo). The study identified potential benefits of taking aspirin as an adjunct to compression but the sample size was small, and neither the mechanism by which aspirin improved healing nor its effects on recurrence were investigated. In 2012 an RCT in Spain (n=51) compared daily administration of aspirin (300mg) in addition to compression bandages with compression alone over a five month period. There was little difference in complete healing rates between groups (21/28 aspirin and 17/23 compression bandages alone) but the average time to healing was shorter (12 weeks in the treated group vs 22 weeks in the compression only group) and the average time for recurrence was longer in the aspirin group (39 days: [SD 6.0] compared with 16.3 days [SD 7.5] in the compression only group). Although this trial provides some limited data about the potential use of aspirin therapy, the sample size (only 20 patients) was too small for us to draw meaningful conclusions. In addition, patients were only followed up for 4 months and no information on placebo was reported. Authors' conclusions Low quality evidence from two trials indicate that there is currently insufficient evidence for us to draw definitive conclusions about the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. We downgraded the evidence to low quality due to potential selection bias and imprecision due to the small sample size. The small number of participants may have a hidden real benefit, or an increase in harm. Due to the lack of reliable evidence, we are unable to draw conclusions about the benefits and harms of oral daily aspirin as an adjunct to compression in VLU healing or recurrence. Further high quality studies are needed in this area.Evidence Based Actions Department From Marilia Medical School - FAMEMA, BrazilFAPESP-Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, BrazilNational Institute for Health ResearchEvidence Based Health Actions Department and Thoracic Surgery Department, Marilia Medical School, Marilia, BrazilDepartment of Medicine, Federal University of São Paulo, São Paulo, BrazilDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, AustraliaDepartment of Medicine, Federal University of São Paulo, São Paulo, BrazilWeb of Scienc

Cladophialophora carrionii: agente raro de cromoblastomicose no estado do Rio de Janeiro, Brasil

A 73 year-old male farm laborer from a rural area presented a 15 year history of extensive tumoral lesions over his left leg. Histological studies of skin biopsy showed pseudoepitheliomatous hyperplasia and granulomatous chronic inflammatory process with muriform cells, confirming chromoblastomycosis (CBM). Cladophialophora carrionii was isolated in culture. Treatment with itraconazole 400 mg/day for 12 months resulted in complete remission of lesions. As far we aware, this is the first case report of CBM caused by Cladophialophora carrionii in Rio de Janeiro State, Brazil.Lavrador, com 73 anos, residente em área rural apresentava há 15 anos lesões tumorais disseminadas na perna esquerda. Exame histopatológico de biópsia de pele mostrou hiperplasia pseudo-epiteliomatosa e processo inflamatório crônico granulomatoso com células muriformes, confirmando o diagnóstico de cromoblastomicose (CBM). Cladophialophora carrionii foi isolado na cultura. Tratamento com itraconazol 400 mg/dia durante 12 meses resultou na completa remissão das lesões. Este é o primeiro relato de CBM causado por C. carrionii no estado do Rio de Janeiro, Brasil

Nonequilibrium Probabilistic Dynamics of the Logistic Map at the Edge of Chaos

We consider nonequilibrium probabilistic dynamics in logistic-like maps $x_{t+1}=1-a|x_t|^z$, $(z>1)$ at their chaos threshold: We first introduce many initial conditions within one among $W>>1$ intervals partitioning the phase space and focus on the unique value $q_{sen}<1$ for which the entropic form $S_q \equiv \frac{1-\sum_{i=1}^{W} p_i^q}{q-1}$ {\it linearly} increases with time. We then verify that $S_{q_{sen}}(t) - S_{q_{sen}}(\infty)$ vanishes like $t^{-1/[q_{rel}(W)-1]}$ [$q_{rel}(W)>1$]. We finally exhibit a new finite-size scaling, $q_{rel}(\infty) - q_{rel}(W) \propto W^{-|q_{sen}|}$. This establishes quantitatively, for the first time, a long pursued relation between sensitivity to the initial conditions and relaxation, concepts which play central roles in nonextensive statistical mechanics.Comment: Final version with new Title and small modifications. REVTeX, 8 pages and 4 eps figure

An activating mutation in the CRHR1 gene is rarely associated with pituitary-dependent hyperadrenocorticism in poodles

OBJECTIVES: Pituitary-dependent hyperadrenocorticism is the most common cause of naturally occurring hypercortisolism in dogs. CRHR1 expression in human and dog corticotrophinomas suggested that this gene affects pituitary tumorigenesis. The present study aimed to investigate mutations in the CRHR1 coding region in poodles with pituitary-dependent hyperadrenocorticism. METHODS: Fifty poodles with pituitary-dependent hyperadrenocorticism and 50 healthy poodles were studied. Genomic DNA was amplified by PCR and analyzed by Sanger sequencing. RESULTS: The novel CRHR1 p.V97M mutation was identified in one dog. This valine residue, located in the amino-terminal extracellular domain, exhibits high affinity for its corticotropin-releasing hormone (CRH) ligand. Bioinformatic analysis revealed structural rearrangements in the mutant protein, with a 17% increase in the surface binding affinity between CRHR1 and CRH. In vitro functional studies showed that mutant CRHR1 induced higher ACTH secretion than the wild type after stimulation with human CRH. CONCLUSION: These results suggest that germline activating mutations in CRHR1 may be a rare cause of pituitary hyperadrenocorticism in poodles

2,4,5-Triaminopyrimidines as blue fluorescent probes for cell viability monitoring: synthesis, photophysical properties, and microscopy applications

Monitoring cell viability is critical in cell biology, pathology, and drug discovery. Most cell viability assays are cell-destructive, time-consuming, expensive, and/or hazardous. Herein, we present a series of newly synthesized 2,4,5-triaminopyrimidine derivatives able to discriminate between live and dead cells. To our knowledge, these compounds are the first fluorescent nucleobase analogues (FNAs) with cell viability monitoring potential. These new fluorescent molecules are synthesized using highly efficient and cost- effective methods and feature unprecedented photophysical properties (longer absorption and emission wavelengths, environment-sensitive emission, and unprecedented brightness within FNAs). Using a live– dead Saccharomyces cerevisiae cell and theoretical assays, the fluorescent 2,4,5-triaminopyrimidine derivatives were found to specifically accumulate inside dead cells by interacting with dsDNA grooves, thus paving the way for the emergence of novel and safe fluorescent cell viability markers emitting in the blue region. As the majority of commercially available viability dyes emit in the green to red region of the visible spectrum, these novel markers might be useful to meet the needs of blue markers for co-staining combinations

ANÁLISE DAS REPETIÇÕES MÁXIMAS ESTIMADAS ATRAVÉS DO TESTE DE UMA REPETIÇÃO MÁXIMA

A adequada prescrição do treinamento de força (TF) deve considerar o volume e a intensidade aplicada aos exercícios. Este experimento teve como objetivo verificar o número de repetições máximas (RM) realizadas em quatro exercícios nos percentuais de 60 e 80% de uma repetição máxima (1RM). A amostra foi constituída de 10 homens treinados (29,5 À 5,8 anos; 85,2 À 7,0 kg; 177 À 10 cm) que realizaram o teste de 1RM nos exercícios desenvolvimento (DS), tríceps na testa (TT), supino reto (SR) e rosca bíceps (RB). A análise estatística foi feita através do método descritivo. Os valores na intensidade de 60% de 1RM foram: DS = 15,1 À 3,7 RM; TT = 16,3 À 4,6 RM; SR = 16,9 À 4,7 RM; RB = 11,0 À 2,3 RM, e os valores obtidos na intensidade de 80% de 1RM foram: DS = 7,9 À 2,2 RM; TT = 8,8 À 3,4 RM; SR = 8,2 À 2,9 RM; RB = 5,0 À 2,2 RM. A partir dos resultados apresentados no presente experimento, pode-se observar que nem todos os exercícios e indivíduos apresentam a mesma média de RM para determinada carga. Sendo assim, seria mais adequada a prescrição do TF através de testes submáximos. ANALYSIS OF THE ESTIMATED MAXIMUM REPETITIONS THROUGH ONE MAXIMUM REPETITION Abstract: The appropriate prescription of the strength training (ST) should to consider the volume and the applied intensity to the exercises. This experiment had as objective verifies the number of repetitions maximum (RM) accomplished in four exercises in the percentile of 60 and 80% of a one maximum repetition (1RM). The sample was constituted of 10 trained men (29.5 À 5.8 years; 85.2 À 7.0 kg; 177 À 10 cm) accomplished the test of 1RM in the exercises shoulder-press (SP), triceps-extension (TE), bench-press (BP) and biceps-curl (BC). The statistical analysis was made through descriptive method. The values in the intensity of 60% of 1RM were: SP = 15.1 À 3.7 RM; TE = 16.3 À 4.6 RM; BP = 16.9 À 4.7 RM; BC = 11 À 2.3 RM, and the values obtained in the intensity of 80% of 1RM were: SP = 7.9 À 2.2 RM; TE = 8.8 À 3.4 RM; BP = 8.2 À 2.9 RM; BC = 5.0 À 2.2 RM. Starting from the results presented in the present experiment, can be observed that nor all of the exercises and individuals present the same average of RM for certain load. Being like this, it would be more appropriate the prescription of TF through submaximal tests

Estratigrafía de alta resolución de depósitos de flujos gravitacionales de la Formación Los Molles (Grupo Cuyo - Jurásico) en la región de La Jardinera, cuenca Neuquina

El Grupo Cuyo en el área del arroyo La Jardinera (Pliensbachiano a Caloviano Temprano) refleja una fisiografía de cuenca de plataforma y talud. Una discordancia de orden mayor define la culminación de una espesa sucesión de turbiditas y representa un límite de secuencia de 2do orden. La más antigua secuencia de 2do orden comprende el tramo basal de la Formación Los Molles e incluye un ciclo transgresivo-regresivo asignado a estratos de base de talud y fondo de cuenca. La secuencia más joven, que incluye el resto del Grupo Cuyo, consiste de una sucesión regresiva puntuada por varios desplazamientos abruptos de elementos fisiográficos (límites de secuencia de 3er orden). Las secuencias depositacionales de 3er orden incluyen depósitos de talud y de base de talud del Aaleniano de la Formación Los Molles, facies de plataforma del Bajociano Temprano en la transición entre las formaciones Los Molles y Lajas, y sedimentitas de plataforma interna a nearshore del Bajociano medio a tardío de la Formación Lajas, que es a su vez cubierta por depósitos del Bathoniano aluvial de la Formación Challacó. Ciclos de más alta frecuencia alternan en la sucesión y han controlado el origen, depositación y abandono de los elementos arquitecturales. Análisis de facies y de elementos arquitecturales indican que los depósitos gravitatorios densos de la Formación Los Molles encuadran en un modelo de rampa submarina. Los tres tipos de flujos gravitacionales (GF) han sido relacionados a caídas del nivel del mar de 4to orden. Los GF1 fueron asignados a flujos hiperpícnicos producidos durante un cortejo temprano de mar bajo de 4to orden, coevo con incisión fluvial en la plataforma, que evolucionaran a flujos turbidíticos en el talud, produciendo cargas de pulsos depositacionales cuya signatura composicional es fluvial. El sistema de GF1 incluye canales relativamente pequeños sobre el talud, lóbulos bien desarrollados en la base del talud y la planicie de fondo de cuenca proximales, así como lóbulos adventicios en la planicie del fondo de cuenca. Los estratos GF2 fueron asignados a flujos hiperpícnicos influenciados por un componente oscilatorio y relacionados a cortejos tardíos de mar bajo de 4to orden, que también incluyen relleno de canales incididos. Ellos están caracterizados en el talud por areniscas onduladas y laminadas ampliamente distribuidas y facies heterolíticas, que incluyen scours de bajo relieve en sus porciones centrales. Ellos representan flujos densos más diluidos y de grano más fino con respecto a los GF1. Los GF3, también asociados con cuñas de mar bajo de 4to orden, comprenden depósitos de flujos en masa y debris de talud y de base de talud, que representan clásicos surges de corta duración causados por debilidades en taludes relativamente abruptos. Los cortejos transgresivos y de mar alto de 4to orden llevaron al abandono de la etapa turbidítica y extensiva depositación de fango.The Pliensbachian to Early Callovian Cuyo Group in the Arroyo La Jardinera area reflects a shelf-slope-basin plain physiography. A major unconformity defines the onset of a thick turbidite succession and represents a 2nd order sequence boundary. The older 2nd order depositional sequence comprises the base of Los Molles Formation and includes a transgressive-regressive cycle ascribed to basin plain and slope rise strata. The younger one, which includes the rest of the Cuyo Group, consists of a regressive succession punctuated by several abrupt shifts of physiographic elements (3rd order sequence boundaries). The 3rd order depositional sequences include Aalenian slope rise and slope deposits in the Los Molles Formation, Early Bajocian shelfal facies at the transition of the Los Molles and Lajas formations, and Middle to Late Bajocian inner shelf to nearshore strata in the Lajas Formation that are overlain by Bathonian alluvial deposits of the Challacó Formation. Higher frequency cycles punctuate the succession and have controlled the origin, deposition and abandonment of the architectural elements. Facies and architectural elements analyses indicate that gravity flow deposits in the Los Molles Formation fit in a submarine ramp model. The three identified gravity flow (GF) types have been related to 4th order relative sea-level falls. The GF1 was ascribed to hyperpycnal flows produced during 4th order early lowstand, coeval to fluvial incision on the shelf, which were ignited in the slope and produced depletive depositional pulses with a fluvial compositional signature. The GF1 system includes relatively small channels in the slope, well-developed lobes in the slope rise and proximal basin plain, and lobe fringes in the basin plain. The GF2 strata were ascribed to hyperpycnal flows influenced by an oscillatory component and related to the 4th order late lowstand systems tract that also includes the incised channels fill. They are characterized in the slope by widespread, undulating and laminated sandstone and heterolithic facies, which include low relief scours at their central portions. They represent more diluted and finer-grained density flows relative to the GF1. The GF3, also associated with the 4th order lowstand wedge, comprises mass and debris flow deposits in the slope and slope rise that represent classical, short-lived surges caused by slope failures on relatively steep slopes. The 4th order transgressive and highstand systems tracts led to the abandonment of the turbidite stages and widespread mud deposition.Fil: Paim, Paulo S. G.. Universidad de Vale do Rio dos Sinos; BrasilFil: Silveira, Ariane. Universidad de Vale do Rio dos Sinos; BrasilFil: Lavina, Ernesto L. C.. Universidad de Vale do Rio dos Sinos; BrasilFil: Faccini, Ubiratan F.. Universidad de Vale do Rio dos Sinos; BrasilFil: Leanza, Hector Armando. Secretaría de Industria y Minería. Servicio Geológico Minero Argentino; Argentina. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Teixeira de Oliveira, J. M. M.. Universidad de Vale do Rio dos Sinos; BrasilFil: D'Avila, Roberto S. F.. Universidad de Vale do Rio dos Sinos; Brasil. Petrobras Argentina S.a; Argentin