RESUMEN
BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. METHODS: Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B∗5701 negative and hepatitis B virus negative), with viral load (VL)â ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the intention-to-treat (ITT)-exposed population (US Food and Drug Administration snapshot analysis, 10% noninferiority margin). RESULTS: Between September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. Forty percent had a baseline VL >100 000 copies/mL, and 13% had <200 CD4 cells/µL. Median weight was 73 kg and median body mass index was 24 kg/m2. At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes. CONCLUSIONS: We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated.
RESUMEN
ABSTRACT Dialdehyde starches (DAS) have been used as biomaterials due to their biocompatibility and biodegradability; nonetheless, sweet potato (Ipomea batatas L.) starch has not been researched. Films based on sweet potato DAS, mixed with native starch (NS), poly-vinyl alcohol (PVA) and glycerin have been developed with protein encapsulation, using central composite design (CCD) and response surface methodology (RSM). Input variables were oxidation degree, NS concentration and polymeric mixture volume, while output variables were film's thickness, equilibrium swelling and BSA (Bovine serum albumin) release. DAS was obtained through hydrogen peroxide (H2O2) oxidation, and the oxidation degree is referred to as H2O2 concentration. Films presented rough surfaces, and formulations containing 10% H2O2 DAS presented micropores. Water uptake was greater with higher DAS content. Film thickness depended on the volume of the polymeric suspension and influenced swelling capacity. According to RSM, the optimal formulation was DAS with 5% H2O2 and 35% NS. These results demonstrate that oxidized sweet potato starch has potential for protein encapsulation and delivery.
RESUMEN Almidones dialdehído (DAS) se han utilizado como biomateriales por su biocompatibilidad y biodegradabilidad; sin embargo, el almidón de camote (Ipomea batatas L.) no ha sido investigado. Se han desarrollado películas de DAS de camote, con almidón nativo (NS), alcohol polivinílico (PVA) y glicerina con encapsulación de proteínas, utilizando un diseño central compuesto (CCD) y metodología de superficie de respuesta (RSM). Las variables de entrada fueron: grado de oxidación, concentración de NS y volumen de la mezcla polimérica, mientras que las variables de salida fueron: espesor de la película, hinchamiento y liberación de BSA (Albúmina de Suero Bovino) en equilibrio. DAS se obtuvo mediante oxidación con peróxido de hidrógeno (H2O2), y el grado de oxidación se define como concentración de H2O2. Las películas presentaron superficies rugosas y las formulaciones con 10% H2O2 DAS presentaron microporos. La absorción de agua fue mayor con mayor contenido de DAS. El espesor de la película dependió del volumen de la mezcla polimérica e influyó en la capacidad de hinchamiento. Según RSM, la formulación óptima fue DAS con 5% H2O2 y 35% NS. Estos resultados demuestran que el almidón de camote oxidado tiene potencial para aplicaciones en la encapsulación y liberación de proteínas.
RESUMEN
Incisional wound closure is a key surgical step to facilitate tissue healing, reduce the risk of infection and obtain esthetic and functional recovery. Cyanoacrylates such as Histoacryl® have become a popular choice in surgical veterinary practice. However, how Histoacryl® is affecting tissue regeneration and bacterial load in the wound in comparison to poliglecaprone (Monocryl®) traditional suture methods remains to be determined. This work aimed to evaluate how wounded tissue responds to traditional suture with Monocryl® (poliglecaprone 25/4-0) and Histoacryl®, as well as provide evidence of their effects on wound healing in mice. Fortyeight hours after the incisional procedure, wound tissue biopsies were prepared for histological and microbiological analysis. Biopsies were fixed and colored with Mallory's trichrome and hematoxylin-eosin stains. For microbiological assays, biopsies were suspended in tryptic soy broth (TSB) and 1/10 diluted to evaluate the number of CFU in nutrient agar plates. Our results show no differences between Histoacryl® and Monocryl® traditional suture suggesting that both methods could be used to treat wounds in small animals such as rodents.
RESUMEN
OBJECTIVE: Early experience of pain and stress in the neonatal intensive care unit is known to have an effect on the neurodevelopment of the infant. However, an automated method to quantify the procedural pain or perinatal stress in premature patients does not exist. APPROACH: In the current study, EEG and ECG data were collected for more than 3 hours from 136 patients in order to quantify stress exposure. Specifically, features extracted from the EEG and heart-rate variability in both quiet and non-quiet sleep segments were used to develop a subspace linear-discriminant analysis stress classifier. MAIN RESULTS: The main novelty of the study lies in the absence of intrusive methods or pain elicitation protocols to develop the stress classifier. Three main findings can be reported. First, we developed different stress classifiers for the different age groups and stress intensities, obtaining an area under the curve in the range [0.78-0.93] for non-quiet sleep and [0.77-0.96] for quiet sleep. Second, a dysmature EEG was found in patients under stress. Third, an enhanced cortical connectivity and increased brain-heart communication was correlated with a higher stress load, while the autonomic activity did not seem to be associated to stress exposure. SIGNIFICANCE: The results shed a light on the pain and stress processing in preterm neonates, suggesting that software tools to investigate dysmature EEG might be helpful to assess stress load in premature patients. These results could be the foundation to assess the impact of stress on infants' development and to tune preventive care.
Asunto(s)
Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Dimensión del Dolor/métodos , Estrés Fisiológico , Sistema Nervioso Autónomo , Encéfalo , Electroencefalografía , Femenino , Frecuencia Cardíaca , Humanos , Recién Nacido , Embarazo , SueñoRESUMEN
In this paper we explore the use of updated tensor decompositions for the monitoring of brain hemodynamics in neonates. For this study, we used concomitant measurements of heart rate, mean arterial blood pressure, arterial oxygen saturation, EEG, and brain oxygenation - measured using near-infrared spectroscopy. These measurements were obtained from 22 neonates undergoing an INSURE procedure (INtubation, SURfactant and Extubation) and sedation using propofol. To develop the monitoring framework using tensors, we used radial basis kernel function (RBF) to construct a similarity matrix for consecutive segments of the signals. These matrices were concatenated forming a tensor. Updating canonical polyadic decomposition was used to evaluate the impact of propofol in the coupling between the different signals. Results indicate, as previously reported, a drop in the interaction between signals due to propofol administration. This shows that tensor decompositions can be useful in order to monitor the coupling between different physiological signals.
Asunto(s)
Hemodinámica , Encéfalo , Humanos , Recién Nacido , Oximetría , Oxígeno , Propofol , Espectroscopía Infrarroja CortaRESUMEN
Early life stress in the neonatal intensive care unit (NICU) predisposes premature infants to adverse health outcomes. Although those patients experience frequent apneas and sleep-wake disturbances during their hospital stay, clinicians still rely on clinical scales to assess pain and stress burden. This study addresses the relationship between stress and apneic spells in NICU patients to implement an automatic stress detector. EEG, ECG and SpO2 were recorded from 40 patients for at least 3 hours and the stress burden was assessed using the Leuven Pain Scale. Different logistic regression models were designed to detect the presence or the absence of stress based on the signals reactivity to each apneic spell. The classification shows that stress can be detected with an area under the curve of 0.94 and a misclassification error of 19.23%. These results were obtained via SpO2 dips and EEG regularity. These findings suggest that stress deepens the physiological reaction to apneas, which could ultimately impact the neurological and behavioral development.
Asunto(s)
Apnea , Enfermedades del Prematuro , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Embarazo , Estrés PsicológicoRESUMEN
OBJECTIVE: In this study, the development of EEG functional connectivity during early development has been investigated in order to provide a predictive age model for premature infants. APPROACH: The functional connectivity has been assessed via the coherency function (its imaginary part (ImCoh) and its mean squared magnitude (MSC)), the phase locking value ([Formula: see text]) and the Hilbert-Schimdt dependence (HSD) in a dataset of 30 patients, partially described and employed in previous studies (Koolen et al 2016 Neuroscience 322 298-307; Lavanga et al 2017 Complexity 2017 1-13). Infants' post-menstrual age (PMA) ranges from 27 to 42 weeks. The topology of the EEG couplings has been investigated via graph-theory indices. MAIN RESULTS: Results show a sharp decrease in ImCoh indices in θ, (4-8) Hz and α, (8-16) Hz bands and MSC in ß, (16-32) Hz band with maturation, while a more modest positive correlation with PMA is found for HSD, [Formula: see text] and MSC in [Formula: see text], θ, α bands. The best performances for the PMA prediction were mean absolute error equal to 1.51 weeks and adjusted coefficient of determination [Formula: see text] equal to 0.8. SIGNIFICANCE: The reported findings suggest a segregation of the cortex connectivity, which favours a diffused tasks architecture on the brain scalp. In summary, the results indicate that the neonates' brain development can be described via lagged-interaction network features.
Asunto(s)
Envejecimiento/fisiología , Encéfalo/fisiología , Recien Nacido Prematuro/fisiología , Modelos Neurológicos , Red Nerviosa/fisiología , Humanos , LactanteRESUMEN
This study investigates the multifractal formalism framework for quiet sleep detection in preterm babies. EEG recordings from 25 healthy preterm infants were used in order to evaluate the performance of multifractal measures for the detection of quiet sleep. Results indicate that multifractal analysis based on wavelet leaders is able to identify quiet sleep epochs, but the classifier performances seem to be highly affected by the infant's age. In particular, from the developed classifiers, the lowest area under the curve (AUC) has been obtained for EEG recordings at very young age (≤ 31 weeks post-menstrual age), and the maximum at full-term age (≥ 37 weeks post-menstrual age). The improvement in classification performances can be due to a change in the multifractality properties of neonatal EEG during the maturation of the infant, which makes the EEG sleep stages more distinguishable.
Asunto(s)
Sueño , Fenómenos Biológicos , Electroencefalografía , Humanos , Lactante , Recién Nacido , Recien Nacido PrematuroRESUMEN
In neonatal intensive care units performing continuous EEG monitoring, there is an unmet need for around-the-clock interpretation of EEG, especially for recognizing seizures. In recent years, a few automated seizure detection algorithms have been proposed. However, these are suboptimal in detecting brief-duration seizures (<; 30s), which frequently occur in neonates with severe neurological problems. Recently, a multi-stage neonatal seizure detector, composed of a heuristic and a data-driven classifier was proposed by our group and showed improved detection of brief seizures. In the present work, we propose to add a third stage to the detector in order to use feedback of the Clinical Neurophysiologist and adaptively retune a threshold of the second stage to improve the performance of detection of brief seizures. As a result, the false alarm rate (FAR) of the brief seizure detections decreased by 50% and the positive predictive value (PPV) increased by 18%. At the same time, for all detections, the FAR decreased by 35% and PPV increased by 5% while the good detection rate remained unchanged.
Asunto(s)
Convulsiones , Algoritmos , Electroencefalografía , Heurística , Humanos , Recién Nacido , Enfermedades del Recién NacidoRESUMEN
BACKGROUND: Drugs acting on the cardiovascular and central nervous system often display relatively fast clinical responses, which may differ in neonates compared to children and adults. Introduction of bedside monitoring tools might be of additional value in the pharmacodynamic (PD) assessment of such drugs in neonates. METHODS: We aim to provide an overview of the frequently used monitoring tools to assess drug effects on the hemodynamic status as well as the cerebral circulation, oxygenation and cerebral metabolism in neonates. RESULTS: The use of blood pressure measurements, heart rate variability, functional echocardiography, nearinfrared spectroscopy and (amplitude-integrated) electroencephalography in neonates is discussed, as well as new parameters introduced by these tools. Based on the 'brain circulation model', the hemodynamic effects on the brain and their interplay are summarized. In this model, 3 processes (i.e. blood processes, vascular smooth muscle processes and tissue processes) and 3 mechanisms (i.e. autoregulation, blood flow metabolism coupling and cerebral oxygen balance) are distinguished, which all may be influenced by drug administration. Finally, propofol, sevoflurane, midazolam and inotropes are used as examples of which PD has been studied using the available hemodynamic and/or cerebral monitoring tools. CONCLUSION: The implementation of (non-)invasive monitoring tools to document hemodynamic and cerebral PD effects in neonates is of relevance both in a neonatal research and intensive clinical care setting. We highlight the need to integrate these tools in future PD research. Furthermore, besides short-term drug effects, long-term outcome of drug therapy in neonates also warrants further attention.
Asunto(s)
Encéfalo/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Monitoreo de Drogas/métodos , Hemodinámica/efectos de los fármacos , Preparaciones Farmacéuticas/administración & dosificación , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Circulación Cerebrovascular/fisiología , Hemodinámica/fisiología , Humanos , Recién Nacido , Consumo de Oxígeno/efectos de los fármacos , Consumo de Oxígeno/fisiología , Preparaciones Farmacéuticas/metabolismoRESUMEN
Introducción: Lactobacillus gasseri es una bacteria láctica del tracto digestivo que tiene características probióticas importantes para el control de organismos patógenos mientras Staphylococcus aureus es una cepa patógena importante en la industria alimentaria debido a los problemas sanitarios que produce en varios países. Objetivo: evaluar las características probióticas de L. gasseri sobre S. aureus en condiciones in vitro. Materiales y métodos: se evaluó la susceptibilidad de ambas cepas a diferentes antibióticos; el efecto de inhibición de L. gasseri y su sobrenadante sobre S. aureus; el crecimiento de la cepa láctica a diferentes pH, temperaturas, sales biliares y bilis bovina; se estableció la cinética de fermentación y en ella se determinó conteo de microorganismos viables en placa, pH, consumo de azúcar, consumo de proteína y porcentaje de ácido láctico; mediante HPLC-DAD se determinaron péptidos y ácido láctico; y en el caso de aminoácidos en el sobrenadante, se determinó mediante HPLC-PDA. Resultados: se encontró resistencia de ambas cepas a los antibióticos penicilina, dicloxacilina, cifoxitin y cefalexin. La cepa láctica y el sobrenadante inhibieron el crecimiento de S. aureus. El crecimiento fue adecuado para las diferentes variables con valores entre 1,5 x 108 a 3,0 x 1014 UFC/150 μl. Se observó la fase exponencial a las 9 horas con valores de 33,33 Ln UFC/150 μl. Finalmente se identificaron, a través de HPLC-DAD, el péptido VA L-TIR-VA L, 11,70 g/l de ácido láctico y el aminoácido tirosina. Conclusión: los resultados demuestran que L. gasseri tiene características probióticas sobre S. aureus en condiciones in vitro.
Introduction. Lactobacillus gasseri is a lactic bacteria of the digestive tract which hasprobiotic properties important for the control of pathogenic organisms, and Staphylococcusaureus is an important pathogenic strain in the food industry, due to the healthproblems in several countries. Objective. Evaluate the features probiotic of L. gasseri onS. aureus in conditions in vitro. Materials and methods. We evaluated the susceptibilityof two different antibiotic resistant strains; the effect of inhibition of L. gasseri and itssupernatant on S. aureus; growth of the strain lactic to different pH, temperatures, salts bile and bile bovine; the kinetics of fermentation was also established and she foundcount of viable microorganism in plate, pH, sugar consumption, consumption of proteinand percentage of lactic acid; and using HPLC-DAD determined peptides and lacticacid, and in the case of amino acids in the supernatant was determined by HPLC-PDA. Results. Found both strains resistant to antibiotics penicillin, dicloxacillin, cifoxitin andcefalexin. The strain of lactic and supernatant inhibited the growth of S. aureus. Thegrowth was suitable for the different variables with values between 1.5 x 108 to 3.0 x1014 UFC / 150 μl. The exponential phase was observed at 9:00 with values of 33.33Ln UFC/150 μl. Finally were identified using HPLC-DAD VA L-TIR-VA L peptide,11.70 g/l of lactic acid and the amino acid tyrosine. Conclusion. The results show thatL. gasseri has probiotic properties over S. aureus in conditions in vitro.
RESUMEN
BACKGROUND: Renal transplantation is the best treatment for end stage renal disease. Acute graft rejection is one of the main complications and may influence graft survival. OBJECTIVE: To determine the incidence and features of acute cellular rejection (ACR) episodes confirmed by biopsy. METHODS: We studied a cohort of 175 patients who underwent renal transplantation between 2004 and 2012 to determine the cumulative incidence of ACR confirmed by biopsy and to identify the associated risk factors using multivariate analysis. RESULTS: The one-year patient survival was 96.6%; the graft survival was 93.7%. The incidence of ACR within one year was 14.3%, of which 46% were observed within 6 months following transplantation. The most frequently observed ACR type was 1B according to the Banff classification system (42%). A relationship between ACR and receipt of a kidney from expanded criteria donors was observed, both in univariate and adjusted multiple log-binomial regression analyses, but only 6.3% of patients received extended criteria donor kidneys. No other relationships between variables were found. CONCLUSION: ACR frequency in this study was similar to that of other cohorts reported previously. We need a bigger sample of renal transplants from expanded criteria donors, PRA and DSA test to support the results.
RESUMEN
Introducción: El drenaje lumbar externo de líquido cefalorraquídeo es una medida promisoria para la prevención de las complicaciones de la isquemia cerebral tardía asociada a la hemorragia subaracnoidea espontánea de origen aneurismático. Métodos: Se incluyeron los estudios controlados que evaluaran los efectos del drenaje lumbar externo en pacientes con hemorragia subaracnoidea aneurismática. Los desenlaces primarios fueron: nuevos infartos cerebrales y discapacidad grave. Los desenlaces secundarios fueron: deterioro clínico causado por isquemia cerebral tardía, mortalidad y necesidad de derivación ventricular definitiva. Los resultados se presentaron en riesgos relativos combinados, con un intervalo de confianza del 95% (IC 95%). Resultados: Fueron incluidos un total de 6 estudios controlados. Los riesgos relativos combinados fueron: nuevos infartos cerebrales, 0,48 (IC 95%: 0,32-0,72); discapacidad grave, 0,5 (IC 95%: 0,29-0,85); deterioro clínico causado por isquemia cerebral tardía, 0,46 (IC 95%: 0,34-0,63); mortalidad, 0,71 (IC 95%: 0,24-2,06) y necesidad de derivación ventricular definitiva, 0,80 (IC 95%: 0,51-1,24). La evaluación de la heterogeneidad demostró índices estadísticamente significativos únicamente en el análisis de discapacidad grave (I2 = 70% y p = 0,01). Conclusión: El drenaje lumbar externo se asoció con una reducción estadísticamente significativa del riesgo de complicaciones causadas por la isquemia cerebral tardía (infartos cerebrales y deterioro clínico), así como del riesgo de discapacidad grave; sin embargo, esto no se tradujo en una menor mortalidad. No obstante, no es prudente emitir recomendaciones definitivas debido a la heterogeneidad cualitativa y cuantitativa entre los estudios. Son necesarios más ensayos clínicos con definiciones homogéneas de sus desenlaces para aclarar sus efectos en los pacientes con hemorragia subaracnoidea aneurismática
Introduction: External lumbar drainage is a promising measure for the prevention of delayed aneurysmal subarachnoid hemorrhage-related ischemic complications. Methods: Controlled studies evaluating the effects of external lumbar drainage in patients with aneurysmal subarachnoid hemorrhage were included. Primary outcomes were: new cerebral infarctions and severe disability. Secondary outcomes were: clinical deterioration due to delayed cerebral ischemia, mortality, and the need of definitive ventricular shunting. Results were presented as pooled relative risks, with their 95% confidence intervals (95% CI). Results: A total of 6 controlled studies were included. Pooled relative risks were: new cerebral infarctions, 0.48 (95% CI: 0.32-0.72); severe disability, 0.5 (95% CI: 0.29-0.85); delayed cerebral ischemia-related clinical deterioration, 0.46 (95% CI: 0.34-0.63); mortality, 0.71 (95% CI: 0.24-2.06), and need of definitive ventricular shunting, 0.80 (95% CI: 0.51-1.24). Assessment of heterogeneity only revealed statistically significant indexes for the analysis of severe disability (I2 = 70% and P = .01). Conclusion: External lumbar drainage was associated with a statistically significant decrease in the risk of delayed cerebral ischemia-related complications (cerebral infarctions and clinical deterioration), as well as the risk of severe disability; however, it was not translated in a lower mortality. Nevertheless, it is not prudent to provide definitive recommendations at this time because of the qualitative and quantitative heterogeneity among included studies. More randomized controlled trials with more homogeneous outcomes and definitions are needed to clarify its impact in patients with aneurysmal subarachnoid hemorrhage
Asunto(s)
Humanos , Masculino , Femenino , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico , Intervalos de Confianza , Infarto Cerebral/complicaciones , Infarto Cerebral/epidemiología , Vasoespasmo Intracraneal/complicaciones , Vasoespasmo Intracraneal/epidemiologíaRESUMEN
Reproductive characteristics of the Pacific angel shark, Squatina californica, were evaluated from 420 specimens obtained from the artisanal fishery in La Paz Bay, Gulf of California, Mexico. Females (99 cm, 6000 g) were larger than males (95 cm, 5000 g) in terms of both total length (L(T)) and body mass (M(T)). The overall sex ratio was significantly different from the expected 1:1, suggesting sexual segregation of mature individuals in La Paz Bay. Males had developed reproductive organs and calcified claspers from 72 cm L(T); the median size at maturity (LT50 ) was 75.6 cm. In females, only the left ovary was functional and mature ovarian follicles were present from 77 cm L(T); the estimated LT50 was 77.7 cm. For the 10 gravid females sampled, uterine fecundity was between two and 10 embryos. Mature, non-gravid females with small and large ovarian follicles appeared simultaneously with gravid females with follicles that did not exceed 1.9 cm diameter.
Asunto(s)
Reproducción , Tiburones/fisiología , Animales , Tamaño Corporal , Femenino , Fertilidad , Explotaciones Pesqueras , Masculino , México , Folículo Ovárico/fisiología , Océano Pacífico , Caracteres Sexuales , Razón de MasculinidadRESUMEN
OBJECTIVES: To define how peroxisome proliferator-activated receptor (PPAR) ß/δ expression level in mesenchymal stem cells (MSCs) could predict and direct both their immunosuppressive and therapeutic properties. PPARß/δ interacts with factors such as nuclear factor-kappa B (NF-κB) and regulates the expression of molecules including vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1. Since these molecules are critical for MSC function, we investigated the role of PPARß/δ on MSC immunosuppressive properties. METHODS: We either treated human MSCs (hMSCs) with the irreversible PPARß/δ antagonist (GSK3787) or derived MSCs from mice deficient for PPARß/δ (PPARß/δ-/- MSCs). We used the collagen-induced arthritis (CIA) as model of immune-mediated disorder and the MSC-immune cell coculture assays. RESULTS: Modulation of PPARß/δ expression in hMSCs either using GSK3787 or hMSCs from different origin reveals that MSC immunosuppressive potential is inversely correlated with Ppard expression. This was consistent with the higher capacity of PPARß/δ-/- MSCs to inhibit both the proliferation of T lymphocytes, in vitro, and arthritic development and progression in CIA compared with PPARß/δ+/+ MSCs. When primed with proinflammatory cytokines to exhibit an immunoregulatory phenotype, PPARß/δ-/- MSCs expressed a higher level of mediators of MSC immunosuppression including VCAM-1, ICAM-1 and nitric oxide (NO) than PPARß/δ+/+ MSCs. The enhanced NO2 production by PPARß/δ-/- MSCs was due to the increased retention of NF-κB p65 subunit on the κB elements of the inducible nitric oxide synthase promoter resulting from PPARß/δ silencing. CONCLUSIONS: Our study is the first to show that the inhibition or knockdown of PPARß/δ in MSCs primes their immunoregulatory functions. Thus, the regulation of PPARß/δ expression provides a new strategy to generate therapeutic MSCs with a stable regulatory phenotype.
Asunto(s)
Artritis Experimental/inmunología , Tolerancia Inmunológica/genética , Células Madre Mesenquimatosas/inmunología , PPAR delta/metabolismo , PPAR-beta/metabolismo , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/genética , Proliferación Celular/genética , Citocinas/metabolismo , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Linfocitos T/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
It is now well established that beta cell replacement through pancreatic islet transplantation results in significant improvement in the quality-of-life of type 1 diabetes (T1D) patients. This is achieved through improved control and prevention of severe drops in blood sugar levels. Islet transplant therapy is on the verge of becoming standard-of-care in the USA. Yet, as with other established transplantation therapies, there remain hurdles to overcome to bring islet transplantation to full fruition as a long-lasting therapy of T1D. One of these hurdles is establishing reliable new sites, other than the liver, where durable efficacy and survival of transplanted islets can be achieved. In this article, we discuss the anterior chamber of the eye as a new site for clinical islet transplantation in the treatment of T1D. We specifically focus on the common conceptions, and preconceptions, on the requirements of islet mass, and whether or not the anterior chamber can accommodate sufficient islets to achieve meaningful efficacy and significant impact on hyperglycemia in clinical application.
RESUMEN
INTRODUCTION: External lumbar drainage is a promising measure for the prevention of delayed aneurysmal subarachnoid hemorrhage-related ischemic complications. METHODS: Controlled studies evaluating the effects of external lumbar drainage in patients with aneurysmal subarachnoid hemorrhage were included. Primary outcomes were: new cerebral infarctions and severe disability. Secondary outcomes were: clinical deterioration due to delayed cerebral ischemia, mortality, and the need of definitive ventricular shunting. Results were presented as pooled relative risks, with their 95% confidence intervals (95% CI). RESULTS: A total of 6 controlled studies were included. Pooled relative risks were: new cerebral infarctions, 0.48 (95% CI: 0.32-0.72); severe disability, 0.5 (95% CI: 0.29-0.85); delayed cerebral ischemia-related clinical deterioration, 0.46 (95% CI: 0.34-0.63); mortality, 0.71 (95% CI: 0.24-2.06), and need of definitive ventricular shunting, 0.80 (95% CI: 0.51-1.24). Assessment of heterogeneity only revealed statistically significant indexes for the analysis of severe disability (I(2)=70% and P=.01). CONCLUSION: External lumbar drainage was associated with a statistically significant decrease in the risk of delayed cerebral ischemia-related complications (cerebral infarctions and clinical deterioration), as well as the risk of severe disability; however, it was not translated in a lower mortality. Nevertheless, it is not prudent to provide definitive recommendations at this time because of the qualitative and quantitative heterogeneity among included studies. More randomized controlled trials with more homogeneous outcomes and definitions are needed to clarify its impact in patients with aneurysmal subarachnoid hemorrhage.
Asunto(s)
Líquido Cefalorraquídeo , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Hemorragia Subaracnoidea/terapia , Succión/métodos , Isquemia Encefálica/etiología , Isquemia Encefálica/prevención & control , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Hemorragia Subaracnoidea/complicacionesRESUMEN
Biological sampling of whitesnout guitarfish Rhinobatos leucorhynchus, caught as by-catch in the commercial fisheries on the Pacific coast of Ecuador, was conducted from specimens caught between April 2013 and January 2015, in order to provide further information on the reproductive biology of this species, for which data are limited. Samples comprised 1024 specimens (458 males and 566 females), with the sex ratio (1:1·23) significantly in favour of females. The total length (LT) ranged from 20·5 to 106·0 cm and showed sexual dimorphism, with females attaining a larger size. The relationship between body mass (MT) and LT was not significantly different between sexes. The length at 50% maturity for males based on internal reproductive organs was 60·9 cm LT , which was slightly larger than when based on clasper condition alone (58·5 cm LT). The LT at 50% maturity for females was 57·8 cm, and the LT at maternity was 65·1 cm. Fecundity ranged from one to seven embryos and LT at birth was 20-26 cm. According to oocyte development, two peaks of ovulation were observed (May to June and November to December). The ovarian cycle was estimated at 6 months and gestation between 5 and 6 months. Embryos showed different sizes all year-round, indicating an asynchronous cycle.
Asunto(s)
Elasmobranquios/fisiología , Reproducción , Animales , Ecuador , Elasmobranquios/anatomía & histología , Femenino , Fertilidad , Masculino , Ovulación , Océano Pacífico , Razón de MasculinidadRESUMEN
The aim of this study was to investigate force depression in Type I and Type II muscle fibers. Experiments were performed using skinned fibers from rabbit soleus and psoas muscles. Force depression was quantified after active fiber shortening from an average sarcomere length (SL) of 3.2µ m to an average SL of 2.6 µm at an absolute speed of 0.115f iber length/s and at a relative speed corresponding to 17% of the unloaded shortening velocity (V0) in each type of fibers. Force decay and mechanical work during shortening were also compared between fiber types. After mechanical testing, each fiber was subjected to myosin heavy chain (MHC) analysis in order to confirm its type (Type I expressing MHC I, and Type II expressing MHC IId). Type II fibers showed greater steady-state force depression after active shortening at a speed of 0.115 fiber length/s than Type I fibers (14.5±1.5% versus 7.8±1.7%). Moreover, at this absolute shortening speed, Type I fibers showed a significantly greater rate of force decay during shortening and produced less mechanical work than Type II fibers. When active shortening was performed at the same relative speed (17% V0), the difference in force depression between fiber types was abolished. These results suggest that no intrinsic differences were at the origin of the disparate force depressions observed in Type I and Type II fibers when actively shortened at the same absolute speed, but rather their distinct force-velocity relationships.
Asunto(s)
Fibras Musculares de Contracción Rápida/fisiología , Fibras Musculares de Contracción Lenta/fisiología , Animales , Contracción Muscular/fisiología , Cadenas Pesadas de Miosina , Conejos , Sarcómeros/fisiologíaRESUMEN
Presentamos un caso clínico de una paciente sin síntomas específicos de vasculitis, con reactantes de fase aguda normales, pero con el diagnóstico anatomopatológico de arteritis de Takayasu que nos fue remitida para realizar un PET-TAC con 18F-FDG. Los hallazgos de la exploración permitieron constatar actividad inflamatoria en las paredes vasculares de la aorta y tras la instauración del tratamiento adecuado, una segunda exploración con 18F-FDG, valoró la respuesta terapéutica correctamente. Se discute las aportaciones de la PET-TAC con 18F-FDG en el manejo de esta entidad patológica (AU)
We present a patient without specific symptoms of vasculitis, with normal acute phase reactants, but with the pathological diagnosis of Takayasu arteritis that was referred for a PET-CT with 18F-FDG. Scan findings showed inflammatory activity in the vessel walls of the aorta and after the appropriate treatment, a second scan with 18F-FDG, correctly assessed the therapeutic response. We discuss the contributions of PET-CT with 18F-FDG in the management of this pathological entity (AU)