Kinetics and Mechanism of Camptothecin Release from Transferrin-Gated Mesoporous Silica Nanoparticles through a pH-Responsive Surface Linker.

Stimuli-responsive nanomaterials have emerged as a promising strategy for inclusion in anticancer therapy. In particular, pH-responsive silica nanocarriers have been studied to provide controlled drug delivery in acidic tumor microenvironments. However, the intracellular microenvironment that the nanosystem must face has an impact on the anticancer effect; therefore, the design of the nanocarrier and the mechanisms that govern drug release play a crucial role in optimizing efficacy. Here, we synthesized and characterized mesoporous silica nanoparticles with transferrin conjugated on their surface via a pH-sensitive imine bond (MSN-Tf) to assess camptothecin (CPT) loading and release. The results showed that CPT-loaded MSN-Tf (MSN-Tf@CPT) had a size of ca. 90 nm, a zeta potential of -18.9 mV, and a loaded content of 13.4%. The release kinetic data best fit a first-order model, and the predominant mechanism was Fickian diffusion. Additionally, a three-parameter model demonstrated the drug-matrix interaction and impact of transferrin in controlling the release of CPT from the nanocarrier. Taken together, these results provide new insights into the behavior of a hydrophobic drug released from a pH-sensitive nanosystem.

Estimation of liver fibrosis using elastography in cholestatic diseases: systematic review and meta-analysis.

INTRODUCTION: staging fibrosis extent in liver disease is highly relevant for appropriate management. Liver biopsy remains the reference standard for assessment, but noninvasive methods such as elastography are becoming increasingly accurate and relevant. However, evidence regarding elastography in cholestatic diseases is lower than in other etiologies. METHODS: we searched MEDLINE, EMBASE and Web of Science for publications on the diagnostic accuracy of transient elastography and sonoelastography in cholestatic diseases (PBC and PSC) using biopsy as the reference standard. A systematic review and meta-analysis of the results was then carried out. RESULTS: a total of 13 studies were included. Using transient elastography in PBC sensitivity and specificity were estimated to be 0.76 and 0.93; 0.88 and 0.9; and 0.91 and 0.95 for ≥ F2, ≥ F3 and = F4, respectively. For sonoelastography in PBC sensitivity and specificity estimates were 0.79 and 0.82; 0.95 and 0.86; and 0.94 and 0.85 for ≥ F2, ≥ F3 y = F4, respectively. In PSC, transient elastography had a sensivity and specificity of 0.76 and 0.88; 0.91 and 0.86; and 0.71 and 0.93 for ≥ F2, ≥ F3 and = F4, respectively. CONCLUSION: elastography has adequate diagnostic accuracy in the assessment of fibrosis stages in cholestatic liver diseases.

Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials / Factor estimulante de colonias de granulocitos en el fallo hepático agudo sobre crónico: revisión sistemática y metaanálisis de estudios aleatorizados controlados

Background and aims: A dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF. Methods: Systematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60–90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator. Results: The initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I2=74%, Chi2=11.57, p=0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio=0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio=0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF. Conclusion. In a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF...(AU)

Antecedentes y objetivos: La respuesta inmune disfuncional es clave en la patogénesis del fallo hepático agudo sobre crónico (ACLF). Se ha sugerido que la utilización de factor estimulante de colonias de granulocitos (G-CSF) aumenta la supervivencia de los pacientes con ACLF al mejorar la disfunción inmune y promover la regeneración hepática. El objetivo del estudio es evaluar el beneficio en supervivencia que proporciona la administración de G-CSF en comparación con el tratamiento médico estándar (SMT) en pacientes con ACLF. Métodos: Se llevó a cabo una revisión sistemática y meta-análisis de estudios aleatorizados y controlados. El objetivo principal fue analizar la supervivencia a los 60-90 días. Se realizó una búsqueda en Ovid Medline, EMBASE, y el registro central de estudios controlados de Cochrane desde su inicio hasta agosto 2021. También se realizaron búsquedas manuales en la bibliografía de artículos relevantes y presentaciones a congresos. Se utilizó la herramienta revisada de Cochrane para analizar la calidad y el riesgo de sesgos. Los datos fueron extraídos por dos investigadores independientes y las discrepancias fueron resueltas por un tercer investigador. Resultados: La búsqueda inicial identificó 142 estudios. De estos, 4 aleatorizados y controlados fueron elegidos para el análisis cuantitativo, incluyendo un total de 310 pacientes (154 G-CSF y 156 SMT). Se objetivó un alto grado de heterogeneidad entre los estudios (I2 = 74%, Chi 2 = 11.57, p = 0.009). La administración de G-CSF no aumentó la supervivencia en el grupo de pacientes con ACLF (modelo de efectos aleatorios, risk ratio = 0.64 [95% CI 0.39, 1.07]). Sin embargo, cuando se analizó el subgrupo de estudios realizados en Asia, sí se objetivó una disminución significativa de la mortalidad (risk ratio = 0.53 [95% CI 0.35, 0.81]). Las escalas de gravedad (MELD y Child) y la movilización de células CD34+ periféricas no mejoró significativamente tras la administración de G-CSF....(AU)

Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: A dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF. METHODS: Systematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60-90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator. RESULTS: The initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I2=74%, Chi2=11.57, p=0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio=0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio=0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF. CONCLUSION: In a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF. The beneficial effects observed in Asian studies, as opposed to the European region, suggest that specific populations may benefit from further research aiming to identify certain subgroups with favourable outcomes when using G-CSF.

Monitoring of Thermal Comfort and Air Quality for Sustainable Energy Management inside Hospitals Based on Online Analytical Processing and the Internet of Things.

There is a need to ensure comfortable conditions for hospital staff and patients from the point of view of thermal comfort and air quality so that they do not affect their performance. We consider the need for hospital employees and patients to enjoy conditions of greater well-being during their stay. This is understood as a comfortable thermal sensation and adequate air quality, depending on the task they are performing. The contribution of this article is the formulation of the fundamentals of a system and platform for monitoring thermal comfort and Indoor Air Quality (IAQ) in hospitals, based on an Internet of Things platform composed of a low-cost sensor node network that is capable of measuring critical variables such as humidity, temperature, and Carbon Dioxide (CO2). As part of the platform, a multidimensional data model with an On-Line Analytical Processing (OLAP) approach is presented that offers query flexibility, data volume reduction, as well as a significant reduction in query response times. The experimental results confirm the suitability of the platform's data model, which facilitates operational and strategic decision making in complex hospitals.

Anti-Hu-mediated paraneoplastic chronic intestinal pseudo-obstruction associated with extraskeletal myxoid chondrosarcoma.

Chronic intestinal pseudo-obstruction (CIPO) is characterized by symptoms and signs of bowel obstruction in the absence of an anatomical cause. Almost 50 % of cases are secondary to systemic diseases of neurological, paraneoplastic, autoimmune, metabolic, or infectious origin.

Forecasting emergency admissions due to respiratory diseases in high variability scenarios using time series: A case study in Chile.

Respiratory diseases are ranked in the top ten group of the most frequent illness in the globe. Emergency admissions are proof of this issue, especially in the winter season. For this study, the city of Santiago de Chile was chosen because of the high variability of the time series for admissions, the quality of data collected in the governmental repository DEIS (selected period: 2014-2018), and the poor ventilation conditions of the city, which in winter contributes to increase the pollution level, and therefore, respiratory emergency admissions. Different forecasting models were reviewed using the Akaike Information Criteria (AIC) with other error estimators, such as the Root Mean Square Error (RMSE), for selecting the best approach. At the end, Seasonal Autoregressive Integrated Moving Average (SARIMA) model, with parameters (p,d,q)(P,D,Q)s=(2,1,3)(3,0,2)7, was selected. The Mean Average Percentage Error (MAPE) for this model was 7.81%. After selection, an investigation of its performance was made using a cross-validation through a rolling window analysis, forecasting up to 30 days ahead (testing period of one year). The results showed that error do not exceed a MAPE of 20%. This allows taking better resource managing decisions in real scenarios: reactive staff hiring is avoided given the reduction of uncertainty for the medium term forecast, which translates into lower costs. Finally, a methodology for the selection of forecasting models is proposed, which includes other constraints from resource management, as well as the different impacts for social well-being.

Single-Dose Bioavailability for Prophylactic Coverage in Patients Undergoing Dental Implant Surgery.

PURPOSE: The use of antibiotic prophylaxis in dental implant surgery is a routine dental practice to prevent implant failure. Current systematic reviews have yet to confirm the effectiveness of antibiotic treatment at reducing postoperative infection rates in implant procedures. The aim of this study was to quantify amoxicillin plasma levels at the peripheral venous blood and at the surgical implant site in patients undergoing dental treatment. MATERIALS AND METHODS: A prospective study was conducted. Patients undergoing dental implant surgery were selected, and preoperative doses of 1 g of amoxicillin, in the form of an oral tablet, were administered 1 hour prior to implant surgery. The blood samples (1.5 mL) were collected from both the venous and implant sites. Data on the antibiotics were measured using high-pressure liquid chromatography. The quantification method was validated for linearity, selectivity, and detection limits. Statistical analysis of plasma antibiotic was performed, comparing both samples and the age, height, weight, and body mass index (BMI) (Wilcoxon test, P < .05; STATA v.10.0). RESULTS: Thirty-two patients (mean age: 56.28 ± 12.2 years; range: 31 to 79 years; 20 men) were selected. Both blood samples were taken at a mean 1.16 ± 0.37 hours after antibiotic intake. The mean amoxicillin concentration at the implant site reached 5 ± 2.63 µg/mL (range: 2.04 to 11.18 µg/mL), while the venous blood level was 4.21 ± 2.12 µg/mL (range: 1.6 to 9.98 µg/mL) (P = .33). No correlations were observed between age, height, weight, and BMI with antibiotic plasma levels. CONCLUSION: These findings demonstrate that plasma concentrations of a prophylactic dose of amoxicillin are higher than the minimum inhibitory concentration needed to prevent the common dental bacteria involved in peri-implantitis and periodontal diseases.