Au@16-pH-16/miR-21 mimic nanosystem: An efficient treatment for obesity through browning and thermogenesis induction.

Despite the abundance of registered clinical trials worldwide, the availability of effective drugs for obesity treatment is limited due to their associated side effects. Thus, there is growing interest in therapies that stimulate energy expenditure in white adipose tissue. Recently, we demonstrated that the delivery of a miR-21 mimic using JetPEI effectively inhibits weight gain in an obese mouse model by promoting metabolism, browning, and thermogenesis, suggesting the potential of miR-21 mimic as a treatment for obesity. Despite these promising results, the implementation of more advanced delivery system techniques for miR-21 mimic would greatly enhance the advancement of safe and efficient treatment approaches for individuals with obesity in the future. Our objective is to explore whether a new delivery system based on gold nanoparticles and Gemini surfactants (Au@16-ph-16) can replicate the favorable effects of the miR-21 mimic on weight gain, browning, and thermogenesis. We found that dosages as low as 0.2 µg miR-21 mimic /animal significantly inhibited weight gain and induced browning and thermogenic parameters. This was evidenced by the upregulation of specific genes and proteins associated with these processes, as well as the biogenesis of beige adipocytes and mitochondria. Significant increases in miR-21 levels were observed in adipose tissue but not in other tissue types. Our data indicates that Au@16-ph-16 could serve as an effective delivery system for miRNA mimics, suggesting its potential suitability for the development of future clinical treatments against obesity.

Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic Resistance.

Compacted Au@16-mph-16/DNA-AMOX (NSi) nanosystems were prepared from amoxicillin (AMOX) and precursor Au@16-mph-16 gold nanoparticles (Ni) using a Deoxyribonucleic acid (DNA) biopolymer as a glue. The synthesized nanocarrier was tested on different bacterial strains of Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae to evaluate its effectiveness as an antibiotic as well as its internalization. Synthesis of the nanosystems required previous structural and thermodynamic studies using circular dichroism (CD) and UV-visible techniques to guarantee optimal complex formation and maximal DNA compaction, characteristics which facilitate the correct uptake of the nanocarrier. Two nanocomplexes with different compositions and structures, denoted NS1 and NS2, were prepared, the first involving external Au@16-mph-16 binding and the second partial intercalation. The Ni and NSi nanosystems obtained were characterized via transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS) techniques to measure their charge, aggregation state and hydrodynamic size, and to verify their presence inside the bacteria. From these studies, it was concluded that the zeta potential values for gold nanoparticles, NS1, and NS2 nanosystems were 67.8, -36.7, and -45.1 mV. Moreover, the particle size distribution of the Au@16-mph-16 gold nanoparticles and NS2 nanoformulation was found to be 2.6 nm and 69.0 nm, respectively. However, for NS1 nanoformulation, a bimodal size distribution of 44 nm (95.5%) and 205 nm (4.5%) was found. Minimal inhibitory concentration (MIC) values were determined for the bacteria studied using a microdilution plates assay. The effect on Escherichia coli bacteria was notable, with MIC values of 17 µM for both the NS1 and NS2 nanosystems. The Staphylococcus aureus chart shows a greater inhibition effect of NS2 and NP2 in non-diluted wells, and clearly reveals a great effect on Streptococcus pneumoniae, reaching MIC values of 0.53 µM in more diluted wells. These results are in good agreement with TEM internalization studies of bacteria that reveal significant internalization and damage in Streptococcus pneumoniae. In all the treatments carried out, the antibiotic capacity of gold nanosystems as enhancers of amoxicillin was demonstrated, causing both the precursors and the nanosystems to act very quickly, and thus favoring microbial death with a small amount of antibiotic. Therefore, these gold nanosystems may constitute an effective therapy to combat resistance to antibiotics, in addition to avoiding the secondary effects derived from the administration of high doses of antibiotics.

Propuesta para mejorar la formación en profesionalismo y en competencias transversales en los estudios de medicina de las universidades de Cataluña / Proposal to improve training in professionalism and transversal competences in medical studies at the universities of Catalonia

Introducción: En un grupo de trabajo de la Administración de la Generalitat de Cataluña y de los decanos de las facultades con estudios de Medicina de las universidades catalanas se creó una comisión para elaborar una propuesta para fomentar la formación en profesionalismo, en humanidades y en competencias transversales de los graduados en Medicina. Desarrollo: Dicha comisión, compuesta por docentes de todas las facultades, elaboró un documento con tres objetivos específicos: a) mostrar el estado real de dicha formación en los currículos; b) proponer actividades docentes concretas para mejorar dicha formación, considerando las buenas prácticas que se están realizando en las universidades; y c) sugerir criterios y métodos de evaluación de la formación en profesionalismo o de competencias transversales y, también, evaluar competencias específicas que pueden favorecer el desarrollo de las competencias genéricas. Conclusiones: Se espera que las sugerencias presentadas puedan servir para aumentar la formación en valores profesionales, en humanidades y en competencias transversales de los futuros profesionales de la medicina, con el objetivo final de mejorar la salud de la población.(AU)

Introduction: In a working group of the Administration of the regional government of Catalonia and the deans of the faculties with medical studies of the Catalan universities, a commission was created to prepare a document to promote training in professionalism and transversal competences of graduates in Medicine. Development: This commission, made up of teachers from all the faculties, prepared a document with three specific objectives: a) show the real state of said training in the curricula; b) propose specific teaching activities to improve said training, considering those good practices that are being carried out in universities; and c) suggest criteria and methods of evaluation of training in professionalism or of transversal competences and, also, evaluate specific competences that can improve the development of generic competences. Conclusions: It is hoped that the suggestions presented can serve to increase training in professional values, in the humanities and in transversal competences of future medical professionals with the ultimate goal of improving the health of the population.(AU)

Gold Nanosystems Covered with Doxorubicin/DNA Complexes: A Therapeutic Target for Prostate and Liver Cancer.

Different gold nanosystems covered with DNA and doxorubicin (Doxo) were designed and synthesized for cancer therapy, starting from Au@16-Ph-16 cationic nanoparticles and DNA-Doxo complexes prepared under saturation conditions. For the preparation of stable, biocompatible, and small-sized compacted Au@16-Ph-16/DNA-Doxo nanotransporters, the conditions for the DNA-Doxo compaction process induced by gold nanoparticles were first explored using fluorescence spectroscopy, circular dichroism and atomic force microscopy techniques. The reverse process, which is fundamental for Doxo liberation at the site of action, was found to occur at higher CAu@16-Ph-16 concentrations using these techniques. Zeta potential, dynamic light scattering and UV-visible spectroscopy reveal that the prepared compacted nanosystems are stable, highly charged and of adequate size for the effective delivery of Doxo to the cell. This fact is verified by in vitro biocompatibility and internalization studies using two prostate cancer-derived cell lines (LNCaP and DU145) and one hepatocellular carcinoma-derived cell line (SNU-387), as well as a non-tumor prostate (PNT2) cell line and a non-hepatocarcinoma hepatoblastoma cell line (Hep-G2) model used as a control in liver cells. However, the most outstanding results of this work are derived from the use of the CI+NI combined treatments which present strong action in cancer-derived cell lines, while a protective effect is observed in non-tumor cell lines. Hence, novel therapeutic targets based on gold nanoparticles denote high selectivity compared to conventional treatment based on free Doxo at the same concentration. The results obtained show the viability of both the proposed methodology for internalization of compacted nanocomplexes inside the cell and the effectiveness of the possible treatment and minimization of side effects in prostate and liver cancer.

Use of Nanoparticles to Prevent Resistance to Antibiotics-Synthesis and Characterization of Gold Nanosystems Based on Tetracycline.

Antimicrobial resistance (AMR) is a serious public health problem worldwide which, according to the World Health Organization (WHO), requires research into new and more effective drugs. In this work, both gold nanoparticles covered with 16-3-16 cationic gemini surfactant (Au@16-3-16) and DNA/tetracycline (DNA/TC) intercalated complexes were prepared to effectively transport tetracycline (TC). Synthesis of the Au@16-3-16 precursor was carried out by using trihydrated gold, adding sodium borohydride as a reducing agent and the gemini surfactant 16-3-16 as stabilizing agent. Circular dichroism and atomic force microscopy techniques were then used to ascertain the optimal R range of the relationship between the concentrations of Au@16-3-16 and the DNA/TC complex (R = CAu@16-3-16/CDNA) that allow the obtainment of stable and compact nanosystems, these characteristics being fundamental for their use as antibiotic transporters. Stability studies over time were carried out for distinct selected Au@16-3-16 and Au@16-3-16/DNA-TC nanoformulations using the ultraviolet−visible spectrophotometry technique, checking their stability for at least one month. In addition, in order to know the charge and size distribution of the nanocomplexes, DLS and zeta potential measurements were performed in the solution. The results showed that the characterized nanosystems were highly charged, stable and of a reduced size (<100 nm) that allows them to cross bacterial membranes effectively (>1 µm). Once the different physicochemical characteristics of the gold nanosystems were measured, Au@16-3-16 and Au@16-3-16/DNA-TC were tested on Escherichia coli and Staphylococcus aureus to study their antibacterial properties and internalization capacity in microbes. Differences in the interaction of the precursors and the compacted nanosystems generated were observed in Gram-positive and Gram-negative bacteria, possibly due to membrane damage or electrostatic interaction with internalization by endocytosis. In the internalization experiments, depending on the treatment application time, the greatest bacterial destruction was observed for all nanoformulations explored at 18 h of incubation. Importantly, the results obtained demonstrate that both new nanosystems based on TC and Au@16-3-16 precursors have optimal antimicrobial properties and would be beneficial for use in patients, avoiding possible side effects.

miR-21 mimic blocks obesity in mice: A novel therapeutic option.

MicroRNAs (miRNAs) are promising drug targets for obesity and metabolic disorders. Recently, miRNA mimics are providing a unique mechanism of action that guides the process for drug development and sets out the context of their therapeutic application. miRNA (miR)-21 expression in white adipose tissue (WAT) has been associated with obesity. We aimed to analyze miR-21 expression levels in relation to diabetes and obesity to determine the effect that miR-21 mimic has on processes involved in WAT functionality, to dissect the underlying molecular mechanisms, and to study the potential therapeutic application of the miR-21 mimic against obesity. We found higher miR-21 levels in WAT from non-diabetic obese compared to normoweight humans and mice. Moreover, in 3T3-L1 adipocytes, miR-21 mimic affect genes involved in WAT functionality regulation and significantly increase the expression of genes involved in browning and thermogenesis. Interestingly, in vivo treatment with the miR-21 mimic blocked weight gain induced by a high-fat diet in obese mice, without modifying food intake or physical activity. This was associated with metabolic enhancement, WAT browning, and brown adipose tissue (AT) thermogenic programming through vascular endothelial growth factor A (VEGF-A), p53, and transforming growth factor ß1 (TGF-ß1) signaling pathways. Our findings suggest that miR-21 mimic-based therapy may provide a new opportunity to therapeutically manage obesity and consequently, its associated alterations.

Assessment of Age Effects on Ovarian Hemodynamics Using Doppler Ultrasound and Progesterone Concentrations in Cycling Spanish Purebred Mares.

In equine reproduction, accurate and timely detection of the moment of ovulation is of great importance. Power Doppler ultrasound technology is a non-invasive method that enables to assess the morpho-echogenic features and blood flow changes during the estral cycle in mares. The objective of the present study was to evaluate the influence of age on ultrasonographic parameters (follicular diameter, follicular blood flow-FBF, corpus luteum (CL) area and corpus luteum blood flow-CLBF) and blood plasma progesterone concentrations in cycling Spanish Purebred mares (15 less than 8 years old and 15 equal o higher than 8 years old). The ultrasound images obtained were analyzed with the Image Colour Summarizer software, which allows the quantification of the pixels of each image. Young mares had significantly higher FBF, CLBF and plasma progesterone levels. Moreover, linear regression analysis showed that blood progesterone levels could be predicted in both groups from CLBF with moderate precision and accuracy. In conclusion, Power Doppler was useful to assess ovarian hemodynamics. Our results support that age is a factor that significantly influences FBF and CLBF as well as blood progesterone concentration in mares. More studies would be needed to develop high precision and accuracy predictive models of blood progesterone concentration from CLBF measured by Power Doppler.

Lysozyme-AuNPs Interactions: Determination of Binding Free Energy.

Investigation and optimization of lysozyme (Lys) adsorption onto gold nanoparticles, AuNPs, were carried out. The purpose of this study is to determine the magnitude of the AuNPs-lysozyme interaction in aqueous media by simple spectrophotometric means, and to obtain the free energy of binding of the system for the first time. In order to explore the possibilities of gold nanoparticles for sensing lysozyme in aqueous media, the stability of the samples and the influence of the gold and nanoparticle concentrations in the detection limit were studied. ζ potential measurements and the shift of the surface plasmon band showed a state of saturation with an average number of 55 Lys per gold nanoparticle. Lysozyme-AuNPs interactions induce aggregation of citrate-stabilized AuNPs at low concentrations by neutering the negative charges of citrate anions; from those aggregation data, the magnitude of the interactions has been measured by using Benesi-Hildebrand plots. However, at higher protein concentrations aggregation has been found to decrease. Although the nanocluster morphology remains unchanged in the presence of Lys, slight conformational changes of the protein occur. The influence of the size of the nanoclusters was also investigated for 5, 10, and 20 nm AuNPs, and 10 nm AuNPs was found the most appropriate.

Biocompatible DNA/5-Fluorouracil-Gemini Surfactant-Functionalized Gold Nanoparticles as Promising Vectors in Lung Cancer Therapy.

The design and preparation of novel nanocarriers to transport cancer drugs for chemotherapy purposes is an important line of research in the medical field. A new 5-fluorouracil (5-Fu) transporter was designed based on the use of two new biocompatible gold nanosystems: (i) a gold nanoparticle precursor, Au@16-Ph-16, stabilized with the positively charged gemini surfactant 16-Ph-16, and (ii) the compacted nanocomplexes formed by the precursor and DNA/5-Fu complexes, Au@16-Ph-16/DNA-5-Fu. The physicochemical properties of the obtained nanosystems were studied by using UV-visible spectroscopy, TEM, dynamic light scattering, and zeta potential techniques. Method tuning also requires the use of circular dichroism, atomic force microscopy, and fluorescence spectroscopy techniques for the prior selection of the optimal relative Au@16-Ph-16 and DNA concentrations (R = CAu@16-Ph-16/CDNA), biopolymer compaction/decompaction, and 5-Fu release from the DNA/5-Fu complex. TEM experiments revealed the effective internalization of the both precursor and Au@16-Ph-16/DNA-5-Fu-compacted nanosystems into the cells. Moreover, cytotoxicity assays and internalization experiments using TEM and confocal microscopy showed that the new strategy for 5-Fu administration enhanced efficacy, biocompatibility and selectivity against lung cancer cells. The differential uptake among different formulations is discussed in terms of the physicochemical properties of the nanosystems.

[99mTc]Tc-iPSMA SPECT brain imaging as a potential specific diagnosis of metastatic brain tumors and high-grade gliomas.

BACKGROUND: PSMA (prostate-specific membrane antigen) protein is heavily expressed in the proliferating microvasculature of high-grade gliomas (HGG) and brain metastases (BM). This research aimed to assess [99mTc]Tc-iPSMA SPECT brain imaging as a potential specific diagnosis of HGG and BM by PSMA-targeting in their proliferating vasculature. METHODS: Forty-one patients, with suspected brain tumors, as detected by enhanced MRI scanning, were enrolled to undergo preoperative [99mTc]Tc-iPSMA SPECT brain imaging. Semiquantitative image analyses, to evaluate the maximum target-to-background ratio (TBRmax), were performed. All diagnoses were histopathologically confirmed. PSMA expression was evaluated by immunohistochemistry (IHC) in 11 brain tumor tissues. TBRmax values were correlated with IHC results and tumor WHO grade (HGG vs LGG). RESULTS: [99mTc]Tc-iPSMA images showed increased uptake in BM, HGG, and recurrent gliomas (TBRmax of 25.1 ± 7.1, 18.5 ± 9.0, 15.0 ± 9.9, respectively), and was negative in treatment-naive patients with LGG and reactive gliosis. PSMA was highly expressed in the vascular endothelium of grade IV gliomas and BM, while its expression was extremely low in LGG and completely absent in gliosis. By using 2.8 as a threshold value for TBRmax, the specificity, sensitivity, PPV, NPV and accuracy were 100%, 94%, 100%, 77% and 95%, respectively. CONCLUSIONS: The results of this pilot study show that [99mTc]Tc-iPSMA SPECT brain imaging is a specific and potentially useful neuroimaging tool for assessing tumoral neovasculature formation in gliomas and brain metastases.

Antidiabetic Activity of Aloe vera Leaves.

This research evaluated the potential of using the methanol extract of Aloe vera (L.) Burm.f (AVM) to prevent the formation of AGEs by means of the BSA/glucose assay, BSA-methylglyoxal assay, arginine-methylglyoxal assay, fructosamine, Nɛ-(carboxymethyl) lysine (CML), thiol groups, and carbonyl protein in vitro. The effect of AVM was also evaluated with regard to inhibiting the enzymes α-amylase, α-glucosidase, and pancreatic lipase. For this, the plant was dried, ground, and subsequently macerated with methanol. Aloe vera methanol extract (AVM) significantly decreased the formation of AGEs, as well as the formation of fructosamine, CML, and carbonyl protein. The concentration of 5 mg/ml of AVM presented the best results. AVM significantly inhibited the α-amylase and α-glucosidase enzymes. As regards the content of thiol groups, a significant increase was observed during the four weeks of the experiment. So, we can conclude that Aloe vera methanol extract decreases the formation of AGEs and may inhibit the increase in postprandial glucose, suggesting that AVM can prevent diabetes complications associated with AGE.

99mTc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans.

Overexpression of the chemokine-4 receptor (CXCR4) in brain tumors is associated with high cancer cell invasiveness. Recently, we reported the preclinical evaluation of 99mTc-CXCR4-L (cyclo-D-Tyr-D-[NMe]Orn[EDDA-99mTc-6-hydrazinylnicotinyl]-Arg-NaI-Gly) as a SPECT radioligand capable of specifically detecting the CXCR4 protein. This research aimed to estimate the biokinetic behavior and radiation dosimetry of 99mTc-CXCR4-L in healthy subjects, as well as to correlate the radiotracer uptake by brain tumors in patients, with the histological grade of differentiation and CXCR4 expression evaluated by immunohistochemistry. 99mTc-CXCR4-L was obtained from freeze-dried kits prepared under GMP conditions (radiochemical purities >97%). Whole-body scans from six healthy volunteers were acquired at 0.3, 1, 2, 4, 6, and 24 h after 99mTc-CXCR4-L administration (0.37 GBq). Time-activity curves of different source organs were obtained from the image sequence to adjust the biokinetic models. The OLINDA/EXM code was employed to calculate the equivalent and effective radiation doses. Nine patients with evidence of brain tumor injury (6 primaries and 3 recurrent), determined by MRI, underwent cerebral SPECT at 3 h after administration of 99mTc-CXCR4-L (0.74 GBq). Data were expressed as a T/B (tumor uptake/background) ratio. Biopsy examinations included histological grading and anti-CXCR4 immunohistochemistry. Results showed a fast blood activity clearance (T 1/2 α = 0.81 min and T 1/2 ß = 12.19 min) with renal and hepatobiliary elimination. The average equivalent doses were 6.10E - 04, 1.41E - 04, and 3.13E - 05 mSv/MBq for the intestine, liver, and kidney, respectively. The effective dose was 3.92E - 03 mSv/MBq. SPECT was positive in 7/9 patients diagnosed as grade II oligodendroglioma (two patients), grade IV glioblastoma (two patients), grade IV gliosarcoma (one patient), metastasis, and diffuse astrocytoma with T/B ratios of 1.3, 2.3, 13, 7, 19, 5.5, and 3.9, respectively, all of them with positive immunohistochemistry. A direct relationship between the grade of differentiation and the expression of CXCR4 was found. The two negative SPECT studies showed negative immunohistochemistry with a diagnosis of reactive gliosis. This "proof-of-concept" research warrants further clinical studies to establish the usefulness of 99mTc-CXCR4-L in the diagnosis and prognosis of brain tumors.

Measuring nanoparticle-induced resonance energy transfer effect by electrogenerated chemiluminescent reactions.

Electrogenerated chemiluminescence (ECL) efficiencies, redox potentials, photoluminescent (PL) (quenching and coupling) effects, and AFM images for the [Ru(bpy)3]2+/Au@tiopronin system were determined in aqueous solutions of the gold nanoparticles (NPs) at pH 7.0. The most remarkable finding was that ECL measurements can display the nanoparticle-induced resonance energy transfer (NP-RET) effect. Its effectiveness was quantified through a coefficient, K (NP-RET)ECL , which measures how much an ECL reaction has been enhanced. Moreover, the NP-RET effect was also checked using PL measurements, in such a way that a coefficient, K (NP-RET)PL , was determined; both constants, K (NP-RET)ECL and K (NP-RET)PL being in close agreement. It is important to highlight the fact that the NP-RET effect is only displayed in diluted solutions in which there is no NPs self-aggregation. The existence of the NPs self-aggregation behavior is revealed through AFM measurements.

What controls the unusual melting profiles of small AuNPs/DNA complexes.

The effect of the addition of low concentrations of an inner electrolyte on ds-DNA CT-DNA (calf thymus DNA) and ss-DNA conformational changes induced by small N-(2-mercaptopropionyl)glycine gold nanoparticles (AuNPs) is here studied in detail by using different spectroscopic and structural techniques. The high affinity of ss-DNA to AuNPs compared with ds-DNA is easily demonstrated by the results of competitive binding with SYBR Green I (SG). Additionally, it is proven that at 25.0 °C, AuNPs/ds-DNA and AuNPs/ss-DNA complexes undergo a transition from extended-coil to more compact structures when the AuNPs concentration (CAuNPs) is increased, which for the ds-DNA system is accompanied by partial denaturation. Particularly, for the AuNPs/ss-DNA system all of these techniques confirm that at a high CAuNPs, the compaction process is followed by a discrete transition to aggregation and an increase in structure size. A thorough analysis of the conformational changes described indicates that these processes are larger in low salt concentration and at high temperature. However, the most striking feature of this work is the abnormal melting temperature profiles (Tm) registered at high R = CAuNPs/CDNA ratios, which are remarkable and of interest for chemical sensing. At a suitable R ratio, which varies depending on CNaCl, a complex melting profile for the AuNPs/ds-DNA system was registered with two characteristic transitions: Tm,1 = 65.0 °C and Tm,2 = 95.0 °C. The highly sensitive atomic force microscopy technique performed at 25.0 °C and 65.0 °C also showed a different behaviour in both ss- and AuNPs/ds-DNA systems, which explains the characteristic melting curves. Specifically for the AuNPs/ss-DNA system, AFM at 25.0 °C revealed the formation of large-sized aggregates formed by AuNPs/ss-DNA compact structures linked by AuNPs. However, when both AuNPs/ds-DNA and AuNPs/ss-DNA complexes were incubated at 65.0 °C, the formation of highly stable ordered structures was always visualized at high R. Therefore, this shows that some key parameters for effective control of the formation of DNA/RNA-linked particles are: the selection of an optimal temperature below the ds-DNA melting point, an appropriate CAuNPs, and the addition of low CNaCl. The optimization of these parameters for each AuNPs/DNA system could improve biological sensing and DNA/RNA delivery.

Prioritization for liver transplantation using the MELD score in Chile: Inequities generated by MELD exceptions.: A collaboration between the Chilean Liver Transplant Programs, the Public Health Institute and the National Transplant Coordinator.

INTRODUCTION AND AIM: The MELD score has been established as an efficient and rigorous prioritization system for liver transplant (LT). Our study aimed to evaluate the effectiveness of the MELD score as a system for prioritization for LT, in terms of decreasing the dropout rate in the waiting list and maintaining an adequate survival post-LT in Chile. MATERIALS AND METHODS: We analyzed the Chilean Public Health Institute liver transplant registry of candidates listed from October 15th 2011 to December 31st 2014. We included adult candidates (>15 years old) listed for elective cadaveric LT with a MELD score of 15 or higher. Statistical analysis included survival curves (Kaplan-Meier), log-rank statistics and multivariate logistic regression. RESULTS: 420 candidates were analyzed. Mean age was 53.6±11.8 years, and 244 were men (58%). Causes of LT included: Liver cirrhosis without exceptions (HC) 177 (66.4%); hepatocellular carcinoma (HCC) 111 (26.4%); cirrhosis with non-HCC exceptions 102 (24.3%) and non-cirrhotic candidates 30 (7.2%). LT rate was 43.2%. The dropout rate was 37.6% at 1-year. Even though the LT rate was higher, the annual dropout rate was significantly higher in cirrhotic candidates (without exceptions) compared with cirrhotics with HCC, and non-HCC exceptions plus non-cirrhotic candidates (47.9%; 37.2% and 24.2%, respectively, with p=0.004). Post-LT survival was 84% per year, with no significant differences between the three groups (p=0.95). CONCLUSION: Prioritization for LT using the MELD score system has not decreased the dropout rate in Chile (persistent low donor's rate). Exceptions generate inequities in dropout rate, disadvantaging patients without exceptions.

Respuesta de los autores: Eliminación de la palabra 'fuga' de la terminología asistencial sanitaria / Reply: Excise the Spanish term fuga (escape) from our medical language

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El alta voluntaria y la fuga en los servicios de urgencias: un reto con implicaciones éticas y médico-legales / Emergency department patients who leave after voluntary discharge or without discharge: a challenge with ethical, medical, and legal implications

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In Vitro Inhibitory Activity of Acca sellowiana Fruit Extract on End Products of Advanced Glycation.

INTRODUCTION: Hyperglycemia plays an important role in the pathogenesis of diabetic complications, as it increases protein glycation, as well as the progressive accumulation of advanced glycation end products (AGEs), which are complex structures that produce fluorescence. The glycation reaction raises the levels of protein carbonyl, N ε-(carboxymethyl)lysine (CML), and fructosamine and decreases the level of thiol groups. METHODS: In the present study, the antiglycation activity was determined by fluorescence intensity using the bovine serum albumin (BSA)/glucose, CML method, and the level of fructosamine. The oxidation of proteins was determined by the carbonyl protein content and thiol groups. RESULTS: The results show that the hexane extract of Acca sellowiana (FOH) at different concentrations (0.30-5 mg/ml) significantly inhibited the formation of AGEs in the BSA/glucose model during the 4 weeks of the study. FOH reduced the levels of fructosamine and CML. Our results showed a significant effect of FOH in the prevention of oxidative damage of proteins, as well as an effect on the oxidation of thiol groups and carbonyl proteins. CONCLUSION: The present study indicates that FOH is effective in inhibiting the glycation of proteins in vitro, so it can prevent or ameliorate the chronic conditions of diabetes associated with the formation of AGEs.