The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer.

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.

Development of Bioactive Glass-Collagen-Hyaluronic Acid-Polycaprolactone Scaffolds for Tissue Engineering Applications.

In this work, bioactive glass (BG) particles synthesized by a sol-gel method, hyaluronic acid (HYA) and collagen (COL) extracted from chicken eggshell membrane (ESM), and as-purchased polycaprolactone (PCL) were used to obtain a novel bioactive scaffold using the gel-pressing technique. Two composite mixtures in weight percent were obtained and identified as SCF-1 and SCF-2, and were characterized by using FTIR, XRD, and SEM techniques. Subsequently, the composite materials applied as coatings were evaluated in simulated body fluid solutions using electrochemical techniques. The results of bioactivity and biodegradability evaluations, carried out by immersing in simulated body fluid and phosphate-buffered saline solution, showed that the SCF-1 sample presented the best biocompatibility. In accordance with the potentiodynamic results, the 316L-SS and the SCF-1-coated SS showed a very similar corrosion potential (E corr ), around -228 mV, and current density (i corr ) values in close proximity, while the SCF-2-coated SS showed more positive E corr around -68 mV and lower i corr value in one order of magnitude. These results agree with those obtained by electrochemical impedance spectroscopy, which show a corrosion mechanism governed by activation and finite diffusion through the porous layer. In addition, results were complemented by dynamic compression testing under oscillating forces to identify the developed scaffolds' response under external forces, where the SCF-1 scaffold presented a maximum compression. The degradation resistance, bioactivity, and mechanically obtained measurements provided interesting results for potential further studies in tissue engineering.

PCSK9 Gene Participates in the Development of Primary Dyslipidemias.

Dyslipidemias are a group of diseases, which are characterized by abnormal blood concentrations of cholesterol, triglycerides and/or low-density lipoprotein-cholesterol (LDL-c). Dyslipidemia is a determinant condition for the progress of an atherosclerotic plaque formation. The resulting atherogenicity is due to at least two mechanisms: first, to the accumulation in the plasma of lipid particles that have the capacity to alter the function of the endothelium and deposit at the atheromatous plaque, and second, at an insufficient concentration of multifactorial type of high density lipoprotein-cholesterol (HDL-c), whose function is to protect against the development of atherosclerosis. Its highest prevalence is encountered among individuals with diabetes, hypertension or overweight. Hyperlipidemia is one of the main predisposing factors for the development of cardiovascular disease. Hyperlipidemia can be the result of a genetic condition, the secondary expression of a primary process or the consequence of exogenous factors (food, cultural, socio-economic, etc.), all of which lead to the elevation of plasma lipid levels. The objective of this study was to carry out an analysis of the genes involved in the development of dyslipidemias that lead to cardiovascular disease with special emphasis on the proprotein convertase subtilin/kexin type 9 (PCSK9) gene. The PCSK9 gene participates in the development of primary dyslipidemias, mainly familial hypercholesterolemia, currently the pharmacological treatment of choice to reduce LDL-c are statins, however, it has been observed that these have been insufficient to eliminate cardiovascular risk, especially in subjects with primary forms of hypercholesterolemia related to genetic mutations, or statin intolerance.

Effect of Pleurotus agaves mushroom addition on the physicochemical and sensory properties of blue maize tortillas produced with traditional and ecological nixtamalization.

The physicochemical, nutritional and sensory properties of flours, doughs and tortillas made with traditional nixtamalization (TN) and ecological nixtamalization (EN) and enriched (9%) with the traditional maguey mushroom (Pleurotus agaves) were analysed. EN resulted in flours and tortillas having a greater content of bioactive compounds than that of TN flours, which represents a production process of maize tortillas containing high amounts of antioxidants. The addition of mushrooms to EN flours improved their sensory properties, whereas the addition of mushrooms to TN flours decreased them. The amount of P. agaves added to tortillas was equivalent to 3% enrichment with ß-glucans. The edible mushroom P. agaves, highly appreciated in many Mexican regions, improved the nutritional and sensory quality of blue maize tortillas when added to flours prepared by EN. A new product was developed using local traditional foods of complementary nutritional value.

Validación del Índice Funcional para Osteoartritis de Manos (FIHOA) en pacientes con artritis reumatoidea / Validation of the Functional Index for Hand Osteoarthritis (FIHOA) in patients with rheumatoid arthritis

El FIHOA fue desarrollado para evaluar la capacidad funcional de pacientes con OA de manos. Objetivo: Validar FIHOA en pacientes con AR. Métodos: Estudio analítico, observacional prospectivo de corte transversal. Se incluyeron pacientes consecutivos con diagnóstico de AR (ACR/EULAR 2010). Se consignaron datos demográficos y características de la enfermedad. Todos los pacientes completaron los siguientes cuestionarios autoadministrados: FIHOA, HAQ-A, HAQ-UP-A y Quick DASH. En un subgrupo de pacientes, una terapista ocupacional valoró la capacidad funcional de la mano por medio del test de SODA-A. Se evaluó la reproducibilidad de FIHOA. Análisis estadístico: Estadística descriptiva. Confiabilidad con test de Cronbach. Validez de constructo con correlación de Spearman. Reproducibilidad test re-test. Modelo de regresión lineal. Resultados: Se incluyeron 100 pacientes. La prueba alfa de Cronbach fue de 0,94. No se evidenciaron preguntas redundantes. El FIHOA mostró excelente correlación con HAQ-A (r=0,89); HAQ-UP-A (r=0,89); Quick DASH (r=0,90) y SODA-A (r=-0,80); y buena correlación con DAS28-ERS (r=0,65), y con otros parámetros de la enfermedad. La reproducibilidad fue 0,73. La regresión lineal múltiple mostró como principal determinante del FIHOA a la presencia de rigidez matinal seguida por el uso de corticoides y el EVA general de pacientes. Conclusión: El FIHOA resultó ser confiable, válido y reproducible en pacientes con AR

FIHOA was developed to evaluate the functional capacity of patients with OA hands. Objetive: To validate FIHOA in patients with RA. Methods: Analytical, observational, prospective cross-sectional study. Consecutive patients with diagnosis of RA (ACR/EULAR 2010) were included. Demographic and RA characteristics were recorded. Patients completed the following self-administered questionnaires: FIHOA, HAQ-A, HAQ-UP-A and Quick DASH. For a patient subgroup, an occupational therapist performed an objective evaluation of the functional capacity of the hands using the SODA-A. Reproducibility was assessed. Statistical analysis: Descriptive statistics. Reliability with the Cronbach test. Construct validity with Spearman correlation. Reproducibility with test-retest reliability. Linear regression model. Results: One hundred patients were included. Cronbach's alpha test was 0.94. There were no redundant questions. FIHOA showed an excellent correlation with HAQ-A (r=0.89); HAQUP-A (r=0.89); Quick DASH (r=0.90) and SODA-A (r=-0.80); and a good correlation with DAS28- ERS (r=0.65) and with other disease parameters. Questionnaire reproducibility was 0.73. A multiple linear regression showed morning stiffness as the main determinant of FIHOA, followed by glucocorticoid use and patient global assessment. Conclusion: FIHOA was found to be reliable, valid and reproducible in patients with RA

Primary Sjögren's syndrome: Extraglandular manifestations and hydroxychloroquine therapy.

The use of hydroxychloroquine (HCQ) in Primary Sjögren's Syndrome (pSS) has been assessed in different studies over the last years, with conflicting results regarding its efficacy in sicca syndrome and extraglandular manifestations (EGM). The goal of this study was to compare the incidence rate of EGM in pSS patients with and without HCQ therapy.We performed a multicenter retrospective study, including patients with pSS (European classification criteria) with at least 1 year of follow-up. Subjects with concomitant fibromyalgia, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis were excluded. Demographics and pSS characteristics were recorded. The EGM were defined by EULAR-SS disease activity index (ESSDAI). Patients were divided into two groups according to their use or not of HCQ therapy. We evaluated the use of HCQ and its relationship to EGM. HCQ therapy was defined as the continuous use of the drug for at least 3 months. A descriptive analysis of demographics and pSS characteristics was performed. We compared the incidence of EGM between groups defined by HCQ therapy using chi2 test or Fisher's exact test. A total of 221 patients were included (97.3% women), mean age, 55.7 years (SD 14). Mean age at diagnosis, 48.8 years (SD 15); median disease duration, 60 months (IQR 35-84). One hundred and seventy patients (77%) received HCQ. About half of the patients had at least one EGM during the course of the disease, 20% of them developed an EGM before the onset of the sicca syndrome and 26% simultaneously with dryness symptom. Overall, EGM were less frequent in those on HCQ therapy (36.5% vs 63.5%, p < 0.001). Considering each EGM individually, the following manifestations were more frequent in the non-treated group: arthritis (p < 0.001), fatigue (p < 0.001), purpura (p = 0.01), Raynaud phenomenon (p = 0.003), and hypergammaglobulinemia (p = 0.006). Immunosuppressive treatment was indicated on 28 patients (12.7%), 13 of which were receiving also HCQ. The first reason for those treatments was the presence of arthritis in 12/28 patients (42.8%), and the drug used in all the cases was methotrexate. Only three patients required immunosuppressive therapy with cyclophosphamide, due to the presence of glomerulonephritis, vasculitis, and interstitial lung disease. None of the patients received biologic therapy. The lower incidence of EGM was observed in patients on HCQ therapy supports its efficacy in pSS. However, further large scale prospective studies are needed to confirm these findings.

Impact of Continuous Two-Team Approach in Autologous Breast Reconstruction.

Background Autologous breast reconstruction has been noted in the literature to provide superior aesthetic outcomes and patient satisfaction. Additionally, free perforator flap tissue transfer has the potential for lower abdominal donor site morbidity. However, it has been noted that the percentage of women who are undergoing autologous breast reconstruction in the United States is decreasing. Factors related to the technical difficulty, prolonged operative times, and decreasing reimbursement have been implicated as the causes. Methods A retrospective review of electronic medical records over a 5-year period was performed with evaluation of 77 autologous breast reconstructions at a single institution. Patient demographics, comorbidities, number of surgeons involved, operative times, length of stay, and postoperative complications were measured. Wilcoxon rank-sum, Pearson's chi-squared, and proportional odds likelihood ratio tests were performed to compare continuous, categorical, and ordinal outcomes, respectively. Propensity score weighting was used to adjust for presurgical covariates and laterality. Results Operative time and length of stay were both significantly lower in the two- versus the single-microsurgeon groups in the unadjusted setting. When covariates and laterality were adjusted for, operative times still remained significantly shorter in the two-microsurgeon group; there were no differences in complications. Conclusion Based on our findings, we propose that the two-microsurgeon approach can be utilized in more time-consuming microsurgical cases, such as autologous breast reconstruction, to safely decrease operative times and potentially alleviate surgeon fatigue, reduce operative costs, and thus increase overall surgeon productivity.

Correlación de diferentes métodos de valoración de la rigidez matinal con índices de actividad y discapacidad en pacientes con artritis reumatoidea / Correlation of different methods of assessment of morning stiffness with activity and disability indexes in patients with rheumatoid arthritis

La rigidez matinal (RM) es un síntoma complejo en los pacientes con AR. Existen diferentes formas de valorar la RM. Sin embargo, la mejor manera de evaluarla es aún controversial. Objetivos: Comparar la severidad y la duración de la RM, evaluada por el médico y por cuestionarios autorreportados, con la actividad de la enfermedad y la capacidad funcional en pacientes con AR. Métodos: Estudio observacional de corte transversal. Se incluyeron pacientes con diagnóstico de AR. Se consignaron datos demográficos, características de la AR y medidas clinimétricas. Los pacientes fueron asignados aleatoriamente a uno de dos grupos: el primer grupo fue interrogado sobre la duración de la RM en minutos; el segundo grupo fue evaluado mediante un cuestionario autorreportado que cuantificaba la severidad de la RM (EVA numérica y no numérica) y la duración (en minutos y en escala de Likert). Resultados: Participaron 111 pacientes (86% mujeres). La edad media fue de 52 años y la mediana de duración de la enfermedad fue 8 años. El 51% presentaba RM. La correlación de la RM en minutos medida por el médico fue buena con HAQ-A y aceptable con DAS28 y CDAI; mientras que la severidad medida por EVA correlacionó mejor con los índices de actividad de la AR que con discapacidad. Cuando la intensidad de la RM fue evaluada por EVA se observó que un valor >5,5 cm se asoció con actividad severa de la enfermedad (Sensibilidad: 44%; Especificidad: 100%). Conclusión: La duración de la rigidez matinal, evaluada en minutos por el médico, estaría relacionada tanto con la actividad de la enfermedad como con la discapacidad. La intensidad de la rigidez matinal se asoció más fuertemente con la actividad inflamatoria en los pacientes con AR

Desempeño del RAPID3 (Routine Assessment of Patient Index Data) en pacientes con osteoartritis de rodilla, cadera o mano / RAPID3 (Routine Assessment of Patient Index Data) performance in patients with osteoarthritis of the knee, hip or hand

RAPID3 es un cuestionario autorreportado desarrollado originalmente para valorar pacientes con AR. Recientemente fue empleado en pacientes con OA de rodillas y/o caderas con buenos resultados. Objetivo: Determinar si existe correlación entre el RAPID3 y otros cuestionarios en pacientes con OA de manos (AUSCAN), cadera y/o rodilla (WOMAC) y comparar el tiempo para su realización y cálculo. Material y métodos: Estudio analítico observacional de corte transversal. Se incluyeron pacientes consecutivos ≥50 años con diagnóstico de OA de rodillas, caderas y/o manos que completaron el RAPID3; además el AUSCAN y/o WOMAC según la localización de la OA. Se midió el tiempo para completar y calcular los cuestionarios. Resultados: Se incluyeron 104 pacientes. Al comparar RAPID3 con WOMAC y AUSCAN se observó una correlación de 0,66 y 0,62 respectivamente (p<0,01). Al evaluar RAPID3 con la subescala de función del WOMAC, la correlación fue de 0,75 (p<0,01) y con WOMAC Ab de 0,68 (p<0,001). El tiempo para completar y calcular el RAPID3 fue menor que para los otros cuestionarios. Conclusión: Se observó buena correlación entre RAPID3, WOMAC y AUSCAN, requiriendo un menor tiempo para su realización y cálculo. Por lo tanto, podría ser una herramienta útil para evaluar pacientes con OA de rodilla, caderas y/o manos

Novel application assigned to toluquinol: inhibition of lymphangiogenesis by interfering with VEGF-C/VEGFR-3 signalling pathway.

BACKGROUND AND PURPOSE: Lymphangiogenesis is an important biological process associated with the pathogenesis of several diseases, including metastatic dissemination, graft rejection, lymphoedema and other inflammatory disorders. The development of new drugs that block lymphangiogenesis has become a promising therapeutic strategy. In this study, we investigated the ability of toluquinol, a 2-methyl-hydroquinone isolated from the culture broth of the marine fungus Penicillium sp. HL-85-ALS5-R004, to inhibit lymphangiogenesis in vitro, ex vivo and in vivo. EXPERIMENTAL APPROACH: We used human lymphatic endothelial cells (LECs) to analyse the effect of toluquinol in 2D and 3D in vitro cultures and in the ex vivo mouse lymphatic ring assay. For in vivo approaches, the transgenic Fli1:eGFPy1 zebrafish, mouse ear sponges and cornea models were used. Western blotting and apoptosis analyses were carried out to search for drug targets. KEY RESULTS: Toluquinol inhibited LEC proliferation, migration, tubulogenesis and sprouting of new lymphatic vessels. Furthermore, toluquinol induced apoptosis of LECs after 14 h of treatment in vitro, blocked the development of the thoracic duct in zebrafish and reduced the VEGF-C-induced lymphatic vessel formation and corneal neovascularization in mice. Mechanistically, we demonstrated that this drug attenuates VEGF-C-induced VEGFR-3 phosphorylation in a dose-dependent manner and suppresses the phosphorylation of Akt and ERK1/2. CONCLUSIONS AND IMPLICATIONS: Based on these findings, we propose toluquinol as a new candidate with pharmacological potential for the treatment of lymphangiogenesis-related pathologies. Notably, its ability to suppress corneal neovascularization paves the way for applications in vascular ocular pathologies.

Perinatal and childhood factors and risk of breast cancer subtypes in adulthood.

BACKGROUND: Accumulated exposure to hormones and growth factors during early life may influence the future risk of breast cancer (BC). This study examines the influence of childhood-related, socio-demographic and anthropometric variables on BC risk, overall and by specific pathologic subtypes. METHODS: This is a case-control study where 1539 histologically-confirmed BC cases (23-85 years) and 1621 population controls, frequency matched by age, were recruited in 10 Spanish provinces. Perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with BC risk, globally and according to menopausal status and pathologic subtypes, was evaluated using logistic and multinomial regression models, adjusting for tumor specific risk factors. RESULTS: Birth characteristics were not related with BC risk. However, women with high socioeconomic level at birth presented a decreased BC risk (OR=0.45; 95% CI=0.29-0.70), while those whose mothers were aged over 39 years at their birth showed an almost significant excess risk of hormone receptor positive tumors (HR+) (OR=1.35; 95% CI=0.99-1.84). Women who were taller than their girl mates before puberty showed increased postmenopausal BC risk (OR=1.26; 95% CI=1.03-1.54) and increased HR+ BC risk (OR=1.26; 95% CI=1.04-1.52). Regarding prepubertal weight, while those women who were thinner than average showed higher postmenopausal BC risk (OR=1.46; 95% CI=1.20-1.78), associated with HR+ tumors (OR=1.34; 95% CI=1.12-1.61) and with triple negative tumors (OR=1.56; 95% CI=1.03-2.35), those who were heavier than average presented lower premenopausal BC risk (OR=0.64; 95% CI=0.46-0.90) and lower risk of epidermal growth factor receptor positive tumors (OR=0.61; 95% CI=0.40-0.93). CONCLUSION: These data reflect the importance of hormones and growth factors in the early stages of life, when the mammary gland is in development and therefore more vulnerable to proliferative stimuli.

Insights Into Oxygen Adsorption on Ag-Cu Nanocluster as an Oxidation Catalyst by Ab Initio Atomistic Thermodynamics.

To understand the catalytic activity of Ag-Cu cluster as catalyst of ethylene oxidation, bare Ag and Cu and Ag core/Cu12 shell and Cu core/Ag12 shell are built and optimized by density functional theory calculations incorporating the effect of the atmospheric environment. Consequently different oxygen adsorption sites on the cluster are considered: top site of the shell atoms, bridge site of the shell atoms and hollow site of the shell atoms. For each adsorption site, a few coverages are considered, both oxygen-rich condition and oxygen-poor condition. The phase diagrams of oxygen and 13-atom Ag-Cu clusters are finally determined. The pressure-temperature phase diagrams are determined for the oxygen and 13-atom Ag-Cu clusters, which reveal important insights into this system and its catalytic properties. The phase diagrams of oxygen and 13-atom Ag-Cu clusters are finally determined. The results predict the most stable phase: structure and adsorption of oxygen at certain temperature and certain pressure. Under oxygen-poor condition, the cluster structures are most likely to be changed. This information must be helpful to understand the catalytic process of Ag-Cu cluster as catalyst of ethylene oxidation.

Consumo de antiinflamatorios no esteroideos en pacientes que concurren por primera vez a un servicio de reumatología / Consumption of nonsteroidal anti-inflammaroty drug in patients attending for the first time a rehumatologic Unit

Introducción: El uso de antiinflamatorios no esteroideos (AINES) conlleva una mayor probabilidad de enfermedad gastrointestinal y cardiovascular en pacientes con factores de riesgo. Por tal motivo, se desarrollaron diversas recomendaciones con el fin de prevenir dichas complicaciones. Objetivo: Evaluar la frecuencia del consumo de AINES al momento de consultar por primera vez a un Servicio de Reumatología de demanda espontánea; y analizar tanto la conducta del médico así como el correcto cumplimiento de las recomendaciones para la toma de estos fármacos al finalizar la consulta. Material y métodos: Estudio observacional de corte transversal. Resultados: Se incluyeron 304 pacientes, 59,5% consumían AINES. La mayoría de estos pacientes presentaban riesgo gastrointestinal moderado/alto, sólo 28,3% recibían adecuada protección. De aquellos pacientes que recibían AINES, se consideró que requerían dicho tratamiento el 50%. Al finalizar la consulta, se tomó una conducta correcta en el 89% de los casos en relación al riesgo gastrointestinal. Conclusión: Más de la mitad de los pacientes consumían AINES. Se observó un buen cumplimiento de las recomendaciones por los médicos tratantes al finalizar la primera consulta. Sin embargo, es importante mencionar que el uso indiscriminado de AINES tanto por parte de los pacientes como por parte de los médicos sigue siendo alto.

Introduction: The use of Non-Steroidal Anti-Inflammatory DrugsNSAID (NSAIDS) leads to a higher probability of gastrointestinaland cardiovascular disease in patients with risk factors. Therefore,a number of recommendations were developed to prevent thesecomplications. The aim of this study was to evaluate the intake frequencyof NSAID by patients who attend to a rheumatology departmentfor the first time; and to analyze the attending physicians´ prescriptionas well as the correct implementation of the recommendationsfor the use of these drugs once this first visit was ended.Methods: We perform a cross-sectional observational study.Results: Three hundred and four patients were included, 59.5%were taking NSAIDs. Most of these patients had moderate/high gastrointestinalrisk and only 28.3% received adequate protection. Ofpatients receiving NSAIDs, it was considered that only 50% requiredsuch treatment. At the end of the first visit, the attending physiciansmade the correct implementation of the recommendations in 89%of cases in regard to gastrointestinal risk.Conclusion: More than half of the patients were taking NSAIDS.A good compliance with the recommendations by the attendingphysicians at the end of the first visit was observed. However, it isnoteworthy that the indiscriminate use of NSAIDs, both by patientsand by physicians, remains high.

Application of a modified sequential organ failure assessment score to critically ill patients.

The purpose of the present study was to explore the usefulness of the Mexican sequential organ failure assessment (MEXSOFA) score for assessing the risk of mortality for critically ill patients in the ICU. A total of 232 consecutive patients admitted to an ICU were included in the study. The MEXSOFA was calculated using the original SOFA scoring system with two modifications: the PaO2/FiO2 ratio was replaced with the SpO2/FiO2 ratio, and the evaluation of neurologic dysfunction was excluded. The ICU mortality rate was 20.2%. Patients with an initial MEXSOFA score of 9 points or less calculated during the first 24 h after admission to the ICU had a mortality rate of 14.8%, while those with an initial MEXSOFA score of 10 points or more had a mortality rate of 40%. The MEXSOFA score at 48 h was also associated with mortality: patients with a score of 9 points or less had a mortality rate of 14.1%, while those with a score of 10 points or more had a mortality rate of 50%. In a multivariate analysis, only the MEXSOFA score at 48 h was an independent predictor for in-ICU death with an OR = 1.35 (95%CI = 1.14-1.59, P < 0.001). The SOFA and MEXSOFA scores calculated 24 h after admission to the ICU demonstrated a good level of discrimination for predicting the in-ICU mortality risk in critically ill patients. The MEXSOFA score at 48 h was an independent predictor of death; with each 1-point increase, the odds of death increased by 35%.

Application of a modified sequential organ failure assessment score to critically ill patients

The purpose of the present study was to explore the usefulness of the Mexican sequential organ failure assessment (MEXSOFA) score for assessing the risk of mortality for critically ill patients in the ICU. A total of 232 consecutive patients admitted to an ICU were included in the study. The MEXSOFA was calculated using the original SOFA scoring system with two modifications: the PaO2/FiO2 ratio was replaced with the SpO2/FiO2 ratio, and the evaluation of neurologic dysfunction was excluded. The ICU mortality rate was 20.2%. Patients with an initial MEXSOFA score of 9 points or less calculated during the first 24 h after admission to the ICU had a mortality rate of 14.8%, while those with an initial MEXSOFA score of 10 points or more had a mortality rate of 40%. The MEXSOFA score at 48 h was also associated with mortality: patients with a score of 9 points or less had a mortality rate of 14.1%, while those with a score of 10 points or more had a mortality rate of 50%. In a multivariate analysis, only the MEXSOFA score at 48 h was an independent predictor for in-ICU death with an OR = 1.35 (95%CI = 1.14-1.59, P < 0.001). The SOFA and MEXSOFA scores calculated 24 h after admission to the ICU demonstrated a good level of discrimination for predicting the in-ICU mortality risk in critically ill patients. The MEXSOFA score at 48 h was an independent predictor of death; with each 1-point increase, the odds of death increased by 35%.

Pharmacological potential of biogenic amine-polyamine interactions beyond neurotransmission.

Histamine, serotonin and dopamine are biogenic amines involved in intercellular communication with multiple effects on human pathophysiology. They are products of two highly homologous enzymes, histidine decarboxylase and l-aromatic amino acid decarboxylase, and transmit their signals through different receptors and signal transduction mechanisms. Polyamines derived from ornithine (putrescine, spermidine and spermine) are mainly involved in intracellular effects related to cell proliferation and death mechanisms. This review summarizes structural and functional evidence for interactions between components of all these amine metabolic and signalling networks (decarboxylases, transporters, oxidases, receptors etc.) at cellular and tissue levels, distinct from nervous and neuroendocrine systems, where the crosstalk among these amine-related components can also have important pathophysiological consequences. The discussion highlights aspects that could help to predict and discuss the effects of intervention strategies.

Mycobacterium mucogenicum and other non-tuberculous mycobacteria in potable water of a trauma hospital: a potential source for human infection.

This study examined the frequency of occurrence of non-tuberculous mycobacteria (NTM) in potable water samples from a main trauma hospital in Mexico City. Sixty-nine potable water samples were collected, 23 from each source: cistern, kitchen tap and bathroom showers. Of the 69 samples, 36 harboured NTM species. Twenty-nine of the 36 isolates were Mycobacterium mucogenicum, two Mycobacterium rhodesiae, one Mycobacterium peregrinum, one Mycobacterium fortuitum and three were Mycobacterium spp. Hospital potable water harbouring NTM represents a potential source for nosocomial infections, therefore we suggest that hospital potable water microbiological guidelines should include testing for NTM species.

Regulatory cross-talk of mouse liver polyamine and methionine metabolic pathways: a systemic approach to its physiopathological consequences.

Both polyamines and methionine derivatives are nitrogen compounds directly related to the regulation of gene expression. In silico predictions and experimental evidence suggest a cross-talk between polyamine and methionine metabolism in mammalian tissues. Since liver is the major organ that controls nitrogen metabolism of the whole organism, it is the best tissue to further test this hypothesis in vivo. In this work, we studied the effects of the chronic administration of a methionine-supplemented diet (0.5% Met in drinking water for 5 months) on the liver of mice (designated as MET-mice). Metabolic and proteomic approaches were performed and the data obtained were subjected to biocomputational analysis. Results showed that a supplemental methionine intake can indeed regulate biogenic amine metabolism in an in vivo model by multiple mechanisms including metabolic regulation and specific gene demethylation. Furthermore, putative systemic effects were investigated by molecular and cellular biology methods. Among other results, altered expression levels of multiple inflammation and cell proliferation/death balance markers were found and macrophage activation was observed. Overall, the results presented here will be of interest across a variety of biomedical disciplines, including nutrition, orphan diseases, immunology and oncology.

A re-evaluation of the mitogenic effect of serotonin on vascular endothelial cells.

Serotonin is an extracellular mediator recognized by seven different types of receptors, thus giving rise to pleiotropic intracellular responses. One of these responses is the activation of proliferation for a number of cell types. The induction of proliferation of otherwise quiescent endothelial cells is a key step of angiogenesis. Previously published work concerning the effect of serotonin on endothelial cell proliferation is controversial. The present work is aimed to re-evaluate the mitogenic role of serotonin on endothelial cells, since a pro-angiogenic role for serotonin could be hypothesized if its mitogenic potential on these cells were confirmed. By using three different types of endothelial cells and three experimental approaches, we demonstrate that serotonin cannot be considered a general mitogen for endothelial cells.

In silico analysis of arginine catabolism as a source of nitric oxide or polyamines in endothelial cells.

We use a modeling and simulation approach to carry out an in silico analysis of the metabolic pathways involving arginine as a precursor of nitric oxide or polyamines in aorta endothelial cells. Our model predicts conditions of physiological steady state, as well as the response of the system to changes in the control parameter, external arginine concentration. Metabolic flux control analysis allowed us to predict the values of flux control coefficients for all the transporters and enzymes included in the model. This analysis fulfills the flux control coefficient summation theorem and shows that both the low affinity transporter and arginase share the control of the fluxes through these metabolic pathways.