How quality of life is measured in studies of nutritional intervention: a systematic review.

BACKGROUND: Nutrition care can positively affect multiple aspects of patient's health; outcomes are commonly evaluated on the basis of their impact on a patient's (i) illness-specific conditions and (ii) health-related quality of life (HRQoL). Our systematic review examined how HRQoL was measured in studies of nutritional interventions. To help future researchers select appropriate Quality of Life Questionnaires (QoLQ), we identified commonly-used instruments and their uses across populations in different regions, of different ages, and with different diseases. METHODS: We searched EMCare, EMBASE, and Medline databases for studies that had HRQoL and nutrition intervention terms in the title, the abstract, or the MeSH term classifications "quality of life" and any of "nutrition therapy", "diet therapy", or "dietary supplements" and identified 1,113 studies for possible inclusion.We then reviewed titles, abstracts, and full texts to identify studies for final inclusion. RESULTS: Our review of titles, abstracts, and full texts resulted in the inclusion of 116 relevant studies in our final analysis. Our review identified 14 general and 25 disease-specific QoLQ. The most-used general QoLQ were the Short-Form 36-Item Health Survey (SF-36) in 27 studies and EuroQol 5-Dimension, (EQ-5D) in 26 studies. The European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC-QLQ), a cancer-specific QoLQ, was the most frequently used disease-specific QoLQ (28 studies). Disease-specific QoLQ were also identified for nutrition-related diseases such as diabetes, obesity, and dysphagia. Sixteen studies used multiple QoLQ, of which eight studies included both general and disease-specific measures of HRQoL. The most studied diseases were cancer (36 studies) and malnutrition (24 studies). There were few studies focused on specific age-group populations, with only 38 studies (33%) focused on adults 65 years and older and only 4 studies focused on pediatric patients. Regional variation in QoLQ use was observed, with EQ-5D used more frequently in Europe and SF-36 more commonly used in North America. CONCLUSIONS: Use of QoLQ to measure HRQoL is well established in the literature; both general and disease-specific instruments are now available for use. We advise further studies to examine potential benefits of using both general and disease-specific QoLQ to better understand the impact of nutritional interventions on HRQoL.

Red Blood Cells Protein Profile Is Modified in Breast Cancer Patients.

Metastasis is the primary cause of death for most breast cancer (BC) patients who succumb to the disease. During the hematogenous dissemination, circulating tumor cells interact with different blood components. Thus, there are microenvironmental and systemic processes contributing to cancer regulation. We have recently published that red blood cells (RBCs) that accompany circulating tumor cells have prognostic value in metastatic BC patients. RBC alterations are related to several diseases. Although the principal known role is gas transport, it has been recently assigned additional functions as regulatory cells on circulation. Hence, to explore their potential contribution to tumor progression, we characterized the proteomic composition of RBCs from 53 BC patients from stages I to III and IV, compared with 33 cancer-free controls. In this work, we observed that RBCs from BC patients showed a different proteomic profile compared to cancer-free controls and between different tumor stages. The differential proteins were mainly related to extracellular components, proteasome, and metabolism. Embryonic hemoglobins, not expected in adults' RBCs, were detected in BC patients. Besides, lysosome-associated membrane glycoprotein 2 emerge as a new RBCs marker with diagnostic and prognostic potential for metastatic BC patients. Seemingly, RBCs are acquiring modifications in their proteomic composition that probably represents the systemic cancer disease, conditioned by the tumor microenvironment.

A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer.

Breast cancers of the luminal B subtype are frequent tumors with high proliferation and poor prognosis. Epigenetic alterations have been found in breast tumors and in biological fluids. We aimed to profile the cell-free DNA (cfDNA) methylome of metastatic luminal B breast cancer (LBBC) patients using an epigenomic approach to discover potential noninvasive biomarkers. Plasma cfDNA was analyzed using the Infinium MethylationEpic array in a cohort of 14 women, including metastatic LBBC patients and nontumor controls. The methylation levels of cfDNA and tissue samples were validated with droplet digital PCR. The methylation and gene expression data of 582 primary luminal breast tumors and 79 nontumor tissues were obtained from The Cancer Genome Atlas (TCGA). We found an episignature of 1,467 differentially methylated CpGs that clearly identified patients with LBBC. Among the genes identified, the promoter hypermethylation of WNT1 was validated in cfDNA, showing an area under the ROC curve (AUC) of 0.86 for the noninvasive detection of metastatic LBBC. Both paired cfDNA and primary/metastatic breast tumor samples showed hypermethylation of WNT1. TCGA analysis revealed significant WNT1 hypermethylation in the primary tumors of luminal breast cancer patients, with a negative association between WNT1 methylation and gene expression. In this proof-of-principle study, we discovered an episignature associated with metastatic LBBC using a genome-wide cfDNA methylation approach. We also identified the promoter hypermethylation of WNT1 in cfDNA as a potential noninvasive biomarker for luminal breast cancer. Our results support the use of EPIC arrays to identify new epigenetic noninvasive biomarkers in breast cancer.

Economic Impact of Reducing Reexcision Rates after Breast-Conserving Surgery in a Large, Integrated Health System.

BACKGROUND: Reexcision after breast-conserving surgery (BCS) is costly for patients, but few studies have captured the economic burden to a healthcare system. We quantified operating room (OR) charges as well as OR time and then modeled expected savings of a reexcision reduction initiative. METHODS: We performed a retrospective cohort review of all breast cancer patients with BCS between January 1, 2016 and December 31, 2020. Operating room charges of disposable supplies and implants as well as operative time were calculated. RESULTS: During the 5-year period, the 8804 patients who underwent BCS, 1628 (18.5%) required reexcision. The reexcision cohort was younger (61 vs. 64 years, p < 0.001), more likely to have ductal carcinoma in situ (DCIS) (23.7% vs. 15.2%, p < 0.001), and had larger tumors (T1+T2 73.2% vs. 83.1%, p < 0.001). Reexcision costs represented 39% of total costs, the cost per patient for surgery was fourfold higher for reexcision patients. Reexcision operations comprised 14% of total operating room (OR) time (1848 of 13,030 hours). The reexcision rate for 54 surgeons varied from 7.2-39.0% with 46% (n = 25) having a reexcision rate >20%. A model simulating reducing reexcision rates to 20% or below for all surgeons reduced the reexcision rate to 16.2% overall. Using per procedure data, the model predicted a decrease in reexcision operations by 18% (327 operations), OR costs by 14% ($287,534), and OR time by 11% (204 hours). CONCLUSIONS: Reexcision after BCS represents 39% of direct OR costs and 14% of OR time in our healthcare system. Modest improvements in surgeon reexcision rates may lead to significant economic and OR time savings.

Control inadecuado del dolor agudo postoperatorio: prevalencia, prevención y consecuencias. Revisión de la situación en Latinoamérica / Inadequate management of acute postoperative pain: prevalence, prevention, and consequences. Review of the situation in Latin America

Resumen: Introducción: El dolor postoperatorio tiene un alto impacto, es una de las principales causas médicas de retraso en el alta hospitalaria. Asimismo, es causa frecuente de readmisión hospitalaria, retrasos en la recuperación y mayores costos para el sistema de salud y los pacientes. El objetivo del presente trabajo es conocer mejor la situación del dolor agudo postoperatorio en Latinoamérica mediante una revisión bibliográfica para poder establecer su prevalencia y evaluar su magnitud. Material y métodos: Se efectuó una búsqueda bibliográfica en SciELO y PubMed tratando de recopilar la información más detallada, precisa y actualizada. Resultados: En Latinoamérica la falta de políticas claras para la evaluación y el tratamiento del dolor postoperatorio, así como de formación, conduce a un control inadecuado del mismo con una prevalencia de dolor agudo postoperatorio moderado/severo superior a 40%. Conclusiones: El manejo del dolor agudo postoperatorio continúa siendo un problema en Latinoamérica. Muchos pacientes refieren dolor moderado o severo tras la cirugía, lo que puede conducir a dolor crónico. Se necesitan más estudios al respecto para poder establecer aún con mayor precisión la prevalencia del dolor agudo postoperatorio y los efectos derivados de su pobre control.

Abstract: Introduction: Postoperative pain has a profound impact. It is one of the main causes of delayed hospital discharge and it is associated with hospital readmission, recovery problems, and higher costs both for the healthcare system and the patients. The aim of this work is to shed light on the postoperative acute pain management in Latin America through a review of the literature, in order to have a better understanding of its prevalence and the extent of the problem. Material and methods: A bibliographical search was performed in SciELO and PubMed trying to gather the most precise, detailed and updated information. Results: In Latin America, the absence of clear policies for the evaluation and treatment of postoperative pain, as well as the lack of training, leads to its inadequate control with a prevalence of moderate/severe acute postoperative pain greater than 40%. Conclusions: Postoperative acute pain continues to be a problem in Latin America. Many patients still suffer moderate to severe pain after surgery, leading to a chronic or persistent painful condition. More studies are needed to get a clear picture of the prevalence of acute postoperative pain and the deleterious effects of an inadequate management.

Short-Term Ex Vivo Culture of CTCs from Advance Breast Cancer Patients: Clinical Implications.

BACKGROUND: Circulating tumor cells (CTC) have relevance as prognostic markers in breast cancer. However, the functional properties of CTCs or their molecular characterization have not been well-studied. Experimental models indicate that only a few cells can survive in the circulation and eventually metastasize. Thus, it is essential to identify these surviving cells capable of forming such metastases. METHODS: We isolated viable CTCs from 50 peripheral blood samples obtained from 35 patients with advanced metastatic breast cancer using RosetteSepTM for ex vivo culture. The CTCs were seeded and monitored on plates under low adherence conditions and with media supplemented with growth factors and Nanoemulsions. Phenotypic analysis was performed by immunofluorescence and gene expression analysis using RT-PCR and CTCs counting by the Cellsearch® system. RESULTS: We found that in 75% of samples the CTC cultures lasted more than 23 days, predicting a shorter Progression-Free Survival in these patients, independently of having ≥5 CTC by Cellsearch®. We also observed that CTCs before and after culture showed a different gene expression profile. CONCLUSIONS: the cultivability of CTCs is a predictive factor. Furthermore, the subset of cells capable of growing ex vivo show stem or mesenchymal features and may represent the CTC population with metastatic potential in vivo.

Epidemiology and O-Serotypes of Extraintestinal Pathogenic Escherichia coli Disease in Patients Undergoing Transrectal Ultrasound Prostate Biopsy: A Prospective Multicenter Study.

PURPOSE: Extraintestinal pathogenic Escherichia coli (ExPEC) are a leading cause of invasive infections in adults. The study aimed to evaluate the incidence of microbiologically confirmed invasive ExPEC disease in patients undergoing transrectal ultrasound-guided prostate needle biopsy (TRUS-PNB), O-serotype distribution and antibiotic resistance profiles of associated E. coli isolates. MATERIALS AND METHODS: Adult men (≥18 years) undergoing TRUS-PNB were enrolled. The TRUS-PNB procedure was performed according to local standard of care, including preferences of prophylactic antibiotics. Clinical and microbiological data were collected. RESULTS: Of the 4,951 patients (mean age 66.9 years) enrolled 4,935 (99.7%) underwent TRUS-PNB (95.1% received prophylactic antibiotics); 98.9% completed the study. Overall incidence of invasive ExPEC disease was 0.67% (33/4,935 patients; 95% CI 0.46-0.94); highest incidence was in the U.S. (0.97%, 14/1,446; 95% CI 0.53-1.62). Prevalence of the 10 selected O-serotypes O1, O2, O4, O6, O8, O15, O16, O18, O25 and O75 was 52.0% (95% CI 31.3-72.2). E. coli isolates showed highest resistance rates to levofloxacin and ciprofloxacin (76%; 95% CI 54.8-90.6 for both). Among fluoroquinolone-resistant ExPEC isolates, prevalence of the 10 selected O-serotypes was 60%. CONCLUSIONS: This study provides an estimate of microbiologically confirmed invasive ExPEC disease incidence following TRUS-PNB. Information on E. coli O-serotype distribution and associated antibiotic resistance profiles from invasive ExPEC disease cases in the first 30 days following TRUS-PNB may help guiding antibiotic use and inform development of a prophylactic ExPEC vaccine.

Characterization of Escherichia coli isolates potentially covered by ExPEC4V and ExPEC10V, that were collected from post-transrectal ultrasound-guided prostate needle biopsy invasive urinary tract and bloodstream infections.

There is an increasing incidence of infectious complications caused by extraintestinal pathogenic Escherichia coli (ExPEC) after transrectal ultrasound-guided prostate needle biopsy (TRUS-PNB), and a need for prophylaxis methods effective against associated antibiotic-resistant organisms. We aimed to identify the O-serotypes of ExPEC isolates collected in a sample of 60 patients with invasive ExPEC disease (IED) after TRUS-PNB, by serotype-specific agglutination and polymerase chain reaction (PCR) assays. The prevalence of O-serotypes included in a tetravalent ExPEC vaccine was 38.3% by agglutination and 46.7% by PCR, while the prevalence of O-serotypes included in a decavalent vaccine was 58.3% and 73.3%, respectively. Therefore, compared to the tetravalent vaccine, the decavalent vaccine would theoretically provide coverage for serotypes carried by a higher proportion of circulating ExPEC in patients undergoing TRUS-PNB, including a high proportion of antibiotic-resistant organisms.

Analysis of a Real-World Cohort of Metastatic Breast Cancer Patients Shows Circulating Tumor Cell Clusters (CTC-clusters) as Predictors of Patient Outcomes.

Circulating tumor cell (CTC) enumeration has emerged as a powerful biomarker for the assessment of prognosis and the response to treatment in metastatic breast cancer (MBC). Moreover, clinical evidences show that CTC-cluster counts add prognostic information to CTC enumeration, however, their significance is not well understood, and more clinical evidences are needed. We aim to evaluate the prognostic value of longitudinally collected single CTCs and CTC-clusters in a heterogeneous real-world cohort of 54 MBC patients. Blood samples were longitudinally collected at baseline and follow up. CTC and CTC-cluster enumeration was performed using the CellSearch® system. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using Cox proportional hazards modelling. Elevated CTC counts and CTC-clusters at baseline were significantly associated with a shorter survival time. In joint analysis, patients with high CTC counts and CTC-cluster at baseline were at a higher risk of progression and death, and longitudinal analysis showed that patients with CTC-clusters had significantly shorter survival compared to patients without clusters. Moreover, patients with CTC-cluster of a larger size were at a higher risk of death. A longitudinal analysis of a real-world cohort of MBC patients indicates that CTC-clusters analysis provides additional prognostic value to single CTC enumeration, and that CTC-cluster size correlates with patient outcome.

Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells.

Traditionally, studies to address the characterization of mechanisms promoting tumor aggressiveness and progression have been focused only on primary tumor analyses, which could provide relevant information but have limitations to really characterize the more aggressive tumor population. To overcome these limitations, circulating tumor cells (CTCs) represent a noninvasive and valuable tool for real-time profiling of disseminated tumor cells. Therefore, the aim of the present study was to explore the value of CTC enumeration and characterization to identify markers associated with the outcome and the aggressiveness of triple-negative breast cancer (TNBC). For that aim, the CTC population from 32 patients diagnosed with TNBC was isolated and characterized. This population showed important cell plasticity in terms of expression of epithelia/mesenchymal and stemness markers, suggesting the relevance of epithelial to mesenchymal transition (EMT) intermediate phenotypes for efficient tumor dissemination. Importantly, the CTC signature demonstrated prognostic value to predict the patients' outcome and pointed to a relevant role of tissue inhibitor of metalloproteinases 1 (TIMP1) and androgen receptor (AR) for TNBC biology. Furthermore, we also analyzed the usefulness of the AR and TIMP1 blockade to target TNBC proliferation and dissemination using in vitro and in vivo zebra fish and mouse models. Overall, the molecular characterization of CTCs from advanced TNBC patients identifies highly specific biomarkers with potential applicability as noninvasive prognostic markers and reinforced the value of TIMP1 and AR as potential therapeutic targets to tackle the most aggressive breast cancer.

CTCs Expression Profiling for Advanced Breast Cancer Monitoring.

The study of circulating tumor cells (CTCs) has a huge clinical interest in advance and metastatic breast cancer patients. However, many approaches are biased by the use of epithelial markers, which underestimate non-epithelial CTCs phenotypes. CTCs enumeration provides valuable prognostic information; however, molecular characterization could be the best option to monitor patients throughout the disease since it may provide more relevant clinical information to the physicians. In this work, we aimed at enumerating and performing a molecular characterization of CTCs from a cohort of 20 patients with metastatic breast cancer (MBC), monitoring the disease at different time points of the therapy, and at progression when it occurred. To this end, we used a CTC negative enrichment protocol that allowed us to recover a higher variety of CTCs phenotypes. With this strategy, we were able to obtain gene expression data from CTCs from all the patients. In addition, we found that high expression levels of PALB2 and MYC were associated with a worse outcome. Interestingly, we identified that CTCs with an EpCAMhighVIMlowALDH1A1high signature showed both shorter overall survival (OS) and progression-free survival (PFS), suggesting that CTCs with epithelial-stem features had the most aggressive phenotype.

Targeting Acr3 from Ensifer medicae to the plasma membrane or to the tonoplast of tobacco hairy roots allows arsenic extrusion or improved accumulation. Effect of acr3 expression on the root transcriptome.

Transgenic tobacco hairy roots expressing the bacterial arsenite efflux pump Acr3 from Ensifer medicae were generated. The gene product was targeted either to the plasma membrane (ACR3 lines) or to the tonoplast by fusing the ACR3 protein to the tonoplast integral protein TIP1.1 (TIP-ACR3 lines). Roots expressing Acr3 at the tonoplast showed greater biomass than those expressing Acr3 at the plasma membrane. Furthermore, higher contents of malondialdehyde (MDA) and RNA degradation in ACR3 lines were indicative of higher oxidative stress. The determination of ROS-scavenging enzymes depicted the transient role of peroxidases in ROS detoxification, followed by the action of superoxide dismutase during both short- and medium-term exposure periods. Regarding As accumulation, ACR3 lines accumulated up to 20-30% less As, whereas TIP-ACR3 achieved a 2-fold increase in As accumulation in comparison to control hairy roots. Strategies that presumably induce As uptake, such as phosphate deprivation or dehydration followed by rehydration in the presence of As, fostered As accumulation up to 10 800 µg g-1. Finally, the effects of the heterologous expression of acr3 on the root transcriptome were assessed. Expression at the plasma membrane induced drastic changes in gene expression, with outstanding overexpression of genes related to electron transport, ATP synthesis and ATPases, suggesting that As efflux is the main detoxification mechanism in these lines. In addition, genes encoding heat shock proteins and those related to proline synthesis and drought tolerance were activated. On the other hand, TIP-ACR3 lines showed a similar gene expression profile to that of control roots, with overexpression of the glutathione and phytochelatin synthesis pathways, together with secondary metabolism pathways as the most important resistance mechanisms in TIP-ACR3, for which As allocation into the vacuole allowed better growth and stress management. Our results suggest that modulation of As accumulation can be achieved by subcellular targeting of Acr3: expression at the tonoplast enhances As accumulation in roots, whereas expression at the plasma membrane could promote As efflux. Thus, both approaches open the possibilities for developing safer crops when grown on As-polluted paddy soils, but expression at the tonoplast leads to better growth and less stressed roots, since the high energy cost of As efflux likely compromises growth in ACR3 lines.

Topically Applied Etamsylate: A New Orphan Drug for HHT-Derived Epistaxis (Antiangiogenesis through FGF Pathway Inhibition).

Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by recurrent and spontaneous epistaxis (nose bleeds), telangiectases on skin and mucosa, internal organ arteriovenous malformations, and dominant autosomal inheritance. Mutations in Endoglin and ACVRL1 / ALK1 , genes mainly expressed in endothelium, are responsible in 90% of the cases for the pathology. These genes are involved in the transforming growth factor-ß(TGF-ß) signaling pathway. Epistaxis remains as one of the most common symptoms impairing the quality of life of patients, becoming life-threatening in some cases. Different strategies have been used to decrease nose bleeds, among them is antiangiogenesis. The two main angiogenic pathways in endothelial cells depend on vascular endothelial growth factor and fibroblast growth factor (FGF). The present work has used etamsylate, the diethylamine salt of the 2,5-dihydroxybenzene sulfonate anion, also known as dobesilate, as a FGF signaling inhibitor. In endothelial cells, in vitro experiments show that etamsylate acts as an antiangiogenic factor, inhibiting wound healing and matrigel tubulogenesis. Moreover, etamsylate decreases phosphorylation of Akt and ERK1/2. A pilot clinical trial (EudraCT: 2016-003982-24) was performed with 12 HHT patients using a topical spray of etamsylate twice a day for 4 weeks. The epistaxis severity score (HHT-ESS) and other pertinent parameters were registered in the clinical trial. The significant reduction in the ESS scale, together with the lack of significant side effects, allowed the designation of topical etamsylate as a new orphan drug for epistaxis in HHT (EMA/OD/135/18).

Psychometric properties of the resilience scale in Mexican patients with chronic hemodialysis / Propiedades psicométricas de la escala de medición de resiliencia en pacientes mexicanos con hemodiálisis crónica

Abstract Introduction Resilience consists of a series personalized skills to cope with adverse situations and overcome them, and even emerge strengthened. Resilience in patients with chronic renal insufficiency (CRI) treated with hemodialysis (HD) has been evaluated with general questionnaires that are not specific for this population. Objective To evaluate the psychometric properties of a resilience questionnaire in patients treated with chronic HD. Method The study included 280 patients with CRI (aged 18 to 85, 44% women) treated with HD for at least two months in six hemodialysis units in Mexico, who completed Beck's depression and anxiety inventories, an inventory of cognitive distortions, and the Mexican Resilience Measurement Scale (RESI-M). Results Owing to the duplication of more than one factor, two of the 43 items were eliminated in the exploratory factor analysis. We confirmed five factors that explained 63.4% of the total variance, with a Cronbach's alpha of .96 (the alpha ranges in the five factors from .85 to .95). The confirmatory analysis showed a theoretical structural model that fits the empirical data in an acceptable, balanced, and parsimonious way. The five factors correlate positively with each other and negatively with anxiety and depression symptoms and distorted thoughts. Discussion and conclusion The RESI-M scale is valid and reliable for assessing resilience in patients treated with chronic HD. Resilience factors evaluated with RESI-M are a potential therapeutic target to reduce depression and anxiety symptoms in these patients.

Resumen Introducción La resiliencia consiste en una serie de habilidades personalizadas que sirven para afrontar situaciones adversas y superarlas, e incluso salir fortalecido. La resiliencia en pacientes con insuficiencia renal crónica (IRC) tratados con hemodiálisis (HD) se ha evaluado con cuestionarios generales, no específicos para esta población. Objetivo Evaluar las propiedades psicométricas de un cuestionario de resiliencia en pacientes tratados con HD crónica. Método Se incluyeron 280 pacientes con IRC (edad 18 a 85 años, 44% mujeres) tratados con HD al menos dos meses en seis unidades de hemodiálisis en México, que respondieron los inventarios de depresión y ansiedad de Beck, un inventario de distorsiones cognitivas y la escala de medición de resiliencia con mexicanos (RESI-M). Resultados Por duplicidad en más de un factor, se eliminaron dos de 43 reactivos en el análisis factorial exploratorio. Se confirmaron cinco factores que explicaron 63.4% de la varianza total, con alfa de Cronbach de .96 (el alfa en los cinco factores va de .85 a .95). El análisis confirmatorio mostró un modelo estructural teórico que se ajusta aceptable, equilibrada y parsimoniosamente a los datos empíricos. Los cinco factores se correlacionan positivamente entre ellos y negativamente con los síntomas de ansiedad, depresión y los pensamientos distorsionados. Discusión y conclusión La escala RESI-M es válida y confiable para evaluar resiliencia en pacientes tratados con HD crónica. Los factores de resiliencia evaluados con la RESI-M son un blanco terapéutico potencial para disminuir los síntomas depresivos y ansiosos en estos pacientes.

CTCs-derived xenograft development in a triple negative breast cancer case.

Triple-negative breast cancer (TNBC) is characterized by high rates of metastasis and no available molecular targets. CTCs derived xenografts (CDX) have demonstrated to be a promising tool for understanding cancer biology. In our study, a CDX from a TNBC patient was developed for the first time. After CDX characterization, WNT signaling was found as the main mechanism related with this tumor biology and potential CTCs markers were identified and subsequently validated in TNBC patients. In this cohort high levels of MELK expression were associated with poorer survival rates. Overall, our study demonstrates that CTCs from TNBC are tumorigenic and CDXs are a useful model to obtain valuable information about the tumor.

Unidades del dolor del siglo xxi. ¿protocolos de consenso o medicina basada en la evidencia? / 21st century pain units. consensus protocols or evidence-based medicine? / Unidades da dor do século xxi. protocolos de consenso ou medicina baseada na evidência?

Resumen La investigación en medicina tiene por objetivo generar nuevos conocimientos que ayuden al diagnóstico, el tratamiento y la prevención de enfermedades. Pero la medicina no es una ciencia exacta, sino una actividad humana heterogénea que se basa solo parcialmente en la ciencia, con varios factores no científicos que influyen en la forma de desarrollar esta actividad. El dolor, como síntoma o como enfermedad, es probablemente el trastorno que más afecta y preocupa a las personas y el que con mayor frecuencia motiva una consulta médica. A pesar de la magnitud del problema, y del interés médico y social por el dolor, la atención y el tratamiento de las personas con dolor crónico es un tema infravalorado o tratado inadecuadamente. Con base en múltiples preguntas que se plantean a lo largo del desarrollo del presente documento, nuestro objetivo es, por un lado, el de señalar que los cambios que se han producido en el manejo del dolor crónico hacen de los llamados protocolos de consenso un ejercicio obsoleto en la medicina del siglo XXI. Por otro lado, en términos de bioética, responder a la pregunta ¿se ajustan los protocolos de consenso al principio de beneficencia del paciente individual?

Abstract Research in medicine is intended to generate new knowledge to help in the diagnosis, treatment and prevention of disease. However, medicine is not an exact science; rather, it is a heterogeneous human activity based only partially on science and involves several non-scientific factors that influence the way it is developed. Pain, as a symptom or as a disease, is probably the disorder that most affects and worries people, and is what most often prompts medical consultation. Despite the magnitude of the problem, and the medical and social interest in pain, the care and treatment of persons with chronic pain is an issue that is undervalued or inadequately addressed. Based on variety of questions posed throughout this document, the objective is, on the one hand, to point out that the changes that have occurred in the way chronic pain is managed make the so-called consensus protocols an obsolete exercise in 21st century medicine. On the other hand, in terms of bioethics, the authors answer the question: Do consensus protocols conform to the principle of beneficence for the individual patient?

Resumo A pesquisa em medicina tem por objetivo gerar novos conhecimentos que ajudem no diagnóstico, tratamento e prevenção de doenças. Porém, a medicina não é uma ciência exata, mas sim uma atividade humana heterogênea que está apenas parcialmente baseada na ciência, com vários fatores não científicos que influenciam na maneira em que essa atividade é desenvolvida. A dor, como sintoma ou como doença, é provavelmente o transtorno que mais afeta e preocupa as pessoas e o que com maior frequência motiva uma consulta médica. Apesar da magnitude do problema e do interesse médico e social pela dor, o atendimento e o tratamento das pessoas com dor crônica é um tema subestimado ou tratado inadequadamente. Com base em múltiplas perguntas que são levantadas ao longo do desenvolvimento do presente trabalho, nosso objetivo é, por um lado, indicar que as mudanças que ocorreram na abordagem da dor crônica fazem dos chamados "protocolos de consenso" um exercício obsoleto na medicina do século XXI. Por outro lado, em termos de bioética, buscamos responder à pergunta: os protocolos de consenso se ajustam aos princípios de beneficência do paciente individual?

Removal of copper from aqueous solutions by rhizofiltration using genetically modified hairy roots expressing a bacterial Cu-binding protein.

The aim of this work was to develop a biotechnological tool to hyperaccumulate high copper (Cu) concentrations from wastewaters. Transgenic tobacco hairy roots were obtained by expressing, either the wild-type version of the gene copC from Pseudomonas fluorescens in the cytoplasm of plant cells (CuHR), or a modified version targeted to the vacuole (CuHR-V). Control hairy roots transformed with the empty vector (HR) were also generated. The roots were incubated in the presence of solutions containing Cu (from 1 to 50 mM). At 5 mM external copper, transgenic hairy roots accumulated twice the amount of copper accumulated by control hairy roots. However, at 50 mM Cu, accumulation in both transgenic and control roots reached similar values. Maximum Cu accumulation achieved by transgenic hairy roots was 45,000 µg g-1 at 50 mM external Cu. Despite the high Cu accumulation, transgenic hairy roots, particularly CuHR-V, showed less toxicity symptoms, in correlation with lower activity of several antioxidant enzymes and lower malondialdehyde (MDA) levels. Moreover, CuHR-V roots displayed low values of the oxidative stress index (OSI) - a global parameter proposed for oxidative stress - indicating that targeting CopC to the vacuole could alleviate the oxidative stress caused by Cu. Our results suggest that expressing copC in transgenic hairy roots is a suitable strategy to obtain Cu-hyperaccumulator hairy roots with less toxicity stress symptoms. ABBREVIATIONS: APX: ascorbate peroxidase; ATSDR: Agency for Toxic Substances and Disease Registry (U.S.); BCF: bioconcentration factor; CuHR: copper-hairy roots; EDTA: ethylenediamine tetracetic acid; EPA: Environmental Protection Agency (U.S.); GSH: glutathione; HM: heavy metals; HR: control hairy roots; ICP-OES: Inductively Coupled Plasma/Optical Emission Spectrometry; MDA: malondialdehyde; NBT: nitroblue tetrazolium; OD: optical density; OSI: oxidative stress index; PCR: polymerase chain reaction; PVP: polyvynilpirrolidone; PX: peroxidase; ROS: reactive oxygen species; SOD: superoxide dismutase.

Aldosterone synthase gene polymorphism and renal histopathologic changes in kidney transplant patients receiving a calcineurin inhibitor.

INTRODUCTION: Aldosterone participates in the pathogenesis of calcineurin inhibitor nephrotoxicity (CIN), producing renal vasoconstriction and transforming growth factor beta (TGFß) expression. The objective of this study was to assess aldosterone polymorphisms and relationships to plasma aldosterone levels and the development of renal histological lesions in kidney transplant patients. MATERIAL AND METHODS: Patients with kidney graft biopsy were divided according to the presence or absence of CIN. We determined aldosterone synthase (AS) -344 T/C and int 2 W/C gene polymorphisms and plasma aldosterone levels. Histological, biochemical and clinical variables were measured. RESULTS: Calcineurin inhibitor (CI) levels were significantly higher in patients with the int 2 WW genotype than in patients with WC or CC genotypes. There was a greater degree of interstitial fibrosis in patients with int 2 CC genotype. No relationship was found between the different polymorphisms and a higher degree and/or frequency of CIN. There was also no relationship with plasma aldosterone levels. CONCLUSION: The frequency of the different polymorphisms studied was not related to plasma aldosterone levels or the development of CIN; however, the int 2 CC genotype was related to a greater degree of interstitial fibrosis, whereas the WW genotype was related to higher CI serum levels.