Use of Residual Malt from an Artisanal Beer Brewing Process in the Biosynthesis of Silver Nanoparticles Mediated by Nucleating and Structure-Directing Agents.

Biosynthesized silver nanoparticles (AgNPs) are widely used in varied applications, which are morphology dependent. Consequently, a morphology-controlled synthesis is mandatory. Although there are several studies focused on the plant extract-based biosynthesis of metallic nanoparticles, the use of extracts obtained from agro-wastes is scant. Furthermore, information regarding morphology modification through the use of additional agents is even more scarce. Thus, in this study, AgNPs were synthesized using a malt extract (ME) obtained from an artisanal beer brewing process residue. Additionally, sodium chloride (NaCl), gum arabic (GA), and talc (T) were used in an attempt to modify the morphology of AgNPs. XRD, DLS, SEM, and TEM results demonstrate that stable AgNPs of different sizes and shapes were synthesized. FTIR, HPLC analysis, and the quantification of total proteins, free amino acids, reducing sugars, and total polyphenols before and after AgNPs synthesis showed that ME biomolecules allowed them to act as a source of reducing and stabilizing agents. Therefore, this study provides evidence that ME can be successfully used to biosynthesize AgNPs. Additionally, the antibacterial activity of AgNPs against Gram-negative and Gram-positive bacteria was evaluated. Results indicate that AgNPs show a higher antibacterial activity against Gram-positive bacteria.

HPLC-UV evaluation of a microwave assisted method as an active drug loading technique for exosome-based drug delivery system.

This paper evaluates the potential of a microwave radiation (MR) assisted method as an active drug loading technique for exosomes using polyphenolic nutraceuticals as model drugs (i.e. resveratrol (RV), rosmarinic acid (RA), pterostilbene (PT) and epigallocatechin gallate (EG)). MR is evaluated as a single step method and as part of a two-step method consisting of incubation (IN) followed by MR. The effect of exposure time, loading method and type of nutraceutical on the loading efficiency were investigated using high performance liquid chromatography (HPLC), X-ray diffraction (XRD) and flow cytometry. Additionally, dynamic light scattering (DLS) was used to determine the size of exosomes. Loading efficiency results indicated that MR is a promising method to be used as loading process. Results also suggested that due to different levels of hydrophobicity, related to the number of OH groups, the absorption of polyphenols into the bilayer of EVs is different for each molecule. According to XRD results, MR could not be used with any cargo drug since radiation could affect the chemical composition and the degree of crystallinity of such molecules, consequently affecting their performance. Flow cytometry results indicated that loading methods negatively affect exosome concentration.

Neurologic complications in herpes simplex encephalitis: clinical, immunological and genetic studies.

Patients with herpes simplex virus (HSV) encephalitis (HSE) often develop neuronal autoantibody-associated encephalitis (AE) post-infection. Risk factors of AE are unknown. We tested the hypotheses that predisposition for AE post-HSE may be involved, including genetic variants at specific loci, human leucocyte (HLA) haplotypes, or the blood innate immune response against HSV, including type I interferon (IFN) immunity. Patients of all ages with HSE diagnosed between 1 January 2014 and 31 December 2021 were included in one of two cohorts depending on whether the recruitment was at HSE onset (Spanish Cohort A) or by the time of new neurological manifestations (international Cohort B). Patients were assessed for the type of neurological syndromes; HLA haplotypes; blood type I-IFN signature [RNA quantification of 6 or 28 IFN-response genes (IRG)] and toll-like receptor (TLR3)-type I IFN-related gene mutations. Overall, 190 patients (52% male) were recruited, 93 in Cohort A and 97 in Cohort B. Thirty-nine (42%) patients from Cohort A developed neuronal autoantibodies, and 21 (54%) of them developed AE. Three syndromes (choreoathetosis, anti-NMDAR-like encephalitis and behavioural-psychiatric) showed a high (≥95% cases) association with neuronal autoantibodies. Patients who developed AE post-HSE were less likely to carry the allele HLA-A*02 (4/21, 19%) than those who did not develop AE (42/65, 65%, P = 0.0003) or the Spanish general population (2005/4335, 46%, P = 0.0145). Blood IFN signatures using 6 or 28 IRG were positive in 19/21 (91%) and 18/21 (86%) patients at HSE onset, and rapidly decreased during follow-up. At Day 21 after HSE onset, patients who later developed AE had higher median IFN signature compared with those who did not develop AE [median Zs-6-IRG 1.4 (0.6; 2.0) versus 0.2 (-0.4; 0.8), P = 0.03]. However, a very high median Zs-6-IRG (>4) or persistently increased IFN signature associated with uncontrolled viral infection. Whole exome sequencing showed that the percentage of TLR3-IFN-related mutations in patients who developed AE was not different from those who did not develop AE [3/37 (8%) versus 2/57 (4%), P = 0.379]. Multivariate logistic regression showed that a moderate increase of the blood IFN signature at Day 21 (median Zs-6-IRG >1.5 but <4) was the most important predictor of AE post-HSE [odds ratio 34.8, interquartile ratio (1.7-691.9)]. Altogether, these findings show that most AE post-HSE manifest with three distinct syndromes, and HLA-A*02, but not TLR3-IFN-related mutations, confer protection from developing AE. In addition to neuronal autoantibodies, the blood IFN signature in the context of HSE may be potentially useful for the diagnosis and monitoring of HSE complications.

Pharmacological Activities and Chemical Stability of Natural and Enzymatically Acylated Anthocyanins: A Comparative Review.

Anthocyanins (ANCs) are naturally occurring water-soluble pigments responsible for conferring red, blue, and purple colors to fruits, vegetables, flowers, and grains. Due to their chemical structure, they are highly susceptible to degradation by external factors, such as pH, light, temperature, and oxygen. Naturally acylated anthocyanins have proven to be more stable in response to external factors and exhibit superior biological effects as compared with their non-acylated analogues. Therefore, synthetic acylation represents a viable alternative to make the application of these compounds more suitable for use. Enzyme-mediated synthetic acylation produces derivatives that are highly similar to those obtained through the natural acylation process, with the main difference between these two pathways being the catalytic site of the enzymes involved in the synthesis; acyltransferases catalyze natural acylation, while lipases catalyze synthetic acylation. In both cases, their active sites perform the addition of carbon chains to the hydroxyl groups of anthocyanin glycosyl moieties. Currently, there is no comparative information regarding natural and enzymatically acylated anthocyanins. In this sense, the aim of this review is to compare natural and enzyme-mediated synthetic acylated anthocyanins in terms of chemical stability and pharmacological activity with a focus on inflammation and diabetes.

Corrigendum: Ligand-based CAR T-cell: Different strategies to drive T-cells in future new treatments.

[This corrects the article DOI: 10.3389/fimmu.2022.932559.].

Ligand-based CAR-T cell: Different strategies to drive T cells in future new treatments.

Chimeric antigen receptor (CAR)-based therapies are presented as innovative treatments for multiple malignancies. Despite their clinical success, there is scientific evidence of the limitations of these therapies mainly due to immunogenicity issues, toxicities associated with the infusion of the product, and relapses of the tumor. As a result, novel approaches are appearing aiming to solve and/or mitigate the harmful effects of CAR-T therapies. These include strategies based on the use of ligands as binding moieties or ligand-based CAR-T cells. Several proposals are currently under development, with some undergoing clinical trials to assess their potential benefits. In addition to these, therapies such as chimeric autoantibody receptor (CAAR), B-cell receptor antigen for reverse targeting (BAR), and even chimeric human leukocyte antigen (HLA) antibody receptor (CHAR) have emerged, benefiting from the advantages of antigenic ligands as antibody-binding motifs. This review focuses on the potential role that ligands can play in current and future antitumor treatments and in other types of diseases, such as autoimmune diseases or problems associated with transplantation.

SARS-CoV-2 T-cell response in COVID-19 convalescent patients with and without lung sequelae.

A specific T-cell response persists in the majority of COVID-19 patients 6 months after hospital discharge. This response is more prominent in those who required critical care during the acute COVID-19 episode but is reduced in patients with lung sequelae. https://bit.ly/3fBuVA4.

Post-mortem neuropathologic examination of a 6-case series of CAR T-cell treated patients.

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for the treatment of refractory hematopoietic malignancies. Adverse events are common, and neurotoxicity is one of the most important. However, the physiopathology is unknown and neuropathologic information is scarce. Materials and methods: Post-mortem examination of 6 brains from patients that underwent CAR T-cell therapy from 2017 to 2022. In all cases, polymerase chain reaction (PCR) in paraffin blocks for the detection of CAR T cells was performed. Results: Two patients died of hematologic progression, while the others died of cytokine release syndrome, lung infection, encephalomyelitis, and acute liver failure. Two out of 6 presented neurological symptoms, one with extracranial malignancy progression and the other with encephalomyelitis. The neuropathology of the latter showed severe perivascular and interstitial lymphocytic infiltration, predominantly CD8+, together with a diffuse interstitial histiocytic infiltration, affecting mainly the spinal cord, midbrain, and hippocampus, and a diffuse gliosis of basal ganglia, hippocampus, and brainstem. Microbiological studies were negative for neurotropic viruses, and PCR failed to detect CAR T -cells. Another case without detectable neurological signs showed cortical and subcortical gliosis due to acute hypoxic-ischemic damage. The remaining 4 cases only showed a mild patchy gliosis and microglial activation, and CAR T cells were detected by PCR only in one of them. Conclusions: In this series of patients that died after CAR T-cell therapy, we predominantly found non-specific or minimal neuropathological changes. CAR T-cell related toxicity may not be the only cause of neurological symptoms, and the autopsy could detect additional pathological findings.

Satisfacción en simulación clínica en estudiantes de medicina / Medical students' satisfaction with clinical simulation

Introducción: El avance tecnológico ha generado cambios en los procesos de enseñanza-aprendizaje. Con la simulación clínica existen resultados controversiales. La satisfacción del estudiante se relaciona con el nivel de aprendizaje adquirido. Objetivo: Identificar el nivel de satisfacción con el uso de simulación clínica durante la formación académica de estudiantes de medicina. Métodos: Estudio descriptivo, transversal y observacional, realizado entre agosto-noviembre de 2019 en el Laboratorio de Simulación Clínica de la Universidad de Monterrey. Se incluyeron estudiantes de medicina, y se excluyendo los repetidores y con inasistencias. Se eliminaron las encuestas incompletas en variables principales. La muestra censal fue n = 509. Se utilizó la encuesta de Calidad y Satisfacción en Simulación Clínica (Alfa de Cronbach .861), tipo Likert de 1-5, con 3 componentes: aprendizaje significativo, estructura de la simulación y relación interpersonal. Se realizaron estadísticas descriptivas. Resultados: Predominaron el sexo masculino 54,8 por ciento (279) y la edad promedio 21,8 años (DE 4.1). La mediana del puntaje de la escala resultó 73 (15-75). El nivel de satisfacción más alto se obtuvo en el séptimo semestre con 74 (15-75) y en Cirugía general con 75 (75-59). Los reactivos con mayor porcentaje de respuesta "Muy de acuerdo" fueron: "La capacitación del profesorado es adecuada" 90,8 por ciento (462) y La simulación es un método docente útil para el aprendizaje 89,4 por ciento (455); y con menor puntuación La duración del caso es adecuada 61,1 por ciento (311) y En simulación, es útil el ver las propias actuaciones grabadas 61,3 por ciento (312). Conclusión: Existe un alto nivel de satisfacción con el uso de simulación clínica durante la formación de estudiantes de medicina(AU)

Introduction: Technological development has produced changes in the teaching-learning processes. Clinical simulation also shows controversial results. Student satisfaction is related to acquired level of learning. Objective: To identify the level of satisfaction of medical students with the use of clinical simulation during their academic training. Methods: Descriptive, cross-sectional and observational study carried out, between August and November, 2019, at the Clinical Simulation Laboratory of University of Monterrey. Medical students were included, except for students repeating their studies and those who were used to being absent. Surveys incomplete on main variables were eliminated. The census sample was n=509. The Quality and Satisfaction Survey of Clinical Simulation (Cronbach's Alpha .861) was used, Likert type 1-5, with three components: significant learning, simulation structure and interpersonal relationship. Descriptive statistics were made. Results: The male sex predominated 54.8 percent (279), while the average age was 21.8 years (SD 4.1). The median of the scale score was 73 (15-75). The highest level of satisfaction was obtained in the seventh semester, accounting for 74 (15-75) and in General Surgery, accounting for 75 (75-59). The items with the highest percentage of Strongly agree were Teacher training is adequate (90.8 percent: 462) and Simulation is a useful teaching method for learning (89.4 percent: 455). The lower score corresponded to The case duration is adequate (61.1 percent 311) and In simulation, it is useful to watch recorded performances themselves (61.3 percent 312). Conclusion: There is a high level of satisfaction with the use of clinical simulation during the training of medical students(AU)

Enzymatic synthesis of phlorizin fructosides.

Phlorizin is a low soluble dihydrochalcone with relevant pharmacological properties. In this study, enzymatic fructosylation was approached to enhance the water solubility of phlorizin, and consequently its bioavailability. Three enzymes were assayed for phlorizin fructosylation in aqueous reactions using sucrose as fructosyl donor. Levansucrase (EC 2.4.1.10) from Gluconacetobacter diazotrophicus (Gd_LsdA) was 6.5-fold more efficient than invertase (EC 3.2.1.26) from Rhodotorula mucilaginosa (Rh_Inv), while sucrose:sucrose 1-fructosyltransferase (EC 2.4.1.99) from Schedonorus arundinaceus (Sa_1-SST) failed to modify the non-sugar acceptor. Gd_LsdA synthesized series of phlorizin mono- di- and tri-fructosides with maximal conversion efficiency of 73 %. The three most abundant products were identified by ESI-MS and NMR analysis as ß-D-fructofuranosyl-(2→6)-phlorizin (P1a), phlorizin-4'-O-ß-D-fructofuranosyl-(2→6)-D-fructofuranoside (P2c) and phlorizin-4-O-monofructofuranoside (P1b), respectively. Purified P1a was 16 times (30.57 g L-1 at 25 °C) more soluble in water than natural phlorizin (1.93 g L-1 at 25 °C) and exhibited 44.56 % free radical scavenging activity. Gd_LsdA is an attractive candidate enzyme for the scaled synthesis of phlorizin fructosides in the absence of co-solvent.

Consensus on hemophilia in Mexico.

Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles, and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion-transmitted infections), or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology characterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.

La hemofilia es un trastorno hemorrágico con patrón de herencia ligado al sexo, caracterizado por una incapacidad en la amplificación de la coagulación ocasionada por la deficiencia del factor VIII (hemofilia A o clásica) o del factor IX (hemofilia B). La secuenciación de los genes involucrados en la hemofilia ha permitido la descripción y registro de las principales mutaciones, así como la correlación con los diversos grados de severidad. Las manifestaciones hemorrágicas se relacionan con los niveles de factor deficiente circulante, afectando principalmente al sistema musculoesquelético y en particular a las grandes articulaciones (rodillas, tobillos y codos). El presente documento hace una revisión y consenso de los principales aspectos genéticos de la hemofilia, desde el patrón de herencia y el concepto de mujeres portadoras, la fisiopatología y clasificación de la enfermedad, los estudios básicos y de confirmación ante la sospecha de hemofilia, y de los diversos esquemas de tratamiento basados en la infusión del factor de coagulación deficiente hasta las terapias innovadoras libres de factor, así como de las recomendaciones para el manejo de las complicaciones asociadas al tratamiento (desarrollo de inhibidores y/o infecciones transmitidas por transfusión) o secundarias a los eventos hemorrágicos a nivel articular (artropatía hemofílica). La parte final del documento revisa los aspectos clínicos y de tratamiento relevantes de una patología hemorragica caracterizada por la deficiencia adquirida del FVIII mediada por anticuerpos neutralizantes denominada hemofilia adquirida.

Consenso de hemofilia en México / Mexican Consensus in Haemophilia

resumen está disponible en el texto completo

Abstract Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion transmitted infections) or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology charachterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.

Auto- medicación y auto-prescripción en el personal de salud del primer nivel de atención de México, Bolivia y Ecuador / Selfmedication and selfprescription in health care workers in primary care in Mexico, Bolivia and Ecuador

Introducción. La prevalencia general de la automedicación en la población general fluctúa de 27.3% a 61.3%. En trabajadores de la salud está menos documentado (Definido como auto prescripción), así como su frecuencia y las características del personal médico. Material y métodos. Se trata de un estudio comparativo transversal de 3 países, México (178), Bolivia (250) y Ecuador (130) en población de Médicos Familiares y Médicos Generales de Primer nivel de atención en salud; sexo y edad indistintos, activos en consulta pública o institucional. El muestreo fue por conveniencia calculado por fórmula. Se usó una encuesta con datos demográficos, Frecuencia de automedicación y auto prescripción, patologías donde se usaron, y razones de uso y fuentes de información. Se capturaron y analizaron en SPSS versión 20. Se utilizaron estadísticas descriptivas e inferenciales como ji-cuadrada y Kruskal Wallis. Aprobado por el comité de ética de dos países. Resultados. De los participantes 58.0% son médicos familiares, la mayoría femeninas (p<.05), con pareja, y con promedio de edad de 39.3. Laboran en el sistema público 42.2%. Se automedicaron y auto prescribieron más medicamentos los médicos en México y menos en Ecuador (p<.0001). En general, en el último mes, 61.5% de los profesionales estudiados se auto medicó (media 2.99 veces), y menor porcentaje se auto prescribió 35.8%, (media 1.28 veces) principalmente analgésicos y antibióticos (p<.0001) y por patologías respiratorias (p<.05). Las variables numéricas no cumplieron los supuestos de normalidad. Conclusión. Más de la mitad de los profesionales estudiados se auto medicó y más de un tercio se auto prescribió (antibióticos y analgésicos), esto más en México (AU)

Introduction. The general prevalence of selfmedication in the general population fluctuates from 27.3% to 61.3%. It is less documented in health workers (denominated as selfprescription), as well as its frequency and the characteristics of medical personnel. Material and methods. This is a cross- sectional, comparative study of 3 countries, Mexico (178), Bolivia (250) and, Ecuador (130) in the population of Family Physicians and General Practitioners of the first level of care; indistinct sex and age, active practice in public or institutional consultation. Sampling was for convenience calculated by a formula. A survey with demographic data, II Frequency of self-medication and self-prescription, pathologies where they were used, reasons for use and, sources of information were used. They were captured and analyzed in SPSS version 20. Descriptive and inferential statistics such as chi-square and Kruskal Wallis were used. It was approved by the ethic committee from two countries. Results. Of the participants, 58.0% are family doctors, the majority female (p <.05), with a partner, and with an average age of 39.3 years; 42.2% work in the public system. More physicians in Mexico and fewer in Ecuador used self-medicated and self- prescribed medications (p <.0001). In general in the last month, 61.5% of the professionals self-medicated (average 2.99 times), and a lower percentage (35.8%,)self-prescribed (average 1.28 times) mainly pain relievers and antibiotics (p <.0001) and for respiratory pathologies (p <.05). The numerical variables did not meet the assumptions of normality. Conclusion. More than half of the professionals studied practice self-medication and more than third antibiotics and analgesics as self-prescription this more in Mexico (AU)

Validación de Shared Decision Making Questionnaire - physician version (SDM-Q-Doc) en español / Validation of the Shared Decision Making Questionnaire - physician version (SDM-Q-Doc) in Spanish

OBJETIVO: Validar Shared Decision Making Questionnaire - physician version (SDM-Q-Doc) en español. DISEÑO: Estudio transversal, multicéntrico y de validación clinimétrica. EMPLAZAMIENTO: Unidades de Atención Primaria. PARTICIPANTES: En la fase de adaptación transcultural fueron 31 médicos de familia y en la de validación 219, todos activos en la práctica médica a nivel institucional y/o privado. MEDICIONES PRINCIPALES: Adaptación transcultural (traducción directa, síntesis y conciliación de la versión por un comité de expertos, traducción inversa, conciliación de la traducción inversa con autores del cuestionario original, análisis de comprensión en una muestra de pacientes) y aspectos psicométricos (fiabilidad y validez). RESULTADOS: Se realizó la adaptación transcultural, la pregunta guía 2 se homologó al SDM-Q-9. No se observaron valores negativos en la correlación de item corregido - con la correlación total; todos son mayores que 0,80. El Alfa de Cronbach fue de 0,963. El item 1 explicó una varianza del 77,2 %. La prueba de Kaiser-Meyer-Olkin (KMO) fue de 0,924 con una esfericidad de Barlett estadísticamente significativa. La matriz de correlación de Pearson demuestra una correlación positiva; en general la relación inter-item es mayor a 0,606. CONCLUSIONES: Se ha validado un cuestionario útil, corto y accesible para aplicarse en Atención Primaria, para medir la toma de decisiones compartidas desde la perspectiva del médico

OBJECTIVE: To validate the Shared Decision Making Questionnaire - physician version (SDM-Q- Doc) in Spanish. DESIGN: Cross-sectional, multicenter, clinimetric validation study. SETTING: Primary Care Units. PARTICIPANTS: In the cross-cultural adaptation phase there were 31 family doctors, and in the validation phase there were 219, all active medical professionals at the institutional and / or private level. MAIN MEASURES: Cross-cultural adaptation (direct translation, synthesis and reconciliation of the version by an expert committee, reverse translation, reconciliation of the reverse translation with authors of the original questionnaire, comprehension analysis in a sample of patients) and psychometric aspects (reliability and validity). RESULTS: Cross-cultural adaptation was performed, guide question 2 was homologated to SDM-Q-9. No negative values were observed in the corrected item-total correlation- with the total correlation; all are higher than 0.80. Cronbach's Alpha was 0.963. Item 1 explained a variance of 77.2%. The Kaiser-Meyer-Olkin (KMO) test was 0.924 with a statistically significant Barlett Sphericity. Pearson's correlation matrix shows a positive correlation; in general the inter-item relationship is greater than 0.606. CONCLUSIONS: A useful, short and accessible questionnaire to be applied in Primary Care has been validated to measure shared decision-making from the physician's perspective

Androgen Receptor and Its Splicing Variant 7 Expression in Peripheral Blood Mononuclear Cells and in Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer.

Androgen receptor (AR) signaling remains crucial in castration-resistant prostate cancer (CRPC). Since it is also essential in immune cells, we studied whether the expression of AR full-length (ARFL) and its splicing variant ARV7 in peripheral blood mononuclear cells (PBMC) predicts systemic treatment response in mCRPC in comparison with circulating-tumor cells (CTC). We measured ARFL and ARV7 mRNA in PBMC and CTC from patients prior to receiving abiraterone (AA), enzalutamide (E), or taxanes by a pre-amplification plus quantitative reverse-transcription PCR. They were also tested in LNCaP-ARV7-transfected and in 22RV1 docetaxel-resistant (22RV1DR) cells. We studied 171 PBMC from 136 patients and from 24 non-cancer controls, and 47 CTC from 22 patients. High PBMC ARV7 levels correlated with worse AA/E and better taxane response. In taxane-treated patients high PBMC ARFL also correlated with longer progression-free survival (PFS). High ARV7 and ARFL expression were independently associated with better biochemical-PFS. Conversely, high CTC ARV7 and ARFL correlated with shorter radiological-PFS and overall survival, respectively. High ARV7 in 22RV1DR and LNCaP-ARV7 cells correlated with taxane resistance. In conclusion, ARFL and ARV7 at PBMC or CTC have a different predictive role in the taxane response, suggesting a potential influence of the AR pathway from PBMC in such response modulation.

Actitudes de los médicos familiares mexicanos sobre el uso de placebos en la práctica clínica.

INTRODUCTION: The use of placebo has spread in clinical practice despite being controversial. In Mexico, the practice of family medicine is predominantly institutional and works with an essential medications list. OBJECTIVE: To determine the frequency and family doctor attitude regarding the use of placebos in clinical practice. METHOD: Cross-sectional, observational, multicenter study of 307 family doctors with active practice in 27 states of the Mexican Republic. A questionnaire was used with sociodemographic data and consensus-developed questions about frequency of use and attitudes. For analysis, the square-chi test was used. RESULTS: 75% used placebos (95% CI=69.7-79.4%); 122 (39.7%) used pure placebos, mainly water (p < 0.05), and 220 (71.6%), impure placebos, mainly vitamins and laboratory tests. They were used more in patients with medically unexplained physical symptoms (178, 45.5%), including 122 (31.2%) "healthy worried" patients, or who had chronic conditions (40, 12.5%). Reasons for prescription: 249 (81%) for the psychological effect, when they showed benefit (176, 57%), even when it implied deceiving (78, 25%) or insufficient evidence of efficacy (57, 19%). The main reason was because of patient insistence. CONCLUSIONS: More impure placebos were used, mainly in healthy worried patients and in those with chronic conditions.

INTRODUCCIÓN: El uso de placebo se ha extendido en la práctica a pesar de ser polémico. En México, la práctica de medicina familiar es predominante institucional y trabaja con un cuadro básico de medicamentos. OBJETIVO: Determinar la frecuencia y actitud del médico familiar en la utilización de placebos en la práctica clínica. MÉTODO: Estudio transversal, observacional, multicéntrico, en 307 médicos familiares con práctica activa, en 27 estados de la República Mexicana. Se usó cuestionario con datos sociodemográficos, preguntas sobre frecuencia de uso y actitudes elaboradas por consenso. Se analizó con chi cuadrada. RESULTADOS: 75 % utilizó placebos (IC 95 % = 69.7-79.4 %); 122 (39.7 %) placebos puros, principalmente agua (p < 0.05), y 220 (71.6 %) placebos impuros, principalmente vitaminas y exámenes de laboratorio. Los usaron más en pacientes con síntomas físicos no explicados médicamente (178, 45.5 %), incluidos 122 (31.2 %) pacientes "sanos preocupados" o con padecimientos crónicos (40, 12.5 %). Motivos de prescripción: 249 (81 %) por el efecto psicológico, cuando demostraron beneficio (176, 57 %), aun cuando implicara engaño (78, 25 %) o evidencia de eficacia insuficiente (57, 19 %). El principal motivo fue por insistencia del paciente. CONCLUSIONES: Se utilizaron más placebos impuros, principalmente en pacientes sanos preocupados y en aquellos con padecimientos crónicos.

Actitudes de los médicos familiares mexicanos sobre el uso de placebos en la práctica clínica / Attitudes of Mexican family physicians on the use of placebos in clinical practice

Resumen Introducción: El uso de placebo se ha extendido en la práctica a pesar de ser polémico. En México, la práctica de medicina familiar es predominante institucional y trabaja con un cuadro básico de medicamentos. Objetivo: Determinar la frecuencia y actitud del médico familiar en la utilización de placebos en la práctica clínica. Método: Estudio transversal, observacional, multicéntrico, en 307 médicos familiares con práctica activa, en 27 estados de la República Mexicana. Se usó cuestionario con datos sociodemográficos, preguntas sobre frecuencia de uso y actitudes elaboradas por consenso. Se analizó con chi cuadrada. Resultados: 75 % utilizó placebos (IC 95 % = 69.7-79.4 %); 122 (39.7 %) placebos puros, principalmente agua (p < 0.05), y 220 (71.6 %) placebos impuros, principalmente vitaminas y exámenes de laboratorio. Los usaron más en pacientes con síntomas físicos no explicados médicamente (178, 45.5 %), incluidos 122 (31.2 %) pacientes “sanos preocupados” o con padecimientos crónicos (40, 12.5 %). Motivos de prescripción: 249 (81 %) por el efecto psicológico, cuando demostraron beneficio (176, 57 %), aun cuando implicara engaño (78, 25 %) o evidencia de eficacia insuficiente (57, 19 %). El principal motivo fue por insistencia del paciente. Conclusiones: Se utilizaron más placebos impuros, principalmente en pacientes sanos preocupados y en aquellos con padecimientos crónicos.

Abstract Introduction: The use of placebo has spread in clinical practice despite being controversial. In Mexico, the practice of family medicine is predominantly institutional and works with an essential medications list. Objective: To determine the frequency and family doctor attitude regarding the use of placebos in clinical practice. Method: Cross-sectional, observational, multicenter study of 307 family doctors with active practice in 27 states of the Mexican Republic. A questionnaire was used with sociodemographic data and consensus-developed questions about frequency of use and attitudes. For analysis, the square-chi test was used. Results: 75% used placebos (95% CI=69.7-79.4%); 122 (39.7%) used pure placebos, mainly water (p < 0.05), and 220 (71.6%), impure placebos, mainly vitamins and laboratory tests. They were used more in patients with medically unexplained physical symptoms (178, 45.5%), including 122 (31.2%) “healthy worried” patients, or who had chronic conditions (40, 12.5%). Reasons for prescription: 249 (81%) for the psychological effect, when they showed benefit (176, 57%), even when it implied deceiving (78, 25%) or insufficient evidence of efficacy (57, 19%). The main reason was because of patient insistence. Conclusions: More impure placebos were used, mainly in healthy worried patients and in those with chronic conditions.

Fructosylation of phenolic compounds by levansucrase from Gluconacetobacter diazotrophicus.

Fructosylation can significantly improve the solubility, stability and bioactivity of phenolic compounds, increasing their health benefits. Levansucrase from Gluconacetobacter diazotrophicus (LsdA, EC 2.4.1.10) was found to transfer the fructosyl unit of sucrose to different classes of phenolic compounds. Among the various acceptors tested, the isoflavone puerarin and the phenol coniferyl alcohol were the most efficiently fructosylated compounds, with conversion rates of 93% and 25.1%, respectively. In both cases, mono-, di-, and trifructosides were synthesized at a ratio of 37:14:1 and 32:8:1, respectively. Structural characterization of the puerarin mono-fructoside revealed that the enzyme transferred the fructosyl moiety of sucrose to the O6-position of the glucosyl unit of puerarin. The water solubility of fructosyl-ß-(2→6)-puerarin was increased 23-fold, up to 16.2 g L-1, while its antioxidant capacity was only decreased 1.25-fold compared with that of puerarin.

Functionalization of natural compounds by enzymatic fructosylation.

Enzymatic fructosylation of organic acceptors other than sugar opens access to the production of new molecules that do not exist in nature. These new glycoconjugates may have improved physical-chemical and bioactive properties like solubility, stability, bioavailability, and bioactivity. This review focuses on different classes of acceptors including alkyl alcohols, aromatic alcohols, alkaloids, flavonoids, and xanthonoids, which were tested for the production of fructoderivatives using enzymes from the glycoside hydrolase (GH) families 32 and 68 that use sucrose as donor substrate. The enzymatic strategies and the reaction conditions required for the achievement of these complex reactions are discussed, in particular with regard to the type of acceptors. The solubility and pharmacokinetic and antioxidant activity of some of these new ß-D-fructofuranosides in comparison is reviewed and compared with their glucoside analogs to highlight the differences between these molecules for technological applications.