Unveiling the tartrazine binding mode with ds-DNA by UV-visible spectroscopy, electrochemical, and QM/MM methods.

Here, we studied the interaction between the food colorant tartrazine (TZ) and double stranded DNA (dsDNA), using spectroscopic, electrochemical, and computational methods such as QM/MM combined with TD-DFT. Despite the UV-vis spectroscopy is widely used to study the interaction between molecules, for the case of TZ there are discrepancies in the analyses presented in the literature available, presenting both hyperchromic and hypochromic effects and consequently different rationalizations for their results. Herein we propose the combination of UV-vis experiments with the design of high-level computational models capable of reproducing the experimental behavior to finally define the proper binding mode at the molecular scale together with the rationalization of the experimental optical response due to the complex formation. To complement the UV-vis experiments, we propose the use of electrochemical measurements, to support the results obtained through UV-vis spectroscopy, as it has been successfully used for the determination of interaction modes between small molecules and biomolecules in any condition. Our UV-vis spectroscopy experiments showed only a hypochromic effect of the absorption spectra of TZ after interaction with DNA, indicative of TZ being deeply buried in the DNA structure. The effect of ionic strength in the experimental procedures led to the dissociation of TZ, thus indicating that the interaction mode was groove binding. On the other hand, the electrochemical studies showed an irreversible reduction peak of TZ, which after the interaction with DNA exhibited a positive shift in potential that can be attributed to groove binding. The binding constant for TZ-DNA was calculated as 4.45x104M-1 (UV-vis) and 5.75x104M-1 (electrochemistry), in line with other groove binder azo dyes. Finally, through the QM/MM calculations we found that the minor-groove binding mode interacting in zones rich in adenine and thymine was the model best suited to reproduce the experimental UV-vis response.

Expression of PD-L1 in renal cancer, prognostic features and clinical utility of its routine staining.

INTRODUCTION: The expression of PD-L1 in renal cell carcinoma (RCC) is associated with worse survival and prognostic clinical-pathological features. However, they seem to respond better to new therapeutic agents. Knowing the behavior of RCC according to the presence of PD-L1 has implications for medical counseling and therapeutic approaches. OBJECTIVE: To identify the presence of PD-L1 in renal tumor cells and analyze its association with patients' prognostic factors, overall survival (OS) and cancer-specific survival (CSS). METHODOLOGY: Retrospective analysis of RCC tissue samples, obtained between 2018 and 2021. Immunohistochemistry analysis with mouse monoclonal Anti PD-L1, clone 22C3. Definition of PD-L1 "positive" as a Tumor Proportion Score ≥1%. Comparison of prognostic factors according to the presence or absence of PD-L1, and univariate analysis for OS and CSS. RESULTS: 14% (n = 11) of the sample were PD-L1(+). Average age was 59 years. There were no statistically significant differences between PD-L1 status and TNM stages, nuclear grade and histology. PD-L1(+) had worse OS with a HR of 5.27 (CI: 1.1-23.7; P = .03) and CSS showed a unfavorable tendency for PD-L1(+) with a HR of 4.79 (CI: 0.79-28.95; P = .08). CONCLUSION: The prevalence of PD-L1 in RCC is considerable. In this study PD-L1(+) was associated with unfavorable OS and CSS. It seems reasonable to incorporate its routine use in RCC.

Avances en tuberculosis en el 54º congreso chileno de enfermedades respiratorias. 2ª parte: nuevas normas técnicas chilenas para el control y eliminación de la tuberculosis / New Chilean technical standards for the control and elimination of tuberculosis

La incidencia de la tuberculosis (TBC) en Chile se ha ido incrementando en el último quinquenio, excepto al inicio de la pandemia de Covid-19, donde la pesquisa de TBC se redujo en forma importante. El escenario epidemiológico actual dista del objetivo propuesto en la Estrategia Nacional de Salud (ENS) de la década 2011-2020 (un plan nacional de gobierno para enfermedades relevantes en la población) que consistía en alcanzar una tasa de incidencia de todas las formas de TBC menor a 5 / 100.000 habitantes. La nueva ENS para la década 2021-2030 propone reducir la incidencia de la enfermedad mediante el diagnóstico oportuno y precoz focalizando las intervenciones en las poblaciones de riesgo de la enfermedad (grupos vulnerables), a modo de pesquisa activa y no solo como pesquisa por consultas espontáneas de sintomáticos respiratorios, o tamizajes masivos que pueden no seleccionar a la población de riesgo. También propone intervenir en la prevención priorizando el estudio y tratamiento de la población con Infección Tuberculosa Latente (ITL) de mayor riesgo de progresión hacia la enfermedad. Por último, se pretende mejorar la eficiencia del proceso de tratamiento de la TBC, optimizando el acceso y adherencia a las terapias de los casos activos de TBC como medida de incrementar la proporción de curación. Una nueva norma ministerial para el manejo y control de la TBC puede ayudar enormemente a esta propuesta. Esta norma entrada plenamente en vigencia el año 2022 entrega las herramientas operacionales para cumplir el objetivo señalado para la nueva ENS. La norma incorpora actividades tendientes a lograr una mayor cobertura de estudio y tratamiento de la ITL en grupos específicos, donde se incluyen, además de los contactos infantiles, a los contactos adultos y a otros grupos vulnerables. La terapia para esta condición se realizará utilizando la asociación de Isoniazida con Rifapentina de preferencia. Esta terapia se aplica bajo supervisión en una dosis semanal durante 3 meses (12 dosis) y ha demostrado mejor adherencia y menor toxicidad hepática. Para el diagnóstico oportuno de TBC la pesquisa se ha focalizado en los sintomáticos respiratorios (tos con expectoración) de más de 2 semanas en personas que pertenecen a alguno de los grupos vulnerables, o que tienen rasgos clínicos muy sugerentes de la enfermedad (fiebre, sudoración vespertina, hemoptisis, compromiso del estado general). Como herramienta diagnóstica deja de utilizarse la baciloscopía por su baja sensibilidad y es sustituida por pruebas moleculares, siendo la plataforma automatizada de amplificación de ADN del complejo M. tuberculosis más utilizada y disponible en los servicios de salud públicos el GeneXpert MTB/RIF Ultra, que además entrega información de la susceptibilidad a la rifampicina a través de la identificación de una mutación específica del genoma (gen rpoB). Con esta tecnología se agiliza el proceso diagnóstico (puede obtener resultados durante el día de ejecución, habitualmente no demoraría más de 2 horas) y es de alta sensibilidad (sensibilidad muy similar al cultivo). El tratamiento de la TBC sensible a los fármacos del esquema primario (rifampicina = R, isoniazida = H, etambutol = E y pirazinamida = Z) consiste en la administración diaria en la fase inicial (con los 4 fármacos) durante 2 meses y en la fase de continuación (con isoniazida y rifampicina) durante 4 meses, totalmente supervisado. La TBC con resistencia a rifampicina tiene tratamiento con un esquema acortado oral de 9 meses con nuevos fármacos: bedaquilina, linezolid, clofazimina y levofloxacino (6 meses con los 4 fármacos, seguido de 3 meses con clofazimina y levofloxacino). Estas terapias de alta calidad son seguras y prometen mejores resultados de curación. La nueva norma significa una mayor cobertura para la erradicación de los reservorios de la enfermedad y una mayor precisión en el diagnóstico de las fuentes de trasmisión comunitaria de la enfermedad, siendo un aporte significativo hacia la eliminación de la TBC en el país.

The incidence of tuberculosis (TB) in Chile has been increasing in the last five years except at the beginning of the Covid-19 pandemic where TB screening has clearly decreased. The current epidemiological scenario is far from the goal proposed in the National Health Strategy (NHS) of the decade 2011-2020 (a national government plan for relevant diseases in the population) which was to achieve an incidence rate of all forms of TB less than 5/100,000 inhabitants. The new NHS for the decade 2021-2030 proposes to reduce the incidence of the disease through timely and early diagnosis by focusing interventions on populations at risk of the disease (vulnerable groups), as an active screening and not only as screening for spontaneous consultations of respiratory symptomatic or mass screenings that may not select the population at risk. It also proposed to intervene in prevention prioritizing the study and treatment of the population with Latent Tuberculosis Infection (LTI) at higher risk of progression to the disease. Finally, it intends to improve the efficiency of the TB treatment process, optimizing access and adherence to therapies of active TB cases as a measure to increase the cure rate. A new ministerial standard for the management and control of TB can greatly help this proposal. This standard, fully effective in 2022, provides the operational tools to meet the objective set for the new NHS. The standard incorporates activities aimed at achieving greater coverage of study and treatment of LTI in specific groups, which include, in addition to child contacts, adult contacts and other vulnerable groups. Therapy for this condition will be performed using the combination of isoniazid with rifapentine preferably. Therapy is administered under supervision and patients receive therapy once a week for 12 doses for 3 months. This therapy has shown better adherence and lower liver toxicity. For the timely diagnosis of TB, case finding has focused on respiratory symptoms (cough and expectoration) for more than 2 weeks, in individuals that belong to one of the vulnerable groups, or that have additional clinical features very suggestive of the disease (fever, afternoon sweats, hemoptysis, compromise of the general condition). Smear sputum as a diagnostic tool is no longer used due to low sensitivity and it was replaced by molecular tests in automated platform for DNA amplification of the mycobacterium TB complex. The more used and available in public health services is GeneXpert MTB / RIF Ultra, which also provides information on susceptibility to rifampicin through the identification of a specific genome mutation (rpoB gene). With this technology, the diagnostic process is streamlined (you can obtain results during the day of execution, usually it would not take more than 2 hours) and sensitivity is high (sensitivity very similar to culture). Treatment of TB sensitive to first line drugs (rifampicin, isoniazid, ethambutol and pyrazinamide) consists of daily administration in the initial phase (with four drugs) for 2 months and in the continuation phase (with isoniazid and rifampicin) for 4 months, fully supervised. In rifampicin resistant TB, the treatment is a shortened oral regimen of 9 months with new drugs: bedaquiline, linezolid, clofazimine and levofloxacin (six months with four drugs, followed by three months with clofazimine and levofloxacin). These high-quality therapies are safe and promise better healing results. The new national standards mean a greater coverage for the eradication of the reservoirs of the disease and a greater precision in the diagnosis of the sources of community transmission of tuberculosis, being a significant contribution towards the path of control and elimination of TB in the country.

Pulpectomía mecanizada en molares primarios: caso clínico / Mechanized pulpectomy in primary molars: a clinical case

Las pulpectomías en molares primarios están indica-das en casos de diagnóstico de pulpitis irreversible o necrosis y reabsorción radicular mínima o nula. Son tratamientos laboriosos y extensos, que sólo pueden ser llevados a cabo en pacientes colaboradores. En búsqueda de simplificar esta terapéutica y mejorar su eficacia, se propone la mecanización de la pre-paración de los conductos de molares primarios. Diversos autores aseguran que esta técnica opti-miza el tiempo clínico y mejora la calidad del trata-miento, obteniendo gran aceptación en la literatura actual. Se presenta la secuencia de procedimientos, resolución y controles de dos tratamientos de pul-pectomía con instrumentación mecanizada en mola-res primarios (AU)

Pulpectomies in primary molars are indicated in cases of irreversible pulpitis or necrosis with mini-mal or no root resorption. They are laborious and ex-tensive treatments, which only can be carried out in cooperative patients. In order to simplify this therapy and improve its effectiveness, the mechanization of root canal preparation is proposed. Several authors assume that this technique optimizes preparation time and improves the quality of treatment, obtaining great acceptance in the current literature. We report the sequence of procedures, resolution, and controls of two pulpectomies with mechanized instrumenta-tion in primary molars (AU)

Estudio de caso a una persona con EVC hemorrágico basado en el modelo de Virginia Henderson / Case study of a person with hemorrhagic CVD based on the Cirginia Henderson model

Introducción: la enfermedad vascular cerebral (EVC) es un déficit neurológico súbito causado por alteraciones en la circulación cerebral; considerada por la Organización Mundial de la Salud (OMS) como la segunda causa global de muerte en el mundo, en el 2020 ocupó el séptimo lugar como causa de muerte, en México es un problema de salud pública y una importante causa de discapacidad. Objetivo: realizar un estudio de caso a una persona con EVC hemorrágico a través del proceso de atención de enfermería. Método: plan de cuidados con el modelo de Virginia Henderson; fuentes de información: directa, hoja de enfermería y expediente clínico. Se graficaron signos vitales y presión intracraneal PIC. Análisis de artículos vigentes en PubMed, Redalyc, SciELO, Elsevier. Descripción del caso: masculino hipertenso en descontrol y fumador moderado. En el servicio de urgencias presenta datos de deterioro rostro caudal en fase bulbar, se da manejo avanzado de la vía aérea e ingresa a quirófano para colocación de ventriculostomía. Con probable mortalidad del 97 %. Consideraciones éticas: principios éticos para la investigación en la Escuela Nacional de Enfermería y Obstetricia, ENEO, Código Deontológico de Enfermería, Código de Ética para las Enfermeras y Enfermeros de México y NOM 004 del expediente clínico. Conclusiones: se emplearon cuidados especializados a necesidades alteradas según modelo de Henderson que continúa siendo actual como filosofía adaptativa para valoración integral del ente de nuestros cuidados. Mejoró mi curva de aprendizaje en conocimiento sensible e intelectual con enfoque crítico y neurológico acorde a la enfermería basada en la evidencia. Las EVC son causa de muerte y discapacidad, no deben ser subestimadas sino objeto de atención de instituciones gubernamentales y de salud a nivel mundial pues falta generar cultura de prevención.

Introduction: CVD is a sudden neurological deficit caused by alterations in cerebral circulation; considered by the WHO as the second global cause of death in the world, in 2020 it ranked seventh as a cause of death in Mexico and an important cause of disability. Objective: to carry out a case study of a person with Hemorrhagic CVD through the Nursing Care Process. Method: care plan with the Henderson model; Information sources: direct, Nursing Sheet and Clinical file. Vital signs and ICP were graphed. Analysis of current articles in PubMed, Redalyc, SciELO, ELSEVIER. Case description: patient is uncontrolled hypertensive and a moderate smoker. In the emergency department, he presented data of facial caudal deterioration in the bulbar phase, advanced management of the airway was given, and he entered the operating room for ventriculostomy placement. With Mortality of 97%. Ethical considerations: ethical principles for research in the ENEO, Nursing Code of Ethics, Code of ethics for nurses in Mexico and NOM 004 of the clinical file. Conclusions: specialized care was used for altered needs according to the Henderson model, which continues to be current as an adaptive philosophy for comprehensive assessment of the entity of our care. It improved my learning curve in sensitive and intellectual knowledge with a critical and neurological approach according to evidence-based nursing. CVDs are a cause of death and disability, they should not be underestimated, but rather the object of attention from governmental and health institutions worldwide since it is necessary to generate a culture of prevention.

Situación epidemiológica de la tuberculosis en Chile 2020-2021: repercusiones de la pandemia de COVID-19 / Epidemiological situation of tuberculosis in Chile 2020-2021: repercussions of the COVID-19 pandemic

La situación epidemiológica y operacional de la tuberculosis en el mundo se vio afectada por la pandemia de COVID-19 durante los años 2020 y 2021. A nivel global, el número de casos de tuberculosis notificados disminuyó en un 18% el año 2020 con respecto al año anterior, y el número de muertes por esta causa mostró un aumento en el mismo año. En Chile, se observó una caída similar en el número de casos diagnosticados el año 2020, en directa relación con una disminución del 70% en el número de muestras procesadas para diagnóstico de tuberculosis pulmonar. El presente trabajo detalla indicadores epidemiológicos y operacionales del control de la tuberculosis en Chile para los años 2020 y 2021, y analiza su relación con el impacto de la pandemia COVID-19 sobre las actividades del Programa Nacional de Tuberculosis.

The COVID-19 pandemic during 2020 and 2021 affected the epidemiological and operational situation of tuberculosis control worldwide. Globally, there was a reduction of 18% in the number of notified cases of tuberculosis in 2020 in comparison to the previous year, and the number of deaths increased in the same year. In Chile, there was a similar fall in the number of notified cases, in direct relation to a decrease of 70% in the number of diagnostic tests performed for pulmonary tuberculosis at a national level. This article details the epidemiological and operational indicators of tuberculosis control in Chile during 2020-2021, and analyzes their relation with the impact of COVID-19 pandemic on the activities of the National Tuberculosis Program.

Tuberculosis infantil en Chile: ¿de dónde provienen los casos? / Childhood tuberculosis in Chile: where do the cases come from?

La tuberculosis es la principal causa de muerte por un agente infeccioso a nivel mundial y se estima que un 6% de los casos nuevos corresponde a tuberculosis infantil. La presencia de tuberculosis en niños es una señal de la existencia de transmisión del agente en la comunidad. Esta investigación busca describir las características epidemiológicas de la tuberculosis infantil en Chile entre 2011 y 2020. METODOLOGÍA: estudio descriptivo de los casos de tuberculosis infantil registrados en Chile entre los años 2011 y 2020. RESULTADOS: se registraron 544 casos de tuberculosis en menores de 15 años en el período analizado, con una tasa de incidencia anual entre 1,1 y 2,2 casos por 100.000. Se observa un importante aumento de casos en los últimos tres años, especialmente en el grupo de menores de 5 años. 63,2% corresponden a tuberculosis pulmonar, y de ellos 62,3% fueron confirmados por bacteriología. La mayoría de los casos no presenta comorbilidades que impliquen inmunosupresión y la incidencia de meningitis tuberculosa en menores de 5 años es baja. La proporción de contactos es de 29% y la de extranjeros de 17%, ambas variables en aumento en los últimos años. CONCLUSIÓN: La tuberculosis en niños sigue siendo un problema de salud poco frecuente en Chile. Sin embargo, su aumento en los últimos años debe alertar sobre un incremento de la transmisión comunitaria de la enfermedad, por lo que se debe reforzar la detección oportuna de casos contagiantes, la investigación de contactos y el tratamiento preventivo.

Tuberculosis is the leading cause of death from a single infectious agent worldwide and it is estimated that 6% of new cases are children. Childhood tuberculosis reflects ongoing transmission within communities. This study aims to describe the epidemiological characteristics of childhood tuberculosis in Chile between 2011 and 2020. METHODOLOGY: descriptive study of the cases of tuberculosis under 15 years-old registered in Chile from 2011 to 2020. RESULTS: 544 cases were registered in the period analyzed, with an annual incidence rate between 1.1 and 2.2 cases per 100,000. A significant increase in cases is observed in the last three years, especially in the group under 5 years-old. 63.2% correspond to pulmonary tuberculosis, and among them 62.3% are confirmed by bacteriology. Most of the cases do not have comorbidities and the incidence of tuberculous meningitis in children under 5 years is low. Contacts are 29% of the cases and foreigners are 17%, both percentages are increasing in the last years. CONCLUSION: Childhood tuberculosis remains a low frequency health problem in Chile. However, its increase in recent years implies an increase in the community transmission. Active case finding, contact tracing and preventive treatment should be reinforced.

Eficiencia del tratamiento de casos nuevos de tuberculosis sensible en Chile / Treatment efficiency in new cases of susceptible tuberculosis in Chile

Resumen La terapia de la tuberculosis con el esquema primario recomendado por la OMS no logra la curación de todos los casos a nivel mundial, pero en general alcanza un éxito de curación de al menos el 85% de los casos en el año 2018. El mismo año en Chile la eficiencia del tratamiento es solo de 76%, principalmente por la alta proporción de muertes y pérdida de seguimiento durante la terapia. Datos preliminares muestran que la cohorte ingresada en 2019 tuvo un éxito de tratamiento cercano a 74%. En Chile los fracasos de tratamiento son infrecuentes, debido principalmente a la vigilancia nacional de la susceptibilidad a fármacos. Para reducir la letalidad es necesario reforzar las estrategias para el diagnóstico precoz de la tuberculosis, mediante nuevos algoritmos que incorporen la biología molecular y la radiología en casos sospechosos de esta enfermedad, fomentar el adecuado manejo de las comorbilidades, establecer una adecuada red de apoyo social y disponer de centros de hospitalización cuando se requieren. Además, se debe fortalecer la adherencia a la terapia de los pacientes con estrategias de incentivo y facilitación de la asistencia.

Tuberculosis therapy with the primary regimen recommended by the World Health Organization does not cure all cases globally, but it reached success in at least 85% of cases in the year 2018. The same year in Chile, treatment efficiency is achieved in only 76%, mainly due to the high proportion of deaths and loss of follow-up during therapy. Preliminary data show that in the 2019 cohort the success was achieved only in about 74% of new cases. Treatment failures in Chile are rare due to national surveillance of drug susceptibility. To reduce fatality, it is necessary to reinforce the strategies for early diagnosis of tuberculosis through new algorithms. Such strategies should include molecular biology and radiology in suspected TB cases, to promote proper management of comorbidities, establish an adequate social support network and have centers available for prolonged hospitalization when needed. In addition, patient's adherence to therapy should be strengthened with strategies that encourage and facilitate attendance.

Tuberculosis con resistencia a rifampicina en Chile / Tuberculosis with resistance to rifampicin in Chile

Resumen El éxito de los tratamientos acortados de la tuberculosis se debe a la asociación de fármacos bactericidas y esterilizantes, principalmente Rifampicina e Isoniazida. Cuando la Rifampicina no puede ser utilizada por resistencia, los tratamientos son más prolongados y el éxito en la curación se reduce. La resistencia a Rifampicina frecuentemente se acompaña de resistencia a Isoniazida (Multidrogoresistencia o MDR). La OMS informa que en 2019 se diagnosticaron sólo el 44% de los casos estimados de tuberculosis con resistencia a Rifampicina (se proyectaba 465.000 casos) y se trató sólo al 38% de los casos estimados, quedando una gran proporción de casos sin diagnosticar y sin tratar. En Chile la vigilancia de la susceptibilidad a fármacos de primera línea en cepas de Mycobacterium tuberculosis se efectúa mediante biología molecular desde 2014, observándose un progresivo incremento de casos resistentes a Rifampicina desde 1% (23 casos) para ese año hasta 2,2% (65 casos) en 2019. La mayoría de casos de resistencia a Rifampicina corresponden a resistencia inicial. En casos con resistencia a Rifampicina realizamos estudio de susceptibilidad a fármacos de segunda línea en el laboratorio de referencia nacional. La terapia de TB-MDR tradicional tiene baja eficacia, con abandonos frecuentes por su largo tiempo de terapia y toxicidad. Nuevos tratamientos sin inyectables y el uso de Clofazimina, Fluorquinolonas, Linezolid y Bedaquilina tienen una mejor tasa de curación. Recientemente, el Programa de Control de la Tuberculosis de Chile dispone de esta terapia más eficaz y de menor duración por vía oral con estos fármacos.

The high success rate of shortened Tuberculosis (TB) treatments has been achieved by the association of bactericidal and sterilizing drugs. The main drugs are Rifampicin and Isoniazide. When Rifampicin cannot be used by resistance, the treatment is prolonged and success in healing is significantly reduced. Resistance to Rifampicin is often accompanied by resistance to Isoniazide (Multidrug resistance or MDR). WHO reports that only 44% of estimated TB cases with resistance to Rifampicin were diagnosed in 2019 (465,000 cases projected) and only 38% of estimated cases were treated, with a large proportion of cases remaining undiagnosed and untreated. In Chile, monitoring of susceptibility to first-line drugs is conducted in strains of Mycobacterium tuberculosis by molecular biology since 2014, observing a progressive increase in cases with Rifampicin resistance from 1% for that year (23 cases) to 2.2% in 2019 (65 cases). Most cases of resistance to Rifampicin correspond to cases of initial resistance. In cases with resistance to Rifampicin we carry out susceptibility study to second-line drugs in a national reference laboratory. MDR-TB therapy has low efficacy, with frequent abandonments for its long therapy time and toxicity. New non-injectable treatments and use of Clofazimine, Fluorquinolones, Linezolid and Bedaquiline are achieving a better cure rate. Recently, Chile's TB Control Program has this most effective and shorter-lasting oral therapy with these drugs.

Effectiveness of a formulation containing peptides and vitamin C in treating signs of facial ageing: three clinical studies.

OBJECTIVE: Vitamin C and peptides are widely used in cosmetic products but there is a paucity of clinical studies showing that the formulations are effective in treating signs of facial ageing. These 3 clinical studies evaluated the effectiveness of an anti-ageing formula containing natural vitamin C (10%), biopeptides (rice and lupin), hyaluronic acid, and Vichy volcanic mineralising water, in amber glass ampoules with no preservatives (Peptide-C ampoules). METHODS: Dansyl chloride fluorescence labelling compared cell turnover for Peptide-C ampoules vs untreated skin in 32 female subjects. Study 2, an open clinical study, evaluated the efficacy on wrinkles of Peptide-C ampoules by investigator clinical scoring based on Dynamical Atlas visual assessment (N = 40) and subject self-assessment questionnaires (N = 47). Study 3, an open clinical study, evaluated wrinkles by instrumental quantification with 3D fringe projection analysis (N = 40) and subject questionnaires (N = 51). RESULTS: The mean cell turnover was faster for skin treated with Peptide-C ampoules compared to untreated skin (17.1 days vs. 19.2 days; P < 0.0001). In study 2, after 28 days application of Peptide-C ampoules, clinical grading of crow's-feet wrinkles, forehead wrinkles and nasolabial folds decreased by 9%, 11% and 5%, respectively (all P < 0.05 vs baseline). Of 47 subjects, 77%, 64% and 79% indicated their skin seemed smoothed out, fine lines were less visible, and skin complexion was more radiant, respectively. In study 3, the number of wrinkles decreased by 11.5% after 29 days application of Peptide-C ampoules vs baseline (P < 0.05) and 65% of subjects responded the fine lines were less visible. CONCLUSION: This formulation of a combination of anti-ageing ingredients in ampoules, allowing a minimalist formula, showed significant results on improving facial wrinkles and radiance.

OBJECTIF: La vitamine C et les peptides sont régulièrement utilisés dans les produits dermocosmétiques mais il existe peu d'études cliniques sur l'efficacité des formulations sur les signes du vieillissement cutané du visage. Trois études cliniques ont évalué l'efficacité d'une formule anti-âge contenant de la vitamine C naturelle (10%), des biopeptides (riz et lupin), de l'acide hyaluronique et de l'eau minéralisante volcanique de Vichy, dans un format d'ampoules en verre ambré, sans conservateur (ampoules Peptide-C). MÉTHODES: Une première étude a comparé par la technique de chlorure de Dansyl le renouvellement cellulaire avec la formulation ampoules Peptide-C et la peau non traitée chez 32 sujets féminins. La seconde étude, en ouvert, a évalué l'efficacité clinique sur les rides des ampoules Peptide-C en se reposant sur les Atlas Dynamiques (N=40) et les questionnaires d'auto-évaluation des sujets (N=47). La troisième étude, ouverte, a évalué les rides par quantification instrumentale avec l'analyse de projection de franges 3D (N=40) et les questionnaires d'autoévaluation des sujets (N=51). RÉSULTATS: Le renouvellement cellulaire était plus rapide pour la peau traitée avec des ampoules de Peptide-C comparées à la peau non traitée (17.1 jours contre 19.2 jours ; p<.0001). Dans l'étude 2, après 28 jours d'application des ampoules Peptide-C, l'évaluation clinique des rides de la patte d'oie, du front et des plis naso-labiaux a montré une amélioration de 9 %, 11 % et 5 %, respectivement (tous p<0,05 vs baseline). Sur 47 sujets, 77%, 64% et 79% ont indiqué que leur peau semblait respectivement lissée, que les ridules étaient moins visibles et que le teint de la peau était plus radieux. Dans l'étude 3, le nombre de rides a diminué de 11,5 % après 29 jours d'application des ampoules Peptide-C par rapport à la baseline (p<0,05) et 65 % des sujets ont répondu que les ridules étaient moins visibles. CONCLUSION: Cette combinaison d'ingrédients anti-âge dans un format d'ampoules, et une formulation minimaliste, a montré des résultats significatifs sur l'amélioration des rides faciales et de l'éclat du teint.

Experiencia piloto con esquema rifapentina-isoniazida semanal por 3 meses para tratamiento de la infección tuberculosa latente en el Programa Nacional de Tuberculosis de Chile / Pilot experience with weekly rifapentine-isoniazid treatment for 3 months for latent tuberculosis infection at the Tuberculosis National Program of Chile

INTRODUCCIÓN: La prevención de la tuberculosis activa en los grupos de riesgo es clave para el control y eliminación de la tuberculosis. El tratamiento de la infección tuberculosa latente (TITL) con rifapentina e isoniazida en dosis semanales por 12 semanas es más corto que con otros esquemas, tiene menor hepatotoxicidad, mejor adherencia y es costo-efectivo. El OBJETIVO del estudio es evaluar la factibilidad de implementar este esquema a nivel programático en Chile. MÉTODOS: Se hizo una intervención piloto en territorios seleccionados entre mayo de 2018 y marzo de 2019. En esos territorios se reemplazó el esquema normado de TITL con isoniazida 6 meses por el esquema rifapentina-isoniazida 12 semanas. Además, se amplió la población objetivo, incluyendo a contactos mayores de 14 años. El tratamiento consistió en la administración conjunta de isoniazida y rifapentina por vía oral con frecuencia semanal, por 12 semanas, de forma supervisada por personal de salud. RESULTADOS: Ingresaron 238 pacientes al piloto, de los cuales 53% fueron mujeres y 54,2% fueron mayores de 14 años. Del total de pacientes, 203 (85,3%) completaron el tratamiento, 22 (9,2%) lo abandonaron, 8 (3,4%) presentaron reacciones adversas y 5 tuvieron otros motivos de egreso. CONCLUSIÓN: Tanto el TITL con rifapentinaisoniazida por 3 meses en dosis semanales supervisadas, como la incorporación de contactos adultos a TITL, son factibles de implementar a nivel programático en Chile.

INTRODUCTION: Prevention of active tuberculosis in risk groups is crucial in tuberculosis control and elimination. Treatment of latent tuberculosis (TITL) with rifapentine and isoniazid in weekly doses for 12 weeks is shorter than other pharmacological treatments, with less liver toxicity, better patient compliance and it is cost-effective. The OBJECTIVE of this study is to evaluate the feasibility to implement this treatment at a programmatic level in Chile. METHODS: A pilot intervention was conducted in selected territories between May 2018 and March 2019. Within these territories, the regulated treatment with isoniazid 6 months was replaced by the 12 weeks treatment with weekly rifapentine-isoniazide. Additionally, the target population was expanded to include contacts over 14 years old, currently not included in the national guidelines. Treatment consisted in oral administration of rifapentine and isoniazide together once a week for 12 weeks, under supervision of trained health workers. RESULTS: From 238 patients entered to the protocol, 53% of them were women and 54.2% were older than 14 years-old. Out of the total number of patients, 203 (85.3%) completed treatment, 22 (9.2%) abandoned, 8 (3.4%) had adverse drug reactions, and 5 ended treatment for different causes. CONCLUSION: Both TITL with rifapentine-isoniazide in 12 supervised weekly doses, and the inclusion of adult contacts in TITL, are feasible to implement at a programmatic level in Chile.

Situación epidemiológica de la tuberculosis en Chile en el escenario global 2018 / Epidemiological situation of tuberculosis in Chile, 2018

La primera 'Reunión de Alto Nivel de la Asamblea General de las Naciones Unidas ' sobre la lucha contra la tuberculosis se concretó en septiembre de 2018. En ella los Estados Miembros suscribieron compromisos con metas para el año 2022. En Chile, la incidencia de tuberculosis aumentó en 2017, alcanzando 15,6 casos por 100.000 habitantes, con amplia heterogeneidad entre regiones del país. La mortalidad específica por tuberculosis se mantiene estable, alcanzando 1,2 por 100.000 en el año 2016, con importantes diferencias en distribución geográfica. Entre los casos de tuberculosis diagnosticados en 2017, el grupo vulnerable más frecuente fue el de adultos mayores (21,4%), seguido de las personas extranjeras (15,5%). El mismo año se diagnosticaron 37 casos de TB-MDR/RR (multidrogo-resistente y mono resistente a rifampicina), cifra en crecimiento durante el último quinquenio. El índice de pesquisa fue de 22,6, levemente superior al año anterior. Los resultados de la cohorte de tratamiento 2016 para casos nuevos fueron: 78,9% altas, 10,5% fallecidos y 6,6% pérdida de seguimiento. Las cohortes de pacientes antes tratados, coinfectados TB-VIH y pacientes con TB-MDR tienen resultados significativamente peores. Finalmente, la cobertura de estudios de contactos en 2017 fue de 86,4% en general y 91,8% en contactos menores de 15 años. La tuberculosis es un importante problema de salud pública en Chile y el mundo. En 2018 se ha reactivado la agenda internacional de la lucha contra la tuberculosis y se han adquirido nuevos compromisos para acelerar los avances hacia las metas de la Estrategia Fin a la Tuberculosis.

The first High Level Meeting of the General Assembly of the United Nations on ending Tuberculosis was performed in September 2018. In the meeting, the Member States subscribed new commitments and goals for 2022. In Chile in 2017, the tuberculosis incidence rate increased to 15.6 cases per 100,000, with important heterogeneity within geographic regions. Specific tuberculosis mortality rate remains stable, reaching 1.2 per 100,000 in 2016, also with heterogeneity within regions. Among the cases diagnosed in 2017, the most frequent risk group was the elderly (21.4% of cases), followed by foreign migrants (15.5%). In the same year, 37 cases of TB-MDR/RR (multidrug-resistant and Rifampicin-monoresistant TB) were diagnosed, and this number has grown steadily during the last 5 years. Treatment outcomes of the 2016 new cases cohort are as follows: 78.9% completed treatment, 10.5% deceased, and 6.6% lost to follow-up. Results in previously treated patients, HIV-TB co-infected patients, and TB-MDR patients, are significantly worse. The household contacts investigation coverage was 86.4% in all age, and 91.8% in under 15 years old. Tuberculosis remains a relevant public health issue in Chile and globally. The international tuberculosis agenda was reactivated in 2018, and this involved the generation of new global commitments in order to accelerate the accomplishment of the global goals in the End TB Strategy.

Clinical assessment of patients with isolated hip fractures associated with an upper limb fracture. / Evaluación clínica de pacientes con fractura de cadera aislada y asociada a fractura de miembro superior.

INTRODUCTION: Some patients with a hip fracture also present a concomitant upper limb fracture. We want to know whether these patients have a worse functional level and whether they have any differences in various clinical parameters compared with patients with an isolated hip fracture. MATERIAL AND METHODS: We retrospectively reviewed 1061 discharge reports from the Orthogeriatrics Unit. We collected information on several clinical parameters of the fractures. Subsequently, we performed a statistical analysis of the data by comparing the associated fracture group with the isolated fracture group. RESULTS: We detected 44 patients with associated upper limb fracture, 90.9% were women (40) and the average age was 84.45years. Eighty-one point eight percent of the upper limb fractures were distal radius or proximal humerus. Pertrochanteric fractures were the most common (none of them were subtrochanteric fractures). Surgical delay was 2.60days and the average hospital stay was 12.30days. Sixty-four point three percent were nail surgery and 31% arthroplasty. The mean Barthel index score was 84.88 (P=.021). Fifty-two point 5 percent of the patients in the study group were referred to a functional support unit (P=.03). The in-hospital mortality rate was 4.2%, with no differences between groups. CONCLUSIONS: Patients with an associated fracture have a higher previous functional capacity and they are more independent. Nevertheless, after the fracture they need more help from the healthcare system for optimal functional recovery.

Incidental Leydig Cell Tumor in Patient with Hormone Resistant Prostate Cancer.

We hereby present the case of a 55 years old patient with clinical diagnosis of high-risk prostate cancer T2bN1Mo Gleason 9 (4 + 5) treated with androgen deprivation therapy and external beam radiotherapy. Despite treatment, castration levels were not achieved and clinical progression was evidenced by the appearance of bone metastases and progression of PSA. After several hormonal treatments without any PSA or testosterone response, surgical castration was performed by bilateral orchiectomy. The pathology results showed an incidental Leydig cell tumor in the right testicle.

Influence of oxygen transfer on Pseudomonas putida effects on growth rate and biodesulfurization capacity.

The growth rate and desulfurization capacity accumulated by the cells during the growth of Pseudomonas putida KTH2 under different oxygen transfer conditions in a stirred and sparged tank bioreactor have been studied. Hydrodynamic conditions were changed using different agitation conditions. During the culture, several magnitudes associated to growth, such as the specific growth rate, the dissolved oxygen concentration and the carbon source consumption have been measured. Experimental results indicate that cultures are influenced by the fluid dynamic conditions into the bioreactor. An increase in the stirrer speed from 400 to 700 rpm has a positive influence on the cell growth rate. Nevertheless, the increase of agitation from 700 to 2000 rpm hardly has any influence on the growth rate. The effect of fluid dynamics on the cells development of the biodesulfurization (BDS) capacity of the cells during growth is different. The activities of the intracellular enzymes involved in the 4S pathway change with dissolved oxygen concentration. The enzyme activities have been evaluated in cells at several growth time and different hydrodynamic conditions. An increase of the agitation from 100 to 300 rpm has a positive influence on the development of the overall BDS capacity of the cells during growth. This capacity shows a decrease for higher stirrer speeds and the activity of the enzymes monooxygenases DszC and DszA decreases dramatically. The highest value of the activity of DszB enzyme was obtained with cells cultured at 100 rpm, while this activity decreases when the stirrer speed was increased higher than this value.

Does the Pulsatile Preservation Machine Have Any Impact in the Discard Rate of Kidneys From Older Donors After Brain Death?

BACKGROUND: Donors after brain death (DBD) older than 60 years have become 46.8% of our current activity, with higher risk of renal discard rate (RDR). Assessment of kidney suitability requires complementary strategies: macroscopic evaluation, kidney biopsy score (KBS), and renal hemodynamic evaluation with the Pulsatile Perfusion Machine (PPM). METHODS: Descriptive, cross-sectional, comparative study of kidneys procured and RDR, comparing 3 time periods: 2000 to June 2004, when only KBS were used; July 2004 to 2008 (introduction of PPM and learning period); and 2009 to 2013 (experienced use of PPM). Transplantation criteria were KBS <3 and PPM renal resistance <0.4 mm Hg/mL/min and arterial renal flow >70 mL/min. RESULTS: Between 2000 and 2013, a 59.2% reduction in DBD kidneys was observed. However, older kidneys had an increase from 33.5% to 46.8%. The RDR had increased, comparing the first to the third period from 25.4% to 38.3%. However, the RDR was lower when kidneys were evaluated with PPM than those evaluated only with KBS and preserved in cold storage (CS) (21.4% versus 43.7%). There was a significant difference in cold ischemia time, because CS kidney was grafted before PPM. During the third period, more kidneys with KBS ≥4 were assigned to PPM. CONCLUSIONS: Notwithstanding the decrease in DBD-procured kidneys and the increase in older kidneys during last period, the use of PPM allowed low DR compared with CS. A bias in the results of PPM could be generated when kidneys with higher KBS were excluded from PPM. The use of KBS only to decide acceptance could preclude the use of an additional tool to evaluate suitability.

Evaluación de la composición nutricional, antinutricional y biodisponibilidad in vitro de diferentes extractos foliares / Evaluation of the nutritional and antinutritional composition and in vitro bioavailability of foliar extracts

Foliar extracts (FEs) are an alternative to address food and nutrition insecurity. FEs and leaves of cassava, bean, sweet potato and alfalfa were evaluated for nutrient and antinutrient composition and in vitro nutrient bioavailability. Bean FE had a high average ± (SD) iron concentration (1006 ± 8.49 mg/kg), as did cassava FE for zinc (110.1 ± 6.72 mg/kg) and soluble protein (34.23 ± 3.81 g/kg) concentration. For the cassava, bean and alfalfa FEs in vitro protein digestibility was greater than 71.18 percent; in vitro iron dialyzability was less than 2.29 percent; the phytate:zinc molar ratio was less than 0.08, and the in vitro all-trans-β-carotene bioavailability was greater than 23.85 percent. These values suggest a high protein, zinc and all-trans- β -carotene bioavailability and a low iron bioavailability. FEs can be a nutritious alternative for those countries with low dietary diversity.

Los extractos foliares (EF) son utilizados como complemento nutricional en países como Nicaragua y Tanzania. Se evaluaron hojas y EF de yuca, fríjol, batata y alfalfa, y se cuantificó los componentes nutricionales, antinutricionales y biodisponibilidad por métodos in vitro. En promedio (DE), el EF de fríjol tiene una elevada concentración de hierro (1006,23 (8,49) mg/kg); el EF de yuca tiene alta concentración de zinc (110,65 (6,72) mg/ kg) y proteína soluble (34,23 (3,81) g/kg). Así mismo, la digestibilidad in vitro de proteína en los EFs de yuca, fríjol y alfalfa fueron superiores a 71,18 por ciento; hierro dializable in vitro menor a 2,29 por ciento; la relación molar fitato:zinc inferior a 0,08 y la bioaccesibilidad all-trans-β -caroteno superior a 23,85 por ciento. Estos valores sugieren una alta asimilación de proteína, zinc y all-trans-β -caroteno, y una baja asimilabilidad de hierro. Los EFs pueden ser una alternativa nutricional en la alimentación en países que carecen de diversificación alimentaria.

International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit)--Part II: Wrinkles on the middle and lower face, neck and chest.

BACKGROUND: Azzalure® (Galderma SA), a newly approved European botulinum neurotoxin type A (BoNT-A), is derived from Dysport™ (Ipsen Ltd.), which has a 20-year history of product consistency and has been widely used for various aesthetic and therapeutic applications. Azzalure® and Dysport™ are collectively referred to as BoNT-A (Speywood Unit) after the unit of their activity, and are distinct from other commercial BoNT-A preparations. Consensus has been developed for the treatment of upper facial wrinkles with BoNT-A (Speywood Unit). OBJECTIVE: To provide consensus recommendations on the treatment with BoNT-A (Speywood Unit) for wrinkles on the middle and lower face, neck and chest region. METHODS: The members of the International Board on Botulinum toxin Azzalure (IBBA) convened to develop consensus based on their extensive experience. RESULTS: The recommended final concentration of BoNT-A (Speywood Unit) is 200 Speywood Units/ml after reconstitution. The consensus recommendations were provided for nine indications, including lower eyelid wrinkles, bunny lines, drooping nasal tip, perioral wrinkles, masseter hypertrophy, drooping mouth corners, dimpled chin, platysmal bands and décolleté wrinkles. For each indication, anatomy of the region to be treated was discussed, as were potential side-effects. The consensus recommendations included the number and location of the injection points, dose range of each point and the total injection, as well as specific injection technique. CONCLUSION: These recommendations provide a guideline for physicians who wish to perform safe and efficacious treatment with BoNT-A (Speywood Unit) on the less commonly treated middle and lower face, neck and chest region.

International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit)--Part I: Upper facial wrinkles.

BACKGROUND: Azzalure (Galderma SA) is a newly approved European botulinum neurotoxin type A (BoNT-A). It is derived from Dysport (Ipsen Pharma), which has a long history of usages in various applications. Azzalure and Dysport are collectively referred to as BoNT-A (Speywood Unit) and are different from other BoNT-A preparations. OBJECTIVE: To provide consensus recommendations on the treatment of upper face wrinkles with BoNT-A (Speywood Unit). METHODS: The members of the International Board on Botulinum toxin Azzalure (IBBA) convened to develop consensus on the treatment of upper facial wrinkles based on their own extensive experience. RESULTS: The consensus recommendations address the general issues regarding treatment and provide specific guidelines on the anatomy, injection points, dose, injection technique and safety precautions concerning each common upper face indication. The recommended final concentration of BoNT-A (Speywood Unit) is 200 s.U/mL (10 s.U/0.05 mL) after reconstitution. For glabellar lines, the members recommend a total of five injection points with 10 s.U/point. For forehead wrinkles, the members recommend four to six injections into the frontalis with 5-10 s.U/point. For crow's feet, the members recommend three injections per side with 5-10 s.U/point at the lateral part of the orbicularis oculi. For lateral eyebrow lift, the members recommend one point at each eyebrow tail and an additional one in each side of the frontalis with 5-10 s.U/point. CONCLUSION: This guideline provides a framework for physicians who wish to perform safe and efficacious injection of BoNT-A (Speywood Unit).