Using Machine Learning to Leverage Biomarker Change and Predict Colorectal Cancer Recurrence.

PURPOSE: The risk of colorectal cancer (CRC) recurrence after primary treatment varies across individuals and over time. Using patients' most up-to-date information, including carcinoembryonic antigen (CEA) biomarker profiles, to predict risk could improve personalized decision making. METHODS: We used electronic health record data from an integrated health system on a cohort of patients diagnosed with American Joint Committee on Cancer stage I-III CRC between 2008 and 2013 (N = 3,970) and monitored until recurrence or end of follow-up. We addressed missingness in recurrence outcomes and longitudinal CEA measures, and engineered CEA features using current and past biomarker values for inclusion in a risk prediction model. We used a discrete time Superlearner model to evaluate various algorithms for predicting recurrence. We evaluated the time-varying discrimination and calibration of the algorithms and assessed the role of individual predictors. RESULTS: Recurrence was documented in 448 (11.3%) patients. XGBoost with depth = 1 (XGB-D1) predicted recurrence substantially better than all other algorithms at all time points, with AUC ranging from 0.87 (95% CI, 0.86 to 0.88) at 6 months to 0.94 (95% CI, 0.92 to 0.96) at 54 months. The only variable used by XGB-D1 was 6-month change in log CEA. Predicted 1-year risk of recurrence was nearly zero for patients whose log CEA did not increase in the last 6 months, between 12.2% and 34.1% for patients whose log CEA increased between 0.10 and 0.40, and 43.6% for those with a log CEA increase >0.40. Compared with XGB, penalized regression approaches (lasso, ridge, and elastic net) performed poorly, with AUCs ranging from 0.58 to 0.69. CONCLUSION: A flexible, machine learning approach that incorporated longitudinal CEA information yielded a simple and high-performing model for predicting recurrence on the basis of 6-month change in log CEA.

Effect of fried sunflower oil intake on mandibular biomechanical competence of growing rats.

Previous studies by us demonstrated that the consumption of thermally oxidized oil diet adversely affects body growth, lipid metabolism, bone mass and femur biomechanical competence. AIM: The aim of this study was to evaluate the effects of a diet containing fried sunflower oil on the mandible of growing rats. MATERIALS AND METHOD: Male Wistar rats (21±1 day old) (n=21) were assigned at weaning to one of three diets for 8 weeks: a control diet (C), a diet containing sunflower oil (SFO) or a diet containing sunflower oil that had been repeatedly heated (SFOx); both SFO and SFOx were mixed with commercial rat chow at 13% (w/w). The consistency and viscosity of the 3 diets were similar. Zoometrics and food intake were recorded weekly. At wk=8, mandibular growth was assessed by measurements of anatomical points of cleaned bones, and mandible biomechanical competence was assessed to estimate the structural properties of the bone. Statistical analysis was performed by SPSS v. 20.0. RESULTS: Rats fed SFOx diet attained the lowest final body weight (P=0.0074), mandibular weight (P=0.0001) and mandibular \length (P=0.0002). Load bearing capacity (Wf;N), load of yielding (Wy;N) and stiffness (Wy/dy;N/mm) of the mandible were negatively affected by both sunflower oil diets (fresh and fried) (P=0.001; P=0.002; P=0.003, respectively) though SFOx induced the most significant reduction in Wy/dy (C:44.4(5.4) > SFO:36.1(2.1) > SFOx: 26.3(3.7) N/ mm; P=0.003). The deleterious effect of SFOx on mandibular growth was more accentuated on the posterior part of the bone (C:11.4(0.3)=SFO:11.2(0.2)>SFOx: 10.7(0.2) mm; p=0.0005); the anterior/ posterior ratio (C:1.25(0.02)=SFO:1.27(0.02)

En estudios previos hemos demostrado los efectos adversos del consumo de una dieta rica en aceite termooxidado sobre el crecimiento corporal, el metabolismo de los lípidos, la masa ósea y la competencia biomecánica del fémur. OBJETIVO: El objetivo de este trabajo fue investigar el efecto de una dieta rica en aceite de girasol termooxidado (AGX) sobre los parámetros morfométricos y biomecánicos de la mandíbula de rata en crecimiento. Materiales y Método: Ratas macho Wistar de 22±1 días de edad (n=21) recibieron durante 8 semanas una de 3 dietas: control (C); dieta comercial, una dieta suplementada con aceite de girasol (AG) y una dieta suplementada con AGX. La consistencia y la viscosidad de las dietas fueron similares. Los parámetros zoométricos y el consumo de dieta se registraron semanalmente. A T=8, los animales se eutanasiaron y se obtuvieron las hemimandíbulas. El crecimiento mandibular se estimó por medidas morfométricas entre puntos anatómicos y las propiedades estructurales por biomecánica. El análisis estadístico se realizó por SPSS v. 20.0. RESULTADOS: Las ratas alimentadas con AGX presentaron menor peso corporal final (p=0.0074), peso mandibular (p=0.0001) y longitud mandibular (p=0.0002). Las propiedades estructurales de la mandíbula, Wf (p=0.001), Wy (p=0.002) y Wy/dy (p=0.003), se vieron afectadas negativamente en ratas alimentadas con AG o AGX, respecto a C; pero la rigidez ósea (Wy/dy) en AGX fue significativamente menor (C:44.4(5.4) > SFO:36.1(2.1) > SFOx: 26.3(3.7) N/mm; p=0.003). El efecto deletéreo del AGX sobre el crecimiento mandibular fue más acentuado en la región posterior (C:11.4(0.3)=SFO:11.2(0.2)>SFOx: 10.7(0.2) mm; p=0.0005). La relación anterior/posterior (C=1.25 (0.02); AG= 1.27(0.02) y AGX=1.32(0.03), p=0.001) indica que AGX indujo deformación mandibular. CONCLUSIONES: El efecto adverso del consumo de una dieta rica en AGX durante el crecimiento podría afectar los parámetros morfométricos y la biomecánica ósea en términos de rigidez ósea.

Disease mechanisms as Subtypes: Mitochondrial and bioenergetic dysfunction.

Parkinson disease (PD) is the second most common neurodegenerative disease in the world. Despite its enormous human and societal cost, there is no disease-modifying therapy for PD. This unmet medical need reflects our limited understanding of PD pathogenesis. One of the most important clues comes from the recognition that PD motor symptoms arises from the dysfunction and degeneration of a very select group of neurons in the brain. These neurons have a distinctive set of anatomic and physiologic traits that reflect their role in brain function. These traits elevate mitochondrial stress, potentially making them particularly vulnerable to age, as well as to genetic mutations and environmental toxins linked to PD incidence. In this chapter, the literature supporting this model is outlined, along with gaps in our knowledge base. The translational implications of this hypothesis are then discussed, with a focus on why disease-modification trials have failed to date and what this means for the development of new strategies for altering disease course.

Actividad antimicrobiana de extractos de plantas frente a Staphylococcus aislados de pacientes con conjuntivitis bacteriana / Antimicrobial Activity of Plant Extracts against Isolated Staphylococcus Infection in Patients with Bacterial Conjunctivitis / Atividade antimicrobiana de extratos vegetais contra Staphylococcus isolados de pacientes com conjuntivite bacteriana

Staphylococcus aureus y Staphylococcus epidermidis son los principales agentes etiológicos de las conjuntivitis bacterianas, que al tratarse con antibióticos de manera empírica, incrementan la resistencia antimicrobiana después de exposiciones repetidas. Se están buscando alternativas naturales para el tratamiento de infecciones bacterianas autolimitadas de la conjuntiva. Objetivo: determinar la actividad antimicrobiana de ocho extractos de las plantas frente a bacterias aisladas de pacientes con conjuntivitis bacterianas. Materiales y métodos: se tomaron muestras de 15 pacientes con conjuntivitis bacterianas. Se cultivaron en agar sangre y chocolate durante 24 h a 37 °C y se identificaron mediante el sistema automatizado vitek y pruebas de susceptibilidad antimicrobiana por el método de Kirby-Bauer. A cada aislamiento identificado con el género Staphylococcus se le evaluó su susceptibilidad frente a siete extractos: Ocimum basilicum, Sambucus nigra L., Delphinium elatum, Calendula officinalis, Bixa ore-llana (parte aérea y fruto independiente), Clinopodium brownei y Laurus nobilis, con un uso tradicional reportado para el tratamiento de infecciones oculares. Resultados: las bacterias aisladas con más frecuencia fueron S. epidermidis, S. hominis y S. aureus, las cuales presentaron resistencia antimicrobiana a oxacilina, tetraciclinas y eritromicina. Todos los aislamientos fueron inhibidos por los extractos de O. basilicum (cmi: >0.9 mg/mL) y L. nobilis (cmi: hasta 15 mg/mL). Conclusión: los extractos de C. officinalis y D. elatum tuvieron actividad antimicrobiana solo frente a los aislados con mayor sensibilidad antimi-crobiana. Los extractos etanólicos de O. basilicum y L. nobilis pueden ser una alternativa de tratamiento de las infecciones de la conjuntiva.

Staphylococcus aureus and Staphylococcus epidermidis are the primary etiological agents of bacterial conjunctivitis which are empirically treated with antibiotics. This results in an increase in antimicrobial resistance due to repeated exposure. Currently, natural treatment alternatives are being sought for self-limited bacterial infections of the conjunctiva. Objective: To determine the antimicrobial activity of eight extracts from Colombian plants against bacteria isolated from patients with bacterial conjunctivitis. Materials and methods: Samples were taken from 15 patients with bacterial conjunctivitis which were grown on blood and chocolate agar for 24 h at 37 °C. These samples were identified by the vitek automated system and antimicrobial susceptibility tests by the Kirby Bauer method. Each isolate identified with the genus Staphylococcus was evaluated for susceptibility to the following eight plant extracts of seven plant: Ocimum basilicum (basil), Sambucus nigra L. (elderberry), Delphinium elatum(belladonna), Calendula officinalis (marigold), Bixa orellana (annatto) (aerial part and independent fruit), Clinopodium brownei (pennyroyal), and Laurus nobilis (laurel), with traditional use previously reported for treating eye infections. Results: The most frequently isolated bacteria were S. epidermidis, S. hominis, and S. aureus, which exhibited antimicrobial resistance mainly to oxacillin, tetracyclines, and erythromycin. All isolates were inhibited by O. basilicum extracts (mic > 0.9 mg/mL) and L. nobilis (mic < 15 mg/mL). Conclusion: The extracts of C. officinalis y D. elatum showed antimicrobial activity only against isolates with higher antimicrobial sensitivity. Ethanolic extracts of O. basilicum y L. nobilis can be used as an alternative treatment for infections of the anterior segment of the eye.

Staphylococcus aureus e Staphylococcus epidermidis são os principais agentes etiológicos da conjuntivite bacteriana, estes são tratados empiricamente com antibióticos, causando aumento da resistência antimicrobiana após repetidas exposições aos mesmos. Atualmente, estão sendo estudadas alternativas naturais para o tratamento de infecções bacterianas autolimitadas da conjuntiva. Objetivo: determinar a atividade antimicrobiana de oito extratos de sete vegetais contra bactérias isoladas de pacientes com conjuntivite bacteriana. Materiais e métodos: foram retiradas amostras de 15 pacientes com conjuntivite bacteriana. As amostras foram cultivadas em ágar sangue e ágar chocolate por 24 horas a 37°C e os isolados foram identificados pelo sistema automatizado vitek, além de testes de susce-tibilidade antimicrobiana pelo método Kirby Bauer. Cada isolado identificado como sendo pertencente ao gênero Staphylococcus foi avaliado quanto à suscetibilidade a oito extratos vegetais: Ocimum basili-cum (manjericão), Sambucus nigra L. (sabugueiro), Delphinium elatum (belladona), Calendula officinalis(calêndula), Bixa orellana (urucum; parte aérea e fruto independente), Clinopodium brownei (poejo) e Laurus nobilis (louro), anteriormente relatados como uso tradicional para o tratamento de infecções ocu-lares. Resultados: as bactérias mais frequentemente isoladas foram S. epidermidis, S. hominis e S. aureus, que apresentaram resistência antimicrobiana principalmente à oxacilina, tetraciclinas e eritromicina. Todos os isolados foram inibidos por extratos de O. basilicum (cim: >0,9 mg/mL) e L. nobilis (cim: até 15 mg/mL). Conclusão: os extratos de C. officinalis e D. elatum apresentaram atividade antimicrobiana apenas contra os isolados com maior sensibilidade antimicrobiana. Os extratos etanólicos de O. basilicum e L. nobilis podem ser uma alternativa de tratamento para infecções conjuntivais.

Rehabilitación propioceptiva del síndrome de hombro doloroso / Proprioceptive rehabilitation of painful shoulder syndrome / Reabilitação proprioceptiva da síndrome do ombro doloroso

El hombro es una de las regiones anatómicas de mayor movilidad en la vida cotidiana, siendo una de las causas de consulta más frecuentes en el área de fisioterapia para su rehabilitación, pues la primera línea de acción es el tratamiento conservador del hombro; por ello, es de suma importancia conocer y evaluar el complejo articular del hombro, así como también de la región cervicotorácica, con los resultados de la valoración establecer una estrategia de tratamiento que pueden ir desde la terapia manual, el masaje terapéutico, cambios de temperatura hasta el empleo de otros agentes físicos. Paciente femenino de 42 años, con ocupación de asistente odontológica; no reporta discapacidad previa. Como antecedente médico se presenta accidente de tránsito en motocicleta sin producir fractura de hueso ni luxación, ocurrido ocho años antes de la consulta en fisiatría, la paciente tiene afectado el desarrollo de las actividades de la vida cotidiana. Recibió serie de tratamientos durante 10 sesiones, en las cuales se aplican agentes físicos, dado que anteriormente recibió tratamiento farmacológico sin resultados favorables. Se aplica protocolo de rehabilitación fundamentado en las técnicas de propiocepción y al finalizar la terapia la paciente reporta dolor leve, y mejora en la realización de actividades de la vida diaria.

The shoulder is one of the anatomical regions of greater mobility in daily life, being one of the most frequent causes of consultation in the area of physiotherapy for rehabilitation, since the first line of action is the conservative treatment of the shoulder; therefore, it is of utmost importance to know and evaluate the articular complex of the shoulder, as well as the cervicothoracic region, with the results of the assessment to establish a treatment strategy that can range from manual therapy, therapeutic massage, temperature changes to the use of other physical agents. Female patient, 42 years old, with occupation as a dental assistant; she reports no previous disability. As medical history, she had a traffic accident on a motorcycle without bone fracture or dislocation, which occurred eight years before the physiatry consultation, the patient has affected the development of activities of daily living. She received a series of treatments during 10 sessions, in which physical agents are applied, since she had previously received pharmacological treatment without favorable results. Rehabilitation protocol based on proprioception techniques is applied and at the end of therapy the patient reports mild pain and improvement in the performance of activities of daily living.

O ombro é uma das regiões anatômicas de maior mobilidade na vida diária, sendo uma das causas mais freqüentes de consulta na área de fisioterapia para reabilitação, pois a primeira linha de ação é o tratamento conservador do ombro; portanto, é extremamente importante conhecer e avaliar o complexo articular do ombro, bem como a região cervicotorácica, com os resultados da avaliação para estabelecer uma estratégia de tratamento que pode variar desde a terapia manual, massagem terapêutica, mudanças de temperatura até o uso de outros agentes físicos. Paciente do sexo feminino, 42 anos de idade, trabalhando como assistente odontológica; nenhuma deficiência anterior foi relatada. O histórico médico inclui um acidente de trânsito em uma motocicleta sem fratura ou deslocamento ósseo, que ocorreu oito anos antes da consulta ao fisiatra; as atividades de vida diária do paciente são afetadas. Ela recebeu uma série de tratamentos durante 10 sessões, nas quais foram aplicados agentes físicos, já que ela havia recebido anteriormente tratamento farmacológico sem resultados favoráveis. Um protocolo de reabilitação baseado em técnicas de propriocepção foi aplicado e ao final da terapia o paciente relatou dor leve e melhora no desempenho das atividades da vida diária.

Ca2+ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons.

How do neurons match generation of adenosine triphosphate by mitochondria to the bioenergetic demands of regenerative activity? Although the subject of speculation, this coupling is still poorly understood, particularly in neurons that are tonically active. To help fill this gap, pacemaking substantia nigra dopaminergic neurons were studied using a combination of optical, electrophysiological, and molecular approaches. In these neurons, spike-activated calcium (Ca2+) entry through Cav1 channels triggered Ca2+ release from the endoplasmic reticulum, which stimulated mitochondrial oxidative phosphorylation through two complementary Ca2+-dependent mechanisms: one mediated by the mitochondrial uniporter and another by the malate-aspartate shuttle. Disrupting either mechanism impaired the ability of dopaminergic neurons to sustain spike activity. While this feedforward control helps dopaminergic neurons meet the bioenergetic demands associated with sustained spiking, it is also responsible for their elevated oxidant stress and possibly to their decline with aging and disease.

The potential of pumpkin seed oil as a functional food-A comprehensive review of chemical composition, health benefits, and safety.

The growing interest in foods that can be beneficial to human health is bringing into focus some products that have been used locally for centuries but have recently gained worldwide attention. One of these foods is pumpkin seed oil, which has been used in culinary and traditional medicine, but recent data also show its use in the pharmaceutical and cosmetic industries. In addition, some sources refer to it as a potential functional food, mainly because it is obtained from pumpkin seeds, which contain many functional components. However, the production process of the oil may affect the content of these components and consequently the biological activity of the oil. In this review, we have focused on summarizing scientific data that explore the potential of pumpkin seed oil as a functional food ingredient. We provide a comprehensive overview of pumpkin seed oil chemical composition, phytochemical content, biological activity, and safety, as well as the overview of production processes and contemporary use. The main phytochemicals in pumpkin seed oil with health-related properties are polyphenols, phytoestrogens, and fatty acids, but carotenoids, squalene, tocopherols, and minerals may also contribute to health benefits. Most studies have been conducted in vitro and support the claim that pumpkin seed oil has antioxidant and antimicrobial activities. Clinical studies have shown that pumpkin seed oil may be beneficial in the treatment of cardiovascular problems of menopausal women and ailments associated with imbalance of sex hormones.

Actividad antioxidante y cuantificación de fenoles y flavonoides de plantas colombianas empleadas en infecciones urinarias / Antioxidant activity and quantification of phenols and flavonoids of Colombian plants used in urinary tract infections

RESUMEN Las plantas medicinales son de interés farmacéutico, debido a que tienen diferentes propiedades biológicas, entre las que se destaca, la actividad antioxidante y, de la cual, se conoce que existe una relación con la concentración de los compuestos fenólicos, por su capacidad de reducir los radicales libres. Es así, que se propuso evaluar la actividad antioxidante y la cuantificación de fenoles y flavonoides totales, de 11 extractos etanólicos de plantas, empleadas en la medicina tradicional, para el tratamiento de infecciones urinarias (IU). Se evaluó la actividad antioxidante, por los métodos de DPPH y FRAP y se cuantificó el contenido fenólico y de flavonoides, por el método Folin-Ciocalteu y tricloruro de aluminio, respectivamente. Se encontró que, de los 11 extractos evaluados, los que presentaron el mayor contenido de estos metabolitos y de potencial antioxidante fueron: Uncaria tomentosa, Sedum praealtum y Kohleria hirsuta. Este trabajo permitió contribuir al conocimiento fitoquímico y antioxidante de plantas, usadas para tratar IU y se sugiere que U. tomentosa, S. praealtum y K. hirsuta sean objeto de futuros estudios biodirigidos, así como la evaluación de otras actividades biológicas.

ABSTRACT Medicinal plants are of pharmaceutical interest because they possess different biological properties, among which their antioxidant activity stands out, and therefore it is known that there is a relationship with the concentration of phenolic compounds due to their ability to reduce free radicals. Therefore, it was proposed to evaluate the antioxidant activity and the quantification of phenols and flavonoids of 11 ethanolic extracts of plants used in traditional medicine for the treatment of urinary infections (UI). The antioxidant activity was evaluated by the DPPH and FRAP methods and the phenolic and flavonoid content was quantified by the Folin-Ciocalteu and aluminum trichloride method, respectively. It was found that of the 11 extracts evaluated, those with the highest content of these metabolites and antioxidant potential were three: Uncaria tomentosa, Sedum praealtum and Kohleria hirsuta. This work made it possible to contribute to the phytochemical and antioxidant knowledge of the plants used for the treatment of UI and it is suggested that U. tomentosa, S. praealtum and K. hirsuta be the object of future bio-directed studies, as well as the evaluation of other activities biological.

Maternal Folic Acid Intake and Methylation Status of Genes Associated with Ventricular Septal Defects in Children: Case-Control Study.

BACKGROUND: DNA methylation is the best epigenetic mechanism for explaining the interactions between nutrients and genes involved in intrauterine growth and development programming. A possible contributor of methylation abnormalities to congenital heart disease is the folate methylation regulatory pathway; however, the mechanisms and methylation patterns of VSD-associated genes are not fully understood. OBJECTIVE: To determine if maternal dietary intake of folic acid (FA) is related to the methylation status (MS) of VSD-associated genes (AXIN1, MTHFR, TBX1, and TBX20). METHODS: Prospective case-control study; 48 mothers and their children were evaluated. The mothers' dietary variables were collected through a food frequency questionnaire focusing on FA and the consumption of supplements with FA. The MS of promoters of genes was determined in the children. RESULTS: The intake of FA supplements was significantly higher in the control mothers. In terms of maternal folic acid consumption, significant differences were found in the first trimester of pregnancy. Significant differences were observed in the MS of MTHFR and AXIN1 genes in VSD and control children. A correlation between maternal FA supplementation and MS of AXIN1 and TBX20 genes was found in control and VSD children, respectively. CONCLUSIONS: A lower MS of AXIN1 genes and a higher MS of TBX20 genes is associated with FA maternal supplementation.

Potencial antimicrobiano de extractos de plantas medicinales y sus mezclas frente a bacterias asociadas con conjuntivitis / Antimicrobial potential of plant extracts and their mixtures against bacteria associated with conjunctivitis

Resumen Introducción. La conjuntivitis bacteriana es una de las infecciones oculares con mayor tasa de consulta oftálmica, siendo el género Staphylococcus el agente etiológico que presenta mayor resistencia a los antibióticos. Objetivo. Determinar el potencial antimicrobiano de extractos de plantas medicinales y sus mezclas frente a bacterias asociadas con conjuntivitis. Métodos. A partir de plantas como Belladona, Caléndula, Albahaca, Achiote y Romerillo se prepararon los extractos etanólicos y se evaluó su potencial antibacteriano frente a S. aureus y S. epidermidis, mediante las técnicas de difusión en disco y dilución en tubo. El efecto de las mezclas se determinó para el extracto con mejor actividad y el antibiótico con mayor halo de inhibición a través de la técnica de tablero. Resultados. Se encontró que el extracto con mayor potencial para S. aureus fue el de achiote (hojas) con un halo de inhibición de 13 mm y CMIs de 15 mg/mL, mientras que para S. epidermidis fueron los de hojas y frutos de achiote con halos de 16,6 y 9,6 mm y CMIs de 15 y 30 mg/mL respectivamente. En relación con las combinaciones, el extracto de achiote y ciprofloxacina mostró un efecto de sinergia parcial para S. aureus con una CFI de 0,83 y un efecto aditivo para S. epidermidis con una CFI de 1,84. Conclusiones. Este trabajo se constituye en la base de futuras investigaciones orientadas hacia el desarrollo de bioproductos de uso ocular que puedan ser considerados como alternativa en el tratamiento de infecciones causadas por Staphylococcus.

Abstract Introduction. Bacterial conjunctivitis is one of the ocular infections with the highest rate of ophthalmic consultation, being the Staphylococcus genus the etiological agent that presents the greatest resistance to antibiotics. Objective. To determine the antimicrobial potential of medicinal plant extracts and their mixtures against bacteria associated with conjunctivitis. Methods. From plants such as Belladonna, Calendula, Basil, Achiote and Romerillo, ethanolic extracts were prepared and their antibacterial potential against S. aureus and S. epidermidis was evaluated by means of disk diffusion and tube dilution techniques. The effect of the mixtures was determined for the extract with the best activity and the antibiotic with the highest inhibition halo through the board technique. Results. It was found that the extract with the highest potential for S. aureus was that of annatto (leaves) with an inhibition halo of 13 mm and MICs of 15 mg / mL, while for S. epidermidis it was those of annatto leaves and fruits with halos of 16.6 and 9.6 mm and MICs of 15 and 30 mg / mL respectively. In relation to the combinations, the annatto extract and ciprofloxacin showed a partial synergistic effect for S. aureus with a CFI of 0.83 and an additive effect for S. epidermidis with a CFI of 1.84. Conclusions. This work constitutes the basis for future research aimed at the development of bioproducts for ocular use that can be considered as an alternative in the treatment of infections caused by Staphylococcus.

Leptospirosis, una zoonosis que impacta a la salud: diagnóstico, tratamiento y nuevas alternativas de control / Leptospirosis a zoonosis that impacts health: diagnosis, treatment and new alternatives of control

La leptospirosis es una zoonosis con potencial epidémico y de difícil diagnóstico que requiere un manejo integral para orientar las medidas de prevención y control; sin embargo, una de las dificultades es la existencia de más de 300 serovares, la supervivencia de la bacteria en el ambiente por más de 180 días y la importancia del agua como vehículo de transmisión. Esto asociado con los efectos adversos de los antibióticos y su efecto sobre la multirresistencia generada por la mayoría de las bacterias, hace que se evalúen nuevas alternativas a partir de la biodiversidad. Por lo tanto, el objetivo de este artículo es abordar la leptospirosis y su diagnóstico enfatizando en el control convencional de la infección y las alternativas de tratamiento a partir del uso de plantas medicinales. Para esto se realizó una revisión exhaustiva de artículos en bases de datos. La información encontrada permitió establecer los aspectos relevantes de la enfermedad, su diagnóstico y tratamiento, tanto con antimicrobianos convencionales como frente a nuevas alternativas de origen natural. Se concluye que es importante realizar investigaciones orientadas hacia la búsqueda de principios activos que puedan contribuir al control de Leptospira spp., agente causal de la leptospirosis, una de las zoonosis más importantes por su impacto en salud humana, veterinaria y del ecosistema(AU)

Leptospirosis is a potentially epidemic zoonosis of difficult diagnosis which requires comprehensive management to indicate appropriate prevention and control measures. However, some of the difficulties are the existence of more than 300 serovars, survival of the bacteria in the environment for more than 180 days, and the role of water as a route of transmission. The above situation, alongside the adverse effects of antibiotics and their effect on the multi-drug resistance developed by most bacteria, lead to the search for new alternatives based on biodiversity. The purpose of the study was therefore to address leptospirosis and its diagnosis highlighting conventional control of the infection as well as treatment options based on the use of medicinal plants. To achieve this end, an exhaustive review was conducted of papers included in databases. The information obtained made it possible to determine the relevant aspects of the disease, its diagnosis and its treatment with conventional antimicrobials as well as new alternatives of a natural origin. Conclusions point to the importance of conducting research aimed at the search for active principles potentially contributing to control of Leptospira spp., the causative agent of leptospirosis, one of the most relevant zoonoses in terms of its impact on the health of humans, animals and the ecosystem(AU)

Relación entre niveles de vitamina D y perfil lipídico en embarazadas de alto riesgo / Relationship between level of vitamin D and lipid profile in high risk pregnant women

En la Argentina, las embarazadas presentan alta prevalencia (80%) de hipovitaminosis D y de sobrepeso u obesidad (27,4%). Ambas condiciones pueden aumentar la morbimortalidad materno-fetal. Bajos niveles de vitamina D se han relacionado con aumento del colesterol total, LDL, triglicéridos (Tg) y descenso de HDL. Objetivo: evaluar los niveles de 25-hidroxivitamina D (25OHD) y su relación con el perfil lipídico en pacientes embarazadas de alto riesgo. Materiales y métodos: estudio de corte transversal entre septiembre de 2016 y abril de 2017. Se excluyeron pacientes que recibieron suplementos de vitamina D, con disfunción tiroidea no compensada, malabsorción, insuficiencia cardíaca, renal o hepática y dislipidemia familiar. Niveles circulantes de 25OHD < 30 ng/ml se consideraron hipovitaminosis. Resultados: se evaluaron 86 embarazadas de 29,3 ± 7,1 años durante la semana 28 ± 6,5. El IMC pregestacional fue 28,3 ± 6,5 kg/m2 y la ganancia de peso 7 ± 4,3 kg. Perfil lipídico: colesterol total 240 ± 54 mg/dl; LDL 156 ± 54 mg/dl; HDL 66 ± 15 mg/dl; Tg 204 ± 80 mg/dl. La media de 25OHD fue de 23,8 ± 9 ng/ml, con una prevalencia de hipovitaminosis D de 77,9 %. Las pacientes con hipovitaminosis D presentaron mayores valores de colesterol total y LDL (p < 0,05), con tendencia no significativa a presentar mayores valores de Tg. Conclusión: en embarazadas de alto riesgo se observó una alta prevalencia de hipovitaminosis D, asociada con mayores concentraciones de colesterol total y LDL. (AU)

In Argentina, pregnant women have a high prevalence (80 %) of hypovitaminosis D and verweight/obesity (27.4%), conditions that can increase maternal-fetal morbidity and mortality. Low levels of 25-hydroxyvitamin D (25OHD) have been linked to an increase in total cholesterol, LDL cholesterol, triglycerides (TG) and a decrease in HDL cholesterol. Objective: to evaluate the levels of vitamin D and its relationship with the lipid profile in high risk pregnant patients. Materials and methods: cross-sectional study between September 2016 and April 2017. Patients who received vitamin D supplements or had non-compensated thyroid dysfunction, malabsorption, heart failure, renal or hepatic failure, or familial dyslipidemia were excluded. Hypovitaminosis D was defined as a circulating level of 25OHD < 30 ng/ml. Results: We assessed 86 women of 29.3 ± 7.1 years during pregnancy week 28 ± 6.5. Pre-gestational BMI was 28.3 ± 6.5 kg/m2. Their weight gain was 7 ± 4.3 kg. Lipid profile: total cholesterol 240 ± 54 mg/dl; LDL cholesterol 156 ± 54 mg/dl; HDL cholesterol 66 ± 15 mg/dL; TG 204 ± 80 mg/dl. The mean 25OHD level was 23.8 ± 9 ng/ml, with a 77.9 % prevalence of hypovitaminosis D. Patients with hypovitaminosis D had higher values of total cholesterol and LDL cholesterol (p<0.05), and a non-significant trend toward higher triglyceridemia. Conclusion: A high prevalence of hypovitaminosis D, associated with high total and LDL cholesterol was found in high risk pregnant women. (AU)

Gastroprotective activity and pharmacological safety evaluation of Eupatorium aschenbornianum.

Eupatorium aschenbornianum has been widely used in traditional Mexican and folk medicine for the treatment of wounds, skin lesions, hemorrhages and gastric ulcers in humans. Phytochemical studies have indicated that hexane extracts of E. aschenbornianum have anti-microbial and anti-fungal activities. In the present study, an accurate and reliable approach using a murine model was pursued to evaluate the anti-ulcer activity, lipid peroxidation properties and acute toxicity of powdered dried stem of E. aschenbornianum. The results indicated that administration of E. aschenbornianum exerted an anti-ulcerative effect and decreased lipid peroxidation in gastric ulcers induced by acetylsalicylic acid. An acute toxicity assay indicated normal behavior and no significant variations in the weight and food consumption of animals. In addition, quantitative analysis of biochemical parameters did not indicate any liver or kidney damage. The results indicated that E. aschenbornianum may be a safe therapeutic agent for the prevention of gastric ulcers.

[Myths and fallacies in relation to the consumption of dairy products]. / Mitos y falacias en relación al consumo de productos lácteos.

INTRODUCTION: In recent years the consumption of milk has declined, which could be due to the many myths and fallacies that exist about this food and other dairy products. Affirmations such as: "cow's milk is ideal for calves not humans", "humans are the only animals that drink milk beyond infancy", "milk lead to mucus production or occurrence of asthma" or "milk increases cholesterol levels", among others, are present in many conversations of the general population. However, due to the high nutritional value of dairy products, the elimination/restriction of these foods of our diet, without the existence of circumstances that support it, can have negative repercussions for health. Therefore, it is necessary to dismantle all these myths with scientific arguments.

INTRODUCCIÓN: En los últimos años el consumo de leche ha descendido, lo que podría deberse a los numerosos mitos y falacias que circulan por distintos medios en torno a este alimento y a otros productos lácteos. Afirmaciones como "la leche de vaca es para los terneros, no para los humanos", "somos el único mamífero que sigue tomando leche en la edad adulta", "la leche produce mocos y asma" o "la leche aumenta el colesterol", entre otras, están presentes en muchas conversaciones de la población general. Sin embargo, por su elevado valor nutricional, la eliminación/restricción de estos alimentos de nuestra dieta, sin la existencia de circunstancias que las avalen, puede tener repercusiones negativas para la salud. Por ello, es necesario desmontar todos estos mitos con argumentos científicos.

Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells.

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

Characterization of phenolic extracts from Brava extra virgin olive oils and their cytotoxic effects on MCF-7 breast cancer cells.

The aim of the present work was to evaluate the phenolic profile of the 'Brava' extra virgin olive oil and assess its potential as a "natural adjuvant" in combination with chemotherapy treatment. The total phenol content of the phenolic extracts was 764 mg gallic acid equivalents/kg and the total antioxidant capacity was 2309, 1881 and 2088 µM trolox equivalents/kg determined by Diphenyl-1-picrylhydrazyl free radical method, Ferric Reducing Antioxidant Power and Trolox Equivalent Antioxidant Capacity assay, respectively. Secoiridoids comprised 83% of the total phenolic compounds. The main secoiridoid from oleuropein was the main isomer of oleuropein aglycone (74 mg/kg). The main secoiridoid from ligstroside was the main isomer of ligstroside aglycone (214 mg/kg). These phenolic extracts showed a significant decrease in cell viability on MCF-7 breast cancer cells in a dose and time dependent manner. 48 h-treatments with different concentrations of the extracts induced intracellular ROS generation and cell death.

Nutraceutical Potential of Phenolics from 'Brava' and 'Mansa' Extra-Virgin Olive Oils on the Inhibition of Enzymes Associated to Neurodegenerative Disorders in Comparison with Those of 'Picual' and 'Cornicabra'.

The increasing interest in the Mediterranean diet is based on the protective effects against several diseases, including neurodegenerative disorders. Polyphenol-rich functional foods have been proposed to be unique supplementary and nutraceutical treatments for these disorders. Extra-virgin olive oils (EVOOs) obtained from 'Brava' and 'Mansa', varieties recently identified from Galicia (northwestern Spain), were selected for in vitro screening to evaluate their capacity to inhibit key enzymes involved in Alzheimer's disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 5-lipoxygenase (5-LOX)), major depressive disorder (MDD) and Parkinson's disease (PD) (monoamine oxidases: hMAO-A and hMAO-B respectively). 'Brava' oil exhibited the best inhibitory activity against all enzymes, when they are compared to 'Mansa' oil: BuChE (IC50 = 245 ± 5 and 591 ± 23 mg·mL-1), 5-LOX (IC50 = 45 ± 7 and 106 ± 14 mg·mL-1), hMAO-A (IC50 = 30 ± 1 and 72 ± 10 mg·mL-1) and hMAO-B (IC50 = 191 ± 8 and 208 ± 14 mg·mL-1), respectively. The inhibitory capacity of the phenolic extracts could be associated with the content of secoiridoids, lignans and phenolic acids.

Strawberry extracts efficiently counteract inflammatory stress induced by the endotoxin lipopolysaccharide in Human Dermal Fibroblast.

A protracted pro-inflammatory state is the common denominator in the development, progression and complication of the common chronic diseases. Dietary antioxidants represent an efficient tool to counteract this inflammatory state. The aim of the present work was to evaluate the effects of strawberry extracts on inflammation evoked by E. Coli lipopolysaccharide in Human Dermal Fibroblast, by measuring reactive oxygen species production, apoptosis rate, antioxidant enzymes activity, mitochondria functionality and also investigating the molecular pathway involved in inflammatory and antioxidant response. The results demonstrated that strawberry pre-treatment reduced intracellular reactive oxygen species levels, apoptotic rate, improved antioxidant defences and mitochondria functionality in lipopolysaccharide -treated cells. Strawberry exerted these protective activities through the inhibition of the NF-kB signalling pathway and the stimulation of the Nrf2 pathway, with a mechanism AMPK-dependent. These results confirm the health benefits of strawberry in the prevention of inflammation and oxidative stress condition in lipopolysaccharide-treated cells.

Plantas medicinales que se comercializan en Bogotá (Colombia) para el tratamiento de enfermedades infecciosas / Medicinal plants which are marketed in Bogotá (Colombia) for treatment of infectious diseases

En este estudio se utilizó el factor de consenso, el nivel de fidelidad y la variedad de uso en la identificación de plantas medicinales para el tratamiento de enfermedades infecciosas que son comercializadas en la plaza de mercado Samper Mendoza de Bogotá (Colombia). Para esto se realizó una encuesta a 61 herbolarios, la información obtenida fue organizada y analizada en el programa estadístico SPSS. Un total de 122 plantas para el tratamiento de enfermedades infecciosas, distribuidas en cuatro categorías (urogenitales, respiratorias, gastrointestinales y piel y ojos) presentaron valores de FIC entre 0.74 y 0.79, indicando un criterio de selección definido con información correctamente transferida y alta eficacia para el control de infecciones. El 74% (90/122) de las plantas presentaron un nivel de fidelidad del 100% y en el 11% (14/122) se evidenció una importancia relativa con valor de uso inferior a 0.115. Este trabajo muestra la utilidad de la etnomedicina en la selección de plantas medicinales y contribuye al conocimiento de especies vegetales colombianas útiles para estudios fitoquímicos orientados a identificar compuestos con potencial antibacterial para el control de enfermedades infecciosas de impacto en salud pública.

This study used the consensus factor, fidelity level and variety of use in the identification of medicinal plants for the treatment of infectious diseases that are marketed in the Samper Mendoza market in Bogotá, Colombia. For this, a survey was conducted on 61 herbalists, the information obtained was organized and analyzed in the SPSS statistical program. A total of 122 plants of the treatment of infectious diseases, distributed in four categories (urogenital, respiratory, gastrointestinal and skin and eyes) presented FIC values between 0.74 and 0.79, indicating a selection criterion defined with correctly transferred information and high efficiency for infection control. 74% (90/122) of the plants had a fidelity level of 100% and 11% (14/122) a relative importance was evidenced with use value less than 0.125. This work shows the utility of ethnomedicine in the selection of medicinal plants and contributes to the knowledge of Colombian plant species useful for phytochemical studies aimed at identifying compounds with antibacterial potential for the control of infectious diseases of public health impact.

Strawberry-Based Cosmetic Formulations Protect Human Dermal Fibroblasts against UVA-Induced Damage.

Extreme exposure of skin to Ultraviolet A (UVA)-radiation may induce a dysregulated production of reactive oxygen species (ROS) which can interact with cellular biomolecules leading to oxidative stress, inflammation, DNA damage, and alteration of cellular molecular pathways, responsible for skin photoaging, hyperplasia, erythema, and cancer. For these reasons, the use of dietary natural bioactive compounds with remarkable antioxidant activity could be a strategic tool to counteract these UVA-radiation-caused deleterious effects. Thus, the purpose of the present work was to test the efficacy of strawberry (50 µg/mL)-based formulations supplemented with Coenzyme Q10 (100 µg/mL) and sun protection factor 10 in human dermal fibroblasts irradiated with UVA-radiation. The apoptosis rate, the amount of intracellular reactive oxygen species (ROS) production, the expression of proteins involved in antioxidant and inflammatory response, and mitochondrial functionality were evaluated. The results showed that the synergic topical use of strawberry and Coenzyme Q10 provided a significant (p < 0.05) photoprotective effect, reducing cell death and ROS, increasing antioxidant defense, lowering inflammatory markers, and improving mitochondrial functionality. The obtained results suggest the use of strawberry-based formulations as an innovative, natural, and useful tool for the prevention of UVA exposure-induced skin diseases in order to decrease or substitute the amount of synthetic sunscreen agents.