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STUDY OBJECTIVE: To assess the efficacy of an ECG-based method called thoracic impedance pneumography to reduce hypoxic events in endoscopy. DESIGN: This was a single center, 1:1 randomized controlled trial. SETTING: The trial was conducted during the placement of percutaneous endoscopic gastrostomy (PEG). PATIENTS: 173 patients who underwent PEG placement were enrolled in the present trial. Indication was oncological in most patients (89%). 58% of patients were ASA class II and 42% of patients ASA class III. INTERVENTIONS: Patients were randomized in the standard monitoring group (SM) with pulse oximetry and automatic blood pressure measurement or in the intervention group with additional thoracic impedance pneumography (TIM). Sedation was performed with propofol by gastroenterologists or trained nurses. MEASUREMENTS: Hypoxic episodes defined as SpO2 < 90% for >15 s were the primary endpoint. Secondary endpoints were minimal SpO2, apnea >10s/>30s and incurred costs. MAIN RESULTS: Additional use of thoracic impedance pneumography reduced hypoxic episodes (TIM: 31% vs SM: 49%; p = 0.016; OR 0.47; NNT 5.6) and elevated minimal SpO2 per procedure (TIM: 90.0% ± 8.9; SM: 84.0% ± 17.6; p = 0.007) significantly. Apnea events >10s and > 30s were significantly more often detected in TIM (43%; 7%) compared to SM (1%; 0%; p < 0.001; p = 0.014) resulting in a time advantage of 17 s before the occurrence of hypoxic events. As a result, adjustments of oxygen flow were significantly more often necessary in SM than in TIM (p = 0.034) and assisted ventilation was less often needed in TIM (2%) compared with SM (9%; p = 0.053). Calculated costs for the additional use of thoracic impedance pneumography were 0.13$ (0.12 /0.11 £) per procedure. CONCLUSIONS: Additional thoracic impedance pneumography reduced the quantity and extent of hypoxic events with less need of assisted ventilation. Supplemental costs per procedure were negligible. KEY WORDS: thoracic impedance pneumography, capnography, sedation, monitoring, gastrointestinal endoscopy, percutaneous endoscopic gastrostomy.
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Propofol , Humanos , Propofol/efectos adversos , Apnea , Estudios Prospectivos , Gastrostomía/efectos adversos , Impedancia Eléctrica , Endoscopía Gastrointestinal/efectos adversos , Hipoxia/etiología , Hipoxia/prevención & controlRESUMEN
We report on photoelectron spectra of SiO2 nanoparticles (d = 157 ± 6 nm) above the Si 2p threshold in the photon energy range 118-248 eV with electron kinetic energy 10-140 eV and analyze the photoelectron yield as a function of photon energy. Comparison of the experimental results with Monte-Carlo simulations on electron transport allows us to quantify the inelastic mean-free path and mean escape depth of photoelectrons in the nanoparticle samples. The influence of the nanoparticle geometry and electron elastic scattering on photoelectron yields is highlighted. The results show that the previously proposed direct proportionality of the photoelectron signal to the inelastic mean-free path or the mean escape depth does not hold for photoelectron kinetic energies below 30 eV due to the strong influence of electron elastic scattering. The present results deviate for photoelectron kinetic energies below 30 eV from the previously proposed direct proportionality of the photoelectron signal to the inelastic mean-free path or the mean escape depth, which is the result of a strong influence of electron elastic scattering. The presented inelastic mean-free paths and mean escape depths appear to be useful for the quantitative interpretation of photoemission experiments on nanoparticles and for modeling of the experimental results.
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Intestinal microbiota, diet, and physical activity are inextricably linked to inflammation occurring in the presence of tumor progression and declining neurocognition. This study aimed to explore how fecal microbiota, inflammatory biomarkers, and neurocognitive behavior are influenced by voluntary exercise and surplus dietary protein and folic acid which are common health choices. Dietary treatments provided over 8 weeks to C57BL/CJ male mice (N = 76) were: Folic Acid (FA) Protein (P) Control (FPC, 17.9% P; 2 mgFA/kg); Folic Acid Deficient (FAD); Folic Acid Supplemented (FAS; 8 mgFA/kg); Low Protein Diet (LPD, 6% P); and High Protein Diet (HPD, 48% P). FAS mice had decreased plasma HCys (p < 0.05), therefore confirming consumption of FA. Objectives included examining influence of exercise using Voluntary Wheel Running (VWR) upon fecal microbiota, inflammatory biomarkers C - reactive protein (CRP), Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), nuclear factor kappa ß subunit (NF-κßp65), Caspase-3 (CASP3), Tumor Necrosis Factor-alpha (TNF-α), and neurocognitive behavior. CRP remained stable, while a significant exercise and dietary effect was notable with decreased VEGF (p < 0.05) and increased CASP3 (p < 0.05) for exercised HPD mice. Consumption of FAS did significantly increase (p < 0.05) muscle TNF-α and the ability to build a nest (p < 0.05) was significantly decreased for both FAD and LPD exercised mice. Rearing behavior was significantly increased (p < 0.05) in mice fed HPD. An emerging pattern with increased dietary protein intake revealed more distance explored in Open Field Testing. At week 1, both weighted and unweighted UniFrac principal coordinates analysis yielded significant clustering (permanova, p ≤ 0.05) associated with the specific diets. Consumption of a HPD diet resulted in the most distinct fecal microbiota composition. At the phylum level-comparing week 1 to week 8-we report a general increase in the Firmicutes/Bacteroidetes ratio, characterized by an outgrowth of Firmicutes by week 8 in all groups except the HPD. MaAsLin2 analysis corroborates this finding and emphasizes an apparent inversion of the microbiome composition at week 8 after HPD. Explicit modification of oncogenic inflammatory biomarkers and fecal microbiome post high FA and protein intake along with voluntary exercise contributed to current underlying evidence that this diet and exercise relationship has broader effects on human health and disease-perhaps importantly as a practical modulation of cancer progression and declining neurocognition.
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BACKGROUND: Nosocomial outbreaks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are frequent despite implementation of conventional infection control measures. An outbreak investigation was undertaken using advanced genomic and statistical techniques to reconstruct likely transmission chains and assess the role of healthcare workers (HCWs) in SARS-CoV-2 transmission. METHODS: A nosocomial SARS-CoV-2 outbreak in a university-affiliated rehabilitation clinic was investigated, involving patients and HCWs, with high coverage of pathogen whole-genome sequences (WGS). The time-varying reproduction number from epidemiological data (Rt) was estimated, and maximum likelihood phylogeny was used to assess genetic diversity of the pathogen. Genomic and epidemiological data were combined into a Bayesian framework to model the directionality of transmission, and a case-control study was performed to investigate risk factors for nosocomial SARS-CoV-2 acquisition in patients. FINDINGS: The outbreak lasted from 14th March to 12th April 2020, and involved 37 patients (31 with WGS) and 39 employees (31 with WGS), 37 of whom were HCWs. Peak Rt was estimated to be between 2.2 and 3.6. The phylogenetic tree showed very limited genetic diversity, with 60 of 62 (96.7%) isolates forming one large cluster of identical genomes. Despite the resulting uncertainty in reconstructed transmission events, the analyses suggest that HCWs (one of whom was the index case) played an essential role in cross-transmission, with a significantly greater fraction of infections (P<2.2e-16) attributable to HCWs (70.7%) than expected given the number of HCW cases (46.7%). The excess of transmission from HCWs was higher when considering infection of patients [79.0%; 95% confidence interval (CI) 78.5-79.5%] and frail patients (Clinical Frailty Scale score >5; 82.3%; 95% CI 81.8-83.4%). Furthermore, frail patients were found to be at greater risk for nosocomial COVID-19 than other patients (adjusted odds ratio 6.94, 95% CI 2.13-22.57). INTERPRETATION: This outbreak report highlights the essential role of HCWs in SARS-CoV-2 transmission dynamics in healthcare settings. Limited genetic diversity in pathogen genomes hampered the reconstruction of individual transmission events, resulting in substantial uncertainty in who infected whom. However, this study shows that despite such uncertainty, significant transmission patterns can be observed.
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COVID-19 , Infección Hospitalaria , Sustancias Explosivas , Teorema de Bayes , Estudios de Casos y Controles , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Genómica , Personal de Salud , Humanos , Filogenia , SARS-CoV-2RESUMEN
El uso y prescripción del cannabis y sus derivados en Reumatología está aún en discusión. La ley de cannabis fue sancionada hace casi 3 años, aunque la reglamentación recién está comenzando. El objetivo de este estudio fue conocer la forma en que el reumatólogo se posiciona frente al uso de cannabis en el marco de su práctica médica. A través de una encuesta realizada durante el Congreso Argentino de Reumatología 2019 se recabó la opinión de 314 médicos que respondieron preguntas acerca del uso, recomendaciones y posturas respecto a la indicación y uso de cannabinoides en su práctica diaria. El 78,3% (246) conocían la existencia de una ley nacional. El 51,6% (162) se mostró en desacuerdo con el uso de cannabinoides en sus pacientes, mientras que el 36,6% (115) respondió estar de acuerdo, el 3,2% (10) refirió estar muy de acuerdo, y 8,6% (27) estaba muy en desacuerdo. Para pacientes con enfermedades reumáticas autoinmunes, el 94,6% (297) refirió que nunca indica cannabinoides, el 4,1% (13) que los indican pocas veces, y el 1,3% (4) algunas veces. Para las enfermedades reumáticas degenerativas, el 90,4% (284) nunca indica cannabinoides, el 6,7% (21) lo hace pocas veces, y el 2,9% (9) lo hace algunas veces. Para la fibromialgia, el 84,4% (265) nunca indica cannabinoides, el 8,3% (26) los indica pocas veces, el 6,4% (20) los indica algunas veces. El principal obstáculo para la prescripción (permitido más de una respuesta) fue no disponer de la suficiente información científica para prescribir (50,3%, 158), el 47,5% (149) contestó que no conoce los componentes de la preparación, el 47,1% (148) no conoce las dosis o la posología, el 41,4% (130) no le resultan confiables los productores, el 38,9% (122) respondió que no le convencen los estudios clínicos en la especialidad. No hubo diferencias significativas entre las variables edad, género, años en la especialidad o lugar de ejercicio y las respuestas descriptas. Conclusión: El uso de cannabis en Reumatología de acuerdo a los especialistas que ejercen en Argentina requiere de un mayor sustento científico y farmacéutico para poder prescribirlo en un marco seguro.
The use and prescription of cannabis and its derivatives in Rheumatology is still under discussion. The cannabis law was enacted near 3 years ago, although the regulation is just beginning. The objective of this study was to know how rheumatologists positions themselves about the use of cannabis in the framework of his medical practice. Through a survey conducted during the 2019 Argentine Congress of Rheumatology, 314 doctors answered questions about the use, recommendations and opinions regarding the indication and use of cannabinoids in their daily practice. 78.3% (246) knew of the existence of a national law. 51.6% (162) disagreed with the use of cannabinoids by their patients, while 36.6% (115) agreed, 3.2% (10) reported to strongly agree, and 8.6% (27) strongly disagreed. For patients with autoimmune rheumatic diseases, 94.6% (297) reported that they never prescribed cannabinoids, 4.1% (13) prescribed them rarely, and 1.3% (4) sometimes. For degenerative rheumatic diseases, 90.4% (284) never prescribed cannabinoids, 6.7% (21) did it rarely, and 2.9% (9) did so sometimes. For fibromyalgia, 84.4% (265) never prescribed cannabinoids, 8.3% (26) prescribed them rarely, 6.4% (20) sometimes. The main obstacle to prescribing (more than one answer allowed) was not having enough scientific information (50.3%, 158), 47.5% (149) were uncertain about the cannabis preparation, 47.1% (148) had no knowledge about doses or posology, 41.4% (130) didn´t trust the producers, 38.9% (122) were no convince by the trials in the field. There were no significant differences between the variables age, gender, years in the specialty or workplace and the responses described. Conclusion: According to specialists in Argentina, the use of cannabis in rheumatology requires more scientific and pharmaceutical data to prescribe cannabinoids in a safer framework.
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Marihuana Medicinal , Reumatología , CannabisRESUMEN
To understand neurochemical brain responses to pain, proton magnetic resonance spectroscopy (1H-MRS) is used in humans in vivo to examine various metabolites. Recent MRS investigations have adopted a functional approach, where acquisitions of MRS are performed over time to track task-related changes. Previous studies suggest glutamate is of primary interest, as it may play a role during cortical processing of noxious stimuli. The objective of this study was to examine the metabolic effect (i.e., glutamate) in the anterior cingulate cortex during noxious stimulation using fMRS. The analysis addressed changes in glutamate and glutamate + glutamine (Glx) associated with the onset of pain, and the degree by which fluctuations in metabolites corresponded with continuous pain outcomes. Results suggest healthy participants undergoing tonic noxious stimulation demonstrated increased concentrations of glutamate and Glx at the onset of pain. Subsequent reports of pain were not accompanied by corresponding changes in glutamate of Glx concentrations. An exploratory analysis on sex revealed large effect size changes in glutamate at pain onset in female participants, compared with medium-sized effects in male participants. We propose a role for glutamate in the ACC related to the detection of a noxious stimulus.
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Ácido Glutámico/metabolismo , Glutamina/metabolismo , Giro del Cíngulo/metabolismo , Dolor/metabolismo , Adulto , Femenino , Neuroimagen Funcional , Giro del Cíngulo/diagnóstico por imagen , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Dolor/diagnóstico por imagen , Adulto JovenRESUMEN
OBJECTIVES: Facing an epidemic of childhood obesity and budget constraints, public health administrations are showing an urgent interest in interventions that are both health effective and cost-effective. Thus, this study intends to analyze the return on investment of these existing programs. STUDY DESIGN: All analyses are based on a comprehensive data set from 249 children with obesity and overweight children who participated in the Children's Health InterventionaL Trial (CHILT), an 11-month outpatient multidisciplinary family-based program. METHODS: Cost-effectiveness was assessed by comparing estimated savings associated with a reduction in weight and improvement of obesity-related health parameters with intervention costs. Projected future savings in health care expenditures were modeled on existing research, using estimates of health care costs associated with juvenile obesity and remission thresholds of obesity-related disease. RESULTS: On average, participants achieved a 0.19-unit reduction in the body mass index standard deviation score, showed reduction in their blood pressure values (systolic = -1.76 mmHg, diastolic = -2.82 mmHg), and showed improvement in their high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol values (HDL = +1.31 mg/dL, LDL = -4.82 mg/dL). The intervention costs were 1799 per participant, and the benefits of avoided future health care costs varied by individual. On an aggregated level, future savings amounted to between 1859 and 1926 per person, translating into a return on investment of 3.3-7.0%. CONCLUSIONS: This study shows that a multicomponent obesity intervention, such as the CHILT, not only results in weight loss and improves important health parameters but also is cost-effective.
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Atención Ambulatoria/economía , Obesidad Infantil/terapia , Adolescente , Atención Ambulatoria/organización & administración , Niño , Análisis Costo-Beneficio , Familia , Femenino , Alemania , Humanos , Masculino , Evaluación de Programas y Proyectos de SaludAsunto(s)
Hernia Inguinal , Hernia Inguinal/cirugía , Herniorrafia , Humanos , Masculino , Escroto/cirugíaRESUMEN
Throughout his professional life, the pathologist Albert Dietrich devoted himself to researching and combating cancer. Due to his considerable reputation and success, he was one of the first doctors to be awarded the Paracelsus Medal for his scientific services in 1952.However, Dietrich's role in the Third Reich was - and still is - far less defined. In May 1933, he became rector of the Eberhard Karls University in Tübingen, which at that time was one of the most Nazi-oriented universities. However, his term of office was short - by the end of 1933 he had already been replaced by the protestant theologian Karl Fezer.This article sheds light on Dietrich's ambivalent relationship to National Socialism and analyzes and discusses the background to his dismissal, his later (also politically influenced) emeritus status (1938/39), and his entry into the NSDAP, which took place at retirement age (1941). The study is based on archival sources partly evaluated for the first time and on a reanalysis of the relevant research literature.The study shows that Dietrich was targeted by individual Nazi decision-makers primarily because he advocated a supposedly "liberalist" university policy. Dietrich thus ultimately stands for a type of university lecturer who renounced a decidedly Nazi stance in public without, however, placing himself in a critical relationship to Nazi ideology. Against this background, statements from the postwar period that saw him retrospectively near Nazi opposition are to be classified as the formation of legends.
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Nacionalsocialismo/historia , Patólogos/historia , Distinciones y Premios , Alemania , Historia del Siglo XX , HumanosRESUMEN
Objetivo: Actualizar los resultados del registro BIOBADASAR sobre seguridad, duración y causas de interrupción del tratamiento luego de 8 años de seguimiento. Métodos: BIOBADASAR es un registro de seguridad de terapias biológicas establecido por la Sociedad Argentina de Reumatología. Se presenta la descripción de BIOBADASAR 3.0, una cohorte compuesta por 53 centros de Argentina seguidos prospectivamente desde agosto de 2010 hasta enero de 2018. Resultados: Se registraron 4656 pacientes, 6234 tratamientos [3765 casos (terapia con biológicos) y 2469 controles (terapia no biológicos)]. Se interrumpió el tratamiento en el 44,6% en los casos vs. 27,9% en los controles. Causa principal de discontinuación fue por ineficacia (40% casos vs. 32% controles). Se presentaron 3154 eventos adversos (2230 en casos vs. 924 en controles), de los cuales el 13,6% fueron graves (9,8% en casos y 3,7% en controles). El evento adverso (EA) más frecuente en ambos grupos fueron las infecciones (43,56% en casos vs. 34,31% en los controles, RR: 3,42; IC 95%: 3,02-3,88), y de ellas las de vías aéreas superiores (14,5%). Las neoplasias se presentaron en 78 casos vs. 45 en controles (RR: 1,98; IC 95%: 1,37-2,86). Conclusiones: En este sexto reporte no se observan tendencias diferentes sobre seguridad, duración y causas de interrupción del tratamiento respecto a informes previos. Las infecciones fueron el principal EA y la ineficacia, seguido por EA y la pérdida de pacientes las principales causas de suspensión del tratamiento. El advenimiento de nuevos agentes biológicos y la necesidad de control en seguridad a largo plazo, fortalece el uso de este tipo de registro.
Objective: Update the results of the BIOBADASAR registry on safety, duration and causes of treatment interruption after 8 years of follow-up. Methods: BIOBADASAR is a safety record of biological therapies established by the Argentine Society of Rheumatology. The description of BIOBADASAR 3.0 is presented, a cohort of 53 centers in Argentina followed prospectively from August 2010 to January 2018. Results: 4656 patients were registered, 6234 treatments [3765 cases (therapy with biologicals) and 2469 controls (non-biological therapy)]. Treatment was interrupted in 44.6% in cases vs. 27.9% in controls. Main cause of discontinuation was due to inefficiency (40% cases vs. 32% controls). There were 3154 adverse events (2230 in cases vs. 924 in controls), of which 13.6% were tombs (9.8% in cases and 3.7% in controls). The most frequent adverse event (AE) in both groups were infections (43.56% in cases vs. 34.31% in controls, RR: 3.42, 95% CI: 3.02-3.88), and the upper airway pathways (14.5%). Neoplasms were published in 78 cases versus 45 controls (RR: 1.98, 95% CI: 1.37-2.86). Conclusions: In this article, there are no different trends regarding safety, duration and causes of interruption of treatment compared to previous reports. Infections were the main causes of treatment discontinuation. The advent of new biological agents and the need for control over long-term security, strengthens the use of this type of registration.
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Terapéutica , Factores Biológicos , Informe de InvestigaciónRESUMEN
BACKGROUND: A low phase angle (PA) has been associated with negative outcome in specific diseases. However, many patients suffer from several co-morbidities. This study aims at identifying the impact of the type and the severity of diseases on PA in a retrospective cohort study of older people. METHODS: We included all people ≥65 years who underwent a PA measurement (Nutriguard®) between 1990 and 2011 at the Geneva University Hospitals. PA was standardized for gender, age and body mass index according to German reference values. Co-morbidities were reported in form of the Cumulative Illness Rating Scale which considers 14 different organs/systems (disease categories), each rated from 0 (healthy) to 4 (severe illness) (severity grades). The association between the diseases categories and standardized PA was evaluated by a multivariate linear regression. For each significant disease category, we performed univariate regression models. The adjusted R2 was used to identify the best predictors of standardized PA. We considered that the severity grade affected standardized PA if there was a progressive decrease in the regression coefficients. RESULTS: We included 1181 people (37% women). The multivariate regression model showed that the disease categories explain 17% of the variance of standardized PA. Many disease categories affect standardized PA and the ones best associated with standardized PA were the hematopoietic and vascular (R2 7.4%), the musculo-skeletal (R2 5.5%) and the respiratory (R2 4.0%) diseases. The regression coefficients in the univariate linear regression model decreased progressively with higher severity grades in respiratory (-0.15, -0.27, -0.55, -0.67) and musculo-skeletal diseases (-0.09, -0.46, -0.85, -0.86). CONCLUSIONS: Many different diseases affect standardized PA. The higher the severity grade in musculo-skeletal and respiratory diseases, the lower is the standardized PA.
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Impedancia Eléctrica , Estado de Salud , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Comorbilidad , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Valores de Referencia , Estudios RetrospectivosRESUMEN
BACKGROUND: The liver may be injured in situations where it is submitted to ischemia, such as partial hepatectomy and liver transplantation. In all cases, ischemia is followed by reperfusion and, although it is essential for the reestablishment of tissue function, reperfusion may cause greater damage than ischemia, an injury characterized as ischemia-reperfusion (I/R) damage. The aim of this work was to analyze the effect of ischemic preconditioning with the use of methylene blue (MB; 15 mg/kg) 5 or 15 minutes before I/R (IRMB5' and IRMB15', respectively) on the hepatic injury occurring after I/R. METHODS: Twenty-eight male Wistar rats were used, and liver samples submitted to partial ischemia (IR) or not (NI) were obtained from the same animal. The samples were divided into 7 groups. Data were analyzed statistically by means of the nonparametric Mann-Whitney test and Wilcoxon Matched test, with the level of significance set at 5% (P < .05). RESULTS: The rate of oxygen consumption by state 3 mitochondria was inhibited in all ischemic groups compared with the sham group (SH vs IR: P = .0052; SH vs IRMB5': P = .0006; SH vs IRMB15': P = .0048), which did not occur in the nonischemic contralateral portion of the same liver (SH vs NI: P = .7652; SH vs NIMB5': P = .059; SH vs NIMB15': P = .3153). The inhibition of the rate of oxygen consumption by state 3 mitochondria was maintained in the presence of MB (IR vs IRMB5': P = .4563; IR vs IRMB15': P = .9021). The respiratory control ratio was reduced in all ischemic groups compared with the sham group, owing to the inhibition of oxygen consumption in state 3 (SH vs IR: P = .0151; SH vs IRMB5': P = .005; SH vs IRMB15': P = .0007). CONCLUSIONS: Methylene blue had no effect on the mitochondrial respiratory parameters studied, but was able to reduce lipid peroxidation, preventing the production of reactive oxygen species (SH vs IRMB15': P = .0210).
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Inhibidores Enzimáticos/administración & dosificación , Precondicionamiento Isquémico/métodos , Hígado/irrigación sanguínea , Azul de Metileno/administración & dosificación , Daño por Reperfusión/prevención & control , Animales , Isquemia/etiología , Isquemia/fisiopatología , Hígado/lesiones , Hígado/cirugía , Masculino , Mitocondrias/fisiología , Consumo de Oxígeno , Ratas , Ratas Wistar , Daño por Reperfusión/etiologíaRESUMEN
Exercise during pregnancy has beneficial effects on maternal and offspring's health in humans and mice. The underlying mechanisms remain unclear. This comparative study aimed to determine the long-term effects of an exercise program on metabolism, weight gain, body composition and changes in hormones [insulin, leptin, brain-derived neurotrophic factor (BDNF)]. Pregnant women (n=34) and mouse dams (n=44) were subjected to an exercise program compared with matched controls (period I). Follow-up in the offspring was performed over 6 months in humans, corresponding to postnatal day (P) 21 in mice (period II). Half of the mouse offspring was challenged with a high-fat diet (HFD) for 6 weeks between P70 and P112 (period III). In period I, exercise during pregnancy led to 6% lower fat content, 40% lower leptin levels and an increase of 50% BDNF levels in humans compared with controls, which was not observed in mice. After period II in humans and mice, offspring body weight did not differ from that of the controls. Further differences were observed in period III. Offspring of exercising mouse dams had significantly lower fat mass and leptin levels compared with controls. In addition, at P112, BDNF levels in offspring were significantly higher from exercising mothers while this effect was completely blunted by HFD feeding. In this study, we found comparable effects on maternal and offspring's weight gain in humans and mice but different effects in insulin, leptin and BDNF. The long-term potential protective effects of exercise on biomarkers should be examined in human studies.
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Obesidad/prevención & control , Acondicionamiento Físico Humano/fisiología , Complicaciones del Embarazo/prevención & control , Efectos Tardíos de la Exposición Prenatal/prevención & control , Aumento de Peso/fisiología , Adiposidad/fisiología , Adulto , Animales , Biomarcadores/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Insulina/sangre , Leptina/sangre , Ratones , Ratones Endogámicos C57BL , Madres , Obesidad/sangre , Obesidad/etiología , Obesidad/fisiopatología , Condicionamiento Físico Animal/fisiología , Acondicionamiento Físico Humano/métodos , Aptitud Física/fisiología , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/fisiopatología , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/fisiopatologíaRESUMEN
Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis. Moreover, circulating soluble JAM-A (sJAM-A) levels were significantly increased in MM patients as compared with controls. Notably, in vitro JAM-A inhibition impaired MM migration, colony formation, chemotaxis, proliferation and viability. In vivo treatment with an anti-JAM-A monoclonal antibody (αJAM-A moAb) impaired tumor progression in a murine xenograft MM model. These results demonstrate that therapeutic targeting of JAM-A has the potential to prevent MM progression, and lead us to propose JAM-A as a biomarker in MM, and sJAM-A as a serum-based marker for clinical stratification.
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Biomarcadores de Tumor , Molécula A de Adhesión de Unión/sangre , Mieloma Múltiple/sangre , Mieloma Múltiple/mortalidad , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Médula Ósea/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Expresión Génica , Humanos , Molécula A de Adhesión de Unión/genética , Masculino , Ratones , Terapia Molecular Dirigida , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , PronósticoRESUMEN
BACKGROUND: Anemia and malnutrition are highly prevalent, frequently concomitant and associated with negative outcomes and mortality in the elderly. OBJECTIVES: To evaluate the association between these two entities, and test the hypothesis that protein-energy deficit could be etiology of anemia. DESIGN: Prospective case-control study. SETTING: Geriatric and Rehabilitation Hospital, Geneva University Hospitals, Switzerland. PARTICIPANTS: 392 patients (mean age 84.8 years old, 68.6% female). MAIN OUTCOME MEASURES: Hematological (hemoglobin (Hb)), chemical (iron work up, cyanocobalamin, folates, renal function, C-Reactive Protein (CRP)) and nutrition (albumin, prealbumin) parameters, and mini nutritional assessment short form (MNA-SF). RESULTS: The prevalence of anemia (defined as Hb<120 g/l) was 39.3%. Anemic patients were more frequently malnourished or at risk of malnutrition according to the MNA-SF (p=0.047), with lower serum albumin (p <0.001) and prealbumin (p <0.001) levels. Thirty-eight percent of these patients had multiple causes and 14.3% had no cause found for anemia. Among the latter 90.9% of patients with unexplained anemia had albumin levels lower than 35g/l. After exclusion of iron,vitamin B12 and folic acid deficits, anemic patients had lower albumin (p<0.001) and prealbumin (p 0.007) levels. Albumin level explained 84.5% of the variance in anemia. In multivariate analysis albumin levels remain associated with Hb only in anemic patients, explaining 6.4% of Hb variance (adj R2) and 14.7% (adj R2) after excluding inflammatory parameters (CRP>10). CONCLUSIONS: Albumin levels are strongly associated with anemia in the elderly. Screening for undernutrition should be included in anemia assessment in those patients. Further prospective studies are warranted in order to explore the effect of protein and energy supplementation on hemoglobin level.
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Anemia/etiología , Hospitalización , Desnutrición/complicaciones , Anciano , Anciano de 80 o más Años , Anemia/sangre , Anemia/epidemiología , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Proteínas en la Dieta/administración & dosificación , Ingestión de Energía , Femenino , Geriatría , Hemoglobinas/análisis , Humanos , Masculino , Desnutrición/diagnóstico , Desnutrición/epidemiología , Evaluación Nutricional , Estado Nutricional , Prealbúmina/análisis , Estudios Prospectivos , Albúmina Sérica/análisis , Suiza/epidemiologíaRESUMEN
BACKGROUND: Obese children and adolescents often exhibit progressively declining motor skills. To support young obese patients adequately, it is necessary to assess their individual physical and motor abilities, taking the degree of obesity into account. PATIENTS: A total of 5 924 children and adolescents (mean age: 12.7±2.5 years, range 6.0-18.0 years, 3 195 girls) were examined in a standardised multicentre evaluation survey (APV). Fitness parameters were correlated with age- and gender-specific BMI-SDS (Standard Deviation Score) Methods: Anthropometric data were collected and patients performed the modified Munich fitness test (mMFT: maximal power, coordination, trunk flexibility) and a 6-min walk-test (aerobic endurance capacity). RESULTS: 33% of patients were extremely obese (BMI>99.5th percentile). Mean BMI-SDS was + 2.32±0.53 (â-Δ=+ 0.06; p<0.001). The data indicated significant negative correlations between BMI-SDS and selected components of motor performance, especially maximal power (r=- 0,134), and particularly aerobic endurance capacity (r=- 0,214; all p<0.001). Motor performance was significantly below average (n=27 473, 6-18 years), especially among extremely obese patients. Performance in all motor tasks was lower in girls compared to boys, except for trunk flexibility (p<0.001). CONCLUSION: Correlations were found between BMI-SDS and motor performance. Extremely obese patients and obese girls showed the most pronounced motor deficits. These results emphasize the importance of standardized evaluation of individual motor performance in children and adolescents with obesity.
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Trastornos de la Destreza Motora/epidemiología , Obesidad Infantil/epidemiología , Aptitud Física , Adolescente , Índice de Masa Corporal , Niño , Bases de Datos Factuales , Femenino , Alemania , Humanos , Estudios Longitudinales , Masculino , Trastornos de la Destreza Motora/diagnóstico , Obesidad Infantil/diagnóstico , Estadística como AsuntoRESUMEN
BACKGROUND: Current guidelines for the prevention of obesity in childhood and adolescence are presented. METHODS: A literature search was performed in Medline via PubMed, and appropriate studies were analysed. RESULTS: Programs to prevent childhood obesity were to date mainly school-based. Effects were limited to date. Analyses tailored to different age groups show that prevention programs have the best effects in younger children (< 12 years). Evidence based recommendations for preschool- and early school age imply the need for interventions addressing parents and teachers alike. During adolescence, school-based interventions were most effective when adolescents were directly addressed. To date, obesity prevention programs have mainly focused on behavior oriented prevention. Recommendations for condition oriented prevention have been suggested by the German Alliance of Non-communicable Diseases and include one hour of physical activity at school, promotion of healthy food choices by taxing unhealthy foods, mandatory quality standards for meals at kindergarten and schools as well as a ban on unhealthy food advertisement addressing children. CONCLUSION: Behavior oriented prevention programs showed hardly any or only limited effects in the long term. Certain risk groups for the development of obesity are not reached effectively by available programs. Due to the heterogeneity of available studies, universally valid conclusions cannot be drawn. The combination with condition oriented prevention, which has to counteract on an obesogenic environment, is crucial for sustainable success of future obesity prevention programs.