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Attentional focus instructions are verbal strategies that could maximize the effects of exercise. The objective of this review was to explore and synthesize the available evidence on the incorporation of attentional focus instruction in the exercise of people with musculoskeletal disorders. A search of 11 databases was carried out until October 2020. Of 4,227 studies identified in the searches, 15 were included. The studies showed deficiencies in the conceptualization and definition of attentional focus instructions. The available evidence indicates that external focus is effective in improving motor learning and function. However, methodological limitations, clinical heterogeneity, the small number of articles included, and new experimental studies challenge the conclusions of the systematic reviews available to date. Attentional focus instructions in musculoskeletal disorders is an emerging field and requires further research. This review is a guide for future studies.

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BACKGROUND: Cerebral white matter consists mainly of axons surrounded by myelin sheaths, which are grouped to form association, commissural, and projection fasciculi. The aim of our work was to quantify and compare under the microscope the axons of the white matter association fasciculi in the cerebral hemispheres of cow (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus) indirectly by identification of their myelin sheaths. MATERIALS AND METHODS: The samples were taken from 30 cerebral hemispheres: 10 cow, 10 pig and 10 rabbit (15 right and 15 left). They were obtained following a protocol based on the Talairach-Tournoux coordinate system for human and primate brains. The slides were stained with Luxol Fast Blue, observed by optical microscopy, and photographed at 600×. Samples were also prepared for observation in scanning transmission electron microscopy with osmium tetroxide. The myelin sheaths/axons were counted with the ImageJ software. RESULTS: Statistically significant differences in the number of myelin sheaths per 410 µm² were found in the inferior and superior longitudinal fasciculi between the left and right hemispheres of cows, with predominance of the right hemisphere; and in the inferior occipitofrontal fasciculus of the rabbit with predominance of the left hemisphere. CONCLUSIONS: The use of animal models for experiments in the cerebral fasciculi, especially pig, could give us a greater understanding of the behaviour of demyelinating and neurodegenerative diseases in humans.

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Antimicrobials are among the most commonly prescribed classes of medications in Neonatal Intensive Care Units; however, its use has been constantly associated with a number of medication errors in clinical practice. In contrast to this situation, there is no common agreement when it comes to determining the right dosing, administration, or handling of antibiotics in this population. In order to help improve the use of antibiotics, decrease the rate of medication errors and optimize clinical results in the newborn, this review aims to provide recommendations to support and guide the correct preparation of some of the most relevant antibiotics used in neonatal wards.

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Resumen Los antimicrobianos corresponden al grupo de medicamentos más utilizados en Unidades de Cuidados Intensivos Neonatales; no obstante, su uso ha sido asociado a constantes errores de medicación en la práctica clínica. Paradojalmente, aún no existe consenso en torno a la administración adecuada de estos medicamentos y existen importantes brechas de conocimiento en torno a los procesos de dosificación, administración y manipulación de antimicrobianos en esta población. Con el fin de mejorar el uso de antimicrobianos, disminuir errores y optimizar los resultados clínicos en el recién nacido, la presente revisión tiene por objetivo entregar recomendaciones y servir de guía para la correcta preparación de aquellos antimicrobianos de mayor relevancia en neonatología.

Abstract Antimicrobials are among the most commonly prescribed classes of medications in Neonatal Intensive Care Units; however, its use has been constantly associated with a number of medication errors in clinical practice. In contrast to this situation, there is no common agreement when it comes to determining the right dosing, administration, or handling of antibiotics in this population. In order to help improve the use of antibiotics, decrease the rate of medication errors and optimize clinical results in the newborn, this review aims to provide recommendations to support and guide the correct preparation of some of the most relevant antibiotics used in neonatal wards.

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Maternal nutrient restriction (NR) causes small for gestational age (SGA) offspring, which are at higher risk for accelerated postnatal growth and developing insulin resistance in adulthood. Skeletal muscle is essential for whole-body glucose metabolism, as 80% of insulin-mediated glucose uptake occurs in this tissue. Maternal NR can alter fetal skeletal muscle mass, expression of glucose transporters, insulin signaling, and myofiber type composition. It also leads to accumulation of intramuscular triglycerides (IMTG), which correlates to insulin resistance. Using a 50% NR treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the NR group. Thus, we classified those fetuses into NR(Non-SGA; n = 11) and NR(SGA; n = 11). The control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and gastrocnemius and soleus muscles were collected. In fetal plasma, total insulin was lower in NR(SGA) fetuses compared NR(Non-SGA) and control fetuses (P < 0.01), whereas total IGF-1 was lower in NR(SGA) fetuses compared with control fetuses (P < 0.05). Within gastrocnemius, protein expression of insulin receptor (INSRB; P < 0.05) and the glucose transporters, solute carrier family 2 member 1 and solute carrier family 2 member 4, was higher (P < 0.05) in NR(SGA) fetuses compared with NR(Non-SGA) fetuses; IGF-1 receptor protein was increased (P < 0.01) in NR(SGA) fetuses compared with control fetuses, and a lower (P < 0.01) proportion of type I myofibers (insulin sensitive and oxidative) was observed in SGA fetuses. For gastrocnemius muscle, the expression of lipoprotein lipase (LPL) messenger RNA (mRNA) was upregulated (P < 0.05) in both NR(SGA) and NR(Non-SGA) fetuses compared with control fetuses, whereas carnitine palmitoyltransferase 1B (CPT1B) mRNA was higher (P < 0.05) in NR(Non-SGA) fetuses compared with control fetuses, but there were no differences (P > 0.05) for protein levels of LPL or CPT1B. Within soleus, there were no differences (P > 0.05) for any characteristic except for the proportion of type I myofibers, which was lower (P < 0.05) in NR(SGA) fetuses compared with control fetuses. Accumulation of IMTG did not differ (P > 0.05) in gastrocnemius or soleus muscles. Collectively, the results indicate molecular differences between SGA and Non-SGA fetuses for most characteristics, suggesting that maternal NR induces a spectral phenotype for the metabolic programming of those fetuses.

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PURPOSE: Outcomes for patients with metastatic colorectal cancer (mCRC) have been improved by the identification of biomarkers predictive and prognostic of clinical outcome. The present retrospective analysis was undertaken to assess the utility of key biomarkers and clinical parameters in predicting outcomes in Spanish patients with mCRC. METHODS: We retrospectively analyzed tumor samples from a series of patients aged > 18 years with mCRC who were treated at the Hospital General Universitario Gregorio Marañón Spain. Real-time polymerase chain reaction was used to detect KRAS, NRAS, BRAF, and PIK3CA mutations. The key outcome of interest was overall survival (OS). Survival curves were estimated using the Kaplan-Meier method and stratified by the variables of greatest clinical interest. Differences were tested using the log-rank test. RESULTS: Median OS in the overall population was 24.4 months. Triple WT patients (WT KRAS, NRAS, and BRAF) and quadruple WT patients (WT KRAS, NRAS, BRAF, and PIK3CA) had significantly better OS than those who did not have triple or quadruple WT tumors. OS was significantly better in patients with left- vs. right-sided tumors, patients with resected primary tumors and metastases vs. those without resection, and patients with isolated hepatic and isolated pulmonary metastases. CONCLUSIONS: This retrospective, observational study has confirmed the prognostic value of the location and resection status of the primary tumor and metastases in Spanish patients with mCRC. Triple WT status, in particular, was prognostic in this patient population, with PIK3CA adding to the prognostic value in the quadruple WT population.

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Resumen Introducción: Enterocolitis necrosante (ECN) representa una elevada mortalidad y morbilidad post-quirúrgica, gastrointestinal y del neuro-desarrollo. Existe limitada información en Chile. Objetivo: Describir el comportamiento clínico/epidemiológico de recién nacidos que cursaron con ECN. Pacientes y Métodos: Estudio multicéntrico descriptivo de pacientes con ECN de siete hospitales de Santiago, Chile, durante el 2016. Se realizó estadística descriptiva y análisis univariable/multivariable (software SPSS v22). Resultados: Se recolectaron 75 casos. Mediana de edad al diagnóstico fue 11 días, el promedio de edad gestacional 29 semanas y peso de nacimiento 1.285 g. La incidencia fue 2,6 por 1.000/recién nacidos vivos y letalidad de 18,6%, mayor en ≤ 750 g, ≤ 25 semanas y ECN quirúrgica. Hubo aislamiento microbiológico en 45,3% y se utilizaron 19 distintos esquemas antimicrobianos empíricos para el tratamiento de ECN. El análisis multivariable mostró tendencia a que la ECN fuese quirúrgica en usuarios de catéter umbilical arterial, PCR > 10 mg/L y aislamiento microbiológico, y hubo tendencia a fallecer en usuarios de catéter umbilical arterial. Discusión: Es el primer estudio multicéntrico que recopila información de datos locales. La incidencia fue similar a la descrita en la literatura médica, en cambio la letalidad fue algo menor. No existen consensos del tratamiento antimicrobiano a utilizar. Con estos resultados esperamos avanzar en mejorar el diagnóstico y unificar tratamientos antimicrobianos, para reducir cifras de morbimortalidad.

Abstract Background: Necrotizing enterocolitis (NEC) presents high mortality and postoperative, gastrointestinal and neurodevelopmental morbidity. There is limited information about NEC in Chile. Aim: To describe the clinical/epidemiological behavior of newborns who underwent NEC. Methods: Multicenter descriptive study of patients with NEC from seven hospitals of Santiago, Chile, during 2016. Descriptive statistics and univariate/multivariate analysis were performed (SPSS v22 software). Results: 75 cases were collected. Median days of life at diagnosis was 11, gestational age was 29 weeks, birth weight 1,114 g. The incidence was 2.6 per 1,000 live newborns and mortality was 18.6%, higher in ≤ 750 g, ≤ 25 weeks and surgical NEC. There was 45.3% microbiological isolation and 19 different empirical antibiotic schemes were used for the treatment of NEC. The multivariate analysis showed a higher risk of surgery in umbilical arterial catheter users, CRP > 10 mg/L and positive microbiological isolation. The highest risk of death was in umbilical arterial catheter users. Discussion: This ie the first multicenter study that collects local data information. The incidence was similar to that found in medical reports but with a lower mortality. There is no consensus of antibiotic treatment to use. With these results we hope to advance in improving the diagnosis and unify antimicrobial treatments, to reduce morbidity and mortality figures.

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Resumen Los antimicrobianos son los medicamentos más utilizados en los neonatos durante su primer mes de vida cuando se encuentran en unidades neonatales, principalmente por el alto riesgo que presentan de adquirir infecciones graves como la sepsis. La mayoría de estos antimicrobianos se utilizan con dosis extrapoladas en base a las recomendaciones en población adulta y niños mayores, a pesar de que la fisiopatología en los recién nacidos es absolutamente diferente. Lo anterior lleva a un mayor riesgo a que ocurran más efectos adversos los que pueden conducir a una mayor toxicidad y a fallas terapéuticas, entre otros. En la última década se han realizado mayores estudios farmacocinéticos de antimicrobianos en neonatos; esta reciente evidencia ha permitido nuevas recomendaciones de dosificación considerando el peso y la edad gestacional del recién nacido, entre otras variables, de acuerdo al antimicrobiano estudiado. En base a una mayor evidencia sobre el comportamiento farmacocinético de los antimicrobianos en neonatos, se ha elaborado este documento para así facilitar y promover su correcto uso en las unidades neonatales.

Abstract Antibiotics are the most widely used medications in neonates during their first month of life in neonatal units, mainly due to the high risk they present of acquiring serious infections such as sepsis. Most of these antibiotics are used with extrapolated doses based on the suggestions in the adult population and older children, despite the fact that the pathophysiology in newborns is absolutely different. This leads to a higher risk of more adverse effects occurring, which can lead to greater toxicity and therapeutic failures, among others. In the last decade more and more pharmacokinetic studies of antibiotics have been carried out in neonates, this recent evidence has led to new dosage recommendations taking into account the weight and gestational age of the newborn, among other variables, in agreement to the antibiotic studied. Therefore, based on the need to order and summarize the most up-to-date and most evidence-based information on antibiotics in neonates, this document was prepared to facilitate and promote its correct use in neonatal units.

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BACKGROUND: Vancomycin is used for treating coagulase-negative staphylococcus infections in neonates. However, concerns about the appropriate empirical dosing required for optimal efficacy, still remain. AIM: To assess the relationship between the initial doses of vancomycin used in a Neonatal Intensive Care Unit (NICU) with the possibility of achieving therapeutic target of AUC024h/MIC > 400 µg/h/mL. METHODS: Retrospective and descriptive study carried out between February 2016 and March 2018. All neonates treated with vancomycin for suspected/proven Gram-positive infection and with at least one trough serum concentration level were included. Probability of target attainment (PTA) was evaluated through resampling of AUC and MIC values. RESULTS: Final dataset included 38 patients and 49 trough vancomycin levels; 94.7% of these cases (n = 36) were confirmed Gram-positive infections. The median AUC/MIC values for the trough values vancomycin < 10 µg/mL group and for the ≥ 10 µg/mL group were 327 (IQR 174-395) and 494 (IQR 318-631) respectively (p = 0.035). Current empirical dosing strategy has a 47.7% PTA (AUC/MIC > 400) when taking institutional MICs into account. CONCLUSIONS: It is not possible to assure achieving a AUC/MIC > 400 µg/h/mL when considering institutional sensibilities. Current empiric dosing strategies should be reconsidered and further investigation needs to be done to help determine the appropriate empirical dosing required for optimal efficacy in neonates.

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Resumen Introducción: Vancomicina es un antimicrobiano ampliamente utilizado para infecciones por Staphylococcus coagulasa negativa en neonatos; sin embargo, no existe claridad sobre la dosis empírica que asegure su eficacia terapéutica. Objetivo: Evaluar la relación entre las dosis iniciales de vancomicina utilizadas en una Unidad de Cuidado Intensivo Neonatal (UCIN) con la eventualidad de alcanzar el objetivo terapéutico de área bajo la curva sobre concentración inhibitoria mínima (ABC/CIM) mayor a 400 µg/h/mL. Materiales y Método: Estudio descriptivo y retrospectivo, realizado entre febrero 2016 y marzo 2018. Se incluyeron neonatos en tratamiento con vancomicina por sospecha/confirmación de infección por cocáceas grampositivas y medición de concentraciones plasmáticas de vancomicina al inicio del tratamiento. La probabilidad de alcanzar el objetivo terapéutico se evaluó mediante re-muestreo de valores de ABC y CIM. Resultados: Se incluyeron 38 pacientes con 49 concentraciones plasmáticas de vancomicina. Los aislados microbiológicos se confirmaron en 94,7% de los pacientes (n = 36). Los valores de ABC/CIM en dos grupos (según niveles valle de vancomicina < 10 µg/mL y ≥ 10 µg/mL), fueron de una mediana de 327 (IQ 25-75 = 174-395) y 494 (IQ 25-75 = 318-631), respectivamente (p = 0,035). Las dosis empíricas utilizadas logran logran un objetivo terapéutico (ABC/CIM > 400) de sólo 47,7% considerando CIMs en nuestra institución. Conclusiones: Teniendo en cuenta las sensibilidades institucionales, no es posible asegurar alcanzar ABC/CIM > 400 µg/h/mL. Se debe seguir investigando para replantear las actuales estrategias de dosificación y así determinar la más apropiada para neonatos.

Abstract Background: Vancomycin is used for treating coagulase-negative staphylococcus infections in neonates. However, concerns about the appropriate empirical dosing required for optimal efficacy, still remain. Aim: To assess the relationship between the initial doses of vancomycin used in a Neonatal Intensive Care Unit (NICU) with the possibility of achieving therapeutic target of AUC024h/MIC > 400 µg/h/mL. Methods: Retrospective and descriptive study carried out between February 2016 and March 2018. All neonates treated with vancomycin for suspected/proven Gram-positive infection and with at least one trough serum concentration level were included. Probability of target attainment (PTA) was evaluated through resampling of AUC and MIC values. Results: Final dataset included 38 patients and 49 trough vancomycin levels; 94.7% of these cases (n = 36) were confirmed Gram-positive infections. The median AUC/MIC values for the trough values vancomycin < 10 µg/mL group and for the ≥ 10 µg/mL group were 327 (IQR 174-395) and 494 (IQR 318-631) respectively (p = 0.035). Current empirical dosing strategy has a 47.7% PTA (AUC/MIC > 400) when taking institutional MICs into account. Conclusions: It is not possible to assure achieving a AUC/MIC > 400 µg/h/mL when considering institutional sensibilities. Current empiric dosing strategies should be reconsidered and further investigation needs to be done to help determine the appropriate empirical dosing required for optimal efficacy in neonates.

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