Endoscopic scoring system utilization for inflammatory bowel disease activity assessment: A multicenter real-world study from Argentina.

BACKGROUND: The frequency and patterns of use of scores for the assessment of endoscopic activity in inflammatory bowel disease patients are not known. AIM: To describe the prevalence of adequate use of endoscopic scores in IBD patients who underwent colonoscopy in a real-life setting. MATERIALS AND METHODS: A multicenter observational study comprising six community hospitals in Argentina was undertaken. Patients with a diagnosis of Crohn's disease or ulcerative colitis who underwent colonoscopy for endoscopic activity assessment between 2018 and 2022 were included. Colonoscopy reports of included subjects were manually reviewed to determine the proportion of colonoscopies that included an endoscopic score report. We determined the proportion of colonoscopy reports that included all of the IBD colonoscopy report quality elements proposed by BRIDGe group. Endoscopist's specialty, years of experience as well as expertise in IBD were assessed. RESULTS: A total of 1556 patients were included for analysis (31.94% patients with Crohn's disease). Mean age was 45.94±15.46. Endoscopic score reporting was found in 58.41% of colonoscopies. Most frequently used scores were Mayo endoscopic score (90.56%) and SES-CD (56.03%) for ulcerative colitis and Crohn's disease, respectively. In addition, 79.11% of endoscopic reports failed to comply with all recommendations on endoscopic reporting for inflammatory bowel disease. CONCLUSIONS: A significant proportion of endoscopic reports of inflammatory bowel disease patients do not include the description of an endoscopic score to assess mucosal inflammatory activity in a real-world setting. This is also associated with a lack of compliance in recommended criteria for proper endoscopic reporting.

Instrumented Timed Up and Go Test (iTUG)-More Than Assessing Time to Predict Falls: A Systematic Review.

The Timed Up and Go (TUG) test is a widely used tool for assessing the risk of falls in older adults. However, to increase the test's predictive value, the instrumented Timed Up and Go (iTUG) test has been developed, incorporating different technological approaches. This systematic review aims to explore the evidence of the technological proposal for the segmentation and analysis of iTUG in elderlies with or without pathologies. A search was conducted in five major databases, following PRISMA guidelines. The review included 40 studies that met the eligibility criteria. The most used technology was inertial sensors (75% of the studies), with healthy elderlies (35%) and elderlies with Parkinson's disease (32.5%) being the most analyzed participants. In total, 97.5% of the studies applied automatic segmentation using rule-based algorithms. The iTUG test offers an economical and accessible alternative to increase the predictive value of TUG, identifying different variables, and can be used in clinical, community, and home settings.

Assessment of EPInfant scale for exercise intensity perceptual self-regulation in healthy children. / Evaluación de la escala EPInfant para la auto-regulación perceptual de la intensidad del ejercicio en niños sanos.

INTRODUCTION: The EPInfant scale has been validated for the perceptual estimation of physical exer tion in Chilean children, but its usefulness for self-regulation of exercise intensity is unknown. The objective of the study was to evaluate the criterion validity of the EPInfant scale to regulate and re produce exercise intensity in a sample of healthy children. SUBJECTS AND METHOD: 15 children between the ages of eight and 12 were selected for an incremental exercise test (IET) and three perceptually regulated exercise tests (PRET) on a treadmill. The tests were performed with a 48-hour interval between them. In the PRET, the exercise load was adjusted perceptually for five minutes, randomly considering levels 3, 6, and 9 of the EPInfant scale. The average heart rate (HR) during PRET was considered as the perceptually reproduced intensity. Variance analysis, simple linear regression, and reliability analysis were used to determine the reproducibility of HR during PRET. RESULTS: There was a significant difference in HR between perceptual levels during PRET (p < 0.001). Additionally, a correlation was observed between HR during the IET and the PRET (r = 0.83, r2 = 0.69). The intra class correlation coefficient was 0.76, 0.83. and 0.93 at perceptual levels 3, 6, and 9; and the mean dis cordance between HR during the IET and the PRET was -2.4 beats/min. CONCLUSION: In the studied sample, the EPInfant scale was valid to allow the perceptual regulation and reproduction of exercise intensity in a treadmill.

Echocardiographic changes with non-invasive ventilation and CPAP in obesity hypoventilation syndrome.

RATIONALE: Despite a significant association between obesity hypoventilation syndrome (OHS) and cardiac dysfunction, no randomised trials have assessed the impact of non-invasive ventilation (NIV) or CPAP on cardiac structure and function assessed by echocardiography. OBJECTIVES: We performed a secondary analysis of the data from the largest multicentre randomised controlled trial of OHS (Pickwick project, n=221) to determine the comparative efficacy of 2 months of NIV (n=71), CPAP (n=80) and lifestyle modification (control group, n=70) on structural and functional echocardiographic changes. METHODS: Conventional transthoracic two-dimensional and Doppler echocardiograms were obtained at baseline and after 2 months. Echocardiographers at each site were blinded to the treatment arms. Statistical analysis was performed using intention-to-treat analysis. RESULTS: At baseline, 55% of patients had pulmonary hypertension and 51% had evidence of left ventricular hypertrophy. Treatment with NIV, but not CPAP, lowered systolic pulmonary artery pressure (-3.4 mm Hg, 95% CI -5.3 to -1.5; adjusted P=0.025 vs control and P=0.033 vs CPAP). The degree of improvement in systolic pulmonary artery pressure was greater in patients treated with NIV who had pulmonary hypertension at baseline (-6.4 mm Hg, 95% CI -9 to -3.8). Only NIV therapy decreased left ventricular hypertrophy with a significant reduction in left ventricular mass index (-5.7 g/m2; 95% CI -11.0 to -4.4). After adjusted analysis, NIV was superior to control group in improving left ventricular mass index (P=0.015). Only treatment with NIV led to a significant improvement in 6 min walk distance (32 m; 95% CI 19 to 46). CONCLUSION: In patients with OHS, medium-term treatment with NIV is more effective than CPAP and lifestyle modification in improving pulmonary hypertension, left ventricular hypertrophy and functional outcomes. Long-term studies are needed to confirm these results. TRIAL REGISTRATION NUMBER: Pre-results, NCT01405976 (https://clinicaltrials.gov/).

Cultured bovine embryo biopsy conserves methylation marks from original embryo.

A major limitation of embryo epigenotyping by chromatin immunoprecipitation analysis is the reduced amount of sample available from an embryo biopsy. We developed an in vitro system to expand trophectoderm cells from an embryo biopsy to overcome this limitation. This work analyzes whether expanded trophectoderm (EX) is representative of the trophectoderm (TE) methylation or adaptation to culture has altered its epigenome. We took a small biopsy from the trophectoderm (30-40 cells) of in vitro produced bovine-hatched blastocysts and cultured it on fibronectin-treated plates until we obtained ∼4 × 104 cells. The rest of the embryo was allowed to recover its spherical shape and, subsequently, TE and inner cell mass were separated. We examined whether there were DNA methylation differences between TE and EX of three bovine embryos using whole-genome bisulfite sequencing. As a consequence of adaptation to culture, global methylation, including transposable elements, was higher in EX, with 5.3% of quantified regions showing significant methylation differences between TE and EX. Analysis of individual embryos indicated that TE methylation is more similar to its EX counterpart than to TE from other embryos. Interestingly, these similarly methylated regions are enriched in CpG islands, promoters and transcription units near genes involved in biological processes important for embryo development. Our results indicate that EX is representative of the embryo in terms of DNA methylation, thus providing an informative proxy for embryo epigenotyping.

Efficacy of Different Treatment Alternatives for Obesity Hypoventilation Syndrome. Pickwick Study.

RATIONALE: The incidence of obesity hypoventilation syndrome (OHS) may be increasing in parallel with the present obesity epidemic. Despite extensive noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) use in patients with OHS, information regarding efficacy is limited. OBJECTIVES: We performed a large, multicenter randomized controlled study to determine the comparative efficacy of NIV, CPAP, and lifestyle modification (control group) using daytime PaCO2 as the main outcome measure. METHODS: Sequentially screened patients with OHS with severe sleep apnea were randomized into the above-mentioned groups for a 2-month follow up. Arterial blood gas parameters, clinical symptoms, health-related quality-of-life assessments, polysomnography, spirometry, 6-minute-walk distance, dropouts, compliance, and side effects were evaluated. Statistical analysis was performed using intention-to-treat analysis, although adjustments for CPAP and NIV compliance were also analyzed. MEASUREMENTS AND MAIN RESULTS: In total, 351 patients were selected, and 221 were randomized. NIV yielded the greatest improvement in PaCO2 and bicarbonate, with significant differences relative to the control group but not relative to the CPAP group. In the CPAP group, PaCO2 improvement was significantly different than in the control group only after CPAP compliance adjustment. Additionally, clinical symptoms and polysomnographic parameters improved similarly with NIV and CPAP relative to the control. However, some health-related quality-of-life assessments, the spirometry, and 6-minute-walk distance results improved more with NIV than with CPAP. Dropouts were similar between groups, and compliance and secondary effects were similar between NIV and CPAP. CONCLUSIONS: NIV and CPAP were more effective than lifestyle modification in improving clinical symptoms and polysomnographic parameters, although NIV yielded better respiratory functional improvements than did CPAP. Long-term studies must demonstrate whether this functional improvement has relevant implications. Clinical trial registered with www.clinicaltrials.gov (NCT01405976).

[Meaning of becoming mother and son/daughter through massage]. / Significado de ser madre e hijo/a por medio del masaje.

OBJECTIVE: Revealing the experience of mothers when massaging their children to know the phenomenon in the context of a mother-child healthy development. METHOD: This is a qualitative study with a phenomenological approach carried out with 11 women who massaged their children and answered the guiding question: What did the experience of massaging your child mean to you? RESULTS: The experience of massaging their children meant the development of their being a mother and of being a son/daughter, in addition to developing the attachment relationship between them. The massage can operationalize this integrality, become a tool of communication, stimulation and promotion of secure attachment, by promoting the loving interaction between mother and child. CONCLUSION: This practice should be considered as an option in the programs that promote the comprehensive health of the mother and child.

Datathons: fostering equitability in data reuse in ecology.

Approaches to rapidly collecting global biodiversity data are increasingly important, but biodiversity blind spots persist. We organized a three-day Datathon event to improve the openness of local biodiversity data and facilitate data reuse by local researchers. The first Datathon, organized among microbial ecologists in Uruguay and Argentina assembled the largest microbiome dataset in the region to date and formed collaborative consortia for microbiome data synthesis.

Giant cell myocarditis associated with amoxicillin hypersensitivity reaction.

We report a case of sudden unexpected death in an adult woman from florid myocarditis with necrosis, replacement fibrosis, and diffuse infiltration of the myocardium by eosinophils and conspicuous giant cells. Clinical history revealed that 3 weeks prior to death, shortly after commencing antibiotic therapy for the treatment of traumatic wound of a finger, she presented to the emergency room with a hypersensitivity reaction characterized by facial rash with edema and generalized pruritus. She was treated with antihistamines and discharged. The clinico-pathological correlation suggests a link between drug hypersensitivity and the giant cell myocarditis.

Quantitative determination of lurbinectedin, its unbound fraction and its metabolites in human plasma utilizing ultra-performance LC-MS/MS.

AIMS: Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods to quantify total lurbinectedin, its plasma protein binding to derive the unbound fraction and its main metabolites 1',3'-dihydroxy-lurbinectedin (M4) and N-desmethyl-lurbinectedin (M6) in human plasma, were developed and validated. MATERIALS & METHODS: For lurbinectedin, sample extraction was performed using supported liquid extraction. For metabolites, liquid-liquid extraction with stable isotope-labeled analogue internal standards was used. Plasma protein binding was evaluated using rapid equilibrium dialysis. In vitro investigations at different plasma protein concentrations were carried out to estimate dissociation rate constants to albumin and alpha-1-acid glycoprotein (AAG). RESULTS: Calibration curves displayed good linearity over 0.1 to 50 ng/mL for lurbinectedin and 0.5 to 20 ng/mL for the metabolites. Methods were validated in accordance with established guidance. The inter-day precision and accuracy ranged from 5.1% to 10.7%, and from -5% to 6% (lurbinectedin in plasma); from 3.1% to 6.6%, and from 4% to 6% (lurbinectedin in plasma:PBS); from 4.5% to 12.9%, and from 4% to 9% (M4); and from 7.5% to 10.5%, and from 6% to 12% (M6). All methods displayed good linearity (r2 >0.99). Recovery was evaluated for lurbinectedin in plasma:PBS (66.4% to 86.6%), M4 (7.82% to 13.4%) and M6 (22.2% to 34.3%). The method for lurbinectedin in plasma has been applied in most clinical studies, while the plasma:PBS and metabolites methods were used to evaluate the impact of special conditions on lurbinectedin PK. Lurbinectedin plasma protein binding was 99.6% and highly affected by AAG concentration. CONCLUSIONS: These UPLC-MS/MS methods enable the rapid and sensitive quantification of lurbinectedin and its main metabolites in clinical samples.

Implications of Climate Change: How Does Increased Water Temperature Influence Biofilm and Water Quality of Chlorinated Drinking Water Distribution Systems?

Temperature variation can promote physico-chemical and microbial changes in the water transported through distribution systems and influence the dynamics of biofilms attached to pipes, thus contributing to the release of pathogens into the bulk drinking water. An experimental real-scale chlorinated DWDS was used to study the effect of increasing temperature from 16 to 24°C on specific pathogens, bacterial-fungal communities (biofilm and water samples) and determine the risk of material accumulation and mobilisation from the pipes into the bulk water. Biofilm was developed for 30 days at both temperatures in the pipe walls, and after this growth phase, a flushing was performed applying 4 gradual steps by increasing the shear stress. The fungal-bacterial community characterised by Illumina MiSeq sequencing, and specific pathogens were studied using qPCR: Mycobacterium spp., Mycobacterium avium complex, Acanthamoeba spp., Pseudomonas aeruginosa, Legionella pneumophilia, and Stenotrophomonas maltophilia. Sequencing data showed that temperature variation significantly modified the structure of biofilm microbial communities from the early stages of biofilm development. Regarding bacteria, Pseudomonas increased its relative abundance in biofilms developed at 24°C, while fungal communities showed loss of diversity and richness, and the increase in dominance of Fusarium genus. After the mobilisation phase, Pseudomonas continued being the most abundant genus at 24°C, followed by Sphingobium and Sphingomonas. For biofilm fungal communities after the mobilisation phase, Helotiales incertae sedis and Fusarium were the most abundant taxa. Results from qPCR showed a higher relative abundance of Mycobacterium spp. on day 30 and M. avium complex throughout the growth phase within the biofilms at higher temperatures. The temperature impacts were not only microbial, with physical mobilisation showing higher discolouration response and metals release due to the increased temperature. While material accumulation was accelerated by temperature, it was not preferentially to either stronger or weaker biofilm layers, as turbidity results during the flushing steps showed. This research yields new understanding on microbial challenges that chlorinated DWDS will undergo as global temperature rises, this information is needed in order to protect drinking water quality and safety while travelling through distribution systems.

Addition of exogenous proteins detected in oviductal secretions to in vitro culture medium does not improve the efficiency of in vitro fertilization in pigs.

This work was designed to study whether HSP70-1A, HSP90α, ezrin or PDI4, proteins previously identified in porcine oviductal secretions, have a role in zona pellucida (ZP) resistance to enzymatic digestion, in vitro fertilization (IVF) and sperm viability. In vitro matured porcine cumulus oocyte complexes were denuded and i) incubated for 1 h in TALP medium supplemented or not with each exogenous oviductal protein and in presence or absence of heparin to assess ZP digestion time by pronase; and ii) inseminated with fresh ejaculated boar spermatozoa in medium supplemented or not with each exogenous oviductal protein to assess their effect on fertilization results. Finally, spermatozoa were incubated in Tyrode's medium (0, 1 and 20 h) supplemented or not with HSP-701A, HSP-90α or ezrin, to assess simultaneously sperm viability and acrosome status by means of flow cytometry. Although all proteins increased the ZP digestion time, this increase was lower than 1 min, being ezrin the protein with a stronger effect. Presence of heparin in the medium reinforced the ZP hardening effect of ezrin and HSP-701A up to one more min, but not HSP-90α nor PDI4. Sperm penetration, but not IVF efficiency, increased when gametes were cocultured in medium containing PDIA4 whereas sperm penetration and polyspermy rates decreased in presence of ezrin and HSP proteins. This reduction was not the result of a detrimental effect of proteins on sperm viability or acrosome reaction. In conclusion, addition of exogenous proteins detected in oviductal secretions to artificial media does not reproduce the effect of adding such secretions nor improve the final efficiency of the porcine IVF system.

RESPIRATORY MUSCLE IMPAIRMENT EVALUATED WITH MEP/MIP RATIO IN CHILDREN AND ADOLESCENTS WITH CHRONIC RESPIRATORY DISEASE.

OBJECTIVE: To evaluate the strength of respiratory muscles and to compare maximum inspiratory (MIP) and expiratory (MEP) pressure and MEP/MIP ratio between patients with chronic respiratory diseases and healthy individuals. METHODS: Case-control study. Individuals with neuromuscular disease and post-infectious bronchiolitis obliterans were considered. In addition, they were also matched according to anthropometric and demographic characteristics with healthy children and adolescents. MIP, MEP in the three groups, and pulmonary function only in patients with chronic respiratory diseases were recorded. RESULTS: A total of 52 subjects with CRD (25 with neuromuscular disease, and 27 with post-infectious bronchiolitis obliterans) and 85 healthy individuals were included, with an average age of 11.3±2.1 years. Patients with neuromuscular disease and post-infectious bronchiolitis obliterans presented lower MIP and MEP when compared with healthy individuals, although MEP/MIP ratio was lower in patients with neuromuscular disease (0.87±0.3) and higher in patients with post-infectious bronchiolitis obliterans (1.1±0.3) compared to the healthy group (0.97±0.2). Only in patients with neuromuscular disease a negative correlation was observed between MEP/MIP ratio and age (r=-0.50; p=0.01). CONCLUSIONS: Differences in the pattern of muscular weakness between patients with chronic respiratory diseases were observed. In patients with neuromuscular disease, a decrease in the MEP/MIP ratio depending on MIP was verified; and in those patients with post-infectious bronchiolitis obliterans, an increase in the MEP/MIP ratio depending on MIP was also observed.

Correction to: DNA methylation changes during preimplantation development reveal interspecies differences and reprogramming events at imprinted genes.

An amendment to this paper has been published and can be accessed via the original article.

DNA methylation changes during preimplantation development reveal inter-species differences and reprogramming events at imprinted genes.

Preimplantation embryos experience profound resetting of epigenetic information inherited from the gametes. Genome-wide analysis at single-base resolution has shown similarities but also species differences between human and mouse preimplantation embryos in DNA methylation patterns and reprogramming. Here, we have extended such analysis to two key livestock species, the pig and the cow. We generated genome-wide DNA methylation and whole-transcriptome datasets from gametes to blastocysts in both species. In oocytes from both species, a distinctive bimodal methylation landscape is present, with hypermethylated domains prevalent over hypomethylated domains, similar to human, while in the mouse the proportions are reversed.An oocyte-like pattern of methylation persists in the cleavage stages, albeit with some reduction in methylation level, persisting to blastocysts in cow, while pig blastocysts have a highly hypomethylated landscape. In the pig, there was evidence of transient de novo methylation at the 8-16 cell stages of domains unmethylated in oocytes, revealing a complex dynamic of methylation reprogramming. The methylation datasets were used to identify germline differentially methylated regions (gDMRs) of known imprinted genes and for the basis of detection of novel imprinted loci. Strikingly in the pig, we detected a consistent reduction in gDMR methylation at the 8-16 cell stages, followed by recovery to the blastocyst stage, suggesting an active period of imprint stabilization in preimplantation embryos. Transcriptome analysis revealed absence of expression in oocytes of both species of ZFP57, a key factor in the mouse for gDMR methylation maintenance, but presence of the alternative imprint regulator ZNF445. In conclusion, our study reveals species differences in DNA methylation reprogramming and suggests that porcine or bovine models may be closer to human in key aspects than in the mouse model.

A bio-inspired sighted robot chases like a hoverfly.

Here we present a novel bio-inspired visual processing system, which enables a robot to locate and follow a target, using an artificial compound eye called CurvACE. This visual sensor actively scanned the environment at an imposed frequency (50 Hz) with an angular scanning amplitude of [Formula: see text] and succeeded in locating a textured cylindrical target with hyperacuity, i.e. much finer resolution than the coarse inter-receptor angle of the compound eye. Equipped with this small, lightweight visual scanning sensor, a Mecanum-wheeled mobile robot named ACEbot was able to follow a target at a constant distance by localizing the right and left edges of the target. The localization of the target's contrasted edges is based on a bio-inspired summation of Gaussian receptive fields in the visual system. By means of its auto-adaptive pixels, ACEbot consistently achieved similar pursuit performances under various lighting conditions with a high level of repeatability. The robotic pursuit pattern mimics finely the behavior of the male fly Syritta Pipens L. while pursuing the female. The high similarity in the trajectories as well as the biomimicry of the visual system provides strong support for the hypothesis that flies do maintain center the target and constant its subtended angle during smooth pursuit. Moreover, we discuss the fact that such simple strategy can also provide a trajectory compatible with motion camouflage.

Validity and reliability of the modified Tal score in Chilean children. A multicenter study. / Validez y confiabilidad de la escala de Tal modificada en niños chilenos. Estudio multicéntrico.

INTRODUCTION: In pediatrics, it is decisive to assess the severity of bronchial obstruction; to this end, different clinical scoring scales have been developed, including the modified Tal score. The objective of this study was to determine its validity and reliability in children seen at two emergency departments of Concepción, Chile. POPULATION AND METHODS: Prospective, cohort study. Children younger than 36 months old diagnosed with bronchitis and/or bronchiolitis during the winter and spring months of 2015 were included. Concurrent criterion validity was determined based on the correlation between the score and oxygen saturation, as a reference standard. Predictive validity was assessed based on the association between the score and the probability of a new visit to the emergency department in the following 7 days. The area under the ROC curve was estimated. Reliability between kinesiologists and physicians was established based on the intraclass correlation coefficient (ICC). A p value < 0.05 was considered statistically significant. RESULTS: A total of 102 children were assessed; a weak correlation between the score and oxygen saturation was observed among kinesiologists (Rho = -0.41). An association was observed between the score and the probability of a new visit to the emergency department. The area under the curve measured by both health care providers was > 0.80. Inter-observer reliability between physicians and kinesiologists showed a weak correlation (ICC = 0.17). CONCLUSIONS: The modified Tal score shows an adequate predictive validity, but a poor validity when correlated to oxygen saturation, and a weak inter-observer reliability.

Introducción: En pediatría, evaluar la gravedad de la obstrucción bronquial es determinante; por esto, se han creado escalas de puntuación clínica, como la escala de Tal modificada. El objetivo fue determinar su validez y confiabilidad en niños atendidos en unidades de emergencia de Concepción, Chile. Población y métodos: Estudio de cohorte prospectivo. Se incluyeron niños < 36 meses con diagnóstico de bronquitis y/o bronquiolitis durante meses de invierno y primavera de 2015. La validez de criterio concurrente se determinó mediante la correlación entre el puntaje de la escala y la saturación de oxígeno, como estándar de referencia. La validez predictiva se evaluó mediante la asociación entre el puntaje de la escala y la probabilidad de nueva atención en la Unidad de Emergencia dentro de 7 días. Se calculó el área bajo la curva mediante curva ROC. La confiabilidad entre kinesiólogos y médicos se determinó mediante el coeficiente de correlación intraclase (CCI). Un valor de p < 0,05 se consideró estadísticamente significativo. Resultados: Se evaluaron 102 niños; se observó correlación débil entre la puntuación de la escala y la saturación de oxígeno en kinesiólogos (Rho= -0,41). Existió asociación entre la puntuación y la probabilidad de nueva atención en centros de emergencia. El área bajo la curva medida por ambos profesionales fue > 0,80. La confiabilidad interobservador entre médicos y kinesiólogos presentó correlación débil (CCI= 0,17). Conclusiones: La escala de Tal modificada presenta una adecuada validez predictiva, pero pobre validez al correlacionarla con la saturación de oxígeno y una débil confiabilidad interobservador.

Bionalytical validation study for the determination of unbound ambrisentan in human plasma using rapid equilibrium dialysis followed by ultra performance liquid chromatography coupled to mass spectrometry.

Ambrisentan is a highly selective endothelin-1 type A receptor antagonist indicated for use in the treatment of pulmonary hypertension. In this study an assay was developed and validated for the quantification of total and unbound (free) concentrations of ambrisentan in human plasma. Plasma samples were dialysed against phosphate buffered saline in a rapid equilibrium dialysis device to obtain dialysate and plasma for unbound and total ambrisentan, respectively. Subsequently, ambrisentan and deuterated ambrisentan (internal standard) were extracted from plasma or plasma dialysate by solid-phase extraction and separated by ultra performance liquid chromatography using on a reversed-phase C18 column. Detection was conducted with a tandem mass spectrometer with an electrospray ionization source and analysed in positive ion mode with multiple reaction monitoring. Calibration curves were generated over a linear concentration range of 0.1-200 ng/mL in plasma and 0.1-10 ng/mL in plasma ultrafiltrate; with a recovery for ambrisentan of 69.4% and 77.5%, respectively. This assay has been shown to be reproducible and sensitive. The lower limit of quantification in both cases was 0.1 ng/mL; reaching a sensitivity not previously described in the literature. The inter- and intra-batch precision and accuracy were in both cases ≤±15%. The procedure was applied to assess total and free plasma concentrations of ambrisentan in healthy volunteers. Plasma protein binding of ambrisentan was approximately 99%.

Exploratory factor analysis of a score for grading the severity of bronchial obstruction evaluated in children younger than 3 years old, Chile, 2015. / Análisis factorial exploratorio de una escala de gravedad de obstrucción bronquial evaluada en menores de tres años, Chile, 2015.

INTRODUCTION: The modified Tal's score has been used in Chile to determine the severity of bronchial obstruction. Its validity has been reported already; however, its structure as a scale to significantly quantify the severity of bronchial obstruction has not been analyzed. OBJETIVE: To identify the relationship pattern among the score's items and the severity of bronchial obstruction in a sample of children younger than 3 years seen in two health care centers in the province of Concepción, Chile. METHOD: Exploratory factor analysis. Nonrandom, voluntary selection of participants younger than 36 months, August-November 2015. Participants were assessed independently and subsequently by a physician and a physical therapist. The following measurements were applied: central tendency, exploratory factor analysis, subgroups of participants younger and older than 6 months, and internal consistency. RESULTS: A total of 204 measurements were done in 102 children. With a 39% explained variance, items incline towards to two different concepts: one factor groups respiratory rate, wheezing, and retractions, and the other determines only cyanosis, with a Cronbach's alpha of 0.5. Once cyanosis is removed from the analysis, the original one-factor matrix sample shows a 38% total explained variance and a 0.62 internal consistency. CONCLUSIONS: Based on its items, the score's structure does not fit adequately to this sample. Cyanosis appears as a dissociated item within the structure. Once the model is adjusted to only 3 items, the stability of Chronbach's alpha as a measure of internal consistency increases but at an objectionable value, which will undoubtedly vary once it is applied to a different sample.

INTRODUCCIÓN: La escala de Tal modificada es utilizada en Chile para determinar la gravedad de la obstrucción bronquial. Existen informes de su validez; sin embargo, carece de antecedentes del análisis de su estructura como escala para cuantificar de forma significativa la gravedad de la obstrucción bronquial. OBJETIVO: Identificar el patrón de relación entre los ítems de la escala y la dimensión gravedad de la obstrucción bronquial en una muestra de menores de tres años que consultan en dos centros de salud de la provincia de Concepción, Chile. MÉTODO: Análisis factorial exploratorio. Selección no aleatoria y voluntaria de participantes, menores de 36 meses, agosto-noviembre de 2015. Evaluados de manera independiente por médico y kinesiólogo, en tiempo seguido. Se aplican medidas de tendencia central, análisis factorial exploratorio, por subgrupo de menores y mayores de 6 meses, y consistencia interna. RESULTADOS: 204 mediciones a 102 menores. Con una varianza explicada de 39%, los ítems se dirigen a dos conceptos diferentes, un factor que agrupa frecuencia respiratoria, sibilancia y retracción, y otro que solo lo determina cianosis, con alfa de Cronbach de 0,5. Al extraer cianosis del análisis, muestra matriz monofactorial con 38% de varianza total explicada y consistencia interna de 0,62. CONCLUSIONES: Por medio de sus ítems, la estructura de la escala no se ajusta adecuadamente para esta muestra. Cianosis se muestra como un ítem disociado en la estructura. Al ajustar el modelo a solo tres ítems, la estabilidad del alfa como medida de consistencia interna aumenta, pero a un valor cuestionable, lo que, sin duda, variará al ser aplicada en otra muestra.

Psychometric properties of scales used for grading the severity of bronchial obstruction in pediatrics: A systematic review and meta-analysis. / Propiedades psicométricas de las escalas de gravedad de obstrucción bronquial en pediatría. Revisión sistemática y metaanálisis.

INTRODUCTION: In pediatrics, identifying the severity of bronchial obstruction in an early manner is a decisive factor. OBJETIVE: To assess the psychometric properties of the scales for grading the severity of bronchial obstruction in pediatric patients. POPULATION AND METHOD: This was a systematic review of studies on the validity and reliability of scales for grading the severity of bronchial obstruction conducted in infants and children younger than 3 years old. The search was conducted in Medline, WoS, EMBASE, SciELO, and Google Scholar. The correlation coefficient corresponding to each article was included in a random effects model to establish the criterion validity and reliability using the weighted averages of coefficients as per the sample size. RESULTS: A total of 9 articles were included, which accounted for 2699 children; 3 articles had an adequate or excellent methodological quality. Four articles established the concurrent criterion validity considering oxygen saturation, with a weighted correlation coefficient of -0.627 (95% confidence interval [CI]: -0.767 to -0.431, p < 0.001); 2 articles established the convergent criterion validity, with a weighted correlation coefficient of 0.809 (95% CI: 0.721 to 0.871, p < 0.001); 6 articles established the inter-observer reliability, with a weighted correlation coefficient of0.500for kappa and 0.891 for the intraclass correlation coefficient. CONCLUSION: The assessment of psychometric properties to support the use of scales for grading the construct "severity of bronchial obstruction" showed a moderate to adequate criterion validity. The percentage of agreement among observers in terms of the studied measure (severity of bronchial obstruction) was adequate; however, weaknesses such as the article design should be taken into account since it may affect the internal validity of results.

INTRODUCCIÓN: En pediatría, es determinante establecer precozmente la gravedad de la obstrucción bronquial (GOB). OBJETIVO: Evaluar las propiedades psicométricas de escalas de medición de GOB en pacientes pediátricos. POBLACIÓN Y MÉTODO: Revisión sistemática de estudios sobre validez y confiabilidad de escalas de GOB realizados en niños menores de 3 años. Se buscó en Medline, WoS, EMBASE, SciELO, Google Scholar. Los coeficientes de correlación de cada artículo fueron metaanalizados mediante el modelo de efectos aleatorios para determinar la validez de criterio y la confiabilidad a través de promedios ponderados de los coeficientes según el tamaño de la muestra. RESULTADOS: Se incluyeron 9 artículos con un total de 2699 niños; 3 artículos presentaron calidad metodológica buena o excelente. Cuatro artículos determinaron la validez de criterio concurrente considerando la saturación de oxígeno; coeficiente de correlación ponderado -0,627 (IC 95%: de -0,767 a -0,431; p < 0,001); 2 artículos determinaron la validez de criterio convergente; coeficiente de correlación ponderado 0,809 (IC 95%: de 0,721 a 0,871; p < 0,001); 6 artículos determinaron la confiabilidad interobservador; coeficiente de correlación ponderado de 0,500 para kappa y 0,891 para coeficiente de correlación intraclase. CONCLUSIÓN: La evaluación de las propiedades psicométricas para apoyar la utilidad de escalas para la estimación del constructo GOB mostró una validez de criterio de moderada a adecuada. El porcentaje de acuerdo entre observadores respecto de la medida observada (GOB) se muestra adecuado; sin embargo, hay que considerar las debilidades presentadas en el diseño de los artículos, lo cual podría afectar a la validez interna de los resultados.