The Modified-Classroom Observation Schedule to Measure Intentional Communication (M-COSMIC): Evaluation of reliability and validity

The Modified – Classroom Observation Schedule to Measure Intentional Communication (M-COSMIC) was developed as an ecologically valid measure of social-communication behaviour, delineating forms, functions, and intended partners of children’s spontaneous communication acts. Forty one children with autism spectrum disorder (ASD) aged 48 to 73 months were filmed within small-group settings at school. Communication behaviours during a five-minute teacher-led activity and a 10-minute free play session were coded from video-tape. Inter-rater reliability was high. Many M-COSMIC codes were significantly associated as predicted with Social and Communication domain scores on the Autism Diagnostic Observation Schedule (ADOS) and with scores on standardised language assessments. Agreement was more variable, however, at the level of individual M-COSMIC codes and ADOS items. Higher rates of responding, compliance behaviours and following pointing gestures and gaze occurred during the more structured teacher-led activity, compared to the free play. Results demonstrate preliminary construct validity of the M-COSMIC, showing its potential to describe and evaluate spontaneous social-communication skills in young children with ASD for research and applied purposes

Muscle strength and gait speed rather than lean mass are better indicators for poor cognitive function in older men

We aimed to examine muscle strength, function and mass in relation to cognition in older men. This cross-sectional data-set included 292 men aged ≥60 yr. Handgrip strength (kg) was measured by dynamometry, gait speed by 4-metre walk (m/s) and appendicular lean mass (kg) by dual-energy x-ray absorptiometry. Cognition was assessed across four domains: psychomotor function, attention, visual learning and working memory. Composite scores for overall cognition were calculated. Bivariate analyses indicated that handgrip strength and gait speed were positively associated with cognitive function. After accounting for confounders, positive associations between individual muscle (or physical) measures and cognitive performance were sustained for handgrip strength and psychomotor function, gait speed and psychomotor function, gait speed and attention, handgrip strength and overall cognition, and gait speed and overall cognition. In multivariable models, handgrip strength and gait speed independently predicted psychomotor function and overall cognition. No associations were detected between lean mass and cognition after adjusting for confounders. Thus, low muscle strength and slower gait speed, rather than low lean mass, were associated with poor cognition in older men

Adapting and testing a brief intervention to reduce maternal anxiety during pregnancy (ACORN): study protocol for a randomised controlled trial.

BACKGROUND: National guidelines in the UK, United States of America, Canada, and Australia have recently stressed the importance of identifying and treating antenatal anxiety and depression. However, there is little research into the most effective and acceptable ways of helping women manage their symptoms of anxiety and stress during pregnancy. Research indicates the necessity to consider the unique needs and concerns of perinatal populations to ensure treatment engagement, highlighting the need to develop specialised treatments which could be integrated within routine antenatal healthcare services. This trial aims to develop a brief intervention for antenatal anxiety, with a focus on embedding the delivery of the treatment within routine antenatal care. METHODS/DESIGN: This study is a two-phase feasibility trial. In phase 1 we will develop and pilot a brief intervention for antenatal anxiety, blended with group support, to be led by midwives. This intervention will draw on cognitive behavioural principles and wider learning from existing interventions that have been used to reduce anxiety in expectant mothers. The intervention will then be tested in a pilot randomised controlled trial in phase 2. The following outcomes will be assessed: (1) number of participants meeting eligibility criteria, (2) number of participants consenting to the study, (3) number of participants randomised, (4) number of sessions completed by those in the intervention arm, and (5) number of participants completing the post-intervention outcome measures. Secondary outcomes comprise: detailed feedback on acceptability, which will guide further development of the intervention; and outcome data on symptoms of maternal and paternal anxiety and depression, maternal quality of life, quality of couple relationship, mother-child bonding, infant temperament and infant sleep. DISCUSSION: The study will provide important data to inform the design of a future full-scale randomised controlled trial of a brief intervention for anxiety during pregnancy. This will include information on its acceptability and feasibility regarding implementation within current antenatal services, which will inform whether ultimately this provision could be rolled out widely in healthcare settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95282830 . Registered on 29 October 2014

Sarcopenic obesity and falls in the elderly

Background: Sarcopenic obesity refers to age-related loss of skeletal muscle mass and function, in the face of obesity. We aimed to examine the association of falls with sarcopenic obesity and its components, among elderly individuals in the population.Methods: Participants were 353 men and 245 women aged 65-98 yr of the Geelong Osteoporosis Study. Body fat and lean mass were measured using dual energy X-ray absorptiometry; body fat mass was expressed as a percentage of weight (%BF) and appendicular lean mass was adjusted for height (rALM, kg/m2). Poor physical performance was assessed using the timed up-&-go (TUG) test. Sarcopenic obesity referred to low-rALM (Tscore<- 1), poor physical performance (TUG>10 s) and obesity (%BF >25% for men, >35% for women). Fallers were identified by self-report as having had at least one fall in the previous 12 mo. Associations between sarcopenic obesity (and its components) and falls were determined using logistic regression after adjusting for age and sex.Results: In total, 219 (36.6%) had low-rALM, 205 (34.2%) had poor physical performance, 466 (77.9%) were obese and 69 (11.5%) had all three thereby meeting our criteria for sarcopenic obesity. There were 170 (28.4%) fallers; falls were more common for those with sarcopenic obesity than without (28 (40.6%) vs 142 (26.8%); p=0.017). The likelihood of a fall in association with sarcopenic obesity and its components were: sarcopenic obesity OR=1.65 (95%CI 0.96-2.85), sarcopenia OR=1.52 (0.93-2.47), poor physical performance and obesity OR=1.74 (1.16-2.61), low-rALM OR=1.41 (0.96-2.06), poor physical performance OR=1.88 (1.26-2.80), obesity OR=0.88 (0.57-1.35).Conclusion: While obesity per se was not associated with falls, there was an increased risk of falls individuals with sarcopenic obesity that was of borderline statistical significance and this appears to be largely a consequence of poor physical performance

Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men

Components of the renin–angiotensin–aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. “Likely” primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, “possible” primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin  0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health

Reference Intervals for bone impact microindentation in healthy adults: a multi-centre international study

Impact microindentation (IMI) is a novel technique for assessing bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. The aim of this study was to define the reference intervals for men and women by evaluating healthy adults from the United States of America, Europe and Australia. Participants included community-based volunteers and participants drawn from clinical and population-based studies. BMSi was measured on the tibial diaphysis using an OsteoProbe in 479 healthy adults (197 male and 282 female, ages 25 to 98 years) across seven research centres, between 2011 and 2018. Associations between BMSi, age, sex and areal bone mineral density (BMD) were examined following an a posteriori method. Unitless BMSi values ranged from 48 to 101. The mean (+/- standard deviation) BMSi for men was 84.4 +/- 6.9 and for women, 79.0 +/- 9.1. Healthy reference intervals for BMSi were identified as 71.0 to 97.9 for men and 59.8 to 95.2 for women. This study provides healthy reference data that can be used to calculate T- and Z-scores for BMSi and assist in determining the utility of BMSi in fracture prediction. These data will be useful for positioning individuals within the population and for identifying those with BMSi at the extremes of the population.Metabolic health: pathophysiological trajectories and therap

Ventilación líquida. Metaanálisis y revisión sistemática de la literatura

Introducción: En 1990 con base en las propiedades de los pfc (perfluorocarbonos) se realizó el primer ensayo clínico de ventilación líquida en humanos, en seis recién nacidos prematuros con insuficiencia respiratoria grave observándose mejoría significativa en la oxigenación y en la distensibilidad pulmonar. ¿Qué son los pfc? Producidas en la Segunda Guerra Mundial, son sustancias químicas cuyas propiedades dependen de la unión de los átomos de Fluor-Carbono. Su utilidad para la ventilación mecánica depende de su capacidad de disolver 20 veces más O2 y 3 veces más CO2, que el plasma, evaporándose más rápidamente que el agua a temperatura corporal. Los pfc han sido aprobados para aplicaciones biomédicas como transportadores de oxigeno aplicados intravenosos en situaciones de desastres o en individuos que rechazan ser transfundidos, sin embargo, el interés se ha despertado para su uso en la ventilación mecánica y en el síndrome de insuficiencia respiratoria aguda (sira). Por ello, el objetivo de este metaanálisis y revisión sistemática es la valoración de su uso, en especial de la década de los 90 hasta 2020. Analizando lo que dice la literatura y cómo ha funcionado en pacientes con Covid-19 y sira que ameritaron internamiento en unidades de cuidados intensivos. Material y métodos: Se buscaron revisiones sistemáticas, metaanálisis y ensayos clínicos de las revistas The New England Journal of Medicine, The Lancet , Science, Journal of Apply Physiology, Crit Care Med, Chest, Lung, Journal of Pediatrics, American Journal of Respiratory and Critical Care Medicine, Medicina Intensiva, Revista de la Facultad de Medicina de la UNAM, utilizando las bases de datos de Pubmed, medline, y www.mdconsult.com. Se buscó que los artículos estuvieran enfocados en los resultados del uso de la Ventilación Líquida, tanto en recién nacidos, prematuros, en lactantes y en adultos. El estudio se llevó a cabo de agosto de 2021 a febrero de 2022 y se realizó en el Departamento de Neumología de la Facultad de Medicina de la Universidad Autónoma del Estado de México. Resultados y Discusión: Para el año 2000 existían 1104 publicaciones sobre ventilación líquida, y 564 de ellas eran ensayos clínicos en humanos (medline), que demostraban que la Ventilación Líquida Parcial resulta más ventajosa en neonatos. En adultos sólo ha habido pocos resultados buenos con la Ventilación Líquida Total que mantiene recirculando los pfc dentro de un sistema cerrado. En las revisiones de la Fundación Cochrane se ha demostrado en dos revisiones sistemáticas y en dos metaanálisis que no hay pruebas de efectos beneficiosos de la ventilación líquida parcial en adultos con lesión pulmonar aguda. Sin embargo, surge la pregunta del uso de los pfc asociados al surfactante artificial y de mayor número de estudios con grandes grupos comparativos. La pandemia ocasionada por el Covid-19 ha generalizado el uso de la ventilación mecánica en las unidades de cuidados intensivos. Conclusiones: La ventilación líquida con pfc es una realidad y constituye una nueva alternativa terapéutica para el manejo de los enfermos con síndrome de insuficiencia respiratoria aguda. Su uso con la ventilación líquida parcial no ha demostrado la utilidad esperada en adultos, que seguramente requerirán de la ventilación líquida total. En los neonatos con la ventilación líquida parcial existe ya suficiente evidencia para tenerla como una alternativa en los prematuros y el uso combinado con la administración de surfactante no se debe pasar por alto en los Hospitales de Perinatología a nivel mundial

A New Method for Isolation of Interstitial Fluid from Human Solid Tumors Applied to Proteomic Analysis of Ovarian Carcinoma Tissue

Major efforts have been invested in the identification of cancer biomarkers in plasma, but the extraordinary dynamic range in protein composition, and the dilution of disease specific proteins make discovery in plasma challenging. Focus is shifting towards using proximal fluids for biomarker discovery, but methods to verify the isolated sample's origin are missing. We therefore aimed to develop a technique to search for potential candidate proteins in the proximal proteome, i.e. in the tumor interstitial fluid, since the biomarkers are likely to be excreted or derive from the tumor microenvironment. Since tumor interstitial fluid is not readily accessible, we applied a centrifugation method developed in experimental animals and asked whether interstitial fluid from human tissue could be isolated, using ovarian carcinoma as a model. Exposure of extirpated tissue to 106 g enabled tumor fluid isolation. The fluid was verified as interstitial by an isolated fluid:plasma ratio not significantly different from 1.0 for both creatinine and Na+, two substances predominantly present in interstitial fluid. The isolated fluid had a colloid osmotic pressure 79% of that in plasma, suggesting that there was some sieving of proteins at the capillary wall. Using a proteomic approach we detected 769 proteins in the isolated interstitial fluid, sixfold higher than in patient plasma. We conclude that the isolated fluid represents undiluted interstitial fluid and thus a subproteome with high concentration of locally secreted proteins that may be detected in plasma for diagnostic, therapeutic and prognostic monitoring by targeted methods

Identification of a gene signature for discriminating metastatic from primary melanoma using a molecular interaction network approach

Understanding the biological factors that are characteristic of metastasis in melanoma remains a key approach to improving treatment. In this study, we seek to identify a gene signature of metastatic melanoma. We configured a new network-based computational pipeline, combined with a machine learning method, to mine publicly available transcriptomic data from melanoma patient samples. Our method is unbiased and scans a genome-wide protein-protein interaction network using a novel formulation for network scoring. Using this, we identify the most influential, differentially expressed nodes in metastatic as compared to primary melanoma. We evaluated the shortlisted genes by a machine learning method to rank them by their discriminatory capacities. From this, we identified a panel of 6 genes, ALDH1A1, HSP90AB1, KIT, KRT16, SPRR3 and TMEM45B whose expression values discriminated metastatic from primary melanoma (87% classification accuracy). In an independent transcriptomic data set derived from 703 primary melanomas, we showed that all six genes were significant in predicting melanoma specific survival (MSS) in a univariate analysis, which was also consistent with AJCC staging. Further, 3 of these genes, HSP90AB1, SPRR3 and KRT16 remained significant predictors of MSS in a joint analysis (HR = 2.3, P = 0.03) although, HSP90AB1 (HR = 1.9, P = 2 × 10−4) alone remained predictive after adjusting for clinical predictors